Maryland environmental public health tracking outreach with Spanish-speaking persons living in Baltimore city or county.

PubMed

Braggio, John T; Mitchell, Clifford S; Fierro-Luperini, Sonia

2015-01-01

The 2000 Pew reports became the impetus for the National Environmental Public Health Tracking (EPHT) Program, but there was no mention that Spanish-speaking persons are at increased risk of exposure to environmental hazards. To undertake successful EPHT outreach on Spanish-speaking persons (Hispanics), it is necessary to better understand their environmental health profile and barriers to health care access. Behavioral Risk Factor Surveillance System (BRFSS) survey questions were administered orally in Spanish to Spanish-speaking study participants. Volunteers were tested at a non-for-profit social service and referral agency in Baltimore. To control for acculturation, only Spanish-speaking persons who had lived in the United States for less than 10 years were selected. Responses to 40 BRFSS survey questions asked during the assessment and completion of 3 intervention activities. This study provides new information about Spanish-speaking persons, most of whom (85.3%) would not have been included in the landline administration of the BRFSS survey. Although 29.9% of the participants reported indoor pesticide use and another 9.2% reported outdoor pesticide use, lifetime (3.5%) and current (1.2%) asthma prevalence was significantly lower than asthma prevalence reported by Maryland Hispanics and all Maryland residents. There were significantly lower cholesterol screening (21.5%) and a significantly higher prevalence of diabetes (12.5%) in Spanish-speaking participants than in Maryland Hispanics and all Maryland residents. Among study participants, only 7.8% had health insurance and 39.9% reported that they could not see a doctor. Of the 3 outreach efforts completed, the most promising one involved asking Spanish-English-speaking health care professionals to distribute Spanish comic books about pesticides exposures and health outcomes in community settings where Spanish-only speakers and children were found. The effectiveness of passive and community-based EPHT interventions directed toward Spanish-only speakers has to be evaluated.

Taurine supplementation for prevention of stroke-like episodes in MELAS: a multicentre, open-label, 52-week phase III trial.

PubMed

Ohsawa, Yutaka; Hagiwara, Hiroki; Nishimatsu, Shin-Ichiro; Hirakawa, Akihiro; Kamimura, Naomi; Ohtsubo, Hideaki; Fukai, Yuta; Murakami, Tatsufumi; Koga, Yasutoshi; Goto, Yu-Ichi; Ohta, Shigeo; Sunada, Yoshihide

2018-04-17

The aim of this study was to evaluate the efficacy and safety of high-dose taurine supplementation for prevention of stroke-like episodes of MELAS (mitochondrial myopathy, encephalopathy, lactic acidosis and stroke-like episodes), a rare genetic disorder caused by point mutations in the mitochondrial DNA that lead to a taurine modification defect at the first anticodon nucleotide of mitochondrial tRNA Leu(UUR) , resulting in failure to decode codons accurately. After the nationwide survey of MELAS, we conducted a multicentre, open-label, phase III trial in which 10 patients with recurrent stroke-like episodes received high-dose taurine (9 g or 12 g per day) for 52 weeks. The primary endpoint was the complete prevention of stroke-like episodes during the evaluation period. The taurine modification rate of mitochondrial tRNA Leu(UUR) was measured before and after the trial. The proportion of patients who reached the primary endpoint (100% responder rate) was 60% (95% CI 26.2% to 87.8%). The 50% responder rate, that is, the number of patients achieving a 50% or greater reduction in frequency of stroke-like episodes, was 80% (95% CI 44.4% to 97.5%). Taurine reduced the annual relapse rate of stroke-like episodes from 2.22 to 0.72 (P=0.001). Five patients showed a significant increase in the taurine modification of mitochondrial tRNA Leu(UUR) from peripheral blood leukocytes (P<0.05). No severe adverse events were associated with taurine. The current study demonstrates that oral taurine supplementation can effectively reduce the recurrence of stroke-like episodes and increase taurine modification in mitochondrial tRNA Leu(UUR) in MELAS. UMIN000011908. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Genetics Home Reference: maternally inherited diabetes and deafness

MedlinePlus

... Maassen JA. Mutation in mitochondrial tRNA(Leu)(UUR) gene in a large pedigree with maternally transmitted type II diabetes mellitus ... are genome editing and CRISPR-Cas9? What is precision medicine? What ...

The expanding clinical phenotype of the tRNA{sup Leu(UUR)} A{r_arrow}G mutation at np 3243 of mitochondrial DNA: Diabetic embryopathy associated with mitochondrial cytopathy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Feigenbaum, A.; Chitayat, D.; Robinson, B.

1996-04-24

We describe a family which demonstrates and expands the extreme clinical variability now known to be associated with the A{r_arrow}G transition at nucleotide position 3243 of the mitochondrial DNA. The propositus presented at birth with clinical manifestations consistent with diabetic embryopathy including anal atresia, caudal dysgenesis, and multicystic dysplastic kidneys. His co-twin was normal at birth, but at 3 months of life, presented with intractable seizures later associated with developmental delay. The twins` mother developed diabetes mellitus type I at the age of 20 years and gastrointestinal problems at 22 years. Since age 19 years, the maternal aunt has hadmore » recurrent strokes, seizures, mental deterioration and deafness, later diagnosed as MELAS syndrome due to the tRNA{sup Leu(UUR)} A{r_arrow}G mutation. A maternal uncle had diabetes mellitus type I, deafness, and normal intellect, and died at 35 years after recurrent strokes. This pedigree expands the known clinical phenotype associated with tRNA{sup Leu(UUR)} A{r_arrow}G mutation and raises the possibility that, in some cases, diabetic embryopathy may be due to a mitochondrial cytopathy that affects both the mother`s pancreas (and results in diabetes mellitus and the metabolic dysfunction associated with it) and the embryonic/fetal and placental tissues which make the embryo more vulnerable to this insult. 33 refs., 1 tab.« less

Investigations of Photochemistry Using Holography and Photoacoustic Spectroscopy.

DTIC Science & Technology

1984-09-28

Donald M. Burland PERFORMING ORGANIZATION NAME AND ADDRESS 10. PROGRAM ELEMENT. PROJECT. TASK CD International Business Machines, Inc. AE OKUI UUR San...Hans Coufal Institution: International Business Machines Corporation San Jose Research Laboratory 5600 Cottle Road, San Jose, CA 95193 " Funding

Mitochondrial DNA sequence context in the penetrance of mitochondrial t-RNA mutations: A study across multiple lineages with diagnostic implications

PubMed Central

Queen, Rachel A.; Steyn, Jannetta S.; Lord, Phillip

2017-01-01

Mitochondrial DNA (mtDNA) mutations are well recognized as an important cause of inherited disease. Diseases caused by mtDNA mutations exhibit a high degree of clinical heterogeneity with a complex genotype-phenotype relationship, with many such mutations exhibiting incomplete penetrance. There is evidence that the spectrum of mutations causing mitochondrial disease might differ between different mitochondrial lineages (haplogroups) seen in different global populations. This would point to the importance of sequence context in the expression of mutations. To explore this possibility, we looked for mutations which are known to cause disease in humans, in animals of other species unaffected by mtDNA disease. The mt-tRNA genes are the location of many pathogenic mutations, with the m.3243A>G mutation on the mt-tRNA-Leu(UUR) being the most frequently seen mutation in humans. This study looked for the presence of m.3243A>G in 2784 sequences from 33 species, as well as any of the other mutations reported in association with disease located on mt-tRNA-Leu(UUR). We report a number of disease associated variations found on mt-tRNA-Leu(UUR) in other chordates, as the major population variant, with m.3243A>G being seen in 6 species. In these, we also found a number of mutations which appear compensatory and which could prevent the pathogenicity associated with this change in humans. This work has important implications for the discovery and diagnosis of mtDNA mutations in non-European populations. In addition, it might provide a partial explanation for the conflicting results in the literature that examines the role of mtDNA variants in complex traits. PMID:29161289

Environmental Public Health Tracking: a cost-effective system for characterizing the sources, distribution and public health impacts of environmental hazards.

PubMed

Saunders, P J; Middleton, J D; Rudge, G

2017-09-01

The contemporary environment is a complex of interactions between physical, biological, socio-economic systems with major impacts on public health. However, gaps in our understanding of the causes, extent and distribution of these effects remain. The public health community in Sandwell West Midlands has collaborated to successfully develop, pilot and establish the first Environmental Public Health Tracking (EPHT) programme in Europe to address this 'environmental health gap' through systematically linking data on environmental hazards, exposures and diseases. Existing networks of environmental, health and regulatory agencies developed a suite of innovative methods to routinely share, integrate and analyse data on hazards, exposures and health outcomes to inform interventions. Effective data sharing and horizon scanning systems have been established, novel statistical methods piloted, plausible associations framed and tested, and targeted interventions informed by local concerns applied. These have influenced changes in public health practice. EPHT is a powerful tool for identifying and addressing the key environmental public health impacts at a local level. Sandwell's experience demonstrates that it can be established and operated at virtually no cost. The transfer of National Health Service epidemiological skills to local authorities in 2013 provides an opportunity to expand the programme to fully exploit its potential. © The Author 2016. Published by Oxford University Press on behalf of Faculty of Public Health. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com

MELAS syndrome with mitochondrial tRNA(Leu(UUR)) gene mutation in a Chinese family.

PubMed Central

Huang, C C; Chen, R S; Chen, C M; Wang, H S; Lee, C C; Pang, C Y; Hsu, H S; Lee, H C; Wei, Y H

1994-01-01

The clinical features of a patient in a Chinese family with mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes (MELAS syndrome) are reported. The study revealed that hearing and visual impairments and miscarriages may be early clinical presentations in MELAS. A heteroplasmic A to G transition in the tRNA(Leu(UUR)) gene was noted at the nucleotide pair 3243 in the mitochondrial DNA of muscle, blood, and hair follicles of the proband and his maternal relatives. Quantitative analysis of the mutated mitochondrial DNA revealed variable proportions in different tissues and subjects of maternal lineage in the family. Muscle tissue contained a higher proportion of the mutant mitochondria than other tissues examined. The function of the reproductive system of the proband seems to be impaired. In one clinically healthy sibling, the 3243rd point mutation was found in sperm mitochondrial DNA, although sperm motility was not affected. It seems that biochemical defects in mitochondrial respiration and oxidative phosphorylation are tissue specific expressions of the 3243rd point mutation in the mitochondrial DNA of the affected target tissues. Images PMID:8201329

Integration of Dust Prediction Systems and Vegetation Phenology to Track Pollen for Asthma Alerts in Public Health

NASA Technical Reports Server (NTRS)

Luvall, Jeffrey; Sprigg, William; Huete, Alfredo; Levetin, Estelle; VandeWater, Peter; Nickovic, Slobodan; Pejanovic, Goran; Budge, Amelia; Heidi Krapfl; Myers, Orrin;

The ROS-sensitive microRNA-9/9* controls the expression of mitochondrial tRNA-modifying enzymes and is involved in the molecular mechanism of MELAS syndrome.

PubMed

Meseguer, Salvador; Martínez-Zamora, Ana; García-Arumí, Elena; Andreu, Antonio L; Armengod, M-Eugenia

2015-01-01

Mitochondrial dysfunction activates mitochondria-to-nucleus signaling pathways whose components are mostly unknown. Identification of these components is important to understand the molecular mechanisms underlying mitochondrial diseases and to discover putative therapeutic targets. MELAS syndrome is a rare neurodegenerative disease caused by mutations in mitochondrial (mt) DNA affecting mt-tRNA(Leu(UUR)). Patient and cybrid cells exhibit elevated oxidative stress. Moreover, mutant mt-tRNAs(Leu(UUR)) lack the taurine-containing modification normally present at the wobble uridine (U34) of wild-type mt-tRNA(Leu(UUR)), which is considered an etiology of MELAS. However, the molecular mechanism is still unclear. We found that MELAS cybrids exhibit a significant decrease in the steady-state levels of several mt-tRNA-modification enzymes, which is not due to transcriptional regulation. We demonstrated that oxidative stress mediates an NFkB-dependent induction of microRNA-9/9*, which acts as a post-transcriptional negative regulator of the mt-tRNA-modification enzymes GTPBP3, MTO1 and TRMU. Down-regulation of these enzymes by microRNA-9/9* affects the U34 modification status of non-mutant tRNAs and contributes to the MELAS phenotype. Anti-microRNA-9 treatments of MELAS cybrids reverse the phenotype, whereas miR-9 transfection of wild-type cells mimics the effects of siRNA-mediated down-regulation of GTPBP3, MTO1 and TRMU. Our data represent the first evidence that an mt-DNA disease can directly affect microRNA expression. Moreover, we demonstrate that the modification status of mt-tRNAs is dynamic and that cells respond to stress by modulating the expression of mt-tRNA-modifying enzymes. microRNA-9/9* is a crucial player in mitochondria-to-nucleus signaling as it regulates expression of nuclear genes in response to changes in the functional state of mitochondria. © The Author 2014. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Correction of the consequences of mitochondrial 3243A>G mutation in the MT-TL1 gene causing the MELAS syndrome by tRNA import into mitochondria

PubMed Central

Karicheva, Olga Z.; Kolesnikova, Olga A.; Schirtz, Tom; Vysokikh, Mikhail Y.; Mager-Heckel, Anne-Marie; Lombès, Anne; Boucheham, Abdeldjalil; Krasheninnikov, Igor A.; Martin, Robert P.; Entelis, Nina; Tarassov, Ivan

2011-01-01

Mutations in human mitochondrial DNA are often associated with incurable human neuromuscular diseases. Among these mutations, an important number have been identified in tRNA genes, including 29 in the gene MT-TL1 coding for the tRNALeu(UUR). The m.3243A>G mutation was described as the major cause of the MELAS syndrome (mitochondrial encephalomyopathy with lactic acidosis and stroke-like episodes). This mutation was reported to reduce tRNALeu(UUR) aminoacylation and modification of its anti-codon wobble position, which results in a defective mitochondrial protein synthesis and reduced activities of respiratory chain complexes. In the present study, we have tested whether the mitochondrial targeting of recombinant tRNAs bearing the identity elements for human mitochondrial leucyl-tRNA synthetase can rescue the phenotype caused by MELAS mutation in human transmitochondrial cybrid cells. We demonstrate that nuclear expression and mitochondrial targeting of specifically designed transgenic tRNAs results in an improvement of mitochondrial translation, increased levels of mitochondrial DNA-encoded respiratory complexes subunits, and significant rescue of respiration. These findings prove the possibility to direct tRNAs with changed aminoacylation specificities into mitochondria, thus extending the potential therapeutic strategy of allotopic expression to address mitochondrial disorders. PMID:21724600

Correction of the consequences of mitochondrial 3243A>G mutation in the MT-TL1 gene causing the MELAS syndrome by tRNA import into mitochondria.

PubMed

Karicheva, Olga Z; Kolesnikova, Olga A; Schirtz, Tom; Vysokikh, Mikhail Y; Mager-Heckel, Anne-Marie; Lombès, Anne; Boucheham, Abdeldjalil; Krasheninnikov, Igor A; Martin, Robert P; Entelis, Nina; Tarassov, Ivan

2011-10-01

Mutations in human mitochondrial DNA are often associated with incurable human neuromuscular diseases. Among these mutations, an important number have been identified in tRNA genes, including 29 in the gene MT-TL1 coding for the tRNA(Leu(UUR)). The m.3243A>G mutation was described as the major cause of the MELAS syndrome (mitochondrial encephalomyopathy with lactic acidosis and stroke-like episodes). This mutation was reported to reduce tRNA(Leu(UUR)) aminoacylation and modification of its anti-codon wobble position, which results in a defective mitochondrial protein synthesis and reduced activities of respiratory chain complexes. In the present study, we have tested whether the mitochondrial targeting of recombinant tRNAs bearing the identity elements for human mitochondrial leucyl-tRNA synthetase can rescue the phenotype caused by MELAS mutation in human transmitochondrial cybrid cells. We demonstrate that nuclear expression and mitochondrial targeting of specifically designed transgenic tRNAs results in an improvement of mitochondrial translation, increased levels of mitochondrial DNA-encoded respiratory complexes subunits, and significant rescue of respiration. These findings prove the possibility to direct tRNAs with changed aminoacylation specificities into mitochondria, thus extending the potential therapeutic strategy of allotopic expression to address mitochondrial disorders.

[MELAS: Mitochondrial Encephalomyopathy, Lactic Acidosis and Stroke-Like Episodes].

PubMed

Murakami, Hidetomo; Ono, Kenjiro

2017-02-01

Mitochondrial disease is caused by a deficiency in the energy supply to cells due to mitochondrial dysfunction. Mitochondrial encephalomyopathy, lactic acidosis and stroke-like episodes (MELAS) is a mitochondrial disease that presents with stroke-like episodes such as acute onset of neurological deficits and characteristic imaging findings. Stroke-like episodes in MELAS have the following features: 1) neurological deficits due to localization of lesions in the brain, 2) episodes often accompany epilepsy, 3) lesions do not follow the vascular supply area, 4) lesions are more often seen in the posterior brain than in the anterior brain, 5) lesions spread to an adjacent area in the brain, and 6) neurological symptoms often disappear together with imaging findings, but later relapse. About 80% of patients with MELAS have an A-to-G transition mutation at the nucleotide pair 3243 in the dihydrouridine loop of mitochondrial tRNA^Leu(UUR), which causes the absence of posttranscriptional taurine modification at the wobble nucleotide of mitochondrial tRNA^Leu(UUR) and disrupts protein synthesis. However, the precise pathophysiology of stroke-like episodes is under investigation, with possible hypotheses for these episodes including mitochondrial angiopathy, mitochondrial cytopathy, and neuron-astrocyte uncoupling. With regard to treatment, L-arginine and taurine have recently been suggested for relief of clinical symptoms.

Mitochondrial gene arrangement of the horseshoe crab Limulus polyphemus L.: conservation of major features among arthropod classes

NASA Technical Reports Server (NTRS)

Staton, J. L.; Daehler, L. L.; Brown, W. M.; Jacobs, D. K. (Principal Investigator)

1997-01-01

Numerous complete mitochondrial DNA sequences have been determined for species within two arthropod groups, insects and crustaceans, but there are none for a third, the chelicerates. Most mitochondrial gene arrangements reported for crustaceans and insect species are identical or nearly identical to that of Drosophila yakuba. Sequences across 36 of the gene boundaries in the mitochondrial DNA (mtDNA) of a representative chelicerate. Limulus polyphemus L., also reveal an arrangement like that of Drosophila yakuba. Only the position of the tRNA(LEU)(UUR) gene differs; in Limulus it is between the genes for tRNA(LEU)(CUN) and ND1. This positioning is also found in onychophorans, mollusks, and annelids, but not in insects and crustaceans, and indicates that tRNA(LEU)(CUN)-tRNA(LEU)(UUR)-ND1 was the ancestral gene arrangement for these groups, as suggested earlier. There are no differences in the relative arrangements of protein-coding and ribosomal RNA genes between Limulus and Drosophila, and none have been observed within arthropods. The high degree of similarity of mitochondrial gene arrangements within arthropods is striking, since some taxa last shared a common ancestor before the Cambrian, and contrasts with the extensive mtDNA rearrangements occasionally observed within some other metazoan phyla (e.g., mollusks and nematodes).

A Spatial Analysis of Acute Myocardial Infarction Rates in New York State in Relation to Hospitals Along State Jurisdictional Borders.

PubMed

Stamm, Abigail J; Savadatti, Sanghamitra S; Kumar, Sanjaya; Hwang, Syni-An

Patients experiencing acute myocardial infarction (AMI) are likely to visit the nearest hospital providing appropriate services since timely care is a critical determinant in the treatment and progression of AMI. We comparatively examined AMI rates in border and nonborder census tracts. The New York State (NYS) Environmental Public Health Tracking (EPHT) program, in conjunction with the Statewide Planning and Research Cooperative System, will work on developing memoranda of understanding with neighboring states to be able to more comprehensively access NYS residents' out-of-state health records. To determine whether AMI rates in the NYS border census tracts differ from AMI rates in nonborder census tracts as a preliminary exploration of the utilization of out-of-state care for acute health conditions by NYS border residents. We reviewed data on inpatient and emergency department visits in NYS with discharge dates from 2005 to 2014 retrospectively. We used the NYS EPHT tier 1 system database to locate hospitals. We geocoded all cases to NYS 2010 census tracts. We mapped differences between border and nonborder tracts and analyzed resulting spatial patterns. We computed tract-level AMI rates and differences between border and nonborder AMI rates. The age-adjusted AMI rates differed by 8.2 cases per 10 000 people (95% confidence interval, 6.94-12.60). Maps showed patterns of differences in AMI rates, especially along the NYS border with New England and other geographically closer out-of-state hospitals. AMI rates that were geographically closer to out-of-state hospitals were lower, suggesting that people residing in border census tracts are utilizing out-of-state care. Our study adds to literature on the geographical component of health care accessibility and utilization in the context of acute conditions such as AMI and lends impetus to access out-of-state health records to better understand health care facility access and utilization for NYS residents.

Waterborne Commerce of the United States, Calendar Year 1980. Part 4. Waterways and Harbors, Pacific Coast, Alaska and Hawaii.

DTIC Science & Technology

1982-09-01

PROGRAM ELEMENT. PROJECT. TASK Waterborne Comerce Statistics Center AESWRCUI UUR P. 0. Box 61280 *New Orleans, La. 70161 WRSC-CC 11I. CONTROLLING ... controlled cargo end Special Category Items." The 1980 statistics on waterborne exports of domestic and foreign merchandise and non-Department of Defense...Government materials 4119 Empty containers Group 34-fabricated Metal Products, 9999* Department of Defense controlled cargo snd special category Except

Age and growth comparisons of Hovsgol grayling (Thymallus nigrescens Dorogostaisky, 1923), Baikal grayling (T. baicalensis Dybowski, 1874), and lenok (Brachymystax lenok Pallas, 1773) in lentic and lotic habitats of Northern Mongolia

USGS Publications Warehouse

Tsogtsaikhan, Pureviin; Mendsaikhan, Budiin; Jargalmaa, Ganzorigiin; Ganzorig, Batsaikhanii; Weidel, Brian C.; Filosa, Christopher; Free, Christopher; Young, Talia; Jensen, Olaf P.

2017-01-01

Despite concern over the conservation status of many Mongolian salmonids and the importance of their ecological role in Mongolia's aquatic ecosystems, little is known about their basic biology. Hovsgol grayling (Thymallus nigrescens) is endemic to Lake Hovsgol, Mongolia and listed as endangered on the Mongolian Red List. Baikal grayling (T. baicalensis) and lenok (Brachymystax lenok) are found in lakes and rivers throughout the Selenge drainage. A detailed study of the age and growth of these three salmonids was conducted based on 1,682 samples collected from July 2006 to July 2013 in Lake Hovsgol, its outlet the Eg River, and one of the Eg's largest tributaries, the Uur River. Our results suggest that Hovsgol grayling in particular can reach a much older maximum age (17 years in our samples) than previously believed based on aging from scales. Female Hovsgol grayling were heavier at a given length than their male counterparts. Lenok had a greater average length-at-age in Lake Hovsgol compared to the rivers and greater weight-at-length in the warmer Uur River than in the Eg; female lenok from the rivers had a greater average length-at-age than their male counterparts. This study provides critical new information for the management and conservation of these threatened salmonid species in Mongolia.

Evaluation of a Pilot Surveillance System: Health and Environment Linked for Information Exchange in Atlanta (HELIX-Atlanta)

NASA Technical Reports Server (NTRS)

Meyer, P.; Shire, J.; Qualters, Judy; Daley, Randolph; Fiero, Leslie Todorov; Autry, Andy; Avchen, Rachel; Stock, Allison; Correa, Adolofo; Siffel, Csaba;

A Study of Strategic Lessons Learned in Vietnam. Volume 8. Results of the War

DTIC Science & Technology

1980-05-09

and magnitude as to literally put uur system on trial.. They [Am’ericans] still want leaders who operate within the parameters of consent of the...governed. But they also desDerately want the leaders to know that the parameters of consenrt are changing drastically, radically, a barn-yard wide. Make no...mistake about it, this electorate no !Tnjer wants to be governed by leaders wed to the old parameters of consent, nor by those who would try to soothe

Development of a multilocus sequence typing scheme for Ureaplasma.

PubMed

Zhang, J; Kong, Y; Feng, Y; Huang, J; Song, T; Ruan, Z; Song, J; Jiang, Y; Yu, Y; Xie, X

2014-04-01

Ureaplasma is a commensal of the human urogenital tract but is always associated with invasive diseases such as non-gonococcal urethritis and infertility adverse pregnancy outcomes. To better understand the molecular epidemiology and population structure of Ureaplasma, a multilocus sequence typing (MLST) scheme based on four housekeeping genes (ftsH, rpL22, valS, thrS) was developed and validated using 283 isolates, including 14 serovars of reference strains and 269 strains obtained from clinical patients. A total of 99 sequence types (STs) were revealed: the 14 type strains of the Ureaplasma serovars were assigned to 12 STs, and 87 novel and special STs appeared among the clinical isolates. ST1 and ST22 were the predominant STs, which contained 68 and 70 isolates, respectively. Two clonal lineages (CC1 and CC2) were shown by eBURST analysis, and linkage disequilibrium was revealed through a standardized index of association (I A (S)). The neighbor-joining tree results of 14 Ureaplasma serovars showed two genetically significantly distant clusters, which was highly congruent with the species taxonomy of ureaplasmas [Ureaplasma parvum (UPA) and Ureaplasma urealyticum (UUR)]. Analysis of the biotypes of 269 clinical isolates revealed that all the isolates of CC1 were UPA and those of CC2 were UUR. Additionally, CC2 was found more often in symptomatic patients with vaginitis, tubal obstruction, and cervicitis. In conclusion, this MLST scheme is adequate for investigations of molecular epidemiology and population structure with highly discriminating capacity.

The mitochondrial myopathy encephalopathy, lactic acidosis with stroke-like episodes (MELAS) syndrome: a review of treatment options.

PubMed

Scaglia, Fernando; Northrop, Jennifer L

2006-01-01

Mitochondrial encephalomyopathies are a multisystemic group of disorders that are characterised by a wide range of biochemical and genetic mitochondrial defects and variable modes of inheritance. Among this group of disorders, the mitochondrial myopathy, encephalopathy, lactic acidosis with stroke-like episodes (MELAS) syndrome is one of the most frequently occurring, maternally inherited mitochondrial disorders. As the name implies, stroke-like episodes are the defining feature of the MELAS syndrome, often occurring before the age of 15 years. The clinical course of this disorder is highly variable, ranging from asymptomatic, with normal early development, to progressive muscle weakness, lactic acidosis, cognitive dysfunction, seizures, stroke-like episodes, encephalopathy and premature death. This syndrome is associated with a number of point mutations in the mitochondrial DNA, with over 80% of the mutations occurring in the dihydrouridine loop of the mitochondrial transfer RNA(Leu(UUR)) [tRNA(Leu)((UUR))] gene. The pathophysiology of the disease is not completely understood; however, several different mechanisms are proposed to contribute to this disease. These include decreased aminoacylation of mitochondrial tRNA, resulting in decreased mitochondrial protein synthesis; changes in calcium homeostasis; and alterations in nitric oxide metabolism. Currently, no consensus criteria exist for treating the MELAS syndrome or mitochondrial dysfunction in other diseases. Many of the therapeutic strategies used have been adopted as the result of isolated case reports or limited clinical studies that have included a heterogeneous population of patients with the MELAS syndrome, other defects in oxidative phosphorylation or lactic acidosis due to disorders of pyruvate metabolism. Current approaches to the treatment of the MELAS syndrome are based on the use of antioxidants, respiratory chain substrates and cofactors in the form of vitamins; however, no consistent benefits have been observed with these treatments.

Screening of effective pharmacological treatments for MELAS syndrome using yeasts, fibroblasts and cybrid models of the disease.

PubMed

Garrido-Maraver, Juan; Cordero, Mario D; Moñino, Irene Domínguez; Pereira-Arenas, Sheila; Lechuga-Vieco, Ana V; Cotán, David; De la Mata, Mario; Oropesa-Ávila, Manuel; De Miguel, Manuel; Bautista Lorite, Juan; Rivas Infante, Eloy; Alvarez-Dolado, Manuel; Navas, Plácido; Jackson, Sandra; Francisci, Silvia; Sánchez-Alcázar, José A

2012-11-01

MELAS (mitochondrial encephalomyopathy, lactic acidosis and stroke-like episodes) is a mitochondrial disease most usually caused by point mutations in tRNA genes encoded by mitochondrial DNA (mtDNA). Approximately 80% of cases of MELAS syndrome are associated with a m.3243A > G mutation in the MT-TL1 gene, which encodes the mitochondrial tRNALeu (UUR). Currently, no effective treatments are available for this chronic progressive disorder. Treatment strategies in MELAS and other mitochondrial diseases consist of several drugs that diminish the deleterious effects of the abnormal respiratory chain function, reduce the presence of toxic agents or correct deficiencies in essential cofactors. We evaluated the effectiveness of some common pharmacological agents that have been utilized in the treatment of MELAS, in yeast, fibroblast and cybrid models of the disease. The yeast model harbouring the A14G mutation in the mitochondrial tRNALeu(UUR) gene, which is equivalent to the A3243G mutation in humans, was used in the initial screening. Next, the most effective drugs that were able to rescue the respiratory deficiency in MELAS yeast mutants were tested in fibroblasts and cybrid models of MELAS disease. According to our results, supplementation with riboflavin or coenzyme Q(10) effectively reversed the respiratory defect in MELAS yeast and improved the pathologic alterations in MELAS fibroblast and cybrid cell models. Our results indicate that cell models have great potential for screening and validating the effects of novel drug candidates for MELAS treatment and presumably also for other diseases with mitochondrial impairment. © 2012 The Authors. British Journal of Pharmacology © 2012 The British Pharmacological Society.

A Wide Range of 3243A>G/tRNALeu(UUR) (MELAS) Mutation Loads May Segregate in Offspring through the Female Germline Bottleneck

PubMed Central

Pallotti, Francesco; Binelli, Giorgio; Fabbri, Raffaella; Valentino, Maria L.; Vicenti, Rossella; Macciocca, Maria; Cevoli, Sabina; Baruzzi, Agostino; DiMauro, Salvatore; Carelli, Valerio

2014-01-01

Segregation of mutant mtDNA in human tissues and through the germline is debated, with no consensus about the nature and size of the bottleneck hypothesized to explain rapid generational shifts in mutant loads. We investigated two maternal lineages with an apparently different inheritance pattern of the same pathogenic mtDNA 3243A>G/tRNALeu(UUR) (MELAS) mutation. We collected blood cells, muscle biopsies, urinary epithelium and hair follicles from 20 individuals, as well as oocytes and an ovarian biopsy from one female mutation carrier, all belonging to the two maternal lineages to assess mutant mtDNA load, and calculated the theoretical germline bottleneck size (number of segregating units). We also evaluated “mother-to-offspring” segregations from the literature, for which heteroplasmy assessment was available in at least three siblings besides the proband. Our results showed that mutation load was prevalent in skeletal muscle and urinary epithelium, whereas in blood cells there was an inverse correlation with age, as previously reported. The histoenzymatic staining of the ovarian biopsy failed to show any cytochrome-c-oxidase defective oocyte. Analysis of four oocytes and one offspring from the same unaffected mother of the first family showed intermediate heteroplasmic mutant loads (10% to 75%), whereas very skewed loads of mutant mtDNA (0% or 81%) were detected in five offspring of another unaffected mother from the second family. Bottleneck size was 89 segregating units for the first mother and 84 for the second. This was remarkably close to 88, the number of “segregating units” in the “mother-to-offspring” segregations retrieved from literature. In conclusion, a wide range of mutant loads may be found in offspring tissues and oocytes, resulting from a similar theoretical bottleneck size. PMID:24805791

Screening of effective pharmacological treatments for MELAS syndrome using yeasts, fibroblasts and cybrid models of the disease

PubMed Central

Garrido-Maraver, Juan; Cordero, Mario D; Moñino, Irene Domínguez; Pereira-Arenas, Sheila; Lechuga-Vieco, Ana V; Cotán, David; De la Mata, Mario; Oropesa-Ávila, Manuel; De Miguel, Manuel; Bautista Lorite, Juan; Rivas Infante, Eloy; Álvarez-Dolado, Manuel; Navas, Plácido; Jackson, Sandra; Francisci, Silvia; Sánchez-Alcázar, José A

2012-01-01

BACKGROUND AND PURPOSE MELAS (mitochondrial encephalomyopathy, lactic acidosis and stroke-like episodes) is a mitochondrial disease most usually caused by point mutations in tRNA genes encoded by mitochondrial DNA (mtDNA). Approximately 80% of cases of MELAS syndrome are associated with a m.3243A > G mutation in the MT-TL1 gene, which encodes the mitochondrial tRNALeu (UUR). Currently, no effective treatments are available for this chronic progressive disorder. Treatment strategies in MELAS and other mitochondrial diseases consist of several drugs that diminish the deleterious effects of the abnormal respiratory chain function, reduce the presence of toxic agents or correct deficiencies in essential cofactors. EXPERIMENTAL APPROACH We evaluated the effectiveness of some common pharmacological agents that have been utilized in the treatment of MELAS, in yeast, fibroblast and cybrid models of the disease. The yeast model harbouring the A14G mutation in the mitochondrial tRNALeu(UUR) gene, which is equivalent to the A3243G mutation in humans, was used in the initial screening. Next, the most effective drugs that were able to rescue the respiratory deficiency in MELAS yeast mutants were tested in fibroblasts and cybrid models of MELAS disease. KEY RESULTS According to our results, supplementation with riboflavin or coenzyme Q10 effectively reversed the respiratory defect in MELAS yeast and improved the pathologic alterations in MELAS fibroblast and cybrid cell models. CONCLUSIONS AND IMPLICATIONS Our results indicate that cell models have great potential for screening and validating the effects of novel drug candidates for MELAS treatment and presumably also for other diseases with mitochondrial impairment. PMID:22747838

Pathology of mitochondria in MELAS syndrome: an ultrastructural study.

PubMed

Felczak, Paulina; Lewandowska, Eliza; Stępniak, Iwona; Ołdak, Monika; Pollak, Agnieszka; Lechowicz, Urszula; Pasennik, Elżbieta; Stępień, Tomasz; Wierzba-Bobrowicz, Teresa

Ultrastructural changes in skeletal muscle biopsy in a 24-year-old female patient with clinically suspected mitochondrial encephalomyopathy lactic acidosis and stroke-like episodes (MELAS) syndrome are presented. We observed proliferation and/or pleomorphism of mitochondria in skeletal muscle and smooth muscle cells of arterioles, as well as in pericytes of capillaries. Paracrystalline inclusions were found only in damaged mitochondria of skeletal muscle. Genetic testing revealed a point mutation in A3243G tRNALeu(UUR) typical for MELAS syndrome. We conclude that differentiated pathological changes of mitochondria in the studied types of cells may be associated with the different energy requirements of these cells.

Asthma and Air Quality in the Presence of Fires - A Foundation for Public Health Policy in Florida

NASA Technical Reports Server (NTRS)

Crosson, William; Al-Hamdan, Mohammad; Estes, Maurice, Jr.; Estes, Sue; Luvall, Jeffrey; Sifford, Cody; Young, Linda

2012-01-01

Outdoor air quality and its associated impacts on respiratory problems in Florida are of public health significance. Air quality in Florida can be poor during the extended wildfire season, threatening persons with compromised respiratory systems each year. Studies have demonstrated that particulate matter, which is generally elevated in the vicinity of wildfires, is associated with increases in hospital admissions and occurrences of acute asthma exacerbations. However, few studies have examined the modifying effect of socio-demographic characteristics of cities or regional areas on the relationship between air quality and health outcomes. In an ongoing university/multi-agency project, asthma hospital/emergency room (patient) data are being used to create a health outcome indicator of human response to environmental air quality. Environmental data are derived from satellite measurements, with special attention being given to the effect of wildfires and prescribed burns on air quality. This presentation will focus on the environmental data sets particulate matter, location of fires, smoke plumes that are being collected and processed for linkage with health data. After this linkage has been performed, space-time models of asthma rates as a function of air quality data and socio-demographic variables will be developed and validated. The Florida Department of Health (FDOH) will work with county health department staff and representatives from the medical community to establish a protocol with triggers for issuing public health advisories/alerts based on the developed and validated health outcome indicators. From this effort, a science-based policy for issuing public health advisories/alerts for asthma relating to air quality will be developed, giving FDOH the ability to (1) predict, with stated levels of uncertainty, case load of hospital admissions based on air quality, (2) reduce asthma exacerbations by forewarning asthmatics to limit outside activities on poor air quality days, (3) apply management practices on the rates of hospital/emergency room visits for asthma, and (4) provide information that would help translate interventions into policy decisions, thereby reducing the economic burden and increasing well being of asthmatics. Further, the results of the study will be incorporated into Florida s Environmental Public Health Tracking (EPHT) program, which is part of the Centers for Disease Control and Prevention's (CDC's) EPHT network.

Performance comparison between the mycobacteria growth indicator tube system and Löwenstein-Jensen medium in the routine detection of Mycobacterium tuberculosis at public health care facilities in Rio de Janeiro, Brazil: preliminary results of a pragmatic clinical trial.

PubMed

Moreira, Adriana da Silva Rezende; Huf, Gisele; Vieira, Maria Armanda; Fonseca, Leila; Ricks, Monica; Kritski, Afrânio Lineu

2013-01-01

In view of the fact that the World Health Organization has recommended the use of the mycobacteria growth indicator tube (MGIT) 960 system for the diagnosis of tuberculosis and that there is as yet no evidence regarding the clinical impact of its use in health care systems, we conducted a pragmatic clinical trial to evaluate the clinical performance and cost-effectiveness of the use of MGIT 960 at two health care facilities in the city of Rio de Janeiro, Brazil, where the incidence of tuberculosis is high. Here, we summarize the methodology and preliminary results of the trial. (ISRCTN.org Identifier: ISRCTN79888843 [http://isrctn.org/]) In view of the fact that the World Health Organization has recommended the use of the mycobacteria growth indicator tube (MGIT) 960 system for the diagnosis of tuberculosis and that there is as yet no evidence regarding the clinical impact of its use in health care systems, we conducted a pragmatic clinical trial to evaluate the clinical performance and cost-effectiveness of the use of MGIT 960 at two health care facilities in the city of Rio de Janeiro, Brazil, where the incidence of tuberculosis is high. Here, we summarize the methodology and preliminary results of the trial. (ISRCTN.org Identifier: ISRCTN79888843 [http://isrctn.org/]).

Gaining and sustaining schistosomiasis control: study protocol and baseline data prior to different treatment strategies in five African countries.

PubMed

Ezeamama, Amara E; He, Chun-La; Shen, Ye; Yin, Xiao-Ping; Binder, Sue C; Campbell, Carl H; Rathbun, Stephen; Whalen, Christopher C; N'Goran, Eliézer K; Utzinger, Jürg; Olsen, Annette; Magnussen, Pascal; Kinung'hi, Safari; Fenwick, Alan; Phillips, Anna; Ferro, Josefo; Karanja, Diana M S; Mwinzi, Pauline N M; Montgomery, Susan; Secor, W Evan; Hamidou, Amina; Garba, Amadou; King, Charles H; Colley, Daniel G

2016-05-26

The Schistosomiasis Consortium for Operational Research and Evaluation (SCORE) was established in 2008 to answer strategic questions about schistosomiasis control. For programme managers, a high-priority question is: what are the most cost-effective strategies for delivering preventive chemotherapy (PCT) with praziquantel (PZQ)? This paper describes the process SCORE used to transform this question into a harmonized research protocol, the study design for answering this question, the village eligibility assessments and data resulting from the first year of the study. Beginning in 2009, SCORE held a series of meetings to specify empirical questions and design studies related to different schedules of PCT for schistosomiasis control in communities with high (gaining control studies) and moderate (sustaining control studies) prevalence of Schistosoma infection among school-aged children. Seven studies are currently being implemented in five African countries. During the first year, villages were screened for eligibility, and data were collected on prevalence and intensity of infection prior to randomisation and the implementation of different schemes of PZQ intervention strategies. These studies of different treatment schedules with PZQ will provide the most comprehensive data thus far on the optimal frequency and continuity of PCT for schistosomiasis infection and morbidity control. We expect that the study outcomes will provide data for decision-making for country programme managers and a rich resource of information to the schistosomiasis research community. The trials are registered at International Standard Randomised Controlled Trial registry (identifiers: ISRCTN99401114 , ISRCTN14849830 , ISRCTN16755535 , ISRCTN14117624 , ISRCTN95819193 and ISRCTN32045736 ).

The protocols for the 10/66 dementia research group population-based research programme.

PubMed

Prince, Martin; Ferri, Cleusa P; Acosta, Daisy; Albanese, Emiliano; Arizaga, Raul; Dewey, Michael; Gavrilova, Svetlana I; Guerra, Mariella; Huang, Yueqin; Jacob, K S; Krishnamoorthy, E S; McKeigue, Paul; Rodriguez, Juan Llibre; Salas, Aquiles; Sosa, Ana Luisa; Sousa, Renata M M; Stewart, Robert; Uwakwe, Richard

2007-07-20

Latin America, China and India are experiencing unprecedentedly rapid demographic ageing with an increasing number of people with dementia. The 10/66 Dementia Research Group's title refers to the 66% of people with dementia that live in developing countries and the less than one tenth of population-based research carried out in those settings. This paper describes the protocols for the 10/66 population-based and intervention studies that aim to redress this imbalance. Cross-sectional comprehensive one phase surveys have been conducted of all residents aged 65 and over of geographically defined catchment areas in ten low and middle income countries (India, China, Nigeria, Cuba, Dominican Republic, Brazil, Venezuela, Mexico, Peru and Argentina), with a sample size of between 1000 and 3000 (generally 2000). Each of the studies uses the same core minimum data set with cross-culturally validated assessments (dementia diagnosis and subtypes, mental disorders, physical health, anthropometry, demographics, extensive non communicable disease risk factor questionnaires, disability/functioning, health service utilisation, care arrangements and caregiver strain). Nested within the population based studies is a randomised controlled trial of a caregiver intervention for people with dementia and their families (ISRCTN41039907; ISRCTN41062011; ISRCTN95135433; ISRCTN66355402; ISRCTN93378627; ISRCTN94921815). A follow up of 2.5 to 3.5 years will be conducted in 7 countries (China, Cuba, Dominican Republic, Venezuela, Mexico, Peru and Argentina) to assess risk factors for incident dementia, stroke and all cause and cause-specific mortality; verbal autopsy will be used to identify causes of death. The 10/66 DRG baseline population-based studies are nearly complete. The incidence phase will be completed in 2009. All investigators are committed to establish an anonymised file sharing archive with monitored public access. Our aim is to create an evidence base to empower advocacy, raise awareness about dementia, and ensure that the health and social care needs of older people are anticipated and met.

The protocols for the 10/66 dementia research group population-based research programme

PubMed Central

Prince, Martin; Ferri, Cleusa P; Acosta, Daisy; Albanese, Emiliano; Arizaga, Raul; Dewey, Michael; Gavrilova, Svetlana I; Guerra, Mariella; Huang, Yueqin; Jacob, KS; Krishnamoorthy, ES; McKeigue, Paul; Rodriguez, Juan Llibre; Salas, Aquiles; Sosa, Ana Luisa; Sousa, Renata MM; Stewart, Robert; Uwakwe, Richard

2007-01-01

Background Latin America, China and India are experiencing unprecedentedly rapid demographic ageing with an increasing number of people with dementia. The 10/66 Dementia Research Group's title refers to the 66% of people with dementia that live in developing countries and the less than one tenth of population-based research carried out in those settings. This paper describes the protocols for the 10/66 population-based and intervention studies that aim to redress this imbalance. Methods/design Cross-sectional comprehensive one phase surveys have been conducted of all residents aged 65 and over of geographically defined catchment areas in ten low and middle income countries (India, China, Nigeria, Cuba, Dominican Republic, Brazil, Venezuela, Mexico, Peru and Argentina), with a sample size of between 1000 and 3000 (generally 2000). Each of the studies uses the same core minimum data set with cross-culturally validated assessments (dementia diagnosis and subtypes, mental disorders, physical health, anthropometry, demographics, extensive non communicable disease risk factor questionnaires, disability/functioning, health service utilisation, care arrangements and caregiver strain). Nested within the population based studies is a randomised controlled trial of a caregiver intervention for people with dementia and their families (ISRCTN41039907; ISRCTN41062011; ISRCTN95135433; ISRCTN66355402; ISRCTN93378627; ISRCTN94921815). A follow up of 2.5 to 3.5 years will be conducted in 7 countries (China, Cuba, Dominican Republic, Venezuela, Mexico, Peru and Argentina) to assess risk factors for incident dementia, stroke and all cause and cause-specific mortality; verbal autopsy will be used to identify causes of death. Discussion The 10/66 DRG baseline population-based studies are nearly complete. The incidence phase will be completed in 2009. All investigators are committed to establish an anonymised file sharing archive with monitored public access. Our aim is to create an evidence base to empower advocacy, raise awareness about dementia, and ensure that the health and social care needs of older people are anticipated and met. PMID:17659078

Mitochondrial tRNALeu(UUR) C3275T, tRNAGln T4363C and tRNALys A8343G mutations may be associated with PCOS and metabolic syndrome.

PubMed

Ding, Yu; Xia, Bo-Hou; Zhang, Cai-Juan; Zhuo, Guang-Chao

2018-02-05

Polycystic ovary syndrome (PCOS) is a very prevalent endocrine disease affecting reproductive women. Clinically, patients with this disorder are more vulnerable to develop type 2 diabetes mellitus (T2DM), cardiovascular events, as well as metabolic syndrome (MetS). To date, the molecular mechanism underlying PCOS remains largely unknown. Previously, we showed that mitochondrial dysfunction caused by mitochondrial DNA (mtDNA) mutation was an important cause for PCOS. In the current study, we described the clinical and biochemical features of a three-generation pedigree with maternally transmitted MetS, combined with PCOS. A total of three matrilineal relatives exhibited MetS including obesity, high triglyceride (TG) and Hemoglobin A1c (HbA1c) levels, and hypertension. Whereas one patient from the third generation manifestated PCOS. Mutational analysis of the whole mitochondrial genes from the affected individuals identified a set of genetic variations belonging to East Asia haplogroup B4b1c. Among these variants, the homoplasmic C3275T mutation disrupted a highly evolutionary conserved base-pairing (28A-46C) on the variable region of tRNA Leu(UUR) , whereas the T4363C mutation created a new base-pairing (31T-37A) in the anticodon stem of tRNA Gln , furthermore, the A8343G mutation occurred at the very conserved position of tRNA Lys and may result the failure in mitochondrial tRNAs (mt-tRNAs) metabolism. Biochemical analysis revealed the deficiency in mitochondrial functions including lower levels of mitochondrial membrane potential (MMP), ATP production and mtDNA copy number, while a significantly increased reactive oxygen species (ROS) generation was observed in polymononuclear leukocytes (PMNs) from the individuals carrying these mt-tRNA mutations, suggesting that these mutations may cause mitochondrial dysfunction that was responsible for the clinical phenotypes. Taken together, our data indicated that mt-tRNA mutations were associated with MetS and PCOS in this family, which shaded additional light into the pathophysiology of PCOS that were manifestated by mitochondrial dysfunction. Copyright © 2017 Elsevier B.V. All rights reserved.

The clinical characteristics of patients with mitochondrial tRNA Leu(UUR)m.3243A > G mutation: Compared with type 1 diabetes and early onset type 2 diabetes.

PubMed

Zhu, Jie; Yang, Peng; Liu, Xiang; Yan, Li; Rampersad, Sharvan; Li, Feng; Li, Hong; Sheng, Chunjun; Cheng, Xiaoyun; Zhang, Manna; Qu, Shen

2017-08-01

This study presents nine patients with mitochondrial tRNA Leu (UUR) m.3243A>G mutation and compares the clinical characteristics and diabetes complications with type 1 diabetes (T1DM) or early onset type 2 diabetes (T2DM). The study covers 9 patients with MIDD, 33 patients with T1DM and 86 patients (age of onset ≤35years) with early onset T2DM, matched for sex, age at onset of diabetes, duration of diabetes. All patients with MIDD were confirmed as carrying the m.3243A>G mitochondrial DNA mutation. Serum HbA1c, beta-cell function, retinal and renal complications of diabetes, bone metabolic markers, lumbar spine and femoral neck BMD bone mineral density were compared to characterize the clinical features of all patients. Nine patients were from five unrelated families, and the mean (SD) onset age of those patients was 31.2±7.2year. Two patients required insulin at presentation, and six patients progressed to insulin requirement after a mean of 7.2years. β-Cell function in the MIDD group was intermediate between T1DM and early-onset T2DM. In MIDD, four patients were diagnosed as diabetic retinopathy (4/9) and five patients (5/9) had macroalbuminuria. The number of patients with diabetic retinopathy and macroalbuminuria in the MIDD group was comparable to T1DM or early-onset T2DM. The rate of osteoporosis (BMD T-score<-2.5 SD) in the patient with MIDD was higher than the T1DM or early-onset T2DM group. Our study indicates that of the nine subjects with MIDD, three patients (1-II-1, 1-II-3, 1-II-4) who came from the same family had a history of acute pancreatitis. Compared with T1DM or early-onset T2DM matched for sex, age, duration of diabetes, MIDD patients had the highest rate of osteoporosis. Copyright © 2017 Elsevier Inc. All rights reserved.

When should MELAS (Mitochondrial myopathy, Encephalopathy, Lactic Acidosis, and Stroke-like episodes) be the diagnosis?

PubMed

Lorenzoni, Paulo José; Werneck, Lineu Cesar; Kay, Cláudia Suemi Kamoi; Silvado, Carlos Eduardo Soares; Scola, Rosana Herminia

2015-11-01

Mitochondrial myopathy, Encephalopathy, Lactic Acidosis, and Stroke-like episodes (MELAS) is a rare mitochondrial disorder. Diagnostic criteria for MELAS include typical manifestations of the disease: stroke-like episodes, encephalopathy, evidence of mitochondrial dysfunction (laboratorial or histological) and known mitochondrial DNA gene mutations. Clinical features of MELAS are not necessarily uniform in the early stages of the disease, and correlations between clinical manifestations and physiopathology have not been fully elucidated. It is estimated that point mutations in the tRNALeu(UUR) gene of the DNAmt, mainly A3243G, are responsible for more of 80% of MELAS cases. Morphological changes seen upon muscle biopsy in MELAS include a substantive proportion of ragged red fibers (RRF) and the presence of vessels with a strong reaction for succinate dehydrogenase. In this review, we discuss mainly diagnostic criterion, clinical and laboratory manifestations, brain images, histology and molecular findings as well as some differential diagnoses and current treatments.

Summary of selected U.S. Geological survey data on domestic well water quality for the Centers for Disease Control's National Environmental Public Health Tracking Program

USGS Publications Warehouse

Bartholomay, Roy C.; Carter, Janet M.; Qi, Sharon L.; Squillace, Paul J.; Rowe, Gary L.

2007-01-01

About 10 to 30 percent of the population in most States uses domestic (private) water supply. In many States, the total number of people served by domestic supplies can be in the millions. The water quality of domestic supplies is inconsistently regulated and generally not well characterized. The U.S. Geological Survey (USGS) has two water-quality data sets in the National Water Information System (NWIS) database that can be used to help define the water quality of domestic-water supplies: (1) data from the National Water-Quality Assessment (NAWQA) Program, and (2) USGS State data. Data from domestic wells from the NAWQA Program were collected to meet one of the Program's objectives, which was to define the water quality of major aquifers in the United States. These domestic wells were located primarily in rural areas. Water-quality conditions in these major aquifers as defined by the NAWQA data can be compared because of the consistency of the NAWQA sampling design, sampling protocols, and water-quality analyses. The NWIS database is a repository of USGS water data collected for a variety of projects; consequently, project objectives and analytical methods vary. This variability can bias statistical summaries of contaminant occurrence and concentrations; nevertheless, these data can be used to define the geographic distribution of contaminants. Maps created using NAWQA and USGS State data in NWIS can show geographic areas where contaminant concentrations may be of potential human-health concern by showing concentrations relative to human-health water-quality benchmarks. On the basis of national summaries of detection frequencies and concentrations relative to U.S. Environmental Protection Agency (USEPA) human-health benchmarks for trace elements, pesticides, and volatile organic compounds, 28 water-quality constituents were identified as contaminants of potential human-health concern. From this list, 11 contaminants were selected for summarization of water-quality data in 16 States (grantee States) that were funded by the Environmental Public Health Tracking (EPHT) Program of the Centers for Disease Control and Prevention (CDC). Only data from domestic-water supplies were used in this summary because samples from these wells are most relevant to human exposure for the targeted population. Using NAWQA data, the concentrations of the 11 contaminants were compared to USEPA human-health benchmarks. Using NAWQA and USGS State data in NWIS, the geographic distribution of the contaminants were mapped for the 16 grantee States. Radon, arsenic, manganese, nitrate, strontium, and uranium had the largest percentages of samples with concentrations greater than their human-health benchmarks. In contrast, organic compounds (pesticides and volatile organic compounds) had the lowest percentages of samples with concentrations greater than human-health benchmarks. Results of data retrievals and spatial analysis were compiled for each of the 16 States and are presented in State summaries for each State. Example summary tables, graphs, and maps based on USGS data for New Jersey are presented to illustrate how USGS water-quality and associated ancillary geospatial data can be used by the CDC to address goals and objectives of the EPHT Program.

MenAfriVac as an Antitetanus Vaccine

PubMed Central

Borrow, Ray; Tang, Yuxiao; Yakubu, Ahmadu; Kulkarni, Prasad S.; LaForce, F. Marc

2015-01-01

Background. The group A meningococcal conjugate vaccine, PsA-TT, uses tetanus toxoid (TT) as a carrier protein (PsA-TT). TT as a carrier protein in other conjugate vaccines is known to be immunogenic and generates a robust anti-TT response. Methods. Clinical studies in Africa assessed whether PsA-TT generated tetanus serologic responses when tested in African populations (toddlers to adults). Second, the high acceptance of PsA-TT mass immunization campaigns in the 1- to 29-year age group meant that a sizeable fraction of women of reproductive age received PsA-TT. Incidence data for neonatal tetanus were reviewed for countries with and without PsA-TT campaigns to check whether this had any impact on the incidence. Results. PsA-TT generated robust tetanus serologic responses in 1- to 29-year-olds, similar to those expected after a booster dose of TT. Neonatal cases of tetanus fell by 25% in countries that completed PsA-TT campaigns in 1- to 29-year-olds. Conclusions. Although these data are not yet definitive, they are consistent with the hypothesis that improved community immunity to tetanus as a result of the PsA-TT campaigns may be having an impact on the incidence of neonatal tetanus in sub-Saharan Africa. Clinical Trials Registration. ISRCTN17662153 (PsA-TT 001); ISRTCN78147026 (PsA-TT 002); ISRCTN87739946 (PsA-TT 003); ISRCTN46335400 (PsA-TT 003a); ISRCTN82484612 (PsA-TT 004); CTRI/2009/091/000368 (PsA-TT 005); PACTR ATMR2010030001913177 (PsA-TT 006); and PACTR201110000328305 (PsA-TT 007). PMID:26553690

Safety and efficacy of a freeze-dried trivalent antivenom for snakebites in the Brazilian Amazon: An open randomized controlled phase IIb clinical trial

PubMed Central

Mendonça-da-Silva, Iran; Magela Tavares, Antônio; Sachett, Jacqueline; Sardinha, José Felipe; Zaparolli, Lilian; Gomes Santos, Maria Fátima; Lacerda, Marcus

2017-01-01

Background In tropical areas, a major concern regarding snakebites treatment effectiveness relates to the failure in liquid antivenom (AV) distribution due to the lack of an adequate cold chain in remote areas. To minimize this problem, freeze-drying has been suggested to improve AV stability. Methods and findings This study compares the safety and efficacy of a freeze-dried trivalent antivenom (FDTAV) and the standard liquid AV provided by the Brazilian Ministry of Health (SLAV) to treat Bothrops, Lachesis and Crotalus snakebites. This was a prospective, randomized, open, phase IIb trial, carried out from June 2005 to May 2008 in the Brazilian Amazon. Primary efficacy endpoints were the suppression of clinical manifestations and return of hemostasis and renal function markers to normal ranges within the first 24 hours of follow-up. Primary safety endpoint was the presence of early adverse reactions (EAR) in the first 24 hours after treatment. FDTAV thermal stability was determined by estimating AV potency over one year at 56°C. Of the patients recruited, 65 and 51 were assigned to FDTAV and SLAV groups, respectively. Only mild EARs were reported, and they were not different between groups. There were no differences in fibrinogen (p = 0.911) and clotting time (p = 0.982) recovery between FDTAV and SLAV treated groups for Bothrops snakebites. For Lachesis and Crotalus snakebites, coagulation parameters and creatine phosphokinase presented normal values 24 hours after AV therapy for both antivenoms. Conclusions/Significance Since promising results were observed for efficacy, safety and thermal stability, our results indicate that FDTAV is suitable for a larger phase III trial. Trial registration ISRCTNregistry: ISRCTN12845255; DOI: 10.1186/ISRCTN12845255 (http://www.isrctn.com/ISRCTN12845255). PMID:29176824

Safety and efficacy of a freeze-dried trivalent antivenom for snakebites in the Brazilian Amazon: An open randomized controlled phase IIb clinical trial.

PubMed

Mendonça-da-Silva, Iran; Magela Tavares, Antônio; Sachett, Jacqueline; Sardinha, José Felipe; Zaparolli, Lilian; Gomes Santos, Maria Fátima; Lacerda, Marcus; Monteiro, Wuelton Marcelo

2017-11-01

In tropical areas, a major concern regarding snakebites treatment effectiveness relates to the failure in liquid antivenom (AV) distribution due to the lack of an adequate cold chain in remote areas. To minimize this problem, freeze-drying has been suggested to improve AV stability. This study compares the safety and efficacy of a freeze-dried trivalent antivenom (FDTAV) and the standard liquid AV provided by the Brazilian Ministry of Health (SLAV) to treat Bothrops, Lachesis and Crotalus snakebites. This was a prospective, randomized, open, phase IIb trial, carried out from June 2005 to May 2008 in the Brazilian Amazon. Primary efficacy endpoints were the suppression of clinical manifestations and return of hemostasis and renal function markers to normal ranges within the first 24 hours of follow-up. Primary safety endpoint was the presence of early adverse reactions (EAR) in the first 24 hours after treatment. FDTAV thermal stability was determined by estimating AV potency over one year at 56°C. Of the patients recruited, 65 and 51 were assigned to FDTAV and SLAV groups, respectively. Only mild EARs were reported, and they were not different between groups. There were no differences in fibrinogen (p = 0.911) and clotting time (p = 0.982) recovery between FDTAV and SLAV treated groups for Bothrops snakebites. For Lachesis and Crotalus snakebites, coagulation parameters and creatine phosphokinase presented normal values 24 hours after AV therapy for both antivenoms. Since promising results were observed for efficacy, safety and thermal stability, our results indicate that FDTAV is suitable for a larger phase III trial. ISRCTNregistry: ISRCTN12845255; DOI: 10.1186/ISRCTN12845255 (http://www.isrctn.com/ISRCTN12845255).

Pregnancy Exercise and Nutrition With Smartphone Application Support: A Randomized Controlled Trial.

PubMed

Kennelly, Maria A; Ainscough, Kate; Lindsay, Karen L; OʼSullivan, Elizabeth; Gibney, Eileen R; McCarthy, Mary; Segurado, Ricardo; DeVito, Giuseppe; Maguire, Orla; Smith, Thomas; Hatunic, Mensud; McAuliffe, Fionnuala M

2018-05-01

To evaluate the effect of a healthy lifestyle package (an antenatal behavior change intervention supported by smartphone application technology) on the incidence of gestational diabetes mellitus (GDM) in overweight and obese women. Women with body mass indexes (BMIs) 25-39.9 were enrolled into this randomized controlled trial. The intervention consisted of specific dietary and exercise advice that addressed behavior change supported by a tailor-designed smartphone application. Women in the control group received usual care. The primary outcome was the incidence of GDM at 28-30 weeks of gestation. To reduce GDM from 15% to 7.2%, we estimated that 506 women would be required to have 80% power to detect this effect size at a significance of .05, that is, 253 in each group. Between March 2013 and February 2016, 565 women were recruited with a mean BMI of 29.3 and mean gestational age of 15.5 weeks. The incidence of GDM did not differ between the two groups, 37 of 241 (15.4%) in the intervention group compared with 36 of 257 (14.1%) in the control group (relative risk 1.1, 95% CI 0.71-1.66, P=.71). A mobile health-supported behavioral intervention did not decrease the incidence of GDM. ISRCTN registry, https://www.isrctn.com/, ISRCTN29316280.

The m.3291T>C mt-tRNALeu(UUR) mutation is definitely pathogenic and causes multisystem mitochondrial disease

PubMed Central

Yarham, John W.; Blakely, Emma L.; Alston, Charlotte L.; Roberts, Mark E.; Ealing, John; Pal, Piyali; Turnbull, Douglass M.; McFarland, Robert; Taylor, Robert W.

2013-01-01

Mitochondrial tRNA point mutations are important causes of human disease, and have been associated with a diverse range of clinical phenotypes. Definitively proving the pathogenicity of any given mt-tRNA mutation requires combined molecular, genetic and functional studies. Subsequent evaluation of the mutation using a pathogenicity scoring system is often very helpful in concluding whether or not the mutation is causing disease. Despite several independent reports linking the m.3291T>C mutation to disease in humans, albeit in association with several different phenotypes, its pathogenicity remains controversial. A lack of conclusive functional evidence and an over-emphasis on the poor evolutionary conservation of the affected nucleotide have contributed to this controversy. Here we describe an adult patient who presented with deafness and lipomas and evidence of mitochondrial abnormalities in his muscle biopsy, who harbours the m.3291T > C mutation, providing conclusive evidence of pathogenicity through analysis of mutation segregation with cytochrome c oxidase (COX) deficiency in single muscle fibres, underlining the importance of performing functional studies when assessing pathogenicity. PMID:23273904

Myocardial dysfunction in mitochondrial diabetes treated with Coenzyme Q10.

PubMed

Salles, João Eduardo; Moisés, Valdir A; Almeida, Dirceu R; Chacra, Antonio R; Moisés, Regina S

2006-04-01

Maternally-inherited diabetes and deafness (MIDD) has been related to an A to G transition in the mitochondrial tRNA Leu (UUR) gene at the base pair 3243. Although some previous articles have reported that this mutation may be a cause of cardiomyopathy in diabetes, the degree of cardiac involvement and a specific treatment has not been established. Here, we reported a case of a patient with MIDD who developed congestive heart failure and the therapeutic usefulness of Coenzyme Q10 (CoQ10). In our patient, after the introduction of Coenzyme Q10 150 mg/day, there was a gradual improvement on left ventricular function evaluated by echocardiography. The fractional shortening (FS) and ejection fraction (EF) increased from 26 to 34% and from 49 to 64%, respectively. No side effects were noted. Three months after CoQ10 discontinuation, the parameters of systolic function evaluated by echocardiography decreased, suggesting that CoQ10 had a beneficial effect. Identification of diabetes and cardiomyopathy due to mitochondrial gene mutation may have therapeutic implications and Coenzyme Q10 is a possible adjunctive treatment in such patients.

Unusual occurrence of intestinal pseudo obstruction in a patient with maternally inherited diabetes and deafness (MIDD) and favorable outcome with coenzyme Q10.

PubMed

Bergamin, Carla S; Rolim, Luiz Clemente; Dib, Sergio A; Moisés, Regina S

2008-11-01

Maternally inherited diabetes and deafness (MIDD) has been related to an A to G transition in the mitochondrial tRNA Leu (UUR) gene at the base pair 3243. This subtype of diabetes is characterized by maternal transmission, young age at onset and bilateral hearing impairment. Besides diabetes and deafness, the main diagnostic features, a wide range of multisystemic symptoms may be associated with the A3243G mutation. Organs that are most metabolically active, such as muscles, myocardium, retina, cochlea, kidney and brain are frequently affected. Gastrointestinal tract symptoms are also common in patients with mitochondrial disease and constipation and diarrhea are the most frequent manifestations. However, there are few prior reports of intestinal pseudo obstruction in MIDD patients. Here we report the case of a patient with MIDD associated with the mtDNA A3243G mutation who developed chronic intestinal pseudo obstruction, and the introduction of Coenzyme Q10 as adjunctive therapy led to a solution of the pseudo obstruction.

The effect of an affordable daycare program on health and economic well-being in Rajasthan, India: protocol for a cluster-randomized impact evaluation study.

PubMed

Nandi, Arijit; Maloney, Shannon; Agarwal, Parul; Chandrashekar, Anoushaka; Harper, Sam

2016-06-09

The provision of affordable and reliable daycare services is a potentially important policy lever for empowering Indian women. Access to daycare might reduce barriers to labor force entry and generate economic opportunities for women, improve education for girls caring for younger siblings, and promote nutrition and learning among children. However, empirical evidence concerning the effects of daycare programs in low-and-middle-income countries is scarce. This cluster-randomized trial will estimate the effect of a community-based daycare program on health and economic well-being over the life-course among women and children living in rural Rajasthan, India. This three-year study takes place in rural communities from five blocks in the Udaipur District of rural Rajasthan. The intervention is the introduction of a full-time, affordable, community-based daycare program. At baseline, 3177 mothers with age eligible children living in 160 village hamlets were surveyed. After the baseline, these hamlets were randomized to the intervention or control groups and respondents will be interviewed on two more occasions. Primary social and economic outcomes include women's economic status and economic opportunity, women's empowerment, and children's educational attainment. Primary health outcomes include women's mental health, as well as children's nutritional status. This interdisciplinary research initiative will provide rigorous evidence concerning the effects of daycare in lower-income settings. In doing so it will address an important research gap and has the potential to inform policies for improving the daycare system in India in ways that promote health and economic well-being. (1) The ISRCTN clinical trial registry (ISRCTN45369145), http://www.isrctn.com/ISRCTN45369145 , registered on May 16, 2016 and (2) The American Economic Association's registry for randomized controlled trials (AEARCTR-0000774), http://www.socialscienceregistry.org/trials/774 , registered on July 15, 2015.

Quantifying Hospital-Acquired Carriage of Extended-Spectrum Beta-Lactamase-Producing Enterobacteriaceae Among Patients in Dutch Hospitals.

PubMed

Kluytmans-van den Bergh, Marjolein F Q; van Mens, Suzan P; Haverkate, Manon R; Bootsma, Martin C J; Kluytmans, Jan A J W; Bonten, Marc J M

2018-01-01

BACKGROUND Extended-spectrum β-lactamase-producing Enterobacteriaceae (ESBL-E) are emerging worldwide. Contact precautions are recommended for known ESBL-E carriers to control the spread of ESBL-E within hospitals. OBJECTIVE This study quantified the acquisition of ESBL-E rectal carriage among patients in Dutch hospitals, given the application of contact precautions. METHODS Data were used from 2 cluster-randomized studies on isolation strategies for ESBL-E: (1) the SoM study, performed in 14 Dutch hospitals from 2011 through 2014 and (2) the R-GNOSIS study, for which data were limited to those collected in a Dutch hospital in 2014. Perianal cultures were obtained, either during ward-based prevalence surveys (SoM), or at admission and twice weekly thereafter (R-GNOSIS). In both studies, contact precautions were applied to all known ESBL-E carriers. Estimates for acquisition of ESBL-E were based on the results of admission and discharge cultures from patients hospitalized for more than 2 days (both studies) and a Markov chain Monte Carlo (MCMC) model, applied to all patients hospitalized (R-GNOSIS). RESULTS The absolute risk of acquisition of ESBL-E rectal carriage ranged from 2.4% to 2.9% with an ESBL-E acquisition rate of 2.8 to 3.8 acquisitions per 1,000 patient days. In addition, 28% of acquisitions were attributable to patient-dependent transmission, and the per-admission reproduction number was 0.06. CONCLUSIONS The low ESBL-E acquisition rate in this study demonstrates that it is possible to control the nosocomial transmission of ESBL in a low-endemic, non-ICU setting where Escherichia coli is the most prevalent ESBL-E and standard and contact precautions are applied for known ESBL-E carriers. TRIAL REGISTRATION Nederlands Trialregister, NTR2799, http://www.trialregister.nl/trialreg/admin/rctview.asp?TC=2799; ISRCTN Registry, ISRCTN57648070, http://www.isrctn.com/ISRCTN57648070 Infect Control Hosp Epidemiol 2018;39:32-39.

Making a decision about trial participation: the feasibility of measuring deliberation during the informed consent process for clinical trials.

PubMed

Gillies, Katie; Elwyn, Glyn; Cook, Jonathan

2014-07-30

Informed consent of trial participants is both an ethical and a legal requirement. When facing a decision about trial participation, potential participants are provided with information about the trial and have the opportunity to have any questions answered before their degree of 'informed-ness' is assessed, usually subjectively, and before they are asked to sign a consent form. Currently, standardised methods for assessing informed consent have tended to be focused on aspects of understanding and associated outcomes, rather than on the process of consent and the steps associated with decision-making. Potential trial participants who were approached regarding participation in one of three randomised controlled trials were asked to complete a short questionnaire to measure their deliberation about trial participation. A total of 136 participants completed the 10-item questionnaire (DelibeRATE) before they made an explicit decision about trial participation (defined as signing the clinical trial consent form). Overall DelibeRATE scores were compared and investigated for differences between trial consenters and refusers. No differences in overall DelibeRATE scores were identified. In addition, there was no significant difference between overall score and the decision to participate, or not, in the parent trial. To our knowledge, this is the first study to prospectively measure the deliberation stage of the informed consent decision-making process of potential trial participants across different conditions and clinical areas. Although there were no differences detected in overall scores or scores of trial consenters and refusers, we did identify some interesting findings. These findings should be taken into consideration by those designing trials and others interested in developing and implementing measures of potential trial participants decision making during the informed consent process for research. International Standard Randomised Controlled Trial Number (ISRCTN) Register ISRCTN60695184 (date of registration: 13 May 2009), ISRCTN80061723 (date of registration: 8 March 2010), ISRCTN69423238 (date of registration: 18 November 2010).

Ethical Challenges and Lessons Learned During the Clinical Development of a Group A Meningococcal Conjugate Vaccine.

PubMed

Martellet, Lionel; Sow, Samba O; Diallo, Aldiouma; Hodgson, Abraham; Kampmann, Beate; Hirve, Siddhivinayak; Tapia, Milagritos; Haidara, Fadima Cheick; Ndiaye, Assane; Diarra, Bou; Ansah, Patrick Odum; Akinsola, Adebayo; Idoko, Olubukola T; Adegbola, Richard A; Bavdekar, Ashish; Juvekar, Sanjay; Viviani, Simonetta; Enwere, Godwin C; Marchetti, Elisa; Chaumont, Julie; Makadi, Marie-Francoise; Pallardy, Flore; Kulkarni, Prasad S; Preziosi, Marie-Pierre; LaForce, F Marc

2015-11-15

The group A meningococcal vaccine (PsA-TT) clinical development plan included clinical trials in India and in the West African region between 2005 and 2013. During this period, the Meningitis Vaccine Project (MVP) accumulated substantial experience in the ethical conduct of research to the highest standards. Because of the public-private nature of the sponsorship of these trials and the extensive international collaboration with partners from a diverse setting of countries, the ethical review process was complex and required strategic, timely, and attentive communication to ensure the smooth review and approval for the clinical studies. Investigators and their site teams fostered strong community relationships prior to, during, and after the studies to ensure the involvement and the ownership of the research by the participating populations. As the clinical work proceeded, investigators and sponsors responded to specific questions of informed consent, pregnancy testing, healthcare, disease prevention, and posttrial access. Key factors that led to success included (1) constant dialogue between partners to explore and answer all ethical questions; (2) alertness and preparedness for emerging ethical questions during the research and in the context of evolving international ethics standards; and (3) care to assure that approaches were acceptable in the diverse community contexts. Many of the ethical issues encountered during the PsA-TT clinical development are familiar to groups conducting field trials in different cultural settings. The successful approaches used by the MVP clinical team offer useful examples of how these problems were resolved. ISRCTN17662153 (PsA-TT-001); ISRTCN78147026 (PsA-TT-002); ISRCTN87739946 (PsA-TT-003); ISRCTN46335400 (PsA-TT-003a); ISRCTN82484612 (PsA-TT-004); CTRI/2009/091/000368 (PsA-TT-005); PACTR ATMR2010030001913177 (PsA-TT-006); PACTR201110000328305 (PsA-TT-007). © The Author 2015. Published by Oxford University Press on behalf of the Infectious Diseases Society of America.

Limited clinical relevance of imaging techniques in the follow-up of patients with advanced chronic lymphocytic leukemia: results of a meta-analysis.

PubMed

Eichhorst, Barbara F; Fischer, Kirsten; Fink, Anna-Maria; Elter, Thomas; Wendtner, Clemens M; Goede, Valentin; Bergmann, Manuela; Stilgenbauer, Stephan; Hopfinger, Georg; Ritgen, Matthias; Bahlo, Jasmin; Busch, Raymonde; Hallek, Michael

2011-02-10

The clinical value of imaging is well established for the follow-up of many lymphoid malignancies but not for chronic lymphocytic leukemia (CLL). A meta-analysis was performed with the dataset of 3 German CLL Study Group phase 3 trials (CLL4, CLL5, and CLL8) that included 1372 patients receiving first-line therapy for CLL. Response as well as progression during follow-up was reassessed according to the National Cancer Institute Working Group1996 criteria. A total of 481 events were counted as progressive disease during treatment or follow-up. Of these, 372 progressions (77%) were detected by clinical symptoms or blood counts. Computed tomography (CT) scans or ultrasound were relevant in 44 and 29 cases (9% and 6%), respectively. The decision for relapse treatment was determined by CT scan or ultrasound results in only 2 of 176 patients (1%). CT scan results had an impact on the prognosis of patients in complete remission only after the administration of conventional chemotherapy but not after chemoimmunotherapy. In conclusion, physical examination and blood count remain the methods of choice for staging and clinical follow-up of patients with CLL as recommended by the International Workshop on Chronic Lymphocytic Leukemia 2008 guidelines. These trials are registered at http://www.isrctn.org as ISRCTN 75653261 and ISRCTN 36294212 and at http://www.clinicaltrials.gov as NCT00281918.

Reducing Depression Through an Online Intervention: Benefits From a User Perspective

PubMed Central

Griffiths, Kathleen M

2016-01-01

Background Internet interventions are increasingly being recognized as effective in the treatment and prevention of mental health conditions; however, the usefulness of such programs from the perspective of the participants is often not reported. Objective This study explores the experiences of participants of a 12-week randomized controlled trial of an automated self-help training program (e-couch), with and without an Internet support group, targeting depression. Methods The study comprised a community sample of 298 participants who completed an online survey both prior to and on completion of an intervention for preventing or reducing depressive symptoms. Results Overall, participants reported a high level of confidence in the ability of an online intervention to improve a person’s understanding of depression. However, confidence that a website could help people learn skills for preventing depression was lower. Benefits reported by participants engaged in the intervention included increased knowledge regarding depression and its treatment, reduced depressive symptoms, increased work productivity, and improved ability to cope with everyday stress. A minority of participants reported concerns or problems resulting from participation in the interventions. Conclusions The findings provide consumer support for the effectiveness of this online intervention. Trial Registration International Standard Randomized Controlled Trial Number (ISRCTN): 65657330;http://www.isrctn.com/ISRCTN65657330 (Archived by WebCite at http://www.webcitation.org/6cwH8xwF0) PMID:26747378

The Use of GIS and Remotely Sensed Data in Environmental Public Health Tracking (EPHT): The HELIX-Atlanta Experience

NASA Technical Reports Server (NTRS)

Al-Hamdan, Mohammad Z.; Crosson, William L.; Limaye, Ashutosh S.; Estes, Maurice G., Jr.; Watts, Carol; Rickman, Douglas L.; Quattrochi, Dale A.; Qualters, Judith R.; Sinclair, Amber H.; Tolsma, Dennis D.;

Digital IAPT: the effectiveness & cost-effectiveness of internet-delivered interventions for depression and anxiety disorders in the Improving Access to Psychological Therapies programme: study protocol for a randomised control trial.

PubMed

Richards, Derek; Duffy, Daniel; Blackburn, Brid; Earley, Caroline; Enrique, Angel; Palacios, Jorge; Franklin, Matthew; Clarke, Gabriella; Sollesse, Sarah; Connell, Sarah; Timulak, Ladislav

2018-03-02

Depression and anxiety are common mental health disorders worldwide. The UK's Improving Access to Psychological Therapies (IAPT) programme is part of the National Health Service (NHS) designed to provide a stepped care approach to treating people with anxiety and depressive disorders. Cognitive Behavioural Therapy (CBT) is widely used, with computerised and internet-delivered cognitive behavioural therapy (cCBT and iCBT, respectively) being a suitable IAPT approved treatment alternative for step 2, low- intensity treatment. iCBT has accumulated a large empirical base for treating depression and anxiety disorders. However, the cost-effectiveness and impact of these interventions in the longer-term is not routinely assessed by IAPT services. The current study aims to evaluate the clinical and cost-effectiveness of internet-delivered interventions for symptoms of depression and anxiety disorders in IAPT. The study is a parallel-groups, randomised controlled trial examining the effectiveness and cost-effectiveness of iCBT interventions for depression and anxiety disorders, against a waitlist control group. The iCBT treatments are of 8 weeks duration and will be supported by regular post-session feedback by Psychological Wellbeing Practitioners. Assessments will be conducted at baseline, during, and at the end of the 8-week treatment and at 3, 6, 9, and 12-month follow-up. A diagnostic interview will be employed at baseline and 3-month follow-up. Participants in the waitlist control group will complete measures at baseline and week 8, at which point they will receive access to the treatment. All adult users of the Berkshire NHS Trust IAPT Talking Therapies Step 2 services will be approached to participate and measured against set eligibility criteria. Primary outcome measures will assess anxiety and depressive symptoms using the GAD-7 and PHQ-9, respectively. Secondary outcome measures will allow for the evaluation of long-term outcomes, mediators and moderators of outcome, and cost-effectiveness of treatment. Analysis will be conducted on a per protocol and intention-to-treat basis. This study seeks to evaluate the immediate and longer-term impact, as well as the cost effectiveness of internet-delivered interventions for depression and anxiety. This study will contribute to the already established literature on internet-delivered interventions worldwide. The study has the potential to show how iCBT can enhance service provision, and the findings will likely be generalisable to other health services. Current Controlled Trials ISRCTN ISRCTN91967124. DOI: https://doi.org/10.1186/ISRCTN91967124 . Web: http://www.isrctn.com/ISRCTN91967124 . Clinicaltrials.gov : NCT03188575. Trial registration date: June 8, 2017 (prospectively registered).

A randomised controlled trial of three or one breathing technique training sessions for breathlessness in people with malignant lung disease.

PubMed

Johnson, Miriam J; Kanaan, Mona; Richardson, Gerry; Nabb, Samantha; Torgerson, David; English, Anne; Barton, Rachael; Booth, Sara

2015-09-07

About 90 % of patients with intra-thoracic malignancy experience breathlessness. Breathing training is helpful, but it is unknown whether repeated sessions are needed. The present study aims to test whether three sessions are better than one for breathlessness in this population. This is a multi-centre randomised controlled non-blinded parallel arm trial. Participants were allocated to three sessions or single (1:2 ratio) using central computer-generated block randomisation by an independent Trials Unit and stratified for centre. The setting was respiratory, oncology or palliative care clinics at eight UK centres. Inclusion criteria were people with intrathoracic cancer and refractory breathlessness, expected prognosis ≥3 months, and no prior experience of breathing training. The trial intervention was a complex breathlessness intervention (breathing training, anxiety management, relaxation, pacing, and prioritisation) delivered over three hour-long sessions at weekly intervals, or during a single hour-long session. The main primary outcome was worst breathlessness over the previous 24 hours ('worst'), by numerical rating scale (0 = none; 10 = worst imaginable). Our primary analysis was area under the curve (AUC) 'worst' from baseline to 4 weeks. All analyses were by intention to treat. Between April 2011 and October 2013, 156 consenting participants were randomised (52 three; 104 single). Overall, the 'worst' score reduced from 6.81 (SD, 1.89) to 5.84 (2.39). Primary analysis [n = 124 (79 %)], showed no between-arm difference in the AUC: three sessions 22.86 (7.12) vs single session 22.58 (7.10); P value = 0.83); mean difference 0.2, 95 % CIs (-2.31 to 2.97). Complete case analysis showed a non-significant reduction in QALYs with three sessions (mean difference -0.006, 95 % CIs -0.018 to 0.006). Sensitivity analyses found similar results. The probability of the single session being cost-effective (threshold value of £20,000 per QALY) was over 80 %. There was no evidence that three sessions conferred additional benefits, including cost-effectiveness, over one. A single session of breathing training seems appropriate and minimises patient burden. Registry: ISRCTN; ISRCTN49387307; http://www.isrctn.com/ISRCTN49387307 ; registration date: 25/01/2011.

A randomized assessment of adding the kinase inhibitor lestaurtinib to first-line chemotherapy for FLT3-mutated AML.

PubMed

Knapper, Steven; Russell, Nigel; Gilkes, Amanda; Hills, Robert K; Gale, Rosemary E; Cavenagh, James D; Jones, Gail; Kjeldsen, Lars; Grunwald, Michael R; Thomas, Ian; Konig, Heiko; Levis, Mark J; Burnett, Alan K

2017-03-02

The clinical benefit of adding FMS-like tyrosine kinase-3 (FLT3)-directed small molecule therapy to standard first-line treatment of acute myeloid leukemia (AML) has not yet been established. As part of the UK AML15 and AML17 trials, patients with previously untreated AML and confirmed FLT3-activating mutations, mostly younger than 60 years, were randomly assigned either to receive oral lestaurtinib (CEP701) or not after each of 4 cycles of induction and consolidation chemotherapy. Lestaurtinib was commenced 2 days after completing chemotherapy and administered in cycles of up to 28 days. The trials ran consecutively. Primary endpoints were overall survival in AML15 and relapse-free survival in AML17; outcome data were meta-analyzed. Five hundred patients were randomly assigned between lestaurtinib and control: 74% had FLT3 -internal tandem duplication mutations, 23% FLT3 -tyrosine kinase domain point mutations, and 2% both types. No significant differences were seen in either 5-year overall survival (lestaurtinib 46% vs control 45%; hazard ratio, 0.90; 95% CI 0.70-1.15; P = .3) or 5-year relapse-free survival (40% vs 36%; hazard ratio, 0.88; 95% CI 0.69-1.12; P = .3). Exploratory subgroup analysis suggested survival benefit with lestaurtinib in patients receiving concomitant azole antifungal prophylaxis and gemtuzumab ozogamicin with the first course of chemotherapy. Correlative studies included analysis of in vivo FLT3 inhibition by plasma inhibitory activity assay and indicated improved overall survival and significantly reduced rates of relapse in lestaurtinib-treated patients who achieved sustained greater than 85% FLT3 inhibition. In conclusion, combining lestaurtinib with intensive chemotherapy proved feasible in younger patients with newly diagnosed FLT3 -mutated AML, but yielded no overall clinical benefit. The improved clinical outcomes seen in patients achieving sustained FLT3 inhibition encourage continued evaluation of FLT3-directed therapy alongside front-line AML treatment. The UK AML15 and AML17 trials are registered at www.isrctn.com/ISRCTN17161961 and www.isrctn.com/ISRCTN55675535 respectively. © 2017 by The American Society of Hematology.

Effectiveness of Computer Tailoring Versus Peer Support Web-Based Interventions in Promoting Physical Activity Among Insufficiently Active Canadian Adults With Type 2 Diabetes: Protocol for a Randomized Controlled Trial

PubMed Central

Côté, José

2016-01-01

Background Type 2 diabetes is a major challenge for Canadian public health authorities, and regular physical activity is a key factor in the management of this disease. Given that less than half of people with type 2 diabetes in Canada are sufficiently active to meet the Canadian Diabetes Association's guidelines, effective programs targeting the adoption of regular physical activity are in demand for this population. Many researchers have argued that Web-based interventions targeting physical activity are a promising avenue for insufficiently active populations; however, it remains unclear if this type of intervention is effective among people with type 2 diabetes. Objective This research project aims to evaluate the effectiveness of two Web-based interventions targeting the adoption of regular aerobic physical activity among insufficiently active adult Canadian Francophones with type 2 diabetes. Methods A 3-arm, parallel randomized controlled trial with 2 experimental groups and 1 control group was conducted in the province of Quebec, Canada. A total of 234 participants were randomized at a 1:1:1 ratio to receive an 8-week, fully automated, computer-tailored, Web-based intervention (experimental group 1); an 8-week peer support (ie, Facebook group) Web-based intervention (experimental group 2); or no intervention (control group) during the study period. Results The primary outcome of this study is self-reported physical activity level (total min/week of moderate-intensity aerobic physical activity). Secondary outcomes are attitude, social influence, self-efficacy, type of motivation, and intention. All outcomes are assessed at baseline and 3 and 9 months after baseline with a self-reported questionnaire filled directly on the study websites. Conclusions By evaluating and comparing the effectiveness of 2 Web-based interventions characterized by different behavior change perspectives, findings of this study will contribute to advances in the field of physical activity promotion in adult populations with type 2 diabetes. Trial Registration International Standard Randomized Controlled Trial Number (ISRCTN): ISRCTN15747108; http://www.isrctn.com/ISRCTN15747108 (Archived by WebCite at http://www.webcitation.org/6eJTi0m3r) PMID:26869015

Cost-Effectiveness of a Specialist Geriatric Medical Intervention for Frail Older People Discharged from Acute Medical Units: Economic Evaluation in a Two-Centre Randomised Controlled Trial (AMIGOS).

PubMed

Tanajewski, Lukasz; Franklin, Matthew; Gkountouras, Georgios; Berdunov, Vladislav; Edmans, Judi; Conroy, Simon; Bradshaw, Lucy E; Gladman, John R F; Elliott, Rachel A

2015-01-01

Poor outcomes and high resource-use are observed for frail older people discharged from acute medical units. A specialist geriatric medical intervention, to facilitate Comprehensive Geriatric Assessment, was developed to reduce the incidence of adverse outcomes and associated high resource-use in this group in the post-discharge period. To examine the costs and cost-effectiveness of a specialist geriatric medical intervention for frail older people in the 90 days following discharge from an acute medical unit, compared with standard care. Economic evaluation was conducted alongside a two-centre randomised controlled trial (AMIGOS). 433 patients (aged 70 or over) at risk of future health problems, discharged from acute medical units within 72 hours of attending hospital, were recruited in two general hospitals in Nottingham and Leicester, UK. Participants were randomised to the intervention, comprising geriatrician assessment in acute units and further specialist management, or to control where patients received no additional intervention over and above standard care. Primary outcome was incremental cost per quality adjusted life year (QALY) gained. We undertook cost-effectiveness analysis for 417 patients (intervention: 205). The difference in mean adjusted QALYs gained between groups at 3 months was -0.001 (95% confidence interval [CI]: -0.009, 0.007). Total adjusted secondary and social care costs, including direct costs of the intervention, at 3 months were £4412 (€5624, $6878) and £4110 (€5239, $6408) for the intervention and standard care groups, the incremental cost was £302 (95% CI: 193, 410) [€385, $471]. The intervention was dominated by standard care with probability of 62%, and with 0% probability of cost-effectiveness (at £20,000/QALY threshold). The specialist geriatric medical intervention for frail older people discharged from acute medical unit was not cost-effective. Further research on designing effective and cost-effective specialist service for frail older people discharged from acute medical units is needed. ISRCTN registry ISRCTN21800480 http://www.isrctn.com/ISRCTN21800480.

Efficacy of Clarithromycin-Naproxen-Oseltamivir Combination in the Treatment of Patients Hospitalized for Influenza A(H3N2) Infection: An Open-label Randomized, Controlled, Phase IIb/III Trial.

PubMed

Hung, Ivan F N; To, Kelvin K W; Chan, Jasper F W; Cheng, Vincent C C; Liu, Kevin S H; Tam, Anthony; Chan, Tuen-Ching; Zhang, Anna Jinxia; Li, Patrick; Wong, Tin-Lun; Zhang, Ricky; Cheung, Michael K S; Leung, William; Lau, Johnson Y N; Fok, Manson; Chen, Honglin; Chan, Kwok-Hung; Yuen, Kwok-Yung

2017-05-01

Influenza causes excessive hospitalizations and deaths. The study assessed the efficacy and safety of a clarithromycin-naproxen-oseltamivir combination for treatment of serious influenza. From February to April 2015, we conducted a prospective open-label, randomized, controlled trial. Adult patients hospitalized for A(H3N2) influenza were randomly assigned to a 2-day combination of clarithromycin 500 mg, naproxen 200 mg, and oseltamivir 75 mg twice daily, followed by 3 days of oseltamivir or to oseltamivir 75 mg twice daily without placebo for 5 days as a control method (1:1). The primary end point was 30-day mortality. The secondary end points were 90-day mortality, serial nasopharyngeal aspirate (NPA) virus titer, percentage of neuraminidase-inhibitor-resistant A(H3N2) virus (NIRV) quasispecies, pneumonia severity index (PSI), and duration of hospital stay. Among the 217 patients with influenza A(H3N2) enrolled, 107 were randomly assigned to the combination treatment. The median age was 80 years, and 53.5% were men. Adverse events were uncommon. Ten patients died during the 30-day follow-up. The combination treatment was associated with lower 30-day mortality (P = .01), less frequent high dependency unit admission (P = .009), and shorter hospital stay (P < .0001). The virus titer and PSI (days 1-3; P < .01) and the NPA specimens with NIRV quasispecies ≥ 5% (days 1-2; P < .01) were significantly lower in the combination treatment group. Multivariate analysis showed that combination treatment was the only independent factor associated with lower 30-day mortality (OR, 0.06; 95% CI, 0.004-0.94; P = .04). Combination treatment reduced both 30- and 90-day mortality and length of hospital stay. Further study of the antiviral and immunomodulatory effects of this combination treatment of severe influenza is warranted. BioMed Central; No.: ISRCTN11273879 DOI 10.1186/ISRCTN11273879; URL: www.isrctn.com/ISRCTN11273879. Copyright © 2016 American College of Chest Physicians. Published by Elsevier Inc. All rights reserved.

Fatigue in Patients with Multiple Sclerosis: Is It Related to Pro- and Anti-Inflammatory Cytokines?

PubMed Central

Malekzadeh, Arjan; Van de Geer-Peeters, Wietske; De Groot, Vincent; Elisabeth Teunissen, Charlotte; Beckerman, Heleen; TREFAMS-ACE Study Group

2015-01-01

Objective. To investigate the pathophysiological role of pro- and anti-inflammatory cytokines in primary multiple sclerosis-related fatigue. Methods. Fatigued and non-fatigued patients with multiple sclerosis (MS) were recruited and their cytokine profiles compared. Patients with secondary fatigue were excluded. Fatigue was assessed with the self-reported Checklist Individual Strength (CIS20r), subscale fatigue. A CIS20r fatigue cut-off score of 35 was applied to differentiate between non-fatigued (CIS20r fatigue ≤34) and fatigued (CIS20r fatigue ≥35) patients with MS. Blood was collected to determine the serum concentrations of pro-inflammatory cytokines (IL-1β, IL-2, IL-6, IL-8, IL-12p70, IL-17, TNFα, and IFN-γ) and anti-inflammatory cytokines (IL-4, IL-5, IL-10, and IL-13). We controlled for the confounding effect of age, gender, duration of MS, disease severity, type of MS, and use of immunomodulatory drugs. Results. Similar cytokine levels were observed between MS patients with (n = 21) and without fatigue (n = 14). Adjusted multiple regression analyses showed a single significant positive relationship, that of IL-6 with CIS20r fatigue score. The explained variance of the IL-6 model was 21.1%, once adjusted for the confounding effect of age. Conclusion. The pro-inflammatory cytokine interleukin-6 (IL-6) may play a role in the pathophysiology of primary fatigue in patients with MS. Trial Registrations. ISRCTN69520623, ISRCTN58583714, and ISRCTN82353628. PMID:25722532

Does Aerobic Exercise Increase 24-Hour Ambulatory Blood Pressure Among Workers With High Occupational Physical Activity?-A RCT.

PubMed

Korshøj, Mette; Krause, Niklas; Clays, Els; Søgaard, Karen; Krustrup, Peter; Holtermann, Andreas

2017-04-01

High occupational physical activity (OPA) increases cardiovascular risk and aerobic exercise has been recommended for reducing this risk. This paper investigates the effects of an aerobic exercise intervention on 24-hour ambulatory blood pressure (ABP) among cleaners with high OPA. Hundred and sixteen cleaners between 18 and 65 years were randomized. During the 4-month intervention period, the aerobic exercise group (AE) (n = 57) performed worksite aerobic exercise (2 × 30 minutes/week), while the reference group (REF) (n = 59) attended lectures. Between-group differences in 4-month ABP changes were evaluated by intention-to-treat analysis using a repeated-measure 2 × 2 multiadjusted mixed-models design. Relative to REF, 24-hour ABP significantly increased in AE: systolic 3.6 mm Hg (95% confidence interval (CI) 1.6-5.7) and diastolic 2.3 mm Hg (95% CI 0.9-3.8). Cleaners with high aerobic workload exhibited particularly high 24-hour ABP increases: systolic 6.0 mm Hg (95% CI 2.4-9.6), and diastolic 3.8 mm Hg (95% CI 1.3-6.4). Aerobic exercise increased 24-hour ABP among cleaners. This adverse effect raises questions about the safety and intended benefits of aerobic exercise, especially among workers with high OPA and a demanding aerobic workload. http://www.controlled-trials.com/ISRCTN86682076. Unique identifier ISRCTN86682076. Trial Number ISRCTN86682076. © The Author 2017. Published by Oxford University Press on behalf of American Journal of Hypertension, Ltd.

The relaxation exercise and social support trial-resst: study protocol for a randomized community based trial

PubMed Central

2011-01-01

Background Studies suggests a possible link between vaginal discharge and common mental distress, as well as highlight the implications of the subjective burden of disease and its link with mental health. Methods/Design This is a community-based intervention trial that aims to evaluate the impact of a psycho-social intervention on medically unexplained vaginal discharge (MUVD) in a group of married, low-income Lebanese women, aged 18-49, and suffering from low to moderate levels of anxiety and/or depression. The intervention consisted of 12 sessions of structured social support, problem solving techniques, group discussions and trainer-supervised relaxation exercises (twice per week over six weeks). Women were recruited from Hey el Selloum, a southern disadvantaged suburb of Beirut, Lebanon, during an open recruitment campaign. The primary outcome was self-reported MUVD, upon ruling out reproductive tract infections (RTIs), through lab analysis. Anxiety and/or depression symptoms were the secondary outcomes for this trial. These were assessed using an Arabic validated version of the Hopkins Symptoms Checklist-25 (HSCL-25). Assessments were done at baseline and six months using face-to face interviews, pelvic examinations and laboratory tests. Women were randomized into either intervention or control group. Intent to treat analysis will be used. Discussion The results will indicate whether the proposed psychosocial intervention was effective in reducing MUVD (possibly mediated by common mental distress). Trial Registration The trial is registered at the Wellcome Trust Registry, ISRCTN assigned: ISRCTN: ISRCTN98441241 PMID:21864414

Mitochondrial DNA mutations in diabetes mellitus patients in Chinese Han population.

PubMed

Wang, Suijun; Wu, Songhua; Zheng, Taishan; Yang, Zhen; Ma, Xiaojing; Jia, Weiping; Xiang, Kunsan

2013-12-01

Mutations of mitochondrial DNA are associated with diabetes mellitus (DM). The present case-control study aimed to investigate the mutations of mitochondrial DNA in DM patients of Chinese Han ethnicity. A total of 770 DM patients and 309 healthy control individuals were enrolled. The mitochondrial DNA was extracted from blood cells and analyzed by the polymerase chain reaction-restriction fragment length polymorphism assay. In the diabetes group, there were 13 (1.69%) individuals carrying the mt3243 A → G mutation while none of the healthy control had this mutation. Though the 14709, 3316, 3394, and 12026 mutation variants were identified in 9, 17, 18 and 28 in DM patients respectively, there were no significant differences compared with control group. And the 3256, 8296, 8344, 8363, 3426 and 12258 mutations were not detected in either group. In the diabetes group, two double mutations were identified: A3243G+T3394C and A3243G+A12026G. Our data suggested that mitochondrial gene tRNA(Leu(UUR)) 3243 A → G mutation may be one risk of prevalence of DM and associated with worse clinical status in Chinese Han population. © 2013 Elsevier B.V. All rights reserved.

Framework for Understanding LENR Processes, Using Ordinary Condensed Matter Physics

NASA Astrophysics Data System (ADS)

Chubb, Scott

2005-03-01

As I have emphasizedootnotetextS.R. Chubb, Proc. ICCF10 (in press). Also, http://www.lenr-canr.org/acrobat/ChubbSRnutsandbol.pdf http://www.lenr-canr.org/acrobat/ChubbSRnutsandbol.pdf, S.R. Chubb, Trans. Amer. Nuc. Soc. 88 , 618 (2003)., in discussions of Low Energy Nuclear Reactions(LENRs), mainstream many-body physics ideas have been largely ignored. A key point is that in condensed matter, delocalized, wave-like effects can allow large amounts of momentum to be transferred instantly to distant locations, without any particular particle (or particles) acquiring high velocity through a Broken Gauge Symmetry. Explicit features in the electronic structure explain how this can occur^1 in finite size PdD crystals, with real boundaries. The essential physics^1 can be related to standard many-body techniquesootnotetextBurke,P.G. and K.A. Berrington, Atomic and Molecular Processes:an R matrix Approach (Bristol: IOP Publishing, 1993).. In the paper, I examine this relationship, the relationship of the theory^1 to other LENR theories, and the importance of certain features (for example, boundaries^1) that are not included in the other LENR theories.

[Diabetes mellitus associated with the mitochondrial mutation A3243G: frequency and clinical presentation].

PubMed

Salles, João Eduardo N; Kalinin, Larissa Bresgunov; Ferreira, Sandra Roberta G; Kasamatsu, Teresa; Moisés, Regina S

2007-06-01

Maternal inherited diabetes and deafness (MIDD) has been related to an A to G transition in the mitochondrial RNA Leu (UUR) at base pair 3243. The prevalence of MIDD in the diabetes population ranges between 0.5-3.0% depending on the ethnic background. To examine the frequency and clinical features of diabetes associated with this mutation in Brazilian patients with glucose intolerance. The study population comprised: 78 type 1 diabetic subjects (group I), 148 patients with type 2 diabetes (group II), 15 patients with either type 1 or type 2 diabetes and hearing loss (group III) and 492 Japanese Brazilians with varying degrees of glucose intolerance. DNA was extracted from peripheral blood leucocytes and the A3243G mutation was determined by PCR amplification and Apa 1 digestion. In some individuals DNA was also extracted from buccal mucosa and hair follicles. The 3243 bp mutation was found in three individuals, all from group III, resulting in a prevalence of 0.4%. These subjects had an early age of diagnosis of diabetes, low or normal body mass index and requirement of insulin therapy. In conclusion MIDD is rare in our population and should be investigate in patients with diabetes and deafness.

The influence of parenteral glutamine supplementation on glucose homeostasis in critically ill polytrauma patients--A randomized-controlled clinical study.

PubMed

Grintescu, Ioana Marina; Luca Vasiliu, Irina; Cucereanu Badica, Ioana; Mirea, Liliana; Pavelescu, Daniela; Balanescu, Andreea; Grintescu, Ioana Cristina

2015-06-01

Rapid onset of resistance to insulin is a prominent component of stress metabolism in multiple trauma patients. Recent studies have clarified the role of amino acids (especially glutamine) in glucose transportation and the benefits of parenteral alanyl-glutamine supplementation (0.3-0.6 g/kg/day) in glucose homeostasis. The aims of this study are to evaluate the incidence of hyperglycemic episodes and the need for exogenous insulin to maintain stable glucose levels in critically ill polytrauma patients supplemented with parenteral glutamine dipeptide (Dipeptiven(®)) versus standard nutritional support. This was an open-label randomized-controlled trial of 82 polytrauma patients aged 20-60 years old, randomly assigned into two equal groups independent of sex, age and Injury Severity Score. We excluded patients with diabetes mellitus, or renal or hepatic failure. One group received parenteral Dipeptiven(®) supplementation of 0.5 g/kg/day and the other received standard isocaloric isoproteinic nutritional support. We found that 63% of patients in the glutamine-supplemented group had no hyperglycemic episodes; only 37% required exogenous insulin (mean daily requirement of 44 units/day). In the control group, 51% of patients required insulin (mean daily requirement 63 unit/day; p = 0.0407). The effect of glutamine supplementation on glucose homeostasis is associated with a lower incidence of hyperglycemia among critically ill polytrauma patients, and leads to a lower mean daily dose of insulin. Controlled-trials.com Identifier: ISRCTN71592366 (http://www.controlled-trials.com/ISRCTN71592366/ISRCTN71592366). Copyright © 2014 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.

A Mobile Phone App to Support Young People in Making Shared Decisions in Therapy (Power Up): Study Protocol

PubMed Central

Martin, Kate; Webber, Helen; Craven, Michael P; Hollis, Chris; Deighton, Jessica; Law, Roslyn; Fonagy, Peter; Wolpert, Miranda

2017-01-01

Background Evidence suggests that young people want to be active participants in their care and involved in decisions about their treatment. However, there is a lack of digital shared decision-making tools available to support young people in child and adolescent mental health services (CAMHS). Objective The primary aim of this paper is to present the protocol of a feasibility trial for Power Up, a mobile phone app to empower young people in CAMHS to make their voices heard and participate in decisions around their care. Methods In the development phase, 30 young people, parents, and clinicians will take part in interviews and focus groups to elicit opinions on an early version of the app. In the feasibility testing phase, 60 young people from across 7 to 10 London CAMHS sites will take part in a trial looking at the feasibility and acceptability of measuring the impact of Power Up on shared decision making. Results Data collection for the development phase ended in December 2016. Data collection for the feasibility testing phase will end in December 2017. Conclusions Findings will inform the planning of a cluster controlled trial and contribute to the development and implementation of a shared decision-making app to be integrated into CAMHS. Trial Registration ISRCTN77194423; http://www.isrctn.com/ISRCTN77194423 (Archived by WebCite at http://www.webcitation.org/6td6MINP0). ClinicalTrials.gov NCT02987608; https://clinicaltrials.gov/ct2/show/NCT02987608 (Archived by WebCite at http://www.webcitation.org/6td6PNBZM) PMID:29084708

Treatment of acute diverticulitis laparoscopic lavage vs. resection (DILALA): study protocol for a randomised controlled trial.

PubMed

Thornell, Anders; Angenete, Eva; Gonzales, Elisabeth; Heath, Jane; Jess, Per; Läckberg, Zoltan; Ovesen, Henrik; Rosenberg, Jacob; Skullman, Stefan; Haglind, Eva

2011-08-01

Perforated diverticulitis is a condition associated with substantial morbidity. Recently published reports suggest that laparoscopic lavage has fewer complications and shorter hospital stay. So far no randomised study has published any results. DILALA is a Scandinavian, randomised trial, comparing laparoscopic lavage (LL) to the traditional Hartmann's Procedure (HP). Primary endpoint is the number of re-operations within 12 months. Secondary endpoints consist of mortality, quality of life (QoL), re-admission, health economy assessment and permanent stoma. Patients are included when surgery is required. A laparoscopy is performed and if Hinchey grade III is diagnosed the patient is included and randomised 1:1, to either LL or HP. Patients undergoing LL receive > 3L of saline intraperitoneally, placement of pelvic drain and continued antibiotics. Follow-up is scheduled 6-12 weeks, 6 months and 12 months. A QoL-form is filled out on discharge, 6- and 12 months. Inclusion is set to 80 patients (40+40). HP is associated with a high rate of complication. Not only does the primary operation entail complications, but also subsequent surgery is associated with a high morbidity. Thus the combined risk of treatment for the patient is high. The aim of the DILALA trial is to evaluate if laparoscopic lavage is a safe, minimally invasive method for patients with perforated diverticulitis Hinchey grade III, resulting in fewer re-operations, decreased morbidity, mortality, costs and increased quality of life. British registry (ISRCTN) for clinical trials ISRCTN82208287http://www.controlled-trials.com/ISRCTN82208287.

Quality of Acute Psychedelic Experience Predicts Therapeutic Efficacy of Psilocybin for Treatment-Resistant Depression.

PubMed

Roseman, Leor; Nutt, David J; Carhart-Harris, Robin L

2017-01-01

Introduction: It is a basic principle of the "psychedelic" treatment model that the quality of the acute experience mediates long-term improvements in mental health. In the present paper we sought to test this using data from a clinical trial assessing psilocybin for treatment-resistant depression (TRD). In line with previous reports, we hypothesized that the occurrence and magnitude of Oceanic Boundlessness (OBN) (sharing features with mystical-type experience) and Dread of Ego Dissolution (DED) (similar to anxiety) would predict long-term positive outcomes, whereas sensory perceptual effects would have negligible predictive value. Materials and Methods: Twenty patients with treatment resistant depression underwent treatment with psilocybin (two separate sessions: 10 and 25 mg psilocybin). The Altered States of Consciousness (ASC) questionnaire was used to assess the quality of experiences in the 25 mg psilocybin session. From the ASC, the dimensions OBN and DED were used to measure the mystical-type and challenging experiences, respectively. The Self-Reported Quick Inventory of Depressive Symptoms (QIDS-SR) at 5 weeks served as the endpoint clinical outcome measure, as in later time points some of the subjects had gone on to receive new treatments, thus confounding inferences. In a repeated measure ANOVA, Time was the within-subject factor (independent variable), with QIDS-SR as the within-subject dependent variable in baseline, 1-day, 1-week, 5-weeks. OBN and DED were independent variables. OBN-by-Time and DED-by-Time interactions were the primary outcomes of interest. Results: For the interaction of OBN and DED with Time (QIDS-SR as dependent variable), the main effect and the effects at each time point compared to baseline were all significant ( p = 0.002 and p = 0.003, respectively, for main effects), confirming our main hypothesis. Furthermore, Pearson's correlation of OBN with QIDS-SR (5 weeks) was specific compared to perceptual dimensions of the ASC ( p < 0.05). Discussion: This report further bolsters the view that the quality of the acute psychedelic experience is a key mediator of long-term changes in mental health. Future therapeutic work with psychedelics should recognize the essential importance of quality of experience in determining treatment efficacy and consider ways of enhancing mystical-type experiences and reducing anxiety. Trial Registration: ISRCTN, number ISRCTN14426797, http://www.isrctn.com/ISRCTN14426797.

Protocol and baseline data for a multi-year cohort study of the effects of different mass drug treatment approaches on functional morbidities from schistosomiasis in four African countries.

PubMed

Shen, Ye; King, Charles H; Binder, Sue; Zhang, Feng; Whalen, Christopher C; Evan Secor, W; Montgomery, Susan P; Mwinzi, Pauline N M; Olsen, Annette; Magnussen, Pascal; Kinung'hi, Safari; Phillips, Anna E; Nalá, Rassul; Ferro, Josefo; Aurelio, H Osvaldo; Fleming, Fiona; Garba, Amadou; Hamidou, Amina; Fenwick, Alan; Campbell, Carl H; Colley, Daniel G

2017-09-29

The Schistosomiasis Consortium for Operational Research and Evaluation (SCORE) focus is on randomized trials of different approaches to mass drug administration (MDA) in endemic countries in Africa. Because their studies provided an opportunity to evaluate the effects of mass treatment on Schistosoma-associated morbidity, nested cohort studies were developed within SCORE's intervention trials to monitor changes in a suite of schistosomiasis disease outcomes. This paper describes the process SCORE used to select markers for prospective monitoring and the baseline prevalence of these morbidities in four parallel cohort studies. In July 2009, SCORE hosted a discussion of the potential impact of MDA on morbidities due to Schistosoma infection that might be measured in the context of multi-year control. Candidate markers were reviewed and selected for study implementation. Baseline data were then collected from cohorts of children in four country studies: two in high endemic S. mansoni sites (Kenya and Tanzania), and two in high endemic S. haematobium sites (Niger and Mozambique), these cohorts to be followed prospectively over 5 years. At baseline, 62% of children in the S. mansoni sites had detectable eggs in their stool, and 10% had heavy infections (≥ 400 eggs/g feces). Heavy S. mansoni infections were found to be associated with increased baseline risk of anemia, although children with moderate or heavy intensity infections had lower risk of physical wasting. Prevalence of egg-positive infection in the combined S. haematobium cohorts was 27%, with 5% of individuals having heavy infection (≥50 eggs/10 mL urine). At baseline, light intensity S. haematobium infection was associated with anemia and with lower scores in the social domain of health-related quality-of-life (HRQoL) assessed by Pediatric Quality of Life Inventory. Our consensus on practical markers of Schistosoma-associated morbidity indicated that height, weight, hemoglobin, exercise tolerance, HRQoL, and ultrasound abnormalities could be used as reference points for gauging treatment impact. Data collected over five years of program implementation will provide guidance for future evaluation of morbidity control in areas endemic for schistosomiasis. These cohort studies are registered and performed in conjunction with the International Standard Randomised Controlled Trial Registry trials ISRCTN16755535 , ISRCTN14117624 , ISRCTN95819193 , and ISRCTN32045736 .

Quality of Acute Psychedelic Experience Predicts Therapeutic Efficacy of Psilocybin for Treatment-Resistant Depression

PubMed Central

Roseman, Leor; Nutt, David J.; Carhart-Harris, Robin L.

2018-01-01

Introduction: It is a basic principle of the “psychedelic” treatment model that the quality of the acute experience mediates long-term improvements in mental health. In the present paper we sought to test this using data from a clinical trial assessing psilocybin for treatment-resistant depression (TRD). In line with previous reports, we hypothesized that the occurrence and magnitude of Oceanic Boundlessness (OBN) (sharing features with mystical-type experience) and Dread of Ego Dissolution (DED) (similar to anxiety) would predict long-term positive outcomes, whereas sensory perceptual effects would have negligible predictive value. Materials and Methods: Twenty patients with treatment resistant depression underwent treatment with psilocybin (two separate sessions: 10 and 25 mg psilocybin). The Altered States of Consciousness (ASC) questionnaire was used to assess the quality of experiences in the 25 mg psilocybin session. From the ASC, the dimensions OBN and DED were used to measure the mystical-type and challenging experiences, respectively. The Self-Reported Quick Inventory of Depressive Symptoms (QIDS-SR) at 5 weeks served as the endpoint clinical outcome measure, as in later time points some of the subjects had gone on to receive new treatments, thus confounding inferences. In a repeated measure ANOVA, Time was the within-subject factor (independent variable), with QIDS-SR as the within-subject dependent variable in baseline, 1-day, 1-week, 5-weeks. OBN and DED were independent variables. OBN-by-Time and DED-by-Time interactions were the primary outcomes of interest. Results: For the interaction of OBN and DED with Time (QIDS-SR as dependent variable), the main effect and the effects at each time point compared to baseline were all significant (p = 0.002 and p = 0.003, respectively, for main effects), confirming our main hypothesis. Furthermore, Pearson's correlation of OBN with QIDS-SR (5 weeks) was specific compared to perceptual dimensions of the ASC (p < 0.05). Discussion: This report further bolsters the view that the quality of the acute psychedelic experience is a key mediator of long-term changes in mental health. Future therapeutic work with psychedelics should recognize the essential importance of quality of experience in determining treatment efficacy and consider ways of enhancing mystical-type experiences and reducing anxiety. Trial Registration: ISRCTN, number ISRCTN14426797, http://www.isrctn.com/ISRCTN14426797 PMID:29387009

A multicentre, pragmatic, parallel group, randomised controlled trial to compare the clinical and cost-effectiveness of three physiotherapy-led exercise interventions for knee osteoarthritis in older adults: the BEEP trial protocol (ISRCTN: 93634563)

PubMed Central

2014-01-01

Background Exercise is consistently recommended for older adults with knee pain related to osteoarthritis. However, the effects from exercise are typically small and short-term, likely linked to insufficient individualisation of the exercise programme and limited attention to supporting exercise adherence over time. The BEEP randomised trial aims to improve patients’ short and long-term outcomes from exercise. It will test the overall effectiveness and cost-effectiveness of two physiotherapy-led exercise interventions (Individually Tailored Exercise and Targeted Exercise Adherence) to improve the individual tailoring of, and adherence to exercise, compared with usual physiotherapy care. Methods/design Based on the learning from a pilot study (ISRCTN 23294263), the BEEP trial is a multi-centre, pragmatic, parallel group, individually randomised controlled trial, with embedded longitudinal qualitative interviews. 500 adults in primary care, aged 45 years and over with knee pain will be randomised to 1 of 3 treatment groups delivered by fully trained physiotherapists in up to 6 NHS services. These are: Usual Physiotherapy Care (control group consisting of up to 4 treatment sessions of advice and exercise), Individually Tailored Exercise (an individualised, supervised and progressed lower-limb exercise programme) or Targeted Exercise Adherence (supporting patients to adhere to exercise and to engage in general physical activity over the longer-term). The primary outcomes are pain and function as measured by the Western Ontario and McMaster Osteoarthritis index. A comprehensive range of secondary outcomes are also included. Outcomes are measured at 3, 6 (primary outcome time-point), 9, 18 and 36 months. Data on adverse events will also be collected. Semi-structured, qualitative interviews with a subsample of 30 participants (10 from each treatment group) will be undertaken at two time-points (end of treatment and 12 to 18 months later) and analysed thematically. Discussion This trial will contribute to the evidence base for management of older adults with knee pain attributable to osteoarthritis in primary care. The findings will have important implications for healthcare commissioners, general practitioners and physiotherapy service providers and it will inform future education of healthcare practitioners. It may also serve to delay or prevent some individuals from becoming surgical candidates. Trial registration ISRCTN: ISRCTN93634563. PMID:25064573

Effectiveness of a fluid chart in outpatient management of suspected dengue fever: A pilot study.

PubMed

Nasir, Nazrila Hairin; Mohamad, Mohazmi; Lum, Lucy Chai See; Ng, Chirk Jenn

2017-01-01

Dengue infection is the fastest spreading mosquito-borne viral disease in the world. One of the complications of dengue is dehydration which, if not carefully monitored and treated, may lead to shock, particularly in those with dengue haemorrhagic fever. WHO has recommended oral fluid intake of five glasses or more for adults who are suspected to have dengue fever. However, there have been no published studies looking at self-care intervention measures to improve oral fluid intake among patients suspected of dengue fever. To assess the feasibility and effectiveness of using a fluid chart to improve oral fluid intake in patients with suspected dengue fever in a primary care setting. This feasibility study used a randomized controlled study design. The data was collected over two months at a primary care clinic in a teaching hospital. The inclusion criteria were: age > 12 years, patients who were suspected to have dengue fever based on the assessment by the primary healthcare clinician, fever for > three days, and thrombocytopenia (platelets < 150 x 109/L). Both groups received a dengue home care card. The intervention group received the fluid chart and a cup (200ml). Baseline clinical and laboratory data, 24-hour fluid recall (control group), and fluid chart were collected. The main outcomes were: hospitalization rates, intravenous fluid requirement and total oral fluid intake. Among the 138 participants who were included in the final analysis, there were fewer hospital admissions in the intervention group (n = 7, 10.0%) than the control group (n = 12, 17.6%) (p = 0.192). Similarly, fewer patients (n = 9, 12.9%) in the intervention group required intravenous fluid compared to the control group (n = 15, 22.1%), (p = 0.154). There was an increase in the amount of daily oral fluid intake in the intervention group (about 3,000 ml) compared to the control group (about 2,500 ml, p = 0.521). However, these differences did not reach statistical significance. This is a feasible and acceptable study to perform in a primary care setting. The fluid chart is a simple, inexpensive tool that may reduce hospitalization and intravenous fluid requirement in suspected dengue patients. A randomized controlled trial with larger sample size is needed to determine this conclusively. International Standard Randomized Controlled Trial Number (ISRCTN) Registry ISRCTN25394628 http://www.isrctn.com/ISRCTN25394628.

Study protocol: the sleeping sound with attention-deficit/hyperactivity disorder project.

PubMed

Sciberras, Emma; Efron, Daryl; Gerner, Bibi; Davey, Margot; Mensah, Fiona; Oberklaid, Frank; Hiscock, Harriet

2010-12-30

Up to 70% of children with Attention-Deficit/Hyperactivity Disorder (ADHD) experience sleep problems including difficulties initiating and maintaining sleep. Sleep problems in children with ADHD can result in poorer child functioning, impacting on school attendance, daily functioning and behaviour, as well as parental mental health and work attendance. The Sleeping Sound with ADHD trial aims to investigate the efficacy of a behavioural sleep program in treating sleep problems experienced by children with ADHD. We have demonstrated the feasibility and the acceptability of this treatment program in a pilot study. This randomised controlled trial (RCT) is being conducted with 198 children (aged between 5 to 12 years) with ADHD and moderate to severe sleep problems. Children are recruited from public and private paediatric practices across the state of Victoria, Australia. Upon receiving informed written consent, families are randomised to receive either the behavioural sleep intervention or usual care. The intervention consists of two individual, face-to-face consultations and a follow-up phone call with a trained clinician (trainee consultant paediatrician or psychologist), focusing on the assessment and management of child sleep problems. The primary outcome is parent- and teacher-reported ADHD symptoms (ADHD Rating Scale IV). Secondary outcomes are child sleep (actigraphy and parent report), behaviour, daily functioning, school attendance and working memory, as well as parent mental health and work attendance. We are also assessing the impact of children's psychiatric comorbidity (measured using a structured diagnostic interview) on treatment outcome. To our knowledge, this is the first RCT of a behavioural intervention aiming to treat sleep problems in children with ADHD. If effective, this program will provide a feasible non-pharmacological and acceptable intervention improving child sleep and ADHD symptoms in this patient group. Current Controlled Trials ISRCTN68819261. ISRCTN: ISRCTN68819261.

A Mobile Phone App to Support Young People in Making Shared Decisions in Therapy (Power Up): Study Protocol.

PubMed

Chapman, Louise; Edbrooke-Childs, Julian; Martin, Kate; Webber, Helen; Craven, Michael P; Hollis, Chris; Deighton, Jessica; Law, Roslyn; Fonagy, Peter; Wolpert, Miranda

2017-10-30

Evidence suggests that young people want to be active participants in their care and involved in decisions about their treatment. However, there is a lack of digital shared decision-making tools available to support young people in child and adolescent mental health services (CAMHS). The primary aim of this paper is to present the protocol of a feasibility trial for Power Up, a mobile phone app to empower young people in CAMHS to make their voices heard and participate in decisions around their care. In the development phase, 30 young people, parents, and clinicians will take part in interviews and focus groups to elicit opinions on an early version of the app. In the feasibility testing phase, 60 young people from across 7 to 10 London CAMHS sites will take part in a trial looking at the feasibility and acceptability of measuring the impact of Power Up on shared decision making. Data collection for the development phase ended in December 2016. Data collection for the feasibility testing phase will end in December 2017. Findings will inform the planning of a cluster controlled trial and contribute to the development and implementation of a shared decision-making app to be integrated into CAMHS. ISRCTN77194423; http://www.isrctn.com/ISRCTN77194423 (Archived by WebCite at http://www.webcitation.org/6td6MINP0). ClinicalTrials.gov NCT02987608; https://clinicaltrials.gov/ct2/show/NCT02987608 (Archived by WebCite at http://www.webcitation.org/6td6PNBZM). ©Louise Chapman, Julian Edbrooke-Childs, Kate Martin, Helen Webber, Michael P Craven, Chris Hollis, Jessica Deighton, Roslyn Law, Peter Fonagy, Miranda Wolpert. Originally published in JMIR Research Protocols (http://www.researchprotocols.org), 30.10.2017.

Evaluation of a population-level strategy to promote tobacco treatment use among insured smokers: a pragmatic, randomized trial.

PubMed

McClure, Jennifer B; Anderson, Melissa L

2018-02-08

Most smokers do not use evidence-based smoking cessation treatment. Increasing utilization of these services is an important public health goal. Health care systems and insurers are well positioned to support this goal within their patient populations. We tested whether a brief, mail-based intervention increased utilization of tobacco cessation services among insured smokers. Adult smokers were identified via automated health plan data and randomized to one of five treatment arms (n = 4767). Randomization was stratified by gender, age, and type of health plan coverage. Three arms received a letter containing motivational content and treatment referral information. Motivational content emphasized either the financial, health, or values-based benefits of quitting. One arm received a referral letter with no motivational content, and one arm received no letter. Enrollment in the referred tobacco cessation program was monitored for 5 months. Treatment was available to all participants through their insurance. Across all four letter conditions, 0.8% of participants enrolled in tobacco treatment compared to 0.9% in the no letter reference group (p = .69). No single letter condition was superior to the others (p = .71), but treatment uptake was greater among participants who received their care and coverage from the health plan versus those with insurance coverage only (1.2% vs. 0.3%, p < .01). A one-time, mailed letter is not a cost-effective strategy for promoting use of covered smoking cessation treatment within large health plan populations, particularly when the message source is an insurance provider only and does not also provide clinical care. Health plans and insurers should consider alternative outreach efforts to promote treatment uptake among smokers. TRN registered retrospectively with ISRCTN registry ( www.isrctn.com ). Registered on 11/01/2018. Registration number: ISRCTN32311137 .

The impact of financial incentives on participants' food purchasing patterns in a supermarket-based randomized controlled trial.

PubMed

Olstad, Dana Lee; Crawford, David A; Abbott, Gavin; McNaughton, Sarah A; Le, Ha Nd; Ni Mhurchu, Cliona; Pollard, Christina; Ball, Kylie

2017-08-25

The impacts of supermarket-based nutrition promotion interventions might be overestimated if participants shift their proportionate food purchasing away from their usual stores. This study quantified whether participants who received price discounts on fruits and vegetables (FV) in the Supermarket Healthy Eating for Life (SHELf) randomized controlled trial (RCT) shifted their FV purchasing into study supermarkets during the intervention period. Participants were 642 females randomly assigned to a 1) skill-building (n = 160), 2) price reduction (n = 161), 3) combined skill-building and price reduction (n = 160), or 4) control (n = 161) group. Participants self-reported the proportion of FV purchased in study supermarkets at baseline, 3- and 6-months post-intervention. Fisher's exact and χ 2 tests assessed differences among groups in the proportion of FV purchased in study supermarkets at each time point. Multinomial logistic regression assessed differences among groups in the change in proportionate FV purchasing over time. Post-intervention, 49% of participants purchased ≥50% of their FV in study supermarkets. Compared to all other groups, the price reduction group was approximately twice as likely (RRR: 1.8-2.2) to have increased proportionate purchasing of FV in study supermarkets from baseline to post-intervention (p< 0.05). Participants who received price reductions on FV were approximately twice as likely to shift their FV purchasing from other stores into study supermarkets during the intervention period. Unless food purchasing data are available for all sources, differential changes in purchasing patterns can make it difficult to discern the true impacts of nutrition interventions. The SHELf trial is registered with Current Controlled Trials Registration ISRCTN39432901, Registered 30 June 2010, Retrospectively registered ( http://www.isrctn.com/ISRCTN39432901 ).

Isolated Human Pulmonary Artery Structure and Function Pre- and Post-Cardiopulmonary Bypass Surgery.

PubMed

Dora, Kim A; Stanley, Christopher P; Al Jaaly, Emad; Fiorentino, Francesca; Ascione, Raimondo; Reeves, Barnaby C; Angelini, Gianni D

2016-02-23

Pulmonary dysfunction is a known complication after cardiac surgery using cardiopulmonary bypass, ranging from subclinical functional changes to prolonged postoperative ventilation, acute lung injury, and acute respiratory distress syndrome. Whether human pulmonary arterial function is compromised is unknown. The aim of the present study was to compare the structure and function of isolated and cannulated human pulmonary arteries obtained from lung biopsies after the chest was opened (pre-cardiopulmonary bypass) to those obtained at the end of cardiopulmonary bypass (post-cardiopulmonary bypass) from patients undergoing coronary artery bypass graft surgery. Pre- and post-cardiopulmonary bypass lung biopsies were received from 12 patients undergoing elective surgery. Intralobular small arteries were dissected, cannulated, pressurized, and imaged using confocal microscopy. Functionally, the thromboxane mimetic U46619 produced concentration-dependent vasoconstriction in 100% and 75% of pre- and post-cardiopulmonary bypass arteries, respectively. The endothelium-dependent agonist bradykinin stimulated vasodilation in 45% and 33% of arteries pre- and post-cardiopulmonary bypass, respectively. Structurally, in most arteries smooth muscle cells aligned circumferentially; live cell viability revealed that although 100% of smooth muscle and 90% of endothelial cells from pre-cardiopulmonary bypass biopsies had intact membranes and were considered viable, only 60% and 58%, respectively, were viable from post-cardiopulmonary bypass biopsies. We successfully investigated isolated pulmonary artery structure and function in fresh lung biopsies from patients undergoing heart surgery. Pulmonary artery contractile tone and endothelium-dependent dilation were significantly reduced in post-cardiopulmonary bypass biopsies. The decreased functional responses were associated with reduced cell viability. URL: http://www.isrctn.com/ISRCTN34428459. Unique identifier: ISRCTN 34428459. © 2016 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley Blackwell.

A cluster-randomized evaluation of an intervention to increase skilled birth attendant utilization in mid- and far-western Nepal.

PubMed

Choulagai, Bishnu P; Onta, Sharad; Subedi, Narayan; Bhatta, Dharma N; Shrestha, Binjwala; Petzold, Max; Krettek, Alexandra

2017-10-01

Skilled birth attendant (SBA) utilization is low in remote and rural areas of Nepal. We designed and implemented an evaluation to assess the effectiveness of a five-component intervention that addressed previously identified barriers to SBA services in mid- and far-western Nepal. We randomly and equally allocated 36 village development committees with low SBA utilization among 1-year intervention and control groups. The eligible participants for the survey were women that had delivered a baby within the past 12 months preceding the survey. Implementation was administered by trained health volunteers, youth groups, mothers' groups and health facility management committee members. Post-intervention, we used difference-in-differences and mixed-effects regression models to assess and analyse any increase in the utilization of skilled birth care and antenatal care (ANC) services. All analyses were done by intention to treat. Our trial registration number was ISRCTN78892490 (http://www.isrctn.com/ISRCTN78892490). Interviewees included 1746 and 2098 eligible women in the intervention and control groups, respectively. The 1-year intervention was effective in increasing the use of skilled birth care services (OR = 1.57; CI 1.19-2.08); however, the intervention had no effect on the utilization of ANC services. Expanding the intervention with modifications, e.g. mobilizing more active and stable community groups, ensuring adequate human resources and improving quality of services as well as longer or repeated interventions will help achieve greater effect in increasing the utilization of SBA. © The Author 2017. Published by Oxford University Press in association with The London School of Hygiene and Tropical Medicine.

One-day compared with 7-day nitrofurantoin for asymptomatic bacteriuria in pregnancy: a randomized controlled trial.

PubMed

Lumbiganon, Pisake; Villar, Jose; Laopaiboon, Malinee; Widmer, Mariana; Thinkhamrop, Jadsada; Carroli, Guillermo; Duc Vy, Nguyen; Mignini, Luciano; Festin, Mario; Prasertcharoensuk, Witoon; Limpongsanurak, Sompop; Liabsuetrakul, Tippawan; Sirivatanapa, Pannee

2009-02-01

To evaluate whether a 1-day nitrofurantoin regimen is as effective as a 7-day regimen in eradicating asymptomatic bacteriuria during pregnancy. A multicenter, double-blind, randomized, placebo controlled noninferiority trial was conducted in antenatal clinics in Thailand, the Philippines, Vietnam, and Argentina. Pregnant women seeking antenatal care between March 2004 and March 2007 who met the inclusion and exclusion criteria were invited to participate in the study. Those who consented were randomly allocated to receive either a 1-day or a 7-day course of 100 mg capsules of nitrofurantoin, which was taken twice daily. The primary outcome was bacteriologic cure on day 14 of treatment. : A total of 1,248 of 24,430 eligible women had asymptomatic bacteriuria, making the overall prevalence of 5.1%. Of these 1,248 women, 778 women were successfully recruited, and 386 and 392 women were randomly allocated to 1-day and 7-day regimens, respectively. Escherichia coli was the most common potentially pathogenic bacteria detected, its prevalence approaching 50%. Bacteriologic cure rates at treatment day 14 were 75.7% and 86.2% for 1-day and 7-day regimens, respectively. The cure rate difference was -10.5% (95% confidence interval -16.1% to -4.9%). Mean birth weight and mean gestational age at delivery were significantly lower in the 1-day regimen group. There were fewer adverse effects in the 1-day regimen group, but the differences were not statistically significant. A 1-day regimen of nitrofurantoin is significantly less effective than a 7-day regimen. Women with asymptomatic bacteriuria in pregnancy should receive the standard 7-day regimen. ISRCTN, isrctn.org, ISRCTN11966080 I.

The REstart or STop Antithrombotics Randomised Trial (RESTART) after stroke due to intracerebral haemorrhage: study protocol for a randomised controlled trial.

PubMed

Al-Shahi Salman, Rustam; Dennis, Martin S; Murray, Gordon D; Innes, Karen; Drever, Jonathan; Dinsmore, Lynn; Williams, Carol; White, Philip M; Whiteley, William N; Sandercock, Peter A G; Sudlow, Cathie L M; Newby, David E; Sprigg, Nikola; Werring, David J

2018-03-05

For adults surviving stroke due to spontaneous (non-traumatic) intracerebral haemorrhage (ICH) who had taken an antithrombotic (i.e. anticoagulant or antiplatelet) drug for the prevention of vaso-occlusive disease before the ICH, it is unclear whether starting antiplatelet drugs results in an increase in the risk of recurrent ICH or a beneficial net reduction of all serious vascular events compared to avoiding antiplatelet drugs. The REstart or STop Antithrombotics Randomised Trial (RESTART) is an investigator-led, randomised, open, assessor-blind, parallel-group, randomised trial comparing starting versus avoiding antiplatelet drugs for adults surviving antithrombotic-associated ICH at 122 hospital sites in the United Kingdom. RESTART uses a central, web-based randomisation system using a minimisation algorithm, with 1:1 treatment allocation to which central research staff are masked. Central follow-up includes annual postal or telephone questionnaires to participants and their general (family) practitioners, with local provision of information about adverse events and outcome events. The primary outcome is recurrent symptomatic ICH. The secondary outcomes are: symptomatic haemorrhagic events; symptomatic vaso-occlusive events; symptomatic stroke of uncertain type; other fatal events; modified Rankin Scale score; adherence to antiplatelet drug(s). The magnetic resonance imaging (MRI) sub-study involves the conduct of brain MRI according to a standardised imaging protocol before randomisation to investigate heterogeneity of treatment effect according to the presence of brain microbleeds. Recruitment began on 22 May 2013. The target sample size is at least 720 participants in the main trial (at least 550 in the MRI sub-study). Final results of RESTART will be analysed and disseminated in 2019. ISRCTN71907627 ( www.isrctn.com/ISRCTN71907627 ). Prospectively registered on 25 April 2013.

Online Alcohol Assessment and Feedback for Hazardous and Harmful Drinkers: Findings From the AMADEUS-2 Randomized Controlled Trial of Routine Practice in Swedish Universities.

PubMed

Bendtsen, Preben; Bendtsen, Marcus; Karlsson, Nadine; White, Ian R; McCambridge, Jim

2015-07-09

Previous research on the effectiveness of online alcohol interventions for college students has shown mixed results. Small benefits have been found in some studies and because online interventions are inexpensive and possible to implement on a large scale, there is a need for further study. This study evaluated the effectiveness of national provision of a brief online alcohol intervention for students in Sweden. Risky drinkers at 9 colleges and universities in Sweden were invited by mail and identified using a single screening question. These students (N=1605) gave consent and were randomized into a 2-arm parallel group randomized controlled trial consisting of immediate or delayed access to a fully automated online assessment and intervention with personalized feedback. After 2 months, there was no strong evidence of effectiveness with no statistically significant differences in the planned analyses, although there were some indication of possible benefit in sensitivity analyses suggesting an intervention effect of a 10% reduction (95% CI -30% to 10%) in total weekly alcohol consumption. Also, differences in effect sizes between universities were seen with participants from a major university (n=365) reducing their weekly alcohol consumption by 14% (95% CI -23% to -4%). However, lower recruitment than planned and differential attrition in the intervention and control group (49% vs 68%) complicated interpretation of the outcome data. Any effects of current national provision are likely to be small and further research and development work is needed to enhance effectiveness. International Standard Randomized Controlled Trial Number (ISRCTN): 02335307; http://www.isrctn.com/ISRCTN02335307 (Archived by WebCite at http://www.webcitation.org/6ZdPUh0R4).

Ruxolitinib vs best available therapy for ET intolerant or resistant to hydroxycarbamide.

PubMed

Harrison, Claire N; Mead, Adam J; Panchal, Anesh; Fox, Sonia; Yap, Christina; Gbandi, Emmanouela; Houlton, Aimee; Alimam, Samah; Ewing, Joanne; Wood, Marion; Chen, Frederick; Coppell, Jason; Panoskaltsis, Nicki; Knapper, Steven; Ali, Sahra; Hamblin, Angela; Scherber, Robyn; Dueck, Amylou C; Cross, Nicholas C P; Mesa, Ruben; McMullin, Mary Frances

2017-10-26

Treatments for high-risk essential thrombocythemia (ET) address thrombocytosis, disease-related symptoms, as well as risks of thrombosis, hemorrhage, transformation to myelofibrosis, and leukemia. Patients resistant/intolerant to hydroxycarbamide (HC) have a poor outlook. MAJIC (ISRCTN61925716) is a randomized phase 2 trial of ruxolitinib (JAK1/2 inhibitor) vs best available therapy (BAT) in ET and polycythemia vera patients resistant or intolerant to HC. Here, findings of MAJIC-ET are reported, where the modified intention-to-treat population included 58 and 52 patients randomized to receive ruxolitinib or BAT, respectively. There was no evidence of improvement in complete response within 1 year reported in 27 (46.6%) patients treated with ruxolitinib vs 23 (44.2%) with BAT ( P = .40). At 2 years, rates of thrombosis, hemorrhage, and transformation were not significantly different; however, some disease-related symptoms improved in patients receiving ruxolitinib relative to BAT. Molecular responses were uncommon; there were 2 complete molecular responses (CMR) and 1 partial molecular response in CALR- positive ruxolitinib-treated patients. Transformation to myelofibrosis occurred in 1 CMR patient, presumably because of the emergence of a different clone, raising questions about the relevance of CMR in ET patients. Grade 3 and 4 anemia occurred in 19% and 0% of ruxolitinib vs 0% (both grades) in the BAT arm, and grade 3 and 4 thrombocytopenia in 5.2% and 1.7% of ruxolitinib vs 0% (both grades) of BAT-treated patients. Rates of discontinuation or treatment switching did not differ between the 2 trial arms. The MAJIC-ET trial suggests that ruxolitinib is not superior to current second-line treatments for ET. This trial was registered at www.isrctn.com as #ISRCTN61925716. © 2017 by The American Society of Hematology.

Impaired mitochondrial Ca{sup 2+} homeostasis in respiratory chain-deficient cells but efficient compensation of energetic disadvantage by enhanced anaerobic glycolysis due to low ATP steady state levels

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kleist-Retzow, Juergen-Christoph von; Hue-Tran Hornig-Do; Schauen, Matthias

2007-08-15

Energy-producing pathways, adenine nucleotide levels, oxidative stress response and Ca{sup 2+} homeostasis were investigated in cybrid cells incorporating two pathogenic mitochondrial DNA point mutations, 3243A > G and 3302A > G in tRNA{sup Leu(UUR)}, as well as Rho{sup 0} cells and compared to their parental 143B osteosarcoma cell line. All cells suffering from a severe respiratory chain deficiency were able to proliferate as fast as controls. The major defect in oxidative phosphorylation was efficiently compensated by a rise in anaerobic glycolysis, so that the total ATP production rate was preserved. This enhancement of glycolysis was enabled by a considerable decreasemore » of cellular total adenine nucleotide pools and a concomitant shift in the AMP + ADP/ATP ratios, while the energy charge potential was still in the normal range. Further important consequences were an increased production of superoxide which, however, was neither escorted by major changes in the antioxidative defence systems nor was it leading to substantial oxidative damage. Most interestingly, the lowered mitochondrial membrane potential led to a disturbed intramitochondrial calcium homeostasis, which most likely is a major pathomechanism in mitochondrial diseases.« less

A psychosocial intervention for the management of functional dysphonia: complex intervention development and pilot randomised trial.

PubMed

Deary, Vincent; McColl, Elaine; Carding, Paul; Miller, Tracy; Wilson, Janet

2018-01-01

Medically unexplained loss or alteration of voice-functional dysphonia-is the commonest presentation to speech and language therapists (SLTs). Besides the impact on personal and work life, functional dysphonia is also associated with increased levels of anxiety and depression and poor general health. Voice therapy delivered by SLTs improves voice but not these associated symptoms. The aims of this research were the systematic development of a complex intervention to improve the treatment of functional dysphonia, and the trialling of this intervention for feasibility and acceptability to SLTs and patients in a randomised pilot study. A theoretical model of medically unexplained symptoms (MUS) was elaborated through literature review and synthesis. This was initially applied as an assessment format in a series of patient interviews. Data from this stage and a small consecutive cohort study were used to design and refine a brief cognitive behavioural therapy (CBT) training intervention for a SLT. This was then implemented in an external pilot patient randomised trial where one SLT delivered standard voice therapy or voice therapy plus CBT to 74 patients. The primary outcomes were of the acceptability of the intervention to patients and the SLT, and the feasibility of changing the SLT's clinical practice through a brief training. This was measured through monitoring treatment flow and through structured analysis of the content of intervention for treatment fidelity and inter-treatment contamination. As measured by treatment flow, the intervention was as acceptable as standard voice therapy to patients. Analysis of treatment content showed that the SLT was able to conduct a complex CBT formulation and deliver novel treatment strategies for fatigue, sleep, anxiety and depression in the majority of patients. On pre-post measures of voice and quality of life, patients in both treatment arms improved. These interventions were acceptable to patients. Emotional and psychosocial issues presented routinely in the study patient group and CBT techniques were used, deliberately and inadvertently, in both treatment arms. This CBT "contamination" of the voice therapy only arm reflects the chief limitation of the study: one therapist delivered both treatments. Registered with the ISRCTN under the title: Training a Speech and Language Therapist in Cognitive Behavioural Therapy to treat Functional Dysphonia - A Randomised Controlled Trial .Trial Identifier: ISRCTN20582523 Registered 19/05/2010; retrospectively registered. http://www.isrctn.com/ISRCTN20582523.

Community and health system intervention to reduce disrespect and abuse during childbirth in Tanga Region, Tanzania: A comparative before-and-after study.

PubMed

Kujawski, Stephanie A; Freedman, Lynn P; Ramsey, Kate; Mbaruku, Godfrey; Mbuyita, Selemani; Moyo, Wema; Kruk, Margaret E

2017-07-01

Abusive treatment of women during childbirth has been documented in low-resource countries and is a deterrent to facility utilization for delivery. Evidence for interventions to address women's poor experience is scant. We assessed a participatory community and health system intervention to reduce the prevalence of disrespect and abuse during childbirth in Tanzania. We used a comparative before-and-after evaluation design to test the combined intervention to reduce disrespect and abuse. Two hospitals in Tanga Region, Tanzania were included in the study, 1 randomly assigned to receive the intervention. Women who delivered at the study facilities were eligible to participate and were recruited upon discharge. Surveys were conducted at baseline (December 2011 through May 2012) and after the intervention (March through September 2015). The intervention consisted of a client service charter and a facility-based, quality-improvement process aimed to redefine norms and practices for respectful maternity care. The primary outcome was any self-reported experiences of disrespect and abuse during childbirth. We used multivariable logistic regression to estimate a difference-in-difference model. At baseline, 2,085 women at the 2 study hospitals who had been discharged from the maternity ward after delivery were invited to participate in the survey. Of these, 1,388 (66.57%) agreed to participate. At endline, 1,680 women participated in the survey (72.29% of those approached). The intervention was associated with a 66% reduced odds of a woman experiencing disrespect and abuse during childbirth (odds ratio [OR]: 0.34, 95% CI: 0.21-0.58, p < 0.0001). The biggest reductions were for physical abuse (OR: 0.22, 95% CI: 0.05-0.97, p = 0.045) and neglect (OR: 0.36, 95% CI: 0.19-0.71, p = 0.003). The study involved only 2 hospitals in Tanzania and is thus a proof-of-concept study. Future, larger-scale research should be undertaken to evaluate the applicability of this approach to other settings. After implementation of the combined intervention, the likelihood of women's reports of disrespectful treatment during childbirth was substantially reduced. These results were observed nearly 1 year after the end of the project's facilitation of implementation, indicating the potential for sustainability. The results indicate that a participatory community and health system intervention designed to tackle disrespect and abuse by changing the norms and standards of care is a potential strategy to improve the treatment of women during childbirth at health facilities. The trial is registered on the ISRCTN Registry, ISRCTN 48258486. ISRCTN Registry, ISRCTN 48258486.

A web-based program to increase knowledge and reduce cigarette and nargila smoking among Arab university students in Israel: mixed-methods study to test acceptability.

PubMed

Essa-Hadad, Jumanah; Linn, Shai; Rafaeli, Sheizaf

2015-02-20

Among Arab citizens in Israel, cigarette and nargila (hookah, waterpipe) smoking is a serious public health problem, particularly among the young adult population. With the dramatic increase of Internet and computer use among Arab college and university students, a Web-based program may provide an easy, accessible tool to reduce smoking rates without heavy resource demands required by traditional methods. The purpose of this research was to examine the acceptability and feasibility of a pilot Web-based program that provides tailored feedback to increase smoking knowledge and reduce cigarette and nargila smoking behaviors among Arab college/university students in Israel. A pilot Web-based program was developed, consisting of a self-administered questionnaire and feedback system on cigarette and nargila smoking. Arab university students were recruited to participate in a mixed-methods study, using both quantitative (pre-/posttest study design) and qualitative tools. A posttest was implemented at 1 month following participation in the intervention to assess any changes in smoking knowledge and behaviors. Focus group sessions were implemented to assess acceptability and preferences related to the Web-based program. A total of 225 participants-response rate of 63.2% (225/356)-completed the intervention at baseline and at 1-month poststudy, and were used for the comparative analysis. Statistically significant reductions in nargila smoking among participants (P=.001) were found. The intervention did not result in reductions in cigarette smoking. However, the tailored Web intervention resulted in statistically significant increases in the intention to quit smoking (P=.021). No statistically significant increases in knowledge were seen at 1-month poststudy. Participants expressed high satisfaction with the intervention and 93.8% (211/225) of those who completed the intervention at both time intervals reported that they would recommend the program to their friends, indicating excellent acceptability and feasibility of the intervention. This was further emphasized in the focus group sessions. A tailored Web-based program may be a promising tool to reduce nargila smoking among Arab university students in Israel. The tailored Web intervention was not successful at significantly reducing cigarette smoking or increasing knowledge. However, the intervention did increase participants' intention to quit smoking. Participants considered the Web-based tool to be an interesting, feasible, and highly acceptable strategy. ISRCTN registry ISRCTN59207794; http://www.isrctn.com/ISRCTN59207794 (Archived by WebCite at http://www.webcitation.org/6VkYOBNOJ).

Normothermic versus hypothermic cardiopulmonary bypass in children undergoing open heart surgery (thermic-2): study protocol for a randomized controlled trial.

PubMed

Baos, Sarah; Sheehan, Karen; Culliford, Lucy; Pike, Katie; Ellis, Lucy; Parry, Andrew J; Stoica, Serban; Ghorbel, Mohamed T; Caputo, Massimo; Rogers, Chris A

2015-05-25

During open heart surgery, patients are connected to a heart-lung bypass machine that pumps blood around the body ("perfusion") while the heart is stopped. Typically the blood is cooled during this procedure ("hypothermia") and warmed to normal body temperature once the operation has been completed. The main rationale for "whole body cooling" is to protect organs such as the brain, kidneys, lungs, and heart from injury during bypass by reducing the body's metabolic rate and decreasing oxygen consumption. However, hypothermic perfusion also has disadvantages that can contribute toward an extended postoperative hospital stay. Research in adults and small randomized controlled trials in children suggest some benefits to keeping the blood at normal body temperature throughout surgery ("normothermia"). However, the two techniques have not been extensively compared in children. The Thermic-2 study will test the hypothesis that the whole body inflammatory response to the nonphysiological bypass and its detrimental effects on different organ functions may be attenuated by maintaining the body at 35°C-37°C (normothermic) rather than 28°C (hypothermic) during pediatric complex open heart surgery. This is a single-center, randomized controlled trial comparing the effectiveness and acceptability of normothermic versus hypothermic bypass in 141 children with congenital heart disease undergoing open heart surgery. Children having scheduled surgery to repair a heart defect not requiring deep hypothermic circulatory arrest represent the target study population. The co-primary clinical outcomes are duration of inotropic support, intubation time, and postoperative hospital stay. Secondary outcomes are in-hospital mortality and morbidity, blood loss and transfusion requirements, pre- and post-operative echocardiographic findings, routine blood gas and blood test results, renal function, cerebral function, regional oxygen saturation of blood in the cerebral cortex, assessment of genomic expression changes in cardiac tissue biopsies, and neuropsychological development. A total of 141 patients have been successfully randomized over 2 years and 10 months and are now being followed-up for 1 year. Results will be published in 2015. We believe this to be the first large pragmatic study comparing clinical outcomes during normothermic versus hypothermic bypass in complex open heart surgery in children. It is expected that this work will provide important information to improve strategies of cardiopulmonary bypass perfusion and therefore decrease the inevitable organ damage that occurs during nonphysiological body perfusion. ISRCTN Registry: ISRCTN93129502, http://www.isrctn.com/ISRCTN93129502 (Archived by WebCitation at http://www.webcitation.org/6Yf5VSyyG).

The FOCUS, AFFINITY and EFFECTS trials studying the effect(s) of fluoxetine in patients with a recent stroke: statistical and health economic analysis plan for the trials and for the individual patient data meta-analysis.

PubMed

Graham, Catriona; Lewis, Steff; Forbes, John; Mead, Gillian; Hackett, Maree L; Hankey, Graeme J; Gommans, John; Nguyen, Huy Thang; Lundström, Erik; Isaksson, Eva; Näsman, Per; Rudberg, Ann-Sofie; Dennis, Martin

2017-12-28

Small trials have suggested that fluoxetine may improve neurological recovery from stroke. FOCUS, AFFINITY and EFFECTS are a family of investigator-led, multicentre, parallel group, randomised, placebo-controlled trials which aim to determine whether the routine administration of fluoxetine (20 mg daily) for six months after an acute stroke improves patients' functional outcome. The core protocol for the three trials has been published (Mead et al., Trials 20:369, 2015). The trials include patients aged 18 years and older with a clinical diagnosis of stroke and persisting focal neurological deficits at randomisation 2-15 days after stroke onset. Patients are randomised centrally via each trials' web-based randomisation system using a common minimisation algorithm. Patients are allocated fluoxetine 20 mg once daily or matching placebo capsules for six months. The primary outcome measure is the modified Rankin scale (mRS) at six months. Secondary outcomes include: living circumstances; the Stroke Impact Scale; EuroQol (EQ5D-5 L); the vitality subscale of the 36-Item Short Form Health Survey (SF36); diagnosis of depression; adherence to medication; serious adverse events including death and recurrent stroke; and resource use at six and 12 months and the mRS at 12 months. Minor variations have been tailored to the national setting in the UK (FOCUS), Australia, New Zealand and Vietnam (AFFINITY) and Sweden (EFFECTS). Each trial is run and funded independently and will report its own results. A prospectively planned individual patient data meta-analysis of all three trials will provide the most precise estimate of the overall effect and establish whether any effects differ between trials or subgroups. This statistical analysis plan describes the core analyses for all three trials and that for the individual patient data meta-analysis. Recruitment and follow-up in the FOCUS trial is expected to be completed by the end of 2018. AFFINITY and EFFECTS are likely to complete follow-up in 2020. FOCUS: ISRCTN , ISRCTN83290762 . Registered on 23 May 2012. EudraCT, 2011-005616-29. Registered on 3 February 2012. Australian New Zealand Clinical Trials Registry, ACTRN12611000774921 . Registered on 22 July 2011. ISRCTN , ISRCTN13020412 . Registered on 19 December 2014. Clinicaltrials.gov, NCT02683213 . Registered on 2 February 2016. EudraCT, 2011-006130-16 . Registered on 8 August 2014.

A Web-Based Program to Increase Knowledge and Reduce Cigarette and Nargila Smoking Among Arab University Students in Israel: Mixed-Methods Study to Test Acceptability

PubMed Central

Linn, Shai; Rafaeli, Sheizaf

2015-01-01

Background Among Arab citizens in Israel, cigarette and nargila (hookah, waterpipe) smoking is a serious public health problem, particularly among the young adult population. With the dramatic increase of Internet and computer use among Arab college and university students, a Web-based program may provide an easy, accessible tool to reduce smoking rates without heavy resource demands required by traditional methods. Objective The purpose of this research was to examine the acceptability and feasibility of a pilot Web-based program that provides tailored feedback to increase smoking knowledge and reduce cigarette and nargila smoking behaviors among Arab college/university students in Israel. Methods A pilot Web-based program was developed, consisting of a self-administered questionnaire and feedback system on cigarette and nargila smoking. Arab university students were recruited to participate in a mixed-methods study, using both quantitative (pre-/posttest study design) and qualitative tools. A posttest was implemented at 1 month following participation in the intervention to assess any changes in smoking knowledge and behaviors. Focus group sessions were implemented to assess acceptability and preferences related to the Web-based program. Results A total of 225 participants—response rate of 63.2% (225/356)—completed the intervention at baseline and at 1-month poststudy, and were used for the comparative analysis. Statistically significant reductions in nargila smoking among participants (P=.001) were found. The intervention did not result in reductions in cigarette smoking. However, the tailored Web intervention resulted in statistically significant increases in the intention to quit smoking (P=.021). No statistically significant increases in knowledge were seen at 1-month poststudy. Participants expressed high satisfaction with the intervention and 93.8% (211/225) of those who completed the intervention at both time intervals reported that they would recommend the program to their friends, indicating excellent acceptability and feasibility of the intervention. This was further emphasized in the focus group sessions. Conclusions A tailored Web-based program may be a promising tool to reduce nargila smoking among Arab university students in Israel. The tailored Web intervention was not successful at significantly reducing cigarette smoking or increasing knowledge. However, the intervention did increase participants’ intention to quit smoking. Participants considered the Web-based tool to be an interesting, feasible, and highly acceptable strategy. Trial Registration Trial Registration: ISRCTN registry ISRCTN59207794; http://www.isrctn.com/ISRCTN59207794 (Archived by WebCite at http://www.webcitation.org/6VkYOBNOJ). PMID:25707034

World Hip Trauma Evaluation (WHiTE): framework for embedded comprehensive cohort studies.

PubMed

Costa, Matthew L; Griffin, Xavier L; Achten, Juul; Metcalfe, David; Judge, Andrew; Pinedo-Villanueva, Rafael; Parsons, Nicholas

2016-10-21

Osteoporotic hip fractures present a significant global challenge to patients, clinicians and healthcare systems. It is estimated that hip fracture accounts for 1.4% of total social and healthcare costs in the established market economies. The World Hip Trauma Evaluation (WHiTE) was set up to measure outcome in a comprehensive cohort of UK patients with hip fracture. All patients in the cohort are treated under a single comprehensive treatment pathway. A core outcome set, including health-related quality of life, is collected on all the patients. This protocol describes the current multicentre project that will be used as a vehicle to deliver a series of embedded observational studies. Research Ethics Committee approval was granted (Rec reference 11/LO/0927, approved 18/8/2011) and each hospital trust provided National Health Service (NHS) approvals. The study is registered with National Institute of Health Research Portfolio (UKCRN ID 12351) and the ISRCTN registry (ISRCTN63982700). Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

Continuous bilateral thoracic paravertebral blockade for analgesia after cardiac surgery: a randomised, controlled trial.

PubMed

Lockwood, Geoff G; Cabreros, Leilani; Banach, Dorota; Punjabi, Prakash P

2017-10-01

Continuous bilateral thoracic paravertebral blockade has been used for analgesia after cardiac surgery, but its efficacy has never been formally tested. Fifty adult patients were enrolled in a double-blind, randomised, controlled study of continuous bilateral thoracic paravertebral infusion of 0.5% lidocaine (1 mg.kg -1 .hr -1 ) for analgesia after coronary surgery. Control patients received a subcutaneous infusion of lidocaine at the same rate through catheters inserted at the same locations as the study group. The primary outcome was morphine consumption at 48 hours using patient-controlled analgesia (PCA). Secondary outcomes included pain, respiratory function, nausea and vomiting. Serum lidocaine concentrations were measured on the first two post-operative days. There was no difference in morphine consumption or in any other outcome measure between the groups. Serum lidocaine concentrations increased during the study, with a maximum of 5.9 mg.l -1 . There were no adverse events as a consequence of the study. Bilateral paravertebral infusion of lidocaine confers no advantage over systemic lidocaine infusion after cardiac surgery. ISRCTN13424423 ( https://www.isrctn.com ).

Comparing cost of indwelling pleural catheter vs talc pleurodesis for malignant pleural effusion.

PubMed

Penz, Erika D; Mishra, Eleanor K; Davies, Helen E; Manns, Braden J; Miller, Robert F; Rahman, Najib M

2014-10-01

Malignant pleural effusion is associated with short life expectancy and significant morbidity. A randomized controlled trial comparing indwelling pleural catheters (IPCs) with talc pleurodesis found that IPCs reduced in-hospital time and the need for additional procedures but were associated with excess adverse events. Using data from the clinical trial, we compared costs associated with use of IPCs and with talc pleurodesis. Resource use and adverse events were captured through case report forms over the 1-year trial follow-up. Costs for outpatient and inpatient visits, diagnostic imaging, nursing, and doctor time were obtained from the UK National Health Service reference costs and University of Kent's Unit Costs of Health and Social Care 2011 and inflated to 2013 using the UK Consumer Price Index. Procedure supply costs were obtained from the manufacturer. Difference in mean costs was compared using nonparametric bootstrapping. All costs were converted to US dollars using the Organisation for Economic Co-operation and Development Purchasing Power Parity Index. Overall mean cost (SD) for managing patients with IPCs and talc pleurodesis was $4,993 ($5,529) and $4,581 ($4,359), respectively. The incremental mean cost difference was $401, with 95% CI of -$1,387 to $2,261. The mean cost related to ongoing drainage in the IPC group was $1,011 ($732) vs $57 ($213) in the talc pleurodesis group (P = .001). This included the cost of drainage bottles, dressing changes in the first month, and catheter removal. There was no significant difference in cost of the initial intervention or adverse events between the groups. For patients with survival < 14 weeks, IPC is significantly less costly than talc pleurodesis, with mean cost difference of -$1,719 (95% CI, -$3,376 to -$85). There is no significant difference in the mean cost of managing patients with IPCs compared with talc pleurodesis. For patients with limited survival, IPC appears less costly. isrctn.org; No.: ISRCTN87514420; URL: www.isrctn.org.

Central Fetal Monitoring With and Without Computer Analysis: A Randomized Controlled Trial.

PubMed

Nunes, Inês; Ayres-de-Campos, Diogo; Ugwumadu, Austin; Amin, Pina; Banfield, Philip; Nicoll, Antony; Cunningham, Simon; Sousa, Paulo; Costa-Santos, Cristina; Bernardes, João

2017-01-01

To evaluate whether intrapartum fetal monitoring with computer analysis and real-time alerts decreases the rate of newborn metabolic acidosis or obstetric intervention when compared with visual analysis. A randomized clinical trial carried out in five hospitals in the United Kingdom evaluated women with singleton, vertex fetuses of 36 weeks of gestation or greater during labor. Continuous central fetal monitoring by computer analysis and online alerts (experimental arm) was compared with visual analysis (control arm). Fetal blood sampling and electrocardiographic ST waveform analysis were available in both arms. The primary outcome was incidence of newborn metabolic acidosis (pH less than 7.05 and base deficit greater than 12 mmol/L). Prespecified secondary outcomes included operative delivery, use of fetal blood sampling, low 5-minute Apgar score, neonatal intensive care unit admission, hypoxic-ischemic encephalopathy, and perinatal death. A sample size of 3,660 per group (N=7,320) was planned to be able to detect a reduction in the rate of metabolic acidosis from 2.8% to 1.8% (two-tailed α of 0.05 with 80% power). From August 2011 through July 2014, 32,306 women were assessed for eligibility and 7,730 were randomized: 3,961 to computer analysis and online alerts, and 3,769 to visual analysis. Baseline characteristics were similar in both groups. Metabolic acidosis occurred in 16 participants (0.40%) in the experimental arm and 22 participants (0.58%) in the control arm (relative risk 0.69 [0.36-1.31]). No statistically significant differences were found in the incidence of secondary outcomes. Compared with visual analysis, computer analysis of fetal monitoring signals with real-time alerts did not significantly reduce the rate of metabolic acidosis or obstetric intervention. A lower-than-expected rate of newborn metabolic acidosis was observed in both arms of the trial. ISRCTN Registry, http://www.isrctn.com, ISRCTN42314164.

Transcranial magnetic stimulation of dorsolateral prefrontal cortex reduces cocaine use: A pilot study.

PubMed

Terraneo, Alberto; Leggio, Lorenzo; Saladini, Marina; Ermani, Mario; Bonci, Antonello; Gallimberti, Luigi

2016-01-01

Recent animal studies demonstrate that compulsive cocaine seeking strongly reduces prelimbic frontal cortex activity, while optogenetic stimulation of this brain area significantly inhibits compulsive cocaine seeking, providing a strong rationale for applying brain stimulation to reduce cocaine consumption. Thus, we employed repetitive transcranial magnetic stimulation (rTMS), to test if dorsolateral prefrontal cortex (DLPFC) stimulation might prevent cocaine use in humans. Thirty-two cocaine-addicted patients were randomly assigned to either the experimental group (rTMS) on the left DLPFC, or to a control group (pharmacological agents) during a 29-day study (Stage 1). This was followed by a 63-day follow-up (Stage 2), during which all participants were offered rTMS treatment. Amongst the patients who completed Stage 1, 16 were in the rTMS group (100%) and 13 in the control group (81%). No significant adverse events were noted. During Stage 1, there were a significantly higher number of cocaine-free urine drug tests in the rTMS group compared to control (p=0.004). Craving for cocaine was also significantly lower in the rTMS group compared to the controls (p=0.038). Out of 13 patients who completed Stage 1 in the control group, 10 patients received rTMS treatment during Stage 2 and showed significant improvement with favorable outcomes becoming comparable to those of the rTMS group. The present preliminary findings support the safety of rTMS in cocaine-addicted patients, and suggest its potential therapeutic role for rTMS-driven PFC stimulation in reducing cocaine use, providing a strong rationale for developing larger placebo-controlled studies. Trial name: Repetitive transcranial magnetic stimulation (rTMS) in cocaine abusers, URL:〈http://www.isrctn.com/ISRCTN15823943?q=&filters=&sort=&offset=8&totalResults=13530&page=1&pageSize=10&searchType=basic-search〉, ISRCTN15823943. Published by Elsevier B.V.

The Effectiveness and Cost-Effectiveness of Web-Based and Home-Based Postnatal Psychoeducational Interventions for First-Time Mothers: Randomized Controlled Trial Protocol

PubMed Central

Chong, Yap-Seng; Jiao, Nana; Luo, Nan

2018-01-01

Background In addition to recuperating from the physical and emotional demands of childbirth, first-time mothers are met with demands of adapting to their social roles while picking up new skills to take care of their newborn. Mothers may not feel adequately prepared for parenthood if they are situated in an unsupported environment. Postnatal psychoeducational interventions have been shown to be useful and can offer a cost-effective solution for improving maternal outcomes. Objective The objective of this study was to examine the effectiveness and cost-effectiveness of Web-based and home-based postnatal psychoeducational programs for first-time mothers on maternal outcomes. Methods A randomized controlled three-group pre- and posttests experimental design is proposed. This study plans to recruit 204 first-time mothers on their day of discharge from a public tertiary hospital in Singapore. Eligible first-time mothers will be randomly allocated to either a Web-based psychoeducation group, a home-based psychoeducation group, or a control group receiving standard care. The outcomes include maternal parental self-efficacy, social support, psychological well-being (anxiety and postnatal depression), and cost evaluation. Data will be collected at baseline, 1 month, 3 months, and 6 months post-delivery. Results The recruitment (n=204) commenced in October 2016 and was completed in February 2017, with 68 mothers in each group. The 6-month follow-up data collection was completed in August 2017. Conclusions This study may identify an effective and cost-effective Web-based postnatal psychoeducational program to improve first-time mothers’ health outcomes. The provision of a widely-accessed Web-based postnatal psychoeducational program will eventually lead to more positive postnatal experiences for first-time mothers and positively influence their future birth plans. Trial Registration International Standard Randomized Controlled Trial Number (ISRCTN): 45202278; http://www.isrctn.com/ISRCTN45202278 (Archived by WebCite at http://www.webcitation.org/6whx0pQ2F). PMID:29386175

Effect of a brief outreach educational intervention on the translation of acute poisoning treatment guidelines to practice in rural Sri Lankan hospitals: a cluster randomized controlled trial.

PubMed

Senarathna, Lalith; Buckley, Nick A; Dibley, Michael J; Kelly, Patrick J; Jayamanna, Shaluka F; Gawarammana, Indika B; Dawson, Andrew H

2013-01-01

In developing countries, including Sri Lanka, a high proportion of acute poisoning and other medical emergencies are initially treated in rural peripheral hospitals. Patients are then usually transferred to referral hospitals for further treatment. Guidelines are often used to promote better patient care in these emergencies. We conducted a cluster randomized controlled trial (ISRCTN73983810) which aimed to assess the effect of a brief educational outreach ('academic detailing') intervention to promote the utilization of treatment guidelines for acute poisoning. This cluster RCT was conducted in the North Central Province of Sri Lanka. All peripheral hospitals in the province were randomized to either intervention or control. All hospitals received a copy of the guidelines. The intervention hospitals received a brief out-reach academic detailing workshop which explained poisoning treatment guidelines and guideline promotional items designed to be used in daily care. Data were collected on all patients admitted due to poisoning for 12 months post-intervention in all study hospitals. Information collected included type of poison exposure, initial investigations, treatments and hospital outcome. Patients transferred from peripheral hospitals to referral hospitals had their clinical outcomes recorded. There were 23 intervention and 23 control hospitals. There were no significant differences in the patient characteristics, such as age, gender and the poisons ingested. The intervention hospitals showed a significant improvement in administration of activated charcoal [OR 2.95 (95% CI 1.28-6.80)]. There was no difference between hospitals in use of other decontamination methods. This study shows that an educational intervention consisting of brief out-reach academic detailing was effective in changing treatment behavior in rural Sri Lankan hospitals. The intervention was only effective for treatments with direct clinician involvement, such as administering activated charcoal. It was not successful for treatments usually administered by non-professional staff such as forced emesis for poisoning. Controlled-Trials.com ISRCTN73983810 ISRCTN73983810.

Two Novel Cognitive Behavioral Therapy–Based Mobile Apps for Agoraphobia: Randomized Controlled Trial

PubMed Central

Christoforou, Marina; Sáez Fonseca, José Andrés

2017-01-01

Background Despite the large body of literature demonstrating the effectiveness of cognitive behavioral treatments for agoraphobia, many patients remain untreated because of various barriers to treatment. Web-based and mobile-based interventions targeting agoraphobia may provide a solution to this problem, but there is a lack of research investigating the efficacy of such interventions. Objective The objective of our study was to evaluate for the first time the effectiveness of a self-guided mobile-based intervention primarily targeting agoraphobic symptoms, with respect to a generic mobile app targeting anxiety. Methods A Web-based randomized controlled trial (RCT) compared a novel mobile app designed to target agoraphobia (called Agoraphobia Free) with a mobile app designed to help with symptoms of anxiety in general (called Stress Free). Both interventions were based on established cognitive behavioral principles. We recruited participants (N=170) who self-identified as having agoraphobia and assessed them online at baseline, midpoint, and end point (posttreatment) over a period of 12 weeks. The primary outcome was symptom severity measured by the Panic and Agoraphobia Scale. Results Both groups had statistically significant improvements in symptom severity over time (difference –5.97, 95% CI –8.49 to –3.44, P<.001 for Agoraphobia Free and –6.35, 95% CI –8.82 to –3.87, P<.001 for Stress Free), but there were no significant between-group differences on the primary outcome (difference 0.38, 95% CI –1.96 to 3.20, P=.64). Conclusions This is, to our knowledge, the first RCT to provide evidence that people who identify as having agoraphobia may equally benefit from a diagnosis-specific and a transdiagnostic mobile-based intervention. We also discuss clinical and research implications for the development and dissemination of mobile mental health apps. Trial Registration International Standard Randomized Controlled Trial Number (ISRCTN): 98453199; http://www.isrctn.com /ISRCTN98453199 (Archived by WebCite at http://www.webcitation.org/6uR5vsdZw) PMID:29175809

Retrospective Methods Analysis of Semiautomated Intracerebral Hemorrhage Volume Quantification From a Selection of the STICH II Cohort (Early Surgery Versus Initial Conservative Treatment in Patients With Spontaneous Supratentorial Lobar Intracerebral Haematomas).

PubMed

Haley, Mark D; Gregson, Barbara A; Mould, W Andrew; Hanley, Daniel F; Mendelow, Alexander David

2018-02-01

The ABC/2 method for calculating intracerebral hemorrhage (ICH) volume has been well validated. However, the formula, derived from the volume of an ellipse, assumes the shape of ICH is elliptical. We sought to compare the agreement of the ABC/2 formula with other methods through retrospective analysis of a selection of the STICH II cohort (Early Surgery Versus Initial Conservative Treatment in Patients With Spontaneous Supratentorial Lobar Intracerebral Haematomas). From 390 patients, 739 scans were selected from the STICH II image archive based on the availability of a CT scan compatible with OsiriX DICOM viewer. ICH volumes were calculated by the reference standard semiautomatic segmentation in OsiriX software and compared with calculated arithmetic methods (ABC/2, ABC/2.4, ABC/3, and 2/3SC) volumes. Volumes were compared by difference plots for specific groups: randomization ICH (n=374), 3- to 7-day postsurgical ICH (n=206), antithrombotic-associated ICH (n=79), irregular-shape ICH (n=703) and irregular-density ICH (n=650). Density and shape were measured by the Barras ordinal shape and density groups (1-5). The ABC/2.4 method had the closest agreement to the semiautomatic segmentation volume in all groups, except for the 3- to 7-day postsurgical ICH group where the ABC/3 method was superior. Although the ABC/2 formula for calculating elliptical ICH is well validated, it must be used with caution in ICH scans where the elliptical shape of ICH is a false assumption. We validated the adjustment of the ABC/2.4 method in randomization, antithrombotic-associated, heterogeneous-density, and irregular-shape ICH. URL: http://www.isrctn.com/ISRCTN22153967. Unique identifier: ISRCTN22153967. © 2018 American Heart Association, Inc.

Reduced Cortisol Metabolism during Critical Illness

PubMed Central

Boonen, Eva; Vervenne, Hilke; Meersseman, Philippe; Andrew, Ruth; Mortier, Leen; Declercq, Peter E.; Vanwijngaerden, Yoo-Mee; Spriet, Isabel; Wouters, Pieter J.; Perre, Sarah Vander; Langouche, Lies; Vanhorebeek, Ilse; Walker, Brian R.; Van den Berghe, Greet

2015-01-01

BACKGROUND Critical illness is often accompanied by hypercortisolemia, which has been attributed to stress-induced activation of the hypothalamic–pituitary–adrenal axis. However, low corticotropin levels have also been reported in critically ill patients, which may be due to reduced cortisol metabolism. METHODS In a total of 158 patients in the intensive care unit and 64 matched controls, we tested five aspects of cortisol metabolism: daily levels of corticotropin and cortisol; plasma cortisol clearance, metabolism, and production during infusion of deuterium-labeled steroid hormones as tracers; plasma clearance of 100 mg of hydrocortisone; levels of urinary cortisol metabolites; and levels of messenger RNA and protein in liver and adipose tissue, to assess major cortisol-metabolizing enzymes. RESULTS Total and free circulating cortisol levels were consistently higher in the patients than in controls, whereas corticotropin levels were lower (P<0.001 for both comparisons). Cortisol production was 83% higher in the patients (P=0.02). There was a reduction of more than 50% in cortisol clearance during tracer infusion and after the administration of 100 mg of hydrocortisone in the patients (P≤0.03 for both comparisons). All these factors accounted for an increase by a factor of 3.5 in plasma cortisol levels in the patients, as compared with controls (P<0.001). Impaired cortisol clearance also correlated with a lower cortisol response to corticotropin stimulation. Reduced cortisol metabolism was associated with reduced inactivation of cortisol in the liver and kidney, as suggested by urinary steroid ratios, tracer kinetics, and assessment of liver-biopsy samples (P≤0.004 for all comparisons). CONCLUSIONS During critical illness, reduced cortisol breakdown, related to suppressed expression and activity of cortisol-metabolizing enzymes, contributed to hypercortisolemia and hence corticotropin suppression. The diagnostic and therapeutic implications for critically ill patients are unknown. (Funded by the Belgian Fund for Scientific Research and others; ClinicalTrials.gov numbers, NCT00512122 and NCT00115479; and Current Controlled Trials numbers, ISRCTN49433936, ISRCTN49306926, and ISRCTN08083905.) PMID:23506003

MELAS Syndrome and Kidney Disease Without Fanconi Syndrome or Proteinuria: A Case Report.

PubMed

Rudnicki, Michael; Mayr, Johannes A; Zschocke, Johannes; Antretter, Herwig; Regele, Heinz; Feichtinger, René G; Windpessl, Martin; Mayer, Gert; Pölzl, Gerhard

2016-12-01

Mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes (MELAS syndrome) represents one of the most frequent mitochondrial disorders. The majority of MELAS cases are caused by m.3243A>G mutation in the mitochondrial MT-TL1 gene, which encodes the mitochondrial tRNA Leu(UUR) . Kidney involvement usually manifests as Fanconi syndrome or focal segmental glomerulosclerosis. We describe a patient with MELAS mutation, cardiomyopathy, and chronic kidney disease without Fanconi syndrome, proteinuria, or hematuria. While the patient was waitlisted for heart transplantation, her kidney function deteriorated from an estimated glomerular filtration rate of 33 to 20mL/min/1.73m 2 within several months. Kidney biopsy was performed to distinguish decreased kidney perfusion from intrinsic kidney pathology. Histologic examination of the biopsy specimen showed only a moderate degree of tubular atrophy and interstitial fibrosis, but quantitative analysis of the m.3243A>G mitochondrial DNA mutation revealed high heteroplasmy levels of 89% in the kidney. Functional assessment showed reduced activity of mitochondrial enzymes in kidney tissue, which was confirmed by immunohistology. In conclusion, we describe an unusual case of MELAS syndrome with chronic kidney disease without apparent proteinuria or tubular disorders associated with Fanconi syndrome, but widespread interstitial fibrosis and a high degree of heteroplasmy of the MELAS specific mutation and low mitochondrial activity in the kidney. Copyright © 2016 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.

The Complete Mitochondrial Genome of Ctenoptilum vasava (Lepidoptera: Hesperiidae: Pyrginae) and Its Phylogenetic Implication

PubMed Central

Hao, Jiasheng; Sun, Qianqian; Zhao, Huabin; Sun, Xiaoyan; Gai, Yonghua; Yang, Qun

2012-01-01

We here report the first complete mitochondrial (mt) genome of a skipper, Ctenoptilum vasava Moore, 1865 (Lepidoptera: Hesperiidae: Pyrginae). The mt genome of the skipper is a circular molecule of 15,468 bp, containing 2 ribosomal RNA genes, 24 putative transfer RNA (tRNA), genes including an extra copy of trnS (AGN) and a tRNA-like insertion trnL (UUR), 13 protein-coding genes and an AT-rich region. All protein-coding genes (PCGs) are initiated by ATN codons and terminated by the typical stop codon TAA or TAG, except for COII which ends with a single T. The intergenic spacer sequence between trnS (AGN) and ND1 genes also contains the ATACTAA motif. The AT-rich region of 429 bp is comprised of nonrepetitive sequences, including the motif ATAGA followed by an 19 bp poly-T stretch, a microsatellite-like (AT)3 (TA)9 element next to the ATTTA motif, an 11 bp poly-A adjacent to tRNAs. Phylogenetic analyses (ML and BI methods) showed that Papilionoidea is not a natural group, and Hesperioidea is placed within the Papilionoidea as a sister to ((Pieridae + Lycaenidae) + Nymphalidae) while Papilionoidae is paraphyletic to Hesperioidea. This result is remarkably different from the traditional view where Papilionoidea and Hesperioidea are considered as two distinct superfamilies. PMID:22577351

Two new mutations in the MT-TW gene leading to the disruption of the secondary structure of the tRNA(Trp) in patients with Leigh syndrome.

PubMed

Mkaouar-Rebai, Emna; Chamkha, Imen; Kammoun, Fatma; Kammoun, Thouraya; Aloulou, Hajer; Hachicha, Mongia; Triki, Chahnez; Fakhfakh, Faiza

2009-07-01

Leigh syndrome is a progressive neurodegenerative disorder occurring in infancy and childhood characterized in most cases by a psychomotor retardation, optic atrophy, ataxia, dystonia, failure to thrive, seizures and respiratory failure. In this study, we performed a systematic sequence analysis of mitochondrial genes associated with LS in Tunisian patients. We sequenced the encoded complex I units: ND2, ND3, ND4, ND5 and ND6 genes and the mitochondrial ATPase 6, tRNA(Val), tRNA(Leu(UUR)), tRNA(Trp) and tRNA(Lys) genes in 10 unrelated patients with Leigh syndrome. We revealed the presence of 34 reported polymorphisms, nine novel nucleotide variants and two new mutations (T5523G and A5559G) in the tested patients. These two mutations were localized in two conserved regions of the tRNA(Trp) and affect, respectively, the D-stem and the T-stem of the mitochondrial tRNA leading to a disruption of the secondary structure of this tRNA. SSP-PCR analysis showed that the T5523G and A5559G mutations were present with respective heteroplasmic rates of 66% and 43 %. We report here the first mutational screening of mitochondrial mutations in Tunisian patients with Leigh syndrome which described two novel mutations associated with this disorder.

Supporting teachers and children in schools: the effectiveness and cost-effectiveness of the Incredible Years teacher classroom management programme in primary school children: a cluster randomised controlled trial, with parallel economic and process evaluations.

PubMed

Ford, Tamsin; Edwards, Vanessa; Sharkey, Siobhan; Ukoumunne, Obioha C; Byford, Sarah; Norwich, Brahm; Logan, Stuart

2012-08-30

Childhood antisocial behaviour has high immediate and long-term costs for society and the individual, particularly in relation to mental health and behaviours that jeopardise health. Managing challenging behaviour is a commonly reported source of stress and burn out among teachers, ultimately resulting in a substantial number leaving the profession. Interventions to improve parenting do not transfer easily to classroom-based problems and the most vulnerable parents may not be easily able to access them. Honing teachers' skills in proactive behaviour management and the promotion of socio-emotional regulation, therefore, has the potential to improve both child and teacher mental health and well-being and the advantage that it might potentially benefit all the children subsequently taught by any teacher that accesses the training. Cluster randomised controlled trial (RCT) of the Incredible Years teacher classroom management (TCM) course with combined economic and process evaluations.One teacher of children aged 4-9 years, from 80 schools in the South West Peninsula will be randomised to attend the TCM (intervention arm) or to "teach as normal" (control arm). The primary outcome measure will be the total difficulties score from the Strengths and Difficulties Questionnaire (SDQ) completed by the current class teachers prior to randomisation, and at 9, 18 and 30 months follow-up, supplemented by parent SDQs. Secondary measures include academic attainment (teacher report supplemented by direct measurement in a sub-sample), children's enjoyment of school, and teacher reports of their professional self-efficacy, and levels of burn out and stress, supplemented by structured observations of teachers classroom management skills in a subsample. Cost data for the economic evaluation will be based on parental reports of services accessed. Cost-effectiveness, using the SDQ as the measure of effect, will be examined over the period of the RCT and over the longer term using decision analytic modelling. The process evaluation will use quantitative and qualitative approaches to assess fidelity to model, as well as explore Head teacher and teachers' experiences of TCM and investigate school factors that influence the translation of skills learnt to practice. This study will provide important information about whether the Teacher Classroom Management course influences child and teacher mental health and well-being in both the short and long term. It will also provide valuable insights into factors that may facilitate or impede any impact.The trial has been registered with ISCTRN (Controlled Trials Ltd) and assigned an ISRCTN number ISRCTN84130388. (http://www.controlled-trials.com/isrctn/search.html?srch=ISRCTN84130388&sort=3&dir=desc&max=10).

Supporting teachers and children in schools: the effectiveness and cost-effectiveness of the incredible years teacher classroom management programme in primary school children: a cluster randomised controlled trial, with parallel economic and process evaluations

PubMed Central

2012-01-01

Background Childhood antisocial behaviour has high immediate and long-term costs for society and the individual, particularly in relation to mental health and behaviours that jeopardise health. Managing challenging behaviour is a commonly reported source of stress and burn out among teachers, ultimately resulting in a substantial number leaving the profession. Interventions to improve parenting do not transfer easily to classroom-based problems and the most vulnerable parents may not be easily able to access them. Honing teachers’ skills in proactive behaviour management and the promotion of socio-emotional regulation, therefore, has the potential to improve both child and teacher mental health and well-being and the advantage that it might potentially benefit all the children subsequently taught by any teacher that accesses the training. Methods/Design Cluster randomised controlled trial (RCT) of the Incredible Years teacher classroom management (TCM) course with combined economic and process evaluations. One teacher of children aged 4–9 years, from 80 schools in the South West Peninsula will be randomised to attend the TCM (intervention arm) or to “teach as normal” (control arm). The primary outcome measure will be the total difficulties score from the Strengths and Difficulties Questionnaire (SDQ) completed by the current class teachers prior to randomisation, and at 9, 18 and 30 months follow-up, supplemented by parent SDQs. Secondary measures include academic attainment (teacher report supplemented by direct measurement in a sub-sample), children’s enjoyment of school, and teacher reports of their professional self-efficacy, and levels of burn out and stress, supplemented by structured observations of teachers classroom management skills in a subsample. Cost data for the economic evaluation will be based on parental reports of services accessed. Cost-effectiveness, using the SDQ as the measure of effect, will be examined over the period of the RCT and over the longer term using decision analytic modelling. The process evaluation will use quantitative and qualitative approaches to assess fidelity to model, as well as explore Head teacher and teachers’ experiences of TCM and investigate school factors that influence the translation of skills learnt to practice. Discussion This study will provide important information about whether the Teacher Classroom Management course influences child and teacher mental health and well-being in both the short and long term. It will also provide valuable insights into factors that may facilitate or impede any impact. The trial has been registered with ISCTRN (Controlled Trials Ltd) and assigned an ISRCTN number ISRCTN84130388. (http://www.controlled-trials.com/isrctn/search.html?srch=ISRCTN84130388&sort=3&dir=desc&max=10) PMID:22935476

Homozygosity for rs738409:G in PNPLA3 is associated with increased mortality following an episode of severe alcoholic hepatitis.

PubMed

Atkinson, Stephen R; Way, Michael J; McQuillin, Andrew; Morgan, Marsha Y; Thursz, Mark R

2017-07-01

Carriage of rs738409:G in PNPLA3 is associated with an increased risk of developing alcohol-related cirrhosis and has a significant negative effect on survival. Short-term mortality in patients with severe alcoholic hepatitis is high; drinking behaviour is a major determinant of outcome in survivors. The aim of this study was to determine whether carriage of rs738409:G has an additional detrimental effect on survival in this patient group. Genotyping was undertaken in 898 cases with severe alcoholic hepatitis, recruited through the UK Steroids or Pentoxifylline for Alcoholic Hepatitis (STOPAH) trial, and 1188 White British/Irish alcohol dependent controls with no liver injury, recruited via University College London. Subsequent drinking behaviour was classified, in cases surviving ≥90days, as abstinent or drinking. The relationship between rs738409 genotype, drinking behaviour and survival was explored. The frequency of rs738409:G was significantly higher in cases than controls (29.5% vs. 18.9%; p=2.15×10 -15 ; odds ratio 1.80 [95% confidence interval (CI) 1.55-2.08]). Case-mortality at days 28, 90 and 450 was 16%, 25% and 41% respectively. There was no association between rs738409:G and 28-day mortality. Mortality in the 90 to 450-day period was higher in survivors who subsequently resumed drinking (hazard ratio [HR] 2.77, 95% CI 1.79-4.29; p<0.0001) and in individuals homozygous for rs738409:G (HR 1.69, 95% CI 1.02-2.81, p=0.04). Homozygosity for rs738409:G in PNPLA3 confers significant additional risk of medium-term mortality in patients with severe alcoholic hepatitis. Rs738409 genotype may be taken into account when considering treatment options for these patients. Individuals misusing alcohol who carry a particular variant of the gene PNPLA3 are more at risk of developing severe alcoholic hepatitis, a condition with a poor chance of survival. The longer-term outcome in people with this condition who survive the initial illness is strongly influenced by their ability to remain abstinent from alcohol. However, carriers of this gene variant are less likely to survive even if they are able to stop drinking completely. Knowing if someone carries this gene variant could influence the way in which they are managed. Clinical trial numbers: EudraCT reference number: 2009-013897-42; ISRCTN reference number: ISRCTN88782125. EudraCT reference number: 2009-013897-42; ISRCTN reference number: ISRCTN88782125. Copyright © 2017 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.

Normothermic Versus Hypothermic Cardiopulmonary Bypass in Children Undergoing Open Heart Surgery (Thermic-2): Study Protocol for a Randomized Controlled Trial

PubMed Central

Baos, Sarah; Sheehan, Karen; Culliford, Lucy; Pike, Katie; Ellis, Lucy; Parry, Andrew J; Stoica, Serban; Ghorbel, Mohamed T; Caputo, Massimo

2015-01-01

Background During open heart surgery, patients are connected to a heart-lung bypass machine that pumps blood around the body (“perfusion”) while the heart is stopped. Typically the blood is cooled during this procedure (“hypothermia”) and warmed to normal body temperature once the operation has been completed. The main rationale for “whole body cooling” is to protect organs such as the brain, kidneys, lungs, and heart from injury during bypass by reducing the body’s metabolic rate and decreasing oxygen consumption. However, hypothermic perfusion also has disadvantages that can contribute toward an extended postoperative hospital stay. Research in adults and small randomized controlled trials in children suggest some benefits to keeping the blood at normal body temperature throughout surgery (“normothermia”). However, the two techniques have not been extensively compared in children. Objective The Thermic-2 study will test the hypothesis that the whole body inflammatory response to the nonphysiological bypass and its detrimental effects on different organ functions may be attenuated by maintaining the body at 35°C-37°C (normothermic) rather than 28°C (hypothermic) during pediatric complex open heart surgery. Methods This is a single-center, randomized controlled trial comparing the effectiveness and acceptability of normothermic versus hypothermic bypass in 141 children with congenital heart disease undergoing open heart surgery. Children having scheduled surgery to repair a heart defect not requiring deep hypothermic circulatory arrest represent the target study population. The co-primary clinical outcomes are duration of inotropic support, intubation time, and postoperative hospital stay. Secondary outcomes are in-hospital mortality and morbidity, blood loss and transfusion requirements, pre- and post-operative echocardiographic findings, routine blood gas and blood test results, renal function, cerebral function, regional oxygen saturation of blood in the cerebral cortex, assessment of genomic expression changes in cardiac tissue biopsies, and neuropsychological development. Results A total of 141 patients have been successfully randomized over 2 years and 10 months and are now being followed-up for 1 year. Results will be published in 2015. Conclusions We believe this to be the first large pragmatic study comparing clinical outcomes during normothermic versus hypothermic bypass in complex open heart surgery in children. It is expected that this work will provide important information to improve strategies of cardiopulmonary bypass perfusion and therefore decrease the inevitable organ damage that occurs during nonphysiological body perfusion. Trial Registration ISRCTN Registry: ISRCTN93129502, http://www.isrctn.com/ISRCTN93129502 (Archived by WebCitation at http://www.webcitation.org/6Yf5VSyyG). PMID:26007621

A Randomized Controlled Trial on The Beneficial Effects of Training Letter-Speech Sound Integration on Reading Fluency in Children with Dyslexia

PubMed Central

Fraga González, Gorka; Žarić, Gojko; Tijms, Jurgen; Bonte, Milene; van der Molen, Maurits W.

2015-01-01

A recent account of dyslexia assumes that a failure to develop automated letter-speech sound integration might be responsible for the observed lack of reading fluency. This study uses a pre-test-training-post-test design to evaluate the effects of a training program based on letter-speech sound associations with a special focus on gains in reading fluency. A sample of 44 children with dyslexia and 23 typical readers, aged 8 to 9, was recruited. Children with dyslexia were randomly allocated to either the training program group (n = 23) or a waiting-list control group (n = 21). The training intensively focused on letter-speech sound mapping and consisted of 34 individual sessions of 45 minutes over a five month period. The children with dyslexia showed substantial reading gains for the main word reading and spelling measures after training, improving at a faster rate than typical readers and waiting-list controls. The results are interpreted within the conceptual framework assuming a multisensory integration deficit as the most proximal cause of dysfluent reading in dyslexia. Trial Registration: ISRCTN register ISRCTN12783279 PMID:26629707

How is a specialist depression service effective for persistent moderate to severe depressive disorder?: a qualitative study of service user experience.

PubMed

Thomson, Louise; Barker, Marcus; Kaylor-Hughes, Catherine; Garland, Anne; Ramana, Rajini; Morriss, Richard; Hammond, Emily; Hopkins, Gail; Simpson, Sandra

2018-06-15

A specialist depression service (SDS) offering collaborative pharmacological and cognitive behaviour therapy treatment for persistent depressive disorder showed effectiveness against depression symptoms versus usual community based multidisciplinary care in a randomised controlled trial (RCT) in specialist mental health services in England. However, there is uncertainty concerning how specialist depression services effect such change. The current study aimed to evaluate the factors which may explain the greater effectiveness of SDS compared to Treatment as Usual (TAU) by exploring the experience of the RCT participants. Qualitative audiotaped and transcribed semi-structured interviews were conducted 12-18 months after baseline with 21 service users (12 SDS, 9 TAU arms) drawn from all three sites. Inductive thematic analysis using a grounded approach contrasted the experiences of SDS with TAU participants. Four themes emerged in relation to service user experience: 1. Specific treatment components of the SDS: which included sub-themes of the management of medication change, explaining and developing treatment strategies, setting realistic expectations, and person-centred and holistic approach; 2. Individual qualities of SDS clinicians; 3. Collaborative team context in SDS: which included sub-themes of communication between healthcare professionals, and continuity of team members; 4. Accessibility to SDS: which included sub-themes of flexibility of locations, frequent consultation as reinforcement, gradual pace of treatment, and challenges of returning to usual care. The study uncovered important mechanisms and contextual factors in the SDS that service users experience as different from TAU, and which may explain the greater effectiveness of the SDS: the technical expertise of the healthcare professionals, personal qualities of clinicians, teamwork, gradual pace of care, accessibility and managing service transitions. Usual care in other specialist mental health services may share many of the features from the SDS. "Trial of the Clinical and Cost Effectiveness of a Specialist Expert Mood Disorder Team for Refractory Unipolar Depressive Disorder" was registered in www.ClinicalTrials.gov ( NCT01047124 ) on 12-01-2010 and the ISRCTN registry was registered in www.isrctn.com ( ISRCTN10963342 ) on 25-11-2015 (retrospectively registered).

Transdiagnostic Cognitive Behavioral Therapy Versus Treatment as Usual in Adult Patients With Emotional Disorders in the Primary Care Setting (PsicAP Study): Protocol for a Randomized Controlled Trial

PubMed Central

Muñoz-Navarro, Roger; Wood, Cristina Mae; Limonero, Joaquín T; Medrano, Leonardo Adrián; Ruiz-Rodríguez, Paloma; Gracia-Gracia, Irene; Dongil-Collado, Esperanza; Iruarrizaga, Iciar; Chacón, Fernando; Santolaya, Francisco

2016-01-01

Background Demand for primary care (PC) services in Spain exceeds available resources. Part of this strong demand is due to the high prevalence of emotional disorders (EDs)—anxiety, depression, and somatic symptom disorders—and related comorbidities such as pain or chronic illnesses. EDs are often under- or misdiagnosed by general practitioners (GPs) and, consequently, treatment is frequently inadequate. Objective We aim to compare the short- and long-term effectiveness of group-delivered transdiagnostic cognitive behavioral therapy (TD-CBT) versus treatment as usual (TAU) in the treatment of EDs in the PC setting in Spain. We also aim to compare the effect of these treatments on disability, quality of life, cognitive-emotional factors, and treatment satisfaction. Methods Here we present the study design of a two-arm, single-blind, randomized controlled trial (N=1126) to compare TAU to TD-CBT for EDs. TAU will consist primarily of pharmacological treatment and practical advice from the GP while TD-CBT will be administered in seven 90-minute group sessions held over a period ranging from 12 to 14 weeks. Psychological assessments are carried out at baseline (ie, pretreatment); posttreatment; and at 3-, 6-, and 12-month follow-up. The study is conducted in approximately 26 PC centers from the National Health System in Spain. Results This study was initiated in December 2013 and will remain open to new participants until recruitment and follow-up has been completed. We expect all posttreatment evaluations to be completed by December 2017, and follow-up will end in December 2018. Conclusions We expect the TD-CBT group to have better results compared to TAU on all posttreatment measures and that this improvement will be maintained during follow-up. This project could serve as a model for use in other areas or services of the National Health System in Spain and even in other countries. ClinicalTrial International Standard Randomized Controlled Trial Number (ISRCTN): 58437086; http://www.isrctn.com/ISRCTN58437086 (Archived by WebCite at http://www.webcitation.org/6mbYjQSn3) PMID:28011446

Granulocyte Colony Stimulating Factor and Physiotherapy after Stroke: Results of a Feasibility Randomised Controlled Trial: Stem Cell Trial of Recovery EnhanceMent after Stroke-3 (STEMS-3 ISRCTN16714730)

PubMed Central

Sprigg, Nikola; O’Connor, Rebecca; Woodhouse, Lisa; Krishnan, Kailash; England, Timothy J.; Connell, Louise A.; Walker, Marion F.; Bath, Philip M.

2016-01-01

Background Granulocyte-colony stimulating factor (G-CSF) mobilises endogenous haematopoietic stem cells and enhances recovery in experimental stroke. Recovery may also be dependent on an enriched environment and physical activity. G-CSF may have the potential to enhance recovery when used in combination with physiotherapy, in patients with disability late after stroke. Methods A pilot 2 x 2 factorial randomised (1:1) placebo-controlled trial of G-CSF (double-blind), and/or a 6 week course of physiotherapy, in 60 participants with disability (mRS >1), at least 3 months after stroke. Primary outcome was feasibility, acceptability and tolerability. Secondary outcomes included death, dependency, motor function and quality of life measured 90 and 365 days after enrolment. Results Recruitment to the trial was feasible and acceptable; of 118 screened patients, 92 were eligible and 32 declined to participate. 60 patients were recruited between November 2011 and July 2013. All participants received some allocated treatment. Although 29 out of 30 participants received all 5 G-CSF/placebo injections, only 7 of 30 participants received all 18 therapy sessions. G-CSF was well tolerated but associated with a tendency to more adverse events than placebo (16 vs 10 patients, p = 0.12) and serious adverse events (SAE) (9 vs 3, p = 0.10). On average, patients received 14 (out of 18 planned) therapy sessions, interquartile range [12, 17]. Only a minority (23%) of participants completed all physiotherapy sessions, a large proportion of sessions (114 of 540, 21%) were cancelled due to patient (94, 17%) and therapist factors (20, 4%). No significant differences in functional outcomes were detected in either the G-CSF or physiotherapy group at day 90 or 365. Conclusions Delivery of G-CSF is feasible in chronic stroke. However, the study failed to demonstrate feasibility for delivering additional physiotherapy sessions late after stroke therefore a definitive study using this trial design is not supported. Future work should occur earlier after stroke, alongside on-going clinical rehabilitation. Trial Registration ISRCTN.com ISRCTN16714730 PMID:27610616

The association of serum choline with linear growth failure in young children from rural Malawi.

PubMed

Semba, Richard D; Zhang, Pingbo; Gonzalez-Freire, Marta; Moaddel, Ruin; Trehan, Indi; Maleta, Kenneth M; Ordiz, M Isabel; Ferrucci, Luigi; Manary, Mark J

2016-07-01

Choline is an essential nutrient for cell structure, cell signaling, neurotransmission, lipid transport, and bone formation. Choline can be irreversibly converted to betaine, a major source of methyl groups. Trimethylene N-oxide (TMAO), a proatherogenic molecule, is produced from the metabolism of dietary choline by the gut microbiome. The relation between serum choline and its closely related metabolites with linear growth in children is unknown. The aim was to characterize the relation between serum choline and its closely related metabolites, betaine and TMAO, with linear growth and stunting in young children. We measured serum choline, betaine, and TMAO concentrations by using liquid chromatography isotopic dilution tandem mass spectrometry in a cross-sectional study in 325 Malawian children, aged 12-59 mo, of whom 62% were stunted. Median (25th, 75th percentile) serum choline, betaine, and TMAO concentrations were 6.4 (4.8, 8.3), 12.4 (9.1, 16.3), and 1.2 (0.7, 1.8) μmol/L, respectively. Spearman correlation coefficients of age with serum choline, betaine, and TMAO were -0.57 (P < 0.0001), -0.26 (P < 0.0001), and -0.10 (P = 0.07), respectively. Correlation coefficients of height-for-age z score with serum choline, betaine-to-choline ratio, and TMAO-to-choline ratio were 0.31 (P < 0.0001), -0.24 (P < 0.0001), and -0.29 (P < 0.0001), respectively. Serum choline concentrations were strongly and significantly associated with stunting. Children with and without stunting had median (25th, 75th percentile) serum choline concentrations of 5.6 (4.4, 7.4) and 7.3 (5.9, 9.1) μmol/L (P < 0.0001). Linear growth failure in young children is associated with low serum choline and elevated betaine-to-choline and TMAO-to-choline ratios. Further work is needed to understand whether low dietary choline intake explains low circulating choline among stunted children living in low-income countries and whether increasing choline intake may correct choline deficiency and improve growth and development. This trial was registered in the ISRCTN registry (www.isrctn.com) as ISRCTN14597012. © 2016 American Society for Nutrition.

Cost Effectiveness of Support for People Starting a New Medication for a Long-Term Condition Through Community Pharmacies: An Economic Evaluation of the New Medicine Service (NMS) Compared with Normal Practice.

PubMed

Elliott, Rachel A; Tanajewski, Lukasz; Gkountouras, Georgios; Avery, Anthony J; Barber, Nick; Mehta, Rajnikant; Boyd, Matthew J; Latif, Asam; Chuter, Antony; Waring, Justin

2017-12-01

The English community pharmacy New Medicine Service (NMS) significantly increases patient adherence to medicines, compared with normal practice. We examined the cost effectiveness of NMS compared with normal practice by combining adherence improvement and intervention costs with the effect of increased adherence on patient outcomes and healthcare costs. We developed Markov models for diseases targeted by the NMS (hypertension, type 2 diabetes mellitus, chronic obstructive pulmonary disease, asthma and antiplatelet regimens) to assess the impact of patients' non-adherence. Clinical event probability, treatment pathway, resource use and costs were extracted from literature and costing tariffs. Incremental costs and outcomes associated with each disease were incorporated additively into a composite probabilistic model and combined with adherence rates and intervention costs from the trial. Costs per extra quality-adjusted life-year (QALY) were calculated from the perspective of NHS England, using a lifetime horizon. NMS generated a mean of 0.05 (95% CI 0.00-0.13) more QALYs per patient, at a mean reduced cost of -£144 (95% CI -769 to 73). The NMS dominates normal practice with a probability of 0.78 [incremental cost-effectiveness ratio (ICER) -£3166 per QALY]. NMS has a 96.7% probability of cost effectiveness compared with normal practice at a willingness to pay of £20,000 per QALY. Sensitivity analysis demonstrated that targeting each disease with NMS has a probability over 0.90 of cost effectiveness compared with normal practice at a willingness to pay of £20,000 per QALY. Our study suggests that the NMS increased patient medicine adherence compared with normal practice, which translated into increased health gain at reduced overall cost. ClinicalTrials.gov Trial reference number NCT01635361 ( http://clinicaltrials.gov/ct2/show/NCT01635361 ). Current Controlled trials: Trial reference number ISRCTN 23560818 ( http://www.controlled-trials.com/ISRCTN23560818/ ; DOI 10.1186/ISRCTN23560818 ). UK Clinical Research Network (UKCRN) study 12494 ( http://public.ukcrn.org.uk/Search/StudyDetail.aspx?StudyID=12494 ). Department of Health Policy Research Programme.

Protocol of the Febuxostat versus Allopurinol Streamlined Trial (FAST): a large prospective, randomised, open, blinded endpoint study comparing the cardiovascular safety of allopurinol and febuxostat in the management of symptomatic hyperuricaemia

PubMed Central

MacDonald, Thomas M; Ford, Ian; Nuki, George; Mackenzie, Isla S; De Caterina, Raffaele; Findlay, Evelyn; Hallas, Jesper; Hawkey, Christopher J; Ralston, Stuart; Walters, Matthew; Webster, John; McMurray, John; Perez Ruiz, Fernando; Jennings, Claudine G

2014-01-01

Introduction Gout affects 2.5% of the UK's adult population and is now the most common type of inflammatory arthritis. The long-term management of gout requires reduction of serum urate levels and this is most often achieved with use of xanthine oxidase inhibitors, such as allopurinol. Febuxostat is the first new xanthine oxidase inhibitor since allopurinol and was licensed for use in 2008. The European Medicines Agency requested a postlicensing cardiovascular safety study of febuxostat versus allopurinol, which has been named the Febuxostat versus Allopurinol Streamlined trial (FAST). Methods and analysis FAST is a cardiovascular safety study using the prospective, randomised, open, blinded endpoint design. FAST is recruiting in the UK and Denmark. Recruited patients are aged over 60 years, prescribed allopurinol for symptomatic hyperuricaemia and have at least one additional cardiovascular risk factor. After an allopurinol lead-in phase where the dose of allopurinol is optimised to achieve European League against Rheumatism (EULAR) urate targets (serum urate <357 µmol/L), patients are randomised to either continue optimal dose allopurinol or to use febuxostat. Patients are followed-up for an average of 3 years. The primary endpoint is first occurrence of the Anti-Platelet Trialists’ Collaboration (APTC) cardiovascular endpoint of non-fatal myocardial infarction, non-fatal stroke or cardiovascular death. Secondary endpoints are all cause mortality and hospitalisations for heart failure, unstable, new or worsening angina, coronary or cerebral revascularisation, transient ischaemic attack, non-fatal cardiac arrest, venous and peripheral arterial vascular thrombotic event and arrhythmia with no evidence of ischaemia. The primary analysis is a non-inferiority analysis with a non-inferiority upper limit for the HR for the primary outcome of 1.3. Ethics and dissemination FAST (ISRCTN72443728) has ethical approval in the UK and Denmark, and results will be published in a peer reviewed journal. Trial Registration number FAST is registered in the EU Clinical Trials Register (EUDRACT No: 2011-001883-23) and International Standard Randomised Controlled Trial Number Register (ISRCTN No: ISRCTN72443728). PMID:25011991

Effectiveness of a Technology-Based Supportive Educational Parenting Program on Parental Outcomes in Singapore: Protocol for a Randomized Controlled Trial.

PubMed

Shorey, Shefaly; Ng, Yvonne Peng Mei; Siew, An Ling; Yoong, Joanne; Mörelius, Evalotte

2018-01-10

Supportive educational programs during the perinatal period are scarce in Singapore. There is no continuity of care available in terms of support from community care nurses in Singapore. Parents are left on their own most of the time, which results in a stressful transition to parenthood. There is a need for easily accessible technology-based educational programs that can support parents during this crucial perinatal period. The aim of this study was to describe the study protocol of a randomized controlled trial on a technology-based supportive educational parenting program. A randomized controlled two-group pretest and repeated posttest experimental design will be used. The study will recruit 118 parents (59 couples) from the antenatal clinics of a tertiary public hospital in Singapore. Eligible parents will be randomly allocated to receive either the supportive educational parenting program or routine perinatal care from the hospital. Outcome measures include parenting self-efficacy, parental bonding, postnatal depression, social support, parenting satisfaction, and cost evaluation. Data will be collected at the antenatal period, immediate postnatal period, and at 1 month and 3 months post childbirth. Recruitment of the study participants commenced in December 2016 and is still ongoing. Data collection is projected to finish within 12 months, by December 2017. This study will identify a potentially clinically useful, effective, and cost-effective supportive educational parenting program to improve parental self-efficacy and bonding in newborn care, which will then improve parents' social support-seeking behaviors, emotional well-being, and satisfaction with parenting. It is hoped that better supported and satisfied parents will consider having more children, which may in turn influence Singapore's ailing birth rate. International Standard Randomized Controlled Trial Number (ISRCTN): 48536064; https://www.isrctn.com/ISRCTN48536064 (Archived by WebCite at http://www.webcitation.org/6wMuEysiO). ©Shefaly Shorey, Yvonne Peng Mei Ng, An Ling Siew, Joanne Yoong, Evalotte Mörelius. Originally published in JMIR Research Protocols (http://www.researchprotocols.org), 10.01.2018.

Effect of a Brief Outreach Educational Intervention on the Translation of Acute Poisoning Treatment Guidelines to Practice in Rural Sri Lankan Hospitals: A Cluster Randomized Controlled Trial

PubMed Central

Senarathna, Lalith; Buckley, Nick A.; Dibley, Michael J.; Kelly, Patrick J.; Jayamanna, Shaluka F.; Gawarammana, Indika B.; Dawson, Andrew H.

2013-01-01

Background In developing countries, including Sri Lanka, a high proportion of acute poisoning and other medical emergencies are initially treated in rural peripheral hospitals. Patients are then usually transferred to referral hospitals for further treatment. Guidelines are often used to promote better patient care in these emergencies. We conducted a cluster randomized controlled trial (ISRCTN73983810) which aimed to assess the effect of a brief educational outreach (‘academic detailing’) intervention to promote the utilization of treatment guidelines for acute poisoning. Methods and Findings This cluster RCT was conducted in the North Central Province of Sri Lanka. All peripheral hospitals in the province were randomized to either intervention or control. All hospitals received a copy of the guidelines. The intervention hospitals received a brief out-reach academic detailing workshop which explained poisoning treatment guidelines and guideline promotional items designed to be used in daily care. Data were collected on all patients admitted due to poisoning for 12 months post-intervention in all study hospitals. Information collected included type of poison exposure, initial investigations, treatments and hospital outcome. Patients transferred from peripheral hospitals to referral hospitals had their clinical outcomes recorded. There were 23 intervention and 23 control hospitals. There were no significant differences in the patient characteristics, such as age, gender and the poisons ingested. The intervention hospitals showed a significant improvement in administration of activated charcoal [OR 2.95 (95% CI 1.28–6.80)]. There was no difference between hospitals in use of other decontamination methods. Conclusion This study shows that an educational intervention consisting of brief out-reach academic detailing was effective in changing treatment behavior in rural Sri Lankan hospitals. The intervention was only effective for treatments with direct clinician involvement, such as administering activated charcoal. It was not successful for treatments usually administered by non-professional staff such as forced emesis for poisoning. Trial Registration Controlled-Trials.com ISRCTN73983810 ISRCTN73983810 PMID:23990989

Translating staff experience into organisational improvement: the HEADS-UP stepped wedge, cluster controlled, non-randomised trial

PubMed Central

Athanasiou, Thanos; Long, Susannah J; Beveridge, Iain; Sevdalis, Nick

2017-01-01

Objectives Frontline insights into care delivery correlate with patients’ clinical outcomes. These outcomes might be improved through near-real time identification and mitigation of staff concerns. We evaluated the effects of a prospective frontline surveillance system on patient and team outcomes. Design Prospective, stepped wedge, non-randomised, cluster controlled trial; prespecified per protocol analysis for high-fidelity intervention delivery. Participants Seven interdisciplinary medical ward teams from two hospitals in the UK. Intervention Prospective clinical team surveillance (PCTS): structured daily interdisciplinary briefings to capture staff concerns, with organisational facilitation and feedback. Main measures The primary outcome was excess length of stay (eLOS): an admission more than 24 hours above the local average for comparable patients. Secondary outcomes included safety and teamwork climates, and incident reporting. Mixed-effects models adjusted for time effects, age, comorbidity, palliation status and ward admissions. Safety and teamwork climates were measured with the Safety Attitudes Questionnaire. High-fidelity PCTS delivery comprised high engagement and high briefing frequency. Results Implementation fidelity was variable, both in briefing frequency (median 80% working days/month, IQR 65%–90%) and engagement (median 70 issues/ward/month, IQR 34–113). 1714/6518 (26.3%) intervention admissions had eLOS versus 1279/4927 (26.0%) control admissions, an absolute risk increase of 0.3%. PCTS increased eLOS in the adjusted intention-to-treat model (OR 1.32, 95% CI 1.10 to 1.58, p=0.003). Conversely, high-fidelity PCTS reduced eLOS (OR 0.79, 95% CI 0.67 to 0.94, p=0.006). High-fidelity PCTS also increased total, high-yield and non-nurse incident reports (incidence rate ratios 1.28–1.79, all p<0.002). Sustained PCTS significantly improved safety and teamwork climates over time. Conclusions This study highlighted the potential benefits and pitfalls of ward-level interdisciplinary interventions. While these interventions can improve care delivery in complex, fluid environments, the manner of their implementation is paramount. Suboptimal implementation may have an unexpectedly negative impact on performance. Trial registration number ISRCTN 34806867 (http://www.isrctn.com/ISRCTN34806867). PMID:28720612

Cost-Effectiveness of Group and Internet Cognitive Behavioral Therapy for Insomnia in Adolescents: Results from a Randomized Controlled Trial.

PubMed

De Bruin, Eduard J; van Steensel, Francisca J A; Meijer, Anne Marie

2016-08-01

To investigate cost-effectiveness of adolescent cognitive behavioral therapy for insomnia (CBTI) in group- and Internet-delivered formats, from a societal perspective with a time horizon of 1 y. Costs and effects data up to 1-y follow-up were obtained from a randomized controlled trial (RCT) comparing Internet CBTI to face-to-face group CBTI. The study was conducted at the laboratory of the Research Institute of Child Development and Education at the University of Amsterdam, and the academic youth mental health care center UvAMinds in Amsterdam. Sixty-two participants meeting Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision criteria for insomnia were randomized to face-to-face group CBTI (GT; n = 31, age = 15.6 y ± 1.8, 71.0% girls) or individual Internet CBTI (IT; n = 31, age = 15.4 y ± 1.5, 83.9% girls). The intervention consisted of six weekly sessions and a 2-mo follow up booster-session of CBTI, consisting of psychoeducation, sleep hygiene, restriction of time in bed, stimulus control, cognitive therapy, and relaxation techniques. GT sessions were held in groups of six to eight adolescents guided by two trained sleep therapists. IT consisted of individual Internet therapy with preprogrammed content similar to GT, and guided by trained sleep therapists. Outcome measures were subjective sleep efficiency (SE) ≥ 85%, and quality-adjusted life-years (QALY). Analyses were conducted from a societal perspective. Incremental cost-effectiveness ratios (ICERs) were calculated using bootstrap sampling, and presented in cost-effectiveness planes. Primary analysis showed costs over 1 y were higher for GT but effects were similar for IT and GT. Bootstrapped ICERs demonstrated there is a high probability of IT being cost-effective compared to GT. Secondary analyses confirmed robustness of results. Internet CBTI is a cost-effective treatment compared to group CBTI for adolescents, although effects were largely similar for both formats. Further studies in a clinical setting are warranted. ID: ISRCTN33922163; trial name: Effectiveness of cognitive behavioral therapy for sleeplessness in adolescents; URL: http://www.isrctn.com/ISRCTN33922163. © 2016 Associated Professional Sleep Societies, LLC.

Educational intervention improves anticoagulation control in atrial fibrillation patients: the TREAT randomised trial.

PubMed

Clarkesmith, Danielle E; Pattison, Helen M; Lip, Gregory Y H; Lane, Deirdre A

2013-01-01

Stroke prevention in atrial fibrillation (AF), most commonly with warfarin, requires maintenance of a narrow therapeutic target (INR 2.0 to 3.0) and is often poorly controlled in practice. Poor patient-understanding surrounding AF and its treatment may contribute to the patient's willingness to adhere to recommendations. A theory-driven intervention, developed using patient interviews and focus groups, consisting of a one-off group session (1-6 patients) utilising an "expert-patient" focussed DVD, educational booklet, self-monitoring diary and worksheet, was compared in a randomised controlled trial (ISRCTN93952605) against usual care, with patient postal follow-ups at 1, 2, 6, and 12-months. Ninety-seven warfarin-naïve AF patients were randomised to intervention (n=46, mean age (SD) 72.0 (8.2), 67.4% men), or usual care (n=51, mean age (SD) 73.7 (8.1), 62.7% men), stratified by age, sex, and recruitment centre. Primary endpoint was time within therapeutic range (TTR); secondary endpoints included knowledge, quality of life, anxiety/depression, beliefs about medication, and illness perceptions. Intervention patients had significantly higher TTR than usual care at 6-months (76.2% vs. 71.3%; p=0.035); at 12-months these differences were not significant (76.0% vs. 70.0%; p=0.44). Knowledge increased significantly across time (F (3, 47) = 6.4; p<0.01), but there were no differences between groups (F (1, 47) = 3.3; p = 0.07). At 6-months, knowledge scores predicted TTR (r=0.245; p=0.04). Patients' scores on subscales representing their perception of the general harm and overuse of medication, as well as the perceived necessity of their AF specific medications predicted TTR at 6- and 12-months. A theory-driven educational intervention significantly improves TTR in AF patients initiating warfarin during the first 6-months. Adverse clinical outcomes may potentially be reduced by improving patients' understanding of the necessity of warfarin and reducing their perception of treatment harm. Improving education provision for AF patients is essential to ensure efficacious and safe treatment. The trial is registered with Current Controlled Trials, ISRCTN93952605, and details are available at www.controlled-trials.com/ISRCTN93952605.

Comparison of two modes of vitamin B12 supplementation on neuroconduction and cognitive function among older people living in Santiago, Chile: a cluster randomized controlled trial. a study protocol [ISRCTN 02694183

PubMed Central

2011-01-01

Background Older people have a high risk of vitamin B12 deficiency; this can lead to varying degrees of cognitive and neurological impairment. CBL deficiency may present as macrocytic anemia, subacute combined degeneration of the spinal cord, or as neuropathy, but is often asymptomatic in older people. Less is known about subclinical vitamin B12 deficiency and concurrent neuroconduction and cognitive impairment. A Programme of Complementary Feeding for the Older Population (PACAM) in Chile delivers 2 complementary fortified foods that provide approximately 1.4 μg/day of vitamin B12 (2.4 μg/day elderly RDA). The aim of the present study is to assess whether supplementation with vitamin B12 will improve neuroconduction and cognitive function in older people who have biochemical evidence of vitamin B12 insufficiency in the absence of clinical deficiency. Methods We designed a cluster double-blind placebo-controlled trial involving community dwelling people aged 70-79 living in Santiago, Chile. We randomized 15 clusters (health centers) involving 300 people (20 per cluster). Each cluster will be randomly assigned to one of three arms: a) a 1 mg vitamin B12 pill taken daily and a routine PACAM food; b) a placebo pill and the milk-PACAM food fortified to provide 1 mg of vitamin B12; c) the routine PACAM food and a placebo pill. The study has been designed as an 18 month follow up period. The primary outcomes assessed at baseline, 4, 9 and 18 months will be: serum levels of vitamin B12, neuroconduction and cognitive function. Conclusions In view of the high prevalence of vitamin B12 deficiency in later life, the present study has potential public health interest because since it will measure the impact of the existing program of complementary feeding as compared to two options that provide higher vitamin B12 intakes that might potentially may contribute in preserving neurophysiologic and cognitive function and thus improve quality of life for older people in Chile. Trial registration ISRCTN: ISRCTN02694183 PMID:21952034

Screening for Prostate Cancer Starting at Age 50-54. A Population-based Cohort Study

PubMed Central

Carlsson, Sigrid; Assel, Melissa; Ulmert, David; Gerdtsson, Axel; Hugosson, Jonas; Vickers, Andrew; Lilja, Hans

2016-01-01

Background Current prostate cancer screening guidelines conflict with respect to the age at which to initiate screening. Objective To evaluate the effect of prostate-specific antigen (PSA) screening, versus zero screening, starting at age 50-54, on prostate cancer mortality. Design, Setting, and Participants This is a population-based cohort study comparing 3,479 men aged 50 through 54 randomized to PSA-screening in the Göteborg population-based prostate cancer screening trial, initiated in 1995, versus 4,060 unscreened men aged 51 to 55 providing cryopreserved blood in the population-based Malmö Preventive Project in the pre-PSA era, during 1982-1985. Outcome measures and Statistical Analysis Cumulative incidence and incidence rate ratios of prostate cancer diagnosis, metastasis, and prostate cancer death. Results and Limitation At 17 years, regular PSA-screening in Göteborg of men in their early 50s carried a more than 2-fold higher risk of prostate cancer diagnosis compared to the unscreened men in Malmö (IRR 2.56, 95% CI 2.18, 3.02), but resulted in a substantial decrease in risk of metastases (IRR 0.43, 95% CI 0.22, 0.79) and prostate cancer death (IRR 0.29, 95% CI 0.11, 0.67). There were 57 fewer prostate cancer deaths per 10,000 men (95% CI 22, 92) in the screened group. At 17 years, the number needed to invite to PSA-screening and the number needed to diagnose to prevent one prostate cancer death was 176 and 16, respectively. The study is limited by lack of treatment information and the comparison of two different birth cohorts. Conclusions PSA screening for prostate cancer can decrease prostate cancer mortality among men aged 50–54, with NNI and NND comparable to those previously reported from the European Randomized Study of Screening for Prostate Cancer for men aged 55-69 years, at similar follow-up. Guideline groups could consider whether guidelines for PSA screening should recommend starting no later than at ages 50-54. Trial registration The Göteborg randomized population-based prostate cancer screening trial is registered with the ISRCTN registry (isrctn.com). Identifier: ISRCTN54449243. PMID:27084245

Self-Management and Clinical Decision Support for Patients With Complex Chronic Conditions Through the Use of Smartphone-Based Telemonitoring: Randomized Controlled Trial Protocol

PubMed Central

Ware, Patrick; Logan, Alexander G; Cafazzo, Joseph A; Chapman, Kenneth R; Segal, Phillip; Ross, Heather J

2017-01-01

Background The rising prevalence of chronic illnesses hinders the sustainability of the health care system because of the high cost of frequent hospitalizations of patients with complex chronic conditions. Clinical trials have demonstrated that telemonitoring can improve health outcomes, but they have generally been limited to single conditions such as diabetes, hypertension, or heart failure. Few studies have examined the impact of telemonitoring on complex patients with multiple chronic conditions, although these patients may benefit the most from this technology. Objective The aim of this study is to investigate the impact of a smartphone-based telemonitoring system on the clinical care and health outcomes of complex patients across several chronic conditions. Methods A mixed-methods, 6-month randomized controlled trial (RCT) of a smartphone-based telemonitoring system is being conducted in specialty clinics. The study will include patients who have been diagnosed with one or more of any of the following conditions: heart failure, chronic obstructive pulmonary disease, chronic kidney disease, uncontrolled hypertension, or insulin-requiring diabetes. The primary outcome will be the health status of patients as measured with SF-36. Patients will be randomly assigned to either the control group receiving usual care (n=73) or the group using the smartphone-based telemonitoring system in addition to usual care (n=73). Results Participants are currently being recruited for the trial. Data collection is anticipated to be completed by the fall of 2018. Conclusions This RCT will be among the first trials to provide evidence of the impact of telemonitoring on costs and health outcomes of complex patients who may have multiple chronic conditions. Trial Registration International Standard Randomized Controlled Trial Number (ISRCTN): 41238563; http://www.isrctn.com/ISRCTN41238563 (Archived by WebCite at http://www.webcitation.org/6ug2Sk0af) and Clinicaltrials.gov NCT03127852; https://clinicaltrials.gov/ct2/show/NCT03127852 (Archived by WebCite at http://www.webcitation.org/6uvjNosBC) PMID:29162557

Two Novel Cognitive Behavioral Therapy-Based Mobile Apps for Agoraphobia: Randomized Controlled Trial.

PubMed

Christoforou, Marina; Sáez Fonseca, José Andrés; Tsakanikos, Elias

2017-11-24

Despite the large body of literature demonstrating the effectiveness of cognitive behavioral treatments for agoraphobia, many patients remain untreated because of various barriers to treatment. Web-based and mobile-based interventions targeting agoraphobia may provide a solution to this problem, but there is a lack of research investigating the efficacy of such interventions. The objective of our study was to evaluate for the first time the effectiveness of a self-guided mobile-based intervention primarily targeting agoraphobic symptoms, with respect to a generic mobile app targeting anxiety. A Web-based randomized controlled trial (RCT) compared a novel mobile app designed to target agoraphobia (called Agoraphobia Free) with a mobile app designed to help with symptoms of anxiety in general (called Stress Free). Both interventions were based on established cognitive behavioral principles. We recruited participants (N=170) who self-identified as having agoraphobia and assessed them online at baseline, midpoint, and end point (posttreatment) over a period of 12 weeks. The primary outcome was symptom severity measured by the Panic and Agoraphobia Scale. Both groups had statistically significant improvements in symptom severity over time (difference -5.97, 95% CI -8.49 to -3.44, P<.001 for Agoraphobia Free and -6.35, 95% CI -8.82 to -3.87, P<.001 for Stress Free), but there were no significant between-group differences on the primary outcome (difference 0.38, 95% CI -1.96 to 3.20, P=.64). This is, to our knowledge, the first RCT to provide evidence that people who identify as having agoraphobia may equally benefit from a diagnosis-specific and a transdiagnostic mobile-based intervention. We also discuss clinical and research implications for the development and dissemination of mobile mental health apps. International Standard Randomized Controlled Trial Number (ISRCTN): 98453199; http://www.isrctn.com /ISRCTN98453199 (Archived by WebCite at http://www.webcitation.org/6uR5vsdZw). ©Marina Christoforou, José Andrés Sáez Fonseca, Elias Tsakanikos. Originally published in the Journal of Medical Internet Research (http://www.jmir.org), 24.11.2017.

MELAS syndrome: Clinical manifestations, pathogenesis, and treatment options.

PubMed

El-Hattab, Ayman W; Adesina, Adekunle M; Jones, Jeremy; Scaglia, Fernando

2015-01-01

Mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes (MELAS) syndrome is one of the most frequent maternally inherited mitochondrial disorders. MELAS syndrome is a multi-organ disease with broad manifestations including stroke-like episodes, dementia, epilepsy, lactic acidemia, myopathy, recurrent headaches, hearing impairment, diabetes, and short stature. The most common mutation associated with MELAS syndrome is the m.3243A>G mutation in the MT-TL1 gene encoding the mitochondrial tRNA(Leu(UUR)). The m.3243A>G mutation results in impaired mitochondrial translation and protein synthesis including the mitochondrial electron transport chain complex subunits leading to impaired mitochondrial energy production. The inability of dysfunctional mitochondria to generate sufficient energy to meet the needs of various organs results in the multi-organ dysfunction observed in MELAS syndrome. Energy deficiency can also stimulate mitochondrial proliferation in the smooth muscle and endothelial cells of small blood vessels leading to angiopathy and impaired blood perfusion in the microvasculature of several organs. These events will contribute to the complications observed in MELAS syndrome particularly the stroke-like episodes. In addition, nitric oxide deficiency occurs in MELAS syndrome and can contribute to its complications. There is no specific consensus approach for treating MELAS syndrome. Management is largely symptomatic and should involve a multidisciplinary team. Unblinded studies showed that l-arginine therapy improves stroke-like episode symptoms and decreases the frequency and severity of these episodes. Additionally, carnitine and coenzyme Q10 are commonly used in MELAS syndrome without proven efficacy. Copyright © 2015 Elsevier Inc. All rights reserved.

Beta-cell function in individuals carrying the mitochondrial tRNA leu (UUR) mutation.

PubMed

Salles, João Eduardo; Kasamatsu, Teresa S; Dib, Sérgio A; Moisés, Regina S

2007-01-01

To assess the beta-cell function in individuals with mitochondrial DNA A3243G mutation with normal glucose tolerance (NGT) or diabetes mellitus (DM). Furthermore, in diabetic individuals, we evaluated the effect of coenzyme Q10 supplementation on insulin secretory response. Eight mutation-positive individuals with NGT (n = 4) or DM (n = 4) were studied. beta-Cell function was evaluated by C-peptide levels before and after a mixed liquid meal (Sustacal) challenge and by first-phase insulin response. Fasting and Sustacal-stimulated C-peptide levels were significantly lower in diabetic patients than that in controls (area under the curve: 104.1 +/- 75.7 vs 520.8 +/- 173.8, P = 0.001), whereas in individuals with NGT, this response was preserved (area under the curve: 537.8 +/- 74.3 vs 520.8 +/- 179.8, P = 0.87). The duration of diabetes was negatively correlated with fasting C-peptide levels (r = -0.961, P = 0.038). Among the 3 patients with residual insulin secretion, the short-term treatment with coenzyme Q10 (3 months) improved C-peptide levels in 2 of them. The first-phase insulin response was diminished in 2 individuals with NGT, the oldest ones. We showed an impaired insulin secretory capacity in individuals carrying the A3243G mutation, this possibly being the primary defect contributing to the development of DM. In addition, our data suggest that this could be a functional defect.

Round and pointed-head grenadier fishes (Actinopterygii: Gadiformes) represent a single sister group: evidence from the complete mitochondrial genome sequences.

PubMed

Satoh, Takashi P; Miya, Masaki; Endo, Hiromitsu; Nishida, Mutsumi

2006-07-01

The gene order of mitochondrial genomes (mitogenomes) has been employed as a useful phylogenetic marker in various metazoan animals, because it may represent uniquely derived characters shared by members of monophyletic groups. During the course of molecular phylogenetic studies of the order Gadiformes (cods and their relatives) based on whole mitogenome sequences, we found that two deep-sea grenadiers (Squalogadus modificatus and Trachyrincus murrayi: family Macrouridae) revealed a unusually identical gene order (translocation of the tRNA(Leu (UUR))). Both are members of the same family, although their external morphologies differed so greatly (e.g., round vs. pointed head) that they have been placed in different subfamilies Macrouroidinae and Trachyrincinae, respectively. Additionally, we determined the whole mitogenome sequences of two other species, Bathygadus antrodes and Ventrifossa garmani, representing a total of four subfamilies currently recognized within Macrouridae. The latter two species also exhibited gene rearrangements, resulting in a total of three different patterns of unique gene order being observed in the four subfamilies. Partitioned Bayesian analysis was conducted using available whole mitogenome sequences from five macrourids plus five outgroups. The resultant trees clearly indicated that S. modificatus and T. murrayi formed a monophyletic group, having a sister relationship to other macrourids. Thus, monophyly of the two species with disparate head morphologies was corroborated by two different lines of evidence (nucleotide sequences and gene order). The overall topology of the present tree differed from any of the previously proposed, morphology-based phylogenetic hypotheses.

Comparison of two modes of vitamin B12 supplementation on neuroconduction and cognitive function among older people living in Sandiago, Chile: A cluster randomized controlled trial. A study protocol(ISRCTN 02694183)

USDA-ARS?s Scientific Manuscript database

BACKGROUND: Older people have a high risk of vitamin B12 deficiency; this can lead to varying degrees of cognitive and neurological impairment. CBL deficiency may present as macrocytic anemia, subacute combined degeneration of the spinal cord, or as neuropathy, but is often asymptomatic in older peo...

Effects of exercise on fitness and cognition in progressive MS: a randomized, controlled pilot trial.

PubMed

Briken, S; Gold, S M; Patra, S; Vettorazzi, E; Harbs, D; Tallner, A; Ketels, G; Schulz, K H; Heesen, C

2014-03-01

Exercise may have beneficial effects on both well-being and walking ability in multiple sclerosis (MS). Exercise is shown to be neuroprotective in rodents and may also enhance cognitive function in humans. It may, therefore, be particularly useful for MS patients with pronounced neurodegeneration. To investigate the potential of standardized exercise as a therapeutic intervention for progressive MS, in a randomized-controlled pilot trial. Patients with progressive MS and moderate disability (Expanded Disability Status Scale (EDSS) of 4-6) were randomized to one of three exercise interventions (arm ergometry, rowing, bicycle ergometry) for 8-10 weeks or a waitlist control group. We analyzed the drop-out rate as a measure of feasibility. The primary endpoint of the study was aerobic fitness. Secondary endpoints were walking ability, cognitive function as measured by a neuropsychological test battery, depression and fatigue. A total of 42 patients completed the trial (10.6% drop-out rate). Significant improvements were seen in aerobic fitness. In addition, exercise improved walking ability, depressive symptoms, fatigue and several domains of cognitive function. This study indicated that aerobic training is feasible and could be beneficial for patients with progressive MS. Larger exercise studies are needed to confirm the effect on cognition. ISRCTN (trial number 76467492) http://isrctn.org.

Rationale and study design of PROVHILO - a worldwide multicenter randomized controlled trial on protective ventilation during general anesthesia for open abdominal surgery.

PubMed

Hemmes, Sabrine N T; Severgnini, Paolo; Jaber, Samir; Canet, Jaume; Wrigge, Hermann; Hiesmayr, Michael; Tschernko, Edda M; Hollmann, Markus W; Binnekade, Jan M; Hedenstierna, Göran; Putensen, Christian; de Abreu, Marcelo Gama; Pelosi, Paolo; Schultz, Marcus J

2011-05-06

Post-operative pulmonary complications add to the morbidity and mortality of surgical patients, in particular after general anesthesia >2 hours for abdominal surgery. Whether a protective mechanical ventilation strategy with higher levels of positive end-expiratory pressure (PEEP) and repeated recruitment maneuvers; the "open lung strategy", protects against post-operative pulmonary complications is uncertain. The present study aims at comparing a protective mechanical ventilation strategy with a conventional mechanical ventilation strategy during general anesthesia for abdominal non-laparoscopic surgery. The PROtective Ventilation using HIgh versus LOw positive end-expiratory pressure ("PROVHILO") trial is a worldwide investigator-initiated multicenter randomized controlled two-arm study. Nine hundred patients scheduled for non-laparoscopic abdominal surgery at high or intermediate risk for post-operative pulmonary complications are randomized to mechanical ventilation with the level of PEEP at 12 cmH(2)O with recruitment maneuvers (the lung-protective strategy) or mechanical ventilation with the level of PEEP at maximum 2 cmH(2)O without recruitment maneuvers (the conventional strategy). The primary endpoint is any post-operative pulmonary complication. The PROVHILO trial is the first randomized controlled trial powered to investigate whether an open lung mechanical ventilation strategy in short-term mechanical ventilation prevents against postoperative pulmonary complications. ISRCTN: ISRCTN70332574.

PhysioDirect: Supporting physiotherapists to deliver telephone assessment and advice services within the context of a randomised trial

PubMed Central

Bishop, Annette; Gamlin, Jill; Hall, Jeanette; Hopper, Cherida; Foster, Nadine E.

2013-01-01

Physiotherapy-led telephone assessment and advice services for patients with musculoskeletal problems have been developed in many services in the UK, but high quality trial data on clinical and cost effectiveness has been lacking. In order to address this ‘The PhysioDirect trial’ (ISRCTN55666618), was a pragmatic randomised trial of a PhysioDirect telephone assessment and advice service. This paper describes the PhysioDirect system used in the trial and how physiotherapists were trained and supported to use the system and deliver the PhysioDirect service. The PhysioDirect system used in the trial was developed in Huntingdon and now serves a population of 350,000 people. When initiating or providing physiotherapy-led telephone assessment and advice services training and support for physiotherapists delivering care in this way is essential. An enhanced skill set is required for telephone assessment and advice particularly in listening and communication skills. In addition to an initial training programme, even experienced physiotherapists benefit from a period of skill consolidation to become proficient and confident in assessing patients and delivering care using the telephone. A computer-based system assists the delivery of a physiotherapy-led musculoskeletal assessment and advice service. Clinical Trials Registration Number (ISRCTN55666618). PMID:23219629

Effect of nutritional supplementation of breastfeeding HIV positive mothers on maternal and child health: findings from a randomized controlled clinical trial

PubMed Central

2011-01-01

Background It has been well established that breastfeeding is beneficial for child health, however there has been debate regarding the effect of lactation on maternal health in the presence of HIV infection and the need for nutritional supplementation in HIV positive lactating mothers. Aims To assess the effect of nutritional supplementation to HIV infected lactating mothers on nutritional and health status of mothers and their infants. Methods A randomized controlled clinical trial to study the impact of nutritional supplementation on breastfeeding mothers. Measurements included anthropometry; body composition indicators; CD4 count, haemoglobin and albumin; as well as incidence rates of opportunistic infections; depression and quality of life scores. Infant measurements included anthropometry, development and rates of infections. Results The supplement made no significant impact on any maternal or infant outcomes. However in the small group of mothers with low BMI, the intake of supplement was significantly associated with preventing loss of lean body mass (1.32 kg vs. 3.17 kg; p = 0.026). There was no significant impact of supplementation on the infants. Conclusions A 50 g daily nutritional supplement to breastfeeding mothers had no or limited effect on mother and child health outcomes. Clinical trial registration ISRCTN68128332 (http://www.controlled-trials.com/ISRCTN68128332) PMID:22192583

Did you get any help? A post-hoc secondary analysis of a randomized controlled trial of psychoeducation for patients with antisocial personality disorder in outpatient substance abuse treatment programs.

PubMed

Thylstrup, Birgitte; Schrøder, Sidsel; Fridell, Mats; Hesse, Morten

2017-01-09

People in treatment for substance use disorder commonly have comorbid personality disorders, including antisocial personality disorder. Little is known about treatments that specifically address comorbid antisocial personality disorder. Self-rated help received for antisocial personality disorder was assessed during follow-ups at 3, 9 and 15 months post-randomization of a randomized trial of psychoeducation for people with comorbid substance use and antisocial personality disorder (n = 175). Randomization to psychoeducation was associated with increased perceived help for antisocial personality disorder. Perceived help for antisocial personality disorder was in turn associated with more days abstinent and higher treatment satisfaction at the 3-month follow-up, and reduced risk of dropping out of treatment after the 3-month follow-up, and perceived help mediated the effects of random assignment on days abstinent at 3-month. Brief psychoeducation for antisocial personality disorder increased patients' self-rated help for antisocial personality disorder in substance abuse treatment, and reporting having received help for antisocial personality disorder was in turn associated with better short-term outcomes, e.g., days abstinent, dropout from treatment and treatment satisfaction. ISRCTN registry, ISRCTN67266318 , retrospectively registered 17/7/2012.

The Functional Fitness MOT Test Battery for Older Adults: Protocol for a Mixed-Method Feasibility Study.

PubMed

de Jong, Lex D; Peters, Andy; Hooper, Julie; Chalmers, Nina; Henderson, Claire; Laventure, Robert Me; Skelton, Dawn A

2016-06-20

Increasing physical activity (PA) brings many health benefits, but engaging people in higher levels of PA after their 60s is not straightforward. The Functional Fitness MOT (FFMOT) is a new approach which aims to raise awareness about the importance of components of fitness (strength, balance, flexibility), highlight benefits of PA, engages older people in health behavior change discussions, and directs them to local activity resources. This battery of tests combined with a brief motivational interview has not been tested in terms of feasibility or effectiveness. To assess whether the FFMOT, provided in a health care setting, is appealing to older patients of a community physiotherapy service and to understand the views and perceptions of the older people undergoing the FFMOT regarding the intervention, as well as the views of the physiotherapy staff delivering the intervention. Secondary aims are to assess the feasibility of carrying out a phase 2 pilot randomized controlled trial of the FFMOT, in the context of a community physiotherapy service, by establishing whether enough patients can be recruited and retained in the study, and enough outcome data can be generated. A mixed-methods feasibility study will be conducted in two physiotherapy outpatient clinics in the United Kingdom. A total of 30 physically inactive, medically stable older adults over the age of 60 will be provided with an individual FFMOT, comprising a set of six standardized, validated, age-appropriate tests aimed at raising awareness of the different components of fitness. The results of these tests will be used to provide the participants with feedback on performance in comparison to sex and age-referenced norms. This will be followed by tailored advice on how to become more active and improve fitness, including advice on local opportunities to be more active. Subsequently, participants will be invited to attend a focus group to discuss barriers and motivators to being more active, health behavior change, and the scope for individuals to improve their PA levels. To inform the design of a future trial, descriptive (eg, recruitment and retention rates), quantitative (Community Healthy Activities Model Program for Seniors; CHAMPS physical activity questionnaire), and qualitative data (focus group discussions, semi-structured staff interviews) will be collected. Recruitment and enrolment for the trial started in September 2015. Follow-up will be completed in June 2016. Results are expected to be available at the end of 2016. Allied health professionals play a key role in encouraging older adults to increase their PA, but with little evidence on how best to do this within their clinical practice. The purpose of this feasibility study is to examine the introduction of a new service: The FFMOT. The views and perceptions of the older people undergoing the FFMOT and relating to its delivery in clinical practice will be explored. Data, which will inform the feasibility of a randomized controlled trial of effectiveness of the FFMOT in promoting improved PA, will be reported. International Standard Randomized Controlled Trial Number (ISRCTN): ISRCTN38950042; http://www.isrctn.com/ISRCTN38950042.

Effectiveness of a Text Messaging-Based Intervention Targeting Alcohol Consumption Among University Students: Randomized Controlled Trial.

PubMed

Thomas, Kristin; Müssener, Ulrika; Linderoth, Catharina; Karlsson, Nadine; Bendtsen, Preben; Bendtsen, Marcus

2018-06-25

Excessive drinking among university students is a global challenge, leading to significant health risks. However, heavy drinking among students is widely accepted and socially normalized. Mobile phone interventions have attempted to reach students who engage in excessive drinking. A growing number of studies suggest that text message-based interventions could potentially reach many students and, if effective, such an intervention might help reduce heavy drinking in the student community. The objective of this study was to test the effectiveness of a behavior change theory-based 6-week text message intervention among university students. This study was a two-arm, randomized controlled trial with an intervention group receiving a 6-week text message intervention and a control group that was referred to treatment as usual at the local student health care center. Outcome measures were collected at baseline and at 3 months after the initial invitation to participate in the intervention. The primary outcome was total weekly alcohol consumption. Secondary outcomes were frequency of heavy episodic drinking, highest estimated blood alcohol concentration, and number of negative consequences attributable to excessive drinking. A total of 896 students were randomized to either the intervention or control group. The primary outcome analysis included 92.0% of the participants in the intervention group and 90.1% of the control group. At follow-up, total weekly alcohol consumption decreased in both groups, but no significant between-group difference was seen. Data on the secondary outcomes included 49.1% of the participants in the intervention group and 41.3% of the control group. No significant between-group difference was seen for any of the secondary outcomes. The present study was under-powered, which could partly explain the lack of significance. However, the intervention, although theory-based, needs to be re-assessed and refined to better support the target group. Apart from establishing which content forms an effective intervention, the optimal length of an alcohol intervention targeting students also needs to be addressed in future studies. International Standard Randomised Controlled Trial Number ISRCTN95054707; http://www.isrctn.com/ISRCTN95054707 (Archived by WebCite at http://www.webcitation.org/70Ax4vXhd). ©Kristin Thomas, Ulrika Müssener, Catharina Linderoth, Nadine Karlsson, Preben Bendtsen, Marcus Bendtsen. Originally published in JMIR Mhealth and Uhealth (http://mhealth.jmir.org), 25.06.2018.

The effectiveness of aerobic training, cognitive behavioural therapy, and energy conservation management in treating MS-related fatigue: the design of the TREFAMS-ACE programme

PubMed Central

2013-01-01

Background TREFAMS is an acronym for TReating FAtigue in Multiple Sclerosis, while ACE refers to the rehabilitation treatment methods under study, that is, Aerobic training, Cognitive behavioural therapy, and Energy conservation management. The TREFAMS-ACE research programme consists of four studies and has two main objectives: (1) to assess the effectiveness of three different rehabilitation treatment strategies in reducing fatigue and improving societal participation in patients with MS; and (2) to study the neurobiological mechanisms of action that underlie treatment effects and MS-related fatigue in general. Methods/Design Ambulatory patients (n = 270) suffering from MS-related fatigue will be recruited to three single-blinded randomised clinical trials (RCTs). In each RCT, 90 patients will be randomly allocated to the trial-specific intervention or to a low-intensity intervention that is the same for all RCTs. This low-intensity intervention consists of three individual consultations with a specialised MS-nurse. The trial-specific interventions are Aerobic Training, Cognitive Behavioural Therapy, and Energy Conservation Management. These interventions consist of 12 individual therapist-supervised sessions with additional intervention-specific home exercises. The therapy period lasts 16 weeks. All RCTs have the same design and the same primary outcome measures: fatigue - measured with the Checklist Individual Strength, and participation - measured with the Impact on Participation and Autonomy questionnaire. Outcomes will be assessed 1 week prior to, and at 0, 8, 16, 26 and 52 weeks after randomisation. The assessors will be blinded to allocation. Pro- and anti-inflammatory cytokines in serum, salivary cortisol, physical fitness, physical activity, coping, self-efficacy, illness cognitions and other determinants will be longitudinally measured in order to study the neurobiological mechanisms of action. Discussion The TREFAMS-ACE programme is unique in its aim to assess the effectiveness of three rehabilitation treatments. The programme will provide important insights regarding the most effective treatment for MS-related fatigue and the mechanisms that underlie treatment response. A major strength of the programme is that the design involves three almost identical RCTs, enabling a close comparison of the treatment strategies and a strong overall meta-analysis. The results will also support clinical practice guidelines for the treatment of MS-related fatigue. Trial registrations Current Controlled Trials ISRCTN69520623, ISRCTN58583714, and ISRCTN82353628 PMID:23938046

Efficacy of Cognitive Behavioral Therapy for Insomnia in Adolescents: A Randomized Controlled Trial with Internet Therapy, Group Therapy and A Waiting List Condition.

PubMed

de Bruin, Eduard J; Bögels, Susan M; Oort, Frans J; Meijer, Anne Marie

2015-12-01

To investigate the efficacy of cognitive behavioral therapy for insomnia (CBTI) in adolescents. A randomized controlled trial of CBTI in group therapy (GT), guided internet therapy (IT), and a waiting list (WL), with assessments at baseline, directly after treatment (post-test), and at 2 months follow-up. Diagnostic interviews were held at the laboratory of the Research Institute of Child Development and Education at the University of Amsterdam. Treatment for GT occurred at the mental health care center UvAMinds in Amsterdam, the Netherlands. One hundred sixteen adolescents (mean age = 15.6 y, SD = 1.6 y, 25% males) meeting DSM-IV criteria for insomnia, were randomized to IT, GT, or WL. CBTI of 6 weekly sessions, consisted of psychoeducation, sleep hygiene, restriction of time in bed, stimulus control, cognitive therapy, and relaxation techniques. GT was conducted in groups of 6 to 8 adolescents, guided by 2 trained sleep therapists. IT was applied through an online guided self-help website with programmed instructions and written feedback from a trained sleep therapist. Sleep was measured with actigraphy and sleep logs for 7 consecutive days. Symptoms of insomnia and chronic sleep reduction were measured with questionnaires. Results showed that adolescents in both IT and GT, compared to WL, improved significantly on sleep efficiency, sleep onset latency, wake after sleep onset, and total sleep time at post-test, and improvements were maintained at follow-up. Most of these improvements were found in both objective and subjective measures. Furthermore, insomnia complaints and symptoms of chronic sleep reduction also decreased significantly in both treatment conditions compared to WL. Effect sizes for improvements ranged from medium to large. A greater proportion of participants from the treatment conditions showed high end-state functioning and clinically significant improvement after treatment and at follow-up compared to WL. This study is the first randomized controlled trial that provides evidence that cognitive behavioral therapy for insomnia is effective for the treatment of adolescents with insomnia, with medium to large effect sizes. There were small differences between internet and group therapy, but both treatments reached comparable endpoints. This study was part of the clinical trial: Effectiveness of cognitive behavioral therapy for sleeplessness in adolescents; URL: http://www.isrctn.com/ISRCTN33922163; registration: ISRCTN33922163. © 2015 Associated Professional Sleep Societies, LLC.

The association of serum choline with linear growth failure in young children from rural Malawi12

PubMed Central

Semba, Richard D; Zhang, Pingbo; Gonzalez-Freire, Marta; Moaddel, Ruin; Trehan, Indi; Maleta, Kenneth M; Ordiz, M Isabel; Ferrucci, Luigi; Manary, Mark J

2016-01-01

Background: Choline is an essential nutrient for cell structure, cell signaling, neurotransmission, lipid transport, and bone formation. Choline can be irreversibly converted to betaine, a major source of methyl groups. Trimethylene N-oxide (TMAO), a proatherogenic molecule, is produced from the metabolism of dietary choline by the gut microbiome. The relation between serum choline and its closely related metabolites with linear growth in children is unknown. Objective: The aim was to characterize the relation between serum choline and its closely related metabolites, betaine and TMAO, with linear growth and stunting in young children. Design: We measured serum choline, betaine, and TMAO concentrations by using liquid chromatography isotopic dilution tandem mass spectrometry in a cross-sectional study in 325 Malawian children, aged 12–59 mo, of whom 62% were stunted. Results: Median (25th, 75th percentile) serum choline, betaine, and TMAO concentrations were 6.4 (4.8, 8.3), 12.4 (9.1, 16.3), and 1.2 (0.7, 1.8) μmol/L, respectively. Spearman correlation coefficients of age with serum choline, betaine, and TMAO were −0.57 (P < 0.0001), −0.26 (P < 0.0001), and −0.10 (P = 0.07), respectively. Correlation coefficients of height-for-age z score with serum choline, betaine-to-choline ratio, and TMAO-to-choline ratio were 0.31 (P < 0.0001), −0.24 (P < 0.0001), and −0.29 (P < 0.0001), respectively. Serum choline concentrations were strongly and significantly associated with stunting. Children with and without stunting had median (25th, 75th percentile) serum choline concentrations of 5.6 (4.4, 7.4) and 7.3 (5.9, 9.1) μmol/L (P < 0.0001). Conclusions: Linear growth failure in young children is associated with low serum choline and elevated betaine-to-choline and TMAO-to-choline ratios. Further work is needed to understand whether low dietary choline intake explains low circulating choline among stunted children living in low-income countries and whether increasing choline intake may correct choline deficiency and improve growth and development. This trial was registered in the ISRCTN registry (www.isrctn.com) as ISRCTN14597012. PMID:27281303

A multicentre, pragmatic, parallel group, randomised controlled trial to compare the clinical and cost-effectiveness of three physiotherapy-led exercise interventions for knee osteoarthritis in older adults: the BEEP trial protocol (ISRCTN: 93634563).

PubMed

Foster, Nadine E; Healey, Emma L; Holden, Melanie A; Nicholls, Elaine; Whitehurst, David Gt; Jowett, Susan; Jinks, Clare; Roddy, Edward; Hay, Elaine M

2014-07-27

Exercise is consistently recommended for older adults with knee pain related to osteoarthritis. However, the effects from exercise are typically small and short-term, likely linked to insufficient individualisation of the exercise programme and limited attention to supporting exercise adherence over time. The BEEP randomised trial aims to improve patients' short and long-term outcomes from exercise. It will test the overall effectiveness and cost-effectiveness of two physiotherapy-led exercise interventions (Individually Tailored Exercise and Targeted Exercise Adherence) to improve the individual tailoring of, and adherence to exercise, compared with usual physiotherapy care. Based on the learning from a pilot study (ISRCTN 23294263), the BEEP trial is a multi-centre, pragmatic, parallel group, individually randomised controlled trial, with embedded longitudinal qualitative interviews. 500 adults in primary care, aged 45 years and over with knee pain will be randomised to 1 of 3 treatment groups delivered by fully trained physiotherapists in up to 6 NHS services. These are: Usual Physiotherapy Care (control group consisting of up to 4 treatment sessions of advice and exercise), Individually Tailored Exercise (an individualised, supervised and progressed lower-limb exercise programme) or Targeted Exercise Adherence (supporting patients to adhere to exercise and to engage in general physical activity over the longer-term). The primary outcomes are pain and function as measured by the Western Ontario and McMaster Osteoarthritis index. A comprehensive range of secondary outcomes are also included. Outcomes are measured at 3, 6 (primary outcome time-point), 9, 18 and 36 months. Data on adverse events will also be collected. Semi-structured, qualitative interviews with a subsample of 30 participants (10 from each treatment group) will be undertaken at two time-points (end of treatment and 12 to 18 months later) and analysed thematically. This trial will contribute to the evidence base for management of older adults with knee pain attributable to osteoarthritis in primary care. The findings will have important implications for healthcare commissioners, general practitioners and physiotherapy service providers and it will inform future education of healthcare practitioners. It may also serve to delay or prevent some individuals from becoming surgical candidates. ISRCTN93634563.

Quality of life after intra-arterial treatment for acute ischemic stroke in the MR CLEAN trial-Update.

PubMed

Schreuders, Jennifer; van den Berg, Lucie A; Fransen, Puck Ss; Berkhemer, Olvert A; Beumer, Debbie; Lingsma, Hester F; van Oostenbrugge, Robert J; van Zwam, Wim H; Majoie, Charles Blm; van der Lugt, Aad; de Kort, Paul Lm; Roos, Yvo Bwem; Dippel, Diederik Wj

2017-10-01

Background Health-related quality of life measured with the EuroQol Group 5-Dimension Self-Report Questionnaire was one of the secondary outcomes in the Multicenter Randomized Clinical trial of Endovascular treatment for Acute ischemic stroke in the Netherlands (MR CLEAN). We reported no statistically significant difference in EuroQol Group 5-Dimension Self-Report Questionnaire score between the intervention and control groups, but deaths were not included. Aims Reanalyze the effect of intra-arterial treatment for large vessel occlusion in acute ischemic stroke patients on health-related quality of life in more detail. We now include patients who died during follow-up. Methods The EuroQol Group 5-Dimension Self-Report Questionnaire questionnaires were obtained 90 days after treatment. We used the Dutch tariff to derive a utility index from the EuroQol Group 5-Dimension Self-Report Questionnaire score. Treatment effect was estimated with the Mann-Whitney U test and linear regression. The effect of treatment on the distribution of EuroQol Group 5-Dimension Self-Report Questionnaire dimension scores was assessed with ordinal logistic regression. Results We obtained EuroQol Group 5-Dimension Self-Report Questionnaire scores from 457 (91.7%) of the 500 patients, including 108 who died before follow-up. Median EuroQol Group 5-Dimension Self-Report Questionnaire score in the intervention group was 0.57, and 0.39 in the control group (p = 0.03). Treatment effect estimated with linear regression was 0.07 (95%CI: -0.001 to 0.143). Treatment specifically affected EuroQol Group 5-Dimension Self-Report Questionnaire dimensions "mobility" (OR: 0.43, 95%CI: 0.29-0.66), "self-care" (OR: 0.60, 95%CI: 0.41-0.89), and "usual activities" (OR: 0.53, 95%CI: 0.36-0.79). Conclusion Treatment had a limited effect on quality of life, as measured with the EuroQol Group 5-Dimension Self-Report Questionnaire. Nevertheless, patients with acute ischemic stroke caused by an intracranial occlusion in the anterior circulation, who had intra-arterial treatment, experience better health-related quality of life than patients without intra-arterial treatment. Trial Registration URL: http://www.isrctn.com/ISRCTN10888758 Unique identifier: ISRCTN10888758.

Protocol of the Febuxostat versus Allopurinol Streamlined Trial (FAST): a large prospective, randomised, open, blinded endpoint study comparing the cardiovascular safety of allopurinol and febuxostat in the management of symptomatic hyperuricaemia.

PubMed

MacDonald, Thomas M; Ford, Ian; Nuki, George; Mackenzie, Isla S; De Caterina, Raffaele; Findlay, Evelyn; Hallas, Jesper; Hawkey, Christopher J; Ralston, Stuart; Walters, Matthew; Webster, John; McMurray, John; Perez Ruiz, Fernando; Jennings, Claudine G

2014-07-10

Gout affects 2.5% of the UK's adult population and is now the most common type of inflammatory arthritis. The long-term management of gout requires reduction of serum urate levels and this is most often achieved with use of xanthine oxidase inhibitors, such as allopurinol. Febuxostat is the first new xanthine oxidase inhibitor since allopurinol and was licensed for use in 2008. The European Medicines Agency requested a postlicensing cardiovascular safety study of febuxostat versus allopurinol, which has been named the Febuxostat versus Allopurinol Streamlined trial (FAST). FAST is a cardiovascular safety study using the prospective, randomised, open, blinded endpoint design. FAST is recruiting in the UK and Denmark. Recruited patients are aged over 60 years, prescribed allopurinol for symptomatic hyperuricaemia and have at least one additional cardiovascular risk factor. After an allopurinol lead-in phase where the dose of allopurinol is optimised to achieve European League against Rheumatism (EULAR) urate targets (serum urate <357 µmol/L), patients are randomised to either continue optimal dose allopurinol or to use febuxostat. Patients are followed-up for an average of 3 years. The primary endpoint is first occurrence of the Anti-Platelet Trialists' Collaboration (APTC) cardiovascular endpoint of non-fatal myocardial infarction, non-fatal stroke or cardiovascular death. Secondary endpoints are all cause mortality and hospitalisations for heart failure, unstable, new or worsening angina, coronary or cerebral revascularisation, transient ischaemic attack, non-fatal cardiac arrest, venous and peripheral arterial vascular thrombotic event and arrhythmia with no evidence of ischaemia. The primary analysis is a non-inferiority analysis with a non-inferiority upper limit for the HR for the primary outcome of 1.3. FAST (ISRCTN72443728) has ethical approval in the UK and Denmark, and results will be published in a peer reviewed journal. FAST is registered in the EU Clinical Trials Register (EUDRACT No: 2011-001883-23) and International Standard Randomised Controlled Trial Number Register (ISRCTN No: ISRCTN72443728). Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

Cell salvage and donor blood transfusion during cesarean section: A pragmatic, multicentre randomised controlled trial (SALVO)

PubMed Central

Khan, Khalid S.; Wilson, Matthew J.; Hooper, Richard; Allard, Shubha; Wrench, Ian; Geoghegan, James; Catling, Sue; Clark, Vicki A.; Ayuk, Paul; Robson, Stephen; Gao-Smith, Fang; Hogg, Matthew; Dodds, Julie

2017-01-01

Background Excessive haemorrhage at cesarean section requires donor (allogeneic) blood transfusion. Cell salvage may reduce this requirement. Methods and findings We conducted a pragmatic randomised controlled trial (at 26 obstetric units; participants recruited from 4 June 2013 to 17 April 2016) of routine cell salvage use (intervention) versus current standard of care without routine salvage use (control) in cesarean section among women at risk of haemorrhage. Randomisation was stratified, using random permuted blocks of variable sizes. In an intention-to-treat analysis, we used multivariable models, adjusting for stratification variables and prognostic factors identified a priori, to compare rates of donor blood transfusion (primary outcome) and fetomaternal haemorrhage ≥2 ml in RhD-negative women with RhD-positive babies (a secondary outcome) between groups. Among 3,028 women randomised (2,990 analysed), 95.6% of 1,498 assigned to intervention had cell salvage deployed (50.8% had salvaged blood returned; mean 259.9 ml) versus 3.9% of 1,492 assigned to control. Donor blood transfusion rate was 3.5% in the control group versus 2.5% in the intervention group (adjusted odds ratio [OR] 0.65, 95% confidence interval [CI] 0.42 to 1.01, p = 0.056; adjusted risk difference −1.03, 95% CI −2.13 to 0.06). In a planned subgroup analysis, the transfusion rate was 4.6% in women assigned to control versus 3.0% in the intervention group among emergency cesareans (adjusted OR 0.58, 95% CI 0.34 to 0.99), whereas it was 2.2% versus 1.8% among elective cesareans (adjusted OR 0.83, 95% CI 0.38 to 1.83) (interaction p = 0.46). No case of amniotic fluid embolism was observed. The rate of fetomaternal haemorrhage was higher with the intervention (10.5% in the control group versus 25.6% in the intervention group, adjusted OR 5.63, 95% CI 1.43 to 22.14, p = 0.013). We are unable to comment on long-term antibody sensitisation effects. Conclusions The overall reduction observed in donor blood transfusion associated with the routine use of cell salvage during cesarean section was not statistically significant. Trial registration This trial was prospectively registered on ISRCTN as trial number 66118656 and can be viewed on http://www.isrctn.com/ISRCTN66118656. PMID:29261655

1,2-Octanediol, a Novel Surfactant, for Treating Head Louse Infestation: Identification of Activity, Formulation, and Randomised, Controlled Trials

PubMed Central

Burgess, Ian F.; Lee, Peter N.; Kay, Katrina; Jones, Ruth; Brunton, Elizabeth R.

2012-01-01

Background Interest in developing physically active pediculicides has identified new active substances. The objective was to evaluate a new treatment for clinical efficacy. Methods and Findings We describe the selection of 1,2-octanediol as a potential pediculicide. Clinical studies were community based. The main outcome measure was no live lice, after two treatments, with follow up visits over 14 days. Study 1 was a proof of concept with 18/20 (90%) participants cured. Study 2 was a multicentre, parallel, randomised, observer-blind study (520 participants) that compared 0.5% malathion liquid with 1,2-octanediol lotion (20% alcohol) applied 2–2.5 hours or 8 hours/overnight. 1,2-octanediol lotion was significantly (p<0.0005) more effective with success for 124/175 (70.9%) RR = 1.50 (97.5% CI, 1.22 to 1.85) for 2–2.5 hours, and 153/174 (87.9%) RR = 1.86 (97.5% CI, 1.54 to 2.26) for 8 hours/overnight compared with 81/171 (47.4%) for malathion. Study 3, a two centre, parallel, randomised, observer-blind study (121 participants), compared 1,2-octanediol lotion, 2–2.5 hours with 1,2-octanediol alcohol free mousse applied for 2–2.5 hours or 8 hours/overnight. The mousse applied for 8 hours/overnight cured 31/40 (77.5%), compared with 24/40 (60.0%) for lotion (RR = 1.29, 95% CI, 0.95 to 1.75; NNT = 5.7) but mousse applied for 2–2.5 hours 17/41 (41.5%) was less effective than lotion (RR = 0.69, 95% CI, 0.44 to 1.08). Adverse events were more common using 1,2-octanediol lotion at both 2–2.5 hours (12.0%, p = 0.001) and 8 hours/overnight (14.9%, p<0.0005), compared with 0.5% malathion (2.3%). Similar reactions were more frequent (p<0.045) using lotion compared with mousse. Conclusions 1,2-octanediol was found to eliminate head louse infestation. It is believed to disrupt the insect's cuticular lipid, resulting in dehydration. The alcohol free mousse is more acceptable exhibiting significantly fewer adverse reactions. Trial registrations Controlled-Trials.com ISRCTN66611560, ISRCTN91870666, ISRCTN28722846 PMID:22523593

The Effects of Social Presence on Adherence-Focused Guidance in Problematic Cannabis Users: Protocol for the CANreduce 2.0 Randomized Controlled Trial

PubMed Central

Amann, Manuel; Haug, Severin; Wenger, Andreas; Baumgartner, Christian; Ebert, David D; Berger, Thomas; Stark, Lars; Walter, Marc

2018-01-01

Background In European countries, including Switzerland, cannabis is the most commonly used illicit drug. Offering a Web-based self-help tool could potentially reach users who otherwise would not seek traditional help. However, such Web-based self-help tools often suffer from low adherence. Objective Through adherence-focused guidance enhancements, the aim of this study was to increase adherence in cannabis users entering a Web-based self-help tool to reduce their cannabis use and, in this way, augment its effectiveness. Methods This paper presents the protocol for a three-arm randomized controlled trial (RCT) to compare the effectiveness of (1) an adherence-focused, guidance-enhanced, Web-based self-help intervention with social presence; (2) an adherence-focused, guidance-enhanced, Web-based self-help intervention without social presence; and (3) a treatment-as-usual at reducing cannabis use in problematic users. The two active interventions, each spanning 6 weeks, consist of modules designed to reduce cannabis use and attenuate common mental disorder (CMD) symptoms, including depression, anxiety, and stress-related disorder symptoms based on the approaches of motivational interviewing and cognitive behavioral therapy. With a target sample size of 528, data will be collected at baseline, 6 weeks, and 3 months after baseline. The primary outcome measurement will be the number of days of cannabis use on the preceding 7 days. Secondary outcomes will include the quantity of cannabis used in standardized cannabis joints, the severity of cannabis dependence, changes in CMD symptoms, and adherence to the program. Data analysis will follow the intention-to-treat principle and employ (generalized) linear mixed models. Results The project commenced in August 2016; recruitment is anticipated to end by December 2018. First results are expected to be submitted for publication in summer 2019. Conclusions This study will provide detailed insights on if and how the effectiveness of a Web-based self-help intervention aiming to reduce cannabis use in frequent cannabis users can be improved by theory-driven, adherence-focused guidance enhancement. Trial Registration International Standard Randomized Controlled Trial Number Registry: ISRCTN11086185; http://www.isrctn.com/ISRCTN11086185 (Archived by WebCite at http://www.webcitation.org/6wspbuQ1M) PMID:29386176

Cost-Effectiveness of Group and Internet Cognitive Behavioral Therapy for Insomnia in Adolescents: Results from a Randomized Controlled Trial

PubMed Central

De Bruin, Eduard J.; van Steensel, Francisca J.A.; Meijer, Anne Marie

2016-01-01

Study Objectives: To investigate cost-effectiveness of adolescent cognitive behavioral therapy for insomnia (CBTI) in group- and Internet-delivered formats, from a societal perspective with a time horizon of 1 y Methods: Costs and effects data up to 1-y follow-up were obtained from a randomized controlled trial (RCT) comparing Internet CBTI to face-to-face group CBTI. The study was conducted at the laboratory of the Research Institute of Child Development and Education at the University of Amsterdam, and the academic youth mental health care center UvAMinds in Amsterdam. Sixty-two participants meeting Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision criteria for insomnia were randomized to face-to-face group CBTI (GT; n = 31, age = 15.6 y ± 1.8, 71.0% girls) or individual Internet CBTI (IT; n = 31, age = 15.4 y ± 1.5, 83.9% girls). The intervention consisted of six weekly sessions and a 2-mo follow up booster-session of CBTI, consisting of psychoeducation, sleep hygiene, restriction of time in bed, stimulus control, cognitive therapy, and relaxation techniques. GT sessions were held in groups of six to eight adolescents guided by two trained sleep therapists. IT consisted of individual Internet therapy with preprogrammed content similar to GT, and guided by trained sleep therapists. Results: Outcome measures were subjective sleep efficiency (SE) ≥ 85%, and quality-adjusted life-years (QALY). Analyses were conducted from a societal perspective. Incremental cost-effectiveness ratios (ICERs) were calculated using bootstrap sampling, and presented in cost-effectiveness planes. Primary analysis showed costs over 1 y were higher for GT but effects were similar for IT and GT. Bootstrapped ICERs demonstrated there is a high probability of IT being cost-effective compared to GT. Secondary analyses confirmed robustness of results. Conclusions: Internet CBTI is a cost-effective treatment compared to group CBTI for adolescents, although effects were largely similar for both formats. Further studies in a clinical setting are warranted. Clinical Trial Registration: ID: ISRCTN33922163; trial name: Effectiveness of cognitive behavioral therapy for sleeplessness in adolescents; URL: http://www.isrctn.com/ISRCTN33922163 Citation: De Bruin EJ, van Steensel FJ, Meijer AM. Cost-effectiveness of group and internet cognitive behavioral therapy for insomnia in adolescents: results from a randomized controlled trial. SLEEP 2016;39(8):1571–1581. PMID:27306272

Effect of CPAP Withdrawal on BP in OSA: Data from Three Randomized Controlled Trials.

PubMed

Schwarz, Esther I; Schlatzer, Christian; Rossi, Valentina A; Stradling, John R; Kohler, Malcolm

2016-12-01

Based on meta-analyses, the BP-lowering effect of CPAP therapy in patients with OSA is reported to be approximately 2 to 3 mm Hg. This figure is derived from heterogeneous trials, which are often limited by poor CPAP adherence, and thus the treatment effect may possibly be underestimated. We analyzed morning BP data from three randomized controlled CPAP withdrawal trials, which included only patients with optimal CPAP compliance. Within the three trials, 149 patients with OSA who were receiving CPAP were randomized to continue therapeutic CPAP (n = 65) or to withdraw CPAP (n = 84) for 2 weeks. Morning BP was measured at home before and after sleep studies in the hospital. CPAP withdrawal was associated with a return of OSA (apnea-hypopnea index [AHI] at a baseline of 2.8/h and at follow-up of 33.2/h). Office systolic BP (SBP) increased in the CPAP withdrawal group compared with the CPAP continuation group by +5.4 mm Hg (95% CI, 1.8-8.9 mm Hg; P = .003) and in the home SBP group by +9.0 mm Hg (95% CI, 5.7-12.3 mm Hg; P < .001). Office diastolic BP (DBP) increased by +5.0 mm Hg (95% CI, 2.7-7.3 mm Hg; P < .001), and home DBP increased by +7.8 mm Hg (95% CI, 5.6-10.4 mm Hg; P < .001). AHI, baseline home SBP, use of statin drugs, sex, and the number of antihypertensive drugs prescribed were all independently associated with SBP change in multivariate analysis, controlling for age, BMI, smoking status, diabetes, and sleepiness. CPAP withdrawal results in a clinically relevant increase in BP, which is considerably higher than in conventional CPAP trials; it is also underestimated when office BP is used. Greater OSA severity is associated with a higher BP rise in response to CPAP withdrawal. ClinicalTrials.gov; No.: NCT01332175 and NCT01797653) URL: www.clinicaltrials.gov and ISRCTN registry (ISRCTN 93153804) URL: http://www.isrctn.com/. Copyright © 2016 American College of Chest Physicians. Published by Elsevier Inc. All rights reserved.

1,2-Octanediol, a novel surfactant, for treating head louse infestation: identification of activity, formulation, and randomised, controlled trials.

PubMed

Burgess, Ian F; Lee, Peter N; Kay, Katrina; Jones, Ruth; Brunton, Elizabeth R

2012-01-01

Interest in developing physically active pediculicides has identified new active substances. The objective was to evaluate a new treatment for clinical efficacy. We describe the selection of 1,2-octanediol as a potential pediculicide. Clinical studies were community based. The main outcome measure was no live lice, after two treatments, with follow up visits over 14 days. Study 1 was a proof of concept with 18/20 (90%) participants cured. Study 2 was a multicentre, parallel, randomised, observer-blind study (520 participants) that compared 0.5% malathion liquid with 1,2-octanediol lotion (20% alcohol) applied 2-2.5 hours or 8 hours/overnight. 1,2-octanediol lotion was significantly (p<0.0005) more effective with success for 124/175 (70.9%) RR = 1.50 (97.5% CI, 1.22 to 1.85) for 2-2.5 hours, and 153/174 (87.9%) RR = 1.86 (97.5% CI, 1.54 to 2.26) for 8 hours/overnight compared with 81/171 (47.4%) for malathion. Study 3, a two centre, parallel, randomised, observer-blind study (121 participants), compared 1,2-octanediol lotion, 2-2.5 hours with 1,2-octanediol alcohol free mousse applied for 2-2.5 hours or 8 hours/overnight. The mousse applied for 8 hours/overnight cured 31/40 (77.5%), compared with 24/40 (60.0%) for lotion (RR = 1.29, 95% CI, 0.95 to 1.75; NNT = 5.7) but mousse applied for 2-2.5 hours 17/41 (41.5%) was less effective than lotion (RR = 0.69, 95% CI, 0.44 to 1.08). Adverse events were more common using 1,2-octanediol lotion at both 2-2.5 hours (12.0%, p = 0.001) and 8 hours/overnight (14.9%, p<0.0005), compared with 0.5% malathion (2.3%). Similar reactions were more frequent (p<0.045) using lotion compared with mousse. 1,2-octanediol was found to eliminate head louse infestation. It is believed to disrupt the insect's cuticular lipid, resulting in dehydration. The alcohol free mousse is more acceptable exhibiting significantly fewer adverse reactions. Controlled-Trials.com ISRCTN66611560, ISRCTN91870666, ISRCTN28722846.

Evaluation of Technology-Based Peer Support Intervention Program for Preventing Postnatal Depression: Protocol for a Randomized Controlled Trial.

PubMed

Shorey, Shefaly; Chee, Cornelia; Chong, Yap-Seng; Ng, Esperanza Debby; Lau, Ying; Dennis, Cindy-Lee

2018-03-14

Multiple international agencies, including the World Health Organization and the International Monetary Fund, have emphasized the importance of maternal mental health for optimal child health and development. Adequate social support is vital for the most vulnerable to postpartum mood disorders. Hence, an urgent need for sustainable social support programs to aid mothers ease into their new parenting role exists. This study protocol aims to examine the effectiveness of a technology-based peer support intervention program among mothers at risk for postnatal depression in the early postpartum period. A randomized controlled 2-group pretest and repeated posttest experimental design will be used. The study will recruit 118 mothers from the postnatal wards of a tertiary public hospital in Singapore. Eligible mothers will be randomly allocated to receive either the peer support intervention program or routine perinatal care from the hospital. Peer volunteers will be mothers who have experienced self-reported depression and will be receiving face-to-face training to support new mothers at risk of depression. Outcome measures include postnatal depression, anxiety, loneliness, and social support. Data will be collected at immediate postnatal period (day of discharge from the hospital), at fourth week and twelfth week post childbirth. The recruitment and training of peer support volunteers (N=20) ended in June 2017, whereas recruitment of study participants commenced in July 2017 and is still ongoing. The current recruitment for new mothers stands at 73, with 36 in the control group and 37 in the intervention group. Data collection is projected to be completed by May 2018. This study will identify a potentially effective and clinically useful method to prevent postnatal depression in new mothers, which is the top cause of maternal morbidity. Receiving social support from others who share similar experiences may enhance the positive parenting experiences of mothers, which in turn can improve the psychosocial well-being of the mothers, tighten mother-child bond, and enhance overall family dynamics for mothers and infants. International Standard Randomized Controlled Trial Number ISRCTN14864807; http://www.isrctn.com/ISRCTN14864807 (Archived by WebCite at http://www.webcitation.org/6xtBNvBTX). ©Shefaly Shorey, Cornelia Chee, Yap-Seng Chong, Esperanza Debby Ng, Ying Lau, Cindy-Lee Dennis. Originally published in JMIR Research Protocols (http://www.researchprotocols.org), 14.03.2018.

Effects of Treatment Length and Chat-Based Counseling in a Web-Based Intervention for Cannabis Users: Randomized Factorial Trial.

PubMed

Jonas, Benjamin; Tensil, Marc-Dennan; Tossmann, Peter; Strüber, Evelin

2018-05-08

Digital interventions show promise in reducing problematic cannabis use. However, little is known about the effect of moderators in such interventions. The therapist-guided internet intervention Quit the Shit provides 50 days of chat-based (synchronous) and time-lagged (asynchronous) counseling. In the study, we examined whether the effectiveness of Quit the Shit is reduced by shortening the program or by removing the chat-based counseling option. We conducted a purely Web-based randomized experimental trial using a two-factorial design (factor 1: real-time-counseling via text-chat: yes vs no; factor 2: intervention duration: 50 days vs 28 days). Participants were recruited on the Quit the Shit website. Follow-ups were conducted 3, 6, and 12 months after randomization. Primary outcome was cannabis-use days during the past 30 days using a Timeline Followback procedure. Secondary outcomes were cannabis quantity, cannabis-use events, cannabis dependency (Severity of Dependence Scale), treatment satisfaction (Client Satisfaction Questionnaire), and working alliance (Working Alliance Inventory-short revised). In total, 534 participants were included in the trial. Follow-up rates were 47.2% (252/534) after 3 months, 38.2% (204/534) after 6 months, and 25.3% (135/534) after 12 months. Provision of real-time counseling (factor 1) was not significantly associated with any cannabis-related outcome but with higher treatment satisfaction (P=.001, d=0.34) and stronger working alliance (P=.008, d=0.22). In factor 2, no significant differences were found in any outcome. The reduction of cannabis use among all study participants was strong (P<.001, d≥1.13). The reduction of program length and the waiver of synchronous communication have no meaningful impact on the effectiveness of Quit the Shit. It therefore seems tenable to abbreviate the program and to offer a self-guided start into Quit the Shit. Due to its positive impact on treatment satisfaction and working alliance, chat-based counseling nevertheless should be provided in Quit the Shit. International Standard Randomized Controlled Trial Number ISRCTN99818059; http://www.isrctn.com/ISRCTN99818059 (Archived by WebCite at http://www.webcitation.org/6uVDeJjfD). ©Benjamin Jonas, Marc-Dennan Tensil, Peter Tossmann, Evelin Strüber. Originally published in the Journal of Medical Internet Research (http://www.jmir.org), 08.05.2018.

An evidence-based gamified mHealth intervention for overweight young adults with maladaptive eating habits: study protocol for a randomized controlled trial.

PubMed

Podina, Ioana R; Fodor, Liviu A; Cosmoiu, Ana; Boian, Rareș

2017-12-12

Cognitive behavior therapy (CBT) is the first-line of treatment for overweight and obesity patients whose problems originate in maladaptive eating habits (e.g., emotional eating). However, in-person CBT is currently difficult to access by large segments of the population. The proposed SIGMA intervention (i.e., the Self-help, Integrated, and Gamified Mobile-phone Application) is a mHealth intervention based on CBT principles. It specifically targets overweight young adults with underlying maladaptive behaviors and cognitions regarding food. The SIGMA app was designed as a serious game and intended to work as a standalone app for weight maintenance or alongside a calorie-restrictive diet for weight loss. It uses a complex and novel scoring system that allows points earned within the game to be supplemented by points earned during outdoor activities with the help of an embedded pedometer. The efficacy of the SIGMA mHealth intervention will be investigated within a randomized, placebo-controlled trial. The intervention will be set to last 2 months with a 3-month follow-up. Selected participants will be young overweight adults with non-clinical maladaptive eating habits embodied by food cravings, binge eating, and emotional eating. The primary outcomes will be represented by changes in (1) self-reported maladaptive thoughts related to eating and body weight, (2) self-reported maladaptive eating behaviors in the range of urgent food cravings, emotional eating or binge eating, (3) as well as biased attentional processing of food items as indexed by reaction times. Secondary outcomes will be represented by changes in weight, Body Mass Index, general mood, and physical activity as indexed by the number of steps per day. Through an evidence-based cognitive behavioral approach and a user-friendly game interface, the SIGMA intervention offers a significant contribution to the development of a cost-effective and preventive self-help tool for young overweight adults with maladaptive eating habits. ISRCTN, ID: 70907354 . Registered on 6 February 2017. The ISRCTN registration is in line with the World Health Organization Trial Registration Data Set. The present paper represents the original version of the protocol. Any changes to the protocol will be communicated to ISRCTN.

A Web-Based and Mobile Health Social Support Intervention to Promote Adherence to Inhaled Asthma Medications: Randomized Controlled Trial

PubMed Central

Koufopoulos, Justin T; Conner, Mark T; Gardner, Peter H

2016-01-01

Background Online communities hold great potential as interventions for health, particularly for the management of chronic illness. The social support that online communities can provide has been associated with positive treatment outcomes, including medication adherence. There are few studies that have attempted to assess whether membership of an online community improves health outcomes using rigorous designs. Objective Our objective was to conduct a rigorous proof-of-concept randomized controlled trial of an online community intervention for improving adherence to asthma medicine. Methods This 9-week intervention included a sample of asthmatic adults from the United Kingdom who were prescribed an inhaled corticosteroid preventer. Participants were recruited via email and randomized to either an “online community” or “no online community” (diary) condition. After each instance of preventer use, participants (N=216) were required to report the number of doses of medication taken in a short post. Those randomized to the online community condition (n=99) could read the posts of other community members, reply, and create their own posts. Participants randomized to the no online community condition (n=117) also posted their medication use, but could not read others’ posts. The main outcome measures were self-reported medication adherence at baseline and follow-up (9 weeks postbaseline) and an objective measure of adherence to the intervention (visits to site). Results In all, 103 participants completed the study (intervention: 37.8%, 39/99; control: 62.2%, 64/117). MANCOVA of self-reported adherence to asthma preventer medicine at follow-up was not significantly different between conditions in either intention-to-treat (P=.92) or per-protocol (P=.68) analysis. Site use was generally higher in the control compared to intervention conditions. Conclusions Joining an online community did not improve adherence to preventer medication for asthma patients. Without the encouragement of greater community support or more components to sustain engagement over time, the current findings do not support the use of an online community to improve adherence. ClinicalTrial International Standard Randomized Controlled Trial Number (ISRCTN): 29399269; http://www.isrctn.com/ISRCTN29399269/29399269 (Archived by WebCite at http://www.webcitation.org/6fUbEuVoT) PMID:27298211

Effect of early supervised physiotherapy on recovery from acute ankle sprain: randomised controlled trial

PubMed Central

Day, Andrew G; Pelland, Lucie; Pickett, William; Johnson, Ana P; Aiken, Alice; Pichora, David R; Brouwer, Brenda

2016-01-01

Objective To assess the efficacy of a programme of supervised physiotherapy on the recovery of simple grade 1 and 2 ankle sprains. Design A randomised controlled trial of 503 participants followed for six months. Setting Participants were recruited from two tertiary acute care settings in Kingston, ON, Canada. Participants The broad inclusion criteria were patients aged ≥16 presenting for acute medical assessment and treatment of a simple grade 1 or 2 ankle sprain. Exclusions were patients with multiple injuries, other conditions limiting mobility, and ankle injuries that required immobilisation and those unable to accommodate the time intensive study protocol. Intervention Participants received either usual care, consisting of written instructions regarding protection, rest, cryotherapy, compression, elevation, and graduated weight bearing activities, or usual care enhanced with a supervised programme of physiotherapy. Main outcome measures The primary outcome of efficacy was the proportion of participants reporting excellent recovery assessed with the foot and ankle outcome score (FAOS). Excellent recovery was defined as a score ≥450/500 at three months. A difference of at least 15% increase in the absolute proportion of participants with excellent recovery was deemed clinically important. Secondary analyses included the assessment of excellent recovery at one and six months; change from baseline using continuous scores at one, three, and six months; and clinical and biomechanical measures of ankle function, assessed at one, three, and six months. Results The absolute proportion of patients achieving excellent recovery at three months was not significantly different between the physiotherapy (98/229, 43%) and usual care (79/214, 37%) arms (absolute difference 6%, 95% confidence interval −3% to 15%). The observed trend towards benefit with physiotherapy did not increase in the per protocol analysis and was in the opposite direction by six months. These trends remained similar and were never statistically or clinically important when the FAOS was analysed as a continuous change score. Conclusions In a general population of patients seeking hospital based acute care for simple ankle sprains, there is no evidence to support a clinically important improvement in outcome with the addition of supervised physiotherapy to usual care, as provided in this protocol. Trial registration ISRCTN 74033088 (www.isrctn.com/ISRCTN74033088) PMID:27852621

Mitochondrial diabetes: molecular mechanisms and clinical presentation.

PubMed

Maassen, J Antonie; 'T Hart, Leen M; Van Essen, Einar; Heine, Rob J; Nijpels, Giel; Jahangir Tafrechi, Roshan S; Raap, Anton K; Janssen, George M C; Lemkes, Herman H P J

2004-02-01

Mutations in mitochondrial DNA (mtDNA) associate with various disease states. A few mtDNA mutations strongly associate with diabetes, with the most common mutation being the A3243G mutation in the mitochondrial DNA-encoded tRNA(Leu,UUR) gene. This article describes clinical characteristics of mitochondrial diabetes and its molecular diagnosis. Furthermore, it outlines recent developments in the pathophysiological and molecular mechanisms leading to a diabetic state. A gradual development of pancreatic beta-cell dysfunction upon aging, rather than insulin resistance, is the main mechanism in developing glucose intolerance. Carriers of the A3243G mutation show during a hyperglycemic clamp at 10 mmol/l glucose a marked reduction in first- and second-phase insulin secretion compared with noncarriers. The molecular mechanism by which the A3243G mutation affects insulin secretion may involve an attenuation of cytosolic ADP/ATP levels leading to a resetting of the glucose sensor in the pancreatic beta-cell, such as in maturity-onset diabetes of the young (MODY)-2 patients with mutations in glucokinase. Unlike in MODY2, which is a nonprogressive form of diabetes, mitochondrial diabetes does show a pronounced age-dependent deterioration of pancreatic function indicating involvement of additional processes. Furthermore, one would expect that all mtDNA mutations that affect ATP synthesis lead to diabetes. This is in contrast to clinical observations. The origin of the age-dependent deterioration of pancreatic function in carriers of the A3243G mutation and the contribution of ATP and other mitochondrion-derived factors such as reactive oxygen species to the development of diabetes is discussed.

Goal Setting for Cognitive Rehabilitation in Mild to Moderate Parkinson's Disease Dementia and Dementia with Lewy Bodies

PubMed Central

Roberts, Julie; Lloyd-Williams, Huw; Gutting, Petra; Hoare, Zoe; Edwards, Rhiannon Tudor; Clare, Linda

2016-01-01

Alongside the physical symptoms associated with Parkinson's disease dementia and dementia with Lewy bodies, health services must also address the cognitive impairments that accompany these conditions. There is growing interest in the use of nonpharmacological approaches to managing the consequences of cognitive disorder. Cognitive rehabilitation is a goal-orientated behavioural intervention which aims to enhance functional independence through the use of strategies specific to the individual's needs and abilities. Fundamental to this therapy is a person's capacity to set goals for rehabilitation. To date, no studies have assessed goal setting in early-stage Parkinson's disease dementia or dementia with Lewy bodies. Semistructured interviews were carried out with 29 participants from an ongoing trial of cognitive rehabilitation for people with these conditions. Here, we examined the goal statements provided by these participants using qualitative content analysis, exploring the types and nature of the goals set. Participants' goals reflected their motivations to learn new skills or improve performance in areas such as technology-use, self-management and orientation, medication management, and social and leisure activities. These results suggest that goal setting is achievable for these participants, provide insight into the everyday cognitive difficulties that they experience, and highlight possible domains as targets for intervention. The trial is registered with ISRCTN16584442 (DOI 10.1186/ISRCTN16584442 13/04/2015). PMID:27446628

Relationship between macular pigment and visual function in subjects with early age-related macular degeneration.

PubMed

Akuffo, Kwadwo Owusu; Nolan, John M; Peto, Tunde; Stack, Jim; Leung, Irene; Corcoran, Laura; Beatty, Stephen

2017-02-01

To investigate the relationship between macular pigment (MP) and visual function in subjects with early age-related macular degeneration (AMD). 121 subjects with early AMD enrolled as part of the Central Retinal Enrichment Supplementation Trial (CREST; ISRCTN13894787) were assessed using a range of psychophysical measures of visual function, including best corrected visual acuity (BCVA), letter contrast sensitivity (CS), mesopic and photopic CS, mesopic and photopic glare disability (GD), photostress recovery time (PRT), reading performance and subjective visual function, using the National Eye Institute Visual Function Questionnaire-25 (NEI VFQ-25). MP was measured using customised heterochromatic flicker photometry. Letter CS, mesopic and photopic CS, photopic GD and mean reading speed were each significantly (p<0.05) associated with MP across a range of retinal eccentricities, and these statistically significant relationships persisted after controlling for age, sex and cataract grade. BCVA, NEI VFQ-25 score, PRT and mesopic GD were unrelated to MP after controlling for age, sex and cataract grade (p>0.05, for all). MP relates positively to many measures of visual function in unsupplemented subjects with early AMD. The CREST trial will investigate whether enrichment of MP influences visual function among those afflicted with this condition. ISRCTN13894787. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

The role of maintenance thalidomide therapy in multiple myeloma: MRC Myeloma IX results and meta-analysis.

PubMed

Morgan, Gareth J; Gregory, Walter M; Davies, Faith E; Bell, Sue E; Szubert, Alexander J; Brown, Julia M; Coy, Nuria N; Cook, Gordon; Russell, Nigel H; Rudin, Claudius; Roddie, Huw; Drayson, Mark T; Owen, Roger G; Ross, Fiona M; Jackson, Graham H; Child, J Anthony

2012-01-05

Thalidomide maintenance has the potential to modulate residual multiple myeloma (MM) after an initial response. This trial compared the effect of thalidomide maintenance and no maintenance on progression-free survival (PFS) and overall survival (OS) in MM patients. After intensive or nonintensive induction therapy, 820 newly diagnosed MM patients were randomized to open-label thalidomide maintenance until progression, or no maintenance. Interphase FISH (iFISH) analysis was performed at study entry. Median PFS was significantly longer with thalidomide maintenance (log-rank P < .001). Median OS was similar between regimens (log-rank P = .40). Patients with favorable iFISH showed improved PFS (P = .004) and a trend toward a late survival benefit. Patients with adverse iFISH receiving thalidomide showed no significant PFS benefit and worse OS (P = .009). Effective relapse therapy enhanced survival after progression, translating into a significant OS benefit. Meta-analysis of this and other studies show a significant late OS benefit (P < .001, 7-year difference hazard ratio = 12.3; 95% confidence interval, 5.5-19.0). Thalidomide maintenance significantly improves PFS and can be associated with improved OS. iFISH testing is important in assessing the clinical impact of maintenance therapy. Overview analysis demonstrated that thalidomide maintenance was associated with a significant late OS benefit. This trial was registered at www.isrctn.org as #ISRCTN68454111.

Characterization of multiple platelet activation pathways in patients with bleeding as a high-throughput screening option: use of 96-well Optimul assay.

PubMed

Lordkipanidzé, Marie; Lowe, Gillian C; Kirkby, Nicholas S; Chan, Melissa V; Lundberg, Martina H; Morgan, Neil V; Bem, Danai; Nisar, Shaista P; Leo, Vincenzo C; Jones, Matthew L; Mundell, Stuart J; Daly, Martina E; Mumford, Andrew D; Warner, Timothy D; Watson, Steve P

2014-02-20

Up to 1% of the population have mild bleeding disorders, but these remain poorly characterized, particularly with regard to the roles of platelets. We have compared the usefulness of Optimul, a 96-well plate-based assay of 7 distinct pathways of platelet activation to characterize inherited platelet defects in comparison with light transmission aggregometry (LTA). Using Optimul and LTA, concentration-response curves were generated for arachidonic acid, ADP, collagen, epinephrine, Thrombin receptor activating-peptide, U46619, and ristocetin in samples from (1) healthy volunteers (n = 50), (2) healthy volunteers treated with antiplatelet agents in vitro (n = 10), and (3) patients with bleeding of unknown origin (n = 65). The assays gave concordant results in 82% of cases (κ = 0.62, P < .0001). Normal platelet function results were particularly predictive (sensitivity, 94%; negative predictive value, 91%), whereas a positive result was not always substantiated by LTA (specificity, 67%; positive predictive value, 77%). The Optimul assay was significantly more sensitive at characterizing defects in the thromboxane pathway, which presented with normal responses with LTA. The Optimul assay is sensitive to mild platelet defects, could be used as a rapid screening assay in patients presenting with bleeding symptoms, and detects changes in platelet function more readily than LTA. This trial was registered at www.isrctn.org as #ISRCTN 77951167.

Mass media representations of the evidence as a possible deterrent to recommending exercise for the treatment of depression: Lessons five years after the extraordinary case of TREAD-UK.

PubMed

Ekkekakis, Panteleimon; Hartman, Mark E; Ladwig, Matthew A

2018-08-01

Exercise or physical activity are recommended options within stepped-care treatment models for depression. However, few physicians present these options to patients, in part because of the impression that the supporting evidence is weak or inconsistent. We speculate that the coocurrence of "counter-messaging" and deficient critical appraisal may lead to such impressions. We focus on TREAD-UK (ISRCTN16900744), the largest trial to investigate "whether physical activity can be an effective treatment for depression within primary care". In media statements, researchers declared that exercise was ineffective in lowering depression. We examined (a) the results of the trial, critiques, and rejoinders, (b) the impact on internet searches, and (c) whether TREAD-UK was critically appraised, as reflected in citing articles. We show that the results of TREAD-UK were misrepresented. The media campaign resulted in a fourfold increase in relevant internet searches. Of articles characterising the results, 57% adopted the interpretation that exercise failed to lower depression, whereas only 17% were critiques. We identify similarities to media portrayals of the OPERA (ISRCTN43769277), DEMO (NCT00103415), and DEMO-II trials (NCT00695552). We note a disconcerting trend of media campaigns that misrepresent the effects of exercise on depression and call for increased scrutiny in peer reviewing both pre- and post-publication.

Metabolic manipulation in chronic heart failure: study protocol for a randomised controlled trial.

PubMed

Beadle, Roger M; Williams, Lynne K; Abozguia, Khaild; Patel, Kiran; Leon, Francisco Leyva; Yousef, Zaheer; Wagenmakers, Anton; Frenneaux, Michael P

2011-06-06

Heart failure is a major cause of morbidity and mortality in society. Current medical therapy centres on neurohormonal modulation with angiotensin converting enzyme inhibitors and β-blockers. There is growing evidence for the use of metabolic manipulating agents as adjunctive therapy in patients with heart failure. We aim to determine the effect of perhexiline on cardiac energetics and alterations in substrate utilisation in patients with non-ischaemic dilated cardiomyopathy. A multi-centre, prospective, randomised double-blind, placebo-controlled trial of 50 subjects with non-ischaemic dilated cardiomyopathy recruited from University Hospital Birmingham NHS Foundation Trust and Cardiff and Vale NHS Trust. Baseline investigations include magnetic resonance spectroscopy to assess cardiac energetic status, echocardiography to assess left ventricular function and assessment of symptomatic status. Subjects are then randomised to receive 200 mg perhexiline maleate or placebo daily for 4 weeks with serum drug level monitoring. All baseline investigations will be repeated at the end of the treatment period. A subgroup of patients will undergo invasive investigations with right and left heart catheterisation to calculate respiratory quotient, and mechanical efficiency. The primary endpoint is an improvement in the phosphocreatine to adenosine triphosphate ratio at 4 weeks. Secondary end points are: i) respiratory quotient; ii) mechanical efficiency; iii) change in left ventricular (LV) function. ClinicalTrials.gov: NCT00841139 ISRCTN: ISRCTN72887836.

The Ball Welding Bar: A New Solution for the Immediate Loading of Screw-Retained, Mandibular Fixed Full Arch Prostheses

PubMed Central

Bacchiocchi, Danilo

2017-01-01

Purpose To present a new intraoral welding technique, which can be used to manufacture screw-retained, mandibular fixed full-arch prostheses. Methods Over a 4-year period, all patients with complete mandibular edentulism or irreparably compromised mandibular dentition, who will restore the masticatory function with a fixed mandibular prosthesis, were considered for inclusion in this study. The “Ball Welding Bar” (BWB) technique is characterised by smooth prosthetic cylinders, interconnected by means of titanium bars which are adjustable in terms of distance from ball terminals and are inserted in the rotating rings of the cylinders. All the components are welded and self-posing. Results Forty-two patients (18 males; 24 females; mean age 64.2 ± 6.7 years) were enrolled and 210 fixtures were inserted to support 42 mandibular screw-retained, fixed full-arch prostheses. After two years of loading, 2 fixtures were lost, for an implant survival rate of 97.7%. Five implants suffered from peri-implant mucositis and 3 implants for peri-implantitis. Three of the prostheses (3/42) required repair for fracture (7.1%): the prosthetic success was 92.9%. Conclusions The BWB technique seems to represent a reliable technique for the fabrication of screw-retained mandibular fixed full-arch prostheses. This study was registered in the ISRCTN register with number ISRCTN71229338. PMID:28835752

Implant Stability in the Posterior Maxilla: A Controlled Clinical Trial

PubMed Central

de Vasconcelos, Mario Ramalho; Lopes Guerra, Isabel Maria; de Campos Felino, Antonio Cabral

2017-01-01

Aim To evaluate the primary and secondary stability of implants in the posterior maxilla. Methods Patients were allocated into three groups: (A) native bone, (B) partially regenerated bone, and (C) nearly totally regenerated bone. Insertion torque (IT) and implant stability quotient (ISQ) were measured at placement, to evaluate whether satisfactory high primary stability (IT ≥ 45 N/cm; ISQ ≥ 60) was achieved; ISQ was measured 15, 30, 45, and 60 days after placement, to investigate the evolution to secondary stability. Results 133 implants (Anyridge®, Megagen) were installed in 59 patients: 55 fixtures were placed in Group A, 57 in Group B, and 21 in Group C. Fifty-two implants had satisfactory high primary stability (IT ≥ 45 N/cm; ISQ ≥ 60). A positive correlation was found between all variables (IT, ISQ at t = 0, t = 60), and statistically higher IT and ISQ values were found for implants with satisfactory high primary stability. Significant differences were found for IT and ISQ between the groups (A, B, and C); however, no drops were reported in the median ISQ values during the healing period. Conclusions The evaluation of the primary and secondary implant stability may contribute to higher implant survival/success rates in critical areas, such as the regenerated posterior maxilla. The present study is registered in the ISRCTN registry with ID ISRCTN33469250. PMID:28626763

Prevention of haematoma progression by tranexamic acid in intracerebral haemorrhage patients with and without spot sign on admission scan: a statistical analysis plan of a pre-specified sub-study of the TICH-2 trial.

PubMed

Ovesen, Christian; Jakobsen, Janus Christian; Gluud, Christian; Steiner, Thorsten; Law, Zhe; Flaherty, Katie; Dineen, Rob A; Bath, Philip M; Sprigg, Nikola; Christensen, Hanne

2018-06-13

We present the statistical analysis plan of a prespecified Tranexamic Acid for Hyperacute Primary Intracerebral Haemorrhage (TICH)-2 sub-study aiming to investigate, if tranexamic acid has a different effect in intracerebral haemorrhage patients with the spot sign on admission compared to spot sign negative patients. The TICH-2 trial recruited above 2000 participants with intracerebral haemorrhage arriving in hospital within 8 h after symptom onset. They were included irrespective of radiological signs of on-going haematoma expansion. Participants were randomised to tranexamic acid versus matching placebo. In this subgroup analysis, we will include all participants in TICH-2 with a computed tomography angiography on admission allowing adjudication of the participants' spot sign status. Primary outcome will be the ability of tranexamic acid to limit absolute haematoma volume on computed tomography at 24 h (± 12 h) after randomisation among spot sign positive and spot sign negative participants, respectively. Within all outcome measures, the effect of tranexamic acid in spot sign positive/negative participants will be compared using tests of interaction. This sub-study will investigate the important clinical hypothesis that spot sign positive patients might benefit more from administration of tranexamic acid compared to spot sign negative patients. Trial registration ISRCTN93732214 ( http://www.isrctn.com ).

Does wine glass size influence sales for on-site consumption? A multiple treatment reversal design.

PubMed

Pechey, Rachel; Couturier, Dominique-Laurent; Hollands, Gareth J; Mantzari, Eleni; Munafò, Marcus R; Marteau, Theresa M

2016-06-07

Wine glass size can influence both perceptions of portion size and the amount poured, but its impact upon purchasing and consumption is unknown. This study aimed to examine the impact of wine glass size on wine sales for on-site consumption, keeping portion size constant. In one establishment (with separate bar and restaurant areas) in Cambridge, England, wine glass size (Standard; Larger; Smaller) was changed over eight fortnightly periods. The bar and restaurant differ in wine sales by the glass vs. by the bottle (93 % vs. 63 % by the glass respectively). Daily wine volume purchased was 9.4 % (95 % CI: 1.9, 17.5) higher when sold in larger compared to standard-sized glasses. This effect seemed principally driven by sales in the bar area (bar: 14.4 % [3.3, 26.7]; restaurant: 8.2 % [-2.5, 20.1]). Findings were inconclusive as to whether sales were different with smaller vs. standard-sized glasses. The size of glasses in which wine is sold, keeping the portion size constant, can affect consumption, with larger glasses increasing consumption. The hypothesised mechanisms for these differential effects need to be tested in a replication study. If replicated, policy implications could include considering glass size amongst alcohol licensing requirements. ISRCTN registry: ISRCTN12018175 . Registered 12(th) May 2015.

Predictors of acute and persisting ischemic brain lesions in patients randomized to carotid stenting or endarterectomy.

PubMed

Rostamzadeh, Ayda; Zumbrunn, Thomas; Jongen, Lisa M; Nederkoorn, Paul J; Macdonald, Sumaira; Lyrer, Philippe A; Kappelle, L Jaap; Mali, Willem P Th M; Brown, Martin M; van der Worp, H Bart; Engelter, Stefan T; Bonati, Leo H

2014-02-01

We investigated predictors for acute and persisting periprocedural ischemic brain lesions among patients with symptomatic carotid stenosis randomized to stenting or endarterectomy in the International Carotid Stenting Study. We assessed acute lesions on diffusion-weighted imaging 1 to 3 days after treatment in 124 stenting and 107 endarterectomy patients and lesions persisting on fluid-attenuated inversion recovery after 1 month in 86 and 75 patients, respectively. Stenting patients had more acute (relative risk, 8.8; 95% confidence interval, 4.4-17.5; P<0.001) and persisting lesions (relative risk, 4.2; 95% confidence interval, 1.6-11.1; P=0.005) than endarterectomy patients. Acute lesion count was associated with age (by trend), male sex, and stroke as the qualifying event in stenting; high systolic blood pressure in endarterectomy; and white matter disease in both groups. The rate of conversion from acute to persisting lesions was lower in the stenting group (relative risk, 0.4; 95% confidence interval, 0.2-0.8; P=0.007), and was only predicted by acute lesion volume. Stenting caused more acute and persisting ischemic brain lesions than endarterectomy. However, the rate of conversion from acute to persisting lesions was lower in the stenting group, most likely attributable to lower acute lesion volumes. Clinical Trial Registration -URL: www.isrctn.org. Unique identifier: ISRCTN25337470.

Implementation of an educational intervention to improve hand washing in primary schools: process evaluation within a randomised controlled trial.

PubMed

Chittleborough, Catherine R; Nicholson, Alexandra L; Young, Elaine; Bell, Sarah; Campbell, Rona

2013-08-15

Process evaluations are useful for understanding how interventions are implemented in trial settings. This is important for interpreting main trial results and indicating how the intervention might function beyond the trial. The purpose of this study was to examine the reach, dose, fidelity, acceptability, and sustainability of the implementation of an educational hand washing intervention in primary schools, and to explore views regarding acceptability and sustainability of the intervention. Process evaluation within a cluster randomised controlled trial, including focus groups with pupils aged 6 to 11, semi-structured interviews with teachers and external staff who coordinated the intervention delivery, and school reports and direct observations of the intervention delivery. The educational package was delivered in 61.4% of schools (85.2% of intervention schools, 37.8% of control schools following completion of the trial). Teachers and pupils reacted positively to the intervention, although concerns were raised about the age-appropriateness of the resources. Teachers adapted the resources to suit their school setting and pupils. Staff coordinating the intervention delivery had limited capacity to follow up and respond to schools. The hand washing intervention was acceptable to schools, but its reach outside of a randomised trial, evidenced in the low proportion of schools in the control arm who received it after the trial had ended, suggests that the model of delivery may not be sustainable. ISRCTN: ISRCTN93576146.

Pancreatitis, very early compared with normal start of enteral feeding (PYTHON trial): design and rationale of a randomised controlled multicenter trial

PubMed Central

2011-01-01

Background In predicted severe acute pancreatitis, infections have a negative effect on clinical outcome. A start of enteral nutrition (EN) within 24 hours of onset may reduce the number of infections as compared to the current practice of starting an oral diet and EN if necessary at 3-4 days after admission. Methods/Design The PYTHON trial is a randomised controlled, parallel-group, superiority multicenter trial. Patients with predicted severe acute pancreatitis (Imrie-score ≥ 3 or APACHE-II score ≥ 8 or CRP > 150 mg/L) will be randomised to EN within 24 hours or an oral diet and EN if necessary, after 72 hours after hospital admission. During a 3-year period, 208 patients will be enrolled from 20 hospitals of the Dutch Pancreatitis Study Group. The primary endpoint is a composite of mortality or infections (bacteraemia, infected pancreatic or peripancreatic necrosis, pneumonia) during hospital stay or within 6 months following randomisation. Secondary endpoints include other major morbidity (e.g. new onset organ failure, need for intervention), intolerance of enteral feeding and total costs from a societal perspective. Discussion The PYTHON trial is designed to show that a very early (< 24 h) start of EN reduces the combined endpoint of mortality or infections as compared to the current practice of an oral diet and EN if necessary at around 72 hours after admission for predicted severe acute pancreatitis. Trial Registration ISRCTN: ISRCTN18170985 PMID:21392395

Intrapulmonary percussive ventilation improves lung function in cystic fibrosis patients chronically colonized with Pseudomonas aeruginosa: a pilot cross-over study.

PubMed

Dingemans, Jozef; Eyns, Hanneke; Willekens, Julie; Monsieurs, Pieter; Van Houdt, Rob; Cornelis, Pierre; Malfroot, Anne; Crabbé, Aurélie

2018-06-01

High levels of shear stress can prevent and disrupt Pseudomonas aeruginosa biofilm formation in vitro. Intrapulmonary percussive ventilation (IPV) could be used to introduce shear stress into the lungs of cystic fibrosis (CF) patients to disrupt biofilms in vivo. We performed a first-of-its-kind pilot clinical study to evaluate short-term IPV therapy at medium (200 bursts per minute, bpm) and high frequency (400 bpm) as compared to autogenic drainage (AD) on lung function and the behavior of P. aeruginosa in the CF lung in four patients who are chronically colonized by P. aeruginosa. A significant difference between the three treatment groups was observed for both the forced expiratory volume in 1 s (FEV1) and the forced vital capacity (FVC) (p < 0.05). More specifically, IPV at high frequency significantly increased FEV1 and FVC compared to AD (p < 0.05) and IPV at medium frequency (p < 0.001). IPV at high frequency enhanced the expression levels of P. aeruginosa planktonic marker genes, which was less pronounced with IPV at medium frequency or AD. In conclusion, IPV at high frequency could potentially alter the behavior of P. aeruginosa in the CF lung and improve lung function. The trail was retrospectively registered at the ISRCTN registry on 6 June 2013, under trial registration number ISRCTN75391385.

Impact of improved recording of work-relatedness in primary care visits at occupational health services on sickness absences: study protocol for a randomised controlled trial.

PubMed

Atkins, Salla; Ojajärvi, Ulla; Talola, Nina; Viljamaa, Mervi; Nevalainen, Jaakko; Uitti, Jukka

2017-07-26

Employment protects and fosters health. Occupational health services, particularly in Finland, have a central role in protecting employee health and preventing work ability problems. However, primary care within occupational health services is currently underused in informing preventive activities. This study was designed to assess whether the recording of work ability problems and improvement of follow-up of work-related primary care visits can reduce sickness absences and work disability pensions after 1 year. A pragmatic trial will be conducted using patient electronic registers and registers of the central pensions agency in Finland. Twenty-two occupational health centres will be randomised to intervention and control groups. Intervention units will receive training to improve recording of work ability illnesses in the primary care setting and improved follow-up procedures. The intervention impact will be assessed through examining rates of sickness absence across intervention and control clinics as well as before and after the intervention. The trial will develop knowledge of the intervention potential of primary care for preventing work disability pensions and sickness absence. The use of routine patient registers and pensions registers to assess the outcomes of a randomised controlled trial will bring forward trial methodology, particularly when using register-based data. If successful, the intervention will improve the quality of occupational health care primary care and contribute to reducing work disability. ISRCTN Registry reference number ISRCTN45728263 . Registered on 18 April 2016.

Implementation of an educational intervention to improve hand washing in primary schools: process evaluation within a randomised controlled trial

PubMed Central

2013-01-01

Background Process evaluations are useful for understanding how interventions are implemented in trial settings. This is important for interpreting main trial results and indicating how the intervention might function beyond the trial. The purpose of this study was to examine the reach, dose, fidelity, acceptability, and sustainability of the implementation of an educational hand washing intervention in primary schools, and to explore views regarding acceptability and sustainability of the intervention. Methods Process evaluation within a cluster randomised controlled trial, including focus groups with pupils aged 6 to 11, semi-structured interviews with teachers and external staff who coordinated the intervention delivery, and school reports and direct observations of the intervention delivery. Results The educational package was delivered in 61.4% of schools (85.2% of intervention schools, 37.8% of control schools following completion of the trial). Teachers and pupils reacted positively to the intervention, although concerns were raised about the age-appropriateness of the resources. Teachers adapted the resources to suit their school setting and pupils. Staff coordinating the intervention delivery had limited capacity to follow up and respond to schools. Conclusions The hand washing intervention was acceptable to schools, but its reach outside of a randomised trial, evidenced in the low proportion of schools in the control arm who received it after the trial had ended, suggests that the model of delivery may not be sustainable. Trial registration ISRCTN: ISRCTN93576146 PMID:23947388

The effect of Neuragen PN® on Neuropathic pain: A randomized, double blind, placebo controlled clinical trial

PubMed Central

2010-01-01

Background A double blind, randomized, placebo controlled study to evaluate the safety and efficacy of the naturally derived topical oil, "Neuragen PN®" for the treatment of neuropathic pain. Methods Sixty participants with plantar cutaneous (foot sole) pain due to all cause peripheral neuropathy were recruited from the community. Each subject was randomly assigned to receive one of two treatments (Neuragen PN® or placebo) per week in a crossover design. The primary outcome measure was acute spontaneous pain level as reported on a visual analog scale. Results There was an overall pain reduction for both treatments from pre to post application. As compared to the placebo, Neuragen PN® led to significantly (p < .05) greater pain reduction. Fifty six of sixty subjects (93.3%) receiving Neuragen PN® reported pain reduction within 30 minutes. This reduction within 30 minutes occurred in only twenty one of sixty (35.0%) subjects receiving the placebo. In a break out analysis of the diabetic only subgroup, 94% of subjects in the Neuragen PN® group achieved pain reduction within 30 minutes vs 11.0% of the placebo group. No adverse events were observed. Conclusions This randomized, placebo controlled, clinical trial with crossover design revealed that the naturally derived oil, Neuragen PN®, provided significant relief from neuropathic pain in an all cause neuropathy group. Participants with diabetes within this group experienced similar pain relief. Trial registration ISRCTN registered: ISRCTN13226601 PMID:20487567

Intervention fidelity in primary care complex intervention trials: qualitative study using telephone interviews of patients and practitioners.

PubMed

Dyas, Jane V; Togher, Fiona; Siriwardena, A Niroshan

2014-01-01

Treatment fidelity has previously been defined as the degree to which a treatment or intervention is delivered to participants as intended. Underreporting of fidelity in primary care randomised controlled trials (RCTs) of complex interventions reduces our confidence that findings are due to the treatment or intervention being investigated, rather than unknown confounders. We aimed to investigate treatment fidelity (for the purpose of this paper, hereafter referred to as intervention fidelity), of an educational intervention delivered to general practice teams and designed to improve the primary care management of insomnia. We conducted telephone interviews with patients and practitioners participating in the intervention arm of the trial to explore trial fidelity. Qualitative analysis was undertaken using constant comparison and a priori themes (categories): 'adherence to the delivery of the intervention', 'patients received and understood intervention' and 'patient enactment'. If the intervention protocol was not adhered to by the practitioner then patient receipt, understanding and enactment levels were reduced. Recruitment difficulties in terms of the gap between initially being recruited into the study and attending an intervention consultation also reduced the effectiveness of the intervention. Patient attributes such as motivation to learn and engage contributed to the success of the uptake of the intervention. Qualitative methods using brief telephone interviews are an effective way of collecting the depth of data required to assess intervention fidelity. Intervention fidelity monitoring should be an important element of definitive trial design. ClinicalTrials. gov id isrctn 55001433 - www.controlled-trials.com/isrctn55001433.

Acupuncture as prophylaxis for menstrual-related migraine: study protocol for a multicenter randomized controlled trial

PubMed Central

2013-01-01

Background Menstrual-related migraine is a common form of migraine affecting >50% of female migraineurs. Acupuncture may be a choice for menstrual-related migraine, when pharmacological prophylaxis is not suitable. However, the efficacy of acupuncture has not been confirmed. We design and perform a randomized controlled clinical trial to evaluate the efficacy of acupuncture compared with naproxen in menstrual-related migraine patients. Methods/Design This is a multicenter, single blind, randomized controlled clinical trial. A total of 184 participants will be randomly assigned to two different groups. Participants will receive verum acupuncture and placebo medicine in the treatment group, while participants in the control group will be treated with sham acupuncture and medicine (Naproxen Sustained Release Tablets). All treatments will be given for 3 months (menstrual cycles). The primary outcome measures are the change of migraine days inside the menstrual cycle and the proportion of responders (defined as the proportion of patients with at least a 50% reduction in the number of menstrual migraine days). The secondary outcome measures are the change of migraine days outside the menstrual cycle, duration of migraine attack, the Visual Analogue Scale (VAS), and intake of acute medication. The assessment will be made at baseline (before treatment), 3 months (menstrual cycles), and 4 months (menstrual cycles) after the first acupuncture session. Discussion The results of this trial will be helpful to supply the efficacy of acupuncture for menstrual-related migraine prophylaxis. Trial registration ISRCTN: ISRCTN57133712 PMID:24195839

Evaluation of the impact of preoperative education in ambulatory laparoscopic cholecystectomy. A prospective, double-blind randomized trial.

PubMed

Subirana Magdaleno, Helena; Caro Tarragó, Aleidis; Olona Casas, Carles; Díaz Padillo, Alba; Franco Chacón, Mario; Vadillo Bargalló, Jordi; Saludes Serra, Judit; Jorba Martín, Rosa

2018-02-01

Outpatient laparoscopic cholecystectomy is a safe procedure and provides a better use of health resources and perceived satisfaction without affecting quality of care. Preoperative education has shown less postoperative stress, pain and nausea in some interventions. The principal objective of this study is to assess the impact of preoperative education on postoperative pain in patients undergoing ambulatory laparoscopic cholecystectomy. Secondary objectives were: to evaluate presence of nausea, morbidity, hospital admissions, readmissions rate, quality of life and satisfaction. Prospective, randomized, and double blind study. Between April 2014 and May 2016, 62 patients underwent outpatient laparoscopic cholecystectomy. ASA I-II, age 18-75, outpatient surgery criteria, abdominal ultrasonography with cholelithiasis. Patient randomization in two groups, group A: intensified preoperative education and group B: control. Sixty-two patients included, 44 women (71%), 18 men (29%), mean age 46,8 years (20-69). Mean BMI 27,5. Outpatient rate 92%. Five cases required admission, two due to nausea. Pain scores obtained using a VAS was at 24-hour, 2,9 in group A and 2,7 in group B. There were no severe complications or readmissions. Results of satisfaction and quality of life scores were similar for both groups. We did not find differences due to intensive preoperative education. However, we think that a correct information protocol should be integrated into the patient's preoperative preparation. Registered in ISRCTN number ISRCTN83787412. Copyright © 2017 AEC. Publicado por Elsevier España, S.L.U. All rights reserved.

Hip and pelvic fracture patients with fear of falling: development and description of the "Step by Step" treatment protocol.

PubMed

Kampe, Karin; Kohler, Michaela; Albrecht, Diana; Becker, Clemens; Hautzinger, Martin; Lindemann, Ulrich; Pfeiffer, Klaus

2017-05-01

Based on a theoretical framework and sound evidence, this article describes a rehabilitation programme for patients with fear of falling after hip and pelvic fracture. Based on exercise science principles, current knowledge from fall prevention, emotion regulation, and the Health Action Process Approach we developed a theoretical framework, from which the components of the intervention were derived. Description of the intervention: The intervention consists of 6 components: (1) relaxation, (2) meaningful activities and mobility-based goals, (3) falls related cognitions and emotions, coping with high risk tasks and situations, (4) individual exercise programme, (5) planning and implementing exercises and activities, and (6) fall risks and hazards. The intervention comprises of 8 individual sessions during 3 to 5 weeks of inpatient rehabilitation and 4 telephone calls and 1 home visit over a 2-month post-discharge period. Each session or telephone call takes about 30-60 minutes. It is provided to geriatric hip and pelvic fracture patients with concerns about falling and no cognitive impairment. To ensure completeness of reporting, the Template for Intervention Description and Replication (TIDierR) is used. Fifty-seven patients were assigned to the intervention group. All 46 completers met all pre-defined criteria for an intervention per protocol. The programme is feasible to administer. We have completed a randomised controlled trial, which will be submitted in due time (for trial protocol: www.isrctn.org ; ISRCTN79191813).

Web-Based Aftercare for Women With Bulimia Nervosa Following Inpatient Treatment: Randomized Controlled Efficacy Trial.

PubMed

Jacobi, Corinna; Beintner, Ina; Fittig, Eike; Trockel, Mickey; Braks, Karsten; Schade-Brittinger, Carmen; Dempfle, Astrid

2017-09-22

Relapse rates in bulimia nervosa (BN) are high even after successful treatment, but patients often hesitate to take up further treatment. An easily accessible program might help maintain treatment gains. Encouraged by the effects of Web-based eating disorder prevention programs, we developed a manualized, Web-based aftercare program (IN@) for women with BN following inpatient treatment. The objective of this study was to determine the efficacy of the web-based guided, 9-month, cognitive-behavioral aftercare program IN@ for women with BN following inpatient treatment. We conducted a randomized controlled efficacy trial in 253 women with DSM-IV (Diagnostic and Statistical Manual of Mental Disorders, fourth edition) BN and compared the results of IN@ with treatment as usual (TAU). Assessments were carried out at hospital admission (T0), hospital discharge/baseline (T1), postintervention (T2; 9 months after baseline), 9-month follow-up (T3; 18 months after baseline). The primary outcome, abstinence from binge eating and compensatory behaviors during the 2 months preceding T2, was analyzed by intention to treat, using logistic regression analyses. Frequencies of binge eating and vomiting episodes, and episodes of all compensatory behaviors were analyzed using mixed effects models. At T2, data from 167 women were available. There were no significant differences in abstinence rates between the TAU group (n=24, 18.9%) and the IN@ group (n=27, 21.4%; odds ratio, OR=1.29; P=.44). The frequency of vomiting episodes in the IN@ group was significantly (46%) lower than in the TAU group (P=.003). Moderator analyses revealed that both at T2 and T3, women of the intervention group who still reported binge eating and compensatory behaviors after inpatient treatment benefited from IN@, whereas women who were already abstinent after the inpatient treatment did not (P=.004; P=.002). Additional treatment utilization was high in both groups between baseline and follow-up. Overall, data from this study suggest moderate effects of IN@. High rates of outpatient treatment utilization after inpatient treatment may have obscured potential intervention effects on abstinence. An aftercare intervention might be more beneficial as part of a stepped-care approach. International Standard Randomized Controlled Trial Number (ISRCTN): 08870215; http://www.isrctn.com/ISRCTN08870215 (Archived by WebCite at http://www.webcitation.org/6soA5bIit). ©Corinna Jacobi, Ina Beintner, Eike Fittig, Mickey Trockel, Karsten Braks, Carmen Schade-Brittinger, Astrid Dempfle. Originally published in the Journal of Medical Internet Research (http://www.jmir.org), 22.09.2017.

Web-Based Aftercare for Women With Bulimia Nervosa Following Inpatient Treatment: Randomized Controlled Efficacy Trial

PubMed Central

Fittig, Eike; Trockel, Mickey; Braks, Karsten; Schade-Brittinger, Carmen; Dempfle, Astrid

2017-01-01

Background Relapse rates in bulimia nervosa (BN) are high even after successful treatment, but patients often hesitate to take up further treatment. An easily accessible program might help maintain treatment gains. Encouraged by the effects of Web-based eating disorder prevention programs, we developed a manualized, Web-based aftercare program (IN@) for women with BN following inpatient treatment. Objective The objective of this study was to determine the efficacy of the web-based guided, 9-month, cognitive-behavioral aftercare program IN@ for women with BN following inpatient treatment. Methods We conducted a randomized controlled efficacy trial in 253 women with DSM-IV (Diagnostic and Statistical Manual of Mental Disorders, fourth edition) BN and compared the results of IN@ with treatment as usual (TAU). Assessments were carried out at hospital admission (T0), hospital discharge/baseline (T1), postintervention (T2; 9 months after baseline), 9-month follow-up (T3; 18 months after baseline). The primary outcome, abstinence from binge eating and compensatory behaviors during the 2 months preceding T2, was analyzed by intention to treat, using logistic regression analyses. Frequencies of binge eating and vomiting episodes, and episodes of all compensatory behaviors were analyzed using mixed effects models. Results At T2, data from 167 women were available. There were no significant differences in abstinence rates between the TAU group (n=24, 18.9%) and the IN@ group (n=27, 21.4%; odds ratio, OR=1.29; P=.44). The frequency of vomiting episodes in the IN@ group was significantly (46%) lower than in the TAU group (P=.003). Moderator analyses revealed that both at T2 and T3, women of the intervention group who still reported binge eating and compensatory behaviors after inpatient treatment benefited from IN@, whereas women who were already abstinent after the inpatient treatment did not (P=.004; P=.002). Additional treatment utilization was high in both groups between baseline and follow-up. Conclusions Overall, data from this study suggest moderate effects of IN@. High rates of outpatient treatment utilization after inpatient treatment may have obscured potential intervention effects on abstinence. An aftercare intervention might be more beneficial as part of a stepped-care approach. Trial Registration International Standard Randomized Controlled Trial Number (ISRCTN): 08870215; http://www.isrctn.com/ISRCTN08870215 (Archived by WebCite at http://www.webcitation.org/6soA5bIit) PMID:28939544

Plasma Ceramides, Mediterranean Diet, and Incident Cardiovascular Disease in the PREDIMED Trial

PubMed Central

Wang, Dong D.; Toledo, Estefanía; Hruby, Adela; Rosner, Bernard A.; Willett, Walter C.; Sun, Qi; Razquin, Cristina; Zheng, Yan; Ruiz-Canela, Miguel; Guasch-Ferré, Marta; Corella, Dolores; Gómez-Gracia, Enrique; Fiol, Miquel; Estruch, Ramón; Ros, Emilio; Lapetra, José; Fito, Montserrat; Aros, Fernando; Serra-Majem, Luis; Lee, Chih-Hao; Clish, Clary B.; Liang, Liming; Salas-Salvadó, Jordi; Martínez-González, Miguel A.; Hu, Frank B.

2017-01-01

Background Although in vitro studies and investigations in animal models and small clinical populations have suggested that ceramides may represent an intermediate link between over-nutrition and certain pathological mechanisms underlying cardiovascular disease (CVD), no prospective studies have investigated the association between plasma ceramides and risk of CVD. Methods The study population consisted of 980 participants from the PREDIMED trial, including 230 incident cases of CVD and 787 randomly selected participants at baseline (including 37 overlapping cases), followed for up to 7.4 years. Participants were randomized to a Mediterranean diet (MedDiet) supplemented with extra-virgin olive oil, a MedDiet supplemented with nuts, or a control diet. Plasma ceramide concentrations were measured on a liquid chromatography tandem mass spectrometry metabolomics platform. The primary outcome was a composite of non-fatal acute myocardial infarction, non-fatal stroke, or cardiovascular death. Hazard Ratios (HRs) were estimated with weighted Cox regression models, using Barlow weights to account for the case-cohort design. Results The multivariable HRs [95% confidence interval (CI)] comparing the extreme quartiles of plasma concentrations of C16:0, C22:0, C24:0 and C24:1 ceramides were 2.39 (1.49–3.83, P trend <0.001), 1.91 (1.21–3.01, P trend =0.003), 1.97 (1.21–3.01, P trend =0.004), and 1.73 (1.09–2.74, P trend =0.011), respectively. The ceramide score, calculated as a weighted sum of concentrations of four ceramides, was associated with a 2.18-fold higher risk of CVD across extreme quartiles (HR =2.18, 95% CI, 1.36–3.49, P trend <0.001). The association between baseline ceramide score and incident CVD varied significantly by treatment groups (P interaction =0.010). Participants with a higher ceramide score and assigned to either of the two active intervention arms of the trial showed similar CVD risk to those with a lower ceramide score, whereas participants with a higher ceramide score and assigned to the control arm presented significantly higher CVD risk. Changes in ceramide concentration were not significantly different between MedDiet and control groups during the first year of follow-up. Conclusions Our study documented a novel positive association between baseline plasma ceramide concentrations and incident CVD. In addition, a Mediterranean dietary intervention may mitigate potential deleterious effects of elevated plasma ceramide concentrations on CVD. Clinical Trial Registration Controlled-Trials.com number, ISRCTN35739639. http://www.isrctn.com/ISRCTN35739639 PMID:28280233

Smartphone App Using Mindfulness Meditation for Women With Chronic Pelvic Pain (MEMPHIS): Protocol for a Randomized Feasibility Trial

PubMed Central

Newton, Sian; Kahan, Brennan C; Forbes, Gordon; Wright, Neil; Cantalapiedra Calvete, Clara; Gibson, Harry A L; Rogozinska, Ewelina; Rivas, Carol; Taylor, Stephanie J C; Birch, Judy; Dodds, Julie

2018-01-01

Background Female chronic pelvic pain (CPP) is defined as intermittent or constant pelvic or lower abdominal pain occurring in a woman for at least 6 months. Up to a quarter of women are estimated to be affected by CPP worldwide and it is responsible for one fifth of specialist gynecological referrals in the United Kingdom. Psychological interventions are commonly utilized. As waiting times and funding capacity impede access to face-to-face consultations, supported self-management (SSM) has emerged as a viable alternative. Mindfulness meditation is a potentially valuable SSM tool, and in the era of mobile technology, this can be delivered to the individual user via a smartphone app. Objective To assess the feasibility of conducting a trial of a mindfulness meditation intervention delivered by a mobile phone app for patients with CPP. The main feasibility objectives were to assess patient recruitment and app adherence, to obtain information to be used in the sample size estimate of a future trial, and to receive feedback on usability of the app. Methods Mindfulness Meditation for Women With Chronic Pelvic Pain (MEMPHIS) is a three-arm feasibility trial, that took place in two hospitals in the United Kingdom. Eligible participants were randomized in a 1:1:1 ratio to one of three treatment arms: (1) the intervention arm, consisting of a guided, spoken mindfulness meditation app; (2) an active control arm, consisting of a progressive muscle relaxation app; and (3) usual care (no app). Participants were followed-up for 6 months. Key feasibility outcomes included the time taken to recruit all patients for the study, adherence, and estimates to be used in the sample size calculation for a subsequent full-scale trial. Upon completion of the feasibility trial we will conduct focus groups to explore app usability and reasons for noncompliance. Results Recruitment for MEMPHIS took place between May 2016 and September 2016. The study was closed March 2017 and the report was submitted to the NIHR on October 26, 2017. Conclusions This feasibility trial will inform the design of a large multicentered trial to assess the clinical effectiveness of mindfulness meditation delivered via a smartphone app for the treatment of CPP. Trial Registration ClinicalTrials.gov: NCT02721108; https://clinicaltrials.gov/ct2/show/NCT02721108 (Archived by WebCite at http://www.webcitation.org/6wLMAkuaU); BioMed Central: ISRCTN10925965; https://www.isrctn.com/ISRCTN10925965 (Archived by WebCite at http://www.webcitation.org/6wLMVLuys) PMID:29335232

Web-Based Decision Aid to Assist Help-Seeking Choices for Young People Who Self-Harm: Outcomes From a Randomized Controlled Feasibility Trial.

PubMed

Rowe, Sarah L; Patel, Krisna; French, Rebecca S; Henderson, Claire; Ougrin, Dennis; Slade, Mike; Moran, Paul

2018-01-30

Adolescents who self-harm are often unsure how or where to get help. We developed a Web-based personalized decision aid (DA) designed to support young people in decision making about seeking help for their self-harm. The aim of this study was to evaluate the feasibility and acceptability of the DA intervention and the randomized controlled trial (RCT) in a school setting. We conducted a two-group, single blind, randomized controlled feasibility trial in a school setting. Participants aged 12 to 18 years who reported self-harm in the past 12 months were randomized to either a Web-based DA or to general information about mood and feelings. Feasibility of recruitment, randomization, and follow-up rates were assessed, as was acceptability of the intervention and study procedures. Descriptive data were collected on outcome measures examining decision making and help-seeking behavior. Qualitative interviews were conducted with young people, parents or carers, and staff and subjected to thematic analysis to explore their views of the DA and study processes. Parental consent was a significant barrier to young people participating in the trial, with only 17.87% (208/1164) of parents or guardians who were contacted for consent responding to study invitations. Where parental consent was obtained, we were able to recruit 81.7% (170/208) of young people into the study. Of those young people screened, 13.5% (23/170) had self-harmed in the past year. Ten participants were randomized to receiving the DA, and 13 were randomized to the control group. Four-week follow-up assessments were completed with all participants. The DA had good acceptability, but qualitative interviews suggested that a DA that addressed broader mental health problems such as depression, anxiety, and self-harm may be more beneficial. A broad-based mental health DA addressing a wide range of psychosocial problems may be useful for young people. The requirement for parental consent is a key barrier to intervention research on self-harm in the school setting. Adaptations to the research design and the intervention are needed before generalizable research about DAs can be successfully conducted in a school setting. International Standard Randomized Controlled Trial registry: ISRCTN11230559; http://www.isrctn.com/ISRCTN11230559 (Archived by WebCite at http://www.webcitation.org/6wqErsYWG). ©Sarah L Rowe, Krisna Patel, Rebecca S French, Claire Henderson, Dennis Ougrin, Mike Slade, Paul Moran. Originally published in JMIR Mental Health (http://mental.jmir.org), 30.01.2018.

Impact of chronic kidney disease on use of evidence-based therapy in stable coronary artery disease: a prospective analysis of 22,272 patients.

PubMed

Kalra, Paul R; García-Moll, Xavier; Zamorano, José; Kalra, Philip A; Fox, Kim M; Ford, Ian; Ferrari, Roberto; Tardif, Jean-Claude; Tendera, Michal; Greenlaw, Nicola; Steg, Ph Gabriel

2014-01-01

To assess the frequency of chronic kidney disease (CKD), define the associated demographics, and evaluate its association with use of evidence-based drug therapy in a contemporary global study of patients with stable coronary artery disease. 22,272 patients from the ProspeCtive observational LongitudinAl RegIstry oF patients with stable coronary arterY disease (CLARIFY) were included. Baseline estimated glomerular filtration rate (eGFR) was calculated (CKD-Epidemiology Collaboration formula) and patients categorised according to CKD stage: >89, 60-89, 45-59 and <45 mL/min/1.73 m2. Mean (SD) age was 63.9±10.4 years, 77.3% were male, 61.8% had a history of myocardial infarction, 71.9% hypertension, 30.4% diabetes and 75.4% dyslipidaemia. Chronic kidney disease (eGFR<60 mL/min/1.73 m2) was seen in 22.1% of the cohort (6.9% with eGFR<45 mL/min/1.73 m2); lower eGFR was associated with increasing age, female sex, cardiovascular risk factors, overt vascular disease, other comorbidities and higher systolic but lower diastolic blood pressure. High use of secondary prevention was seen across all CKD stages (overall 93.4% lipid-lowering drugs, 95.3% antiplatelets, 75.9% beta-blockers). The proportion of patients taking statins was lower in patients with CKD. Antiplatelet use was significantly lower in patients with CKD whereas oral anticoagulant use was higher. Angiotensin-converting enzyme inhibitor use was lower (52.0% overall) and inversely related to declining eGFR, whereas angiotensin-receptor blockers were more frequently prescribed in patients with reduced eGFR. Chronic kidney disease is common in patients with stable coronary artery disease and is associated with comorbidities. Whilst use of individual evidence-based medications for secondary prevention was high across all CKD categories, there remains an opportunity to improve the proportion who take all three classes of preventive therapies. Angiotensin-converting enzyme inhibitors were used less frequently in lower eGRF categories. Surprisingly the reverse was seen for angiotensin-receptor blockers. Further evaluation is required to fully understand these associations. The CLARIFY (ProspeCtive observational LongitudinAl RegIstry oF patients with stable coronary arterY disease) Registry is registered in the ISRCTN registry of clinical trials with the number ISRCTN43070564. http://www.controlled-trials.com/ISRCTN43070564.

A Web-Based Psychoeducational Intervention Program for Depression and Anxiety in an Adult Community in Selangor, Malaysia: Protocol of a Randomized Controlled Trial.

PubMed

Kader Maideen, Siti Fatimah; Mohd-Sidik, Sherina; Rampal, Lekhraj; Mukhtar, Firdaus; Ibrahim, Normala; Phang, Cheng-Kar; Tan, Kit-Aun; Ahmad, Rozali

2016-06-21

Mental disorders are a major public health problem and are debilitating in many nations throughout the world. Many individuals either do not or are not able to access treatment. The Internet can be a medium to convey to the community accessible evidenced-based interventions to reduce these burdens. The objective of this study is to investigate the effectiveness of 4 weeks of a Web-based psychoeducational intervention program for depressive and anxiety symptoms in the community of Selangor, Malaysia. A two-arm randomized controlled trial of a single-blind study will be conducted to meet the objective of this study. We aim to recruit 84 participants each for the intervention and control groups. The recruitment will be from participants who participated in the first phase of this research. The primary outcomes of this study are depressive and anxiety scores, which will be assessed using the Patient Health Questionnaire 9 and Generalized Anxiety Disorder 7, respectively. The secondary outcome includes mental health literacy of the participants, which will be assessed using the self-developed and adapted Mental Health Literacy Questionnaire. The psychoeducational intervention program consists of four sessions, which will be accessed each week. The depressive and anxiety symptoms will be compared between participants who participated in the psychoeducational program compared with the control group. Depressive and anxiety scores and mental health literacy will be assessed at week 1 and at follow-ups at week 5 and week 12, respectively. The psychoeducational intervention program consists of four sessions, which will be accessed at each week. The depressive and anxiety symptoms will be compared between the intervention and control groups using a series of mixed ANOVAs. Depressive and anxiety scores and mental health literacy will be assessed at week 1 and at two follow-ups at week 5 and week 12, respectively. To our knowledge, this study will be the first randomized controlled trial of a Web-based psychoeducational intervention program for depression and anxiety in an adult community in Malaysia. The results from this study will determine the effectiveness of a psychoeducational intervention program in the management of depression and anxiety among adults in the community. If proven to be effective, the intervention can serve as a new modality to manage and reduce the burden of these disorders in the community. International Standard Randomized Controlled Trial Number (ISRCTN): 39656144; http://www.isrctn.com/ISRCTN39656144 (Archived by WebCite at http://www.webcitation.org/6hSVhV71K).

Web-Based Decision Aid to Assist Help-Seeking Choices for Young People Who Self-Harm: Outcomes From a Randomized Controlled Feasibility Trial

PubMed Central

Patel, Krisna; French, Rebecca S; Henderson, Claire; Ougrin, Dennis; Slade, Mike; Moran, Paul

2018-01-01

Background Adolescents who self-harm are often unsure how or where to get help. We developed a Web-based personalized decision aid (DA) designed to support young people in decision making about seeking help for their self-harm. Objective The aim of this study was to evaluate the feasibility and acceptability of the DA intervention and the randomized controlled trial (RCT) in a school setting. Methods We conducted a two-group, single blind, randomized controlled feasibility trial in a school setting. Participants aged 12 to 18 years who reported self-harm in the past 12 months were randomized to either a Web-based DA or to general information about mood and feelings. Feasibility of recruitment, randomization, and follow-up rates were assessed, as was acceptability of the intervention and study procedures. Descriptive data were collected on outcome measures examining decision making and help-seeking behavior. Qualitative interviews were conducted with young people, parents or carers, and staff and subjected to thematic analysis to explore their views of the DA and study processes. Results Parental consent was a significant barrier to young people participating in the trial, with only 17.87% (208/1164) of parents or guardians who were contacted for consent responding to study invitations. Where parental consent was obtained, we were able to recruit 81.7% (170/208) of young people into the study. Of those young people screened, 13.5% (23/170) had self-harmed in the past year. Ten participants were randomized to receiving the DA, and 13 were randomized to the control group. Four-week follow-up assessments were completed with all participants. The DA had good acceptability, but qualitative interviews suggested that a DA that addressed broader mental health problems such as depression, anxiety, and self-harm may be more beneficial. Conclusions A broad-based mental health DA addressing a wide range of psychosocial problems may be useful for young people. The requirement for parental consent is a key barrier to intervention research on self-harm in the school setting. Adaptations to the research design and the intervention are needed before generalizable research about DAs can be successfully conducted in a school setting. Trial Registration International Standard Randomized Controlled Trial registry: ISRCTN11230559; http://www.isrctn.com/ISRCTN11230559 (Archived by WebCite at http://www.webcitation.org/6wqErsYWG) PMID:29382626

The gut microbiota metabolism of pomegranate or walnut ellagitannins yields two urolithin-metabotypes that correlate with cardiometabolic risk biomarkers: Comparison between normoweight, overweight-obesity and metabolic syndrome.

PubMed

Selma, María V; González-Sarrías, Antonio; Salas-Salvadó, Jordi; Andrés-Lacueva, Cristina; Alasalvar, Cesarettin; Örem, Asım; Tomás-Barberán, Francisco A; Espín, Juan C

2018-06-01

Urolithins are microbial metabolites produced after consumption of ellagitannin-containing foods such as pomegranates and walnuts. Parallel to isoflavone-metabolizing phenotypes, ellagitannin-metabolizing phenotypes (urolithin metabotypes A, B and 0; UM-A, UM-B and UM-0, respectively) can vary among individuals depending on their body mass index (BMI), but correlations between urolithin metabotypes (UMs) and cardiometabolic risk (CMR) factors are unexplored. We investigated the association between UMs and CMR factors in individuals with different BMI and health status. UM was identified using UPLC-ESI-qToF-MS in individuals consuming pomegranate or nuts. The associations between basal CMR factors and the urine urolithin metabolomic signature were explored in 20 healthy normoweight individuals consuming walnuts (30 g/d), 49 healthy overweight-obese individuals ingesting pomegranate extract (450 mg/d) and 25 metabolic syndrome (MetS) patients consuming nuts (15 g-walnuts, 7.5 g-hazelnuts and 7.5 g-almonds/d). Correlations between CMR factors and urolithins were found in overweight-obese individuals. Urolithin-A (mostly present in UM-A) was positively correlated with apolipoprotein A-I (P ≤ 0.05) and intermediate-HDL-cholesterol (P ≤ 0.05) while urolithin-B and isourolithin-A (characteristic from UM-B) were positively correlated with total-cholesterol, LDL-cholesterol (P ≤ 0.001), apolipoprotein B (P ≤ 0.01), VLDL-cholesterol, IDL-cholesterol, oxidized-LDL and apolipoprotein B:apolipoprotein A-I ratio (P ≤ 0.05). In MetS patients, urolithin-A only correlated inversely with glucose (P ≤ 0.05). Statin-treated MetS patients with UM-A showed a lipid profile similar to that of healthy normoweight individuals while a poor response to lipid-lowering therapy was observed in MB patients. UMs are potential CMR biomarkers. Overweight-obese individuals with UM-B are at increased risk of cardiometabolic disease, whereas urolithin-A production could protect against CMR factors. Further research is warranted to explore these associations in larger cohorts and whether the effect of lipid-lowering drugs or ellagitannin-consumption on CMR biomarkers depends on individuals' UM. NCT01916239 (https://clinicaltrials.gov/ct2/show/NCT01916239) and ISRCTN36468613 (http://www.isrctn.com/ISRCTN36468613). Copyright © 2017 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.

Acceptability and caregiver-reported outcomes for young children with autism spectrum disorder whose parents attended a preventative population-based intervention for anxiety: A pilot study.

PubMed

Bischof, Natalie L; Rapee, Ronald M; Hudry, Kristelle; Bayer, Jordana K

2018-05-15

This pilot study explored acceptability to parents and outcomes for children of a preventive intervention for anxiety problems in pre-schoolers with autism spectrum disorder (ASD) who were an identified sub-group within a population-based randomised trial of the Cool Little Kids parenting group programme. The population trial included 545 temperamentally inhibited pre-schoolers recruited across eight economically diverse areas of Melbourne, Australia. Within this sample, 26 parents reported that their child had received an ASD diagnosis. Trial measures included baseline inhibited temperament and developmental problems, post-intervention feedback on the programme, and caregiver-reported child mental health outcomes (anxiety diagnoses and internalising symptoms) at 1- and 2-year follow-up. Sample retention for the children with ASD over 2 years was strong (92%). At follow-up, fewer intervention than control children with ASD had anxiety disorders after 1 year (% (n): 25 (3) vs. 77 (10), P = .028) and separation anxiety symptoms after 2 years (M (SD): 4.22 (2.68) vs. 9.38 (5.91), P = .017). Similar effects favouring the intervention group were apparent across other child emotional outcome measures but without statistical significance in this small sample. Parents of the children with ASD reported that Cool Little Kids was "quite useful" in relation to their child's anxiety but also gave feedback that they would appreciate some tailoring of programme content to the context of ASD. These pilot findings suggest Cool Little Kids may be helpful for reducing comorbid anxiety in pre-schoolers with ASD. Further research is warranted to develop an ASD-specific adaptation which can be trialled with a larger sample of children with confirmed ASD diagnosis. Trial registration ISRCTN30996662 http://www.isrctn.com/ISRCTN30996662. Autism Res 2018. © 2018 International Society for Autism Research, Wiley Periodicals, Inc. Many children with autism spectrum disorder (ASD) also have anxiety. This pilot study explored acceptability to parents and outcomes for pre-schoolers with ASD of a parenting group programme to prevent anxiety problems. Among the sample of 26 pre-schoolers with ASD, we found reduced anxiety disorders and separation symptoms when their parents had received the intervention, as reported by caregivers in checklists and clinical interviews. Parents gave feedback that the programme was useful but suggested content be adapted to the context of ASD. © 2018 International Society for Autism Research, Wiley Periodicals, Inc.

Cambio : a file format translation and analysis application for the nuclear response emergency community.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Lasche, George P.

2009-10-01

Cambio is an application intended to automatically read and display any spectrum file of any format in the world that the nuclear emergency response community might encounter. Cambio also provides an analysis capability suitable for HPGe spectra when detector response and scattering environment are not well known. Why is Cambio needed: (1) Cambio solves the following problem - With over 50 types of formats from instruments used in the field and new format variations appearing frequently, it is impractical for every responder to have current versions of the manufacturer's software from every instrument used in the field; (2) Cambio convertsmore » field spectra to any one of several common formats that are used for analysis, saving valuable time in an emergency situation; (3) Cambio provides basic tools for comparing spectra, calibrating spectra, and isotope identification with analysis suited especially for HPGe spectra; and (4) Cambio has a batch processing capability to automatically translate a large number of archival spectral files of any format to one of several common formats, such as the IAEA SPE or the DHS N42. Currently over 540 analysts and members of the nuclear emergency response community worldwide are on the distribution list for updates to Cambio. Cambio users come from all levels of government, university, and commercial partners around the world that support efforts to counter terrorist nuclear activities. Cambio is Unclassified Unlimited Release (UUR) and distributed by internet downloads with email notifications whenever a new build of Cambio provides for new formats, bug fixes, or new or improved capabilities. Cambio is also provided as a DLL to the Karlsruhe Institute for Transuranium Elements so that Cambio's automatic file-reading capability can be included at the Nucleonica web site.« less

Analysis of the mitochondrial genome of cheetahs (Acinonyx jubatus) with neurodegenerative disease.

PubMed

Burger, Pamela A; Steinborn, Ralf; Walzer, Christian; Petit, Thierry; Mueller, Mathias; Schwarzenberger, Franz

2004-08-18

The complete mitochondrial genome of Acinonyx jubatus was sequenced and mitochondrial DNA (mtDNA) regions were screened for polymorphisms as candidates for the cause of a neurodegenerative demyelinating disease affecting captive cheetahs. The mtDNA reference sequences were established on the basis of the complete sequences of two diseased and two nondiseased animals as well as partial sequences of 26 further individuals. The A. jubatus mitochondrial genome is 17,047-bp long and shows a high sequence similarity (91%) to the domestic cat. Based on single nucleotide polymorphisms (SNPs) in the control region (CR) and pedigree information, the 18 myelopathic and 12 non-myelopathic cheetahs included in this study were classified into haplotypes I, II and III. In view of the phenotypic comparability of the neurodegenerative disease observed in cheetahs and human mtDNA-associated diseases, specific coding regions including the tRNAs leucine UUR, lysine, serine UCN, and partial complex I and V sequences were screened. We identified a heteroplasmic and a homoplasmic SNP at codon 507 in the subunit 5 (MTND5) of complex I. The heteroplasmic haplotype I-specific valine to methionine substitution represents a nonconservative amino acid change and was found in 11 myelopathic and eight non-myelopathic cheetahs with levels ranging from 29% to 79%. The homoplasmic conservative amino acid substitution valine to alanine was identified in two myelopathic animals of haplotype II. In addition, a synonymous SNP in the codon 76 of the MTND4L gene was found in the single haplotype III animal. The amino acid exchanges in the MTND5 gene were not associated with the occurrence of neurodegenerative disease in captive cheetahs.

Whole mitochondrial genome screening in maternally inherited non-syndromic hearing impairment using a microarray resequencing mitochondrial DNA chip.

PubMed

Lévêque, Marianne; Marlin, Sandrine; Jonard, Laurence; Procaccio, Vincent; Reynier, Pascal; Amati-Bonneau, Patrizia; Baulande, Sylvain; Pierron, Denis; Lacombe, Didier; Duriez, Françoise; Francannet, Christine; Mom, Thierry; Journel, Hubert; Catros, Hélène; Drouin-Garraud, Valérie; Obstoy, Marie-Françoise; Dollfus, Hélène; Eliot, Marie-Madeleine; Faivre, Laurence; Duvillard, Christian; Couderc, Remy; Garabedian, Eréa-Noël; Petit, Christine; Feldmann, Delphine; Denoyelle, Françoise

2007-11-01

Mitochondrial DNA (mtDNA) mutations have been implicated in non-syndromic hearing loss either as primary or as predisposing factors. As only a part of the mitochondrial genome is usually explored in deafness, its prevalence is probably under-estimated. Among 1350 families with non-syndromic sensorineural hearing loss collected through a French collaborative network, we selected 29 large families with a clear maternal lineage and screened them for known mtDNA mutations in 12S rRNA, tRNASer(UCN) and tRNALeu(UUR) genes. When no mutation could be identified, a whole mitochondrial genome screening was performed, using a microarray resequencing chip: the MitoChip version 2.0 developed by Affymetrix Inc. Known mtDNA mutations was found in nine of the 29 families, which are described in the article: five with A1555G, two with the T7511C, one with 7472insC and one with A3243G mutation. In the remaining 20 families, the resequencing Mitochip detected 258 mitochondrial homoplasmic variants and 107 potentially heteroplasmic variants. Controls were made by direct sequencing on selected fragments and showed a high sensibility of the MitoChip but a low specificity, especially for heteroplasmic variations. An original analysis on the basis of species conservation, frequency and phylogenetic investigation was performed to select the more probably pathogenic variants. The entire genome analysis allowed us to identify five additional families with a putatively pathogenic mitochondrial variant: T669C, C1537T, G8078A, G12236A and G15077A. These results indicate that the new MitoChip platform is a rapid and valuable tool for identification of new mtDNA mutations in deafness.

Metabolically induced heteroplasmy shifting and L-arginine treatment reduce the energetic defect in a neuronal-like model of MELAS

PubMed Central

Desquiret-Dumas, Valerie; Gueguen, Naig; Barth, Magalie; Chevrollier, Arnaud; Hancock, Saege; Wallace, Douglas C; Amati-Bonneau, Patrizia; Henrion, Daniel; Bonneau, Dominique; Reynier, Pascal; Procaccio, Vincent

2012-01-01

The m.3243A>G variant in the mitochondrial tRNALeu (UUR) gene is a common mitochondrial DNA (mtDNA) mutation. Phenotypic manifestations depend mainly on the heteroplasmy, i.e. the ratio of mutant to normal mtDNA copies. A high percentage of mutant mtDNA is associated with a severe, life-threatening neurological syndrome known as MELAS (mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes). MELAS is described as a neurovascular disorder primarily affecting the brain and blood vessels, but the pathophysiology of the disease is poorly understood. We developed a series of cybrid cell lines at two different mutant loads: 70% and 100% in the nuclear background of a neuroblastoma cell line (SH-SY5Y). We investigated the impact of the mutation on the metabolism and mitochondrial respiratory chain activity of the cybrids. The m.3243A>G mitochondrial mutation induced a metabolic switch towards glycolysis in the neuronal cells and produced severe defects in respiratory chain assembly and activity. We used two strategies to compensate for the biochemical defects in the mutant cells: one consisted of lowering the glucose content in the culture medium, and the other involved the addition of L-arginine. The reduction of glucose significantly shifted the 100% mutant cells towards the wild-type, reaching a 90% mutant level and restoring respiratory chain complex assembly. The addition of L-arginine, a nitric oxide (NO) donor, improved complex I activity in the mutant cells in which the defective NO metabolism had led to a relative shortage of NO. Thus, metabolically induced heteroplasmy shifting and L-arginine therapy may constitute promising therapeutic strategies against MELAS. PMID:22306605

Cerebral hyperperfusion and decreased cerebrovascular reactivity correlate with neurologic disease severity in MELAS.

PubMed

Rodan, L H; Poublanc, J; Fisher, J A; Sobczyk, O; Wong, T; Hlasny, E; Mikulis, D; Tein, I

2015-05-01

To study the mechanisms underlying stroke-like episodes (SLEs) in MELAS syndrome. We performed a case control study in 3 siblings with MELAS syndrome (m.3243A>G tRNA(Leu(UUR))) with variable % mutant mtDNA in blood (35 to 59%) to evaluate regional cerebral blood flow (CBF) and arterial cerebrovascular reactivity (CVR) compared to age- and sex-matched healthy study controls and a healthy control population. Subjects were studied at 3T MRI using arterial spin labeling (ASL) to measure CBF; CVR was measured as a change in % Blood Oxygen Level Dependent signal (as a surrogate of CBF) to repeated 10 mmHg step increase in arterial partial pressure of CO2 (PaCO2). MELAS siblings had decreased CVR (p ≤ 0.002) and increased CBF (p < 0.0026) compared to controls; changes correlated with disease severity and % mutant mtDNA (inversely for CVR: r = -0.82 frontal, r = -0.91 occipital cortex; directly for CBF: r = +0.85 frontal, not for occipital infarct penumbra). Mean CVR was reduced more in frontal (p < 0.001) versus occipital cortex (p = 0.002); mean CBF was increased more in occipital (p = 0.001) than frontal (p = 0.0026) cortices compared to controls. CBF correlated inversely with CVR (r = -0.99 in frontal; not in occipital infarct penumbra) suggesting that increased frontal resting flows are at the expense of flow reserve. MELAS disease severity and mutation load were inversely correlated with Interictal CVR and directly correlated with frontal CBF. These metrics offer further insight into the cerebrovascular hemodynamics in MELAS syndrome and may serve as noninvasive prognostic markers to stratify risk for SLEs. Class III. Copyright © 2015 © Elsevier B.V. and Mitochondria Research Society. Published by Elsevier B.V. All rights reserved.

Progress in Diagnosing Mitochondrial Myopathy, Encephalopathy, Lactic Acidosis, and Stroke-like Episodes

PubMed Central

Wang, Ying-Xin; Le, Wei-Dong

2015-01-01

Objective: Mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes (MELAS) is a progressive, multisystem affected mitochondrial disease associated with a number of disease-related defective genes. MELAS has unpredictable presentations and clinical course, and it can be commonly misdiagnosed as encephalitis, cerebral infarction, or brain neoplasms. This review aimed to update the diagnosis progress in MELAS, which may provide better understanding of the disease nature and help make the right diagnosis as well. Data Sources: The data used in this review came from published peer review articles from October 1984 to October 2014, which were obtained from PubMed. The search term is “MELAS”. Study Selection: Information selected from those reported studies is mainly based on the progress on clinical features, blood biochemistry, neuroimaging, muscle biopsy, and genetics in diagnosing MELAS. Results: MELAS has a wide heterogeneity in genetics and clinical manifestations. The relationship between mutations and phenotypes remains unclear. Advanced serial functional magnetic resonance imaging (MRI) can provide directional information on this disease. Muscle biopsy has meaningful value in diagnosing MELAS, which shows the presence of ragged red fibers and mosaic appearance of cytochrome oxidase negative fibers. Genetic studies have reported that approximately 80% of MELAS cases are caused by the mutation m.3243A>G of the mitochondrial transfer RNA (Leu (UUR)) gene (MT-TL1). Conclusions: MELAS involves multiple systems with variable clinical symptoms and recurrent episodes. The prognosis of MELAS patients depends on timely diagnosis. Therefore, overall diagnosis of MELAS should be based on the maternal inheritance family history, clinical manifestation, and findings from serial MRI, muscle biopsy, and genetics. PMID:26112726

Leigh-like subacute necrotising encephalopathy in Yorkshire Terriers: neuropathological characterisation, respiratory chain activities and mitochondrial DNA.

PubMed

Baiker, Kerstin; Hofmann, Sabine; Fischer, Andrea; Gödde, Thomas; Medl, Susanne; Schmahl, Wolfgang; Bauer, Matthias F; Matiasek, Kaspar

2009-11-01

Our knowledge of molecular mechanisms underlying mitochondrial disorders in humans has increased considerably during the past two decades. Mitochondrial encephalomyopathies have sporadically been reported in dogs. However, molecular and biochemical data that would lend credence to the suspected mitochondrial origin are largely missing. This study was aimed to characterise a Leigh-like subacute necrotising encephalopathy (SNE) in Yorkshire Terriers and to shed light on its enzymatic and genetic background. The possible resemblance to SNE in Alaskan Huskies and to human Leigh syndrome (LS) was another focus of interest. Eleven terriers with imaging and/or gross evidence of V-shaped, non-contiguous, cyst-like cavitations in the striatum, thalamus and brain stem were included. Neuropathological examinations focussed on muscle, brain pathology and mitochondrial ultrastructure. Further investigations encompassed respiratory-chain activities and the mitochondrial DNA. In contrast to mild non-specific muscle findings, brain pathology featured the stereotypic triad of necrotising grey matter lesions with relative preservation of neurons in the aforementioned regions, multiple cerebral infarcts, and severe patchy Purkinje-cell degeneration in the cerebellar vermis. Two dogs revealed a reduced activity of respiratory-chain-complexes I and IV. Genetic analyses obtained a neutral tRNA-Leu(UUR) A-G-transition only. Neuropathologically, SNE in Yorkshire Terriers is nearly identical to the Alaskan Husky form and very similar to human LS. This study, for the first time, demonstrated that canine SNE can be associated with a combined respiratory chain defect. Mitochondrial tRNA mutations and large genetic rearrangements were excluded as underlying aetiology. Further studies, amongst relevant candidates, should focus on nuclear encoded transcription and translation factors.

Random insertion and gene disruption via transposon mutagenesis of Ureaplasma parvum using a mini-transposon plasmid

PubMed Central

Aboklaish, Ali F.; Dordet-Frisoni, Emilie; Citti, Christine; Toleman, Mark A; Glass, John I.; Spiller, O. Brad

2015-01-01

While transposon mutagenesis has been successfully used for Mycoplasma spp. to disrupt and determine non-essential genes, previous attempts with Ureaplasma spp. have been unsuccessful. Using a polyethylene glycol-transformation enhancing protocol, we were able to transform three separate serovars of Ureaplasma parvum with a Tn4001-based mini-transposon plasmid containing a gentamicin resistance selection marker. Despite the large degree of homology between Ureaplasma parvum and Ureaplasma urealyticum, all attempts to transform the latter in parallel failed, with the exception of a single clinical U. urealyticum isolate. PCR probing and sequencing were used to confirm transposon insertion into the bacterial genome and identify disrupted genes. Transformation of prototype serovar 3 consistently resulted in transfer only of sequence between the mini-transposon inverted repeats, but some strains showed additional sequence transfer. Transposon insertion occurred randomly in the genome resulting in unique disruption of genes UU047, UU390, UU440, UU450, UU520, UU526, UU582 for single clones from a panel of screened clones. An intergenic insertion between genes UU187 and UU188 was also characterised. Two phenotypic alterations were observed in the mutated strains: Disruption of a DEAD-box RNA helicase (UU582) altered growth kinetics, while the U. urealyticum strain lost resistance to serum attack coincident with disruption of gene UUR10_137 and loss of expression of a 41 kDa protein. Transposon mutagenesis was used successfully to insert single copies of a mini-transposon into the genome and disrupt genes leading to phenotypic changes in Ureaplasma parvum strains. This method can now be used to deliver exogenous genes for expression and determine essential genes for Ureaplasma parvum replication in culture and experimental models. PMID:25444567

Random insertion and gene disruption via transposon mutagenesis of Ureaplasma parvum using a mini-transposon plasmid.

PubMed

Aboklaish, Ali F; Dordet-Frisoni, Emilie; Citti, Christine; Toleman, Mark A; Glass, John I; Spiller, O Brad

2014-11-01

While transposon mutagenesis has been successfully used for Mycoplasma spp. to disrupt and determine non-essential genes, previous attempts with Ureaplasma spp. have been unsuccessful. Using a polyethylene glycol-transformation enhancing protocol, we were able to transform three separate serovars of Ureaplasma parvum with a Tn4001-based mini-transposon plasmid containing a gentamicin resistance selection marker. Despite the large degree of homology between Ureaplasma parvum and Ureaplasma urealyticum, all attempts to transform the latter in parallel failed, with the exception of a single clinical U. urealyticum isolate. PCR probing and sequencing were used to confirm transposon insertion into the bacterial genome and identify disrupted genes. Transformation of prototype serovar 3 consistently resulted in transfer only of sequence between the mini-transposon inverted repeats, but some strains showed additional sequence transfer. Transposon insertion occurred randomly in the genome resulting in unique disruption of genes UU047, UU390, UU440, UU450, UU520, UU526, UU582 for single clones from a panel of screened clones. An intergenic insertion between genes UU187 and UU188 was also characterised. Two phenotypic alterations were observed in the mutated strains: Disruption of a DEAD-box RNA helicase (UU582) altered growth kinetics, while the U. urealyticum strain lost resistance to serum attack coincident with disruption of gene UUR10_137 and loss of expression of a 41 kDa protein. Transposon mutagenesis was used successfully to insert single copies of a mini-transposon into the genome and disrupt genes leading to phenotypic changes in Ureaplasma parvum strains. This method can now be used to deliver exogenous genes for expression and determine essential genes for Ureaplasma parvum replication in culture and experimental models. Copyright © 2014 Elsevier GmbH. All rights reserved.

Early Onset Diabetes - Genetic And Hormonal Analysis In Pakistani Population.

PubMed

Wahid, Maryam; Kamran, Mohammad

2016-01-01

Mitochondrial DNA mutation and hormonal imbalance is involved in the pathogenesis of early onset diabetes but data is lacking in Pakistani population. The study was planned to delineate the clinical presentation of early onset diabetes with possible hormonal and genetic etiological factors and aascertain the possible etiological role of insulin and glucagon in these patients either on oral hypoglycaemic or subcutaneous insulin therapy. Retrospective, analytical case control study with conventional sampling technique carried at Centre for Research in Experimental and Applied Medicine (CREAM) affiliated with the department of Biochemistry and Molecular Biology, Army Medical College Rawalpindi from Dec 2006 to July 2011. Study included the patients (20-35 years of age) with early onset diabetes on oral hypoglycemic (n=240), insulin therapy (n=280), and compared with non-diabetic healthy controls (n=150). A fragment surrounding tRNALeu (UUR) gene was amplified by AmpliTaq from mtDNA which was extracted from peripheral blood leucocytes. Then it was subjected to restriction endonucleases, ApaI for A3242G mutation and HaeIII for G3316A mutation detection. Plasma glucose, glycosylated Hb, osmolality, insulin and glucagon levels along with ABGs analysis was also done. Non diabetic controls comprised of 51% males and 49% females, diabetics on oral hypoglycemic 60% males and 40 % females and on insulin therapy 54% males and 46% females. Insulin dependent diabetics had statistically significant hyperglucagonemia, acidemia and bicarbonate deficit. MtDNA A3242G and G3316A mutations were not detected. relative hyperglucagonemia and acidemia in Insulin dependent diabetics was a potent threat leading to DKA. The absence of two mtDNA mutations in ND1 gene rules out the possibility of involvement of these mutations in early onset diabetes in Pakistani population.

An exploratory cluster randomised trial of a university halls of residence based social norms marketing campaign to reduce alcohol consumption among 1st year students.

PubMed

Moore, Graham F; Williams, Annie; Moore, Laurence; Murphy, Simon

2013-04-18

This exploratory trial examines the feasibility of implementing a social norms marketing campaign to reduce student drinking in universities in Wales, and evaluating it using cluster randomised trial methodology. Fifty residence halls in 4 universities in Wales were randomly assigned to intervention or control arms. Web and paper surveys were distributed to students within these halls (n = 3800), assessing exposure/contamination, recall of and evaluative responses to intervention messages, perceived drinking norms and personal drinking behaviour. Measures included the Drinking Norms Rating Form, the Daily Drinking Questionnaire and AUDIT-C. A response rate of 15% (n = 554) was achieved, varying substantially between sites. Intervention posters were seen by 80% and 43% of students in intervention and control halls respectively, with most remaining materials seen by a minority in both groups. Intervention messages were rated as credible and relevant by little more than half of students, though fewer felt they would influence their behaviour, with lighter drinkers more likely to perceive messages as credible. No differences in perceived norms were observed between intervention and control groups. Students reporting having seen intervention materials reported lower descriptive and injunctive norms than those who did not. Attention is needed to enhancing exposure, credibility and perceived relevance of intervention messages, particularly among heavier drinkers, before definitive evaluation can be recommended. A definitive evaluation would need to consider how it would achieve sufficient response rates, whilst hall-level cluster randomisation appears subject to a significant degree of contamination. ISRCTN: ISRCTN48556384.

Increased amygdala responses to emotional faces after psilocybin for treatment-resistant depression.

PubMed

Roseman, Leor; Demetriou, Lysia; Wall, Matthew B; Nutt, David J; Carhart-Harris, Robin L

2017-12-27

Recent evidence indicates that psilocybin with psychological support may be effective for treating depression. Some studies have found that patients with depression show heightened amygdala responses to fearful faces and there is reliable evidence that treatment with SSRIs attenuates amygdala responses (Ma, 2015). We hypothesised that amygdala responses to emotional faces would be altered post-treatment with psilocybin. In this open-label study, 20 individuals diagnosed with moderate to severe, treatment-resistant depression, underwent two separate dosing sessions with psilocybin. Psychological support was provided before, during and after these sessions and 19 completed fMRI scans one week prior to the first session and one day after the second and last. Neutral, fearful and happy faces were presented in the scanner and analyses focused on the amygdala. Group results revealed rapid and enduring improvements in depressive symptoms post psilocybin. Increased responses to fearful and happy faces were observed in the right amygdala post-treatment, and right amygdala increases to fearful versus neutral faces were predictive of clinical improvements at 1-week. Psilocybin with psychological support was associated with increased amygdala responses to emotional stimuli, an opposite effect to previous findings with SSRIs. This suggests fundamental differences in these treatments' therapeutic actions, with SSRIs mitigating negative emotions and psilocybin allowing patients to confront and work through them. Based on the present results, we propose that psilocybin with psychological support is a treatment approach that potentially revives emotional responsiveness in depression, enabling patients to reconnect with their emotions. ISRCTN, number ISRCTN14426797. Copyright © 2018 The Authors. Published by Elsevier Ltd.. All rights reserved.

Evaluating compliance to a low glycaemic index (GI) diet in women with polycystic ovary syndrome (PCOS).

PubMed

Egan, Nicola; Read, Anna; Riley, Paddy; Atiomo, William

2011-03-08

A low Glycaemic Index (GI) diet may decrease some long-term health risks in Polycystic Ovary Syndrome (PCOS) such as endometrial cancer. This study was performed to assess compliance to a low GI diet in women with PCOS. Food diaries prospectively collected over 6 months from women on a low GI diet or healthy eating diet were analysed retrospectively. The women were recruited for a pilot randomised control trial investigating whether a low GI diet decreased the risk of Endometrial Cancer. Nine women with PCOS completed 33 food diaries (17 from women on a low GI diet and 16 from women on a healthy eating diet) recording 3023 food items (low GI group:n = 1457; healthy eating group:n = 1566). Data was analysed using Foster-Powell international values inserted into an SPSS database as no scientifically valid established nutrition software was found. The main outcome measures were mean item GI and Glyacemic Load (GL), mean meal GL, percentage high GI foods and mean weight loss. Women allocated the low GI diet had a statistically significant lower GI of food items (33.67 vs 36.91, p < 0.05), lower percentage of high GI foods (4.3% vs 12.1%, p < 0.05) and lower GL of food items and meals. Women with PCOS on a low GI diet consumed food items with a significantly lower mean GI and GL compared to the healthy eating diet group. Longer term compliance needs evaluation in subsequent studies to ascertain that this translates to reduced long term health risks. ISRCTN: ISRCTN86420258.

Online CBT life skills programme for low mood and anxiety: study protocol for a pilot randomized controlled trial.

PubMed

Williams, Christopher; McClay, Carrie-Anne; Martinez, Rebeca; Morrison, Jill; Haig, Caroline; Jones, Ray; Farrand, Paul

2016-04-27

Low mood is a common mental health problem with significant health consequences. Studies have shown that cognitive behavioural therapy (CBT) is an effective treatment for low mood and anxiety when delivered one-to-one by an expert practitioner. However, access to this talking therapy is often limited and waiting lists can be long, although a range of low-intensity interventions that can increase access to services are available. These include guided self-help materials delivered via books, classes and online packages. This project aims to pilot a randomized controlled trial of an online CBT-based life skills course with community-based individuals experiencing low mood and anxiety. Individuals with elevated symptoms of depression will be recruited directly from the community via online and newspaper advertisements. Participants will be remotely randomized to receive either immediate access or delayed access to the Living Life to the Full guided online CBT-based life skills package, with telephone or email support provided whilst they use the online intervention. The primary end point will be at 3 months post-randomization, at which point the delayed-access group will be offered the intervention. Levels of depression, anxiety, social functioning and satisfaction will be assessed. This pilot study will test the trial design, and ability to recruit and deliver the intervention. Drop-out rates will be assessed and the completion and acceptability of the package will be investigated. The study will also inform a sample size power calculation for a subsequent substantive randomized controlled trial. ISRCTN ISRCTN12890709.

Walk well: a randomised controlled trial of a walking intervention for adults with intellectual disabilities: study protocol

PubMed Central

2013-01-01

Background Walking interventions have been shown to have a positive impact on physical activity (PA) levels, health and wellbeing for adult and older adult populations. There has been very little work carried out to explore the effectiveness of walking interventions for adults with intellectual disabilities. This paper will provide details of the Walk Well intervention, designed for adults with intellectual disabilities, and a randomised controlled trial (RCT) to test its effectiveness. Methods/design This study will adopt a RCT design, with participants allocated to the walking intervention group or a waiting list control group. The intervention consists of three PA consultations (baseline, six weeks and 12 weeks) and an individualised 12 week walking programme. A range of measures will be completed by participants at baseline, post intervention (three months from baseline) and at follow up (three months post intervention and six months from baseline). All outcome measures will be collected by a researcher who will be blinded to the study groups. The primary outcome will be steps walked per day, measured using accelerometers. Secondary outcome measures will include time spent in PA per day (across various intensity levels), time spent in sedentary behaviour per day, quality of life, self-efficacy and anthropometric measures to monitor weight change. Discussion Since there are currently no published RCTs of walking interventions for adults with intellectual disabilities, this RCT will examine if a walking intervention can successfully increase PA, health and wellbeing of adults with intellectual disabilities. Trial registration ISRCTN: ISRCTN50494254 PMID:23816316

Comparing oil based ointment versus standard practice for the treatment of moderate burns in Greece: a trial based cost effectiveness evaluation

PubMed Central

2011-01-01

Background The local treatment of burn wounds has long been a subject of debate. The objective of this study was to compare the cost and the effectiveness of Moist Exposed Burn Ointment -MEBO versus a combination of povidone iodine plus bepanthenol cream for partial thickness burns. Methods The study was carried out in the Burn Center of a state hospital in Athens, Greece. 211 patients needing conservative therapy were prospectively selected according to the depth of the burn wound. The treatment was allocated according to the Stratified Randomization Design. The outcomes measured were mean cost of in-hospital stay, rate of complications, time of 50% wound healing, pain scores, in hospital stay diminution. We have adopted a societal perspective. Results In the total groups MEBO presented lower cost, (although not significantly different: p = 0.10) and better effectiveness. The data suggest that MEBO is the dominant therapy for superficial partial burn wound with significantly lower costs and significantly higher effectiveness due to a lesser time of recovery and consequently lower time of hospitalization and follow-up. MEBO presented similar percentages of complications with the comparator, lower pain levels and smaller time of no healthy appearance of the burn limits for superficial partial thickness burns. Conclusions The data suggested that topical application of MEBO may be considered for further investigation as a potential first-line treatment modality for superficial partial thickness burns. Trial registration The trial has been registered on the International Standard Randomised Controlled Trial Number Register (ISRCTN) and given the registration number ISRCTN74058791. PMID:22132709

Comparing oil based ointment versus standard practice for the treatment of moderate burns in Greece: a trial based cost effectiveness evaluation.

PubMed

Carayanni, Vilelmine J; Tsati, Evangelia G; Spyropoulou, Georgia C H; Antonopoulou, Fotini N; Ioannovich, John D

2011-12-01

The local treatment of burn wounds has long been a subject of debate. The objective of this study was to compare the cost and the effectiveness of Moist Exposed Burn Ointment -MEBO versus a combination of povidone iodine plus bepanthenol cream for partial thickness burns. The study was carried out in the Burn Center of a state hospital in Athens, Greece. 211 patients needing conservative therapy were prospectively selected according to the depth of the burn wound. The treatment was allocated according to the Stratified Randomization Design. The outcomes measured were mean cost of in-hospital stay, rate of complications, time of 50% wound healing, pain scores, in hospital stay diminution. We have adopted a societal perspective. In the total groups MEBO presented lower cost, (although not significantly different: p = 0.10) and better effectiveness. The data suggest that MEBO is the dominant therapy for superficial partial burn wound with significantly lower costs and significantly higher effectiveness due to a lesser time of recovery and consequently lower time of hospitalization and follow-up. MEBO presented similar percentages of complications with the comparator, lower pain levels and smaller time of no healthy appearance of the burn limits for superficial partial thickness burns. The data suggested that topical application of MEBO may be considered for further investigation as a potential first-line treatment modality for superficial partial thickness burns. The trial has been registered on the International Standard Randomised Controlled Trial Number Register (ISRCTN) and given the registration number ISRCTN74058791.

Can Targeted Intervention Mitigate Early Emotional and Behavioral Problems?: Generating Robust Evidence within Randomized Controlled Trials

PubMed Central

Doyle, Orla; McGlanaghy, Edel; O’Farrelly, Christine; Tremblay, Richard E.

2016-01-01

This study examined the impact of a targeted Irish early intervention program on children’s emotional and behavioral development using multiple methods to test the robustness of the results. Data on 164 Preparing for Life participants who were randomly assigned into an intervention group, involving home visits from pregnancy onwards, or a control group, was used to test the impact of the intervention on Child Behavior Checklist scores at 24-months. Using inverse probability weighting to account for differential attrition, permutation testing to address small sample size, and quantile regression to characterize the distributional impact of the intervention, we found that the few treatment effects were largely concentrated among boys most at risk of developing emotional and behavioral problems. The average treatment effect identified a 13% reduction in the likelihood of falling into the borderline clinical threshold for Total Problems. The interaction and subgroup analysis found that this main effect was driven by boys. The distributional analysis identified a 10-point reduction in the Externalizing Problems score for boys at the 90th percentile. No effects were observed for girls or for the continuous measures of Total, Internalizing, and Externalizing problems. These findings suggest that the impact of this prenatally commencing home visiting program may be limited to boys experiencing the most difficulties. Further adoption of the statistical methods applied here may help to improve the internal validity of randomized controlled trials and contribute to the field of evaluation science more generally. Trial Registration: ISRCTN Registry ISRCTN04631728 PMID:27253184

A longitudinal study of allergy and intestinal helminth infections in semi urban and rural areas of Flores, Indonesia (ImmunoSPIN Study)

PubMed Central

2011-01-01

Background The prevalence of asthma and atopic disease has been reported to be low in low income countries, however helminth infections are likely to be high among these communities. The question of whether helminth infections play a role in allergic diseases can best be addressed by intervention studies. None of the studies so far have been based on a large scale placebo-controlled trial. Method/Design This study was designed to assess how intestinal helminth infections can influence the immune response and atopic and allergic disorders in children in Indonesia. The relations between allergic outcomes and infection and lifestyle factors will be addressed. This study was set up among school-age children in semi urban and rural areas, located in Ende District of Flores Island, Indonesia. A randomized placebo-controlled anthelmintic treatment trial to elucidate the impact of helminth infections on the prevalence of skin prick test (SPT) reactivity and symptoms of allergic diseases will be performed. The children living in these semi-urban and rural areas will be assessed for SPT to allergens before and after 1 and 2 years of treatment as the primary outcome of the study; the secondary outcome is symptoms (asthma and atopic dermatitis); while the tertiary outcome is immune responses (both antibody levels to allergens and cellular immune responses). Discussion The study will provide information on the influence of helminth infections and anthelmintic treatment on immune response, atopy and allergic disorders. Trial registration Current Controlled Trials ISRCTN: ISRCTN83830814 PMID:21457539

Compliance with dietary guidelines affects capillary recruitment in healthy middle-aged men and women.

PubMed

Govoni, Virginia; Sanders, Thomas A B; Reidlinger, Dianne P; Darzi, Julia; Berry, Sarah E E; Goff, Louise M; Seed, Paul T; Chowienczyk, Philip J; Hall, Wendy L

2017-04-01

Healthy microcirculation is important to maintain the health of tissues and organs, most notably the heart, kidney and retina. Single components of the diet such as salt, lipids and polyphenols may influence microcirculation, but the effects of dietary patterns that are consistent with current dietary guidelines are uncertain. It was hypothesized that compliance to UK dietary guidelines would have a favourable effect on skin capillary density/recruitment compared with a traditional British diet (control diet). A 12-week randomized controlled trial in men and women aged 40-70 years was used to test whether skin microcirculation, measured by skin video-capillaroscopy on the dorsum of the finger, influenced functional capillary density (number of capillaries perfused under basal conditions), structural capillary density (number of anatomical capillaries perfused during finger cuff inflation) and capillary recruitment (percentage difference between structural and functional capillary density). Microvascular measures were available for 137 subjects out of the 165 participants randomized to treatment. There was evidence of compliance to the dietary intervention, and participants randomized to follow dietary guidelines showed significant falls in resting supine systolic, diastolic and mean arterial pressure of 3.5, 2.6 and 2.9 mmHg compared to the control diet. There was no evidence of differences in capillary density, but capillary recruitment was 3.5 % (95 % CI 0.2, 6.9) greater (P = 0.04) on dietary guidelines compared with control. Adherence to dietary guidelines may help maintain a healthy microcirculation in middle-aged men and women. This study is registered at www.isrctn.com as ISRCTN92382106.

Geographic Information System and tools of spatial analysis in a pneumococcal vaccine trial.

PubMed

Tanskanen, Antti; Nillos, Leilani T; Lehtinen, Antti; Nohynek, Hanna; Sanvictores, Diozele Hazel M; Simões, Eric Af; Tallo, Veronica L; Lucero, Marilla G

2012-01-20

The goal of this Geographic Information System (GIS) study was to obtain accurate information on the locations of study subjects, road network and services for research purposes so that the clinical outcomes of interest (e.g., vaccine efficacy, burden of disease, nasopharyngeal colonization and its reduction) could be linked and analyzed at a distance from health centers, hospitals, doctors and other important services. The information on locations can be used to investigate more accurate crowdedness, herd immunity and/or transmission patterns. A randomized, placebo-controlled, double-blind trial of an 11-valent pneumococcal conjugate vaccine (11PCV) was conducted in Bohol Province in central Philippines, from July 2000 to December 2004. We collected the information on the geographic location of the households (N = 13,208) of study subjects. We also collected a total of 1982 locations of health and other services in the six municipalities and a comprehensive GIS data over the road network in the area. We calculated the numbers of other study subjects (vaccine and placebo recipients, respectively) within the neighborhood of each study subject. We calculated distances to different services and identified the subjects sharing the same services (calculated by distance). This article shows how to collect a complete GIS data set for human to human transmitted vaccine study in developing country settings in an efficient and economical way. The collection of geographic locations in intervention trials should become a routine task. The results of public health research may highly depend on spatial relationships among the study subjects and between the study subjects and the environment, both natural and infrastructural. ISRCTN: ISRCTN62323832.

Statistical analysis plan for the Laser-1st versus Drops-1st for Glaucoma and Ocular Hypertension Trial (LiGHT): a multi-centre randomised controlled trial.

PubMed

Vickerstaff, Victoria; Ambler, Gareth; Bunce, Catey; Xing, Wen; Gazzard, Gus

2015-11-11

The LiGHT trial (Laser-1st versus Drops-1st for Glaucoma and Ocular Hypertension Trial) is a multicentre randomised controlled trial of two treatment pathways for patients who are newly diagnosed with open-angle glaucoma (OAG) and ocular hypertension (OHT). The main hypothesis for the trial is that lowering intraocular pressure (IOP) with selective laser trabeculoplasty (SLT) as the primary treatment ('Laser-1st') leads to a better health-related quality of life than for those started on IOP-lowering drops as their primary treatment ('Medicine-1st') and that this is associated with reduced costs and improved tolerability of treatment. This paper describes the statistical analysis plan for the study. The LiGHT trial is an unmasked, multi-centre randomised controlled trial. A total of 718 patients (359 per arm) are being randomised to two groups: medicine-first or laser-first treatment. Outcomes are recorded at baseline and at 6-month intervals up to 36 months. The primary outcome measure is health-related quality of life (HRQL) at 36 months measured using the EQ-5D-5L. The main secondary outcome is the Glaucoma Utility Index. We plan to analyse the patient outcome data according to the group to which the patient was originally assigned. Methods of statistical analysis are described, including the handling of missing data, the covariates used in the adjusted analyses and the planned sensitivity analyses. The trial was registered with the ISRCTN register on 23/07/2012, number ISRCTN32038223 .

Alleviating staff stress in care homes for people with dementia: protocol for stepped-wedge cluster randomised trial to evaluate a web-based Mindfulness- Stress Reduction course.

PubMed

Baker, Christine; Huxley, Peter; Dennis, Michael; Islam, Saiful; Russell, Ian

2015-12-21

There has been continuing change in the nature of care homes in the UK with 80 % of residents now living with some form of dementia or memory problem. Caring in this environment can be complex, challenging and stressful for staff; this can affect the quality of care provided to residents, lead to staff strain and burnout, and increase sickness, absence and turnover rates. It is therefore important to find interventions to increase the wellbeing of staff that will not only benefit staff themselves but also residents and care providers. Mindfulness training is known to be effective in treating a variety of physical and mental health conditions. The study uses mixed methods centred on a stepped-wedge cluster randomised trial. Thirty care homes in Wales are implementing a brief web-based mindfulness training course, starting in random sequence. Four to ten consenting staff from each facility undertake the course and complete validated questionnaires at baseline and after eight and 20 weeks. We shall also interview a stratified sample of ten trained staff and analyse the transcripts thematically. The primary outcome is stress; secondary outcomes include job satisfaction, attitudes towards residents and sickness absence rates. With increasing numbers of people living with dementia in care homes and causing stress in their carers, it is important to evaluate support strategies for staff. Mindfulness-based therapies may be of potential benefit and need detailed examination. ISRCTN registry. ISRCTN80487202. Registered 24 July 2013.

Protocol for the "four steps to control your fatigue (4-STEPS)" randomised controlled trial: a self-regulation based physical activity intervention for patients with unexplained chronic fatigue

PubMed Central

2012-01-01

Background Unexplained Chronic Fatigue is a medical condition characterized by the presence of persistent, severe and debilitating medically unexplained fatigue, leading to impaired functioning and lower quality of life. Research suggests that physical activity can contribute to the reduction of fatigue and other somatic symptoms and can thus significantly improve physical functioning and quality of life in these patients. Based on the self-regulation (SR) theory of behaviour change, we developed a brief physical activity program for patients suffering from unexplained chronic fatigue which focuses on the training of self-regulation skills, the "4-STEPS to control your fatigue" program. Methods/Design This is a multi-centre, randomised controlled trial (RCT) that will be carried out in local primary care centres and at the Portuguese Fibromyalgia and Chronic Fatigue Syndrome Patients Association. Patients aged between 18 and 65 and fulfilling operationalized criteria for Idiopathic Chronic Fatigue (ICF) and Chronic Fatigue Syndrome (CFS) will be recruited and randomly allocated to standard care (SC) or standard care plus a self-regulation based physical activity program (4-STEPS). Patients will be assessed at baseline, after the intervention (3 months) and at 12 months follow-up. The primary outcome is fatigue severity. Discussion The results of the RCT will provide information about the effectiveness of a brief self-regulation intervention for promoting physical activity in patients with unexplained chronic fatigue. If the program proves to be effective, it may be considered as an adjunctive treatment for these patients. Trial Registration ISRCTN: ISRCTN70763996 PMID:22429404

Cost-minimization analysis in a blind randomized trial on small-incision versus laparoscopic cholecystectomy from a societal perspective: sick leave outweighs efforts in hospital savings

PubMed Central

Keus, Frederik; de Jonge, Trudy; Gooszen, Hein G; Buskens, Erik; van Laarhoven, Cornelis JHM

2009-01-01

Background After its introduction, laparoscopic cholecystectomy rapidly expanded around the world and was accepted the procedure of choice by consensus. However, analysis of evidence shows no difference regarding primary outcome measures between laparoscopic and small-incision cholecystectomy. In absence of clear clinical benefit it may be interesting to focus on the resource use associated with the available techniques, a secondary outcome measure. This study focuses on a difference in costs between laparoscopic and small-incision cholecystectomy from a societal perspective with emphasis on internal validity and generalisability Methods A blinded randomized single-centre trial was conducted in a general teaching hospital in The Netherlands. Patients with reasonable to good health diagnosed with symptomatic cholecystolithiasis scheduled for cholecystectomy were included. Patients were randomized between laparoscopic and small-incision cholecystectomy. Total costs were analyzed from a societal perspective. Results Operative costs were higher in the laparoscopic group using reusable laparoscopic instruments (difference 203 euro; 95% confidence interval 147 to 259 euro). There were no significant differences in the other direct cost categories (outpatient clinic and admittance related costs), indirect costs, and total costs. More than 60% of costs in employed patients were caused by sick leave. Conclusion Based on differences in costs, small-incision cholecystectomy seems to be the preferred operative technique over the laparoscopic technique both from a hospital and societal cost perspective. Sick leave associated with convalescence after cholecystectomy in employed patients results in considerable costs to society. Trial registration ISRCTN Register, number ISRCTN67485658. PMID:19732431

Multi-dimensional Treatment Foster Care in England: differential effects by level of initial antisocial behaviour.

PubMed

Sinclair, Ian; Parry, Elizabeth; Biehal, Nina; Fresen, John; Kay, Catherine; Scott, Stephen; Green, Jonathan

2016-08-01

Multi-dimensional Treatment Foster Care (MTFC), recently renamed Treatment Foster Care Oregon for Adolescents (TFCO-A) is an internationally recognised intervention for troubled young people in public care. This paper seeks to explain conflicting results with MTFC by testing the hypotheses that it benefits antisocial young people more than others and does so through its effects on their behaviour. Hard-to-manage young people in English foster or residential homes were assessed at entry to a randomised and case-controlled trial of MTFC (n = 88) and usual care (TAU) (n = 83). Primary outcome was the Children's Global Assessment Scale (CGAS) at 12 months analysed according to high (n = 112) or low (n = 59) baseline level of antisocial behaviour on the Health of the Nation Outcome Scales for Children and Adolescents. After adjusting for covariates, there was no overall treatment effect on CGAS. However, the High Antisocial Group receiving MTFC gained more on the CGAS than the Low group (mean improvement 9.36 points vs. 5.33 points). This difference remained significant (p < 0.05) after adjusting for propensity and covariates and was statistically explained by the reduced antisocial behaviour ratings in MTFC. These analyses support the use of MTFC for youth in public care but only for those with higher levels of antisocial behaviour. Further work is needed on whether such benefits persist, and on possible negative effects of this treatment for those with low antisocial behaviour.Trial Registry Name: ISRCTNRegistry identification number: ISRCTN 68038570Registry URL: www.isrctn.com.

Evaluation design of Urban Health Centres Europe (UHCE): preventive integrated health and social care for community-dwelling older persons in five European cities.

PubMed

Franse, Carmen B; Voorham, Antonius J J; van Staveren, Rob; Koppelaar, Elin; Martijn, Rens; Valía-Cotanda, Elisa; Alhambra-Borrás, Tamara; Rentoumis, Tasos; Bilajac, Lovorka; Marchesi, Vanja Vasiljev; Rukavina, Tomislav; Verma, Arpana; Williams, Greg; Clough, Gary; Garcés-Ferrer, Jorge; Mattace Raso, Francesco; Raat, Hein

2017-09-11

Older persons often have interacting physical and social problems and complex care needs. An integrated care approach in the local context with collaborations between community-, social-, and health-focused organisations can contribute to the promotion of independent living and quality of life. In the Urban Health Centres Europe (UHCE) project, five European cities (Greater Manchester, United Kingdom; Pallini (in Greater Athens Area), Greece; Rijeka, Croatia; Rotterdam, the Netherlands; and Valencia, Spain) develop and implement a care template that integrates health and social care and includes a preventive approach. The UHCE project includes an effect and process evaluation. In a one-year pre-post controlled trial, in each city 250 participants aged 75+ years are recruited to receive the UHCE approach and are compared with 250 participants who receive 'care as usual'. Benefits of UHCE approach in terms of healthy life styles, fall risk, appropriate medication use, loneliness level and frailty, and in terms of level of independence and health-related quality of life and health care use are assessed. A multilevel modeling approach is used for the analyses. The process evaluation is used to provide insight into the reach of the target population, the extent to which elements of the UHCE approach are executed as planned and the satisfaction of the participants. The UHCE project will provide new insight into the feasibility and effectiveness of an integrated care approach for older persons in different European settings. ISRCTN registry number is ISRCTN52788952 . Date of registration is 13/03/2017.

Concordance of Macular Pigment Measurement Using Customized Heterochromatic Flicker Photometry and Fundus Autofluorescence in Age-Related Macular Degeneration.

PubMed

Akuffo, Kwadwo Owusu; Beatty, Stephen; Stack, Jim; Peto, Tunde; Leung, Irene; Corcoran, Laura; Power, Rebecca; Nolan, John M

2015-12-01

We compared macular pigment (MP) measurements using customized heterochromatic flicker photometry (Macular Metrics Densitometer) and dual-wavelength fundus autofluorescence (Heidelberg Spectralis HRA + OCT MultiColor) in subjects with early age-related macular degeneration (AMD). Macular pigment was measured in 117 subjects with early AMD (age, 44-88 years) using the Densitometer and Spectralis, as part of the Central Retinal Enrichment Supplementation Trial (CREST; ISRCTN13894787). Baseline and 6-month study visits data were used for the analyses. Agreement was investigated at four different retinal eccentricities, graphically and using indices of agreement, including Pearson correlation coefficient (precision), accuracy coefficient, and concordance correlation coefficient (ccc). Agreement was poor between the Densitometer and Spectralis at all eccentricities, at baseline (e.g., at 0.25° eccentricity, accuracy = 0.63, precision = 0.35, ccc = 0.22) and at 6 months (e.g., at 0.25° eccentricity, accuracy = 0.52, precision = 0.43, ccc = 0.22). Agreement between the two devices was significantly greater for males at 0.5° and 1.0° of eccentricity. At all eccentricities, agreement was unaffected by cataract grade. In subjects with early AMD, MP measurements obtained using the Densitometer and Spectralis are not statistically comparable and should not be used interchangeably in either the clinical or research setting. Despite this lack of agreement, statistically significant increases in MP, following 6 months of supplementation with macular carotenoids, were detected with each device, confirming that these devices are capable of measuring change in MP within subjects over time. (http://www.controlled-trials.com number, ISRCTN13894787.).

A randomised controlled trial of mentalization-based treatment versus structured clinical management for patients with comorbid borderline personality disorder and antisocial personality disorder.

PubMed

Bateman, Anthony; O'Connell, Jennifer; Lorenzini, Nicolas; Gardner, Tessa; Fonagy, Peter

2016-08-30

Antisocial personality disorder (ASPD) is an under-researched mental disorder. Systematic reviews and policy documents identify ASPD as a priority area for further treatment research because of the scarcity of available evidence to guide clinicians and policymakers; no intervention has been established as the treatment of choice for this disorder. Mentalization-based treatment (MBT) is a psychotherapeutic treatment which specifically targets the ability to recognise and understand the mental states of oneself and others, an ability shown to be compromised in people with ASPD. The aim of the study discussed in this paper is to investigate whether MBT can be an effective treatment for alleviating symptoms of ASPD. This paper reports on a sub-sample of patients from a randomised controlled trial of individuals recruited for treatment of suicidality, self-harm, and borderline personality disorder. The study investigates whether outpatients with comorbid borderline personality disorder and ASPD receiving MBT were more likely to show improvements in symptoms related to aggression than those offered a structured protocol of similar intensity but excluding MBT components. The study found benefits from MBT for ASPD-associated behaviours in patients with comorbid BPD and ASPD, including the reduction of anger, hostility, paranoia, and frequency of self-harm and suicide attempts, as well as the improvement of negative mood, general psychiatric symptoms, interpersonal problems, and social adjustment. MBT appears to be a potential treatment of consideration for ASPD in terms of relatively high level of acceptability and promising treatment effects. ISRCTN ISRCTN27660668 , Retrospectively registered 21 October 2008.

Psycho-education for substance use and antisocial personality disorder: a randomized trial.

PubMed

Thylstrup, Birgitte; Schrøder, Sidsel; Hesse, Morten

2015-11-14

Antisocial personality disorder often co-exists with drug and alcohol use disorders. This trial examined the effectiveness of offering psycho-education for antisocial personality disorder in community substance use disorder treatment centers in Denmark. A total of 176 patients were randomly allocated to treatment as usual (TAU, n = 80) or TAU plus a psycho-educative program, Impulsive Lifestyle Counselling (ILC, n = 96) delivered by site clinicians (n = 39). Using follow-up interviews 3 and 9 months after randomization, we examined changes in drug and alcohol use (Addiction Severity Index Composite Scores), percent days abstinent (PDA) within last month, and aggression as measured with the Buss-Perry Aggression Questionnaire-Short Form and the Self-Report of Aggression and Social Behavior Measure. Overall engagement in psychological interventions was modest: 71 (76 %) of participants randomized to psycho-education attended at least one counselling session, and 21 (23 %) attended all six sessions. The Median number of sessions was 2. All patients reduced drug and alcohol problems at 9 months with small within-group effect sizes. Intention-to-treat analyses indicated significant differences between ILC and TAU in mean drugs composite score (p = .018) and in PDA (p = .041) at 3 months. Aggression declined in both groups, but no differences between ILC and TAU were observed in terms of alcohol problems or aggression at any follow-up. Moderate short-term improvements in substance use were associated with randomization to Impulsive Lifestyle Counselling. The findings support the usefulness of providing psycho-education to outpatients with antisocial personality disorder. ISRCTN registry, ISRCTN67266318 , 17/7/2012.

Efficacy of gabapentin for prevention of postherpetic neuralgia: study protocol for a randomized controlled clinical trial.

PubMed

Rullán, Manuel; Bulilete, Oana; Leiva, Alfonso; Soler, Aina; Roca, Antonia; González-Bals, María José; Lorente, Patricia; Llobera, Joan

2017-01-14

Postherpetic neuralgia (PHN) is a chronic neuropathic pain that results from alterations of the peripheral nervous system in areas affected by the herpes zoster virus. The symptoms include pain, paresthesia, dysesthesia, hyperalgesia, and allodynia. Despite the availability of pharmacological treatments to control these symptoms, no treatments are available to control the underlying pathophysiology responsible for this disabling condition. Patients with herpes zoster who are at least 50 years old and have a pain score of 4 or higher on a visual analogue scale (VAS) will be recruited. The aim is to recruit 134 patients from the practices of general physicians. Participants will be randomized to receive gabapentin to a maximum of 1800 mg/day for 5 weeks or placebo. Both arms will receive 1000-mg caplets of valacyclovir three times daily for 7 days (initiated within 72 h of the onset of symptoms) and analgesics as needed. The primary outcome measure is the percentage of patients with a VAS pain score of 0 at 12 weeks from rash onset. The secondary outcomes measures are changes in quality of life (measured by the SF-12 questionnaire), sleep disturbance (measured by the Medical Outcomes Study Sleep Scale), and percentage of patients with neuropathic pain (measured by the Douleur Neuropathique in 4 Questions). Gabapentin is an anticonvulsant type of analgesic that could prevent the onset of PHN by its antihypersensitivity action in dorsal horn neurons. ISRCTN Registry identifier: ISRCTN79871784 . Registered on 2 May 2013.

Vitamin D as supplementary treatment for tuberculosis: a double-blind, randomized, placebo-controlled trial.

PubMed

Wejse, Christian; Gomes, Victor F; Rabna, Paulo; Gustafson, Per; Aaby, Peter; Lisse, Ida M; Andersen, Paul L; Glerup, Henning; Sodemann, Morten

2009-05-01

Vitamin D has been shown to be involved in the host immune response toward Mycobacterium tuberculosis. To test whether vitamin D supplementation of patients with tuberculosis (TB) improved clinical outcome and reduced mortality. We conducted a randomized, double-blind, placebo-controlled trial in TB clinics at a demographic surveillance site in Guinea-Bissau. We included 365 adult patients with TB starting antituberculosis treatment; 281 completed the 12-month follow-up. The intervention was 100,000 IU of cholecalciferol or placebo at inclusion and again 5 and 8 months after the start of treatment. The primary outcome was reduction in a clinical severity score (TBscore) for all patients with pulmonary TB. The secondary outcome was 12-month mortality. No serious adverse effects were reported; mild hypercalcemia was rare and present in both arms. Reduction in TBscore and sputum smear conversion rates did not differ among patients treated with vitamin D or placebo. Overall mortality was 15% (54 of 365) at 1 year of follow-up and similar in both arms (30 of 187 for vitamin D treated and 24 of 178 for placebo; relative risk, 1.19 [0.58-1.95]). HIV infection was seen in 36% (131 of 359): 21% (76 of 359) HIV-1, 10% (36 of 359) HIV-2, and 5% (19 of 357) HIV-1+2. Vitamin D does not improve clinical outcome among patients with TB and the trial showed no overall effect on mortality in patients with TB; it is possible that the dose used was insufficient. Clinical trial registered with www.controlled-trials.com/isrctn (ISRCTN35212132).

Benefits and challenges of using the cohort multiple randomised controlled trial design for testing an intervention for depression.

PubMed

Viksveen, Petter; Relton, Clare; Nicholl, Jon

2017-07-06

Trials which test the effectiveness of interventions compared with the status quo frequently encounter challenges. The cohort multiple randomised controlled trial (cmRCT) design is an innovative approach to the design and conduct of pragmatic trials which seeks to address some of these challenges. In this article, we report our experiences with the first completed randomised controlled trial (RCT) using the cmRCT design. This trial-the Depression in South Yorkshire (DEPSY) trial-involved comparison of treatment as usual (TAU) with TAU plus the offer of an intervention for people with self-reported long-term moderate to severe depression. In the trial, we used an existing large population-based cohort: the Yorkshire Health Study. We discuss our experiences with recruitment, attrition, crossover, data analysis, generalisability of results, and cost. The main challenges in using the cmRCT design were the high crossover to the control group and the lower questionnaire response rate among patients who refused the offer of treatment. However, the design did help facilitate efficient and complete recruitment of the trial population as well as analysable data that were generalisable to the population of interest. Attrition rates were also smaller than those reported in other depression trials. This first completed full trial using the cmRCT design testing an intervention for self-reported depression was associated with a number of important benefits. Further research is required to compare the acceptability and cost effectiveness of standard pragmatic RCT design with the cmRCT design. ISRCTN registry: ISRCTN02484593 . Registered on 7 Jan 2013.

Guided self-help cognitive behavioral intervention for VoicEs (GiVE): study protocol for a pilot randomized controlled trial.

PubMed

Hazell, Cassie M; Hayward, Mark; Cavanagh, Kate; Jones, Anna-Marie; Strauss, Clara

2016-07-26

Cognitive behavior therapy for psychosis (CBTp) is an effective intervention for people who hear distressing voices (auditory hallucinations). However, there continues to be a problem of poor access to CBTp. Constraints on health care funding require this problem to be addressed without a substantial increase in funding. One solution is to develop guided self-help forms of CBTp to improve access, and a symptom-specific focus on, for example, distressing voices (auditory verbal hallucinations) has the potential to enhance effectiveness. We term this cognitive behavior therapy for distressing voices (CBTv). This trial is an external pilot randomized controlled trial comparing the effects of 12-week guided self-help CBTv (with eight therapist support sessions) with a wait list control condition. Informed consent will be obtained from each participant. Half of the 30 participants will be randomized to receive guided self-help CBTv immediately; the remaining half will receive the intervention after a 12-week delay. All participants will continue with their usual treatment throughout the study. Outcomes will be assessed using questionnaires completed at baseline and 12 weeks postrandomization. Interviews will be offered to all those who receive therapy immediately to explore their experiences with the intervention. The outcomes of this trial, both quantitative and qualitative, will inform the design of a definitive randomized controlled trial of guided self-help CBTv. If this intervention is effective, it could help to increase access to CBT for those who hear distressing voices. ISRCTN registration number  ISRCTN77762753 . Registered on 23 July 2015.

Development of a self-managed loaded exercise programme for rotator cuff tendinopathy.

PubMed

Littlewood, Chris; Malliaras, Peter; Mawson, Sue; May, Stephen; Walters, Stephen

2013-12-01

This paper describes a self-managed loaded exercise programme which has been designed to address the pain and disability associated with rotator cuff tendinopathy. The intervention has been developed with reference to current self-management theory and with reference to the emerging benefit of loaded exercise for tendinopathy. This self-managed loaded exercise programme is being evaluated within the mixed methods SELF study (ISRCTN 84709751) which includes a pragmatic randomised controlled trial conducted within the UK National Health Service. Copyright © 2012 Chartered Society of Physiotherapy. Published by Elsevier Ltd. All rights reserved.

Effectiveness of a Web-Based Screening and Fully Automated Brief Motivational Intervention for Adolescent Substance Use: A Randomized Controlled Trial.

PubMed

Arnaud, Nicolas; Baldus, Christiane; Elgán, Tobias H; De Paepe, Nina; Tønnesen, Hanne; Csémy, Ladislav; Thomasius, Rainer

2016-05-24

Mid-to-late adolescence is a critical period for initiation of alcohol and drug problems, which can be reduced by targeted brief motivational interventions. Web-based brief interventions have advantages in terms of acceptability and accessibility and have shown significant reductions of substance use among college students. However, the evidence is sparse among adolescents with at-risk use of alcohol and other drugs. This study evaluated the effectiveness of a targeted and fully automated Web-based brief motivational intervention with no face-to-face components on substance use among adolescents screened for at-risk substance use in four European countries. In an open-access, purely Web-based randomized controlled trial, a convenience sample of adolescents aged 16-18 years from Sweden, Germany, Belgium, and the Czech Republic was recruited using online and offline methods and screened online for at-risk substance use using the CRAFFT (Car, Relax, Alone, Forget, Friends, Trouble) screening instrument. Participants were randomized to a single session brief motivational intervention group or an assessment-only control group but not blinded. Primary outcome was differences in past month drinking measured by a self-reported AUDIT-C-based index score for drinking frequency, quantity, and frequency of binge drinking with measures collected online at baseline and after 3 months. Secondary outcomes were the AUDIT-C-based separate drinking indicators, illegal drug use, and polydrug use. All outcome analyses were conducted with and without Expectation Maximization (EM) imputation of missing follow-up data. In total, 2673 adolescents were screened and 1449 (54.2%) participants were randomized to the intervention or control group. After 3 months, 211 adolescents (14.5%) provided follow-up data. Compared to the control group, results from linear mixed models revealed significant reductions in self-reported past-month drinking in favor of the intervention group in both the non-imputed (P=.010) and the EM-imputed sample (P=.022). Secondary analyses revealed a significant effect on drinking frequency (P=.037) and frequency of binge drinking (P=.044) in the non-imputation-based analyses and drinking quantity (P=.021) when missing data were imputed. Analyses for illegal drug use and polydrug use revealed no significant differences between the study groups (Ps>.05). Although the study is limited by a large drop-out, significant between-group effects for alcohol use indicate that targeted brief motivational intervention in a fully automated Web-based format can be effective to reduce drinking and lessen existing substance use service barriers for at-risk drinking European adolescents. International Standard Randomized Controlled Trial Registry: ISRCTN95538913; http://www.isrctn.com/ISRCTN95538913 (Archived by WebCite at http://www.webcitation.org/6XkuUEwBx).

The Effectiveness of Web-Based Asthma Self-Management System, My Asthma Portal (MAP): A Pilot Randomized Controlled Trial

PubMed Central

Ernst, Pierre; Bartlett, Susan J; Valois, Marie-France; Zaihra, Tasneem; Paré, Guy; Grad, Roland; Eilayyan, Owis; Perreault, Robert; Tamblyn, Robyn

2016-01-01

Background Whether Web-based technologies can improve disease self-management is uncertain. My Asthma Portal (MAP) is a Web-based self-management support system that couples evidence-based behavioral change components (self-monitoring of symptoms, physical activity, and medication adherence) with real-time monitoring, feedback, and support from a nurse case manager. Objective The aim of this study was to compare the impact of access to a Web-based asthma self-management patient portal linked to a case-management system (MAP) over 6 months compared with usual care on asthma control and quality of life. Methods A multicenter, parallel, 2-arm, pilot, randomized controlled trial was conducted with 100 adults with confirmed diagnosis of asthma from 2 specialty clinics. Asthma control was measured using an algorithm based on overuse of fast-acting bronchodilators and emergency department visits, and asthma-related quality of life was assessed using the Mini-Asthma Quality of Life Questionnaire (MAQLQ). Secondary mediating outcomes included asthma symptoms, depressive symptoms, self-efficacy, and beliefs about medication. Process evaluations were also included. Results A total of 49 individuals were randomized to MAP and 51 to usual care. Compared with usual care, participants in the intervention group reported significantly higher asthma quality of life (mean change 0.61, 95% CI 0.03 to 1.19), and the change in asthma quality of life for the intervention group between baseline and 3 months (mean change 0.66, 95% CI 0.35 to 0.98) was not seen in the control group. No significant differences in asthma quality of life were found between the intervention and control groups at 6 (mean change 0.46, 95% CI –0.12 to 1.05) and 9 months (mean change 0.39, 95% CI –0.2 to 0.98). For poor control status, there was no significant effect of group, time, or group by time. For all self-reported measures, the intervention group had a significantly higher proportion of individuals, demonstrating a minimal clinically meaningful improvement compared with the usual care group. Conclusions This study supported the use of MAP to enhance asthma quality of life but not asthma control as measured by an administrative database. Implementation of MAP beyond 6 months with tailored protocols for monitoring symptoms and health behaviors as individuals’ knowledge and self-management skills improve may result in long-term gains in asthma control. ClinicalTrial International Standard Randomized Controlled Trial Number (ISRCTN): 34326236; http://www.isrctn.com/ISRCTN34326236 (Archived by Webcite at http://www.webcitation.org/6mGxoI1R7). PMID:27908846

A Mobile Phone App Intervention Targeting Fruit and Vegetable Consumption: The Efficacy of Textual and Auditory Tailored Health Information Tested in a Randomized Controlled Trial

PubMed Central

2016-01-01

Background Mobile phone apps are increasingly used to deliver health interventions, which provide the opportunity to present health information via different communication modes. However, scientific evidence regarding the effects of such health apps is scarce. Objective In a randomized controlled trial, we tested the efficacy of a 6-month intervention delivered via a mobile phone app that communicated either textual or auditory tailored health information aimed at stimulating fruit and vegetable intake. A control condition in which no health information was given was added. Perceived own health and health literacy were included as moderators to assess for which groups the interventions could possibly lead to health behavior change. Methods After downloading the mobile phone app, respondents were exposed monthly to either text-based or audio-based tailored health information and feedback over a period of 6 months via the mobile phone app. In addition, respondents in the control condition only completed the baseline and posttest measures. Within a community sample (online recruitment), self-reported fruit and vegetable intake at 6-month follow-up was our primary outcome measure. Results In total, 146 respondents (ranging from 40 to 58 per condition) completed the study (attrition rate 55%). A significant main effect of condition was found on fruit intake (P=.049, partial η2=0.04). A higher fruit intake was found after exposure to the auditory information, especially in recipients with a poor perceived own health (P=.003, partial η2=0.08). In addition, health literacy moderated the effect of condition on vegetable intake 6 months later (P<.001, partial η2=.11). A higher vegetable intake was found for recipients with high health literacy after exposure to the textual or auditory intervention compared to the control condition (contrasts P=.07 and P=.004, respectively). In the case of relatively low health literacy, vegetable intake was the highest in the control condition (contrasts text control: P=.03; audio control: P=.04). Conclusions This study provides evidence-based insight into the effects of a mobile health app. The app seems to have the potential to change fruit and vegetable intake up to 6 months later, at least for specific groups. We found different effects for fruit and vegetable intake, respectively, suggesting that different underlying psychological mechanisms are associated with these specific behaviors. Based on our results, it seems worthwhile to investigate additional ways to increase fruit and vegetable intake in recipients with low health literacy. ClinicalTrial International Standard Randomized Controlled Trial Number (ISRCTN): 23466915; http://www.isrctn.com/ISRCTN23466915 (Archived by WebCite at http://www.webcitation.org/6hTtfSvaz) PMID:27287823

The Relaxation Exercise and Social Support Trial (RESST): a community-based randomized controlled trial to alleviate medically unexplained vaginal discharge symptoms.

PubMed

Kobeissi, Loulou; Mahfoud, Ziyad; Khoury, Brigitte; El Kak, Fayssal; Ghantous, Zeina; Khawaja, Marwan; Nakkash, Rima; Ramia, Sami; Zurayk, Huda; Araya, Ricardo; Peters, Tim J

2012-11-09

Symptoms such as medically unexplained vaginal discharge (MUVD) are common and bothersome, leading to potentially unnecessary use of resources. A community-based individually randomized controlled trial to assess the effectiveness of a relatively simple, culturally appropriate multi-component intervention on reducing reported MUVD, among women suffering from low-moderate levels of common mental distress. The setting was a socio-economically deprived, informal settlement in the southern suburbs of Beirut, Lebanon. The intervention comprised up to 12 group sessions implemented over a six-week period, each divided into a psychosocial and a relaxation exercise component. The primary outcome was self-reported MUVD, which was defined as a complaint of vaginal discharge upon ruling out reproductive tract infections (RTIs), through lab analysis. Anxiety and/or depression symptoms were the secondary outcomes for this trial. These were assessed using an Arabic validated version of the Hopkins Symptoms Checklist-25 (HSCL-25). Assessments were done at baseline and six months using face-to face interviews, pelvic examinations and laboratory tests. Women were randomized into either intervention or control group. Blinding on the intervention status was not possible for both logistic and ethical reasons, especially as knowledge of involvement in the intervention was integral to its delivery. Intent to treat analysis was used. Of 75 women randomized to the intervention, 48% reported MUVD at 6 months compared with 63% of 73 in the control group (difference of -15%, 95% confidence interval (CI) -31%, 0%, p=0.067). Adjustments for baseline imbalances and any factors relating to consent had no appreciable effect on these results. The risk of MUVD was reduced in absolute terms by 2.4% for each intervention session attended (95% CI -4.9%, 0.0%, p=0.049). While there was also marginal evidence of a beneficial effect on anxiety, there was no evidence of mediation of the effect on MUVD through measures of common mental disorders. This study confirms that MUVD is an important public health problem. While the benefits of this intervention may appear modest, the intervention offers an opportunity for women to enhance their problem-solving skills as well as use physical relaxation techniques that can help them deal with stressful in their lives. Further research is needed in a variety of contexts, for different populations and preferably involving larger randomized trials of such an intervention. * Title of trial: The Relaxation Exercise and Social Support Trial ISRCTN assigned: ISRCTN98441241 Date of assignation: 10/09/2010 Link: http://www.controlled-trials.com/ISRCTN98441241* Also registered at the Wellcome Trust register:http://www.controlled-trials.com/mrct/trial/469943/98441241.

Effectiveness of Different Web-Based Interventions to Prepare Co-Smokers of Cigarettes and Cannabis for Double Cessation: A Three-Arm Randomized Controlled Trial

PubMed Central

Haug, Severin; Sullivan, Robin; Schaub, Michael Patrick

2014-01-01

Background The relationship between tobacco and cannabis use is strong. When co-smokers try to quit only one substance, this relationship often leads to a substitution effect, that is, the increased use of the remaining substance. Stopping the use of both substances simultaneously is therefore a reasonable strategy, but co-smokers rarely report feeling ready for simultaneous cessation. Thus, the question of how co-smokers can be motivated to attempt a simultaneous cessation has arisen. To reach as many co-smokers as possible, we developed brief Web-based interventions aimed at enhancing the readiness to simultaneously quit tobacco and cannabis use. Objective Our aim was to analyze the efficacy of three different Web-based interventions designed to enhance co-smokers’ readiness to stop tobacco and cannabis use simultaneously. Methods Within a randomized trial, three brief Web-based and fully automated interventions were compared. The first intervention combined the assessment of cigarette dependence and problematic cannabis use with personalized, normative feedback. The second intervention was based on principles of motivational interviewing. As an active psychoeducational control group, the third intervention merely provided information on tobacco, cannabis, and the co-use of the two substances. The readiness to quit tobacco and cannabis simultaneously was measured before and after the intervention (both online) and 8 weeks later (online or over the phone). Secondary outcomes included the frequency of cigarette and cannabis use, as measured at baseline and after 8 weeks. Results A total of 2467 website users were assessed for eligibility based on their self-reported tobacco and cannabis co-use, and 325 participants were ultimately randomized and analyzed. For the post-intervention assessment, generalized estimating equations revealed a significant increase in the readiness to quit tobacco and cannabis in the total sample (B=.33, 95% CI 0.10-0.56, P=.006). However, this effect was not significant for the comparison between baseline and the 8-week follow-up assessment (P=.69). Furthermore, no differential effects between the interventions were found, nor were any significant intervention or time effects found on the frequency of tobacco or cannabis use. Conclusions In the new field of dual interventions for co-smokers of tobacco and cannabis, Web-based interventions can increase the short-term readiness to quit tobacco and cannabis simultaneously. The studied personalized techniques were no more effective than was psychoeducation. The analyzed brief interventions did not change the secondary outcomes, that is the frequency of tobacco and cannabis use. Trial Registration International Standard Randomized Controlled Trial Number (ISRCTN): 56326375; http://www.isrctn.com/ISRCTN56326375 (Archived by WebCite at http://www.webcitation.org/6UUWBh8u0). PMID:25486674

Efficacy of Cognitive Behavioral Therapy for Insomnia in Adolescents: A Randomized Controlled Trial with Internet Therapy, Group Therapy and A Waiting List Condition

PubMed Central

de Bruin, Eduard J.; Bögels, Susan M.; Oort, Frans J.; Meijer, Anne Marie

2015-01-01

Study Objectives: To investigate the efficacy of cognitive behavioral therapy for insomnia (CBTI) in adolescents. Design: A randomized controlled trial of CBTI in group therapy (GT), guided internet therapy (IT), and a waiting list (WL), with assessments at baseline, directly after treatment (post-test), and at 2 months follow-up. Setting: Diagnostic interviews were held at the laboratory of the Research Institute of Child Development and Education at the University of Amsterdam. Treatment for GT occurred at the mental health care center UvAMinds in Amsterdam, the Netherlands. Participants: One hundred sixteen adolescents (mean age = 15.6 y, SD = 1.6 y, 25% males) meeting DSM-IV criteria for insomnia, were randomized to IT, GT, or WL. Interventions: CBTI of 6 weekly sessions, consisted of psychoeducation, sleep hygiene, restriction of time in bed, stimulus control, cognitive therapy, and relaxation techniques. GT was conducted in groups of 6 to 8 adolescents, guided by 2 trained sleep therapists. IT was applied through an online guided self-help website with programmed instructions and written feedback from a trained sleep therapist. Measurements and Results: Sleep was measured with actigraphy and sleep logs for 7 consecutive days. Symptoms of insomnia and chronic sleep reduction were measured with questionnaires. Results showed that adolescents in both IT and GT, compared to WL, improved significantly on sleep efficiency, sleep onset latency, wake after sleep onset, and total sleep time at post-test, and improvements were maintained at follow-up. Most of these improvements were found in both objective and subjective measures. Furthermore, insomnia complaints and symptoms of chronic sleep reduction also decreased significantly in both treatment conditions compared to WL. Effect sizes for improvements ranged from medium to large. A greater proportion of participants from the treatment conditions showed high end-state functioning and clinically significant improvement after treatment and at follow-up compared to WL. Conclusions: This study is the first randomized controlled trial that provides evidence that cognitive behavioral therapy for insomnia is effective for the treatment of adolescents with insomnia, with medium to large effect sizes. There were small differences between internet and group therapy, but both treatments reached comparable endpoints. Clinical Trial Registration: This study was part of the clinical trial: Effectiveness of cognitive behavioral therapy for sleeplessness in adolescents; URL: http://www.isrctn.com/ISRCTN33922163; registration: ISRCTN33922163. Citation: de Bruin EJ, Bögels SM, Oort FJ, Meijer AM. Efficacy of cognitive behavioral therapy for insomnia in adolescents: a randomized controlled trial with internet therapy, group therapy and a waiting list condition. SLEEP 2015;38(12):1913–1926. PMID:26158889

Effectiveness of 6 Months of Tailored Text Message Reminders for Obese Male Participants in a Worksite Weight Loss Program: Randomized Controlled Trial

PubMed Central

Oh, Sohee; Steinhubl, Steven; Kim, Sohye; Bae, Woo Kyung; Han, Jong Soo; Kim, Jeong-Hyun; Lee, Keehyuck; Kim, Mi Jin

2015-01-01

Background Worksite nutrition and physical activity interventions are important to help overweight and obese employees lose weight, but costs and insufficient sustained motivation prevent the majority of these programs from succeeding. Tailored text messaging in aiding weight management has been effective in several studies, but no studies have evaluated the effect of a tailored text message service on weight loss in a worksite health promotion program. Objective We studied the efficacy of a tailored text-messaging intervention for obese male participants in a worksite weight loss program of 6 months duration. Methods The study was an unblinded, randomized controlled trial. Men with a body mass index greater than 25 kg/m2 were recruited from the Korea District Heating Corporation, the Korea Expressway Corporation, and the Korea Gas Corporation. The participants were identified by nurse managers. Participants were randomly allocated to 1 of the following 2 groups for 24 weeks: (1) intervention group, which received tailored text message reminders every other day plus 4 offline education sessions and brief counseling with monthly weight check by nurses for weight control over 6 months and (2) control group, which received the 4 offline education sessions and brief counseling with monthly weight check by nurses about weight control over 6 months. The primary outcome was the difference in weight loss at 6 months. A mixed-model repeated-measures analysis was performed to evaluate the effect of the intervention group’s weight loss compared with the control group. Results A total of 205 obese men were randomized into either the intervention (n=104) or the control group (n=101). At the end of 6 months, the intervention group (n=63) had lost 1.71 kg (95% CI –2.53 to –0.88) and the control group (n=59) had lost 1.56 kg (95% CI –2.45 to –0.66); the difference between the 2 groups was not significant (mean difference –0.15, 95% CI –1.36 to 1.07). At the end of the study, 60% (34/57) of the intervention group rated the message program as helpful for weight control and 46% (26/57) would recommend the text message service to their friends. Conclusions Tailored text message reminders did not have a significant effect on weight loss in obese men as part of a worksite weight loss program. Trial Registration International Standard Randomized Controlled Trial Number (ISRCTN): 39629189; http://www.isrctn.com/ISRCTN39629189?q=39629189&filters=&sort=&offset=1&totalResults=1&page=1&pageSize=10&searchType=basic-search (Archived by WebCite at http://www.webcitation.org/6VsFkwJH6). PMID:25648325

A Mobile Phone App Intervention Targeting Fruit and Vegetable Consumption: The Efficacy of Textual and Auditory Tailored Health Information Tested in a Randomized Controlled Trial.

PubMed

Elbert, Sarah Pietertje; Dijkstra, Arie; Oenema, Anke

2016-06-10

Mobile phone apps are increasingly used to deliver health interventions, which provide the opportunity to present health information via different communication modes. However, scientific evidence regarding the effects of such health apps is scarce. In a randomized controlled trial, we tested the efficacy of a 6-month intervention delivered via a mobile phone app that communicated either textual or auditory tailored health information aimed at stimulating fruit and vegetable intake. A control condition in which no health information was given was added. Perceived own health and health literacy were included as moderators to assess for which groups the interventions could possibly lead to health behavior change. After downloading the mobile phone app, respondents were exposed monthly to either text-based or audio-based tailored health information and feedback over a period of 6 months via the mobile phone app. In addition, respondents in the control condition only completed the baseline and posttest measures. Within a community sample (online recruitment), self-reported fruit and vegetable intake at 6-month follow-up was our primary outcome measure. In total, 146 respondents (ranging from 40 to 58 per condition) completed the study (attrition rate 55%). A significant main effect of condition was found on fruit intake (P=.049, partial η(2)=0.04). A higher fruit intake was found after exposure to the auditory information, especially in recipients with a poor perceived own health (P=.003, partial η(2)=0.08). In addition, health literacy moderated the effect of condition on vegetable intake 6 months later (P<.001, partial η(2)=.11). A higher vegetable intake was found for recipients with high health literacy after exposure to the textual or auditory intervention compared to the control condition (contrasts P=.07 and P=.004, respectively). In the case of relatively low health literacy, vegetable intake was the highest in the control condition (contrasts text control: P=.03; audio control: P=.04). This study provides evidence-based insight into the effects of a mobile health app. The app seems to have the potential to change fruit and vegetable intake up to 6 months later, at least for specific groups. We found different effects for fruit and vegetable intake, respectively, suggesting that different underlying psychological mechanisms are associated with these specific behaviors. Based on our results, it seems worthwhile to investigate additional ways to increase fruit and vegetable intake in recipients with low health literacy. International Standard Randomized Controlled Trial Number (ISRCTN): 23466915; http://www.isrctn.com/ISRCTN23466915 (Archived by WebCite at http://www.webcitation.org/6hTtfSvaz).

Côte d’Ivoire Dual Burden of Disease (CoDuBu): Study Protocol to Investigate the Co-occurrence of Chronic Infections and Noncommunicable Diseases in Rural Settings of Epidemiological Transition

PubMed Central

Eze, Ikenna C; Esse, Clémence; Bassa, Fidèle K; Koné, Siaka; Acka, Felix; Yao, Loukou; Imboden, Medea; Jaeger, Fabienne N; Schindler, Christian; Dosso, Mireille; Laubhouet-Koffi, Véronique; Kouassi, Dinard; N’Goran, Eliézer K; Utzinger, Jürg; Bonfoh, Bassirou

2017-01-01

Background Individual-level concomitance of infectious diseases and noncommunicable diseases (NCDs) is poorly studied, despite the reality of this dual disease burden for many low- and middle-income countries (LMICs). Objective This study protocol describes the implementation of a cohort and biobank aiming for a better understanding of interrelation of helminth and Plasmodium infections with NCD phenotypes like metabolic syndrome, hypertension, and diabetes. Methods A baseline cross-sectional population-based survey was conducted over one year, in the Taabo health and demographic surveillance system (HDSS) in south-central Côte d’Ivoire. We randomly identified 1020 consenting participants aged ≥18 years in three communities (Taabo-Cité, Amani-Ménou, and Tokohiri) reflecting varying stages of epidemiological transition. Participants underwent health examinations consisting of NCD phenotyping (anthropometry, blood pressure, renal function, glycemia, and lipids) and infectious disease testing (infections with soil-transmitted helminths, schistosomes, and Plasmodium). Individuals identified to have elevated blood pressure, glucose, lipids, or with infections were referred to the central/national health center for diagnostic confirmation and treatment. Aliquots of urine, stool, and venous blood were stored in a biobank for future exposome/phenome research. In-person interviews on sociodemographic attributes, risk factors for infectious diseases and NCDs, medication, vaccinations, and health care were also conducted. Appropriate statistical techniques will be applied in exploring the concomitance of infectious diseases and NCDs and their determinants. Participants’ consent for follow-up contact was obtained. Results Key results from this baseline study, which will be published in peer-reviewed literature, will provide information on the prevalence and co-occurrence of infectious diseases, NCDs, and their risk factors. The Taabo HDSS consists of rural and somewhat more urbanized areas, allowing for comparative studies at different levels of epidemiological transition. An HDSS setting is ideal as a basis for longitudinal studies since their sustainable field work teams hold close contact with the local population. Conclusions The collaboration between research institutions, public health organizations, health care providers, and staff from the Taabo HDSS in this study assures that the synthesized evidence will feed into health policy towards integrated infectious disease-NCD management. The preparation of health systems for the dual burden of disease is pressing in low- and middle-income countries. The established biobank will strengthen the local research capacity and offer opportunities for biomarker studies to deepen the understanding of the cross-talk between infectious diseases and NCDs. Trial Registration International Standard Randomized Controlled Trials Number (ISRCTN): 87099939; http://www.isrctn.com/ISRCTN87099939 (Archived by WebCite at http://www.webcitation.org/6uLEs1EsX) PMID:29079553

Effectiveness of a Mobile Phone App for Adults That Uses Physical Activity as a Tool to Manage Cigarette Craving After Smoking Cessation: A Study Protocol for a Randomized Controlled Trial.

PubMed

Hassandra, Mary; Lintunen, Taru; Kettunen, Tarja; Vanhala, Mauno; Toivonen, Hanna-Mari; Kinnunen, Kimmo; Heikkinen, Risto

2015-10-22

Results from studies on the effects of exercise on smoking-related variables have provided strong evidence that physical activity acutely reduces cigarette cravings. Mobile technology may provide some valuable tools to move from explanatory randomized controlled trials to pragmatic randomized controlled trials by testing the acute effectiveness of exercise on quitters under real-life conditions. An mHealth app was developed to be used as a support tool for quitters to manage their cigarette cravings. The primary aim of this paper is to present the protocol of a study examining the effectiveness of the Physical over smoking app (Ph.o.S) by comparing the point prevalence abstinence rate of a group of users to a comparator group during a 6-month follow-up period. After initial Web-based screening, eligible participants are recruited to attend a smoking cessation program for 3 weeks to set a quit smoking date. Fifty participants who succeed in quitting will be randomly allocated to the comparator and experimental groups. Both groups will separately have 1 more counseling session on how to manage cravings. In this fourth session, the only difference in treatment between the groups is that the experimental group will have an extra 10-15 minutes of guidance on how to use the fully automated Ph.o.S app to manage cravings during the follow-up period. Data will be collected at baseline, as well as before and after the quit day, and follow-up Web-based measures will be collected for a period of 6 months. The primary efficacy outcome is the 7-day point prevalence abstinence rate, and secondary efficacy outcomes are number of relapses and cravings, self-efficacy of being aware of craving experience, self-efficacy in managing cravings, and power of control in managing cravings. Recruitment for this project commenced in December 2014, and proceeded until May 2015. Follow-up data collection has commenced and will be completed by the end of December 2015. If the Ph.o.S app is shown to be effective, the study will provide evidence for the use of the app as a support tool for people who are trying to manage cravings during smoking cessation programs. It is anticipated that the results of the study will provide knowledge of how physical activity affects cigarette craving in real-life situations and inform the development and delivery of relapse prevention in smoking cessation treatment. International Standard Randomized Controlled Trial Number (ISRCTN): ISRCTN55259451; http://www.controlled-trials.com/ISRCTN55259451 (Archived by WebCite at http://www.webcitation.org/6cKF2mzEI).

Short Text Messages to Encourage Adherence to Medication and Follow-up for People With Psychosis (Mobile.Net): Randomized Controlled Trial in Finland

PubMed Central

Kannisto, Kati Anneli; Vahlberg, Tero; Hätönen, Heli; Adams, Clive E

2017-01-01

Background A text messaging service (short message service [SMS]) has the potential to target large groups of people with long-term illnesses such as serious mental disorders, who may have difficulty with treatment adherence. Robust research on the impact of mobile technology interventions for these patients remains scarce. Objective The main objective of our study was to investigate the impact of individually tailored short text messages on the rate of psychiatric hospital readmissions, health care service use, and clinical outcomes. In addition, we analyzed treatment costs. Methods Between September 2011 and November 2012, we randomly assigned 1139 people to a tailored text message intervention (n=569) or usual care (n=570). Participants received semiautomated text messages for up to 12 months or usual care. The primary outcome, based on routinely collected health register data, was patient readmission into a psychiatric hospital during a 12-month follow-up period. Secondary outcomes were related to other service use, coercion, medication, adverse events, satisfaction, social functioning, quality of life, and economic factors (cost analysis). Results There was 98.24% (1119/1139) follow-up at 12 months. Tailored mobile telephone text messages did not reduce the rate of hospital admissions (242/563, 43.0% of the SMS group vs 216/556, 38.8% of the control group; relative risk 1.11; 95% CI 0.92-1.33; P=.28), time between hospitalizations (mean difference 7.0 days 95% CI –8.0 to 24.0; P=.37), time spent in a psychiatric hospital during the year (mean difference 2.0 days 95% CI –2.0 to 7.0; P=.35), or other service outcomes. People who received text messages were less disabled, based on Global Assessment Scale scores at the time of their readmission, than those who did not receive text messages (odds ratio 0.68; 95% CI 0.47-0.97; P=.04). The costs of treatment were higher for people in the SMS group than in the control group (mean €10,103 vs €9210, respectively, P<.001). Conclusions High-grade routinely collected data can provide clear outcomes for pragmatic randomized trials. SMS messaging tailored with the input of each individual patient did not decrease the rate of psychiatric hospital visits after the 12 months of follow-up. Although there may have been other, more subtle effects, the results of these were not evident in outcomes of agreed importance to clinicians, policymakers, and patients and their families. Trial Registration International Standard Randomized Controlled Trial Number (ISRCTN): 27704027; http://www.isrctn.com/ISRCTN27704027 (Archived by WebCite at http://www.webcitation.org/6rVzZrbuz). PMID:28701292

Are Mental Health Effects of Internet Use Attributable to the Web-Based Content or Perceived Consequences of Usage? A Longitudinal Study of European Adolescents.

PubMed

Hökby, Sebastian; Hadlaczky, Gergö; Westerlund, Joakim; Wasserman, Danuta; Balazs, Judit; Germanavicius, Arunas; Machín, Núria; Meszaros, Gergely; Sarchiapone, Marco; Värnik, Airi; Varnik, Peeter; Westerlund, Michael; Carli, Vladimir

2016-07-13

Adolescents and young adults are among the most frequent Internet users, and accumulating evidence suggests that their Internet behaviors might affect their mental health. Internet use may impact mental health because certain Web-based content could be distressing. It is also possible that excessive use, regardless of content, produces negative consequences, such as neglect of protective offline activities. The objective of this study was to assess how mental health is associated with (1) the time spent on the Internet, (2) the time spent on different Web-based activities (social media use, gaming, gambling, pornography use, school work, newsreading, and targeted information searches), and (3) the perceived consequences of engaging in those activities. A random sample of 2286 adolescents was recruited from state schools in Estonia, Hungary, Italy, Lithuania, Spain, Sweden, and the United Kingdom. Questionnaire data comprising Internet behaviors and mental health variables were collected and analyzed cross-sectionally and were followed up after 4 months. Cross-sectionally, both the time spent on the Internet and the relative time spent on various activities predicted mental health (P<.001), explaining 1.4% and 2.8% variance, respectively. However, the consequences of engaging in those activities were more important predictors, explaining 11.1% variance. Only Web-based gaming, gambling, and targeted searches had mental health effects that were not fully accounted for by perceived consequences. The longitudinal analyses showed that sleep loss due to Internet use (ß=.12, 95% CI=0.05-0.19, P=.001) and withdrawal (negative mood) when Internet could not be accessed (ß=.09, 95% CI=0.03-0.16, P<.01) were the only consequences that had a direct effect on mental health in the long term. Perceived positive consequences of Internet use did not seem to be associated with mental health at all. The magnitude of Internet use is negatively associated with mental health in general, but specific Web-based activities differ in how consistently, how much, and in what direction they affect mental health. Consequences of Internet use (especially sleep loss and withdrawal when Internet cannot be accessed) seem to predict mental health outcomes to a greater extent than the specific activities themselves. Interventions aimed at reducing the negative mental health effects of Internet use could target its negative consequences instead of the Internet use itself. International Standard Randomized Controlled Trial Number (ISRCTN): 65120704; http://www.isrctn.com/ISRCTN65120704?q=&filters=recruitmentCountry:Lithuania&sort=&offset= 5&totalResults=32&page=1&pageSize=10&searchType=basic-search (Archived by WebCite at http://www.webcitation/abcdefg).

Are Mental Health Effects of Internet Use Attributable to the Web-Based Content or Perceived Consequences of Usage? A Longitudinal Study of European Adolescents

PubMed Central

Hadlaczky, Gergö; Westerlund, Joakim; Wasserman, Danuta; Balazs, Judit; Germanavicius, Arunas; Machín, Núria; Meszaros, Gergely; Sarchiapone, Marco; Värnik, Airi; Varnik, Peeter; Westerlund, Michael; Carli, Vladimir

2016-01-01

Background Adolescents and young adults are among the most frequent Internet users, and accumulating evidence suggests that their Internet behaviors might affect their mental health. Internet use may impact mental health because certain Web-based content could be distressing. It is also possible that excessive use, regardless of content, produces negative consequences, such as neglect of protective offline activities. Objective The objective of this study was to assess how mental health is associated with (1) the time spent on the Internet, (2) the time spent on different Web-based activities (social media use, gaming, gambling, pornography use, school work, newsreading, and targeted information searches), and (3) the perceived consequences of engaging in those activities. Methods A random sample of 2286 adolescents was recruited from state schools in Estonia, Hungary, Italy, Lithuania, Spain, Sweden, and the United Kingdom. Questionnaire data comprising Internet behaviors and mental health variables were collected and analyzed cross-sectionally and were followed up after 4 months. Results Cross-sectionally, both the time spent on the Internet and the relative time spent on various activities predicted mental health (P<.001), explaining 1.4% and 2.8% variance, respectively. However, the consequences of engaging in those activities were more important predictors, explaining 11.1% variance. Only Web-based gaming, gambling, and targeted searches had mental health effects that were not fully accounted for by perceived consequences. The longitudinal analyses showed that sleep loss due to Internet use (ß=.12, 95% CI=0.05-0.19, P=.001) and withdrawal (negative mood) when Internet could not be accessed (ß=.09, 95% CI=0.03-0.16, P<.01) were the only consequences that had a direct effect on mental health in the long term. Perceived positive consequences of Internet use did not seem to be associated with mental health at all. Conclusions The magnitude of Internet use is negatively associated with mental health in general, but specific Web-based activities differ in how consistently, how much, and in what direction they affect mental health. Consequences of Internet use (especially sleep loss and withdrawal when Internet cannot be accessed) seem to predict mental health outcomes to a greater extent than the specific activities themselves. Interventions aimed at reducing the negative mental health effects of Internet use could target its negative consequences instead of the Internet use itself. Trial Registration International Standard Randomized Controlled Trial Number (ISRCTN): 65120704; http://www.isrctn.com/ISRCTN65120704?q=&filters=recruitmentCountry:Lithuania&sort=&offset= 5&totalResults=32&page=1&pageSize=10&searchType=basic-search (Archived by WebCite at http://www.webcitation/abcdefg) PMID:27417665

A longitudinal study of suicidal ideation among homeless, mentally ill individuals.

PubMed

Noël, François; Moniruzzaman, Akm; Somers, Julian; Frankish, Jim; Strehlau, Verena; Schütz, Christian; Krausz, Michael

2016-01-01

Previous cross-sectional studies have indicated that homeless individuals may present with high rates of suicidal ideation, which are strongly associated with completed suicide. We conducted the first known longitudinal study of suicidal ideation in the homeless. We used data collected over 24 months in the Vancouver At Home project (N = 497), comprised two randomized-controlled trials of housing interventions for homeless individuals with mental disorders. Presence of suicidal ideation was determined using the Colorado symptom index. Suicidal ideation significantly decreased over time [odds ratio (OR) = 0.31 at 24 months, 95 % confidence interval (CI) 0.21-0.46]. Baseline diagnoses of mood (OR = 2.18, 95 % CI 1.48-3.21) and anxiety disorders (OR = 2.05, 95 % CI 1.42-2.97), as well as depressive mood (OR = 2.52, 95 % CI 1.90-3.33), use of any substance (OR = 1.59, 95 % CI 1.09-2.32), and polysubstance use (OR = 1.90, 95 % CI 1.40-2.60) were significantly associated with suicidal ideation in the multivariate model. Baseline diagnosis of a psychotic disorder (protective effect), daily substance use, intravenous drug use, recent arrest, multiple physical illnesses and history of traumatic brain injury were significantly associated with suicidal ideation in the unadjusted model only. Interventions targeting depressive symptoms and substance use could help decrease suicide risk in homeless individuals. Mental health services need to be tailored to address the complex needs of socially marginalized individuals. Current controlled trials: ISRCTN57595077 (Vancouver At Home study: Housing First plus Assertive Community Treatment versus congregate housing plus supports versus treatment as usual) and ISRCTN66721740 (Vancouver At Home study: Housing first plus intensive case management versus treatment as usual). Assigned 9 Oct. 2012.

Laparoscopic adjustable gastric bandings: a prospective randomized study of 400 operations performed with 2 different devices.

PubMed

Gravante, Gianpiero; Araco, Antonino; Araco, Francesco; Delogu, Daniela; De Lorenzo, Antonino; Cervelli, Valerio

2007-10-01

To evaluate potential differences between 2 devices used to perform laparoscopic adjustable gastric bandings (the Swedish adjustable gastric band and the Lap-Band). The following groups were considered eligible: (1) patients with a body mass index (calculated as weight in kilograms divided by height in meters squared) of greater than 40; (2) patients with a body mass index between 35 and 40, with associated comorbidities; and (3) patients with a body mass index of greater than 60 who could not undergo derivative procedures. We recruited 400 patients. The mean +/- SD body mass index decreased to 40.6 +/- 3.0 after the first year and to 35.2 +/- 7.0 after 2 years. The average excess weight loss reduction was 48.2% after 1 year and 56.0% after 2 years. The excess weight loss reduction was inversely related to the initial weight: patients with an estimated weight excess of 50 kg or less (108 patients [27.0%]) had an excess weight loss reduction of 55% after 2 years; those with a weight excess of greater than 50 kg (292 patients [73.0%]) had an excess weight loss reduction of 44% (P = .004). We recorded 1 death (0.2%). Transient gastric occlusions (24 patients [6.0%]) and slippages (12 patients [3.0%]) were the most common complications. The devices used (Swedish adjustable gastric band and Lap-Band) were similar in terms of correction of obesity and morbidity. Laparoscopic adjustable gastric banding is a safe and feasible technique with specific indications in moderately obese patients and, secondarily, in highly obese patients who are unfit for more invasive techniques. No differences were found among the devices examined. isrctn.org Identifier: ISRCTN22839090.

Effects of a randomized controlled intervention trial on return to work and health care utilization after long-term sickness absence.

PubMed

Momsen, Anne-Mette H; Stapelfeldt, Christina Malmose; Nielsen, Claus Vinther; Nielsen, Maj Britt D; Aust, Birgit; Rugulies, Reiner; Jensen, Chris

2016-11-09

The aim of the RCT study was to investigate if the effect of a multidisciplinary intervention on return to work (RTW) and health care utilization differed by participants' self-reported health status at baseline, defined by a) level of somatic symptoms, b) health anxiety and c) self-reported general health. A total of 443 individuals were randomized to the intervention (n = 301) or the control group (n = 142) and responded to a questionnaire measuring health status at baseline. Participants were followed in registries measuring RTW and health care utilization. Relative risk (RR) and odds ratio (OR) were used as measures of associations. Results were adjusted for gender, age, educational level, work ability and previous sick leave. Among all responders we found no effect of the intervention on RTW. Among participants with low health anxiety, the one-year probability of RTW was lower in the intervention than in the control group (RR = 0.79 95 % CI 0.68-0.93), but for those with high health anxiety there was no difference between the groups (RR = 1.15 95 % CI 0.84-1.57). Neither general health nor somatic symptoms modified the effect of the intervention on RTW. The intervention had no effect on health care utilization. The multidisciplinary intervention did not facilitate RTW or decrease health care utilization compared to ordinary case management in subgroups with multiple somatic symptoms, health anxiety or low self-rated health. However, the intervention resulted in a reduced chance of RTW among participants with low health anxiety levels. ISRCTN43004323 , and ISRCTN51445682.

COgnitive behavioural therapy versus standardised medical care for adults with Dissociative non-Epileptic Seizures (CODES): statistical and economic analysis plan for a randomised controlled trial.

PubMed

Robinson, Emily J; Goldstein, Laura H; McCrone, Paul; Perdue, Iain; Chalder, Trudie; Mellers, John D C; Richardson, Mark P; Murray, Joanna; Reuber, Markus; Medford, Nick; Stone, Jon; Carson, Alan; Landau, Sabine

2017-06-06

Dissociative seizures (DSs), also called psychogenic non-epileptic seizures, are a distressing and disabling problem for many patients in neurological settings with high and often unnecessary economic costs. The COgnitive behavioural therapy versus standardised medical care for adults with Dissociative non-Epileptic Seizures (CODES) trial is an evaluation of a specifically tailored psychological intervention with the aims of reducing seizure frequency and severity and improving psychological well-being in adults with DS. The aim of this paper is to report in detail the quantitative and economic analysis plan for the CODES trial, as agreed by the trial steering committee. The CODES trial is a multicentre, pragmatic, parallel group, randomised controlled trial performed to evaluate the clinical effectiveness and cost-effectiveness of 13 sessions of cognitive behavioural therapy (CBT) plus standardised medical care (SMC) compared with SMC alone for adult outpatients with DS. The objectives and design of the trial are summarised, and the aims and procedures of the planned analyses are illustrated. The proposed analysis plan addresses statistical considerations such as maintaining blinding, monitoring adherence with the protocol, describing aspects of treatment and dealing with missing data. The formal analysis approach for the primary and secondary outcomes is described, as are the descriptive statistics that will be reported. This paper provides transparency to the planned inferential analyses for the CODES trial prior to the extraction of outcome data. It also provides an update to the previously published trial protocol and guidance to those conducting similar trials. ISRCTN registry ISRCTN05681227 (registered on 5 March 2014); ClinicalTrials.gov NCT02325544 (registered on 15 December 2014).

Evaluation of an interaction-skills training for reducing the burden of family caregivers of patients with severe mental illness: a pre-posttest design.

PubMed

Gharavi, Yasmin; Stringer, Barbara; Hoogendoorn, Adriaan; Boogaarts, Jan; Van Raaij, Bas; Van Meijel, Berno

2018-03-27

Family members who care for patients with severe mental illness experience emotional distress and report a higher incidence of mental illness than those in the general population. They report feeling inadequately prepared to provide the necessary practical and emotional support for these patients. The MAT training, an Interaction-Skills Training program (IST) for caregivers, was developed to meet those needs. This study used a single-arm pretest-posttest design to examine the impact of the training on caregivers' sense of competence (self-efficacy) and burden. One hundred family caregivers recruited from three mental health institutions participated in the training. Burden was assessed using the Involvement Evaluation Questionnaire, and self-efficacy using the Self-Efficacy Questionnaire. Analysis of variance with repeated measures was used to investigate whether participation in the training changed the level of family caregivers' burden and self-efficacy. Pearson's correlation was used to examine the relationships between self-efficacy and burden. Our results indicate that, after the training, self-efficacy increased significantly over time (p < 0.001) and that burden decreased significantly (p < 0.001). However, the results could not demonstrate the expected association between an increase of self-efficacy and decrease of burden. Caregivers expressed high appreciation for the training. After following the IST program, family caregivers of patients with severe mental illness experienced a greater sense of competence and a significant decrease in burden. The training was greatly appreciated and satisfied caregivers' need to acquire the skills required in complex caregiving situations. This study was retrospectively registered (14/01/2018) in the ISRCTN registry with study ID ISRCTN44495131 .

Continuous glucose monitoring detected hypoglycaemia in the Treating to Target in Type 2 Diabetes Trial (4-T).

PubMed

Levy, J C; Davies, M J; Holman, R R

2017-09-01

Hypoglycaemia is a significant risk in insulin treated type 2 diabetes and has been associated with future risk of cardiovascular events. We compared the frequency of low-glucose events using continuous glucose monitoring (CGM) with that of self-reported hypoglycemic events at the end of the first and third years of the Treating to Target in Type 2 Diabetes Trial (4-T), which compared biphasic, prandial and basal insulin regimens added to sulfonylurea and metformin. CGM using a Medtronic Gold system was performed in a subgroup of 4-T participants. CGM detected low-glucose events were defined at thresholds of ≤3.0 (CGM3.0) and ≤2.2 (CGM2.2) mmol/l. Of the 110 participants, 106 and 70 had CGM analysable data at the end of years 1 and 3 respectively. In both years, the frequency of CGM detected low glucose events was several fold higher than that of self-reported hypoglycaemia (symptoms with blood glucose less than 3.1mmol/l [<56mg/dl]). At the end of the first year, CGM3.0 and CGM2.2 mean (95%CI) event frequencies, expressed at events per participant per year, were 120 (85, 155) and 41 (21, 61) compared with 17 (8, 29) self-reported events during CGM, each p=0.001. The disparity at the end of the third year was similar. These data demonstrate the likely under-reporting of hypoglycaemia and of potential hypoglycaemia unawareness in clinical trials. The clinical implications of these findings need to be explored further (ISRCTN No ISRCTN51125379). Copyright © 2017. Published by Elsevier B.V.

A randomised controlled trial on hypnotherapy for irritable bowel syndrome: design and methodological challenges (the IMAGINE study).

PubMed

Flik, Carla E; van Rood, Yanda R; Laan, Wijnand; Smout, André Jpm; Weusten, Bas Lam; Whorwell, Peter J; de Wit, Niek J

2011-12-20

Irritable Bowel Syndrome (IBS) is a common gastro-intestinal disorder in primary and secondary care, characterised by abdominal pain, discomfort, altered bowel habits and/or symptoms of bloating and distension. In general the efficacy of drug therapies is poor. Hypnotherapy as well as Cognitive Behaviour Therapy and short Psychodynamic Therapy appear to be useful options for patients with refractory IBS in secondary care and are cost-effective, but the evidence is still limited. The IMAGINE-study is therefore designed to assess the overall benefit of hypnotherapy in IBS as well as comparing the efficacy of individual versus group hypnotherapy in treating this condition. The design is a randomised placebo-controlled trial. The study group consists of 354 primary care and secondary care patients (aged 18-65) with IBS (Rome-III criteria). Patients will be randomly allocated to either 6 sessions of individual hypnotherapy, 6 sessions of group hypnotherapy or 6 sessions of educational supportive therapy in a group (placebo), with a follow up of 9 months post treatment for all patients. Ten hospitals and four primary care psychological practices in different parts of The Netherlands will collaborate in this study. The primary efficacy parameter is the responder rate for adequate relief of IBS symptoms. Secondary efficacy parameters are changes in the IBS symptom severity, quality of life, cognitions, psychological complaints, self-efficacy as well as direct and indirect costs of the condition. Hypnotherapy is expected to be more effective than the control therapy, and group hypnotherapy is expected not to be inferior to individual hypnotherapy. If hypnotherapy is effective and if there is no difference in efficacy between individual and group hypnotherapy, this group form of treatment could be offered to more IBS patients, at lower costs. ISRCTN: ISRCTN22888906.

Clinical correlates of vitamin D deficiency in established psychosis.

PubMed

Lally, J; Gardner-Sood, P; Firdosi, M; Iyegbe, C; Stubbs, B; Greenwood, K; Murray, R; Smith, S; Howes, O; Gaughran, F

2016-03-22

Suboptimal vitamin D levels have been identified in populations with psychotic disorders. We sought to explore the relationship between vitamin D deficiency, clinical characteristics and cardiovascular disease risk factors among people with established psychosis. Vitamin D levels were measured in 324 community dwelling individuals in England with established psychotic disorders, along with measures of mental health, cardiovascular risk and lifestyle choices. Vitamin D deficiency was defined as serum 25-hydroxyvitamin D (25-OHD) levels below 10 ng/ml (equivalent to <25 nmol/L) and "sufficient" Vitamin D as above 30 ng/ml (>50 nmol/L). The mean 25-OHD serum level was 12.4 (SD 7.3) ng/ml, (range 4.0-51.7 ng/ml). Forty nine percent (n = 158) were vitamin D deficient, with only 14 % (n = 45) meeting criteria for sufficiency. Accounting for age, gender, ethnicity and season of sampling, serum 25-OHD levels were negatively correlated with waist circumference (r = -0.220, p < 0.002), triglycerides (r = -0.160, p = 0.024), total cholesterol (r = -0.144, p = 0.043), fasting glucose (r = -0.191, p = 0.007), HbA1c (r = -0.183, p = 0.01), and serum CRP levels (r = -0.211, p = 0.003) and were linked to the presence of metabolic syndrome. This is the largest cross sectional study of serum 25-OHD levels in community dwelling individuals with established psychosis, indicating a high level of vitamin D deficiency. Lower vitamin D levels are associated with increased cardiovascular disease risk factors and in particular metabolic syndrome. Further research is needed to define appropriate protocols for vitamin D testing and supplementation in practice to see if this can improve cardiovascular disease risk. ISRCTN number is ISRCTN58667926 Date of registration: 23/04/2010.

Treatment of Fabry disease: outcome of a comparative trial with agalsidase alfa or beta at a dose of 0.2 mg/kg.

PubMed

Vedder, Anouk C; Linthorst, Gabor E; Houge, Gunnar; Groener, Johannna E M; Ormel, Els E; Bouma, Berto J; Aerts, Johannes M F G; Hirth, Asle; Hollak, Carla E M

2007-07-11

Two different enzyme preparations, agalsidase alfa (Replagal(TM), Shire) and beta (Fabrazyme(TM), Genzyme), are registered for treatment of Fabry disease. We compared the efficacy of and tolerability towards the two agalsidase preparations administered at identical protein dose in a randomized controlled open label trial. Thirty-four Fabry disease patients were treated with either agalsidase alfa or agalsidase beta at equal dose of 0.2 mg/kg biweekly. Primary endpoint was reduction in left ventricular mass after 12 and 24 months of treatment. Other endpoints included occurrence of treatment failure (defined as progression of cardiac, renal or cerebral disease), glomerular filtration rate, pain, anti-agalsidase antibodies, and globotriaosylceramide levels in plasma and urine. After 12 and 24 months of treatment no reduction in left ventricular mass was seen, which was not different between the two treatment groups. Also, no differences in glomerular filtration rate, pain and decline in globotriaosylceramide levels were found. Antibodies developed only in males (4/8 in the agalsidase alfa group and 6/8 in the agalsidase beta group). Treatment failure within 24 months of therapy was seen in 8/34 patients: 6 male patients (3 in each treatment group) and 2 female patients (both agalsidase alfa). The occurrence of treatment failures did not differ between the two treatment groups; chi(2) = 0.38 p = 0.54. Our study revealed no difference in reduction of left ventricular mass or other disease parameters after 12 and 24 months of treatment with either agalsidase alfa or beta at a dose of 0.2 mg/kg biweekly. Treatment failure occurred frequently in both groups and seems related to age and severe pre-treatment disease. International Standard Randomized Clinical Trial ISRCTN45178534 [http://www.controlled-trials.com/ISRCTN45178534].

Peritoneal drainage or laparotomy for neonatal bowel perforation? A randomized controlled trial.

PubMed

Rees, Clare M; Eaton, Simon; Kiely, Edward M; Wade, Angie M; McHugh, Kieran; Pierro, Agostino

2008-07-01

To determine whether primary peritoneal drainage improves survival and outcome of extremely low birth weight (ELBW) infants with intestinal perforation. Optimal surgical management of ELBW infants with intestinal perforation is unknown. An international multicenter randomized controlled trial was performed between 2002 and 2006. Inclusion criteria were birthweight >or=1000 g and pneumoperitoneum on x-ray (necrotizing enterocolitis or isolated perforation). Patients were randomized to peritoneal drain or laparotomy, minimizing differences in weight, gestation, ventilation, inotropes, platelets, country, and on-site surgical facilities. Patients randomized to drain were allowed to have a delayed laparotomy after at least 12 hours of no clinical improvement. Sixty-nine patients were randomized (35 drain, 34 laparotomy); 1 subsequently withdrew consent. Six-month survival was 18/35 (51.4%) with a drain and 21/33 (63.6%) with laparotomy (P = 0.3; difference 12% 95% CI, -11, 34%). Cox regression analysis showed no significant difference between groups (hazard ratio for primary drain 1.6; P = 0.3; 95% CI, 0.7-3.4). Delayed laparotomy was performed in 26/35 (74%) patients after a median of 2.5 days (range, 0.4-21) and did not improve 6-month survival compared with primary laparotomy (relative risk of mortality 1.4; P = 0.4; 95% CI, 0.6-3.4). Drain was effective as a definitive treatment in only 4/35 (11%) surviving neonates, the rest either had a delayed laparotomy or died. Seventy-four percent of neonates treated with primary peritoneal drainage required delayed laparotomy. There were no significant differences in outcomes between the 2 randomization groups. Primary peritoneal drainage is ineffective as either a temporising measure or definitive treatment. If a drain is inserted, a timely "rescue" laparotomy should be considered. Trial registration number ISRCTN18282954; http://isrctn.org/

The effectiveness of treatment for Severe Acute Malnutrition (SAM) delivered by community health workers compared to a traditional facility based model.

PubMed

Alvarez Morán, J L; Alé, G B Franck; Charle, P; Sessions, N; Doumbia, S; Guerrero, S

2018-03-27

In most health systems, Community Health Workers (CHWs) identify and screen for severe acute malnutrition (SAM) in the community. This study aimed to investigate the potential of integrating SAM identification and treatment delivered by CHWs, in order to improve the coverage of SAM treatment services. This multicentre, randomised intervention study was conducted in Kita, Southwest Mali between February 2015 and February 2016. Treatment for uncomplicated SAM was provided in health facilities in the control area, and by Community Health Workers and health facilities in the intervention area. Clinical outcomes (cure, death and defaulter ratios), treatment coverage and quality of care were examined in both the control and intervention group. Six hundred ninety nine children were admitted to the intervention group and 235 children to the control group. The intervention group reported cure ratios of 94.2% compared to 88.6% in the control group (risk ratio 1.07 [95% CI 1.01; 1.13]). Defaulter ratios were twice as high in the control group compared to the intervention group (10.8% vs 4.5%; RR 0.42 [95% CI 0.25; 0.71]). Differences in mortality ratios were not statistically significant (0.9% in the intervention group compared to 0.8% in the control group). Coverage rates in December 2015 were 86.7% in intervention group compared to 41.6% in the control (p < 0.0001). With minimal training, CHWs are able to appropriately treat SAM in the community. Allowing CHWs to treat SAM reduces defaulter ratios without compromising treatment outcomes and can lead to improved access to treatment. Retrospectively registered in ISRCTN Register with ISRCTN33578874 on March 7th 2018.

The experience of adolescents participating in a randomised clinical trial in the field of mental health: a qualitative study.

PubMed

Midgley, Nick; Isaacs, Danny; Weitkamp, Katharina; Target, Mary

2016-07-28

This descriptive study aimed to investigate adolescents' motivations for participating in a randomised controlled trial (RCT), to explore the understanding that the young people had regarding a number of aspects of the trial design, to examine whether or not they found participation in the trial to be acceptable and what affected this, and to identify whether and how the young people felt that their participation in the RCT impacted on their experience of therapy and on therapeutic change. Seventy-six adolescents who were taking part in a large-scale RCT to evaluate the clinical and cost effectiveness of psychological therapies for depression were interviewed at two time-points after completing therapy. The semi-structured interviews, which included a focus on the young people's experience of the research study, were analysed using framework analysis. The vast majority of adolescents found it acceptable to participate in the clinical trial, and many agreed to participate for reasons of 'conditional altruism'. However consent was often given without great understanding of the key elements of the trial, including the difference between treatment arms and the randomisation process. Although the adolescents were largely positive about their experiences from taking part, the study raises questions about whether clinical outcomes may be influenced by participation in the research elements of the trial. Although adolescents are under-represented in clinical trials, those who do participate are generally positive about the experience; however, careful thought needs to be given to key elements of the trial design and the potential impact of the research participation on clinical outcomes. ISRCTN registry, ISRCTN83033550 . Registered on 15 October 2009.

Testing a counselling intervention in antenatal care for women experiencing partner violence: a study protocol for a randomized controlled trial in Johannesburg, South Africa.

PubMed

Pallitto, Christina; García-Moreno, Claudia; Stöeckl, Heidi; Hatcher, Abigail; MacPhail, Catherine; Mokoatle, Keneoue; Woollett, Nataly

2016-11-05

Intimate partner violence (IPV) during or before pregnancy is associated with many adverse health outcomes. Pregnancy-related complications or poor infant health outcomes can arise from direct trauma as well as physiological effects of stress, both of which impact maternal health and fetal growth and development. Antenatal care can be a key entry point within the health system for many women, particularly in low-resource settings. Interventions to identify violence during pregnancy and offer women support and counselling may reduce the occurrence of violence and mitigate its consequences. Following a formative research phase, a randomized controlled trial will be conducted to test a nurse-led empowerment counselling intervention, originally developed for high-income settings and adapted for urban South Africa. The primary outcome is reduction of partner violence, and secondary outcomes include improvement in women's mental health, safety and self-efficacy. The study aims to recruit 504 pregnant women from three antenatal clinics in Johannesburg who will be randomized to the nurse-led empowerment arm (two 30-min counselling sessions) or enhanced control condition (a referral list) to determine whether participants in the intervention arm have better outcomes as compared to the those in the control arm. This research will provide much needed evidence on whether a short counselling intervention delivered by nurses is efficacious and feasible in low resource settings that have high prevalence of IPV and HIV. The study was registered in the South African Clinical Trials Registry (DOH-27-0414-4720) on 11 August 2014 and in the ISRCTN Registry ( ISRCTN35969343 ) on 23 May 2016).

Effect of short-term hazelnut consumption on DNA damage and oxidized LDL in children and adolescents with primary hyperlipidemia: a randomized controlled trial.

PubMed

Guaraldi, Federica; Deon, Valeria; Del Bo', Cristian; Vendrame, Stefano; Porrini, Marisa; Riso, Patrizia; Guardamagna, Ornella

2018-07-01

Children with primary hyperlipidemia are prone to develop premature atherosclerosis, possibly associated with increased oxidative stress. Nutritional therapy is the primary strategy in the treatment of hyperlipidemia and associated conditions. Dietary interventions with bioactive-rich foods, such as nuts, may contribute to the modulation of both lipid profile and the oxidative/antioxidant status. Our study aimed to assess the impact of a dietary intervention with hazelnuts on selected oxidative stress markers in children and adolescents with primary hyperlipidemia. A single-blind, 8-week, randomized, controlled, three-arm, parallel-group study was performed. Children and adolescents diagnosed with primary hyperlipidemia (n=60) received dietary guidelines and were randomized into three groups: group 1 received hazelnuts with skin (HZN+S), and group 2 hazelnuts without skin (HZN-S), at equivalent doses (15-30 g/day, based on body weight); group 3 (controls) received only dietary recommendations (no nuts). At baseline and after 8 weeks, plasma oxidized low-density lipoprotein (ox-LDL) concentrations, oxidative levels of DNA damage in PBMCs and potential correlation with changes in serum lipids were examined. A reduction of endogenous DNA damage by 18.9%±51.3% (P=.002) and 23.1%±47.9% (P=.007) was observed after HZN+S and HZN-S, respectively. Oxidatively induced DNA strand breaks decreased by 16.0%±38.2% (P=.02) following HZN+S treatment. Ox-LDL levels did not change after HZN+S intervention but positively correlated with total cholesterol and LDL cholesterol. A short-term hazelnut intervention improves cell DNA protection and resistance against oxidative stress but not ox-LDL in hyperlipidemic pediatric patients. The trial was registered at ISRCTN.com, ID no. ISRCTN12261900. Copyright © 2018 Elsevier Inc. All rights reserved.

Endocannabinoid receptor blockade reduces alanine aminotransferase in polycystic ovary syndrome independent of weight loss.

PubMed

Dawson, Alison J; Kilpatrick, Eric S; Coady, Anne-Marie; Elshewehy, Abeer M M; Dakroury, Youssra; Ahmed, Lina; Atkin, Stephen L; Sathyapalan, Thozhukat

2017-07-14

Evidence suggests that endocannabinoid system activation through the cannabinoid receptor 1 (CB1) is associated with enhanced liver injury, and CB1 antagonism may be beneficial. The aim of this study was to determine the impact of rimonabant (CB1 antagonist) on alanine aminotransferase (ALT), a hepatocellular injury marker, and a hepatic inflammatory cytokine profile. Post hoc review of 2 studies involving 50 obese women with PCOS and well matched for weight, randomised to weight reducing therapy; rimonabant (20 mg od) or orlistat (120 mg tds), or to insulin sensitising therapy metformin, (500 mg tds), or pioglitazone (45 mg od). No subject had non-alcoholic fatty liver disease (NAFLD). Treatment with rimonabant for 12 weeks reduced both ALT and weight (p < 0.01), and there was a negative correlation between Δ ALT and Δ HOMA-IR (p < 0.001), but not between Δ ALT and Δ weight. There was a significant reduction of weight with orlistat (p < 0.01); however, orlistat, metformin and pioglitazone had no effect on ALT. The free androgen index fell in all groups (p < 0.05). The inflammatory marker hs-CRP was reduced by pioglitazone (p < 0.001) alone and did not correlate with changes in ALT. The inflammatory cytokine profile for IL-1β, IL-6, IL-7, IL-10, IL12, TNF-α, MCP-1 and INF-γ did not differ between groups. None of the interventions had an effect on biological variability of ALT. Rimonabant through CB1 receptor blockade decreased serum ALT that was independent of weight loss and hepatic inflammatory markers in obese women with PCOS without NAFLD. ISRCTN58369615 (February 2007; retrospectively registered) ISRCTN75758249 (October 2007; retrospectively registered).

'The trial is owned by the team, not by an individual': a qualitative study exploring the role of teamwork in recruitment to randomised controlled trials in surgical oncology.

PubMed

Strong, Sean; Paramasivan, Sangeetha; Mills, Nicola; Wilson, Caroline; Donovan, Jenny L; Blazeby, Jane M

2016-04-26

Challenges exist in recruitment to trials involving interventions delivered by different clinical specialties. Collaboration is required between clinical specialty and research teams. The aim of this study was to explore how teamwork influences recruitment to a multicentre randomised controlled trial (RCT) involving interventions delivered by different clinical specialties. Semi-structured interviews were conducted in three centres with a purposeful sample of members of the surgical, oncology and research teams recruiting to a feasibility RCT comparing definitive chemoradiotherapy with chemoradiotherapy and surgery for oesophageal squamous cell carcinoma. Interviews explored factors known to influence healthcare team effectiveness and were audio-recorded and thematically analysed. Sampling, data collection and analysis were undertaken iteratively and concurrently. Twenty-one interviews were conducted. Factors that influenced how team working impacted upon trial recruitment were centred on: (1) the multidisciplinary team (MDT) meeting, (2) leadership of the trial, and (3) the recruitment process. The weekly MDT meeting was reported as central to successful recruitment and formed the focus for creating a 'study team', bringing together clinical and research teams. Shared study leadership positively influenced healthcare professionals' willingness to participate. Interviewees perceived their clinical colleagues to have strong treatment preferences which led to scepticism regarding whether the treatments were being described to patients in a balanced manner. This study has highlighted a number of aspects of team functioning that are important for recruitment to RCTs that span different clinical specialties. Understanding these issues will aid the production of guidance on team-relevant issues that should be considered in trial management and the development of interventions that will facilitate teamwork and improve recruitment to these challenging RCTs. International Standard Randomised Controlled Trial Number (ISRCTN): ISRCTN89052791 .

The effect of financial incentives on adherence to antipsychotic depot medication: does it change over time?

PubMed

Pavlickova, Hana; Bremner, Stephen A; Priebe, Stefan

2015-08-01

A recent cluster-randomized controlled trial found that offering financial incentives improves adherence to long-acting injectable antipsychotics (LAIs). The present study investigates whether the impact of incentives diminishes over time and whether the improvement in adherence is linked to the amount of incentives offered. Seventy-three teams with 141 patients with psychotic disorders (using ICD-10) were randomized to the intervention or control group. Over 1 year, patients in the intervention group received £15 (US $23) for each LAI, while control patients received treatment as usual. Adherence levels, ie, the percentage of prescribed LAIs that were received, were calculated for quarterly intervals. The amount of incentives offered was calculated from the treatment cycle at baseline. Multilevel models were used to examine the time course of the effect of incentives and the effect of the amount of incentives offered on adherence. Adherence increased in both the intervention and the control group over time by an average of 4.2% per quarterly interval (95% CI, 2.8%-5.6%; P < .001). Despite this general increase, adherence in the intervention group remained improved compared to the control group by between 11% and 14% per quarterly interval. There was no interaction effect between time and treatment group. Further, a higher total amount of incentives was associated with poorer adherence (βbootstrapped = -0.11; 95% CIbootstrapped, -0.20 to -0.01; P = .023). A substantial effect of financial incentives on adherence to LAIs occurs within the first 3 months of the intervention and is sustained over 1 year. A higher total amount of incentives does not increase the effect. ISRCTN.com identifier: ISRCTN77769281 and UKCRN.org identifier: 7033. © Copyright 2015 Physicians Postgraduate Press, Inc.

Third generation drug eluting stent (DES) with biodegradable polymer in diabetic patients: 5 years follow-up.

PubMed

Wiemer, Marcus; Stoikovic, Sinisa; Samol, Alexander; Dimitriadis, Zisis; Ruiz-Nodar, Juan M; Birkemeyer, Ralf; Monsegu, Jacques; Finet, Gérard; Hildick-Smith, David; Tresukosol, Damras; Novo, Enrique Garcia; Koolen, Jacques J; Barbato, Emanuele; Danzi, Gian Battista

2017-02-10

To report the long-term safety and efficacy data of a third generation drug eluting stent (DES) with biodegradable polymer in the complex patient population of diabetes mellitus after a follow-up period of 5 years. After percutaneous coronary intervention patients with diabetes mellitus are under higher risk of death, restenosis and stent thrombosis (ST) compared to non-diabetic patients. In 126 centers worldwide 3067 patients were enrolled in the NOBORI 2 registry, 888 patients suffered from diabetes mellitus (DM), 213 of them (14%) being insulin dependent (IDDM). Five years follow-up has been completed in this study. At 5 years, 89.3% of the patients were available for follow-up. The reported target lesion failure (TLF) rates at 5 years were 12.39% in DM group and 7.34% in non-DM group; (p < 0.0001). In the DM group, the TLF rate in patients with IDDM was significantly higher than in the non-IDDM subgroup (17.84 vs. 10.67%; p < 0.01). The rate of ST at 5 years was not different among diabetic versus non-diabetic patients or IDDM versus NIDDM. Only 10 (<0.4%) very late stent thrombotic events beyond 12 months occurred. The Nobori DES performed well in patients with DM. As expected patients with DM, particularly those with IDDM, had worse outcomes. However, the very low rate of very late stent thrombosis in IDDM patients might have significant clinical value in the treatment of these patients. Clinical trial registration ISRCTN81649913; http://www.controlled-trials.com/isrctn/search.html?srch=81649913&sort=3&dir=desc&max=10.

Music in mind, a randomized controlled trial of music therapy for young people with behavioural and emotional problems: study protocol.

PubMed

Porter, Sam; Holmes, Valerie; McLaughlin, Katrina; Lynn, Fiona; Cardwell, Chris; Braiden, Hannah-Jane; Doran, Jackie; Rogan, Sheelagh

2012-10-01

This article is a report of a trial protocol to determine if improvizational music therapy leads to clinically significant improvement in communication and interaction skills for young people experiencing social, emotional or behavioural problems. Music therapy is often considered an effective intervention for young people experiencing social, emotional or behavioural difficulties. However, this assumption lacks empirical evidence. Music in mind is a multi-centred single-blind randomized controlled trial involving 200 young people (aged 8-16 years) and their parents. Eligible participants will have a working diagnosis within the ambit of international classification of disease 10 mental and behavioural disorders and will be recruited over 15 months from six centres within the Child and Adolescent Mental Health Services of a large health and social care trust in Northern Ireland. Participants will be randomly allocated in a 1:1 ratio to receive standard care alone or standard care plus 12 weekly music therapy sessions delivered by the Northern Ireland Music Therapy Trust. Baseline data will be collected from young people and their parents using standardized outcome measures for communicative and interaction skills (primary endpoint), self-esteem, social functioning, depression and family functioning. Follow-up data will be collected 1 and 13 weeks after the final music therapy session. A cost-effectiveness analysis will also be carried out. This study will be the largest trial to date examining the effect of music therapy on young people experiencing social, emotional or behavioural difficulties and will provide empirical evidence for the use of music therapy among this population. Trial registration. This study is registered in the ISRCTN Register, ISRCTN96352204. Ethical approval was gained in October 2010. © 2012 Blackwell Publishing Ltd.

Baseline Blood Pressure Effect on the Benefit and Safety of Intra-Arterial Treatment in MR CLEAN (Multicenter Randomized Clinical Trial of Endovascular Treatment of Acute Ischemic Stroke in the Netherlands).

PubMed

Mulder, Maxim J H L; Ergezen, Saliha; Lingsma, Hester F; Berkhemer, Olvert A; Fransen, Puck S S; Beumer, Debbie; van den Berg, Lucie A; Lycklama À Nijeholt, Geert; Emmer, Bart J; van der Worp, H Bart; Nederkoorn, Paul J; Roos, Yvo B W E M; van Oostenbrugge, Robert J; van Zwam, Wim H; Majoie, Charles B L M; van der Lugt, Aad; Dippel, Diederik W J

2017-07-01

High blood pressure (BP) is associated with poor outcome and the occurrence of symptomatic intracranial hemorrhage in acute ischemic stroke. Whether BP influences the benefit or safety of intra-arterial treatment (IAT) is not known. We aimed to assess the relation of BP with functional outcome, occurrence of symptomatic intracranial hemorrhage and effect of IAT. This is a post hoc analysis of the MR CLEAN (Multicenter Randomized Clinical Trial of Endovascular Treatment of Acute Ischemic Stroke in the Netherlands). BP was measured at baseline, before IAT or stroke unit admission. We estimated the association of baseline BP with the score on the modified Rankin Scale at 90 days and safety parameters with ordinal and logistic regression analysis. Effect of BP on the effect of IAT was tested with multiplicative interaction terms. Systolic BP (SBP) had the best correlation with functional outcome. This correlation was U-shaped; both low and high baseline SBP were associated with poor functional outcome. Higher SBP was associated with symptomatic intracranial hemorrhage (adjusted odds ratio, 1.25 for every 10 mm Hg higher SBP [95% confidence interval, 1.09-1.44]). Between SBP and IAT, there was no interaction for functional outcome, symptomatic intracranial hemorrhage, or other safety parameters; the absolute benefit of IAT was evident for the whole SBP range. The same was found for diastolic BP. BP does not affect the benefit or safety of IAT in patients with acute ischemic stroke caused by proximal intracranial vessel occlusion. Our data provide no arguments to withhold or delay IAT based on BP. URL: http://www.isrctn.com. Unique identifier: ISRCTN10888758. © 2017 American Heart Association, Inc.

RECAST (Remote Ischemic Conditioning After Stroke Trial): A Pilot Randomized Placebo Controlled Phase II Trial in Acute Ischemic Stroke.

PubMed

England, Timothy J; Hedstrom, Amanda; O'Sullivan, Saoirse; Donnelly, Richard; Barrett, David A; Sarmad, Sarir; Sprigg, Nikola; Bath, Philip M

2017-05-01

Repeated episodes of limb ischemia and reperfusion (remote ischemic conditioning [RIC]) may improve outcome after acute stroke. We performed a pilot blinded placebo-controlled trial in patients with acute ischemic stroke, randomized 1:1 to receive 4 cycles of RIC within 24 hours of ictus. The primary outcome was tolerability and feasibility. Secondary outcomes included safety, clinical efficacy (day 90), putative biomarkers (pre- and post-intervention, day 4), and exploratory hemodynamic measures. Twenty-six patients (13 RIC and 13 sham) were recruited 15.8 hours (SD 6.2) post-onset, age 76.2 years (SD 10.5), blood pressure 159/83 mm Hg (SD 25/11), and National Institutes of Health Stroke Scale (NIHSS) score 5 (interquartile range, 3.75-9.25). RIC was well tolerated with 49 out of 52 cycles completed in full. Three patients experienced vascular events in the sham group: 2 ischemic strokes and 2 myocardial infarcts versus none in the RIC group ( P =0.076, log-rank test). Compared with sham, there was a significant decrease in day 90 NIHSS score in the RIC group, median NIHSS score 1 (interquartile range, 0.5-5) versus 3 (interquartile range, 2-9.5; P =0.04); RIC augmented plasma HSP27 (heat shock protein 27; P <0.05, repeated 2-way ANOVA) and phosphorylated HSP27 ( P <0.001) but not plasma S100-β, matrix metalloproteinase-9, endocannabinoids, or arterial compliance. RIC after acute stroke is well tolerated and appears safe and feasible. RIC may improve neurological outcome, and protective mechanisms may be mediated through HSP27. A larger trial is warranted. URL: http://www.isrctn.com. Unique identifier: ISRCTN86672015. © 2017 American Heart Association, Inc.

Admission Glucose and Effect of Intra-Arterial Treatment in Patients With Acute Ischemic Stroke.

PubMed

Osei, Elizabeth; den Hertog, Heleen M; Berkhemer, Olvert A; Fransen, Puck S S; Roos, Yvo B W E M; Beumer, Debbie; van Oostenbrugge, Robert J; Schonewille, Wouter J; Boiten, Jelis; Zandbergen, Adrienne A M; Koudstaal, Peter J; Dippel, Diederik W J

2017-05-01

Hyperglycemia on admission is common after ischemic stroke. It is associated with unfavorable outcome after treatment with intravenous thrombolysis and after intra-arterial treatment. Whether hyperglycemia influences the effect of reperfusion treatment is unknown. We assessed whether increased admission serum glucose modifies the effect of intra-arterial treatment in patients with acute ischemic stroke. We used data from the MR CLEAN (Multicenter Randomized Clinical Trial of Endovascular Treatment for Acute Ischemic Stroke in the Netherlands). Hyperglycemia was defined as admission serum glucose >7.8 mmol/L. The primary outcome measure was the adjusted common odds ratio for a shift in the direction of a better outcome on the modified Rankin Scale at 90 days, estimated with ordinal logistic regression. Secondary outcome variable was symptomatic intracranial hemorrhage. We assessed treatment effect modification of hyperglycemia and admission serum glucose levels with multiplicative interaction factors and adjusted for prognostic variables. Four hundred eighty-seven patients were included. Mean admission serum glucose was 7.2 mmol/L (SD, 2.2). Fifty-seven of 226 patients (25%) randomized to intra-arterial treatment were hyperglycemic compared with 61 of 261 patients (23%) in the control group. The interaction of either hyperglycemia or admission serum glucose levels and treatment effect on modified Rankin Scale scores was not significant ( P =0.67 and P =0.87, respectively). The same applied for occurrence of symptomatic hemorrhage ( P =0.39 for hyperglycemia, P =0.39 for admission serum glucose). We found no evidence for effect modification of intra-arterial treatment by admission serum glucose in patients with acute ischemic stroke. URL: www.isrctn.com. Unique identifier: ISRCTN10888758. © 2017 American Heart Association, Inc.

The non-alcoholic fraction of beer increases stromal cell derived factor 1 and the number of circulating endothelial progenitor cells in high cardiovascular risk subjects: a randomized clinical trial.

PubMed

Chiva-Blanch, Gemma; Condines, Ximena; Magraner, Emma; Roth, Irene; Valderas-Martínez, Palmira; Arranz, Sara; Casas, Rosa; Martínez-Huélamo, Miriam; Vallverdú-Queralt, Anna; Quifer-Rada, Paola; Lamuela-Raventos, Rosa M; Estruch, Ramon

2014-04-01

Moderate alcohol consumption is associated with a decrease in cardiovascular risk, but fermented beverages seem to confer greater cardiovascular protection due to their polyphenolic content. Circulating endothelial progenitor cells (EPC) are bone-marrow-derived stem cells with the ability to repair and maintain endothelial integrity and function and are considered as a surrogate marker of vascular function and cumulative cardiovascular risk. Nevertheless, no study has been carried out on the effects of moderate beer consumption on the number of circulating EPC in high cardiovascular risk patients. To compare the effects of moderate consumption of beer, non-alcoholic beer and gin on the number of circulating EPC and EPC-mobilizing factors. In this crossover trial, 33 men at high cardiovascular risk were randomized to receive beer (30 g alcohol/d), the equivalent amount of polyphenols in the form of non-alcoholic beer, or gin (30 g alcohol/d) for 4 weeks. Diet and physical exercise were carefully monitored. The number of circulating EPC and EPC-mobilizing factors were determined at baseline and after each intervention. After the beer and non-alcoholic beer interventions, the number of circulating EPC significantly increased by 8 and 5 units, respectively, while no significant differences were observed after the gin period. In correlation, stromal cell derived factor 1 increased significantly after the non-alcoholic and the beer interventions. The non-alcoholic fraction of beer increases the number of circulating EPC in peripheral blood from high cardiovascular risk subjects. http://www.controlled-trials.com/ISRCTN95345245 ISRCTN95345245. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

Higher dietary glycemic index and glycemic load values increase the risk of osteoporotic fracture in the PREvención con DIeta MEDiterránea (PREDIMED)-Reus trial.

PubMed

García-Gavilán, Jesús Francisco; Bulló, Mònica; Camacho-Barcia, Lucia; Rosique-Esteban, Nuria; Hernández-Alonso, Pablo; Basora, Josep; Martínez-González, Miguel Angel; Estruch, Ramón; Fitó, Montserrat; Salas-Salvadó, Jordi

2018-06-01

High glucose and insulin concentrations seem to have a negative impact on bone health. However, the relation between the dietary glycemic index (DGI) and the dietary glycemic load (DGL), which has proved to be effective at modulating blood glucose concentrations after carbohydrate consumption, has yet to be explored in relation to bone health. The aim of the study was to examine the associations between the DGI or DGL and the risk of osteoporotic-related fractures in an elderly Mediterranean population. The study was conducted in 870 subjects aged 55-80 y at high cardiovascular disease risk participating in the PREvención con DIeta MEDiterránea (PREDIMED)-Reus study. The DGI and DGL were estimated from validated food-frequency questionnaires with the use of the international glycemic index and glycemic load values, with glucose as reference. Data on osteoporotic fractures were acquired from a systematic review of medical records. We used Cox proportional hazard models to assess the risk of osteoporotic fracture according to tertiles of average DGI and DGL. A total of 114 new cases of osteoporotic-related fractures were documented after a mean follow-up of 8.9 y. Participants in the highest tertile of DGI and DGL had a significantly higher risk of osteoporotic fractures than those in the lowest tertile after adjusting for potential confounders (HR: 1.80; 95% CI: 1.03, 3.15 and HR: 3.20; 95% CI: 1.25, 8.18, respectively). A high DGI and DGL are associated with a higher risk of osteoporosis-related fractures in an elderly Mediterranean population at high cardiovascular disease risk. This trial was registered at isrctn.com as ISRCTN35739639.

Evaluation of an internet-based aftercare program to improve vocational reintegration after inpatient medical rehabilitation: study protocol for a cluster-randomized controlled trial.

PubMed

Zwerenz, Rüdiger; Gerzymisch, Katharina; Edinger, Jens; Holme, Martin; Knickenberg, Rudolf J; Spörl-Dönch, Sieglinde; Kiwus, Ulrich; Beutel, Manfred E

2013-01-25

Mental disorders are the main reasons for rising proportions of premature pension in most high-income countries. Although inpatient medical rehabilitation has increasingly targeted work-related stress, there is still a lack of studies on the transfer of work-specific interventions into work contexts. Therefore, we plan to evaluate an online aftercare program aiming to improve vocational reintegration after medical rehabilitation. Vocationally strained patients (n = 800) aged between 18 and 59 years with private internet access are recruited in psychosomatic, orthopedic and cardiovascular rehabilitation clinics in Germany. During inpatient rehabilitation, participants in stress management group training are cluster-randomized to the intervention or control group. The intervention group (n = 400) is offered an internet-based aftercare with weekly writing tasks and therapeutic feedback, a patient forum, a self-test and relaxation exercises. The control group (n = 400) obtains regular e-mail reminders with links to publicly accessible information about stress management and coping. Assessments are conducted at the beginning of inpatient rehabilitation, the end of inpatient rehabilitation, the end of aftercare, and 9 months later. The primary outcome is a risk score for premature pension, measured by a screening questionnaire at follow-up. Secondary outcome measures include level of vocational stress, physical and mental health, and work capacity at follow-up. We expect the intervention group to stabilize the improvements achieved during inpatient rehabilitation concerning stress management and coping, resulting in an improved vocational reintegration. The study protocol demonstrates the features of internet-based aftercare in rehabilitation. International Standard Randomised Controlled Trial Number Register (ISRCTN:ISRCTN33957202).

Cognitive behaviour therapy (CBT) for anxiety and depression in adults with mild intellectual disabilities (ID): a pilot randomised controlled trial.

PubMed

Hassiotis, Angela; Serfaty, Marc; Azam, Kiran; Strydom, Andre; Martin, Sue; Parkes, Charles; Blizard, Robert; King, Michael

2011-04-14

Several studies have showed that people with intellectual disabilities (ID) have suitable skills to undergo cognitive behavioural therapy (CBT). Case studies have reported successful use of cognitive behavioural therapy techniques (with adaptations) in people with ID. Modified cognitive behavioural therapy may be a feasible and effective approach for the treatment of depression, anxiety, and other mood disorders in ID. To date, two studies have reported group-based manaulised cognitive behavioural treatment programs for depression in people with mild ID. However, there is no individual manualised programme for anxiety or depression in people with intellectual disabilities. The aims of the study are to determine the feasibility of conducting a randomised controlled trial for CBT in people with ID. The data will inform the power calculation and other aspects of carrying out a definitive randomised controlled trial. Thirty participants with mild ID will be allocated randomly to either CBT or treatment as usual (TAU). The CBT group will receive up to 20 hourly individual CBT over a period of 4 months. TAU is the standard treatment which is available to any adult with an intellectual disability who is referred to the intellectual disability service (including care management, community support, medical, nursing or social support). Beck Youth Inventories (Beck Anxiety Inventory & Beck Depression Inventory) will be administered at baseline; end of treatment (4 months) and at six months to evaluate the changes in depression and anxiety. Client satisfaction, quality of life and the health economics will be secondary outcomes. The broad outcome of the study will be to produce clear guidance for therapists to apply an established psychological intervention and identify how and whether it works with people with intellectual disabilities. ISRCTN: ISRCTN38099525.

The relationship between attachment orientations and the course of depression in coronary artery disease patients: A secondary analysis of the SPIRR-CAD trial.

PubMed

Söllner, Wolfgang; Müller, Markus M; Albus, Christian; Behnisch, Rüdiger; Beutel, Manfred E; de Zwaan, Martina; Fritzsche, Kurt; Habermeier, Anita; Hellmich, Martin; Jordan, Jochen; Jünger, Jana; Ladwig, Karl-Heinz; Michal, Matthias; Petrowski, Katja; Ronel, Joram; Stein, Barbara; Weber, Cora; Weber, Rainer; Herrmann-Lingen, Christoph

2018-05-01

The relationship between attachment orientations and the recovery from depressive symptoms in patients diagnosed with coronary artery disease (CAD) with and without a psychotherapeutic intervention was examined in this study. In a multicenter trial of 570 depressed CAD patients (SPIRR-CAD), assigned to usual care plus either a stepwise psychotherapy intervention or one information session, 522 patients provided attachment data at baseline. Attachment was measured with the Relationship Scales Questionnaire (RSQ), yielding four attachment orientations. The primary outcome was change in Hospital Anxiety and Depression Scale depression (HADS-D) scores from baseline to follow-up at 18 months. Secondary outcomes were HADS-D scores at 1, 6, 12, and 24 months. Independent of treatment assignment, attachment was related to change in depression at 18 months (p < 0.01) with secure attachment resulting in a significant reduction (-2.72, SE = 0.27) in depression compared to dismissive-avoidant (-1.51, SE = 0.35, p = 0.040) and fearful-avoidant (-0.65, SE = 0.61, p = 0.012) attachment. Patients with anxious-preoccupied attachment showed changes similar to secure attachment (-2.01, SE = 0.47). An explorative subgroup analysis across all assessment time points revealed patients with a dismissive-avoidant attachment benefitted from psychotherapy (average mean difference = 0.93, SE = 0.47, p = 0.048). Attachment played an important role for improvement in depressive symptoms. Only dismissive-avoidant patients seemed to benefit from the intervention. The lack of improvement in fearful-avoidant patients shows a need for specific interventions for this group. www.clinicaltrials.govNCT00705965; www.isrctn.com ISRCTN76240576. Copyright © 2018 Elsevier Inc. All rights reserved.

School intervention to improve mental health of students in Santiago, Chile: a randomized clinical trial.

PubMed

Araya, Ricardo; Fritsch, Rosemarie; Spears, Melissa; Rojas, Graciela; Martinez, Vania; Barroilhet, Sergio; Vöhringer, Paul; Gunnell, David; Stallard, Paul; Guajardo, Viviana; Gaete, Jorge; Noble, Sian; Montgomery, Alan A

2013-11-01

Depression can have devastating effects unless prevented or treated early and effectively. Schools offer an excellent opportunity to intervene with adolescents presenting emotional problems. There are very few universal school-based depression interventions conducted in low- and middle-income countries. To assess the effectiveness of a school-based, universal psychological intervention to reduce depressive symptoms among adolescents from low-income families. A 2-arm, parallel, cluster, randomized clinical trial was conducted in secondary schools in deprived socioeconomic areas of Santiago, Chile. Almost all students registered in the selected schools consented to take part in the study. A total of 2512 secondary school students from 22 schools and 66 classes participated. Students in the intervention arm attended 11 one-hour weekly and 2 booster classroom sessions of an intervention based on cognitive-behavioral models. The intervention was delivered by trained nonspecialists. Schools in the control arm received the standard school curriculum. Scores on the self-administered Beck Depression Inventory-II at 3 months (primary) and 12 months (secondary) after completing the intervention. There were 1291 participants in the control arm and 1221 in the intervention arm. Primary outcome data were available for 82.1% of the participants. There was no evidence of any clinically important difference in mean depression scores between the groups (adjusted difference in mean, -0.19; 95% CI, -1.22 to 0.84) or for any of the other outcomes 3 months after completion of the intervention. No significant differences were found in any of the outcomes at 12 months. A well-designed and implemented school-based intervention did not reduce depressive symptoms among socioeconomically deprived adolescents in Santiago, Chile. There is growing evidence that universal school interventions may not be sufficiently effective to reduce or prevent depressive symptoms. isrctn.org Identifier: ISRCTN19466209.

Personalised Hip Therapy: development of a non-operative protocol to treat femoroacetabular impingement syndrome in the FASHIoN randomised controlled trial.

PubMed

Wall, Peter Dh; Dickenson, Edward J; Robinson, David; Hughes, Ivor; Realpe, Alba; Hobson, Rachel; Griffin, Damian R; Foster, Nadine E

2016-10-01

Femoroacetabular impingement (FAI) syndrome is increasingly recognised as a cause of hip pain. As part of the design of a randomised controlled trial (RCT) of arthroscopic surgery for FAI syndrome, we developed a protocol for non-operative care and evaluated its feasibility. In phase one, we developed a protocol for non-operative care for FAI in the UK National Health Service (NHS), through a process of systematic review and consensus gathering. In phase two, the protocol was tested in an internal pilot RCT for protocol adherence and adverse events. The final protocol, called Personalised Hip Therapy (PHT), consists of four core components led by physiotherapists: detailed patient assessment, education and advice, help with pain relief and an exercise-based programme that is individualised, supervised and progressed over time. PHT is delivered over 12-26 weeks in 6-10 physiotherapist-patient contacts, supplemented by a home exercise programme. In the pilot RCT, 42 patients were recruited and 21 randomised to PHT. Review of treatment case report forms, completed by physiotherapists, showed that 13 patients (62%) received treatment that had closely followed the PHT protocol. 13 patients reported some muscle soreness at 6 weeks, but there were no serious adverse events. PHT provides a structure for the non-operative care of FAI and offers guidance to clinicians and researchers in an evolving area with limited evidence. PHT was deliverable within the National Health Service, is safe, and now forms the comparator to arthroscopic surgery in the UK FASHIoN trial (ISRCTN64081839). ISRCTN 09754699. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

Declining responsiveness of Plasmodium falciparum infections to artemisinin-based combination treatments on the Kenyan coast.

PubMed

Borrmann, Steffen; Sasi, Philip; Mwai, Leah; Bashraheil, Mahfudh; Abdallah, Ahmed; Muriithi, Steven; Frühauf, Henrike; Schaub, Barbara; Pfeil, Johannes; Peshu, Judy; Hanpithakpong, Warunee; Rippert, Anja; Juma, Elizabeth; Tsofa, Benjamin; Mosobo, Moses; Lowe, Brett; Osier, Faith; Fegan, Greg; Lindegårdh, Niklas; Nzila, Alexis; Peshu, Norbert; Mackinnon, Margaret; Marsh, Kevin

2011-01-01

The emergence of artemisinin-resistant P. falciparum malaria in South-East Asia highlights the need for continued global surveillance of the efficacy of artemisinin-based combination therapies. On the Kenyan coast we studied the treatment responses in 474 children 6-59 months old with uncomplicated P. falciparum malaria in a randomized controlled trial of dihydroartemisinin-piperaquine vs. artemether-lumefantrine from 2005 to 2008. (ISRCTN88705995). The proportion of patients with residual parasitemia on day 1 rose from 55% in 2005-2006 to 87% in 2007-2008 (odds ratio, 5.4, 95%CI, 2.7-11.1; P<0.001) and from 81% to 95% (OR, 4.1, 95%CI, 1.7-9.9; P = 0.002) in the DHA-PPQ and AM-LM groups, respectively. In parallel, Kaplan-Meier estimated risks of apparent recrudescent infection by day 84 increased from 7% to 14% (P = 0.1) and from 6% to 15% (P = 0.05) with DHA-PPQ and AM-LM, respectively. Coinciding with decreasing transmission in the study area, clinical tolerance to parasitemia (defined as absence of fever) declined between 2005-2006 and 2007-2008 (OR body temperature >37.5°C, 2.8, 1.9-4.1; P<0.001). Neither in vitro sensitivity of parasites to DHA nor levels of antibodies against parasite extract accounted for parasite clearance rates or changes thereof. The significant, albeit small, decline through time of parasitological response rates to treatment with ACTs may be due to the emergence of parasites with reduced drug sensitivity, to the coincident reduction in population-level clinical immunity, or both. Maintaining the efficacy of artemisinin-based therapy in Africa would benefit from a better understanding of the mechanisms underlying reduced parasite clearance rates. Controlled-Trials.com ISRCTN88705995.

Maternal Prenatal Nutrition and Birth Outcomes on Malnutrition among 7- to 10-Year-Old Children: A 10-Year Follow-Up.

PubMed

Zhou, Jing; Zeng, Lingxia; Dang, Shaonong; Pei, Leilei; Gao, Wenlong; Li, Chao; Yan, Hong

2016-11-01

To identify postnatal predictors of malnutrition among 7- to 10-year-old children and to assess the long-term effects of antenatal micronutrient supplementation on malnutrition. A follow-up study was conducted to assess the nutritional status of 7- to 10-year-olds (1747 children) whose mothers participated in a cluster-randomized double-blind controlled trial from 2002 to 2006. The rate of malnourished 7- to 10-year-olds was 11.1%. A mixed-effects logistic regression model adjusted for the cluster-sampling design indicated that mothers with low prepregnant midupper arm circumference had boys with an increased risk of thinness (aOR  2.05, 95% CI  1.11, 3.79) and girls who were more likely to be underweight (aOR 2.01, 95% CI 1.05, 3.85). Antenatal micronutrient supplementation was not significantly associated with malnutrition. Low birth weight was significantly associated with increased odds of malnutrition among boys (aOR 4.34, 95% CI 1.82, 10.39) and girls (aOR  7.50, 95% CI 3.48, 16.13). Being small for gestational age significantly increased the odds of malnutrition among boys (aOR 1.75, 95% CI 1.01, 3.04) and girls (aOR 4.20, 95% CI  2.39, 7.39). In addition, household wealth, parental height, being picky eater, and illness frequency also predicted malnutrition. Both maternal prenatal nutrition and adverse birth outcomes are strong predictors of malnutrition among early school-aged children. Currently, available evidence is insufficient to support long-term effects of antenatal micronutrient supplementation on children's nutrition. www.isrctn.com: ISRCTN08850194. Copyright © 2016 Elsevier Inc. All rights reserved.

Evaluation of an internet-based aftercare program to improve vocational reintegration after inpatient medical rehabilitation: study protocol for a cluster-randomized controlled trial

PubMed Central

2013-01-01

Background Mental disorders are the main reasons for rising proportions of premature pension in most high-income countries. Although inpatient medical rehabilitation has increasingly targeted work-related stress, there is still a lack of studies on the transfer of work-specific interventions into work contexts. Therefore, we plan to evaluate an online aftercare program aiming to improve vocational reintegration after medical rehabilitation. Methods Vocationally strained patients (n = 800) aged between 18 and 59 years with private internet access are recruited in psychosomatic, orthopedic and cardiovascular rehabilitation clinics in Germany. During inpatient rehabilitation, participants in stress management group training are cluster-randomized to the intervention or control group. The intervention group (n = 400) is offered an internet-based aftercare with weekly writing tasks and therapeutic feedback, a patient forum, a self-test and relaxation exercises. The control group (n = 400) obtains regular e-mail reminders with links to publicly accessible information about stress management and coping. Assessments are conducted at the beginning of inpatient rehabilitation, the end of inpatient rehabilitation, the end of aftercare, and 9 months later. The primary outcome is a risk score for premature pension, measured by a screening questionnaire at follow-up. Secondary outcome measures include level of vocational stress, physical and mental health, and work capacity at follow-up. Discussion We expect the intervention group to stabilize the improvements achieved during inpatient rehabilitation concerning stress management and coping, resulting in an improved vocational reintegration. The study protocol demonstrates the features of internet-based aftercare in rehabilitation. Trial registration International Standard Randomised Controlled Trial Number Register (ISRCTN:ISRCTN33957202) PMID:23351836

1-Hz rTMS in the treatment of tinnitus: A sham-controlled, randomized multicenter trial.

PubMed

Landgrebe, Michael; Hajak, Göran; Wolf, Stefan; Padberg, Frank; Klupp, Philipp; Fallgatter, Andreas J; Polak, Thomas; Höppner, Jacqueline; Haker, Rene; Cordes, Joachim; Klenzner, Thomas; Schönfeldt-Lecuona, Carlos; Kammer, Thomas; Graf, Erika; Koller, Michael; Kleinjung, Tobias; Lehner, Astrid; Schecklmann, Martin; Pöppl, Timm B; Kreuzer, Peter; Frank, Elmar; Langguth, Berthold

Chronic tinnitus is a frequent, difficult to treat disease with high morbidity. This multicenter randomized, sham-controlled trial investigated the efficacy and safety of 1-Hz repetitive transcranial magnetic stimulation (rTMS) applied to the left temporal cortex in patients with chronic tinnitus. Tinnitus patients were randomized to receive 10 sessions of either real or sham 1-Hz-rTMS (2000 stimuli, 110% motor threshold) to the left temporal cortex. The primary outcome was the change in the sum score of the tinnitus questionnaire (TQ) of Goebel and Hiller from baseline to end of treatment. A total of 163 patients were enrolled in the study (real rTMS: 75; sham rTMS: 78). At day 12, the baseline mean of 43.1 TQ points in 71 patients assigned to real rTMS changed by -0.5 points; it changed by 0.5 points from a baseline of 42.1 in 75 patients randomized to sham rTMS (adjusted mean difference between groups: -1.0; 95.19% confidence interval: -3.2 to 1.2; p = 0.36). All secondary outcome measures including measures of depression and quality of life showed no significant differences either (p > 0.11). The number of participants with side-effects or adverse events did not differ between groups. Real 1-Hz-rTMS over the left temporal cortex was well tolerated but not superior compared with sham rTMS in improving tinnitus severity. These findings are in contrast to results from studies with smaller sample sizes and put the efficacy of this rTMS protocol for treatment of chronic tinnitus into question. Controlled Trials: http://www.isrctn.com/ISRCTN89848288. Copyright © 2017 Elsevier Inc. All rights reserved.

Potential predictors of susceptibility to occupational stress in Japanese novice nurses - a pilot study.

PubMed

Okita, Shinobu; Daitoku, Satoshi; Abe, Masaharu; Arimura, Emi; Setoyama, Hitoshi; Koriyama, Chihaya; Ushikai, Miharu; Kawaguchi, Hiroaki; Horiuchi, Masahisa

2017-04-04

Occupational stress is a known factor behind employee resignations; thus, early identification of individuals prone to such stress is important. Accordingly, in this pilot study we evaluated potential predictors of susceptibility to occupational stress in Japanese novice nurses. Forty-two female novice nurses at Kagoshima University Hospital were recruited for the study population. Each underwent physical health and urinary examinations, and completed a lifestyle questionnaire at the time of job entry. Each also completed a Brief Job Stress Questionnaire (BJSQ), related to mental health status, at job entry and 5 months post-entry. Psychological stress, somatic symptoms, and combined BJSQ scores were determined for each time point. All three stress condition scores had significantly decreased at 5 months post-entry, suggesting occupational stress. Systolic blood pressure (r = -0.324, p < 0.05) and urinary sodium (r = -0.313, p < 0.05) were significantly negatively correlated with combined BJSQ score at 5 months post-entry. Post-entry stress condition scores were significantly low in subjects reporting substantial 1-year body weight change (≤ ± 3 kg) and short times between dinner and bedtimes (≤2 h), though baseline stress condition scores were not. Urinary sodium concentration, 1-year body weight change, and pre-sleep evening meals were then targeted for multivariate analysis, and confirmed as independent explanatory variables for post-entry stress condition scores. One-year body weight change, times between dinner and bedtimes, and urinary sodium concentration are promising potential predictors of susceptibility to occupational stress, and should be further investigated in future research. ISRCTN ISRCTN17516023. Retrospectively registered 7 December 2016.

The Home-Based Older People's Exercise (HOPE) trial: study protocol for a randomised controlled trial

PubMed Central

2011-01-01

Background Frailty is common in older age, and is associated with important adverse health outcomes including increased risk of disability and admission to hospital or long-term care. Exercise interventions for frail older people have the potential to reduce the risk of these adverse outcomes by increasing muscle strength and improving mobility. Methods/Design The Home-Based Older People's Exercise (HOPE) trial is a two arm, assessor blind pilot randomised controlled trial (RCT) to assess the effectiveness of a 12 week exercise intervention (the HOPE programme) designed to improve the mobility and functional abilities of frail older people living at home, compared with usual care. The primary outcome is the timed-up-and-go test (TUGT), measured at baseline and 14 weeks post-randomisation. Secondary outcomes include the Barthel Index of activities of daily living (ADL), EuroQol Group 5-Dimension Self-Report Questionnaire (EQ-5D) quality of life measure and the geriatric depression scale (GDS), measured at baseline and 14 weeks post-randomisation. We will record baseline frailty using the Edmonton Frail Scale (EFS), record falls and document muscle/joint pain. We will test the feasibility of collection of data to identify therapy resources required for delivery of the intervention. Discussion The HOPE trial will explore and evaluate a home-based exercise intervention for frail older people. Although previous RCTs have used operationalised, non-validated methods of measuring frailty, the HOPE trial is, to our knowledge, the first RCT of an exercise intervention for frail older people that includes a validated method of frailty assessment at baseline. Trial registration ISRCTN: ISRCTN57066881 PMID:21651805

Promoting early presentation of breast cancer in older women: sustained effect of an intervention to promote breast cancer awareness in routine clinical practice.

PubMed

Dodd, Rachael H; Forster, Alice S; Sellars, Sarah; Patnick, Julietta; Ramirez, Amanda J; Forbes, Lindsay J L

2017-06-05

Older women have poorer survival from breast cancer, which may be at least partly due to poor breast cancer awareness leading to delayed presentation and more advanced stage at diagnosis. In a randomised trial, an intervention to promote early presentation of breast cancer in older women increased breast cancer awareness at 1 year compared with usual care (24 versus 4%). We examined its effectiveness in routine clinical practice. We piloted the intervention delivered by practising health professionals to women aged about 70 in four breast screening services. We measured the effect on breast cancer awareness at 1 year compared with comparison services, where women did not receive the intervention. At 1 year, 25% of women in pilot services were breast cancer aware compared with 4% in comparison services (p = 0.001). The components of breast cancer awareness were knowledge of breast cancer non-lump symptoms (pilot: 63% vs comparison: 82% at 1 year; OR = 2.56, 95% CI 1.92-3.42), knowledge of age related risk (pilot: 8% vs comparison: 36% at 1 year; OR = 5.56, 95% CI 4.0-7.74) and reported breast checking (pilot: 70% vs comparison: 78% at 1 year; OR = 1.49, 95% CI 1.13-1.96). The intervention may be as effective in routine clinical practice as in a randomised controlled trial. This intervention has the potential to reduce patient delay in the diagnosis of breast cancer in older women. The PEP trial was registered with the International Standard Registered Clinical/soCial sTudy Number (ISRCTN) as a clinical trial ( ISRCTN31994827 ) on 3rd October 2007.

How informed is declared altruism in clinical trials? A qualitative interview study of patient decision-making about the QUEST trials (Quality of Life after Mastectomy and Breast Reconstruction).

PubMed

Bidad, Natalie; MacDonald, Lindsay; Winters, Zoë E; Edwards, Sarah J L; Emson, Marie; Griffin, Clare L; Bliss, Judith; Horne, Rob

2016-09-02

Randomised controlled trials (RCTs) often fail to recruit sufficient participants, despite altruism being cited as their motivation. Previous investigations of factors influencing participation decisions have been methodologically limited. This study evaluated how women weigh up different motivations after initially expressing altruism, and explored their understanding of a trial and its alternatives. The trial was the 'Quality of Life after Mastectomy and Breast Reconstruction' (QUEST) trial. Thirty-nine women participated in qualitative interviews 1 month post-surgery. Twenty-seven women (10 trial decliners and 17 acceptors) who spontaneously mentioned 'altruism' were selected for thematic analysis. Verbatim transcripts were coded independently by two researchers. Participants' motivations to accept or decline randomisation were cross-referenced with their understanding of the QUEST trials and the process of randomisation. The seven emerging themes were: (1) altruism expressed by acceptors and decliners; (2) overriding personal needs in decliners; (3) pure altruism in acceptors; (4) 'hypothetical altruism' amongst acceptors; (5) weak altruism amongst acceptors; (6) conditional altruism amongst acceptors; and (7) sense of duty to participate. Poor understanding of the trial rationale and its implications was also evident. Altruism was a motivating factor for participation in the QUEST randomised controlled trials where the main outcomes comprised quality of life and allocated treatments comprised established surgical procedures. Women's decisions were influenced by their understanding of the trial. Both acceptors and decliners of the trial expressed 'altruism', but most acceptors lacked an obvious treatment preference, hoped for personal benefits regarding a treatment allocation, or did not articulate complete understanding of the trial. QUEST A, ISRCTN38846532 ; Date assigned 6 January 2010. QUEST B, ISRCTN92581226 ; Date assigned 6 January 2010.

"It's not just about walking.....it's the practice nurse that makes it work": a qualitative exploration of the views of practice nurses delivering complex physical activity interventions in primary care.

PubMed

Beighton, Carole; Victor, Christina; Normansell, Rebecca; Cook, Derek; Kerry, Sally; Iliffe, Steve; Ussher, Michael; Whincup, Peter; Fox-Rushby, Julia; Woodcock, Alison; Harris, Tess

2015-12-12

Physical activity (PA) is important for physical and mental health in adults and older adults. Interventions incorporating theory-based behaviour change techniques (BCTs) can be useful in helping people to increase their PA levels and can be delivered by practice nurses in primary care. We undertook two primary care based complex walking interventions among adults and older adults. Both interventions were underpinned by BCTs and delivered by practice nurses and we sought their views and experiences of delivering over 1400 complex PA consultations. Semi structured interviews with two practice nurse groups (n = 4 and n = 5) and two individual interviews (total n = 11) were conducted by independent facilitators; audio-recorded, transcribed verbatim and analysed using thematic analysis. Five key themes emerged as enablers and/or barriers to delivering the intervention: preparation and training; initial and ongoing support; adherence to the protocol; the use of materials and equipment; and engagement of participants. The themes were organised into a framework of 'pre-trial' and 'delivery of the intervention'. Two additional 'post-trial' themes were identified; changed practice and the future feasibility of the intervention. Nurses believed that taking part in the trial, especially the BCT training, enhanced the quality and delivery of advice and support they provided within routine consultations, although the lack of time available routinely makes this challenging. Delivering an effective behaviour change intervention in primary care requires adequate training and support for practice nurses both initially and throughout the trial as well as adequate consultation time. Enhanced skills from participating in such trials can lead to long-term changes, including more patient-centred consulting. PACE-Lift ISRCTN 42122561 , PACE-UP ISRCTN 98538934 .

Effects of intensive glucose control on platelet reactivity in patients with acute coronary syndromes. Results of the CHIPS Study ("Control de Hiperglucemia y Actividad Plaquetaria en Pacientes con Sindrome Coronario Agudo").

PubMed

Vivas, David; García-Rubira, Juan C; Bernardo, Esther; Angiolillo, Dominick J; Martín, Patricia; Calle-Pascual, Alfonso; Núñez-Gil, Iván; Macaya, Carlos; Fernández-Ortiz, Antonio

2011-05-01

Hyperglycaemia has been associated with increased platelet reactivity and impaired prognosis in patients with acute coronary syndrome (ACS). Whether platelet reactivity can be reduced by lowering glucose in this setting is unknown. The aim of this study was to assess the functional impact of intensive glucose control with insulin on platelet reactivity in patients admitted with ACS and hyperglycaemia. This is a prospective, randomised trial evaluating the effects of either intensive glucose control (target glucose 80-120 mg/dl) or conventional control (target glucose 180 mg/dl or less) with insulin on platelet reactivity in patients with ACS and hyperglycaemia. The primary endpoint was platelet aggregation following stimuli with 20 μM ADP at 24 h and at hospital discharge. Aggregation following collagen, epinephrine and thrombin receptor-activated peptide, as well as P2Y₁₂ reactivity index and surface expression of glycoprotein IIb/IIIa and P-selectin were also measured. Of the 115 patients who underwent random assignment, 59 were assigned to intensive and 56 to conventional glucose control. Baseline platelet functions and inhospital management were similar in both groups. Maximal aggregation after ADP stimulation at hospital discharge was lower in the intensive group (47.9 ± 13.2% vs 59.1 ± 17.3%; p=0.002), whereas no differences were found at 24 h. Similarly all other parameters of platelet reactivity measured at hospital discharge were significantly reduced in the intensive glucose control group. In this randomised trial, early intensive glucose control with insulin in patients with ACS presenting with hyperglycaemia was found to decrease platelet reactivity. Clinical Trial Registration Number http://www.controlledtrials.com/ISRCTN35708451/ISRCTN35708451.

Automated Software System to Promote Anticoagulation and Reduce Stroke Risk: Cluster-Randomized Controlled Trial.

PubMed

Holt, Tim A; Dalton, Andrew; Marshall, Tom; Fay, Matthew; Qureshi, Nadeem; Kirkpatrick, Susan; Hislop, Jenny; Lasserson, Daniel; Kearley, Karen; Mollison, Jill; Yu, Ly-Mee; Hobbs, F D Richard; Fitzmaurice, David

2017-03-01

Oral anticoagulants (OAC) substantially reduce risk of stroke in atrial fibrillation, but uptake is suboptimal. Electronic health records enable automated identification of people at risk but not receiving treatment. We investigated the effectiveness of a software tool (AURAS-AF [Automated Risk Assessment for Stroke in Atrial Fibrillation]) designed to identify such individuals during routine care through a cluster-randomized trial. Screen reminders appeared each time the electronic health records of an eligible patient was accessed until a decision had been taken over OAC treatment. Where OAC was not started, clinicians were prompted to indicate a reason. Control practices continued usual care. The primary outcome was the proportion of eligible individuals receiving OAC at 6 months. Secondary outcomes included rates of cardiovascular events and reports of adverse effects of the software on clinical decision-making. Forty-seven practices were randomized. The mean proportion-prescribed OAC at 6 months was 66.3% (SD=9.3) in the intervention arm and 63.9% (9.5) in the control arm (adjusted difference 1.21% [95% confidence interval -0.72 to 3.13]). Incidence of recorded transient ischemic attack was higher in the intervention practices (median 10.0 versus 2.3 per 1000 patients with atrial fibrillation; P =0.027), but at 12 months, we found a lower incidence of both all cause stroke ( P =0.06) and hemorrhage ( P =0.054). No adverse effects of the software were reported. No significant change in OAC prescribing occurred. A greater rate of diagnosis of transient ischemic attack (possibly because of improved detection or overdiagnosis) was associated with a reduction (of borderline significance) in stroke and hemorrhage over 12 months. URL: http://www.isrctn.com. Unique Identifier: ISRCTN55722437. © 2017 American Heart Association, Inc.

Correlates of whole-blood polyunsaturated fatty acids among young children with moderate acute malnutrition.

PubMed

Yaméogo, C W; Cichon, B; Fabiansen, C; Rytter, M J H; Faurholt-Jepsen, D; Stark, K D; Briend, A; Shepherd, S; Traoré, A S; Christensen, V B; Michaelsen, K F; Friis, H; Lauritzen, L

2017-07-13

Severe acute malnutrition (SAM) has been associated with low polyunsaturated fatty acid (PUFA) status. However, investigations regarding PUFA status and correlates in children with moderate acute malnutrition (MAM) from low-income countries are scarce. The aim of this study was to describe whole-blood PUFA levels in children with moderate acute malnutrition (MAM) and to identify correlates of PUFAs. We conducted a cross-sectional study using baseline data from a prospective nutritional intervention trial among 1609 children with MAM aged 6-23 months in Burkina Faso,West Africa. Whole-blood PUFAs were measured by gas chromatography and expressed as percent of total whole-blood fatty acids (FA%). Potential correlates of PUFAs including infection, inflammation, hemoglobin, anthropometry (difference between children diagnosed as having MAM based on low mid-upper-arm-circumference (MUAC) only, low MUAC and weight-for-height z-score (WHZ), or low WHZ only) and diet were assessed by linear regression adjusted for age and sex. Children with MAM had low concentrations of whole-blood PUFAs, particularly n-3 PUFAs. Moreover, children diagnosed with MAM based only on low MUAC had 0.32 (95% confidence interval (CI), 0.14; 0.50) and 0.40 (95% CI, 0.16; 0.63) FA% lower arachidonic acid (AA) than those recruited based on both low WHZ as well as low MUAC and those recruited with low WHZ only, respectively. Infection and inflammation were associated with low levels of all long-chain (LC)-PUFAs, while hemoglobin was positively associated with whole-blood LC-PUFAs. While PUFA deficiency was not a general problem, overall whole-blood PUFA concentrations, especially of n-3 PUFAs, were low. Infection, inflammation, hemoglobin, anthropometry and diet were correlates of PUFAs concentrations in children with MAM. The trial is registered at http://www.isrctn.com ( ISRCTN42569496 ).

Cost-Effectiveness of Cranberries vs Antibiotics to Prevent Urinary Tract Infections in Premenopausal Women: A Randomized Clinical Trial

PubMed Central

Bosmans, Judith E.; Beerepoot, Mariëlle A. J.; Prins, Jan M.; ter Riet, Gerben; Geerlings, Suzanne E.

2014-01-01

Background Urinary tract infections (UTIs) are common and result in an enormous economic burden. The increasing prevalence of antibiotic-resistant microorganisms has stimulated interest in non-antibiotic agents to prevent UTIs. Objective To evaluate the cost-effectiveness of cranberry prophylaxis compared to antibiotic prophylaxis with trimethoprim-sulfamethoxazole (TMP-SMX) over a 12 month period in premenopausal women with recurrent UTIs. Materials and Methods An economic evaluation was performed alongside a randomized trial. Primary outcome was the number of UTIs during 12 months. Secondary outcomes included satisfaction and quality of life. Healthcare utilization was measured using questionnaires. Missing data were imputed using multiple imputation. Bootstrapping was used to evaluate the cost-effectiveness of the treatments. Results Cranberry prophylaxis was less effective than TMP-SMX prophylaxis, but the differences in clinical outcomes were not statistically significant. Costs after 12 months in the cranberry group were statistically significantly higher than in the TMP-SMX group (mean difference €249, 95% confidence interval 70 to 516). Cost-effectiveness planes and cost-effectiveness acceptability curves showed that cranberry prophylaxis to prevent UTIs is less effective and more expensive than (dominated by) TMP-SMX prophylaxis. Conclusion In premenopausal women with recurrent UTIs, cranberry prophylaxis is not cost-effective compared to TMP-SMX prophylaxis. However, it was not possible to take into account costs attributed to increased antibiotic resistance within the framework of this randomized trial; modeling studies are recommended to investigate these costs. Moreover, although we based the dosage of cranberry extract on available evidence, this may not be the optimal dosage. Results may change when this optimal dosage is identified. Trial Registration ISRCTN.org ISRCTN50717094 PMID:24705418

Effect of Right Insular Involvement on Death and Functional Outcome After Acute Ischemic Stroke in the IST-3 Trial (Third International Stroke Trial).

PubMed

Sposato, Luciano A; Cohen, Geoffrey; Wardlaw, Joanna M; Sandercock, Peter; Lindley, Richard I; Hachinski, Vladimir

2016-12-01

In patients with acute ischemic stroke, whether involvement of the insular cortex influences outcome is controversial. Much of the apparent adverse outcome may relate to such strokes usually being severe. We examined the influence of right and left insular involvement on stroke outcomes among patients from the IST-3 study (Third International Stroke Trial) who had visible ischemic stroke on neuroimaging. We used multiple logistic regression to compare outcomes of left versus right insular and noninsular strokes across strata of stroke severity, on death, proportion dead or dependent, and level of disability (ordinalized Oxford Handicap Score) at 6 months, with adjustment for the effects of age, lesion size, and presence of atrial fibrillation. Of 3035 patients recruited, 2099 had visible ischemic strokes limited to a single hemisphere on computed tomography/magnetic resonance scans. Of these, 566 and 714 had infarction of right and left insula. Six months after randomization, right insular involvement was associated with increased odds of death when compared with noninsular strokes on the left side (adjusted odds ratio, 1.83; 95% confidence interval, 1.33-2.52), whereas the adjusted odds ratio comparing mortality after insular versus noninsular strokes on the left side was not significant. Among mild/moderate strokes, outcomes for right insular involvement were worse than for left insular, but among more severe strokes, the difference in outcomes was less substantial. We found an association between right insular involvement and higher odds of death and worse functional outcome. The difference between right- and left-sided insular lesions on outcomes seemed to be most evident for mild/moderate strokes. URL: http://www.isrctn.com. Unique identifier: ISRCTN25765518. © 2016 American Heart Association, Inc.

Geographic Information System and tools of spatial analysis in a pneumococcal vaccine trial

PubMed Central

2012-01-01

Background The goal of this Geographic Information System (GIS) study was to obtain accurate information on the locations of study subjects, road network and services for research purposes so that the clinical outcomes of interest (e.g., vaccine efficacy, burden of disease, nasopharyngeal colonization and its reduction) could be linked and analyzed at a distance from health centers, hospitals, doctors and other important services. The information on locations can be used to investigate more accurate crowdedness, herd immunity and/or transmission patterns. Method A randomized, placebo-controlled, double-blind trial of an 11-valent pneumococcal conjugate vaccine (11PCV) was conducted in Bohol Province in central Philippines, from July 2000 to December 2004. We collected the information on the geographic location of the households (N = 13,208) of study subjects. We also collected a total of 1982 locations of health and other services in the six municipalities and a comprehensive GIS data over the road network in the area. Results We calculated the numbers of other study subjects (vaccine and placebo recipients, respectively) within the neighborhood of each study subject. We calculated distances to different services and identified the subjects sharing the same services (calculated by distance). This article shows how to collect a complete GIS data set for human to human transmitted vaccine study in developing country settings in an efficient and economical way. Conclusions The collection of geographic locations in intervention trials should become a routine task. The results of public health research may highly depend on spatial relationships among the study subjects and between the study subjects and the environment, both natural and infrastructural. Trial registration number ISRCTN: ISRCTN62323832 PMID:22264271

Managing the link and strengthening transition from child to adult mental health Care in Europe (MILESTONE): background, rationale and methodology.

PubMed

Tuomainen, H; Schulze, U; Warwick, J; Paul, M; Dieleman, G C; Franić, T; Madan, J; Maras, A; McNicholas, F; Purper-Ouakil, D; Santosh, P; Signorini, G; Street, C; Tremmery, S; Verhulst, F C; Wolke, D; Singh, S P

2018-06-04

Transition from distinct Child and Adolescent Mental Health (CAMHS) to Adult Mental Health Services (AMHS) is beset with multitude of problems affecting continuity of care for young people with mental health needs. Transition-related discontinuity of care is a major health, socioeconomic and societal challenge globally. The overall aim of the Managing the Link and Strengthening Transition from Child to Adult Mental Health Care in Europe (MILESTONE) project (2014-19) is to improve transition from CAMHS to AMHS in diverse healthcare settings across Europe. MILESTONE focuses on current service provision in Europe, new transition-related measures, long term outcomes of young people leaving CAMHS, improving transitional care through 'managed transition', ethics of transitioning and the training of health care professionals. Data will be collected via systematic literature reviews, pan-European surveys, and focus groups with service providers, users and carers, and members of youth advocacy and mental health advocacy groups. A prospective cohort study will be conducted with a nested cluster randomised controlled trial in eight European Union (EU) countries (Belgium, Croatia, France, Germany, Ireland, Italy, Netherlands, UK) involving over 1000 CAMHS users, their carers, and clinicians. Improving transitional care can facilitate not only recovery but also mental health promotion and mental illness prevention for young people. MILESTONE will provide evidence of the organisational structures and processes influencing transition at the service interface across differing healthcare models in Europe and longitudinal outcomes for young people leaving CAMHS, solutions for improving transitional care in a cost-effective manner, training modules for clinicians, and commissioning and policy guidelines for service providers and policy makers. "MILESTONE study" registration: ISRCTN ISRCTN83240263 Registered 23 July 2015; ClinicalTrials.gov NCT03013595 Registered 6 January 2017.

Influence of Gestational Age at Initiation of Antihypertensive Therapy: Secondary Analysis of CHIPS Trial Data (Control of Hypertension in Pregnancy Study).

PubMed

Pels, Anouk; Mol, Ben Willem J; Singer, Joel; Lee, Terry; von Dadelszen, Peter; Ganzevoort, Wessel; Asztalos, Elizabeth; Magee, Laura A

2018-06-01

For hypertensive women in CHIPS (Control of Hypertension in Pregnancy Study), we assessed whether the maternal benefits of tight control could be achieved, while minimizing any potentially negative effect on fetal growth, by delaying initiation of antihypertensive therapy until later in pregnancy. For the 981 women with nonsevere, chronic or gestational hypertension randomized to less-tight (target diastolic blood pressure, 100 mm Hg), or tight (target, 85 mm Hg) control, we used mixed-effects logistic regression to examine whether the effect of less-tight (versus tight) control on major outcomes was dependent on gestational age at randomization, adjusting for baseline factors as in the primary analysis and including an interaction term between gestational age at randomization and treatment allocation. Gestational age was considered categorically (quartiles) and continuously (linear or quadratic form), and the optimal functional form selected to provide the best fit to the data based on the Akaike information criterion. Randomization before (but not after) 24 weeks to less-tight (versus tight) control was associated with fewer babies with birth weight <10th centile ( P interaction =0.005), but more preterm birth ( P interaction =0.043), and no effect on perinatal death or high-level neonatal care >48 hours ( P interaction =0.354). For the mother, less-tight (versus tight) control was associated with more severe hypertension at all gestational ages but particularly so before 28 weeks ( P interaction =0.076). In women with nonsevere, chronic, or gestational hypertension, there seems to be no gestational age at which less-tight (versus tight) control is the preferred management strategy to optimize maternal or perinatal outcomes. URL: https://www.isrctn.com. Unique identifier: ISRCTN71416914. © 2018 The Authors.

Improving the organisation of maternal health service delivery and optimising childbirth by increasing vaginal birth after caesarean section through enhanced women-centred care (OptiBIRTH trial): study protocol for a randomised controlled trial (ISRCTN10612254).

PubMed

Clarke, Mike; Savage, Gerard; Smith, Valerie; Daly, Deirdre; Devane, Declan; Gross, Mechthild M; Grylka-Baeschlin, Susanne; Healy, Patricia; Morano, Sandra; Nicoletti, Jane; Begley, Cecily

2015-11-30

The proportion of pregnant women who have a caesarean section shows a wide variation across Europe, and concern exists that these proportions are increasing. Much of the increase in caesarean sections in recent years is due to a cascade effect in which a woman who has had one caesarean section is much more likely to have one again if she has another baby. In some places, it has become common practice for a woman who has had a caesarean section to have this procedure again as a matter of routine. The alternative, vaginal birth after caesarean (VBAC), which has been widely recommended, results in fewer undesired results or complications and is the preferred option for most women. However, VBAC rates in some countries are much lower than in other countries. The OptiBIRTH trial uses a cluster randomised design to test a specially developed approach to try to improve the VBAC rate. It will attempt to increase VBAC rates from 25 % to 40 % through increased women-centred care and women's involvement in their care. Sixteen hospitals in Germany, Ireland and Italy agreed to join the study, and each hospital was randomly allocated to be either an intervention or a control site. If the OptiBIRTH intervention succeeds in increasing VBAC rates, its application across Europe might avoid the 160,000 unnecessary caesarean sections that occur every year at an extra direct annual cost of more than €150 million. Current Controlled Trials ISRCTN10612254 , registered 3 April 2013.

The 'cardiac-lung mass' artifact: an echocardiographic sign of lung atelectasis and/or pleural effusion

PubMed Central

Karabinis, Andreas; Saranteas, Theodosios; Karakitsos, Dimitrios; Lichtenstein, Daniel; Poularas, John; Yang, Clifford; Stefanadis, Christodoulos

2008-01-01

Introduction We conducted an ultrasound study to investigate echocardiographic artifacts in mechanically ventilated patients with lung pathology. Methods A total of 205 mechanically ventilated patients who exhibited lung atelectasis and/or pleural effusion were included in this 36-month study. The patients underwent lung echography and transthoracic echocardiography, with a linear 5 to 10 MHz and with a 1.5 to 3.6 MHz wide-angle phased-array transducer, respectively. Patients were examined by two experienced observers who were blinded to each other's interpretation. Results A total of 124 patients (60,48%) were hospitalized because of multiple trauma; 60 patients (29,26%) because of respiratory insufficiency, and 21 (10,24%) because of recent postoperative surgery. The mean duration ( ± standard deviation) of hospitalization was 35 ± 27 days. An intracardiac artifact was documented in 17 out of 205 patients (8.29%) by echocardiography. It was visible only in the apical views, whereas subsequent transesophageal echocardiography revealed no abnormalities. The artifact consisted of a mobile component that exhibited, on M-mode, a pattern of respiratory variation similar to the lung 'sinusoid sign'. Lung echography revealed lung atelectasis and/or pleural effusion adjacent to the heart, and a similar M-mode pattern was observed. The artifact was recorded within the left cardiac chambers in 11 cases and within the right cardiac chambers in six. Conclusions Lung atelectasis and/or pleural effusion may create a mirror image, intracardiac artifact in mechanically ventilated patients. The latter was named the 'cardiac-lung mass' artifact to underline the important diagnostic role of both echocardiography and lung echography in these patients. Trial registration This trial is ISRCTN registered: ISRCTN 49216096. PMID:18826590

Characterization of Pharmacologic and Pharmacokinetic Properties of CCX168, a Potent and Selective Orally Administered Complement 5a Receptor Inhibitor, Based on Preclinical Evaluation and Randomized Phase 1 Clinical Study.

PubMed

Bekker, Pirow; Dairaghi, Daniel; Seitz, Lisa; Leleti, Manmohan; Wang, Yu; Ertl, Linda; Baumgart, Trageen; Shugarts, Sarah; Lohr, Lisa; Dang, Ton; Miao, Shichang; Zeng, Yibin; Fan, Pingchen; Zhang, Penglie; Johnson, Daniel; Powers, Jay; Jaen, Juan; Charo, Israel; Schall, Thomas J

2016-01-01

The complement 5a receptor has been an attractive therapeutic target for many autoimmune and inflammatory disorders. However, development of a selective and potent C5aR antagonist has been challenging. Here we describe the characterization of CCX168 (avacopan), an orally administered selective and potent C5aR inhibitor. CCX168 blocked the C5a binding, C5a-mediated migration, calcium mobilization, and CD11b upregulation in U937 cells as well as in freshly isolated human neutrophils. CCX168 retains high potency when present in human blood. A transgenic human C5aR knock-in mouse model allowed comparison of the in vitro and in vivo efficacy of the molecule. CCX168 effectively blocked migration in in vitro and ex vivo chemotaxis assays, and it blocked the C5a-mediated neutrophil vascular endothelial margination. CCX168 was effective in migration and neutrophil margination assays in cynomolgus monkeys. This thorough in vitro and preclinical characterization enabled progression of CCX168 into the clinic and testing of its safety, tolerability, pharmacokinetic, and pharmacodynamic profiles in a Phase 1 clinical trial in 48 healthy volunteers. CCX168 was shown to be well tolerated across a broad dose range (1 to 100 mg) and it showed dose-dependent pharmacokinetics. An oral dose of 30 mg CCX168 given twice daily blocked the C5a-induced upregulation of CD11b in circulating neutrophils by 94% or greater throughout the entire day, demonstrating essentially complete target coverage. This dose regimen is being tested in clinical trials in patients with anti-neutrophil cytoplasmic antibody-associated vasculitis. Trial Registration ISRCTN registry with trial ID ISRCTN13564773.

Characterization of Pharmacologic and Pharmacokinetic Properties of CCX168, a Potent and Selective Orally Administered Complement 5a Receptor Inhibitor, Based on Preclinical Evaluation and Randomized Phase 1 Clinical Study

PubMed Central

Bekker, Pirow; Dairaghi, Daniel; Seitz, Lisa; Leleti, Manmohan; Wang, Yu; Ertl, Linda; Baumgart, Trageen; Shugarts, Sarah; Lohr, Lisa; Dang, Ton; Miao, Shichang; Zeng, Yibin; Fan, Pingchen; Zhang, Penglie; Johnson, Daniel; Powers, Jay; Jaen, Juan; Charo, Israel; Schall, Thomas J.

2016-01-01

The complement 5a receptor has been an attractive therapeutic target for many autoimmune and inflammatory disorders. However, development of a selective and potent C5aR antagonist has been challenging. Here we describe the characterization of CCX168 (avacopan), an orally administered selective and potent C5aR inhibitor. CCX168 blocked the C5a binding, C5a-mediated migration, calcium mobilization, and CD11b upregulation in U937 cells as well as in freshly isolated human neutrophils. CCX168 retains high potency when present in human blood. A transgenic human C5aR knock-in mouse model allowed comparison of the in vitro and in vivo efficacy of the molecule. CCX168 effectively blocked migration in in vitro and ex vivo chemotaxis assays, and it blocked the C5a-mediated neutrophil vascular endothelial margination. CCX168 was effective in migration and neutrophil margination assays in cynomolgus monkeys. This thorough in vitro and preclinical characterization enabled progression of CCX168 into the clinic and testing of its safety, tolerability, pharmacokinetic, and pharmacodynamic profiles in a Phase 1 clinical trial in 48 healthy volunteers. CCX168 was shown to be well tolerated across a broad dose range (1 to 100 mg) and it showed dose-dependent pharmacokinetics. An oral dose of 30 mg CCX168 given twice daily blocked the C5a-induced upregulation of CD11b in circulating neutrophils by 94% or greater throughout the entire day, demonstrating essentially complete target coverage. This dose regimen is being tested in clinical trials in patients with anti-neutrophil cytoplasmic antibody-associated vasculitis. Trial Registration ISRCTN registry with trial ID ISRCTN13564773. PMID:27768695

Sympathetic activity and early mobilization in patients in intensive and intermediate care with severe brain injuries: a preliminary prospective randomized study.

PubMed

Rocca, A; Pignat, J-M; Berney, L; Jöhr, J; Van de Ville, D; Daniel, R T; Levivier, M; Hirt, L; Luft, A R; Grouzmann, E; Diserens, K

2016-09-13

Patients who experience severe brain injuries are at risk of secondary brain damage, because of delayed vasospasm and edema. Traditionally, many of these patients are kept on prolonged bed rest in order to maintain adequate cerebral blood flow, especially in the case of subarachnoid hemorrhage. On the other hand, prolonged bed rest carries important morbidity. There may be a clinical benefit in early mobilization and our hypothesis is that early gradual mobilization is safe in these patients. The aim of this study was to observe and quantify the changes in sympathetic activity, mainly related to stress, and blood pressure in gradual postural changes by the verticalization robot (Erigo®) and after training by a lower body ergometer (MOTOmed-letto®), after prolonged bed rest of minimum 7 days. Thirty patients with severe neurological injuries were randomized into 3 groups with different protocols of mobilization: Standard, MOTOmed-letto® or Erigo® protocol. We measured plasma catecholamines, metanephrines and blood pressure before, during and after mobilization. Blood pressure does not show any significant difference between the 3 groups. The analysis of the catecholamines suggests a significant increase in catecholamine production during Standard mobilization with physiotherapists and with MOTOmed-letto® and no changes with Erigo®. This preliminary prospective randomized study shows that the mobilization of patients with severe brain injuries by means of Erigo® does not increase the production of catecholamines. It means that Erigo® is a well-tolerated method of mobilization and can be considered a safe system of early mobilization of these patients. Further studies are required to validate our conclusions. The study was registered in the ISRCTN registry with the trial registration number ISRCTN56402432 . Date of registration: 08.03.2016. Retrospectively registered.

Sensitivity and specificity of the hyperdense artery sign for arterial obstruction in acute ischemic stroke.

PubMed

Mair, Grant; Boyd, Elena V; Chappell, Francesca M; von Kummer, Rüdiger; Lindley, Richard I; Sandercock, Peter; Wardlaw, Joanna M

2015-01-01

In acute ischemic stroke, the hyperdense artery sign (HAS) on noncontrast computed tomography (CT) is thought to represent intraluminal thrombus and, therefore, is a surrogate of arterial obstruction. We sought to assess the accuracy of HAS as a marker of arterial obstruction by thrombus. The Third International Stroke Trial (IST-3) was a randomized controlled trial testing the use of intravenous thrombolysis for acute ischemic stroke in patients who did not clearly meet the prevailing license criteria. Some participating IST-3 centers routinely performed CT or MR angiography at baseline. One reader assessed all relevant scans independently, blinded to all other data; we checked observer reliability. We combined IST-3 data with a systematic review and meta-analysis of all studies that assessed the accuracy of HAS using angiography (any modality). IST-3 had 273 patients with baseline CT or MR angiography and was the largest study of HAS accuracy. The meta-analysis (n=902+273=1175, including IST-3) found sensitivity and specificity of HAS for arterial obstruction on angiography to be 52% and 95%, respectively. HAS was more commonly identified in proximal than distal arteries (47% versus 37%; P=0.015), and its sensitivity increased with thinner CT slices (r=-0.73; P=0.001). Neither extent of obstruction nor time after stroke influenced HAS accuracy. When present in acute ischemic stroke, HAS indicates a high likelihood of arterial obstruction, but its absence indicates only a 50/50 chance of normal arterial patency. Thin-slice CT improves sensitivity of HAS detection. http://www.controlled-trials.com/ISRCTN25765518. Unique identifier: ISRCTN25765518. © 2014 American Heart Association, Inc.

Cost-effectiveness of invitation to food supplementation early in pregnancy combined with multiple micronutrients on infant survival: analysis of data from MINIMat randomized trial, Bangladesh.

PubMed

Shaheen, Rubina; Persson, Lars Åke; Ahmed, Shakil; Streatfield, Peter Kim; Lindholm, Lars

2015-05-28

Absence of cost-effectiveness (CE) analyses limits the relevance of large-scale nutrition interventions in low-income countries. We analyzed if the effect of invitation to food supplementation early in pregnancy combined with multiple micronutrient supplements (MMS) on infant survival represented value for money compared to invitation to food supplementation at usual time in pregnancy combined with iron-folic acid. Outcome data, infant mortality (IM) rates, came from MINIMat trial (Maternal and Infant Nutrition Interventions, Matlab, ISRCTN16581394). In MINIMat, women were randomized to early (E around 9 weeks of pregnancy) or usual invitation (U around 20 weeks) to food supplementation and daily doses of 30 mg, or 60 mg iron with 400 μgm of folic acid, or MMS with 15 micronutrients including 30 mg iron and 400 μgm of folic acid. In MINIMat, EMMS significantly reduced IM compared to UFe60F (U plus 60 mg iron 400 μgm Folic acid). We present incremental CE ratios for incrementing UFe60F to EMMS. Costing data came mainly from a published study. By incrementing UFe60F to EMMS, one extra IM could be averted at a cost of US$907 and US$797 for NGO run and government run CNCs, respectively, and at US$1024 for a hypothetical scenario of highest cost. These comparisons generated one extra life year (LY) saved at US$30, US$27, and US$34, respectively. Incrementing UFe60F to EMMS in pregnancy seems worthwhile from health economic and public health standpoints. Maternal and Infant Nutrition Interventions, Matlab; ISRCTN16581394 ; Date of registration: Feb 16, 2009.

Virtually optimized insoles for offloading the diabetic foot: A randomized crossover study.

PubMed

Telfer, S; Woodburn, J; Collier, A; Cavanagh, P R

2017-07-26

Integration of objective biomechanical measures of foot function into the design process for insoles has been shown to provide enhanced plantar tissue protection for individuals at-risk of plantar ulceration. The use of virtual simulations utilizing numerical modeling techniques offers a potential approach to further optimize these devices. In a patient population at-risk of foot ulceration, we aimed to compare the pressure offloading performance of insoles that were optimized via numerical simulation techniques against shape-based devices. Twenty participants with diabetes and at-risk feet were enrolled in this study. Three pairs of personalized insoles: one based on shape data and subsequently manufactured via direct milling; and two were based on a design derived from shape, pressure, and ultrasound data which underwent a finite element analysis-based virtual optimization procedure. For the latter set of insole designs, one pair was manufactured via direct milling, and a second pair was manufactured through 3D printing. The offloading performance of the insoles was analyzed for forefoot regions identified as having elevated plantar pressures. In 88% of the regions of interest, the use of virtually optimized insoles resulted in lower peak plantar pressures compared to the shape-based devices. Overall, the virtually optimized insoles significantly reduced peak pressures by a mean of 41.3kPa (p<0.001, 95% CI [31.1, 51.5]) for milled and 40.5kPa (p<0.001, 95% CI [26.4, 54.5]) for printed devices compared to shape-based insoles. The integration of virtual optimization into the insole design process resulted in improved offloading performance compared to standard, shape-based devices. ISRCTN19805071, www.ISRCTN.org. Copyright © 2017 Elsevier Ltd. All rights reserved.

Physical activity prescription by primary care nurses using health assets: Study design of a randomized controlled trial in patients with cardiovascular risk factors.

PubMed

Riera-Sampol, Aina; Tauler, Pedro; Bennasar-Veny, Miquel; Leiva, Alfonso; Artigues-Vives, Guillem; De Pedro-Gómez, Joan; Pericàs, Jordi; Moreno, Carlos; Arbos, Maite; Aguilo, Antoni

2017-09-01

To analyse the efficacy of a 12-month multifactorial intervention by primary care nurses in increasing adherence to physical activity prescription (150 min/week) in patients with two or more cardiovascular risk factors and with cardiovascular risk up to 15% determined by the REGICOR equation. In Spain, cardiovascular diseases are responsible for 30.5% of deaths. Regular physical activity decreases mortality risk due to cardiovascular diseases but the effectiveness of physical activity prescription in routine in primary care settings has been shown to be low. Multicentre, single-blind, parallel randomized (in two different branches) clinical trial. At least 368 participants will be recruited (184 control and 184 intervention), to show an 8% increase in adherence to the physical activity prescription (1.2% control group and 9.2% intervention group). Participants will be patients aged 35-75 years with at least two cardiovascular risk factors and with a cardiovascular risk of up to 15% measured using the Framingham-REGICOR equation. Intervention will be performed throughout baseline and three follow-up visits. A motivational interview, the trans-theoretical stages of changes of Prochaska and DiClemente and an individualized prescription of physical exercise using physical activity assets will be used in the intervention. Data will be collected at baseline and after the 1-year intervention. The present study will allow us to find out whether this brief multifactorial intervention induces greater adherence to physical activity prescription than usual practice, improving the quality of patient care. International Standard Randomized Controlled Trial Number (ISRCTN): ISRCTN76069254. Protocol version 1.1, 6 July 2015. © 2017 John Wiley & Sons Ltd.

Personalised Hip Therapy: development of a non-operative protocol to treat femoroacetabular impingement syndrome in the FASHIoN randomised controlled trial

PubMed Central

Wall, Peter DH; Dickenson, Edward J; Robinson, David; Hughes, Ivor; Realpe, Alba; Hobson, Rachel; Griffin, Damian R; Foster, Nadine E

2016-01-01

Introduction Femoroacetabular impingement (FAI) syndrome is increasingly recognised as a cause of hip pain. As part of the design of a randomised controlled trial (RCT) of arthroscopic surgery for FAI syndrome, we developed a protocol for non-operative care and evaluated its feasibility. Methods In phase one, we developed a protocol for non-operative care for FAI in the UK National Health Service (NHS), through a process of systematic review and consensus gathering. In phase two, the protocol was tested in an internal pilot RCT for protocol adherence and adverse events. Results The final protocol, called Personalised Hip Therapy (PHT), consists of four core components led by physiotherapists: detailed patient assessment, education and advice, help with pain relief and an exercise-based programme that is individualised, supervised and progressed over time. PHT is delivered over 12–26 weeks in 6–10 physiotherapist-patient contacts, supplemented by a home exercise programme. In the pilot RCT, 42 patients were recruited and 21 randomised to PHT. Review of treatment case report forms, completed by physiotherapists, showed that 13 patients (62%) received treatment that had closely followed the PHT protocol. 13 patients reported some muscle soreness at 6 weeks, but there were no serious adverse events. Conclusion PHT provides a structure for the non-operative care of FAI and offers guidance to clinicians and researchers in an evolving area with limited evidence. PHT was deliverable within the National Health Service, is safe, and now forms the comparator to arthroscopic surgery in the UK FASHIoN trial (ISRCTN64081839). Trial registration number ISRCTN 09754699. PMID:27629405

An evaluation of low volume high-intensity intermittent training (HIIT) for health risk reduction in overweight and obese men.

PubMed

Kelly, Benjamin M; Xenophontos, Soteris; King, James A; Nimmo, Myra A

2017-01-01

Both sprint interval training (SIT) and high-intensity intermittent training (HIIT) have been described as time-efficient strategies for inducing favourable metabolic and cardiorespiratory adaptations in healthy and diseased participants. To date, little attention has been given to profiling the potential health benefits of HIIT or modified HIIT training within overweight and obese cohorts with particular focus on inflammation. Within this pilot trial, we tested the hypothesis that 6 sessions of HIIT performed over 2 weeks with 1-2 days' rest would improve aerobic capacity, glucose metabolism and inflammatory profile in an overweight and obese male cohort. Additionally, we profiled the potential health benefits of 4 HIIT sessions performed over the same period. 18 overweight or obese males (BMI = 31.2 ± 3.6; V̇O 2  = 30.3 ± 4.4 ml.kg.min -1 ) were studied before and 72 h after HIIT. Training sessions consisted of 10 x 1 min intervals at 90% HR peak separated by 1 min recovery periods. Exercise was performed either 6 (group 1, n  = 8) or 4 (group 2, n  = 10) times over a 2 week period. After training no changes were detected from baseline for body composition, aerobic capacity, glucose metabolism or inflammatory profile ( p  > 0.05) in either group. Both 6 and 4 sessions of HIIT performed over a 2-week period are ineffective in improving selected health markers within an overweight and obese cohort. This trial reports data from human participants and was retrospectively registered on 22/02/2017 with the ISRCTN registry, trial number ISRCTN90672085.

An exploratory cluster randomised trial of a university halls of residence based social norms marketing campaign to reduce alcohol consumption among 1st year students

PubMed Central

2013-01-01

Aims This exploratory trial examines the feasibility of implementing a social norms marketing campaign to reduce student drinking in universities in Wales, and evaluating it using cluster randomised trial methodology. Methods Fifty residence halls in 4 universities in Wales were randomly assigned to intervention or control arms. Web and paper surveys were distributed to students within these halls (n = 3800), assessing exposure/contamination, recall of and evaluative responses to intervention messages, perceived drinking norms and personal drinking behaviour. Measures included the Drinking Norms Rating Form, the Daily Drinking Questionnaire and AUDIT-C. Results A response rate of 15% (n = 554) was achieved, varying substantially between sites. Intervention posters were seen by 80% and 43% of students in intervention and control halls respectively, with most remaining materials seen by a minority in both groups. Intervention messages were rated as credible and relevant by little more than half of students, though fewer felt they would influence their behaviour, with lighter drinkers more likely to perceive messages as credible. No differences in perceived norms were observed between intervention and control groups. Students reporting having seen intervention materials reported lower descriptive and injunctive norms than those who did not. Conclusions Attention is needed to enhancing exposure, credibility and perceived relevance of intervention messages, particularly among heavier drinkers, before definitive evaluation can be recommended. A definitive evaluation would need to consider how it would achieve sufficient response rates, whilst hall-level cluster randomisation appears subject to a significant degree of contamination. Trial registration ISRCTN: ISRCTN48556384 PMID:23594918

Effects of Silexan on the Serotonin-1A Receptor and Microstructure of the Human Brain: A Randomized, Placebo-Controlled, Double-Blind, Cross-Over Study with Molecular and Structural Neuroimaging

PubMed Central

Baldinger, Pia; Höflich, Anna S.; Mitterhauser, Markus; Hahn, Andreas; Rami-Mark, Christina; Spies, Marie; Wadsak, Wolfgang; Lanzenberger, Rupert

2015-01-01

Background: Recently, Silexan, a patented active substance comprised of an essential oil produced from Lavandula angustifolia flowers, has been authorized in Germany as a medicinal product for the treatment of states of restlessness related to anxious mood. Its efficacy has been shown in several forms of anxiety disorders. Findings from preclinical and clinical studies attribute a major role to the serotonin-1A receptor in the pathogenesis and treatment of anxiety. Methods: To elucidate the effect of Silexan on serotonin-1A receptor binding, 17 healthy men underwent 2 positron emission tomography measurements using the radioligand [carbonyl-11C]WAY-100635 following the daily intake of 160mg Silexan or placebo for a minimum of 8 weeks (randomized, double-blind, cross-over design). Additionally, structural magnetic resonance imaging and voxel-based morphometry analysis was performed to determine potential effects on gray matter microstructure. Results: Serotonin-1A receptor binding potential was shown to be significantly reduced following the intake of Silexan compared with placebo in 2 large clusters encompassing the temporal gyrus, the fusiform gyrus and the hippocampus on one hand as well as the insula and anterior cingulate cortex on the other hand. No effects of Silexan on gray matter volume could be detected in this investigation. Conclusion: This positron emission tomography study proposes an involvement of the serotonin-1A receptor in the anxiolytic effects of Silexan. The study was registered in the International Standard Randomized Controlled Trial Number Register as ISRCTN30885829 (http://www.controlled-trials.com/isrctn/). PMID:25522403

Randomized placebo-controlled trial of CDB-2914 in new users of a levonorgestrel-releasing intrauterine system shows only short-lived amelioration of unscheduled bleeding

PubMed Central

Warner, P.; Guttinger, A.; Glasier, A.F.; Lee, R.J.; Nickerson, S.; Brenner, R.M.; Critchley, H.O.D.

2010-01-01

BACKGROUND The levonorgestrel-releasing intrauterine system (LNG-IUS) is a highly effective contraceptive. However, during early months of use unscheduled vaginal bleeding is common, sometimes leading to discontinuation. This study aimed to determine whether intermittent administration of progesterone receptor modulator CDB-2914 would suppress unscheduled bleeding during the first 4 months after insertion of the LNG-IUS. METHODS CDB-2914 150 mg, in divided doses, or placebo tablets, were administered over three consecutive days starting on Days 21, 49 and 77 after LNG-IUS insertion, in a double-blind randomized controlled trial of women aged 19–49 years, newly starting use of LNG-IUS. Daily bleeding diaries were completed for 6 months, and summarized across blocks as percentage days bleeding/spotting (BS%). RESULTS Of 69 women randomized to receive CDB-2914, and 67 placebo, 61 and 55, respectively, completed the trial. BS% decreased with time in both arms, but showed a much steeper treatment-phase gradient in the placebo arm (P < 0.0001), so that a benefit of CDB-2914 in the 28 days after first treatment (−11% points, 95% CI −19 to −2), converted to a disadvantage by 64 days after the third treatment (+10% points, 95% CI 1–18). CONCLUSIONS The effect of CDB-2914 on BS% was initially beneficial but then by third treatment was disadvantageous. Nevertheless, only 3% (4/136) of all women discontinued LNG-IUS. These findings give insight into possible mechanisms and suggest future research directions. ISRCTN Trial no. ISRCTN58283041; EudraCT no. 2006-006511-72. PMID:19897857

Inhaled Colistin in Patients with Bronchiectasis and Chronic Pseudomonas aeruginosa Infection

PubMed Central

Foweraker, Juliet E.; Wilkinson, Peter; Kenyon, Robert F.; Bilton, Diana

2014-01-01

Rationale: Chronic infection with Pseudomonas aeruginosa is associated with an increased exacerbation frequency, a more rapid decline in lung function, and increased mortality in patients with bronchiectasis. Objectives: To perform a randomized placebo-controlled study assessing the efficacy and safety of inhaled colistin in patients with bronchiectasis and chronic P. aeruginosa infection. Methods: Patients with bronchiectasis and chronic P. aeruginosa infection were enrolled within 21 days of completing a course of antipseudomonal antibiotics for an exacerbation. Participants were randomized to receive colistin (1 million IU; n = 73) or placebo (0.45% saline; n = 71) via the I-neb twice a day, for up to 6 months. Measurements and Main Results: The primary endpoint was time to exacerbation. Secondary endpoints included time to exacerbation based on adherence recorded by the I-neb, P. aeruginosa bacterial density, quality of life, and safety parameters. All analyses were on the intention-to-treat population. Median time (25% quartile) to exacerbation was 165 (42) versus 111 (52) days in the colistin and placebo groups, respectively (P = 0.11). In adherent patients (adherence quartiles 2–4), the median time to exacerbation was 168 (65) versus 103 (37) days in the colistin and placebo groups, respectively (P = 0.038). P. aeruginosa density was reduced after 4 (P = 0.001) and 12 weeks (P = 0.008) and the St. George’s Respiratory Questionnaire total score was improved after 26 weeks (P = 0.006) in the colistin versus placebo patients, respectively. There were no safety concerns. Conclusions: Although the primary endpoint was not reached, this study shows that inhaled colistin is a safe and effective treatment in adherent patients with bronchiectasis and chronic P. aeruginosa infection. Clinical trial registered with http://www.isrctn.org/ (ISRCTN49790596) PMID:24625200

Using daily text messages to improve adherence to infant micronutrient powder (MNP) packets in rural western China: A cluster-randomized controlled trial

PubMed Central

Wang, Xu; Liu, Chengfang; Zhang, Linxiu; Yue, Ai; Medina, Alexis; Rozelle, Scott

2018-01-01

Objective To evaluate the effectiveness of daily text messages as a means to improve caregivers’ adherence to infant micronutrient powder (MNP) in rural Shaanxi Province of China. Methodology 638 infants aged 6–11 months in 234 villages were involved in a cluster-randomized controlled trial (RCT). All caregivers were given free infant MNP packets at baseline in April 2013 and the follow-up survey was in July 2013. We randomly assigned 318 infants in 117 villages to treatment group (receiving daily text message) and 320 infants in the other 117 villages as control group. Results On average, daily text messages increased the number of MNP packets fed (marginal effect = 4.63; 95% confidence interval (CI) = 0.16, 9.10). The text message is more likely to increase the consumption of MNP packets if the primary caregiver was the mother (marginal effect = 12.19; 95% CI = 0.69, 23.68). Receiving the text message appears to significantly increase the likelihood of full adherence when the primary caregiver can either check (odds ratio = 2.93; 95% CI = 1.34, 6.40) or knows how to send (odds ratio = 3.26; 95% CI = 1.53, 6.97) text messages. Conclusion Daily text messages improved the consumption of infant MNP packets. However, the impact was not large enough to increase the probability of caregivers being fully adherent to the feeding instruction, which is to feed 5–7 packets per week as recommended. In addition, when the mother is the caregiver and when the caregiver can check or knows how to send text messages there is greater adherence by the primary caregivers. Trial registration http://www.isrctn.com/ISRCTN44149146 PMID:29352304

Feasibility of an interactive voice response system for monitoring depressive symptoms in a lower-middle income Latin American country.

PubMed

Janevic, Mary R; Aruquipa Yujra, Amparo C; Marinec, Nicolle; Aguilar, Juvenal; Aikens, James E; Tarrazona, Rosa; Piette, John D

2016-01-01

Innovative, scalable solutions are needed to address the vast unmet need for mental health care in low- and middle-income countries (LMICs). We conducted a feasibility study of a 14-week automated telephonic interactive voice response (IVR) depression self-care service among Bolivian primary care patients with at least moderately severe depressive symptoms. We analyzed IVR call completion rates, the reliability and validity of IVR-collected data, and participant satisfaction. Of the 32 participants, the majority were women (78 % or 25/32) and non-indigenous (75 % or 24/32). Participants had moderate depressive symptoms at baseline (PHQ-8 score mean 13.3, SD = 3.5) and reported good or fair general health status (88 % or 28/32). Fifty-four percent of weekly IVR calls (approximately 7 out of 13 active call-weeks) were completed. Neither PHQ-8 scores nor IVR call completion differed significantly by ethnicity, education, self-reported depression diagnosis, self-reported overall health, number of chronic conditions, or health literacy. The reliability for IVR-collected PHQ-8 scores was good (Cronbach's alpha = 0.83). Virtually every participant (97 %) was "mostly" or "very" satisfied with the program. Many described the program as beneficial for their mood and self-care, albeit limited by some technological difficulties and the lack of human interaction. Findings suggest that IVR could feasibly be used to provide monitoring and self-care education to depressed patients in Bolivia. An expanded stepped-care service offering contact with lay health workers for more depressed individuals and expanded mHealth content may foster greater patient engagement and enhance its therapeutic value while remaining cost-effective. Trial registration ISRCTN ISRCTN 18403214. Registered 14 September 2016. Retrospectively registered.

A multi-center study on the regenerative effects of erythropoietin in burn and scalding injuries: study protocol for a randomized controlled trial.

PubMed

Günter, Christina Irene; Bader, Augustinus; Dornseifer, Ulf; Egert, Silvia; Dunda, Sebastian; Grieb, Gerrit; Wolter, Thomas; Pallua, Norbert; von Wild, Tobias; Siemers, Frank; Mailänder, Peter; Thamm, Oliver; Ernert, Carsten; Steen, Michael; Sievers, Reiner; Reichert, Bert; Rahmanian-Schwarz, Afshin; Schaller, Hans; Hartmann, Bernd; Otte, Max; Kehl, Victoria; Ohmann, Christian; Jelkmann, Wolfgang; Machens, Hans-Günther

2013-05-03

Although it was initially assumed that erythropoietin (EPO) was a hormone that only affected erythropoiesis, it has now been proposed that EPO plays an additional key role in the regulation of acute and chronic tissue damage. This is a large, prospective, randomized, double-blind, multi-center study, funded by the German Federal Ministry of Education and Research, and fully approved by the designated ethics committee. The trial, which is to investigate the effects of EPO in severely burned patients, is in its recruitment phase and is being carried out in 13 German burn care centers. A total of 150 patients are to be enrolled to receive study medication every other day for 21 days (EPO 150 IU/kg body weight or placebo). A follow-up of one year is planned. The primary endpoint of this study is the time until complete re-epithelialization of a defined skin graft donor site is reached. Furthermore, clinical parameters such as wound healing, scar formation (using the Vancouver scar scale), laboratory values, quality of life (SF-36), angiogenic effects, and gene- and protein-expression patterns are to be determined. The results will be carefully evaluated for gender differences. We are seeking new insights into the mechanisms of wound healing in thermally injured patients and more detailed information about the role EPO plays, specifically in these complex interactions. We additionally expect that the biomimetic effects of EPO will be useful in the treatment of acute thermal dermal injuries. EudraCT Number: 2006-002886-38, Protocol Number: 0506, ISRCT Number: http://controlled-trials.com/ISRCTN95777824/ISRCTN95777824.

Cognitive behaviour therapy (CBT) for anxiety and depression in adults with mild intellectual disabilities (ID): a pilot randomised controlled trial

PubMed Central

2011-01-01

Background Several studies have showed that people with intellectual disabilities (ID) have suitable skills to undergo cognitive behavioural therapy (CBT). Case studies have reported successful use of cognitive behavioural therapy techniques (with adaptations) in people with ID. Modified cognitive behavioural therapy may be a feasible and effective approach for the treatment of depression, anxiety, and other mood disorders in ID. To date, two studies have reported group-based manaulised cognitive behavioural treatment programs for depression in people with mild ID. However, there is no individual manualised programme for anxiety or depression in people with intellectual disabilities. The aims of the study are to determine the feasibility of conducting a randomised controlled trial for CBT in people with ID. The data will inform the power calculation and other aspects of carrying out a definitive randomised controlled trial. Methods Thirty participants with mild ID will be allocated randomly to either CBT or treatment as usual (TAU). The CBT group will receive up to 20 hourly individual CBT over a period of 4 months. TAU is the standard treatment which is available to any adult with an intellectual disability who is referred to the intellectual disability service (including care management, community support, medical, nursing or social support). Beck Youth Inventories (Beck Anxiety Inventory & Beck Depression Inventory) will be administered at baseline; end of treatment (4 months) and at six months to evaluate the changes in depression and anxiety. Client satisfaction, quality of life and the health economics will be secondary outcomes. Discussion The broad outcome of the study will be to produce clear guidance for therapists to apply an established psychological intervention and identify how and whether it works with people with intellectual disabilities. Trial registration ISRCTN: ISRCTN38099525 PMID:21492437

Xenon in the treatment of panic disorder: an open label study.

PubMed

Dobrovolsky, Alexander; Ichim, Thomas E; Ma, Daqing; Kesari, Santosh; Bogin, Vladimir

2017-06-13

Current treatments of panic disorder (PD) are limited by adverse effects, poor efficacy, and need for chronic administration. The established safety profile of subanesthetic concentrations of xenon gas, which is known to act as a glutamate subtype NMDA receptor antagonist, coupled with preclinical studies demonstrating its effects in other anxiety related conditions, prompted us to evaluate its feasibility and efficacy in treatment of patients with PD. An open-label clinical trial of xenon-oxygen mixture was conducted in 81 patients with PD; group 1 consisting of patients only with PD (N = 42); and group 2 patients with PD and other comorbidities (N = 39). Based on the analysis of the results of a number of psychometric scales used in this study (SAS, HADS, CGI), several conclusions can be made: (1) xenon is a potentially effective modality in acute treatment of PD; (2) an anti-panic effect of xenon administration persists for at least 6 months after the completion of the active phase of treatment; (3) xenon inhalation is well tolerated, with the drop-out rates being much lower than that of conventional pharmacotherapy (5.8% vs. 15%); (4) the severity of depressive disorders that frequently accompany PD can be significantly reduced with the use of xenon; (5) xenon may be considered as an alternative to benzodiazepines in conjunction with cognitive-behavioral therapy as a safe modality in treatment of anxiety disorder. These data support the need for randomized double-blind clinical trials to further study xenon-based interventions. Trial registration This clinical trial was retrospectively registered on April 14th, 2017 as ISRCTN15184285 in the ISRCTN database.

“It’s Somebody else’s responsibility” - perceptions of general practitioners, heart failure nurses, care home staff, and residents towards heart failure diagnosis and management for older people in long-term care: a qualitative interview study

PubMed Central

2013-01-01

Background Older people in care-facilities may be less likely to access gold standard diagnosis and treatment for heart failure (HF) than non residents; little is understood about the factors that influence this variability. This study aimed to examine the experiences and expectations of clinicians, care-facility staff and residents in interpreting suspected symptoms of HF and deciding whether and how to intervene. Methods This was a nested qualitative study using in-depth interviews with older residents with a diagnosis of heart failure (n=17), care-facility staff (n=8), HF nurses (n=3) and general practitioners (n=5). Results Participants identified a lack of clear lines of responsibility in providing HF care in care-facilities. Many clinical staff expressed negative assumptions about the acceptability and utility of interventions, and inappropriately moderated residents’ access to HF diagnosis and treatment. Care-facility staff and residents welcomed intervention but experienced a lack of opportunity for dialogue about the balance of risks and benefits. Most residents wanted to be involved in healthcare decisions but physical, social and organisational barriers precluded this. An onsite HF service offered a potential solution and proved to be acceptable to residents and care-facility staff. Conclusions HF diagnosis and management is of variable quality in long-term care. Conflicting expectations and a lack of co-ordinated responsibility for care, contribute to a culture of benign neglect that excludes the wishes and needs of residents. A greater focus on rights, responsibilities and co-ordination may improve healthcare quality for older people in care. Trial registration ISRCTN: ISRCTN19781227 PMID:23829674

Diabetes Intervention Accentuating Diet and Enhancing Metabolism (DIADEM-I): a randomised controlled trial to examine the impact of an intensive lifestyle intervention consisting of a low-energy diet and physical activity on body weight and metabolism in early type 2 diabetes mellitus: study protocol for a randomized controlled trial.

PubMed

Taheri, Shahrad; Chagoury, Odette; Zaghloul, Hadeel; Elhadad, Sara; Ahmed, Salma Hayder; Omar, Omar; Payra, Sherryl; Ahmed, Salma; El Khatib, Neda; Amona, Rasha Abou; El Nahas, Katie; Bolton, Matthew; Chaar, Henem; Suleiman, Noor; Jayyousi, Amin; Zirie, Mahmoud; Janahi, Ibrahim; Elhag, Wahiba; Alnaama, Abdulla; Zainel, Abduljaleel; Hassan, Dahlia; Cable, Tim; Charlson, Mary; Wells, Martin; Al-Hamaq, Abdulla; Al-Abdulla, Samya; Abou-Samra, Abdul Badi

2018-05-21

Type 2 diabetes mellitus (T2DM) and obesity are syndemic and will have a significant impact on affected individuals and healthcare services worldwide. Evidence shows that T2DM remission can be achieved with significant weight loss in those who are younger with early diabetes and requiring fewer medications for glycaemic control. DIADEM-I aims to examine the impact of an intensive lifestyle intervention (ILI) using a low-energy diet (LED) meal replacement approach combined with physical activity in younger individuals with early T2DM. The planned study is an ongoing, non-blinded, pragmatic, randomised controlled, parallel-group trial examining the impact of an LED-based ILI on body weight and diabetes remission in younger (18-50 years) T2DM individuals with early diabetes (≤ 3-year duration). The ILI will be compared to usual medical care (UMC). The primary outcome will be weight loss at 12 months. Other key outcomes of interest include diabetes remission, glycaemic control, diabetes complications, cardiovascular health, physical activity, mental health, and quality of life. It is planned for the study to include 138 subjects for assessment of the primary outcome. Safety will be assessed throughout. If DIADEM-I demonstrates a clinically significant effect for younger individuals with early T2DM, it will inform clinical guidelines and services of the future for management of T2DM. ISRCTN: ISRCTN20754766 (date assigned: 7 June 2017); ClinicalTrials.gov, ID: NCT03225339 Registered on 26 June 2017.

Valuing breastfeeding: a qualitative study of women's experiences of a financial incentive scheme for breastfeeding.

PubMed

Johnson, Maxine; Whelan, Barbara; Relton, Clare; Thomas, Kate; Strong, Mark; Scott, Elaine; Renfrew, Mary J

2018-01-08

A cluster randomised controlled trial of a financial incentive for breastfeeding conducted in areas with low breastfeeding rates in the UK reported a statistically significant increase in breastfeeding at 6-8 weeks. In this paper we report an analysis of interviews with women eligible for the scheme, exploring their experiences and perceptions of the scheme and its impact on breastfeeding to support the interpretation of the results of the trial. Semi-structured interviews were carried out with 35 women eligible for the scheme during the feasibility and trial stages. All interviews were recorded and verbatim transcripts analysed using a Framework Analysis approach. Women reported that their decisions about infant feeding were influenced by the behaviours and beliefs of their family and friends, socio-cultural norms and by health and practical considerations. They were generally positive about the scheme, and felt valued for the effort involved in breastfeeding. The vouchers were frequently described as a reward, a bonus and something to look forward to, and helping women keep going with their breastfeeding. They were often perceived as compensation for the difficulties women encountered during breastfeeding. The scheme was not thought to make a difference to mothers who were strongly against breastfeeding. However, women did believe the scheme would help normalise breastfeeding, influence those who were undecided and help women to keep going with breastfeeding and reach key milestones e.g. 6 weeks or 3 months. The scheme was acceptable to women, who perceived it as rewarding and valuing them for breastfeeding. Women reported that the scheme could raise awareness of breastfeeding and encourage its normalisation. This provides a possible mechanism of action to explain the results of the trial. The trial is registered with the ISRCTN registry, number 44898617 , https://www.isrctn.com.

Lessons learned from a double-blind randomised placebo-controlled study with a iota-carrageenan nasal spray as medical device in children with acute symptoms of common cold.

PubMed

Fazekas, Tamas; Eickhoff, Philipp; Pruckner, Nathalie; Vollnhofer, Georg; Fischmeister, Gustav; Diakos, Christopher; Rauch, Margit; Verdianz, Maria; Zoubek, Andreas; Gadner, Helmut; Lion, Thomas

2012-09-05

Common cold is caused by a variety of respiratory viruses. The prevalence in children is high, and it potentially contributes to significant morbidity. Iota-carragenan, a polymer derived from red seaweed, has reduced viral load in nasal secretions and alleviated symptoms in adults with common cold. We have assessed the antiviral and therapeutic activity of a nasal spray containing iota-carrageenan in children with acute symptoms of common cold. A cohort of 153 children between 1-18 years (mean age 5 years), displaying acute symptoms of common cold were randomly assigned to treatment with a nasal spray containing iota-carrageenan (0.12%) as verum or 0.9% sodium chloride solution as placebo for seven days. Symptoms of common cold were recorded and the viral load of respiratory viruses in nasal secretions was determined at two consecutive visits. The results of the present study showed no significant difference between the iota carrageenan and the placebo group on the mean of TSS between study days 2-7. Secondary endpoints, such as reduced time to clearance of disease (7.6 vs 9.4 days; p = 0.038), reduction of viral load (p = 0.026), and lower incidence of secondary infections with other respiratory viruses (p = 0.046) indicated beneficial effects of iota-carrageenan in this population. The treatment was safe and well tolerated, with less side effects observed in the verum group compared to placebo. In this study iota-carrageenan did not alleviate symptoms in children with acute symptoms of common cold, but significantly reduced viral load in nasal secretions that may have important implications for future studies. ISRCTN52519535, http://www.controlled-trials.com/ISRCTN52519535/

A novel experience-based internet intervention for smoking cessation: feasibility randomised controlled trial.

PubMed

Powell, John; Newhouse, Nikki; Martin, Angela; Jawad, Sena; Yu, Ly-Mee; Davoudianfar, Mina; Locock, Louise; Ziebland, Sue

2016-11-11

The internet is frequently used to share experiences of health and illness, but this phenomenon has not been harnessed as an intervention to achieve health behaviour change. The aim of this study was to determine the feasibility of a randomised trial assessing the effects of a novel, experience-based website as a smoking cessation intervention. The secondary aim was to measure the potential impact on smoking behaviour of both the intervention and a comparator website. A feasibility randomised controlled single-blind trial assessed a novel, experience-based website containing personal accounts of quitting smoking as a cessation intervention, and a comparator website providing factual information. Feasibility measures including recruitment, and usage of the interventions were recorded, and the following participant-reported outcomes were also measured: Smoking Abstinence Self-Efficacy Questionnaire, the single-item Motivation to Stop Scale, self-reported abstinence, quit attempts and health status outcomes. Eligible smokers from two English regions were entered into the trial and given access to their allocated website for two weeks. Eighty-seven smokers were randomised, 65 completed follow-up (75 %). Median usage was 15 min for the intervention, and 5 min for the comparator (range 0.5-213 min). Median logins for both sites was 2 (range 1-20). All participant-reported outcomes were similar between groups. It was technically feasible to deliver a novel intervention harnessing the online sharing of personal experiences as a tool for smoking cessation, but recruitment was slow and actual use was relatively low, with attrition from the trial. Future work needs to maximize engagement and to understand how best to assess the value of such interventions in everyday use, rather than as an isolated 'dose of information'. ISRCTN29549695 DOI 10.1186/ISRCTN29549695 . Registered 17/05/2013.

A stepped wedge cluster randomized control trial of dried blood spot testing to improve the uptake of hepatitis C antibody testing within UK prisons

PubMed Central

Whitaker, Rhiannon; Perrett, Stephanie; Zou, Lu; Hickman, Matthew; Lyons, Marion

2015-01-01

Background: The prevalence of hepatitis C (HCV) is elevated within prison populations, yet diagnosis in prisons remains low. Dried blood spot testing (DBST) is a simple procedure for the detection of HCV antibodies; its impact on testing in the prison context is unknown. Methods: We carried out a stepped-wedge cluster-randomized control trial of DBST for HCV among prisoners within five male prisons and one female prison. Each prison was a separate cluster. The order in which the intervention (training in use of DBST for HCV testing and logistic support) was introduced was randomized across clusters. The outcome measure was the HCV testing rate by prison. Imputation analysis was carried out to account for missing data. Planned and actual intervention times differed in some prisons; data were thus analysed by intention to treat (ITT) and by observed step times. Results: There was insufficient evidence of an effect of the intervention on testing rate using either the ITT intervention time (OR: 0.84; 95% CI: 0.68–1.03; P = 0.088) or using the actual intervention time (OR: 0.86; 95% CI: 0.71–1.06; P = 0.153). This was confirmed by the pooled results of five imputed data sets. Conclusions: DBST as a stand-alone intervention was insufficient to increase HCV diagnosis within the UK prison setting. Factors such as staff training and allocation of staff time for regular clinics are key to improving service delivery. We demonstrate that prisons can conduct rigorous studies of new interventions, but data collection can be problematic. Trial registration: International Standard Randomized Controlled Trial Number Register (ISRCTN number ISRCTN05628482). PMID:25061233

The OPERA trial: a protocol for the process evaluation of a randomised trial of an exercise intervention for older people in residential and nursing accommodation

PubMed Central

2011-01-01

Background The OPERA trial is large cluster randomised trial testing a physical activity intervention to address depression amongst people living in nursing and residential homes for older people. A process evaluation was commissioned alongside the trial and we report the protocol for this process evaluation. Challenges included the cognitive and physical ability of the participants, the need to respect the privacy of all home residents, including study non-participants, and the physical structure of the homes. Evaluation activity had to be organised around the structured timetable of homes, leaving limited opportunities for data collection. The aims of this process evaluation are to provide findings that will assist in the interpretation of the clinical trial results, and to inform potential implementation of the physical activity intervention on a wider scale. Methods/design Quantitative data on recruitment of homes and individuals is being collected. For homes in the intervention arm, data on dose and fidelity of the intervention delivered; including individual rates of participation in exercise classes are collected. In the control homes, uptake and delivery of depression awareness training is monitored. These data will be combined with qualitative data from an in-depth study of a purposive sample of eight homes (six intervention and two control). Discussion Although process evaluations are increasingly funded alongside trials, it is still rare to see the findings published, and even rarer to see the protocol for such an evaluation published. Process evaluations have the potential to assist in interpreting and understanding trial results as well as informing future roll-outs of interventions. If such evaluations are funded they should also be reported and reviewed in a similar way to the trial outcome evaluation. Trial Registration ISRCTN No: ISRCTN43769277 PMID:21288341

Reducing the environmental impact of trials: a comparison of the carbon footprint of the CRASH-1 and CRASH-2 clinical trials.

PubMed

Subaiya, Saleena; Hogg, Euan; Roberts, Ian

2011-02-03

All sectors of the economy, including the health research sector, must reduce their carbon emissions. The UK National Institute for Health Research has recently prepared guidelines on how to minimize the carbon footprint of research. We compare the carbon emissions from two international clinical trials in order to identify where emissions reductions can be made. We conducted a carbon audit of two clinical trials (the CRASH-1 and CRASH-2 trials), quantifying the carbon dioxide emissions produced over a one-year audit period. Carbon emissions arising from the coordination centre, freight delivery, trial-related travel and commuting were calculated and compared. The total emissions in carbon dioxide equivalents during the one-year audit period were 181.3 tonnes for CRASH-1 and 108.2 tonnes for CRASH-2. In total, CRASH-1 emitted 924.6 tonnes of carbon dioxide equivalents compared with 508.5 tonnes for CRASH-2. The CRASH-1 trial recruited 10,008 patients over 5.1 years, corresponding to 92 kg of carbon dioxide per randomized patient. The CRASH-2 trial recruited 20,211 patients over 4.7 years, corresponding to 25 kg of carbon dioxide per randomized patient. The largest contributor to emissions in CRASH-1 was freight delivery of trial materials (86.0 tonnes, 48% of total emissions), whereas the largest contributor in CRASH-2 was energy use by the trial coordination centre (54.6 tonnes, 30% of total emissions). Faster patient recruitment in the CRASH-2 trial largely accounted for its greatly increased carbon efficiency in terms of emissions per randomized patient. Lighter trial materials and web-based data entry also contributed to the overall lower carbon emissions in CRASH-2 as compared to CRASH-1. CRASH-1: ISRCTN74459797CRASH-2: ISRCTN86750102.

Poor reporting of scientific leadership information in clinical trial registers.

PubMed

Sekeres, Melanie; Gold, Jennifer L; Chan, An-Wen; Lexchin, Joel; Moher, David; Van Laethem, Marleen L P; Maskalyk, James; Ferris, Lorraine; Taback, Nathan; Rochon, Paula A

2008-02-20

In September 2004, the International Committee of Medical Journal Editors (ICMJE) issued a Statement requiring that all clinical trials be registered at inception in a public register in order to be considered for publication. The World Health Organization (WHO) and ICMJE have identified 20 items that should be provided before a trial is considered registered, including contact information. Identifying those scientifically responsible for trial conduct increases accountability. The objective is to examine the proportion of registered clinical trials providing valid scientific leadership information. We reviewed clinical trial entries listing Canadian investigators in the two largest international and public trial registers, the International Standard Randomized Controlled Trial Number (ISRCTN) register, and ClinicalTrials.gov. The main outcome measures were the proportion of clinical trials reporting valid contact information for the trials' Principal Investigator (PI)/Co-ordinating Investigator/Study Chair/Site PI, and trial e-mail contact address, stratified by funding source, recruiting status, and register. A total of 1388 entries (142 from ISRCTN and 1246 from ClinicalTrials.gov) comprised our sample. We found non-compliance with mandatory registration requirements regarding scientific leadership and trial contact information. Non-industry and partial industry funded trials were significantly more likely to identify the individual responsible for scientific leadership (OR = 259, 95% CI: 95-701) and to provide a contact e-mail address (OR = 9.6, 95% CI: 6.6-14) than were solely industry funded trials. Despite the requirements set by WHO and ICMJE, data on scientific leadership and contact e-mail addresses are frequently omitted from clinical trials registered in the two leading public clinical trial registers. To promote accountability and transparency in clinical trials research, public clinical trials registers should ensure adequate monitoring of trial registration to ensure completion of mandatory contact information fields identifying scientific leadership.

Wolfram (DIDMOAD) syndrome: a multidisciplinary clinical study in nine Turkish patients and review of the literature.

PubMed

Simsek, E; Simsek, T; Tekgül, S; Hosal, S; Seyrantepe, V; Aktan, G

2003-01-01

To study Wolfram syndrome (WFS) with multidisciplinary consultations and compare the results with the literature. Nine patients fulfilled the ascertainment criteria of WFS (insulin-dependent diabetes mellitus and optic atrophy). All patients were evaluated by the departments of paediatrics, ophthalmology, audiology, urology and medical biology. The earliest manifestation of WFS was insulin-dependent diabetes mellitus (at a median age of 6.9 y), followed by optic atrophy (8.9 y), diabetes insipidus (10.2 y) and deafness (10.5 y). Short stature was found in five cases, delayed puberty in two cases and hypergonadotropic hypogonadism in one case. Audiography disclosed hearing loss at high frequency in all patients (100%), but only five patients had clinical subjective hearing problems. Intravenous pyelography revealed hydroureteronephrosis in eight patients. Urodynamics revealed a normal bladder in only one patient. Three patients had a low-capacity, low-compliance bladder, detrusor external sphincteric dyssynergia and emptying problem, while five had an atonic bladder. Ocular findings were optic atrophy, low visual acuity and colour vision defects. Visual field tests revealed concentric and/or peripheral diminution in five patients. Visual evoked potentials were abnormal (reduced amplitude to both flash and pattern stimulation) in seven patients. Cranial magnetic resonance imaging showed mild or moderate atrophy of the optic nerves, chiasm, cerebellum, basal ganglia and brainstem in six patients; there was a partially empty sella in one case. There was no evidence of mitochondrial tRNA(Leu) (UUR) A to G (nucleotide 3243) mutation. Wolfram syndrome should be evaluated in a multidisciplinary manner. Some specific and dynamic tests are necessary to make a more precise estimate of the prevalence and median age of the components of WFS. Short stature is a common feature in WFS. Hypogonadism may be hypogonadotropic or hypergonadotropic. Bladder dysfunction does not always present as a large atonic bladder in WFS. A low-capacity, high-pressure bladder with sphincteric dyssynergia is also common.

L-Arginine Affects Aerobic Capacity and Muscle Metabolism in MELAS (Mitochondrial Encephalomyopathy, Lactic Acidosis and Stroke-Like Episodes) Syndrome.

PubMed

Rodan, Lance H; Wells, Greg D; Banks, Laura; Thompson, Sara; Schneiderman, Jane E; Tein, Ingrid

2015-01-01

To study the effects of L-arginine (L-Arg) on total body aerobic capacity and muscle metabolism as assessed by (31)Phosphorus Magnetic Resonance Spectroscopy ((31)P-MRS) in patients with MELAS (Mitochondrial Encephalomyopathy with Lactic Acidosis and Stroke-like episodes) syndrome. We performed a case control study in 3 MELAS siblings (m.3243A>G tRNA(leu(UUR)) in MTTL1 gene) with different % blood mutant mtDNA to evaluate total body maximal aerobic capacity (VO(2peak)) using graded cycle ergometry and muscle metabolism using 31P-MRS. We then ran a clinical trial pilot study in MELAS sibs to assess response of these parameters to single dose and a 6-week steady-state trial of oral L-Arginine. At baseline (no L-Arg), MELAS had lower serum Arg (p = 0.001). On 3(1)P-MRS muscle at rest, MELAS subjects had increased phosphocreatine (PCr) (p = 0.05), decreased ATP (p = 0.018), and decreased intracellular Mg(2+) (p = 0.0002) when compared to matched controls. With L-arginine therapy, the following trends were noted in MELAS siblings on cycle ergometry: (1) increase in mean % maximum work at anaerobic threshold (AT) (2) increase in % maximum heart rate at AT (3) small increase in VO(2peak). On (31)P-MRS the following mean trends were noted: (1) A blunted decrease in pH after exercise (less acidosis) (2) increase in Pi/PCr ratio (ADP) suggesting increased work capacity (3) a faster half time of PCr recovery (marker of mitochondrial activity) following 5 minutes of moderate intensity exercise (4) increase in torque. These results suggest an improvement in aerobic capacity and muscle metabolism in MELAS subjects in response to supplementation with L-Arg. Intramyocellular hypomagnesemia is a novel finding that warrants further study. Class III evidence that L-arginine improves aerobic capacity and muscle metabolism in MELAS subjects. ClinicalTrials.gov NCT01603446.

The complete mitochondrial genomes of the Fenton′s wood white, Leptidea morsei, and the lemon emigrant, Catopsilia pomona

PubMed Central

Hao, Juan-Juan; Hao, Jia-Sheng; Sun, Xiao-Yan; Zhang, Lan-Lan; Yang, Qun

2014-01-01

Abstract The complete mitochondrial genomes of Leptidea morsei Fenton (Lepidoptera: Pieridae: Dis-morphiinae) and Catopsilia pomona (F.) (Lepidoptera: Pieridae: Coliadinae) were determined to be 15,122 and 15,142 bp in length, respectively, with that of L . morsei being the smallest among all known butterflies. Both mitogenomes contained 37 genes and an A+T-rich region, with the gene order identical to those of other butterflies, except for the presence of a tRNA-like insertion, tRNA Leu (UUR), in C . pomona . The nucleotide compositions of both genomes were higher in A and T (80.2% for L . morsei and 81.3% for C . pomona ) than C and G; the A+T bias had a significant effect on the codon usage and the amino acid composition. The protein-coding genes utilized the standard mitochondrial start codon ATN, except the COI gene using CGA as the initiation codon, as reported in other butterflies. The intergenic spacer sequence between the tRNA Ser (UCN) and ND1 genes contained the ATACTAA motif. The A+T-rich region harbored a poly-T stretch and a conserved ATAGA motif located at the end of the region. In addition, there was a triplicated 23 bp repeat and a microsatellite-like (TA) 9 (AT) 3 element in the A+T-rich region of the L. morsei mitogenome , while in C . pomona, there was a duplicated 24 bp repeat element and a microsatellite-like (TA) 9 element. The phylogenetic trees of the main butterfly lineages (Hesperiidae, Papilionidae, Pieridae, Nymphalidae, Lycaenidae, and Riodinidae) were reconstructed with maximum likelihood and Bayesian inference methods based on the 13 concatenated nucleotide sequences of protein-coding genes, and both trees showed that the Pieridae family is sister to Lycaenidae. Although this result contradicts the traditional morphologically based views, it agrees with other recent studies based on mitochondrial genomic data. PMID:25368074

The Effectiveness of Web-Based Asthma Self-Management System, My Asthma Portal (MAP): A Pilot Randomized Controlled Trial.

PubMed

Ahmed, Sara; Ernst, Pierre; Bartlett, Susan J; Valois, Marie-France; Zaihra, Tasneem; Paré, Guy; Grad, Roland; Eilayyan, Owis; Perreault, Robert; Tamblyn, Robyn

2016-12-01

Whether Web-based technologies can improve disease self-management is uncertain. My Asthma Portal (MAP) is a Web-based self-management support system that couples evidence-based behavioral change components (self-monitoring of symptoms, physical activity, and medication adherence) with real-time monitoring, feedback, and support from a nurse case manager. The aim of this study was to compare the impact of access to a Web-based asthma self-management patient portal linked to a case-management system (MAP) over 6 months compared with usual care on asthma control and quality of life. A multicenter, parallel, 2-arm, pilot, randomized controlled trial was conducted with 100 adults with confirmed diagnosis of asthma from 2 specialty clinics. Asthma control was measured using an algorithm based on overuse of fast-acting bronchodilators and emergency department visits, and asthma-related quality of life was assessed using the Mini-Asthma Quality of Life Questionnaire (MAQLQ). Secondary mediating outcomes included asthma symptoms, depressive symptoms, self-efficacy, and beliefs about medication. Process evaluations were also included. A total of 49 individuals were randomized to MAP and 51 to usual care. Compared with usual care, participants in the intervention group reported significantly higher asthma quality of life (mean change 0.61, 95% CI 0.03 to 1.19), and the change in asthma quality of life for the intervention group between baseline and 3 months (mean change 0.66, 95% CI 0.35 to 0.98) was not seen in the control group. No significant differences in asthma quality of life were found between the intervention and control groups at 6 (mean change 0.46, 95% CI -0.12 to 1.05) and 9 months (mean change 0.39, 95% CI -0.2 to 0.98). For poor control status, there was no significant effect of group, time, or group by time. For all self-reported measures, the intervention group had a significantly higher proportion of individuals, demonstrating a minimal clinically meaningful improvement compared with the usual care group. This study supported the use of MAP to enhance asthma quality of life but not asthma control as measured by an administrative database. Implementation of MAP beyond 6 months with tailored protocols for monitoring symptoms and health behaviors as individuals' knowledge and self-management skills improve may result in long-term gains in asthma control. International Standard Randomized Controlled Trial Number (ISRCTN): 34326236; http://www.isrctn.com/ISRCTN34326236 (Archived by Webcite at http://www.webcitation.org/6mGxoI1R7). ©Sara Ahmed, Pierre Ernst, Susan J Bartlett, Marie-France Valois, Tasneem Zaihra, Guy Paré, Roland Grad, Owis Eilayyan, Robert Perreault, Robyn Tamblyn. Originally published in the Journal of Medical Internet Research (http://www.jmir.org), 01.12.2016.

Development of a Self-Help Web-Based Intervention Targeting Young Cancer Patients With Sexual Problems and Fertility Distress in Collaboration With Patient Research Partners.

PubMed

Winterling, Jeanette; Wiklander, Maria; Obol, Claire Micaux; Lampic, Claudia; Eriksson, Lars E; Pelters, Britta; Wettergren, Lena

2016-04-12

The Internet should be suitable for delivery of interventions targeting young cancer patients. Young people are familiar with the technologies, and this patient group is small and geographically dispersed. Still, only few psycho-educational Web-based interventions are designed for this group. Young cancer patients consider reproductive health, including sexuality, an area of great importance and approximately 50% report sexual problems and fertility-related concerns following cancer treatment. Therefore, we set out to develop a self-help Web-based intervention, Fex-Can, to alleviate such problems. To improve its quality, we decided to involve patients and significant others as research partners. The first 18 months of our collaboration are described in this paper. The intervention will subsequently be tested in a feasibility study followed by a randomized controlled trial. The study aims to describe the development of a Web-based intervention in long-term collaboration with patient research partners (PRPs). Ten former cancer patients and two significant others participated in building the Web-based intervention, using a participatory design. The development process is described according to the design step in the holistic framework presented by van Gemert-Pijnen et al and evaluates the PRPs' impact on the content, system, and service quality of the planned intervention. The collaboration between the research group and the PRPs mainly took place in the form of 1-day meetings to develop the key components of the intervention: educational and behavior change content, multimedia (pictures, video vignettes, and audios), interactive online activities (eg, self-monitoring), and partial feedback support (discussion forum, tailored feedback from experts). The PRPs influenced the intervention's content quality in several ways. By repeated feedback on prototypes, the information became more comprehensive, relevant, and understandable. The PRPs gave suggestions concerning the number of exercises and pointed out texts and pictures needing revision (eg, experienced as normative or stereotypical) to increase the persuasiveness of the program. The system quality was improved by PRPs' feedback on design, technical malfunctions, and navigation on the website. Based on feedback about availability of professional support (technical problems and program content), the organization for support was clarified, which increased service quality. The PRPs also influenced the research project on an overall level by suggesting modifications of inclusion criteria for the RCT and by questioning the implementation plan. With suggestions and continuous feedback from PRPs, it was possible to develop a Web-based intervention with persuasive design, believed to be relevant and attractive for young persons with cancer who have sexual problems or fertility distress. In the next step, the intervention will be tested in a feasibility study, followed by an RCT to test the intervention's effectiveness in reducing sexual problems and fertility distress. International Standard Randomized Controlled Trial Number (ISRCTN): 36621459; http://www.isrctn.com/ISRCTN36621459 (Archived by WebCite at http://www.webcitation.org/6gFX40F6T).

Integrated Care in Prostate Cancer (ICARE-P): Nonrandomized Controlled Feasibility Study of Online Holistic Needs Assessment, Linking the Patient and the Health Care Team

PubMed Central

Dale, Jeremy; Roscoe, Julia; Hamborg, Thomas; Ahmedzai, Sam H; Arvanitis, Theodoros N; Badger, Douglas; James, Nicholas; Mendelsohn, Richard; Khan, Omar; Parashar, Deepak; Patel, Prashant

2017-01-01

Background The potential of technology to aid integration of care delivery systems is being explored in a range of contexts across a variety of conditions in the United Kingdom. Prostate cancer is the most common cancer in UK men. With a 10-year survival rate of 84%, there is a need to explore innovative methods of care that are integrated between primary health care providers and specialist teams in order to address long-term consequences of the disease and its treatment as well as to provide continued monitoring for recurrence. Objective Our aim was to test the feasibility of a randomized controlled trial to compare a model of prostate cancer continuing and follow-up care integration, underpinned by digital technology, with usual care in terms of clinical and cost-effectiveness, patient-reported outcomes, and experience. Methods A first phase of the study has included development of an online adaptive prostate specific Holistic Needs Assessment system (HNA), training for primary care-based nurses, training of an IT peer supporter, and interviews with health care professionals and men with prostate cancer to explore views of their care, experience of technology, and views of the proposed intervention. In Phase 2, men in the intervention arm will complete the HNA at home to help identify and articulate concerns and share them with their health care professionals, in both primary and specialist care. Participants in the control arm will receive usual care. Outcomes including quality of life and well-being, prostate-specific concerns, and patient enablement will be measured 3 times over a 9-month period. Results Findings from phase 1 indicated strong support for the intervention among men, including those who had had little experience of digital technology. Men expressed a range of views on ways that the online system might be used within a clinical pathway. Health care professionals gave valuable feedback on how the output of the assessment might be presented to encourage engagement and uptake by clinical teams. Recruitment to the second phase of the study, the feasibility trial, commenced March 2017. Conclusions To our knowledge, this study is the first in the United Kingdom to trial an online holistic needs assessment for men with prostate cancer, with data shared between patients and primary and secondary care providers. This study addresses recommendations in recent policy documents promoting the importance of data sharing and enhanced communication between care providers as a basis for care integration. We anticipate that this model of care will ultimately provide important benefits for both patients and the National Health Service. Trial Registration International Standard Randomized Controlled Trial Number (ISRCTN): 31380482; http://www.isrctn.com/ISRCTN31380482 (Archived by WebCite at http://www.webcitation.org/6s8I42u5N) PMID:28754653

Short Text Messages to Encourage Adherence to Medication and Follow-up for People With Psychosis (Mobile.Net): Randomized Controlled Trial in Finland.

PubMed

Välimäki, Maritta; Kannisto, Kati Anneli; Vahlberg, Tero; Hätönen, Heli; Adams, Clive E

2017-07-12

A text messaging service (short message service [SMS]) has the potential to target large groups of people with long-term illnesses such as serious mental disorders, who may have difficulty with treatment adherence. Robust research on the impact of mobile technology interventions for these patients remains scarce. The main objective of our study was to investigate the impact of individually tailored short text messages on the rate of psychiatric hospital readmissions, health care service use, and clinical outcomes. In addition, we analyzed treatment costs. Between September 2011 and November 2012, we randomly assigned 1139 people to a tailored text message intervention (n=569) or usual care (n=570). Participants received semiautomated text messages for up to 12 months or usual care. The primary outcome, based on routinely collected health register data, was patient readmission into a psychiatric hospital during a 12-month follow-up period. Secondary outcomes were related to other service use, coercion, medication, adverse events, satisfaction, social functioning, quality of life, and economic factors (cost analysis). There was 98.24% (1119/1139) follow-up at 12 months. Tailored mobile telephone text messages did not reduce the rate of hospital admissions (242/563, 43.0% of the SMS group vs 216/556, 38.8% of the control group; relative risk 1.11; 95% CI 0.92-1.33; P=.28), time between hospitalizations (mean difference 7.0 days 95% CI -8.0 to 24.0; P=.37), time spent in a psychiatric hospital during the year (mean difference 2.0 days 95% CI -2.0 to 7.0; P=.35), or other service outcomes. People who received text messages were less disabled, based on Global Assessment Scale scores at the time of their readmission, than those who did not receive text messages (odds ratio 0.68; 95% CI 0.47-0.97; P=.04). The costs of treatment were higher for people in the SMS group than in the control group (mean €10,103 vs €9210, respectively, P<.001). High-grade routinely collected data can provide clear outcomes for pragmatic randomized trials. SMS messaging tailored with the input of each individual patient did not decrease the rate of psychiatric hospital visits after the 12 months of follow-up. Although there may have been other, more subtle effects, the results of these were not evident in outcomes of agreed importance to clinicians, policymakers, and patients and their families. International Standard Randomized Controlled Trial Number (ISRCTN): 27704027; http://www.isrctn.com/ISRCTN27704027 (Archived by WebCite at http://www.webcitation.org/6rVzZrbuz). ©Maritta Välimäki, Kati Anneli Kannisto, Tero Vahlberg, Heli Hätönen, Clive E Adams. Originally published in the Journal of Medical Internet Research (http://www.jmir.org), 12.07.2017.

A randomised phase 2 trial of intensive induction chemotherapy (CBOP/BEP) and standard BEP in poor-prognosis germ cell tumours (MRC TE23, CRUK 05/014, ISRCTN 53643604).

PubMed

Huddart, Robert A; Gabe, Rhian; Cafferty, Fay H; Pollock, Philip; White, Jeff D; Shamash, Jonathan; Cullen, Michael H; Stenning, Sally P

2015-03-01

Standard chemotherapy for poor-prognosis metastatic nonseminoma has remained bleomycin, etoposide, and cisplatin (BEP) for many years; more effective regimens are required. To explore whether response rates with a new intensive chemotherapy regimen, CBOP/BEP (carboplatin, bleomycin, vincristine, cisplatin/BEP), versus those in concurrent patients treated with standard BEP justify a phase 3 trial. We conducted a phase 2 open-label randomised trial in patients with germ cell tumours of any extracranial primary site and one or more International Germ Cell Cancer Collaborative Group poor-prognosis features. Patients were randomised between 2005 and 2009 at 16 UK centres. BEP (bleomycin 30,000 IU) was composed of four cycles over 12 wk. CBOP/BEP was composed of 2×CBOP, 2×BO, and 3×BEP (bleomycin 15,000 IU). Primary end point was favourable response rate (FRR) comprising complete response or partial response and normal markers. Success required the lower two-sided 90% confidence limit to exclude FRRs <60%; 44 patients on CBOP/BEP gives 90% power to achieve this if the true FRR is ≥80%. Equal numbers were randomised to BEP to benchmark contemporary response rates. A total of 89 patients were randomised (43 CBOP/BEP, 46 BEP); 40 and 41, respectively, completed treatment. CBOP/BEP toxicity, largely haematologic, was high (96% vs 63% on BEP had Common Terminology Criteria for Adverse Events v.3 grade ≥3). FRRs were 74% (90% confidence interval [CI], 61-85) with CBOP/BEP, 61% with BEP (90% CI, 48-73). After a median of 58-mo follow-up, 1-yr progression-free survival (PFS) was 65% and 43%, respectively (hazard ratio: 0.59; 95% CI, 0.33-1.06); 2-yr overall survival (OS) was 67% and 61%. Overall, 3 of 14 CBOP/BEP and 2 of 18 BEP deaths were attributed to toxicity, one after an overdose of bleomycin during CBOP/BEP. The trial was not powered to compare PFS. The primary outcome was met, the CI for CBOP/BEP excluding FRRs <61%, but CBOP/BEP was more toxic. PFS and OS data are promising but require confirmation in an international phase 3 trial. In this study we tested a new, more intensive way to deliver a combination of drugs often used to treat men with testicular cancer. We found that response rates were higher but that the CBOP/BEP regimen caused more short-term toxicity. Because most patients are diagnosed when their cancer is less advanced, it took twice as long to complete the trial as expected. Although we plan to carry out a larger trial, we will need international collaboration. ISRCTN53643604; http://www.controlled-trials.com/ISRCTN53643604. Copyright © 2014 European Association of Urology. Published by Elsevier B.V. All rights reserved.

An Integrated Approach to Control Soil-Transmitted Helminthiasis, Schistosomiasis, Intestinal Protozoa Infection, and Diarrhea: Protocol for a Cluster Randomized Trial.

PubMed

Raso, Giovanna; Essé, Clémence; Dongo, Kouassi; Ouattara, Mamadou; Zouzou, Fabien; Hürlimann, Eveline; Koffi, Veronique A; Coulibaly, Gaoussou; Mahan, Virginie; Yapi, Richard B; Koné, Siaka; Coulibaly, Jean Tenena; Meïté, Aboulaye; Guéhi-Kabran, Marie-Claire; Bonfoh, Bassirou; N'Goran, Eliézer Kouakou; Utzinger, Jürg

2018-06-12

The global strategy to control helminthiases (schistosomiasis and soil-transmitted helminthiasis) emphasizes preventive chemotherapy. However, in the absence of access to clean water, improved sanitation, and adequate hygiene, reinfection after treatment can occur rapidly. Integrated approaches might be necessary to sustain the benefits of preventive chemotherapy and make progress toward interruption of helminthiases transmission. The aim of this study was to assess and quantify the effect of an integrated control package that consists of preventive chemotherapy, community-led total sanitation, and health education on soil-transmitted helminthiasis, schistosomiasis, intestinal protozoa infection, and diarrhea in rural Côte d'Ivoire. In a first step, a community health education program was developed that includes an animated cartoon to promote improved hygiene and health targeting school-aged children, coupled with a health education theater for the entire community. In a second step, a cluster randomized trial was implemented in 56 communities of south-central Côte d'Ivoire with 4 intervention arms: (1) preventive chemotherapy; (2) preventive chemotherapy plus community-led total sanitation; (3) preventive chemotherapy plus health education; and (4) all 3 interventions combined. Before implementation of the aforementioned interventions, a baseline parasitologic, anthropometric, and hygiene-related knowledge, attitudes, practices, and beliefs survey was conducted. These surveys were repeated 18 and 39 months after the baseline cross-sectional survey to determine the effect of different interventions on helminth and intestinal protozoa infection, nutritional indicators, and knowledge, attitudes, practices, and beliefs. Monitoring of diarrhea was done over a 24-month period at 2-week intervals, starting right after the baseline survey. Key results from this cluster randomized trial will shed light on the effect of integrated approaches consisting of preventive chemotherapy, community-led total sanitation, and health education against infections with soil-transmitted helminths, schistosomes, an intestinal protozoa and prevention of diarrhea in a rural part of Côte d'Ivoire. The research provided new insights into the acceptability, strengths, and limitations of an integrated community-based control package targeting helminthiases, intestinal protozoa infections, and diarrhea in rural communities of Côte d'Ivoire. In the longer term, the study will allow determining the effect of the integrated control approach on infection patterns with parasitic worms and intestinal protozoa, diarrheal incidence, anthropometric measures, and hygiene-related knowledge, attitudes, practices, and beliefs. International Standard Randomized Controlled Trial Number (ISRCTN): 53102033; http://www.isrctn.com/ISRCTN53102033 (Archived by WebCite at http://www.webcitation.org/6wpnXEiHo). RR1-10.2196/9166. ©Giovanna Raso, Clémence Essé, Kouassi Dongo, Mamadou Ouattara, Fabien Zouzou, Eveline Hürlimann, Veronique A Koffi, Gaoussou Coulibaly, Virginie Mahan, Richard B Yapi, Siaka Koné, Jean Tenena Coulibaly, Aboulaye Meïté, Marie-Claire Guéhi-Kabran, Bassirou Bonfoh, Eliézer Kouakou N'Goran, Jürg Utzinger. Originally published in JMIR Research Protocols (http://www.researchprotocols.org), 12.06.2018.

Bureaucracy stifles medical research in Britain: a tale of three trials.

PubMed

Snooks, Helen; Hutchings, Hayley; Seagrove, Anne; Stewart-Brown, Sarah; Williams, John; Russell, Ian

2012-08-16

Recent developments aiming to standardise and streamline processes of gaining the necessary approvals to carry out research in the National Health Service (NHS) in the United Kingdom (UK), have resulted in lengthy and costly delays. The national UK governmental Department of Health's Research Governance Framework (RGF) for Health and Social Care requires that appropriate checks be conducted before research involving human participants, their organs, tissues or data can commence in the NHS. As a result, medical research has been subjected to increased regulation and governance, with the requirement for approvals from numerous regulatory and monitoring bodies. In addition, the processes and outcomes of the attribution of costs in NHS research have caused additional difficulties for researchers. The purpose of this paper is to illustrate, through three trial case studies, the difficulties encountered during the set-up and recruitment phases of these trials, related to gaining the necessary ethical and governance approvals and applying for NHS costs to undertake and deliver the research. Empirical evidence about delays and difficulties related to regulation and governance of medical research was gathered during the period 2009-2010 from three UK randomised controlled trials with sites in England, Wales and Scotland (1. SAFER 2- an emergency care based trial of a protocol for paramedics to refer patients directly to community based falls services; 2. COnStRUCT- a trial of two drugs for acute ulcerative colitis; and 3. Family Links - a trial of a public health intervention, a 10 week community based parenting programme). Findings and recommendations were reported in response to a call for evidence from The Academy of Medical Sciences regarding difficulties encountered in conducting medical research arising from R&D governance and regulation, to inform national policy. Difficulties and delays in navigating and gaining the appropriate approvals and NHS costs required to undertake the research were encountered in all three trials, at various points in the bureaucratic processes of ethical and research and information governance approvals. Conduct of each of the three trials was delayed by at least 12 months, with costs increasing by 30 - 40%. Whilst the three trials encountered a variety of challenges, there were common issues. The processes for gaining approvals were overly complex and differed between sites and UK countries; guidance about processes was unclear; and information regarding how to define and claim NHS costs for undertaking the research was inconsistent. The competitive advantage of a publicly funded, open access health system for undertaking health services research and clinical trials within the UK has been outweighed in recent years by stifling bureaucratic structures and processes for governance of research. The recommendations of the Academy of Medical Sciences are welcomed, and the effects of their implementation are awaited with interest. SAFER 2: ISRCTN 60481756; COnStRUCT: ISRCTN22663589; Family Links: ISRCTN 13929732.

A Pilot Randomized Controlled Trial of Cognitive-Behavioral Therapy for Adolescents With Body Dysmorphic Disorder.

PubMed

Mataix-Cols, David; Fernández de la Cruz, Lorena; Isomura, Kayoko; Anson, Martin; Turner, Cynthia; Monzani, Benedetta; Cadman, Jacinda; Bowyer, Laura; Heyman, Isobel; Veale, David; Krebs, Georgina

2015-11-01

Body dysmorphic disorder (BDD) typically starts in adolescence, but evidence-based treatments are yet to be developed and formally evaluated in this age group. We designed an age-appropriate cognitive-behavioral therapy (CBT) protocol for adolescents with BDD and evaluated its acceptability and efficacy in a pilot randomized controlled trial. Thirty adolescents aged 12 to 18 years (mean = 16.0, SD = 1.7) with a primary diagnosis of BDD, together with their families, were randomly assigned to 14 sessions of CBT delivered over 4 months or a control condition of equivalent duration, consisting of written psycho-education materials and weekly telephone monitoring. Blinded evaluators assessed participants at baseline, midtreatment, posttreatment, and at 2-month follow-up. The primary outcome measure was the Yale-Brown Obsessive-Compulsive Scale Modified for BDD, Adolescent Version (mean baseline score = 37.13, SD = 4.98, range = 24-43). The CBT group showed a significantly greater improvement than the control group, both at posttreatment (time × group interaction coefficient [95% CI] = -11.26 [-17.22 to -5.31]; p = .000) and at 2-month follow-up (time × group interaction coefficient [95% CI] = -9.62 [-15.74 to -3.51]; p = .002). Six participants (40%) in the CBT group and 1 participant (6.7%) in the control condition were classified as responders at both time points (χ(2) = 4.658, p = .031). Improvements were also seen on secondary measures, including insight, depression, and quality of life at posttreatment. Both patients and their families deemed the treatment as highly acceptable. Developmentally tailored CBT is a promising intervention for young people with BDD, although there is significant room for improvement. Further clinical trials incorporating lessons learned in this pilot study and comparing CBT and pharmacological therapies, as well as their combination, are warranted. Cognitive-Behaviour Therapy for Adolescents With Body Dysmorphic Disorder; http://www.isrctn.com/; ISRCTN67699666. Copyright © 2015 American Academy of Child and Adolescent Psychiatry. Published by Elsevier Inc. All rights reserved.

'MATRI-SUMAN' a capacity building and text messaging intervention to enhance maternal and child health service utilization among pregnant women from rural Nepal: study protocol for a cluster randomised controlled trial.

PubMed

Singh, Jitendra Kumar; Kadel, Rajendra; Acharya, Dilaram; Lombard, Daniel; Khanal, Saval; Singh, Shri Prakash

2018-06-14

Capacity development of health volunteers and text messaging to pregnant women through mobile phones have shown improved maternal and child health (MCH) outcomes and is associated with increased utilisation of MCH services. However, such interventions are uncommon in Nepal. We aim to carry out an intervention with the hypothesis that capacity building and text messaging intervention will increase the MCH service utilisation. MATRI-SUMAN is a 12-month cluster randomized controlled trial (RCT). The trial involves pregnant women from 52 clusters of six village development committees (VDCs) covering 66,000 populations of Dhanusha district of Nepal. In the intervention clusters, Female Community Health Volunteers (FCHVs) will receive capacity development skills through reinforcement training, supervision and monitoring skills for the promotion of health seeking behaviour among pregnant women and study participants will receive periodic promotional text messaging service about MCH components through mobile phones. A sample of 354with equal numbers in each study arm is estimated using power calculation formula. The primary outcomes of this study are the rate of utilization of skilled birth attendants and consumption of a specified diversified meal. The secondary outcomes are: four antenatal (ANC) visits, weight gain of women during pregnancy, delivery of a baby at the health facility, postnatal care (PNC) visits, positive changes in child feeding practices among mothers, performance of FCHVs in MCH service utilization. The intervention is designed to enhance the capacity of health volunteers for the promotion of health seeking behaviour among pregnant women and text messaging through a mobile phone to expecting mothers to increase MCH service utilization. The trial if proven effective will have policy implications in poor resource settings. ISRCTN60684155, ( https://doi.org/10.1186/ISRCTN60684155 ). The trial was registered retrospectively.

Preconceptional and gestational weight trajectories and risk of delivering a small-for-gestational-age baby in rural Gambia12

PubMed Central

Elmrayed, Seham AA; Sosseh, Fatou; Prentice, Andrew M; Moore, Sophie E

2017-01-01

Background: Maternal nutritional status is a key determinant of small for gestational age (SGA), but some knowledge gaps remain, particularly regarding the role of the energy balance entering pregnancy. Objective: We investigated how preconceptional and gestational weight trajectories (summarized by individual-level traits) are associated with SGA risk in rural Gambia. Design: The sample comprised 670 women in a trial with serial weight data (7310 observations) that were available before and during pregnancy. Individual trajectories from 6 mo before conception to 30 wk of gestation were produced with the use of multilevel modeling. Summary traits were expressed as weight z scores [weight z score at 3 mo preconception (zwt−3 mo), weight z score at conception, weight z score at 3 mo postconception, weight z score at 7 mo postconception (zwt+7 mo), and conditional measures that represented the change from the preceding time] and were related to SGA risk with the use of Poisson regression with confounder adjustment; linear splines were used to account for nonlinearity. Results: Maternal weight at each time point had a consistent nonlinear relation with SGA risk. For example, the zwt−3 mo estimate was stronger in women with values ≤0.5 (RR: 0.736; 95% CI: 0.594, 0.910) than in women with values >0.5 (RR: 0.920; 95% CI: 0.682, 1.241). The former group had the highest observed SGA prevalence. Focusing on weight change, only conditional zwt+7 mo was associated with SGA and only in women with values >−0.5 (RR: 0.579; 95% CI: 0.463, 0.724). Conclusions: Protection against delivering an SGA neonate offered by greater preconceptional or gestational weight may be most pronounced in more undernourished and vulnerable women. Independent of this possibility, greater second- and third-trimester weight gain beyond a threshold may be protective. This trial was registered at http://www.isrctn.com/ as ISRCTN49285450. PMID:28490512

Limited Amount of Formula May Facilitate Breastfeeding: Randomized, Controlled Trial to Compare Standard Clinical Practice versus Limited Supplemental Feeding

PubMed Central

Straňák, Zbyněk; Feyereislova, Simona; Černá, Marcela; Kollárová, Jana; Feyereisl, Jaroslav

2016-01-01

Objectives Breastfeeding is known to reduce infant morbidity and improve well-being. Nevertheless, breastfeeding rates remain low despite public health efforts. Our study aims to investigate the effect of controlled limited formula usage during birth hospitalisation on breastfeeding, using the primary hypothesis that early limited formula feeds in infants with early weight loss will not adversely affect the rate of exclusive or any breastfeeding as measured at discharge, 3 and 6 months of age. Material and Methods We randomly assigned 104 healthy term infants, 24 to 48 hours old, with ≥ 5% loss of birth weight to controlled limited formula (CLF) intervention (10 ml formula by syringe after each breastfeeding, discontinued at onset of lactation) or control group (standard approach, SA). Groups were compared for demographic data and breastfeeding rates at discharge, 3 months and 6 months of age (p-values adjusted for multiple testing). Results Fifty newborns were analysed in CLF and 50 in SA group. There were no differences in demographic data or clinical characteristics between groups. We found no evidence of difference between treatment groups in the rates of exclusive as well as any breastfeeding at discharge (p-value 0.2 and >0.99 respectively), 3 months (p-value 0.12 and 0.10) and 6 months of infants’ age (p-value 0.45 and 0.34 respectively). The percentage weight loss during hospitalisation was significantly higher in the SA group (7.3% in CLF group, 8.4% in SA group, p = 0.002). Conclusion The study shows that controlled limited formula use does not have an adverse effect on rates of breastfeeding in the short and long term. Larger studies are needed to confirm a possible potential in controlled limited formula use to support establishing breastfeeding and to help to improve the rates of breastfeeding overall. Trial Registration ISRCTN registry ISRCTN61915183 PMID:26918700

Reducing the environmental impact of trials: a comparison of the carbon footprint of the CRASH-1 and CRASH-2 clinical trials

PubMed Central

2011-01-01

Background All sectors of the economy, including the health research sector, must reduce their carbon emissions. The UK National Institute for Health Research has recently prepared guidelines on how to minimize the carbon footprint of research. We compare the carbon emissions from two international clinical trials in order to identify where emissions reductions can be made. Methods We conducted a carbon audit of two clinical trials (the CRASH-1 and CRASH-2 trials), quantifying the carbon dioxide emissions produced over a one-year audit period. Carbon emissions arising from the coordination centre, freight delivery, trial-related travel and commuting were calculated and compared. Results The total emissions in carbon dioxide equivalents during the one-year audit period were 181.3 tonnes for CRASH-1 and 108.2 tonnes for CRASH-2. In total, CRASH-1 emitted 924.6 tonnes of carbon dioxide equivalents compared with 508.5 tonnes for CRASH-2. The CRASH-1 trial recruited 10,008 patients over 5.1 years, corresponding to 92 kg of carbon dioxide per randomized patient. The CRASH-2 trial recruited 20,211 patients over 4.7 years, corresponding to 25 kg of carbon dioxide per randomized patient. The largest contributor to emissions in CRASH-1 was freight delivery of trial materials (86.0 tonnes, 48% of total emissions), whereas the largest contributor in CRASH-2 was energy use by the trial coordination centre (54.6 tonnes, 30% of total emissions). Conclusions Faster patient recruitment in the CRASH-2 trial largely accounted for its greatly increased carbon efficiency in terms of emissions per randomized patient. Lighter trial materials and web-based data entry also contributed to the overall lower carbon emissions in CRASH-2 as compared to CRASH-1. Trial Registration Numbers CRASH-1: ISRCTN74459797 CRASH-2: ISRCTN86750102 PMID:21291517

Combined Protocol for Acute Malnutrition Study (ComPAS) in rural South Sudan and urban Kenya: study protocol for a randomized controlled trial.

PubMed

Bailey, Jeanette; Lelijveld, Natasha; Marron, Bethany; Onyoo, Pamela; Ho, Lara S; Manary, Mark; Briend, André; Opondo, Charles; Kerac, Marko

2018-04-24

Acute malnutrition is a continuum condition, but severe and moderate forms are treated separately, with different protocols and therapeutic products, managed by separate United Nations agencies. The Combined Protocol for Acute Malnutrition Study (ComPAS) aims to simplify and unify the treatment of uncomplicated severe and moderate acute malnutrition (SAM and MAM) for children 6-59 months into one protocol in order to improve the global coverage, quality, continuity of care and cost-effectiveness of acute malnutrition treatment in resource-constrained settings. This study is a multi-site, cluster randomized non-inferiority trial with 12 clusters in Kenya and 12 clusters in South Sudan. Participants are 3600 children aged 6-59 months with uncomplicated acute malnutrition. This study will evaluate the impact of a simplified and combined protocol for the treatment of SAM and MAM compared to the standard protocol, which is the national treatment protocol in each country. We will assess recovery rate as a primary outcome and coverage, defaulting, death, length of stay, average weekly weight gain and average weekly mid-upper arm circumference (MUAC) gain as secondary outcomes. Recovery rate is defined across both treatment arms as MUAC ≥125 mm and no oedema for two consecutive visits. Per-protocol and intention-to-treat analyses will be conducted. If the combined protocol is shown to be non-inferior to the standard protocol, updating guidelines to use the combined protocol would eliminate the need for separate products, resources and procedures for MAM treatment. This would likely be more cost-effective, increase availability of services, enable earlier case finding and treatment before deterioration of MAM into SAM, promote better continuity of care and improve community perceptions of the programme. ISRCTN, ISRCTN30393230 . Registered on 16 March 2017.

The efficacy of varenicline in achieving abstinence among waterpipe tobacco smokers - study protocol for a randomized controlled trial.

PubMed

Zahid, Raana; Dogar, Omara; Mansoor, Sonia; Khan, Amina; Kanaan, Mona; Jawad, Mohammed; Ahluwalia, Jasjit S; Siddiqi, Kamran

2017-01-11

Waterpipe tobacco smoking has increased among youth across the globe including in the US, and it continues as a common and traditional form of smoking tobacco in Pakistan. A range of behavioral and pharmacological therapies are available to support people in quitting cigarette smoking; however, little evidence exists for the efficacy of these therapies in achieving abstinence among waterpipe tobacco smokers. The objective of this study is to assess the efficacy of varenicline when added to behavioral support for waterpipe tobacco smoking cessation, by measuring biochemically validated continuous abstinence in waterpipe tobacco smokers. This is a two-arm, double-blind, placebo-controlled randomized trial conducted in four districts in Punjab, Pakistan. Study participants include adults using a waterpipe (with or without concomitant cigarette, bidi or other forms of tobacco smoking) on a daily basis for at least 6 months and who are willing to quit. We will individually randomize 510 participants to one of the two arms of the trial. Participants in the intervention arm will receive varenicline and behavioral support and those in the control arm will receive placebo and behavioral support. The primary outcome will be continuous abstinence for at least 6 months (week 25) which is biochemically verified by a carbon monoxide level of <10 ppm. Secondary outcomes will include biochemically verified 7-day point abstinence at 5, 12 and 25 weeks and any lapses and relapses between the different assessment points. Tertiary outcomes will include assessment of withdrawal symptoms using the Mood and Physical Symptoms Scale (MPSS), smoking dependency using the Lebanon Waterpipe Dependency Scale (LWDS-11) and monitoring adverse outcomes. This is an efficacy trial and would require a subsequent effectiveness trial for a definitive evaluation of the intervention. ISRCTN, ISRCTN94103375 . Registered on 1 December 2015.

An eHealth program versus a standard care supervised health program and associated health outcomes in individuals with mobility disability: study protocol for a randomized controlled trial.

PubMed

Berglind, Daniel; Nyberg, Gisela; Willmer, Mikaela; Persson, Margareta; Wells, Michael; Forsell, Yvonne

2018-04-27

Young adults with mobility disability (MD) are less likely to engage in regular physical activity (PA) compared with their able-bodied peers and inactive adults with a MD are more likely to report one or more chronic diseases compared to those who are physically active. Despite the vast amount of research published in the field of PA interventions over the past decades, little attention has been focused on interventions aiming to increase PA among individuals with MD. Thus, we propose to compare the effects of an eHealth program compared to a usual care supervised health program on levels of PA and other health behaviors. The current intervention will use a randomized controlled trial (RCT) design with two treatment groups (an eHealth program and a usual care supervised health program) in young adults with newly acquired MD. In total, 110 young adults (aged 18-40 years) with a MD, acquired within the past 3 years, will be recruited to participate in a 12-week intervention. The primary study outcome is accelerometer-measured time spent in moderate to vigorous PA. Secondary outcomes includes health-related quality of life, depression, stress, fitness, body composition, diet, musculoskeletal pain, motivation to exercise and work ability. There is a lack of RCTs investigating effective ways to increase levels of PA in young adults with MD. Increased levels of PA among this physically inactive population have the potential to substantially improve health-related outcomes, possibly more so than in the general population. The trial will put strong emphasis on optimizing exercise adherence and investigating feasibility in the two treatment programs. The Ethical Review Board (EPN) at Karolinska Institutet has approved the study (2017/1206-31/1). International Standard Randomised Controlled Trial Number (ISRCTN), reference number ISRCTN22387524 . Prospectively registered February 4, 2018.

Wine glass size and wine sales: a replication study in two bars.

PubMed

Pechey, Rachel; Couturier, Dominique-Laurent; Hollands, Gareth J; Mantzari, Eleni; Zupan, Zorana; Marteau, Theresa M

2017-08-01

Wine glass size may influence perceived volume and subsequently purchasing and consumption. Using a larger glass to serve the same portions of wine was found to increase wine sales by 9.4% (95% CI 1.9, 17.5) in a recent study conducted in one bar. The current study aimed to replicate this previous work in two other bars using a wider range of glass sizes. To match the previous study, a repeated multiple treatment reversal design, during which wine was served in glasses of the same design but different sizes, was used. The study was conducted in two bars in Cambridge, England, using glass sizes of 300, 370, 510 ml (Bar 1) and 300 and 510 ml (Bar 2). Customers purchased their choice of a 750 ml bottle, or standard UK measures of 125, 175 or 250 ml of wine, each of which was served with the same glass. Bar 1 Daily wine volume (ml) purchased was 10.5% (95% CI 1.0, 20.9) higher when sold in 510 ml compared to 370 ml glasses; but sales were not significantly higher with 370 ml versus 300 ml glasses (6.5%, 95% CI -5.2, 19.6). Bar 2 Findings were inconclusive as to whether daily wine purchased differed when using 510 ml versus 300 ml glasses (-1.1%, 95% CI -12.6, 11.9). These results provide a partial replication of previous work showing that introducing larger glasses (without manipulating portion size) increases purchasing. Understanding the mechanisms by which wine glass size influences consumption may elucidate when the effect can be expected and when not. Trial registration This study is a replication study, based on the procedure set out in the trial registration for the study that it attempts to replicate (ISRCTN registry: ISRCTN12018175).

Cluster randomized trials utilizing primary care electronic health records: methodological issues in design, conduct, and analysis (eCRT Study).

PubMed

Gulliford, Martin C; van Staa, Tjeerd P; McDermott, Lisa; McCann, Gerard; Charlton, Judith; Dregan, Alex

2014-06-11

There is growing interest in conducting clinical and cluster randomized trials through electronic health records. This paper reports on the methodological issues identified during the implementation of two cluster randomized trials using the electronic health records of the Clinical Practice Research Datalink (CPRD). Two trials were completed in primary care: one aimed to reduce inappropriate antibiotic prescribing for acute respiratory infection; the other aimed to increase physician adherence with secondary prevention interventions after first stroke. The paper draws on documentary records and trial datasets to report on the methodological experience with respect to research ethics and research governance approval, general practice recruitment and allocation, sample size calculation and power, intervention implementation, and trial analysis. We obtained research governance approvals from more than 150 primary care organizations in England, Wales, and Scotland. There were 104 CPRD general practices recruited to the antibiotic trial and 106 to the stroke trial, with the target number of practices being recruited within six months. Interventions were installed into practice information systems remotely over the internet. The mean number of participants per practice was 5,588 in the antibiotic trial and 110 in the stroke trial, with the coefficient of variation of practice sizes being 0.53 and 0.56 respectively. Outcome measures showed substantial correlations between the 12 months before, and after intervention, with coefficients ranging from 0.42 for diastolic blood pressure to 0.91 for proportion of consultations with antibiotics prescribed, defining practice and participant eligibility for analysis requires careful consideration. Cluster randomized trials may be performed efficiently in large samples from UK general practices using the electronic health records of a primary care database. The geographical dispersal of trial sites presents a difficulty for research governance approval and intervention implementation. Pretrial data analyses should inform trial design and analysis plans. Current Controlled Trials ISRCTN 47558792 and ISRCTN 35701810 (both registered on 17 March 2010).

Statistical analysis plan for the Urodynamics for Prostate Surgery Trial; Randomised Evaluation of Assessment Methods (UPSTREAM).

PubMed

Young, Grace J; Lewis, Amanda L; Lane, J Athene; Winton, Helen L; Drake, Marcus J; Blair, Peter S

2017-10-03

Current management for men with lower urinary tract symptoms (LUTS) is a pathway that results in prostate surgery in a significant proportion. While helpful in relieving benign prostatic obstruction (BPO), surgery may be ineffective for men suffering from difficulties not relating to BPO. The UPSTREAM trial started recruitment in October 2014 with the aim of establishing whether a care pathway including urodynamics (a diagnostic tool for BPO and thus an indication of whether surgery is needed) is no worse for men, in terms of symptomatic outcome, than one without (routine care). This analysis plan outlines the main outcomes of the study and specific design choices, such as non-inferiority margins. The trial is currently recruiting in 26 hospitals across the UK, randomising men to either urodynamics or routine care, with recruitment set to end on the 31 December 2016. All outcomes will be measured 18 months after randomisation to allow sufficient time for surgical procedures and recovery. The primary outcome is based on a non-inferiority design with a margin of 1 point on the International Prostate Symptom Score (IPSS) scale. The key secondary outcome for this trial is surgery rate per arm, which is estimated to be at least 18% lower in the urodynamics arm. Surgery rates, adverse events, flow rate, urinary symptoms and sexual symptoms are secondary outcomes to be assessed for superiority. This is an update to the UPSTREAM protocol, which has already been published in this journal. This a priori statistical analysis plan aims to reduce reporting bias by allowing access to the trial's objectives and plans in advance of recruitment end. The results of the trial are expected to be published soon after the trial end date of 30 September 2018. ISRCTN registry, ISRCTN56164274 . Registered on 8 April 2014.

Result Publication of Chinese Trials in World Health Organization Primary Registries

PubMed Central

Xuemei, Liu; Youping, Li; Senlin, Yin; Shangqi, Song

2010-01-01

Background Result publication is the key step to improve the transparency of clinical trials. Objective To investigate the result publication rate of Chinese trials registered in World Health Organization (WHO) primary registries. Method We searched 11 WHO primary registries for Chinese trials records. The progress of each trial was analyzed. We searched for the full texts of result publications cited in the registration records. For completed trials without citations, we searched PubMed, Embase, Chinese Biomedical Literature Database (Chinese), China Knowledge Resource Integrated Database, and Chinese Science and Technology Periodicals Database for result publications. The search was conducted on July 14, 2009. We also called the investigators of completed trials to ask about results publication. Results We identified 1294 Chinese trials records (428 in ChiCTR,743 in clinicaltrials.gov,55 in ISRCTN, 21 in ACTRN). A total of 443 trials had been completed. The publication rate of the Chinese trials in WHO primary registries is 35.2%(156/443).The publication rate of Chinese trials in clinicaltrials.gov, ChiCTR, ISRCTN, and ACRTN was 36.5% (53/145), 36.3% (89/245), 26.0%(9/44), and 55.6%(5/9), respectively. The publication rate of trials sponsored by industry(23.8%) was lower than that of sponsored by central and local government(31.7%), hospital(35.1%), and universities (40.7%). The publication rate for randomized trials was higher than that of cohort study and case-control study (33.2% versus 16.7%, 22.2%). The publication rate for interventional studies and observational studies was similar(33.4% versus 33.3%). Conclusion The publication rate of the registered Chinese trials was low, with no significant difference between ChiCTR and clinicaltrials.gov. An effective mechanism is needed to promote publication of results for registered trials in China. PMID:20856888

Effect of Lactobacillus paracasei subsp. paracasei, L. casei 431 on immune response to influenza vaccination and upper respiratory tract infections in healthy adult volunteers: a randomized, double-blind, placebo-controlled, parallel-group study.

PubMed

Jespersen, Lillian; Tarnow, Inge; Eskesen, Dorte; Morberg, Cathrine Melsaether; Michelsen, Birgit; Bügel, Susanne; Dragsted, Lars Ove; Rijkers, Ger T; Calder, Philip C

2015-06-01

Probiotics can modulate the immune system in healthy individuals and may help reduce symptoms related to respiratory infections. The objective of the study was to investigate the effect of the probiotic strain Lactobacillus paracasei subsp. paracasei, L. casei 431 (Chr. Hansen A/S) (hereafter, L. casei 431) on immune response to influenza vaccination and respiratory symptoms in healthy adults. A randomized double-blind, placebo-controlled trial was conducted in 1104 healthy subjects aged 18-60 y at 2 centers in Germany and Denmark. Subjects were randomly assigned to receive an acidified milk drink containing ≥10(9) colony-forming units of L. casei 431 (n = 553) or placebo (n = 551) for 42 d. After 21 d, subjects received the seasonal influenza vaccination. The primary outcome was seroprotection rate (anti-influenza antibody titers by hemagglutination inhibition) 21 d after vaccination. Other outcomes were seroconversion rate and mean titers, influenza A-specific antibodies and incidence, and duration and severity of upper respiratory symptoms. Antibiotic use and use of health care resources were recorded. There was no effect of L. casei 431 on immune responses to influenza vaccination. Generalized linear mixed modeling showed a shorter duration of upper respiratory symptoms in the probiotic group than in the placebo group (mean ± SD: 6.4 ± 6.1 vs. 7.3 ± 9.7 d, P = 0.0059) in the last 3 wk of the intervention period. No statistically significant differences were found for incidence or severity. Daily consumption of L. casei 431 resulted in no observable effect on the components of the immune response to influenza vaccination but reduced the duration of upper respiratory symptoms. The trial was registered at www.isrctn.com as ISRCTN08280229. © 2015 American Society for Nutrition.

Resource implications of preparing individual participant data from a clinical trial to share with external researchers.

PubMed

Tudur Smith, Catrin; Nevitt, Sarah; Appelbe, Duncan; Appleton, Richard; Dixon, Pete; Harrison, Janet; Marson, Anthony; Williamson, Paula; Tremain, Elizabeth

2017-07-17

Demands are increasingly being made for clinical trialists to actively share individual participant data (IPD) collected from clinical trials using responsible methods that protect the confidentiality and privacy of clinical trial participants. Clinical trialists, particularly those receiving public funding, are often concerned about the additional time and money that data-sharing activities will require, but few published empirical data are available to help inform these decisions. We sought to evaluate the activity and resources required to prepare anonymised IPD from a clinical trial in anticipation of a future data-sharing request. Data from two UK publicly funded clinical trials were used for this exercise: 2437 participants with epilepsy recruited from 90 hospital outpatient clinics in the SANAD trial and 146 children with neuro-developmental problems recruited from 18 hospitals in the MENDS trial. We calculated the time and resources required to prepare each anonymised dataset and assemble a data pack ready for sharing. The older SANAD trial (published 2007) required 50 hours of staff time with a total estimated associated cost of £3185 whilst the more recently completed MENDS trial (published 2012) required 39.5 hours of staff time with total estimated associated cost of £2540. Clinical trial researchers, funders and sponsors should consider appropriate resourcing and allow reasonable time for preparing IPD ready for subsequent sharing. This process would be most efficient if prospectively built into the standard operational design and conduct of a clinical trial. Further empirical examples exploring the resource requirements in other settings is recommended. SANAD: International Standard Randomised Controlled Trials Registry: ISRCTN38354748 . Registered on 25 April 2003. EU Clinical Trials Register Eudract 2006-004025-28 . Registered on 16 May 2007. International Standard Randomised Controlled Trials Registry: ISRCTN05534585 /MREC 07/MRE08/43. Registered on 26 January 2007.

MEDUCATE trial: effectiveness of an intensive EDUCATional intervention for IT-mediated MEDication management in the outpatient clinic - study protocol for a cluster randomized controlled trial.

PubMed

van Stiphout, F; Zwart-van Rijkom, J E F; Aarts, J E C M; Koffijberg, H; Klarenbeek-deJonge, E; Krulder, M; Roes, K C B; Egberts, A C G; ter Braak, E W M T

2015-05-22

Using information technology for medication management is an opportunity to help physicians to improve the quality of their documentation and communication and ultimately to improve patient care and patient safety. Physician education is necessary to take full advantage of information technology systems. In this trial, we seek to determine the effectiveness of an intensive educational intervention compared with the standard approach in improving information technology-mediated medication management and in reducing potential adverse drug events in the outpatient clinic. We are conducting a multicenter, cluster randomized controlled trial. The participants are specialists and residents working in the outpatient clinic of internal medicine, cardiology, pulmonology, geriatrics, gastroenterology and rheumatology. The intensive educational intervention is composed of a small-group session and e-learning. The primary outcome is discrepancies between registered medication (by physicians) and actually used medication (by patients). The key secondary outcomes are potential adverse events caused by missed drug-drug interactions. The primary and key secondary endpoints are being assessed shortly after the educational intervention is completed. Sample size will be calculated to ensure sufficient power. A sample size of 40 physicians per group and 20 patients per physician will ensure a power of >90 %, which means we will need a total of 80 physicians and 1,600 patients. We performed an exploratory trial wherein we tested the recruitment process, e-learning, time schedule, and methods for data collection, data management and data analysis. Accordingly, we refined the processes and content: the recruitment strategy was intensified, extra measures were taken to facilitate smooth conductance of the e-learning and parts were made optional. First versions of the procedures for data collection were determined. Data entry and analysis was further standardized by using the G-standard database in the telephone questionnaire. ISRCTN registry: ISRCTN50890124 . Registered 10 June 2013.

Arterial Obstruction on Computed Tomographic or Magnetic Resonance Angiography and Response to Intravenous Thrombolytics in Ischemic Stroke

PubMed Central

Mair, Grant; von Kummer, Rüdiger; Adami, Alessandro; White, Philip M.; Adams, Matthew E.; Yan, Bernard; Demchuk, Andrew M.; Farrall, Andrew J.; Sellar, Robin J.; Sakka, Eleni; Palmer, Jeb; Perry, David; Lindley, Richard I.; Sandercock, Peter A.G.

2017-01-01

Background and Purpose— Computed tomographic angiography and magnetic resonance angiography are used increasingly to assess arterial patency in patients with ischemic stroke. We determined which baseline angiography features predict response to intravenous thrombolytics in ischemic stroke using randomized controlled trial data. Methods— We analyzed angiograms from the IST-3 (Third International Stroke Trial), an international, multicenter, prospective, randomized controlled trial of intravenous alteplase. Readers, masked to clinical, treatment, and outcome data, assessed prerandomization computed tomographic angiography and magnetic resonance angiography for presence, extent, location, and completeness of obstruction and collaterals. We compared angiography findings to 6-month functional outcome (Oxford Handicap Scale) and tested for interactions with alteplase, using ordinal regression in adjusted analyses. We also meta-analyzed all available angiography data from other randomized controlled trials of intravenous thrombolytics. Results— In IST-3, 300 patients had prerandomization angiography (computed tomographic angiography=271 and magnetic resonance angiography=29). On multivariable analysis, more extensive angiographic obstruction and poor collaterals independently predicted poor outcome (P<0.01). We identified no significant interaction between angiography findings and alteplase effect on Oxford Handicap Scale (P≥0.075) in IST-3. In meta-analysis (5 trials of alteplase or desmoteplase, including IST-3, n=591), there was a significantly increased benefit of thrombolytics on outcome (odds ratio>1 indicates benefit) in patients with (odds ratio, 2.07; 95% confidence interval, 1.18–3.64; P=0.011) versus without (odds ratio, 0.88; 95% confidence interval, 0.58–1.35; P=0.566) arterial obstruction (P for interaction 0.017). Conclusions— Intravenous thrombolytics provide benefit to stroke patients with computed tomographic angiography or magnetic resonance angiography evidence of arterial obstruction, but the sample was underpowered to demonstrate significant treatment benefit or harm among patients with apparently patent arteries. Clinical Trial Registration— URL: http://www.isrctn.com. Unique identifier: ISRCTN25765518. PMID:28008093

Optimizing treatment with tumour necrosis factor inhibitors in rheumatoid arthritis-a proof of principle and exploratory trial: is dose tapering practical in good responders?

PubMed

Ibrahim, Fowzia; Lorente-Cánovas, Beatriz; Doré, Caroline J; Bosworth, Ailsa; Ma, Margaret H; Galloway, James B; Cope, Andrew P; Pande, Ira; Walker, David; Scott, David L

2017-11-01

RA patients receiving TNF inhibitors (TNFi) usually maintain their initial doses. The aim of the Optimizing Treatment with Tumour Necrosis Factor Inhibitors in Rheumatoid Arthritis trial was to evaluate whether tapering TNFi doses causes loss of clinical response. We enrolled RA patients receiving etanercept or adalimumab and a DMARD with DAS28 under 3.2 for over 3 months. Initially (months 0-6) patients were randomized to control (constant TNFi) or two experimental groups (tapering TNFi by 33 or 66%). Subsequently (months 6-12) control subjects were randomized to taper TNFi by 33 or 66%. Disease flares (DAS28 increasing ⩾0.6 with at least one additional swollen joint) were the primary outcome. Two hundred and forty-four patients were screened, 103 randomized and 97 treated. In months 0-6 there were 8/50 (16%) flares in controls, 3/26 (12%) with 33% tapering and 6/21 (29%) with 66% tapering. Multivariate Cox analysis showed time to flare was unchanged with 33% tapering but was reduced with 66% tapering compared with controls (adjusted hazard ratio 2.81, 95% CI: 0.99, 7.94; P = 0.051). Analysing all tapered patients after controls were re-randomized (months 6-12) showed differences between groups: there were 6/48 (13%) flares with 33% tapering and 14/39 (36%) with 66% tapering. Multivariate Cox analysis showed 66% tapering reduced time to flare (adjusted hazard ratio 3.47, 95% CI: 1.26, 9.58; P = 0.016). Tapering TNFi by 33% has no impact on disease flares and appears practical in patients in sustained remission and low disease activity states. EudraCT, https://www.clinicaltrialsregister.eu, 2010-020738-24; ISRCTN registry, https://www.isrctn.com, 28955701. © The Author 2017. Published by Oxford University Press on behalf of the British Society for Rheumatology.

Psychosocial therapy for Parkinson's-related dementia: study protocol for the INVEST randomised controlled trial.

PubMed

McCormick, Sheree A; McDonald, Kathryn R; Vatter, Sabina; Orgeta, Vasiliki; Poliakoff, Ellen; Smith, Sarah; Silverdale, Monty A; Fu, Bo; Leroi, Iracema

2017-06-19

Parkinson's disease (PD) with mild cognitive impairment (MCI-PD) or dementia (PDD) and dementia with Lewy bodies (DLB) are characterised by motor and 'non-motor' symptoms which impact on quality of life. Treatment options are generally limited to pharmacological approaches. We developed a psychosocial intervention to improve cognition, quality of life and companion burden for people with MCI-PD, PDD or DLB. Here, we describe the protocol for a single-blind randomised controlled trial to assess feasibility, acceptability and tolerability of the intervention and to evaluate treatment implementation. The interaction among the intervention and selected outcome measures and the efficacy of this intervention in improving cognition for people with MCI-PD, PDD or DLB will also be explored. Dyads will be randomised into two treatment arms to receive either 'treatment as usual' (TAU) or cognitive stimulation therapy specifically adapted for Parkinson's-related dementias (CST-PD), involving 30 min sessions delivered at home by the study companion three times per week over 10 weeks. A mixed-methods approach will be used to collect data on the operational aspects of the trial and treatment implementation. This will involve diary keeping, telephone follow-ups, dyad checklists and researcher ratings. Analysis will include descriptive statistics summarising recruitment, acceptability and tolerance of the intervention, and treatment implementation. To pilot an outcome measure of efficacy, we will undertake an inferential analysis to test our hypothesis that compared with TAU, CST-PD improves cognition. Qualitative approaches using thematic analysis will also be applied. Our findings will inform a larger definitive trial. Ethical opinion was granted (REC reference: 15/YH/0531). Findings will be published in peer-reviewed journals and at conferences. We will prepare reports for dissemination by organisations involved with PD and dementia. ISRCTN (ISRCTN11455062). © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Carrageenan nasal spray in virus confirmed common cold: individual patient data analysis of two randomized controlled trials.

PubMed

Koenighofer, Martin; Lion, Thomas; Bodenteich, Angelika; Prieschl-Grassauer, Eva; Grassauer, Andreas; Unger, Hermann; Mueller, Christian A; Fazekas, Tamás

2014-01-01

Clinical trials applying iota-carrageenan nasal spray have previously shown to reduce duration of virus-confirmed common cold. The present study pooled data of two similar clinical trials to provide further evidence for the antiviral effectiveness of carrageenan. Individual patient data were analyzed from two randomized double blind placebo controlled trials assessing the therapeutic effectiveness of carrageenan nasal spray in acute common cold. Patients with virus-confirmed common cold (n = 254, verum 126, placebo 128) were included and the following parameters were appraised: duration of disease, number of patients with relapses, number of respiratory viruses and viral titers at inclusion (visit 1) compared to days 3-5 (visit 2). Carrageenan treated patients showed a significant reduction in duration of disease of almost 2 days (p < 0.05) as well as significantly fewer relapses during 21 days of observation period (p < 0.05). The virus clearance between visit 1 and visit 2 was significantly more pronounced in the carrageenan group (p < 0.05). In both studies, virus-confirmed common cold was caused by three main virus subtypes: human rhinovirus (46%), human coronavirus (25%) and influenza A (14%) virus. Carrageenan nasal spray showed significant antiviral efficacy in all three virus subgroups, the highest effectiveness was observed in human corona virus-infected patients. The reduced duration of disease was 3 days (p < 0.01) and the number of relapses was three times less (p < 0.01) in carrageenan treated corona-virus-infected patients compared to control patients. Administration of carrageenan nasal spray in children as well as in adults suffering from virus-confirmed common cold reduced duration of disease, increased viral clearance and reduced relapses of symptoms. Carrageenan nasal spray appeared as an effective treatment of common cold in children and adults. Pooled data from ISRCTN52519535 and ISRCTN80148028.

Cluster randomized trials utilizing primary care electronic health records: methodological issues in design, conduct, and analysis (eCRT Study)

PubMed Central

2014-01-01

Background There is growing interest in conducting clinical and cluster randomized trials through electronic health records. This paper reports on the methodological issues identified during the implementation of two cluster randomized trials using the electronic health records of the Clinical Practice Research Datalink (CPRD). Methods Two trials were completed in primary care: one aimed to reduce inappropriate antibiotic prescribing for acute respiratory infection; the other aimed to increase physician adherence with secondary prevention interventions after first stroke. The paper draws on documentary records and trial datasets to report on the methodological experience with respect to research ethics and research governance approval, general practice recruitment and allocation, sample size calculation and power, intervention implementation, and trial analysis. Results We obtained research governance approvals from more than 150 primary care organizations in England, Wales, and Scotland. There were 104 CPRD general practices recruited to the antibiotic trial and 106 to the stroke trial, with the target number of practices being recruited within six months. Interventions were installed into practice information systems remotely over the internet. The mean number of participants per practice was 5,588 in the antibiotic trial and 110 in the stroke trial, with the coefficient of variation of practice sizes being 0.53 and 0.56 respectively. Outcome measures showed substantial correlations between the 12 months before, and after intervention, with coefficients ranging from 0.42 for diastolic blood pressure to 0.91 for proportion of consultations with antibiotics prescribed, defining practice and participant eligibility for analysis requires careful consideration. Conclusions Cluster randomized trials may be performed efficiently in large samples from UK general practices using the electronic health records of a primary care database. The geographical dispersal of trial sites presents a difficulty for research governance approval and intervention implementation. Pretrial data analyses should inform trial design and analysis plans. Trial registration Current Controlled Trials ISRCTN 47558792 and ISRCTN 35701810 (both registered on 17 March 2010). PMID:24919485

Effectiveness of a clinical practice guideline implementation strategy for patients with anxiety disorders in primary care: cluster randomized trial.

PubMed

Tello-Bernabé, Eugenia; Sanz-Cuesta, Teresa; del Cura-González, Isabel; de Santiago-Hernando, María L; Jurado-Sueiro, Montserrat; Fernández-Girón, Mercedes; García-de Blas, Francisca; Pensado-Freire, Higinio; Góngora-Maldonado, Francisco; de la Puente-Chamorro, María J; Rodríguez-Pasamontes, Carmen; Martín-Iglesias, Susana

2011-12-01

Anxiety is a common mental health problem seen in primary care. However, its management in clinical practice varies greatly. Clinical practice guidelines (CPGs) have the potential to reduce variations and improve the care received by patients by promoting interventions of proven benefit. However, uptake and adherence to their recommendations can be low. This study involves a community based on cluster randomized trial in primary healthcare centres in the Madrid Region (Spain). The project aims to determine whether the use of implementation strategy (including training session, information, opinion leader, reminders, audit, and feed-back) of CPG for patients with anxiety disorders in primary care is more effective than usual diffusion. The number of patients required is 296 (148 in each arm), all older than 18 years and diagnosed with generalized anxiety disorder, panic disorder, and panic attacks by the Diagnostic and Statistical Manual of Mental Disorders-IV (DSM-IV). They are chosen by consecutive sampling. The main outcome variable is the change in two or more points into Goldberg anxiety scale at six and twelve months. Secondary outcome variables include quality of life (EuroQol 5D), and degree of compliance with the CPG recommendations on treatment, information, and referrals to mental health services. Main effectiveness will be analyzed by comparing the patients percentage improvement on the Goldberg scale between the intervention group and the control group. Logistic regression with random effects will be used to adjust for prognostic factors. Confounding factors or factors that might alter the effect recorded will be taken into account in this analysis. There is a need to identify effective implementation strategies for CPG for the management of anxiety disorders present in primary care. Ensuring the appropriate uptake of guideline recommendations can reduce clinical variation and improve the care patients receive. ISRCTN: ISRCTN83365316.

The long-term (24-month) effect on health and well-being of the Lifestyle Matters community-based intervention in people aged 65 years and over: a qualitative study

PubMed Central

Chatters, Robin; Roberts, Jennifer; Mountain, Gail; Cook, Sarah; Windle, Gill; Craig, Claire; Sprange, Kirsty

2017-01-01

Objectives To assess the long-term effect on health and well-being of the Lifestyle Matters programme. Design Qualitative study of a subset of intervention arm participants who participated in the Lifestyle Matters randomised controlled trial (RCT). Setting The intervention took place at community venues within two sites in the UK. Participants A purposeful sample of 13 participants aged between 66 and 88 years from the intervention arm of the RCT were interviewed at 24 months post randomisation. Interviews aimed to understand how participants had used their time in the preceding 2 years and whether the intervention had any impact on their lifestyle choices, participation in meaningful activities and well-being. Intervention Lifestyle Matters is a 4-month occupational therapy intervention, consisting of group and individual sessions, designed to enable community living older people to make positive lifestyle choices and participate in new or neglected activities through increasing self-efficacy. Results Interviews revealed that the majority of interviewed participants were reportedly active at 24 months, with daily routines and lifestyles not changing significantly over time. All participants raised some form of benefit from attending Lifestyle Matters, including an improved perspective on life, trying new hobbies and meeting new friends. A number of intervention participants spoke of adapting to their changing circumstances, but there were significant and lasting benefits for 2 of 13 intervention participants interviewed. Conclusion The majority of those who experienced the Lifestyle Matters intervention reported minor benefits and increases in self-efficacy, but they did not perceive that it significantly improved their health and well-being. The two participants who had experienced major benefits also reported having had life-changing events, suggesting that this intervention is most effective at the time when lifestyle has to be reconsidered if mental well-being is to be sustained. Trial registration ISRCTN, ISRCTN67209155, post results. PMID:28947449

Activity Increase Despite Arthritis (AIDA): design of a Phase II randomised controlled trial evaluating an active management booklet for hip and knee osteoarthritis [ISRCTN24554946].

PubMed

Williams, Nefyn H; Amoakwa, Elvis; Burton, Kim; Hendry, Maggie; Belcher, John; Lewis, Ruth; Hood, Kerenza; Jones, Jeremy; Bennett, Paul; Edwards, Rhiannon T; Neal, Richard D; Andrew, Glynne; Wilkinson, Clare

2009-09-04

Hip and knee osteoarthritis is a common cause of pain and disability, which can be improved by exercise interventions. However, regular exercise is uncommon in this group because the low physical activity level in the general population is probably reduced even further by pain related fear of movement. The best method of encouraging increased activity in this patient group is not known. A booklet has been developed for patients with hip or knee osteoarthritis. It focuses on changing disadvantageous beliefs and encouraging increased physical activity. This paper describes the design of a Phase II randomised controlled trial (RCT) to test the effectiveness of this new booklet for patients with hip and knee osteoarthritis in influencing illness and treatment beliefs, and to assess the feasibility of conducting a larger definitive RCT in terms of health status and exercise behaviour. A computerised search of four general medical practice patients' record databases will identify patients older than 50 years of age who have consulted with hip or knee pain in the previous twelve months. A random sample of 120 will be invited to participate in the RCT comparing the new booklet with a control booklet, and we expect 100 to return final questionnaires. This trial will assess the feasibility of recruitment and randomisation, the suitability of the control intervention and outcome measurement tools, and will provide an estimate of effect size. Outcomes will include beliefs about hip and knee pain, beliefs about exercise, fear avoidance, level of physical activity, health status and health service costs. They will be measured at baseline, one month and three months. We discuss the merits of testing effectiveness in a phase II trial, in terms of intermediate outcome measures, whilst testing the processes for a larger definitive trial. We also discuss the advantages and disadvantages of testing the psychometric properties of the primary outcome measures concurrently with the trial. Current Controlled Trials ISRCTN24554946.

Improving diets and nutrition through an integrated poultry value chain and nutrition intervention (SELEVER) in Burkina Faso: study protocol for a randomized trial.

PubMed

Gelli, Aulo; Becquey, Elodie; Ganaba, Rasmane; Headey, Derek; Hidrobo, Melissa; Huybregts, Lieven; Verhoef, Hans; Kenfack, Romain; Zongouri, Sita; Guedenet, Hannah

2017-09-06

The SELEVER study is designed to evaluate the impact of an integrated agriculture-nutrition package of interventions (including poultry value chain development, women's empowerment activities, and a behavior change communications strategy to promote improved diets and feeding, care, and hygiene practices) on the diets, health, and nutritional status of women and children in Burkina Faso. This paper presents the rationale and study design. The impact evaluation involves a cluster randomized controlled trial design that will be implemented in 120 rural communities/villages within 60 communes supported by SELEVER in the Boucle de Mouhoun, Centre-Ouest, and Haut-Bassins regions of Burkina Faso. Communities will be randomly assigned to one of three treatment arms, including: (1) SELEVER intervention group; (2) SELEVER with an intensive WASH component; and (3) control group without intervention. Primary outcomes include the mean probability of adequacy of diets for women and children (aged 2-4 years at baseline), infant and young child feeding practices of caregivers of children aged 0-2 years, and household poultry production and sales. Intermediate outcomes along the agriculture and nutrition pathways will also be measured, including child nutrition status and development. The evaluation will follow a mixed-methods approach, including a panel of child-, household-, community-, and market-level surveys, and data collection points during post-harvest and lean seasons, as well as one year after implementation completion to examine sustainability. To our knowledge, this study is the first to rigorously examine from a food systems perspective, the simultaneous impact of scaling-up nutrition-specific and nutrition-sensitive interventions through a livestock value-chain and community-intervention platform, across nutrition, health, and agriculture domains. The findings of this evaluation will provide evidence to support the design of market-based nutrition-sensitive interventions. ISRCTN registry, ISRCTN16686478 . Registered on 2 December 2016.

The CIRCuiTS study (Implementation of cognitive remediation in early intervention services): protocol for a randomised controlled trial.

PubMed

Wykes, Til; Joyce, Eileen; Velikonja, Tjasa; Watson, Andrew; Aarons, Gregory; Birchwood, Max; Cella, Matteo; Dopson, Sue; Fowler, David; Greenwood, Kathy; Johnson, Sonia; McCrone, Paul; Perez, Jesus; Pickles, Andrew; Reeder, Clare; Rose, Diana; Singh, Swaran; Stringer, Dominic; Taylor, Matthew; Taylor, Rumina; Upthegrove, Rachel

2018-03-15

Cognitive problems in people with schizophrenia predict poor functional recovery even with the best possible rehabilitation opportunities and optimal medication. A psychological treatment known as cognitive remediation therapy (CRT) aims to improve cognition in neuropsychiatric disorders, with the ultimate goal of improving functional recovery. Studies suggest that intervening early in the course of the disorder will have the most benefit, so this study will be based in early intervention services, which treat individuals in the first few years following the onset of the disorder. The overall aim is to investigate different methods of CRT. This is a multicentre, randomised, single-blinded, controlled trial based in early intervention services in National Health Service Mental Health Trusts in six English research sites. Three different methods of providing CRT (intensive, group, and independent) will be compared with treatment as usual. We will recruit 720 service users aged between 16 and 45 over 3 years who have a research diagnosis of non-affective psychosis and will be at least 3 months from the onset of the first episode of psychosis. The primary outcome measure will be the degree to which participants have achieved their stated goals using the Goal Attainment Scale. Secondary outcome measures will include improvements in cognitive function, social function, self-esteem, and clinical symptoms. It has already been established that cognitive remediation improves cognitive function in people with schizophrenia. Successful implementation in mental health services has the potential to change the recovery trajectory of individuals with schizophrenia-spectrum disorders. However, the best mode of implementation, in terms of efficacy, service user and team preference, and cost-effectiveness is still unclear. The CIRCuiTS trial will provide guidance for a large-scale roll-out of CRT to mental health services where cognitive difficulties impact recovery and resilience. ISRCTN, ISRCTN14678860 , Registered on 6 June 2016.

Work-focused cognitive behavioral intervention for psychological complaints in patients on sick leave due to work-related stress: Results from a randomized controlled trial.

PubMed

Dalgaard, Vita Ligaya; Andersen, Lars Peter Sønderbo; Andersen, Johan Hviid; Willert, Morten Vejs; Carstensen, Ole; Glasscock, David John

2017-08-22

Work-related stress is a global problem with negative implications for individuals and society. The purpose of the current study was to evaluate a stress management intervention for patients on sick leave due to work-related stress complaints using a three-armed randomized controlled design. Participants were patients referred from three municipalities to the regional Department of Occupational Medicine. Inclusion criteria were: 1) sick leave due to work-related stress complaints, 2) a diagnosis of adjustment disorder or reactions to severe stress (ICD 10 code: F43,2 - F 43,9 not PTSD) or mild depressive episode (F 32.0). Through a double randomization procedure patients (n = 163) were randomized to either an intervention group (n = 58), a 'control group A' receiving a clinical examination (n = 56), or 'control group B' (n = 49) receiving no offers at the department. The intervention comprised six sessions of individual cognitive behavioral therapy and the offer of a small workplace intervention. Questionnaire data were analyzed with multivariate repeated measurements analysis. Primary outcomes assessed were perceived stress and general mental health. Secondary outcomes were sleep quality and cognitive failures. Follow-up was at four and 10 months after baseline. Complaints were significantly reduced in all groups over time. No group effects were observed between the intervention group and control group A that was clinically assessed. Significant group effects were found for perceived stress and memory when comparing the intervention group to group B, but most likely not due to an intervention effect. Psychological complaints improved substantially over time in all groups, but there was no significant treatment effect on any outcomes when the intervention group was compared to control group A that received a clinical assessment. ISRCTN ISRCTN91404229. Registered 03 August 2012 (retrospectively registered).

Aspartame sensitivity? A double blind randomised crossover study.

PubMed

Sathyapalan, Thozhukat; Thatcher, Natalie J; Hammersley, Richard; Rigby, Alan S; Courts, Fraser L; Pechlivanis, Alexandros; Gooderham, Nigel J; Holmes, Elaine; le Roux, Carel W; Atkin, Stephen L

2015-01-01

Aspartame is a commonly used intense artificial sweetener, being approximately 200 times sweeter than sucrose. There have been concerns over aspartame since approval in the 1980s including a large anecdotal database reporting severe symptoms. The objective of this study was to compare the acute symptom effects of aspartame to a control preparation. This was a double-blind randomized cross over study conducted in a clinical research unit in United Kingdom. Forty-eight individual who has self reported sensitivity to aspartame were compared to 48 age and gender matched aspartame non-sensitive individuals. They were given aspartame (100mg)-containing or control snack bars randomly at least 7 days apart. The main outcome measures were acute effects of aspartame measured using repeated ratings of 14 symptoms, biochemistry and metabonomics. Aspartame sensitive and non-sensitive participants differed psychologically at baseline in handling feelings and perceived stress. Sensitive participants had higher triglycerides (2.05 ± 1.44 vs. 1.26 ± 0.84mmol/L; p value 0.008) and lower HDL-C (1.16 ± 0.34 vs. 1.35 ± 0.54 mmol/L; p value 0.04), reflected in 1H NMR serum analysis that showed differences in the baseline lipid content between the two groups. Urine metabonomic studies showed no significant differences. None of the rated symptoms differed between aspartame and control bars, or between sensitive and control participants. However, aspartame sensitive participants rated more symptoms particularly in the first test session, whether this was placebo or control. Aspartame and control bars affected GLP-1, GIP, tyrosine and phenylalanine levels equally in both aspartame sensitive and non-sensitive subjects. Using a comprehensive battery of psychological tests, biochemistry and state of the art metabonomics there was no evidence of any acute adverse responses to aspartame. This independent study gives reassurance to both regulatory bodies and the public that acute ingestion of aspartame does not have any detectable psychological or metabolic effects in humans. ISRCTN Registry ISRCTN39650237.

A multi-centre, randomised controlled trial of cognitive therapy to prevent harmful compliance with command hallucinations.

PubMed

Birchwood, Max; Peters, Emmanuelle; Tarrier, Nicholas; Dunn, Graham; Lewis, Shon; Wykes, Til; Davies, Linda; Lester, Helen; Michail, Maria

2011-09-30

Command hallucinations are among the most distressing, high risk and treatment resistant symptoms for people with psychosis; however, currently, there are no evidence-based treatment options available for this group. A cognitive therapy grounded in the principles of the Social Rank Theory, is being evaluated in terms of its effectiveness in reducing harmful compliance with command hallucinations. This is a single blind, intention-to-treat, multi-centre, randomized controlled trial comparing Cognitive Therapy for Command Hallucinations + Treatment as Usual with Treatment as Usual alone. Eligible participants have to fulfil the following inclusion criteria: i) ≥16 years; ii) ICD-10 diagnosis of schizophrenia or related disorder; iii) command hallucinations for at least 6 months leading to risk of harm to self or others. Following the completion of baseline assessments, eligible participants will be randomly allocated to either the Cognitive Therapy for Command Hallucinations + Treatment as Usual group or the Treatment as Usual group. Outcome will be assessed at 9 and 18 months post randomization with assessors blind to treatment allocation. The primary outcome is compliance behaviour and secondary outcomes include beliefs about voices' power, distress, psychotic symptoms together with a health economic evaluation. Qualitative interviews with services users will explore the acceptability of Cognitive Therapy for Command Hallucinations. Cognitive behaviour therapy is recommended for people with psychosis; however, its focus and evaluation has primarily revolved around the reduction of psychotic symptoms. In this trial, however, the focus of the cognitive behavioural intervention is on individuals' appraisals, behaviour and affect and not necessarily symptoms; this is also reflected in the outcome measures used. If successful, the results will mark a significant breakthrough in the evidence base for service users and clinicians and will provide a treatment option for this group where none currently exist. The trial will open the way for further breakthrough work with the 'high risk' population of individuals with psychosis, which we would intend to pursue. ISRCTN: ISRCTN62304114.

Prostate cancer - evidence of exercise and nutrition trial (PrEvENT): study protocol for a randomised controlled feasibility trial.

PubMed

Hackshaw-McGeagh, Lucy; Lane, J Athene; Persad, Raj; Gillatt, David; Holly, Jeff M P; Koupparis, Anthony; Rowe, Edward; Johnston, Lyndsey; Cloete, Jenny; Shiridzinomwa, Constance; Abrams, Paul; Penfold, Chris M; Bahl, Amit; Oxley, Jon; Perks, Claire M; Martin, Richard

2016-03-07

A growing body of observational evidence suggests that nutritional and physical activity interventions are associated with beneficial outcomes for men with prostate cancer, including brisk walking, lycopene intake, increased fruit and vegetable intake and reduced dairy consumption. However, randomised controlled trial data are limited. The 'Prostate Cancer: Evidence of Exercise and Nutrition Trial' investigates the feasibility of recruiting and randomising men diagnosed with localised prostate cancer and eligible for radical prostatectomy to interventions that modify nutrition and physical activity. The primary outcomes are randomisation rates and adherence to the interventions at 6 months following randomisation. The secondary outcomes are intervention tolerability, trial retention, change in prostate specific antigen level, change in diet, change in general physical activity levels, insulin-like growth factor levels, and a range of related outcomes, including quality of life measures. The trial is factorial, randomising men to both a physical activity (brisk walking or control) and nutritional (lycopene supplementation or increased fruit and vegetables with reduced dairy consumption or control) intervention. The trial has two phases: men are enrolled into a cohort study prior to radical prostatectomy, and then consented after radical prostatectomy into a randomised controlled trial. Data are collected at four time points (cohort baseline, true trial baseline and 3 and 6 months post-randomisation). The Prostate Cancer: Evidence of Exercise and Nutrition Trial aims to determine whether men with localised prostate cancer who are scheduled for radical prostatectomy can be recruited into a cohort and subsequently randomised to a 6-month nutrition and physical activity intervention trial. If successful, this feasibility trial will inform a larger trial to investigate whether this population will gain clinical benefit from long-term nutritional and physical activity interventions post-surgery. Prostate Cancer: Evidence of Exercise and Nutrition Trial (PrEvENT) is registered on the ISRCTN registry, ref number ISRCTN99048944. Date of registration 17 November 2014.

Use of Anticoagulants and Antiplatelet Agents in Stable Outpatients with Coronary Artery Disease and Atrial Fibrillation. International CLARIFY Registry.

PubMed

Fauchier, Laurent; Greenlaw, Nicola; Ferrari, Roberto; Ford, Ian; Fox, Kim M; Tardif, Jean-Claude; Tendera, Michal; Steg, Ph Gabriel

2015-01-01

Few data are available regarding the use of antithrombotic strategies in coronary artery disease patients with atrial fibrillation (AF) in everyday practice. We sought to describe the prevalence of AF and its antithrombotic management in a contemporary population of patients with stable coronary artery disease. CLARIFY is an international, prospective, longitudinal registry of outpatients with stable coronary artery disease, defined as prior (≥12 months) myocardial infarction, revascularization procedure, coronary stenosis >50%, or chest pain associated with evidence of myocardial ischemia. Overall, 33,428 patients were screened, of whom 32,954 had data available for analysis at baseline; of these 2,229 (6.7%) had a history of AF. Median (interquartile range) CHA2DS2-VASc score was 4 (3, 5). Oral anticoagulation alone was used in 25.7%, antiplatelet therapy alone in 52.8% (single 41.8%, dual 11.0%), and both in 21.5%. OAC use was independently associated with permanent AF (p<0.001), CHA2DS2-VASc score (p=0.006), pacemaker (p<0.001), stroke (p=0.04), absence of angina (p=0.004), decreased left ventricular ejection fraction (p<0.001), increased waist circumference (p=0.005), and longer history of coronary artery disease (p=0.008). History of percutaneous coronary intervention (p=0.004) and no/partial reimbursement for cardiovascular medication (p=0.01, p<0.001, respectively) were associated with reduced oral anticoagulant use. In this contemporary cohort of patients with stable coronary artery disease and AF, most of whom are theoretical candidates for anticoagulation, oral anticoagulants were used in only 47.2%. Half of the patients received antiplatelet therapy alone and one-fifth received both antiplatelets and oral anticoagulants. Efforts are needed to improve adherence to guidelines in these patients. ISRCTN registry of clinical trials: ISRCTN43070564.

Music therapy for children and adolescents with behavioural and emotional problems: a randomised controlled trial.

PubMed

Porter, Sam; McConnell, Tracey; McLaughlin, Katrina; Lynn, Fiona; Cardwell, Christopher; Braiden, Hannah-Jane; Boylan, Jackie; Holmes, Valerie

2017-05-01

Although music therapy (MT) is considered an effective intervention for young people with mental health needs, its efficacy in clinical settings is unclear. We therefore examined the efficacy of MT in clinical practice. Two hundred and fifty-one child (8-16 years, with social, emotional, behavioural and developmental difficulties) and parent dyads from six Child and Adolescent Mental Health Service community care facilities in Northern Ireland were randomised to 12 weekly sessions of MT plus usual care [n = 123; 76 in final analyses] or usual care alone [n = 128; 105 in final analyses]. Follow-up occurred at 13 weeks and 26 weeks postrandomisation. Primary outcome was improvement in communication (Social Skills Improvement System Rating Scales) (SSIS) at 13 weeks. Secondary outcomes included social functioning, self-esteem, depression and family functioning. There was no significant difference for the child SSIS at week 13 (adjusted difference in mean 2.4; 95% CI -1.2 to 6.1; p = .19) or for the guardian SSIS (0.5; 95% CI -2.9 to 3.8; p = .78). However, for participants aged 13 and over in the intervention group, the child SSIS communication was significantly improved (6.1, 95% CI 1.6 to 10.5; p = .007) but not the guardian SSIS (1.1; 95% CI -2.9 to 5.2; p = .59). Overall, self-esteem was significantly improved and depression scores were significantly lower at week 13. There was no significant difference in family or social functioning at week 13. While the findings provide some evidence for the integration of music therapy into clinical practice, differences relating to subgroups and secondary outcomes indicate the need for further study. ISRCTN Register; ISRCTN96352204. © 2016 The Authors. Journal of Child Psychology and Psychiatry published by John Wiley & Sons Ltd on behalf of Association for Child and Adolescent Mental Health.

The effect of increased coverage of participatory women's groups on neonatal mortality in Bangladesh: A cluster randomized trial.

PubMed

Fottrell, Edward; Azad, Kishwar; Kuddus, Abdul; Younes, Layla; Shaha, Sanjit; Nahar, Tasmin; Aumon, Bedowra Haq; Hossen, Munir; Beard, James; Hossain, Tanvir; Pulkki-Brannstrom, Anni-Maria; Skordis-Worrall, Jolene; Prost, Audrey; Costello, Anthony; Houweling, Tanja A J

2013-09-01

Community-based interventions can reduce neonatal mortality when health systems are weak. Population coverage of target groups may be an important determinant of their effect on behavior and mortality. A women's group trial at coverage of 1 group per 1414 population in rural Bangladesh showed no effect on neonatal mortality, despite a similar intervention having a significant effect on neonatal and maternal death in comparable settings. To assess the effect of a participatory women's group intervention with higher population coverage on neonatal mortality in Bangladesh. A cluster randomized controlled trial in 9 intervention and 9 control clusters. Rural Bangladesh. Women permanently residing in 18 unions in 3 districts and accounting for 19 301 births during the final 24 months of the intervention. Women's groups at a coverage of 1 per 309 population that proceed through a participatory learning and action cycle in which they prioritize issues that affected maternal and neonatal health and design and implement strategies to address these issues. Neonatal mortality rate. Analysis included 19 301 births during the final 24 months of the intervention. More than one-third of newly pregnant women joined the groups. The neonatal mortality rate was significantly lower in the intervention arm (21.3 neonatal deaths per 1000 live births vs 30.1 per 1000 in control areas), a reduction in neonatal mortality of 38% (risk ratio, 0.62 [95% CI, 0.43-0.89]) when adjusted for socioeconomic factors. The cost-effectiveness was US $220 to $393 per year of life lost averted. Cause-specific mortality rates suggest reduced deaths due to infections and those associated with prematurity/low birth weight. Improvements were seen in hygienic home delivery practices, newborn thermal care, and breastfeeding practices. Women's group community mobilization, delivered at adequate population coverage, is a highly cost-effective approach to improve newborn survival and health behavior indicators in rural Bangladesh. isrctn.org Identifier: ISRCTN01805825.

Associations of Ischemic Lesion Volume With Functional Outcome in Patients With Acute Ischemic Stroke: 24-Hour Versus 1-Week Imaging.

PubMed

Bucker, Amber; Boers, Anna M; Bot, Joseph C J; Berkhemer, Olvert A; Lingsma, Hester F; Yoo, Albert J; van Zwam, Wim H; van Oostenbrugge, Robert J; van der Lugt, Aad; Dippel, Diederik W J; Roos, Yvo B W E M; Majoie, Charles B L M; Marquering, Henk A

2017-05-01

Ischemic lesion volume (ILV) on noncontrast computed tomography at 1 week can be used as a secondary outcome measure in patients with acute ischemic stroke. Twenty-four-hour ILV on noncontrast computed tomography has greater availability and potentially allows earlier estimation of functional outcome. We aimed to assess lesion growth 24 hours after stroke onset and compare the associations of 24-hour and 1-week ILV with functional outcome. We included 228 patients from MR CLEAN trial (Multicenter Randomized Clinical Trial of Endovascular Treatment for Acute Ischemic Stroke in the Netherlands), who received noncontrast computed tomography at 24-hour and 1-week follow-up on which ILV was measured. Relative and absolute lesion growth was determined. Logistic regression models were constructed either including the 24-hour or including the 1-week ILV. Ordinal and dichotomous (0-2 and 3-6) modified Rankin scale scores were, respectively, used as primary and secondary outcome measures. Median ILV was 42 mL (interquartile range, 21-95 mL) and 64 mL (interquartile range: 30-120 mL) at 24 hours and 1 week, respectively. Relative lesion growth exceeding 30% occurred in 121 patients (53%) and absolute lesion growth exceeding 20 mL occurred in 83 patients (36%). Both the 24-hour and 1-week ILVs were similarly significantly associated with functional outcome (both P <0.001). In the logistic analyses, the areas under the curve of the receiver-operator characteristic curves were similar: 0.85 (95% confidence interval, 0.80-0.90) and 0.87 (95% confidence interval, 0.82-0.91) for including the 24-hour and 1-week ILV, respectively. Growth of ILV is common 24-hour poststroke onset. Nevertheless, the 24-hour ILV proved to be a valuable secondary outcome measure as it is equally strongly associated with functional outcome as the 1-week ILV. URL: http://www.isrctn.com. Unique identifier: ISRCTN10888758. © 2017 American Heart Association, Inc.

Factors affecting food choices of older adults from high and low socioeconomic groups: a discrete choice experiment.

PubMed

Kamphuis, Carlijn B M; de Bekker-Grob, Esther W; van Lenthe, Frank J

2015-04-01

Healthiness, price, and convenience are typically indicated as important motives for food choices; however, it is largely unknown to what extent older adults from high and low socioeconomic groups differ in these underlying motives. A discrete choice experiment (DCE) is an innovative way to elicit implicit motives for food choices. The aim was to investigate differences in food motives between socioeconomic groups by means of a DCE. A DCE was carried out during a face-to-face interview among older adults as part of the Health and Living Conditions in Eindhoven and surrounding cities (GLOBE) cohort study, The Netherlands. Participants (n = 399; mean age: 63.3 y) were offered a series of choice sets about a usual dinner at home and were asked to choose in each choice set between 2 meals and an opt-out choice, with different combinations of attribute levels. We included 5 meal attributes (taste, healthiness, preparation time, travel time to shops, and price) and 3 or 4 levels for each attribute. Data were analyzed by multinomial logit models. Healthiness, taste, price, and travel time to the grocery store proved to significantly influence older adults' meal decisions; preparation time was not significant. Healthiness was the most important attribute for all of the participants. More highly educated participants rated a healthy and less expensive meal to be more important than did less educated participants. Those with a high income rated a meal that was healthy and very tasteful to be more important than did those with a lower income. Healthiness, taste, price, and travel time to grocery shops influenced older adults' meal decisions. Higher socioeconomic groups valued health more than did lower socioeconomic groups. DCEs represent a promising method to gain insight into the relative importance of motives for food choices. This trial was registered at www.isrctn.com as ISRCTN60293770. © 2015 American Society for Nutrition.

Talcum powder or aqueous gel to aid external cephalic version: a randomised controlled trial

PubMed Central

2014-01-01

Background External cephalic version (ECV) is offered to reduce the number of Caesarean delivery indicated by breech presentation which occurs in 3-4% of term pregnancies. ECV is commonly performed aided by the application of aqueous gel or talcum powder to the maternal abdomen. We sought to compare gel with powder during ECV on achieving successful version and increasing tolerability. Method We enrolled 95 women (≥ 36 weeks gestation) on their attendance for planned ECV. All participants received terbutaline tocolysis. Regional anaesthesia was not used. ECV was performed in the standard fashion after the application of the allocated aid. If the first round (maximum of 2 attempts) of ECV failed, crossover to the opposing aid was permitted. Results 48 women were randomised to powder and 47 to gel. Self-reported procedure related median [interquartile range] pain scores (using a 10-point visual numerical rating scale VNRS; low score more pain) were 6 [5-9] vs. 8 [7-9] P = 0.03 in favor of gel. ECV was successful in 21/48 (43.8%) vs. 26/47 (55.3%) RR 0.6 95% CI 0.3-1.4 P = 0.3 for powder and gel arms respectively. Crossover to the opposing aid and a second round of ECV was performed in 13/27 (48.1%) following initial failure with powder and 4/21 (19%) after failure with gel (RR 3.9 95% CI 1.0-15 P = 0.07). ECV success rate was 5/13 (38.5%) vs. 1/4 (25%) P = 0.99 after crossover use of gel or powder respectively. Operators reported higher satisfaction score with the use of gel (high score, greater satisfaction) VNRS scores 6 [4.25-8] vs 8 [7-9] P = 0.01. Conclusion Women find gel use to be associated with less pain. The ECV success rate is not significantly different. Trial registration The trial is registered with ISRCTN (identifier ISRCTN87231556). PMID:24468078

Evaluation of a decision aid for women with breech presentation at term: a randomised controlled trial [ISRCTN14570598

PubMed Central

Nassar, N; Roberts, CL; Raynes-Greenow, CH; Barratt, A; Peat, B

2007-01-01

Objectives To evaluate the effectiveness of a decision aid for women with a breech presentation compared with usual care. Design Randomised controlled trial. Setting Tertiary obstetric hospitals offering external cephalic version (ECV). Population Women with a singleton pregnancy were diagnosed antenatally with a breech presentation at term, and were clinically eligible for ECV. Methods Women were randomised to either receive a decision aid about the management options for breech presentation in addition to usual care or to receive usual care only with standard counselling from their usual pregnancy care provider. The decision aid comprised a 24-page booklet supplemented by a 30-minute audio-CD and worksheet that was designed for women to take home and review with a partner. Main outcome measures Decisional conflict (uncertainty), knowledge, anxiety and satisfaction with decision making, and were assessed using self-administered questionnaires. Results Compared with usual care, women reviewing the decision aid experienced significantly lower decisional conflict (mean difference −8.92; 95% CI −13.18, −4.66) and increased knowledge (mean difference 8.40; 95% CI 3.10, 13.71), were more likely to feel that they had enough information to make a decision (RR 1.30; 95% CI 1.14, 1.47), had no increase in anxiety and reported greater satisfaction with decision making and overall experience of pregnancy and childbirth. In contrast, 19% of women in the usual care group reported they would have made a different decision about their care. Conclusions A decision aid is an effective and acceptable tool for pregnant women that provides an important adjunct to standard counselling for the management of breech presentation. Please cite this paper as: Nassar N, Roberts C, Raynes-Greenow C, Barratt A, Peat B, on behalf of the Decision Aid for Breech Presentation Trial Collaborators. Evaluation of a decision aid for women with breech presentation at term: a randomised controlled trial [ISRCTN14570598]. BJOG 2007;114:325–333. PMID:17217360

Association of Dietary Vitamin K1 Intake With the Incidence of Cataract Surgery in an Adult Mediterranean Population: A Secondary Analysis of a Randomized Clinical Trial.

PubMed

Camacho-Barcia, María L; Bulló, Mònica; Garcia-Gavilán, Jesús F; Ruiz-Canela, Miguel; Corella, Dolores; Estruch, Ramón; Fitó, Montserrat; García-Layana, Alfredo; Arós, Fernando; Fiol, Miquel; Lapetra, José; Serra-Majem, Lluis; Pintó, Xavier; García-Arellano, Ana; Vinyoles, Ernest; Sorli, José Vicente; Salas-Salvadó, Jordi

2017-06-01

Cataract, one of the most frequent causes of blindness in developed countries, is strongly associated with aging. The exact mechanisms underlying cataract formation are still unclear, but growing evidence suggests a potential role of inflammatory and oxidative processes. Therefore, antioxidant and anti-inflammatory factors of the diet, such as vitamin K1, could play a protective role. To examine the association between dietary vitamin K1 intake and the risk of incident cataracts in an elderly Mediterranean population. A prospective analysis was conducted in 5860 participants from the Prevención con Dieta Mediterránea Study, a randomized clinical trial executed between 2003 and 2011. Participants were community-dwelling men (44.2%) and women (55.8%), and the mean (SD) age was 66.3 (6.1) years. Dietary vitamin K1 intake was evaluated using a validated food frequency questionnaire. The time to the cataract event was calculated as the time between recruitment and the date of the occurrence to cataract surgery, the time to the last visit of the follow-up, date of death, or the end of the study. Hazard ratios and 95% CIs for cataract incidence were estimated with a multivariable Cox proportional hazards model. Participants were community-dwelling men (44.2%; n = 868) and women (55.8%; n = 1086), and the mean (SD) age was 66.3 (6.1) years. After a median of 5.6 years follow-up, we documented a total of 768 new cataracts. Participants in the highest tertile of dietary vitamin K1 intake had a lower risk of cataracts than those in the lowest tertile (hazard ratio, 0.71; 95% CI, 0.58-0.88; P = .002), after adjusting for potential confounders. High intake of dietary vitamin K1 was associated with a reduced risk of cataracts in an elderly Mediterranean population even after adjusting by other potential confounders. isrctn.org: ISRCTN35739639.

Laparoscopic Lavage for Perforated Diverticulitis With Purulent Peritonitis: A Randomized Trial.

PubMed

Thornell, Anders; Angenete, Eva; Bisgaard, Thue; Bock, David; Burcharth, Jakob; Heath, Jane; Pommergaard, Hans-Christian; Rosenberg, Jacob; Stilling, Nikolaj; Skullman, Stefan; Haglind, Eva

2016-02-02

Perforated diverticulitis with purulent peritonitis has traditionally been treated with open colon resection and stoma formation with risk for reoperations, morbidity, and mortality. Laparoscopic lavage alone has been suggested as definitive treatment. To compare laparoscopic lavage with open colon resection and colostomy (Hartmann procedure) for perforated diverticulitis with purulent peritonitis. Randomized, controlled, multicenter, open-label trial. (ISRCTN registry number: ISRCTN82208287). 9 hospitals in Sweden and Denmark. Patients who have confirmed Hinchey grade III perforated diverticulitis with purulent peritonitis at diagnostic laparoscopy. Randomization between laparoscopic lavage and the Hartmann procedure. Primary outcome was the percentage of patients having 1 or more reoperations within 12 months. Key secondary outcomes were number of reoperations, hospital readmissions, total length of hospital stay during 12 months, and adverse events. A total of 43 and 40 patients were randomly assigned to laparoscopic lavage and the Hartmann procedure with a median (first, third quartiles) follow-up of 372 days (336, 394) and 378 days (226, 396), respectively. Fewer patients in the laparoscopic group (12 of 43; 27.9%) than in the Hartmann group (25 of 40; 62.5%) had at least 1 reoperation within 12 months (relative risk reduction, 59%; relative risk, 0.41 [95% CI, 0.23 to 0.72]; P = 0.004). Mortality and severe adverse events did not differ between groups. Total length of hospital stay (days) within 12 months was shorter for the laparoscopic group than the Hartmann group, with a reduction of 35% (relative risk, 0.65 [CI, 0.45 to 0.94]; P = 0.047). After 12 months, 3 patients in the laparoscopic group and 11 in the Hartmann group had a stoma. Not all patients presenting with suspected diverticulitis were enrolled. Laparoscopic lavage reduced the need for reoperations, had a similar safety profile to the Hartmann procedure, and may be an appropriate treatment of choice for acute perforated diverticulitis with purulent peritonitis. ALF; Sahlgrenska University Hospital, Gothenburg.

Predictors of delayed culture conversion among Ugandan patients.

PubMed

Atwine, Daniel; Orikiriza, Patrick; Taremwa, Ivan; Ayebare, Arnold; Logoose, Suzan; Mwanga-Amumpaire, Juliet; Jindani, Amina; Bonnet, Maryline

2017-04-24

Estimates of month-2 culture conversion, a proxy indicator of tuberculosis (TB) treatment efficacy in phase-2 trials can vary by culture-type and geographically with lower rates reported among African sites. The sub-study aimed at comparing TB detection rates of different culture media, within and across rifampicin-based regimens (R10, 15 and 20 mg/Kg) over a 6-month treatment follow-up period, and to establish predictors of month-2 culture non-conversion among HIV-negative TB patients enrolled at RIFATOX trial site in Uganda. Unlike in other Rifatox Trial sites, it is only in Uganda were Lowenstein-Jensen (LJ) and Mycobacteria growth indicator tube (MGIT) were used throughout 6-months for treatment monitoring. Conversion rates were compared at month-2, 4 and 6 across cultures and treatment-type. Binomial regression analysis performed for predictors of month-2 non-conversion. Of the 100 enrolled patients, 45% had converted based on combined LJ and MGIT by month-2, with no significant differences across treatment arms, p = 0.721. LJ exhibited higher conversion rates than MGIT at month-2 (58.4% vs 56.0%, p = 0.0707) and month-4 (98.9% vs 88.4%, p = 0.0391) respectively, more so within the high-dose rifampicin arms. All patients had converted by month-6. Time-to-TB detection (TTD) on MGIT and social service jobs independently predict month-2 non-conversion. The month-2 culture conversion used in phase 2 clinical trials as surrogate marker of treatment efficacy is influenced by the culture method used for monitoring mycobacterial response to TB treatment. Therefore, multi-centric TB therapeutic trials using early efficacy endpoint should use the same culture method across sites. The Time-to-detection of MTB on MGIT prior to treatment and working in Social service jobs bear an increased risk of culture non-conversion at month-2. ISRCTN ISRCTN55670677 . Registered 09th November 2010. Retrospectively registered.

Atopic Dermatitis Anti-IgE Paediatric Trial (ADAPT): the role of anti-IgE in severe paediatric eczema: study protocol for a randomised controlled trial.

PubMed

Chan, Susan; Cornelius, Victoria; Chen, Tao; Radulovic, Suzana; Wan, Mandy; Jahan, Rahi; Lack, Gideon

2017-03-22

The evidence for systemic treatments for severe childhood eczema is limited and largely based on extrapolation of data from adult studies. Current therapies are often immunosuppressant and may be associated with both short- and long-term side effects. There is increasing in vitro and murine-model evidence for the role of IgE in the immunopathogenesis of atopic eczema. The aim of the study is to assess whether anti-IgE treatment (omalizumab) improves eczema, compared to placebo. The Atopic Dermatitis Anti-IgE Paediatric Trial (ADAPT) is a randomised, double-blind, placebo-controlled study assessing the role of anti-IgE in the management of severe paediatric eczema. Children with severe atopic eczema, with an objective SCORing Atopic Dermatitis (SCORAD) score of over 40 will be recruited. These children are candidates for systemic therapy, have failed systemic therapy or have experienced side effects from systemic therapy. Sixty-two patients aged between 4 and 19 years will receive anti-IgE for 6 months. The primary outcome measure will be the validated eczema score, the objective SCORAD at 24 weeks. This study has 90% power to detect a 33% relative reduction in SCORAD between active and placebo groups, with 5% significance. IgE may have a role to play in eczema, particularly in childhood. This forms the basis for the hypothesis that anti-IgE may be an effective treatment in this patient population. This will be the largest study to evaluate the efficacy of anti-IgE (omalizumab) versus placebo in children with severe eczema. The findings will help to clarify the role of anti-IgE as a potential treatment option in patients with severe childhood eczema. European Clinical Trials Database (EudraCT) Number: 2010-020841-29 . Assigned on 14 May 2010. ISRCTN Registry, Identifier: ISRCTN15090567 . Retrospectively assigned on 3 December 2014. ClinicalTrials.gov, Identifier: NCT02300701 . First received 21 November 2014.

Feasibility and antihypertensive effect of replacing regular salt with mineral salt -rich in magnesium and potassium- in subjects with mildly elevated blood pressure

PubMed Central

2011-01-01

Background High salt intake is linked to hypertension whereas a restriction of dietary salt lowers blood pressure (BP). Substituting potassium and/or magnesium salts for sodium chloride (NaCl) may enhance the feasibility of salt restriction and lower blood pressure beyond the sodium reduction alone. The aim of this study was to determine the feasibility and effect on blood pressure of replacing NaCl (Regular salt) with a novel mineral salt [50% sodium chloride and rich in potassium chloride (25%), magnesium ammonium potassium chloride, hydrate (25%)] (Smart Salt). Methods A randomized, double-blind, placebo-controlled study was conducted with an intervention period of 8-weeks in subjects (n = 45) with systolic (S)BP 130-159 mmHg and/or diastolic (D)BP 85-99 mmHg. During the intervention period, subjects consumed processed foods salted with either NaCl or Smart Salt. The primary endpoint was the change in SBP. Secondary endpoints were changes in DBP, daily urine excretion of sodium (24-h dU-Na), potassium (dU-K) and magnesium (dU-Mg). Results 24-h dU-Na decreased significantly in the Smart Salt group (-29.8 mmol; p = 0.012) and remained unchanged in the control group: resulting in a 3.3 g difference in NaCl intake between the groups. Replacement of NaCl with Smart Salt resulted in a significant reduction in SBP over 8 weeks (-7.5 mmHg; p = 0.016). SBP increased (+3.8 mmHg, p = 0.072) slightly in the Regular salt group. The difference in the change of SBP between study groups was significant (p < 0.002). Conclusions The substitution of Smart Salt for Regular salt in subjects with high normal or mildly elevated BP resulted in a significant reduction in their daily sodium intake as well as a reduction in SBP. Trial Registration ISRCTN: ISRCTN01739816 PMID:21888642

Asperger syndrome and anxiety disorders (PAsSA) treatment trial: a study protocol of a pilot, multicentre, single-blind, randomised crossover trial of group cognitive behavioural therapy

PubMed Central

Langdon, Peter E; Murphy, Glynis H; Wilson, Edward; Shepstone, Lee; Fowler, David; Heavens, David; Malovic, Aida; Russell, Alexandra

2013-01-01

Introduction A number of studies have established that children, adolescents and adults with Asperger syndrome (AS) and high functioning autism (HFA) have significant problems with anxiety. Cognitive behavioural therapy (CBT) is an effective treatment for anxiety in a variety of clinical populations. There is a growing interest in exploring the effectiveness of CBT for people with AS who have mental health problems, but currently there are no known clinical trials involving adults with AS or HFA. Studies with children who have AS have reported some success. The current study aims to examine whether modified group CBT for clinically significant anxiety in an AS population is likely to be efficacious. Methods and analysis This study is a randomised, single-blind crossover trial. At least 36 individuals will be recruited and randomised into a treatment arm or a waiting-list control arm. During treatment, individuals will receive 3 sessions of individual CBT, followed by 21 sessions of group CBT. Primary outcome measures focus on anxiety. Secondary outcome measures focus on everyday social and psychiatric functioning, additional measures of anxiety and fear, depression, health-related quality of life and treatment cost. Assessments will be administered at pregroup and postgroup and at follow-up by researchers who are blinded to group allocation. The trial aims to find out whether or not psychological treatments for anxiety can be adapted and used to successfully treat the anxiety experienced by people with AS. Furthermore, we aim to determine whether this intervention represents good value for money. Ethics and dissemination The trial received a favourable ethical opinion from a National Health Service (NHS) Research Ethics Committee. All participants provided written informed consent. Findings will be shared with all trial participants, and the general public, as well as the scientific community. Trial Registration ISRCTN 30265294 (DOI: 10.1186/ISRCTN30265294), UKCRN 8370. PMID:23901031

Effect of insulin therapy and dietary adjustments on safety and performance during simulated soccer tests in people with type 1 diabetes: study protocol for a randomized controlled trial.

PubMed

Calvo-Marín, Javier; Torrealba-Acosta, Gabriel; Campbell, Matthew; Gaboury, Jesse; Ali, Ajmol; Chen-Ku, Chih Hao

2017-07-20

Despite the reduction in glycemic derangement in patients with type 1 diabetes mellitus (T1D) through dietary and therapeutic adjustments implemented before, during and after continuous exercise, evidence for its effectiveness with intermittent forms of exercise, such as soccer, is still lacking. We designed a study protocol for a randomized, crossover, double-blinded, controlled trial, for the evaluation of the effect that a strategy of dietary and therapeutic modifications may have on safety and performance of persons with T1D in soccer training sessions and cognitive testing. Inclusion criteria comprise: age older than 18 years, more than 2 years since T1D diagnosis, low C-peptide level, a stable insulin regimen, HbA1c less than 9.0% and regular participation in soccer activities. Our primary outcome evaluates safety regarding hypoglycemia events in patients using dietary and therapeutic adjustments, compared with the performance under the implementation of current American Diabetes Association (ADA) usual recommendations for nutritional and pharmacological adjustments for exercise. Additionally, we will evaluate as secondary outcomes: soccer performance, indexed by performance in well-established soccer skill tests, cognitive functions (indexed by Stroop, digital vigilance test (DVT), Corsi block-tapping task (CBP), and rapid visual information processing (RVIP) tests), and glycemic control measured with a continuous glucose monitor (CGM). Dietary and insulin adjustments standardized under a 4-step method strategy have never been tested in a clinical trial setting with intermittent forms of exercise, such as soccer. We hypothesize that through this strategy we will observe better performance by persons with T1D in soccer and cognitive evaluations, and more stable control of glycemic parameters before, during and after exercise execution, indexed by CGM measurements. ISRCTN, ISRCTN17447843. Registered on 5 January 2017.

Anthropometric and physiologic characteristics in white and British Indian vegetarians and nonvegetarians in the UK Biobank

PubMed Central

Tong, Tammy YN; Key, Timothy J; Sobiecki, Jakub G; Bradbury, Kathryn E

2018-01-01

ABSTRACT Background A detailed description of anthropometric and physiologic characteristics of persons in different diet groups is lacking. Objective We aimed to perform cross-sectional analyses of diet group with anthropometric and physiologic characteristics in a large cohort in the United Kingdom. Design The UK Biobank recruited ∼500,000 middle-aged participants throughout the United Kingdom in 2006–2010. Anthropometric indexes (height, weight, waist and hip circumference, body composition) and other physiologic characteristics (heel bone mineral density, grip strength, blood pressure, pulse rate) were measured following standardized protocols. We estimated the age-adjusted means of each characteristic in 6 diet groups (198,166 regular meat eaters, 199,784 low meat eaters, 4381 poultry eaters, 9674 fish eaters, 6366 vegetarians, and 378 vegans) in white women and men, and in 2 diet groups (3322 meat eaters and 1186 vegetarians) in British Indian women and men. Results In white women, after adjustment for age and compared with regular meat eaters, non–red meat eaters had lower adiposity (e.g., 4.5% lower body fat in vegan women) and lower systolic and diastolic blood pressure (−4.2 and −3.3 mm Hg, respectively), and generally lower heel bone mineral density t-score (−0.26). Patterns of differences by diet group were similar in white men. In the Indian population, compared with meat eaters, vegetarian women were shorter (−1.1 cm) and had lower lean mass (−0.5 kg), and both vegetarian women and men had lower grip strength (−1.3 and −1.4 kg, respectively). No significant differences in the other characteristics were observed. Conclusions Differences in anthropometric and physiologic characteristics were observed across diet groups in white participants, but fewer differences were observed in British Indian participants. The observed differences may be important as intermediate markers of long-term health in different diet groups. This observational study was registered at http://www.isrctn.com/ as ISRCTN10125697. PMID:29868910

Clinical Acceptability Of Trimetazidine Modified-Release 80 mg Once Daily Versus Trimetazidine Modified-Release 35 mg Twice Daily In Stable Angina Pectoris.

PubMed

Pozdnyakov, Yuri M

2018-06-01

Trimetazidine (TMZ) is an anti-ischemic metabolic agent that has been shown to be efficacious in angina treatment, both in monotherapy and in combination. A new formulation of TMZ modified-release (MR) 80 mg was developed, which is to be taken once daily (od), instead of twice daily (bid) for the currently available TMZ MR 35 mg, with the aim of simplifying the medication regimen. The present study was an international, multicenter, randomized, double-blind, parallel-group phase III study with a 12-week treatment period. The safety of TMZ MR 80 mg once daily was assessed compared to TMZ MR 35 mg twice daily, in patients previously treated successfully by the latter. Emergent adverse events (EAEs), biological parameters, vital signs, 12-lead resting ECG (electrocardiogram) and Canadian Cardiovascular Society (CCS) classification were recorded. One-hundred and sixty-five patients previously diagnosed with stable angina pectoris on treatment were randomized to receive either TMZ MR 80 mg od or TMZ MR 35 mg bid. In the TMZ MR 80 mg group, fewer patients had ≥ 1 EAE (17.1 vs. 22.9% in the TMZ MR 35 mg group). Serious EAEs were reported by three patients in each group. No EAE required dose modification, withdrawal, or temporary interruption of study treatments. Vital signs, 12-lead ECG, and laboratory parameters did not change. No worsening in CCS classes was observed with either treatment. TMZ MR 80 mg od and TMZ MR 35 mg bid have similar safety profiles. This new once-daily formulation could improve patient compliance with therapy, thereby enhancing clinical benefit. ISRCTN registry, ISRCTN 84362208. Institut de Recherches Internationales Servier and Servier, Moscow, Russian Federation. Plain language summary available for this article.

Acute hypertriglyceridemia induces platelet hyperactivity that is not attenuated by insulin in polycystic ovary syndrome.

PubMed

Aye, Myint Myint; Kilpatrick, Eric S; Aburima, Ahmed; Wraith, Katie S; Magwenzi, Simbarashe; Spurgeon, B; Rigby, Alan S; Sandeman, Derek; Naseem, Khalid M; Atkin, Stephen L

2014-02-28

Atherothrombosis is associated with platelet hyperactivity. Hypertriglyceridemia and insulin resistance (IR) are features of polycystic ovary syndrome (PCOS). The effect of induced hypertriglyceridemia on IR and platelet function was examined in young women with PCOS. Following overnight fasting, 13 PCOS and 12 healthy women were infused with saline or 20% intralipid for 5 hours on separate days. Insulin sensitivity was measured using a hyperinsulinemic euglycaemic clamp in the final 2 hours of each infusion. Platelet responses to adenosine diphosphate (ADP) and prostacyclin (PGI2) were measured by flow cytometric analysis of platelet fibrinogen binding and P-selectin expression using whole blood taken during each infusion (at 2 hours) and at the end of each clamp. Lipid infusion increased triglycerides and reduced insulin sensitivity in both controls (median, interquartile range ) (5.25 [3.3, 6.48] versus 2.60 [0.88, 3.88] mg kg(-1) min(-1), P<0.001) and PCOS (3.15 [2.94, 3.85] versus 1.06 [0.72, 1.43] mg kg(-1) min(-1), P<0.001). Platelet activation by ADP was enhanced and ability to suppress platelet activation by PGI2 diminished during lipid infusion in both groups when compared to saline. Importantly, insulin infusion decreased lipid-induced platelet hyperactivity by decreasing their response to 1 μmol/L ADP (78.7% [67.9, 82.3] versus 62.8% [51.8, 73.3], P=0.02) and increasing sensitivity to 0.01 μmol/L PGI2 (67.6% [39.5, 83.8] versus 40.9% [23.8, 60.9], P=0.01) in controls, but not in PCOS. Acute hypertriglyceridemia induced IR, and increased platelet activation in both groups that was not reversed by insulin in PCOS subjects compared to controls. This suggests that platelet hyperactivity induced by acute hypertriglyceridemia and IR could contribute athero-thrombotic risk. www.isrctn.org. Unique Identifier: ISRCTN42448814.

Acute Hypertriglyceridemia Induces Platelet Hyperactivity That is Not Attenuated by Insulin in Polycystic Ovary Syndrome

PubMed Central

Aye, Myint Myint; Kilpatrick, Eric S.; Aburima, Ahmed; Wraith, Katie S.; Magwenzi, Simbarashe; Spurgeon, B.; Rigby, Alan S.; Sandeman, Derek; Naseem, Khalid M.; Atkin, Stephen L.

2014-01-01

Background Atherothrombosis is associated with platelet hyperactivity. Hypertriglyceridemia and insulin resistance (IR) are features of polycystic ovary syndrome (PCOS). The effect of induced hypertriglyceridemia on IR and platelet function was examined in young women with PCOS. Methods and Results Following overnight fasting, 13 PCOS and 12 healthy women were infused with saline or 20% intralipid for 5 hours on separate days. Insulin sensitivity was measured using a hyperinsulinemic euglycaemic clamp in the final 2 hours of each infusion. Platelet responses to adenosine diphosphate (ADP) and prostacyclin (PGI2) were measured by flow cytometric analysis of platelet fibrinogen binding and P‐selectin expression using whole blood taken during each infusion (at 2 hours) and at the end of each clamp. Lipid infusion increased triglycerides and reduced insulin sensitivity in both controls (median, interquartile range ) (5.25 [3.3, 6.48] versus 2.60 [0.88, 3.88] mg kg−1 min−1, P<0.001) and PCOS (3.15 [2.94, 3.85] versus 1.06 [0.72, 1.43] mg kg−1 min−1, P<0.001). Platelet activation by ADP was enhanced and ability to suppress platelet activation by PGI2 diminished during lipid infusion in both groups when compared to saline. Importantly, insulin infusion decreased lipid‐induced platelet hyperactivity by decreasing their response to 1 μmol/L ADP (78.7% [67.9, 82.3] versus 62.8% [51.8, 73.3], P=0.02) and increasing sensitivity to 0.01 μmol/L PGI2 (67.6% [39.5, 83.8] versus 40.9% [23.8, 60.9], P=0.01) in controls, but not in PCOS. Conclusion Acute hypertriglyceridemia induced IR, and increased platelet activation in both groups that was not reversed by insulin in PCOS subjects compared to controls. This suggests that platelet hyperactivity induced by acute hypertriglyceridemia and IR could contribute athero‐thrombotic risk. Clinical Trial Registration URL: www.isrctn.org. Unique Identifier: ISRCTN42448814. PMID:24584741

Direct versus Indirect Treatment for Preschool Children who Stutter: The RESTART Randomized Trial

PubMed Central

de Sonneville-Koedoot, Caroline; Stolk, Elly; Rietveld, Toni; Franken, Marie-Christine

2015-01-01

Objective Stuttering is a common childhood disorder. There is limited high quality evidence regarding options for best treatment. The aim of the study was to compare the effectiveness of direct treatment with indirect treatment in preschool children who stutter. Methods In this multicenter randomized controlled trial with an 18 month follow-up, preschool children who stutter who were referred for treatment were randomized to direct treatment (Lidcombe Program; n = 99) or indirect treatment (RESTART-DCM treatment; n = 100). Main inclusion criteria were age 3–6 years, ≥3% syllables stuttered (%SS), and time since onset ≥6 months. The primary outcome was the percentage of non-stuttering children at 18 months. Secondary outcomes included stuttering frequency (%SS), stuttering severity ratings by the parents and therapist, severity rating by the child, health-related quality of life, emotional and behavioral problems, and speech attitude. Results Percentage of non-stuttering children for direct treatment was 76.5% (65/85) versus 71.4% (65/91) for indirect treatment (Odds Ratio (OR), 0.6; 95% CI, 0.1–2.4, p = .42). At 3 months, children treated by direct treatment showed a greater decline in %SS (significant interaction time x therapy: β = -1.89; t(282.82) = -2.807, p = .005). At 18 months, stuttering frequency was 1.2% (SD 2.1) for direct treatment and 1.5% (SD 2.1) for indirect treatment. Direct treatment had slightly better scores on most other secondary outcome measures, but no differences between treatment approaches were significant. Conclusions Direct treatment decreased stuttering more quickly during the first three months of treatment. At 18 months, however, clinical outcomes for direct and indirect treatment were comparable. These results imply that at 18 months post treatment onset, both treatments are roughly equal in treating developmental stuttering in ways that surpass expectations of natural recovery. Follow-up data are needed to confirm these findings in the longer term. Trial Registration isrctn.org ISRCTN24362190 PMID:26218228

Fidelity in complex behaviour change interventions: a standardised approach to evaluate intervention integrity

PubMed Central

Mars, Tom; Ellard, David; Carnes, Dawn; Homer, Kate; Underwood, Martin; Taylor, Stephanie J C

2013-01-01

Objectives The aim of this study was to (1) demonstrate the development and testing of tools and procedures designed to monitor and assess the integrity of a complex intervention for chronic pain (COping with persistent Pain, Effectiveness Research into Self-management (COPERS) course); and (2) make recommendations based on our experiences. Design Fidelity assessment of a two-arm randomised controlled trial intervention, assessing the adherence and competence of the facilitators delivering the intervention. Setting The intervention was delivered in the community in two centres in the UK: one inner city and one a mix of rural and urban locations. Participants 403 people with chronic musculoskeletal pain were enrolled in the intervention arm and 300 attended the self-management course. Thirty lay and healthcare professionals were trained and 24 delivered the courses (2 per course). We ran 31 courses for up to 16 people per course and all were audio recorded. Interventions The course was run over three and a half days; facilitators delivered a semistructured manualised course. Outcomes We designed three measures to evaluate fidelity assessing adherence to the manual, competence and overall impression. Results We evaluated a random sample of four components from each course (n=122). The evaluation forms were reliable and had good face validity. There were high levels of adherence in the delivery: overall adherence was two (maximum 2, IQR 1.67–2.00), facilitator competence exhibited more variability, and overall competence was 1.5 (maximum 2, IQR 1.25–2.00). Overall impression was three (maximum 4, IQR 2.00–3.00). Conclusions Monitoring and assessing adherence and competence at the point of intervention delivery can be realised most efficiently by embedding the principles of fidelity measurement within the design stage of complex interventions and the training and assessment of those delivering the intervention. More work is necessary to ensure that more robust systems of fidelity evaluation accompany the growth of complex interventions. Trial Registration ISRCTN No ISRCTN24426731. PMID:24240140

Lessons learned from a double-blind randomised placebo-controlled study with a iota-carrageenan nasal spray as medical device in children with acute symptoms of common cold

PubMed Central

2012-01-01

Background Common cold is caused by a variety of respiratory viruses. The prevalence in children is high, and it potentially contributes to significant morbidity. Iota-carragenan, a polymer derived from red seaweed, has reduced viral load in nasal secretions and alleviated symptoms in adults with common cold. Methods We have assessed the antiviral and therapeutic activity of a nasal spray containing iota-carrageenan in children with acute symptoms of common cold. A cohort of 153 children between 1–18 years (mean age 5 years), displaying acute symptoms of common cold were randomly assigned to treatment with a nasal spray containing iota-carrageenan (0.12%) as verum or 0.9% sodium chloride solution as placebo for seven days. Symptoms of common cold were recorded and the viral load of respiratory viruses in nasal secretions was determined at two consecutive visits. Results The results of the present study showed no significant difference between the iota carrageenan and the placebo group on the mean of TSS between study days 2–7. Secondary endpoints, such as reduced time to clearance of disease (7.6 vs 9.4 days; p = 0.038), reduction of viral load (p = 0.026), and lower incidence of secondary infections with other respiratory viruses (p = 0.046) indicated beneficial effects of iota-carrageenan in this population. The treatment was safe and well tolerated, with less side effects observed in the verum group compared to placebo. Conclusion In this study iota-carrageenan did not alleviate symptoms in children with acute symptoms of common cold, but significantly reduced viral load in nasal secretions that may have important implications for future studies. Trial registration ISRCTN52519535, http://www.controlled-trials.com/ISRCTN52519535/ PMID:22950667

Probiotic capsules and xylitol chewing gum to manage symptoms of pharyngitis: a randomized controlled factorial trial

PubMed Central

Little, Paul; Stuart, Beth; Wingrove, Zoe; Mullee, Mark; Thomas, Tammy; Johnson, Sophie; Leydon, Gerry; Richards-Hall, Samantha; Williamson, Ian; Yao, Lily; Zhu, Shihua; Moore, Michael

2017-01-01

BACKGROUND: Reducing the use of antibiotics for upper respiratory tract infections is needed to limit the global threat of antibiotic resistance. We estimated the effectiveness of probiotics and xylitol for the management of pharyngitis. METHODS: In this parallel-group factorial randomized controlled trial, participants in primary care (aged 3 years or older) with pharyngitis underwent randomization by nurses who provided sequential intervention packs. Pack contents for 3 kinds of material and advice were previously determined by computer-generated random numbers: no chewing gum, xylitol-based chewing gum (15% xylitol; 5 pieces daily) and sorbitol gum (5 pieces daily). Half of each group were also randomly assigned to receive either probiotic capsules (containing 24 × 109 colony-forming units of lactobacilli and bifidobacteria) or placebo. The primary outcome was mean self-reported severity of sore throat and difficulty swallowing (scale 0–6) in the first 3 days. We used multiple imputation to avoid the assumption that data were missing completely at random. RESULTS: A total of 1009 individuals consented, 934 completed the baseline assessment, and 689 provided complete data for the primary outcome. Probiotics were not effective in reducing the severity of symptoms: mean severity scores 2.75 with no probiotic and 2.78 with probiotic (adjusted difference −0.001, 95% confidence interval [CI] −0.24 to 0.24). Chewing gum was also ineffective: mean severity scores 2.73 without gum, 2.72 with sorbitol gum (adjusted difference 0.07, 95% CI −0.23 to 0.37) and 2.73 with xylitol gum (adjusted difference 0.01, 95% CI −0.29 to 0.30). None of the secondary outcomes differed significantly between groups, and no harms were reported. INTERPRETATION: Neither probiotics nor advice to chew xylitol-based chewing gum was effective for managing pharyngitis. Trial registration: ISRCTN, no. ISRCTN51472596 PMID:29255098

Probiotic capsules and xylitol chewing gum to manage symptoms of pharyngitis: a randomized controlled factorial trial.

PubMed

Little, Paul; Stuart, Beth; Wingrove, Zoe; Mullee, Mark; Thomas, Tammy; Johnson, Sophie; Leydon, Gerry; Richards-Hall, Samantha; Williamson, Ian; Yao, Lily; Zhu, Shihua; Moore, Michael

2017-12-18

Reducing the use of antibiotics for upper respiratory tract infections is needed to limit the global threat of antibiotic resistance. We estimated the effectiveness of probiotics and xylitol for the management of pharyngitis. In this parallel-group factorial randomized controlled trial, participants in primary care (aged 3 years or older) with pharyngitis underwent randomization by nurses who provided sequential intervention packs. Pack contents for 3 kinds of material and advice were previously determined by computer-generated random numbers: no chewing gum, xylitol-based chewing gum (15% xylitol; 5 pieces daily) and sorbitol gum (5 pieces daily). Half of each group were also randomly assigned to receive either probiotic capsules (containing 24 × 10 9 colony-forming units of lactobacilli and bifidobacteria) or placebo. The primary outcome was mean self-reported severity of sore throat and difficulty swallowing (scale 0-6) in the first 3 days. We used multiple imputation to avoid the assumption that data were missing completely at random. A total of 1009 individuals consented, 934 completed the baseline assessment, and 689 provided complete data for the primary outcome. Probiotics were not effective in reducing the severity of symptoms: mean severity scores 2.75 with no probiotic and 2.78 with probiotic (adjusted difference -0.001, 95% confidence interval [CI] -0.24 to 0.24). Chewing gum was also ineffective: mean severity scores 2.73 without gum, 2.72 with sorbitol gum (adjusted difference 0.07, 95% CI -0.23 to 0.37) and 2.73 with xylitol gum (adjusted difference 0.01, 95% CI -0.29 to 0.30). None of the secondary outcomes differed significantly between groups, and no harms were reported. Neither probiotics nor advice to chew xylitol-based chewing gum was effective for managing pharyngitis. Trial registration: ISRCTN, no. ISRCTN51472596. © 2017 Joule Inc. or its licensors.

Prenatal Micronutrient Supplementation Is Not Associated with Intellectual Development of Young School-Aged Children.

PubMed

Li, Chao; Zeng, Lingxia; Wang, Duolao; Yang, Wenfang; Dang, Shaonong; Zhou, Jing; Yan, Hong

2015-08-01

Micronutrient supplementation is often prescribed during pregnancy. The effects of prenatal iron and multimicronutrient supplementation on intellectual development in young school-aged children are less than clear. The aim of this study was to examine the long-term effects of prenatal iron plus folic acid or multiple micronutrient (including iron and folic acid) supplementation vs. folic acid supplementation on the intellectual development of young school-aged children in rural China. Young school-aged children (aged 7-10 y, n = 1744) of women who had participated in a trial of prenatal supplementation with various combinations of micronutrients and remained residents in 2 rural counties in China were followed. We measured their intellectual development by Wechsler Intelligence Scale for Children Fourth Edition (WISC-IV). The WISC-IV generated the Full-Scale Intelligence Quotient (FSIQ), Verbal Comprehension Index (VCI), Working Memory Index (WMI), Perceptual Reasoning Index (PRI), and Processing Speed Index (PSI). Multilevel analyses were used to assess the effect of prenatal micronutrient supplementation on the intellectual development of children. The mean differences in FSIQ, VCI, WMI, PRI, and PSI, respectively, were not significant between prenatal folic acid supplementation and either iron plus folic acid [-0.34 (P = 0.65), -0.06 (P = 0.95), -0.22 (P = 0.76), -0.01 (P = 0.99), and -1.26 (P = 0.11)] or multimicronutrient [-0.39 (P = 0.60), -0.64 (P = 0.48), 0.11 (P = 0.87), -0.43 (P = 0.59), and -0.34; (P = 0.65)] supplementation after adjusting for confounders. There is no evidence to suggest a different effect on intellectual development between prenatal iron plus folic acid, multimicronutrient supplementation, and prenatal folic acid supplementation in children aged 7-10 y. This trial was registered at www.isrctn.com as ISRCTN08850194. © 2015 American Society for Nutrition.

Improvement in insulin resistance is greater when infliximab is added to methotrexate during intensive treatment of early rheumatoid arthritis-results from the IDEA study.

PubMed

Bissell, Lesley-Anne; Hensor, Elizabeth M A; Kozera, Lukasz; Mackie, Sarah L; Burska, Agata N; Nam, Jacqueline L; Keen, Helen; Villeneuve, Edith; Donica, Helena; Buch, Maya H; Conaghan, Philip G; Andrews, Jacqueline; Emery, Paul; Morgan, Ann W

2016-12-01

To determine the change in established biomarkers of cardiovascular (CV) risk, namely, total cholesterol/high-density lipoprotein cholesterol ratio (TC/HDL-C), N-terminal pro-brain natriuretic peptide (NT-proBNP) and insulin resistance (IR) in patients with early RA treated with two different treat-to-target strategies. Fasting glucose, lipids, insulin and NT-proBNP were measured at baseline, weeks 26 and 78 in 79 DMARD-naïve RA patients, free of CV disease, as part of a double-blind randomized controlled trial of MTX with either infliximab (IFX) or methylprednisolone as induction therapy. Homeostasis model assessment-estimated IR (HOMA-IR) (glucose*insulin/405) was used to measure IR. Multiple imputation was employed, and linear regression analyses were adjusted for baseline values. Changes in DAS44-CRP did not differ between the treatment arms at weeks 26 and 78. Mean TC/HDL-C, HOMA-IR and NT-proBNP improved in both groups at weeks 26 and 78, although change in NT-proBNP was not statistically significant at week 78. Changes in TC/HDL-C and NT-proBNP were similar between treatment arms, but HOMA-IR values in the IFX + MTX arm were 42% lower than those treated with MTX + methylprednisolone at week 78 (P = 0.003); the difference remained significant after adjustment for baseline BMI, ACPA positivity, smoking status and intramuscular glucocorticoid use (P = 0.007). When implementing a treat-to-target approach, treatment of early RA was associated with improvement in TC/HDL-C, HOMA-IR and NT-proBNP, and a greater long-term improvement in HOMA-IR was seen in those treated with IFX. EU Clinical Trials Register, http://www.clinicaltrialsregister.eu, Eudract-2005-005013-37; ISRTCNregisrty, http://www.isrctn.com, ISRCTN48638981. © The Author 2016. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

History of foster care among homeless adults with mental illness in Vancouver, British Columbia: a precursor to trajectories of risk.

PubMed

Patterson, Michelle L; Moniruzzaman, Akm; Somers, Julian M

2015-02-26

It is well documented that a disproportionate number of homeless adults have childhood histories of foster care placement(s). This study examines the relationship between foster care placement as a predictor of adult substance use disorders (including frequency, severity and type), mental illness, vocational functioning, service use and duration of homelessness among a sample of homeless adults with mental illness. We hypothesize that a history of foster care predicts earlier, more severe and more frequent substance use, multiple mental disorder diagnoses, discontinuous work history, and longer durations of homelessness. This study was conducted using baseline data from two randomized controlled trials in Vancouver, British Columbia for participants who responded to a series of questions pertaining to out-of-home care at 12 months follow-up (n = 442). Primary outcomes included current mental disorders; substance use including type, frequency and severity; physical health; duration of homelessness; vocational functioning; and service use. In multivariable regression models, a history of foster care placement independently predicted incomplete high school, duration of homelessness, discontinuous work history, less severe types of mental illness, multiple mental disorders, early initiation of drug and/or alcohol use, and daily drug use. This is the first Canadian study to investigate the relationship between a history of foster care and current substance use among homeless adults with mental illness, controlling for several other potential confounding factors. It is important to screen homeless youth who exit foster care for substance use, and to provide integrated treatment for concurrent disorders to homeless youth and adults who have both psychiatric and substance use problems. Both trials are registered with the International Standard Randomized Control Trial Number Register and were assigned ISRCTN57595077 (Vancouver At Home Study: Housing First plus assertive community treatment versus congregate housing plus supports versus treatment as usual) and ISRCTN66721740 (Vancouver At Home Study: Housing First plus intensive case management versus treatment as usual) on September 9, 2012.

The impact of prenatal exposure to parasitic infections and to anthelminthic treatment on antibody responses to routine immunisations given in infancy: Secondary analysis of a randomised controlled trial.

PubMed

Nash, Stephen; Mentzer, Alexander J; Lule, Swaib A; Kizito, Dennison; Smits, Gaby; van der Klis, Fiona R M; Elliott, Alison M

2017-02-01

Chronic parasitic infections are associated with active immunomodulation which may include by-stander effects on unrelated antigens. It has been suggested that pre-natal exposure to parasitic infections in the mother impacts immunological development in the fetus and hence the offspring's response to vaccines, and that control of parasitic infection among pregnant women will therefore be beneficial. We used new data from the Entebbe Mother and Baby Study, a trial of anthelminthic treatment during pregnancy conducted in Uganda, to further investigate this hypothesis. 2705 mothers were investigated for parasitic infections and then randomised to albendazole (400mg) versus placebo and praziquantel (40mg/kg) during pregnancy in a factorial design. All mothers received sulfadoxine/pyrimethamine for presumptive treatment of malaria. Offspring received Expanded Programme on Immunisation vaccines at birth, six, 10 and 14 weeks. New data on antibody levels to diphtheria toxin, three pertussis antigens, Haemophilus influenzae type B (HiB) and Hepatitis B, measured at one year (April 2004 -May 2007) from 1379 infants were analysed for this report. Additional observational analyses relating maternal infections to infant vaccine responses were also conducted. Helminth infections were highly prevalent amongst mothers (hookworm 43.1%, Mansonella 20.9%, Schistosoma mansoni 17.3%, Strongyloides 11.7%, Trichuris 8.1%) and 9.4% had malaria at enrolment. In the trial analysis we found no overall effect of either anthelminthic intervention on the measured infant vaccine responses. In observational analyses, no species was associated with suppressed responses. Strongyloidiasis was associated with enhanced responses to pertussis toxin, HiB and Hep B vaccine antigens. Our results do not support the hypothesis that routine anthelminthic treatment during pregnancy has a benefit for the infant's vaccine response, or that maternal helminth infection has a net suppressive effect on the offspring's response to vaccines. ISRCTN.com ISRCTN32849447.

REFINE (REducing Falls in In-patieNt Elderly) using bed and bedside chair pressure sensors linked to radio-pagers in acute hospital care: a randomised controlled trial

PubMed Central

Sahota, Opinder; Drummond, Avril; Kendrick, Denise; Grainge, Matthew J.; Vass, Catherine; Sach, Tracey; Gladman, John; Avis, Mark

2014-01-01

Background: falls in hospitals are a major problem and contribute to substantial healthcare burden. Advances in sensor technology afford innovative approaches to reducing falls in acute hospital care. However, whether these are clinically effective and cost effective in the UK setting has not been evaluated. Methods: pragmatic, parallel-arm, individual randomised controlled trial of bed and bedside chair pressure sensors using radio-pagers (intervention group) compared with standard care (control group) in elderly patients admitted to acute, general medical wards, in a large UK teaching hospital. Primary outcome measure number of in-patient bedside falls per 1,000 bed days. Results: 1,839 participants were randomised (918 to the intervention group and 921 to the control group). There were 85 bedside falls (65 fallers) in the intervention group, falls rate 8.71 per 1,000 bed days compared with 83 bedside falls (64 fallers) in the control group, falls rate 9.84 per 1,000 bed days (adjusted incidence rate ratio, 0.90; 95% confidence interval [CI], 0.66–1.22; P = 0.51). There was no significant difference between the two groups with respect to time to first bedside fall (adjusted hazard ratio (HR), 0.95; 95% CI: 0.67–1.34; P= 0.12). The mean cost per patient in the intervention group was £7199 compared with £6400 in the control group, mean difference in QALYs per patient, 0.0001 (95% CI: −0.0006–0.0004, P= 0.67). Conclusions: bed and bedside chair pressure sensors as a single intervention strategy do not reduce in-patient bedside falls, time to first bedside fall and are not cost-effective in elderly patients in acute, general medical wards in the UK. Trial registration: isrctn.org identifier: ISRCTN44972300. PMID:24141253

The Children and Parents in Focus project: a population-based cluster-randomised controlled trial to prevent behavioural and emotional problems in children

PubMed Central

2013-01-01

Background There is large body of knowledge to support the importance of early interventions to improve child health and development. Nonetheless, it is important to identify cost-effective blends of preventive interventions with adequate coverage and feasible delivery modes. The aim of the Children and Parents in Focus trial is to compare two levels of parenting programme intensity and rate of exposure, with a control condition to address impact and cost-effectiveness of a universally offered evidence-based parenting programme in the Swedish context. Methods/Design The trial has a cluster randomised controlled design comprising three arms: Universal arm (with access to participation in Triple P - Positive Parenting Program, level 2); Universal Plus arm (with access to participation in Triple P - Positive Parenting Program, level 2 as well as level 3, and level 4 group); and Services as Usual arm. The sampling frame is Uppsala municipality in Sweden. Child health centres consecutively recruit parents of children aged 3 to 5 years before their yearly check-ups (during the years 2013–2017). Outcomes will be measured annually. The primary outcome will be children’s behavioural and emotional problems as rated by three informants: fathers, mothers and preschool teachers. The other outcomes will be parents’ behaviour and parents’ general health. Health economic evaluations will analyse cost-effectiveness of the interventions versus care as usual by comparing the costs and consequences in terms of impact on children’s mental health, parent’s mental health and health-related quality of life. Discussion This study addresses the need for comprehensive evaluation of the long-term effects, costs and benefits of early parenting interventions embedded within existing systems. In addition, the study will generate population-based data on the mental health and well-being of preschool aged children in Sweden. Trial registration ISRCTN: ISRCTN16513449. PMID:24131587

A survey of facilitators and barriers to recruitment to the MAGNETIC trial.

PubMed

Kaur, Geetinder; Smyth, Rosalind L; Powell, Colin V E; Williamson, Paula

2016-12-23

Recruitment to randomised controlled trials with children is challenging. It is imperative to understand the factors that boost or hinder recruitment of children to clinical trials. We conducted a survey of facilitators and barriers to recruitment to the MAGNETIC trial, using a previously developed web-based tool. MAGNETIC is a multicentre randomised trial of nebulised magnesium in acute severe asthma, recruiting 508 children from 30 UK sites. Recruiters were asked to grade a list of factors from -3 to +3 depending on whether the factor was perceived as a strong, intermediate or weak barrier (-3 to -1) or facilitator (+1 to + 3), and using (0) if it was thought to be not applicable. Free text responses were invited on strategies applied to counter the identified barriers. The commonly identified facilitators were motivation and experience of study teams, effective communication and coordination between teams at site and between sites and the Clinical Trials Unit, the presence of designated research nurses, good trial management, clinical trial publicity, simple inclusion criteria, effective communication with parents and presentation of trial information in a simple and clear manner. The commonly identified barriers were heavy clinical workload, shift patterns of work, Good Clinical Practice (GCP) training, inadequate number of trained staff, time and setting of consent seeking, non-availability of research staff out of hours and parents' concerns about their child taking an experimental medicine. Having a designated research nurse, arranging GCP training and trial-related training sessions for staff were the most commonly reported interventions. This study highlights important generic and trial-specific facilitators and barriers to recruitment to a paediatric trial in the acute setting and provides information on the recruitment strategies or interventions that were applied to overcome these barriers. This information can be very useful in informing the design and conduct of future clinical trials with children, particularly in the acute or emergency setting. ISRCTN, ISRCTN81456894 . Registered on 15 November 2007.

Targeted treatment in primary care for low back pain: the treatment system and clinical training programmes used in the IMPaCT Back study (ISRCTN 55174281)

PubMed Central

Sowden, Gail; Hill, Jonathan C; Konstantinou, Kika; Khanna, Meenee; Main, Chris J; Salmon, Paula; Somerville, Simon; Wathall, Simon; Foster, Nadine E

2012-01-01

Background. The IMPaCT Back study (IMplementation to improve Patient Care through Targeted treatment for Back pain) is a quality improvement study which aims to investigate the effects of introducing and supporting a subgrouping for targeted treatment system for patients with low back pain (LBP) in primary care. This paper details the subgrouping for targeted treatment system and the clinical training and mentoring programmes aimed at equipping clinicians to deliver it. The subgrouping and targeted treatment system. This system differs from ‘one-size fits all’ usual practice as it suggests that first contact health care practitioners should systematically allocate LBP patients to one of the three subgroups according to key modifiable prognostic indicators for chronicity. Patients in each subgroup (those at low, medium or high risk of chronicity) are then managed according to a targeted treatment system of increasing complexity. The subgrouping tools. Subgrouping tools help guide clinical decision-making about treatment and onward referral. Two subgrouping tools have been used in the IMPaCT Back study, a 9-item version used by participating physiotherapists and a 6-item version used by GPs. The targeted treatments. The targeted treatments include a minimal intervention delivered by GPs (for those patients at low risk of poor outcome) or referral to primary care physiotherapists who can apply physiotherapy approaches to addressing pain and disability (for those at medium risk) and additional cognitive-behavioural approaches to help address psychological and social obstacles to recovery (for those at high risk). The training packages. Building on previous interventions for other pilot studies and randomized trials, we have developed and delivered clinical training and support programmes for GPs and physiotherapists. Discussion. This paper describes in detail the IMPaCT Back study’s subgrouping for targeted treatment system and the training and mentoring packages aimed at equipping clinicians to deliver it, within the IMPaCT Back study. Study registration. ISRCTN55174281. PMID:21708984

Tolerability and safety of the intravenous immunoglobulin octagam® 10% in patients with immune thrombocytopenia: a post-authorisation safety analysis of two non-interventional phase IV trials.

PubMed

Wietek, Stefan; Svorc, Daniel; Debes, Anette; Svae, Tor-Einar

2018-05-01

To provide detailed data on the tolerability and safety of octagam ® 10%, a ready-to-use intravenous immunoglobulin, in a subgroup of patients with immune thrombocytopenia (ITP) involved in an integrated analysis of post-authorisation safety surveillance (PASS) studies. A subgroup analysis was conducted using data collected from two non-interventional studies that included patients with ITP treated with octagam ® 10%. Patients were observed and monitored for possible adverse drug reactions (ADRs) during or after administration of octagam ® 10%, with a particular focus on thromboembolic events (TEEs). ADRs were analysed at the case and event level. In this analysis of 112 patients receiving octagam ® 10% (mean dose 0.4 g/kg/infusion), there were five cases with at least one adverse drug reaction (ADR) associated with 626 infusions of octagam ® 10% (case incidence of 0.8% per infusion). ADRs were of mild or moderate severity. There were a total of 10 events, most commonly back pain (n = 3) and headache (n = 2). Nausea, dizziness and a sensation of heaviness were also reported. The remaining two events involved drug exposure during pregnancy. There were no TEEs or other serious ADRs. In this subgroup analysis of patients who received octagam ® 10% (manufactured using an amended process) in two PASS studies, the overall ADR rate was low, with ADRs occurring in only 0.8% of all infusions. No TEEs or other serious ADRs were reported. Routine clinical use of octagam ® 10% was safe and well tolerated, with no unexpected safety issues, in patients with ITP. The two studies from which data were taken are registered with the International Standard Randomised Controlled Trial Number Registry, numbers ISRCTN58800347 and ISRCTN02245668.

Deranged endocannabinoid responses to hedonic eating in underweight and recently weight-restored patients with anorexia nervosa.

PubMed

Monteleone, Alessio Maria; Di Marzo, Vincenzo; Aveta, Teresa; Piscitelli, Fabiana; Dalle Grave, Riccardo; Scognamiglio, Pasquale; El Ghoch, Marwan; Calugi, Simona; Monteleone, Palmiero; Maj, Mario

2015-02-01

A dysregulation of reward mechanisms was suggested in the pathophysiology of anorexia nervosa (AN), but the role of the endogenous mediators of reward has been poorly investigated. Endocannabinoids, including anandamide and 2-arachidonoylglycerol, and the endocannabinoid-related compounds oleoylethanolamide and palmitoylethanolamide modulate food-related and unrelated reward. Hedonic eating, which is the consumption of food just for pleasure and not homeostatic need, is a suitable paradigm to explore food-related reward. We investigated responses of endocannabinoids and endocannabinoid-related compounds to hedonic eating in AN. Peripheral concentrations of anandamide, 2-arachidonoylglycerol, oleoylethanolamide, and palmitoylethanolamide were measured in 7 underweight and 7 weight-restored AN patients after eating favorite and nonfavorite foods in the condition of no homeostatic needs, and these measurements were compared with those of previously studied healthy control subjects. 1) In healthy controls, plasma 2-arachidonoylglycerol concentrations decreased after both types of meals but were significantly higher in hedonic eating; in underweight AN patients, 2-arachidonoylglycerol concentrations did not show specific time patterns after eating either favorite or nonfavorite foods, whereas in weight-restored patients, 2-arachidonoylglycerol concentrations showed similar increases with both types of meals. 2) Anandamide plasma concentrations exhibited no differences in their response patterns to hedonic eating in the groups. 3) Compared with 2-arachidonoylglycerol, palmitoylethanolamide concentrations exhibited an opposite response pattern to hedonic eating in healthy controls; this pattern was partially preserved in underweight AN patients but not in weight-restored ones. 4) Like palmitoylethanolamide, oleoylethanolamide plasma concentrations tended to be higher in nonhedonic eating than in hedonic eating in healthy controls; moreover, no difference between healthy subjects and AN patients was observed for food-intake-induced changes in oleoylethanolamide concentrations. These data confirm that endocannabinoids and endocannabinoid-related compounds are involved in food-related reward and suggest a dysregulation of their physiology in AN. This trial was registered at ISRCTN.org as ISRCTN64683774. © 2015 American Society for Nutrition.

Metabolomic Changes in Serum of Children with Different Clinical Diagnoses of Malnutrition.

PubMed

Di Giovanni, Valeria; Bourdon, Celine; Wang, Dominic X; Seshadri, Swapna; Senga, Edward; Versloot, Christian J; Voskuijl, Wieger; Semba, Richard D; Trehan, Indi; Moaddel, Ruin; Ordiz, M Isabel; Zhang, Ling; Parkinson, John; Manary, Mark J; Bandsma, Robert Hj

2016-12-01

Mortality in children with severe acute malnutrition (SAM) remains high despite standardized rehabilitation protocols. Two forms of SAM are classically distinguished: kwashiorkor and marasmus. Children with kwashiorkor have nutritional edema and metabolic disturbances, including hypoalbuminemia and hepatic steatosis, whereas marasmus is characterized by severe wasting. The metabolic changes underlying these phenotypes have been poorly characterized, and whether homeostasis is achieved during hospital stay is unclear. We aimed to characterize metabolic differences between children with marasmus and kwashiorkor at hospital admission and after clinical stabilization and to compare them with stunted and nonstunted community controls. We studied children aged 9-59 mo from Malawi who were hospitalized with SAM (n = 40; 21 with kwashiorkor and 19 with marasmus) or living in the community (n = 157; 78 stunted and 79 nonstunted). Serum from patients with SAM was obtained at hospital admission and 3 d after nutritional stabilization and from community controls. With the use of targeted metabolomics, 141 metabolites, including amino acids, biogenic amines, acylcarnitines, sphingomyelins, and phosphatidylcholines, were measured. At admission, most metabolites (128 of 141; 91%) were lower in children with kwashiorkor than in those with marasmus, with significant differences in several amino acids and biogenic amines, including those of the kynurenine-tryptophan pathway. Several phosphatidylcholines and some acylcarnitines also differed. Patients with SAM had profiles that were profoundly different from those of stunted and nonstunted controls, even after clinical stabilization. Amino acids and biogenic amines generally improved with nutritional rehabilitation, but most sphingomyelins and phosphatidylcholines did not. Children with kwashiorkor were metabolically distinct from those with marasmus, and were more prone to severe metabolic disruptions. Children with SAM showed metabolic profiles that were profoundly different from stunted and nonstunted controls, even after clinical stabilization. Therefore, metabolic recovery in children with SAM likely extends beyond discharge, which may explain the poor long-term outcomes in these children. This trial was registered at isrctn.org as ISRCTN13916953. © 2016 American Society for Nutrition.

Effectiveness of a clinical practice guideline implementation strategy for patients with anxiety disorders in primary care: cluster randomized trial

PubMed Central

2011-01-01

Background Anxiety is a common mental health problem seen in primary care. However, its management in clinical practice varies greatly. Clinical practice guidelines (CPGs) have the potential to reduce variations and improve the care received by patients by promoting interventions of proven benefit. However, uptake and adherence to their recommendations can be low. Method/design This study involves a community based on cluster randomized trial in primary healthcare centres in the Madrid Region (Spain). The project aims to determine whether the use of implementation strategy (including training session, information, opinion leader, reminders, audit, and feed-back) of CPG for patients with anxiety disorders in primary care is more effective than usual diffusion. The number of patients required is 296 (148 in each arm), all older than 18 years and diagnosed with generalized anxiety disorder, panic disorder, and panic attacks by the Diagnostic and Statistical Manual of Mental Disorders-IV (DSM-IV). They are chosen by consecutive sampling. The main outcome variable is the change in two or more points into Goldberg anxiety scale at six and twelve months. Secondary outcome variables include quality of life (EuroQol 5D), and degree of compliance with the CPG recommendations on treatment, information, and referrals to mental health services. Main effectiveness will be analyzed by comparing the patients percentage improvement on the Goldberg scale between the intervention group and the control group. Logistic regression with random effects will be used to adjust for prognostic factors. Confounding factors or factors that might alter the effect recorded will be taken into account in this analysis. Discussion There is a need to identify effective implementation strategies for CPG for the management of anxiety disorders present in primary care. Ensuring the appropriate uptake of guideline recommendations can reduce clinical variation and improve the care patients receive. Trial registration ISRCTN: ISRCTN83365316 PMID:22132861

Improving child nutrition and development through community-based childcare centres in Malawi - The NEEP-IE study: study protocol for a randomised controlled trial.

PubMed

Gelli, Aulo; Margolies, Amy; Santacroce, Marco; Sproule, Katie; Theis, Sophie; Roschnik, Natalie; Twalibu, Aisha; Chidalengwa, George; Cooper, Amrik; Moorhead, Tyler; Gladstone, Melissa; Kariger, Patricia; Kutundu, Mangani

2017-06-19

The Nutrition Embedded Evaluation Programme Impact Evaluation (NEEP-IE) study is a cluster randomised controlled trial designed to evaluate the impact of a childcare centre-based integrated nutritional and agricultural intervention on the diets, nutrition and development of young children in Malawi. The intervention includes activities to improve nutritious food production and training/behaviour-change communication to improve food intake, care and hygiene practices. This paper presents the rationale and study design for this randomised control trial. Sixty community-based childcare centres (CBCCs) in rural communities around Zomba district, Malawi, were randomised to either (1) a control group where children were attending CBCCs supported by Save the Children's Early Childhood Health and Development (ECD) programme, or (2) an intervention group where nutritional and agricultural support activities were provided alongside the routine provision of the Save the Children's ECD programme. Primary outcomes at child level include dietary intake (measured through 24-h recall), whilst secondary outcomes include child development (Malawi Development Assessment Tool (MDAT)) and nutritional status (anthropometric measurements). At household level, primary outcomes include smallholder farmer production output and crop-mix (recall of last production season). Intermediate outcomes along theorised agricultural and nutritional pathways were measured. During this trial, we will follow a mixed-methods approach and undertake child-, household-, CBCC- and market-level surveys and assessments as well as in-depth interviews and focus group discussions with project stakeholders. Assessing the simultaneous impact of preschool meals on diets, nutrition, child development and agriculture is a complex undertaking. This study is the first to explicitly examine, from a food systems perspective, the impact of a preschool meals programme on dietary choices, alongside outcomes in the nutritional, child development and agricultural domains. The findings of this evaluation will provide evidence to support policymakers in the scale-up of national programmes. ISRCTN registry, ID: ISRCTN96497560 . Registered on 21 September 2016.

Adaptation of the By-Band randomized clinical trial to By-Band-Sleeve to include a new intervention and maintain relevance of the study to practice.

PubMed

Rogers, C A; Reeves, B C; Byrne, J; Donovan, J L; Mazza, G; Paramasivan, S; Andrews, R C; Wordsworth, S; Thompson, J; Blazeby, J M; Welbourn, R

2017-08-01

Recruitment into surgical RCTs can be threatened if new interventions available outside the trial compete with those being evaluated. Adapting the trial to include the new intervention may overcome this issue, yet this is not often done in surgery. This paper describes the challenges, rationale and methods for adapting an RCT to include a new intervention. The By-Band study was designed in the UK in 2009-2010 to compare the effectiveness of laparoscopic adjustable gastric band and Roux-en-Y gastric bypass for severe obesity. It contained a pilot phase to establish whether recruitment was possible, and the grant proposal specified that an adaptation to include sleeve gastrectomy would be considered if practice changed and recruitment was successful. Information on changing obesity surgery practice, updated evidence and expert opinion about trial design were used to inform the adaptation. The pilot phase recruited over 13 months in 2013-2014 and randomized 80 patients (79 anticipated). During this time, major changes in obesity practice in the UK were observed, with gastric band reducing from 32·6 to 15·8 per cent and sleeve gastrectomy increasing from 9·0 to 28·1 per cent. The evidence base had not changed markedly. The British Obesity and Metabolic Surgery Society and study oversight committees supported an adaptation to include sleeve gastrectomy, and a proposal to do so was approved by the funder. Adaptation of a two-group surgical RCT can allow evaluation of a third procedure and maintain relevance of the RCT to practice. It also optimizes the use of existing trial infrastructure to answer an additional important research question. Registration number: ISRCTN00786323 (http://www.isrctn.com/). © 2017 The Authors. BJS published by John Wiley & Sons Ltd on behalf of BJS Society Ltd.

Measuring skin necrosis in a randomised controlled feasibility trial of heat preconditioning on wound healing after reconstructive breast surgery: study protocol and statistical analysis plan for the PREHEAT trial.

PubMed

Cro, Suzie; Mehta, Saahil; Farhadi, Jian; Coomber, Billie; Cornelius, Victoria

2018-01-01

Essential strategies are needed to help reduce the number of post-operative complications and associated costs for breast cancer patients undergoing reconstructive breast surgery. Evidence suggests that local heat preconditioning could help improve the provision of this procedure by reducing skin necrosis. Before testing the effectiveness of heat preconditioning in a definitive randomised controlled trial (RCT), we must first establish the best way to measure skin necrosis and estimate the event rate using this definition. PREHEAT is a single-blind randomised controlled feasibility trial comparing local heat preconditioning, using a hot water bottle, against standard care on skin necrosis among breast cancer patients undergoing reconstructive breast surgery. The primary objective of this study is to determine the best way to measure skin necrosis and to estimate the event rate using this definition in each trial arm. Secondary feasibility objectives include estimating recruitment and 30 day follow-up retention rates, levels of compliance with the heating protocol, length of stay in hospital and the rates of surgical versus conservative management of skin necrosis. The information from these objectives will inform the design of a larger definitive effectiveness and cost-effectiveness RCT. This article describes the PREHEAT trial protocol and detailed statistical analysis plan, which includes the pre-specified criteria and process for establishing the best way to measure necrosis. This study will provide the evidence needed to establish the best way to measure skin necrosis, to use as the primary outcome in a future RCT to definitively test the effectiveness of local heat preconditioning. The pre-specified statistical analysis plan, developed prior to unblinded data extraction, sets out the analysis strategy and a comparative framework to support a committee evaluation of skin necrosis measurements. It will increase the transparency of the data analysis for the PREHEAT trial. ISRCTN ISRCTN15744669. Registered 25 February 2015.

A randomised controlled feasibility trial for an educational school-based mental health intervention: study protocol.

PubMed

Chisholm, Katharine Elizabeth; Patterson, Paul; Torgerson, Carole; Turner, Erin; Birchwood, Max

2012-03-22

With the burden of mental illness estimated to be costing the English economy alone around £22.5 billion a year 1, coupled with growing evidence that many mental disorders have their origins in adolescence, there is increasing pressure for schools to address the emotional well-being of their students, alongside the stigma and discrimination of mental illness. A number of prior educational interventions have been developed and evaluated for this purpose, but inconsistency of findings, reporting standards, and methodologies have led the majority of reviewers to conclude that the evidence for the efficacy of these programmes remains inconclusive. A cluster randomised controlled trial design has been employed to enable a feasibility study of 'SchoolSpace', an intervention in 7 UK secondary schools addressing stigma of mental illness, mental health literacy, and promotion of mental health. A central aspect of the intervention involves students in the experimental condition interacting with a young person with lived experience of mental illness, a stigma reducing technique designed to facilitate students' engagement in the project. The primary outcome is the level of stigma related to mental illness. Secondary outcomes include mental health literacy, resilience to mental illness, and emotional well-being. Outcomes will be measured pre and post intervention, as well as at 6 month follow-up. The proposed intervention presents the potential for increased engagement due to its combination of education and contact with a young person with lived experience of mental illness. Contact as a technique to reduce discrimination has been evaluated previously in research with adults, but has been employed in only a minority of research trials investigating the impact on youth. Prior to this study, the effect of contact on mental health literacy, resilience, and emotional well-being has not been evaluated to the authors' knowledge. If efficacious the intervention could provide a reliable and cost-effective method to reduce stigma in young people, whilst increasing mental health literacy, and emotional well-being. ISRCTN: ISRCTN07406026.

Metabolomic Changes in Serum of Children with Different Clinical Diagnoses of Malnutrition123

PubMed Central

Di Giovanni, Valeria; Wang, Dominic X; Seshadri, Swapna; Senga, Edward; Versloot, Christian J; Semba, Richard D; Moaddel, Ruin; Ordiz, M Isabel; Zhang, Ling; Parkinson, John; Manary, Mark J; Bandsma, Robert HJ

2016-01-01

Background: Mortality in children with severe acute malnutrition (SAM) remains high despite standardized rehabilitation protocols. Two forms of SAM are classically distinguished: kwashiorkor and marasmus. Children with kwashiorkor have nutritional edema and metabolic disturbances, including hypoalbuminemia and hepatic steatosis, whereas marasmus is characterized by severe wasting. The metabolic changes underlying these phenotypes have been poorly characterized, and whether homeostasis is achieved during hospital stay is unclear. Objectives: We aimed to characterize metabolic differences between children with marasmus and kwashiorkor at hospital admission and after clinical stabilization and to compare them with stunted and nonstunted community controls. Methods: We studied children aged 9–59 mo from Malawi who were hospitalized with SAM (n = 40; 21 with kwashiorkor and 19 with marasmus) or living in the community (n = 157; 78 stunted and 79 nonstunted). Serum from patients with SAM was obtained at hospital admission and 3 d after nutritional stabilization and from community controls. With the use of targeted metabolomics, 141 metabolites, including amino acids, biogenic amines, acylcarnitines, sphingomyelins, and phosphatidylcholines, were measured. Results: At admission, most metabolites (128 of 141; 91%) were lower in children with kwashiorkor than in those with marasmus, with significant differences in several amino acids and biogenic amines, including those of the kynurenine-tryptophan pathway. Several phosphatidylcholines and some acylcarnitines also differed. Patients with SAM had profiles that were profoundly different from those of stunted and nonstunted controls, even after clinical stabilization. Amino acids and biogenic amines generally improved with nutritional rehabilitation, but most sphingomyelins and phosphatidylcholines did not. Conclusions: Children with kwashiorkor were metabolically distinct from those with marasmus, and were more prone to severe metabolic disruptions. Children with SAM showed metabolic profiles that were profoundly different from stunted and nonstunted controls, even after clinical stabilization. Therefore, metabolic recovery in children with SAM likely extends beyond discharge, which may explain the poor long-term outcomes in these children. This trial was registered at isrctn.org as ISRCTN13916953. PMID:27807038

Quality of Life With Ivabradine in Patients With Angina Pectoris: The Study Assessing the Morbidity-Mortality Benefits of the If Inhibitor Ivabradine in Patients With Coronary Artery Disease Quality of Life Substudy.

PubMed

Tendera, Michal; Chassany, Olivier; Ferrari, Roberto; Ford, Ian; Steg, Philippe Gabriel; Tardif, Jean-Claude; Fox, Kim

2016-01-01

To explore the effect of ivabradine on angina-related quality of life (QoL) in patients participating in the Study Assessing the Morbidity-Mortality Benefits of the If Inhibitor Ivabradine in Patients with Coronary Artery Disease (SIGNIFY) QoL substudy. QoL was evaluated in a prespecified subgroup of SIGNIFY patients with angina (Canadian Cardiovascular Society class score, ≥ 2 at baseline) using the Seattle Angina Questionnaire and a generic visual analogue scale on health status. Data were available for 4187 patients (2084 ivabradine and 2103 placebo). There were improvements in QoL in both treatment groups. The primary outcome of change in physical limitation score at 12 months was 4.56 points for ivabradine versus 3.40 points for placebo (E, 0.96; 95% confidence interval, -0.14 to 2.05; P=0.085). The ivabradine-placebo difference in physical limitation score was significant at 6 months (P=0.048). At 12 months, the visual analogue scale and the other Seattle Angina Questionnaire dimensions were higher among ivabradine-treated patients, notably angina frequency (P<0.001) and disease perception (P=0.006). Patients with the worst QoL at baseline (ie, those in the lowest tertile of score) had the best improvement in QoL for 12 months, with improvements in physical limitation and a significant reduction in angina frequency (P=0.034). The effect on QoL was maintained over the study duration, and ivabradine patients had better scores on angina frequency at every visit to 36 months. Treatment with ivabradine did not affect the primary outcome of change in physical limitation score at 12 months. It did produce consistent improvements in other self-reported QoL parameters related to angina pectoris, notably in terms of angina frequency and disease perception. URL: http://www.isrctn.com. Unique identifier: ISRCTN61576291. © 2015 American Heart Association, Inc.

Recovery and decision-making involvement in people with severe mental illness from six countries: a prospective observational study.

PubMed

Loos, Sabine; Clarke, Eleanor; Jordan, Harriet; Puschner, Bernd; Fiorillo, Andrea; Luciano, Mario; Ivánka, Tibor; Magyar, Erzsébet; Krogsgaard-Bording, Malene; Østermark-Sørensen, Helle; Rössler, Wulf; Kawohl, Wolfram; Mayer, Benjamin; Slade, Mike

2017-01-23

Clinical decision-making is the vehicle of health care provision, and level of involvement predicts implementation and satisfaction. The aim of this study was to investigate the impact of decision-making experience on recovery. Data derived from an observational cohort study "Clinical decision making and outcome in routine care for people with severe mental illness" (CEDAR). Adults (aged 18-60) meeting standardised criteria for severe mental illness were recruited from caseloads of outpatient and community mental health services in six European countries. After consenting, they were assessed using standardised measures of decision-making, clinical outcome and stage of recovery at baseline and 1 year later. Latent class analysis was used to identify course of recovery, and proportional odds models to investigate predictors of recovery stage and change. Participants (n = 581) clustered into three stages of recovery at baseline: Moratorium (N = 115; 19.8%), Awareness/Preparation (N = 145; 25.0%) and Rebuilding/Growth (N = 321; 55.2%). Higher stage was cross-sectionally associated with being male, married, living alone or with parents, and having better patient-rated therapeutic alliance and fewer symptoms. The model accounted for 40% of the variance in stage of recovery. An increased chance of worse outcome (change over 1 year to lower stage of recovery) was found for patients with active involvement compared with either shared (OR = 1.84, 95% CI 1.15-2.94) or passive (OR = 1.71, 95% CI = 1.00-2.95) involvement. Overall, both process (therapeutic relationship) and outcome (symptomatology) are cross-sectionally associated with stage of recovery. Patient-rated decision-making involvement and change in stage of recovery are associated. Joint consideration of decision practise within the recovery process between patient and clinician is supposed to be a useful strategy to improve clinical practice (ISRCTN registry: ISRCTN75841675. Retrospectively registered 15 September 2010).

Effect of CPAP on Cardiac Function in Minimally Symptomatic Patients with OSA: Results from a Subset of the MOSAIC Randomized Trial.

PubMed

Craig, Sonya; Kylintireas, Ilias; Kohler, Malcolm; Nicoll, Debby; Bratton, Daniel J; Nunn, Andrew J; Leeson, Paul; Neubauer, Stefan; Stradling, John R

2015-09-15

Minimally symptomatic obstructive sleep apnea (OSA) is highly prevalent, and the effects of continuous positive airway pressure (CPAP) on myocardial function in these patients are unknown. The MOSAIC randomized, controlled trial of CPAP for minimally symptomatic OSA assessed the effect of CPAP on myocardial function in a subset of patients. Two centers taking part in the MOSAIC trial randomized 238 patients in parallel to 6 months of CPAP (120) or standard care (118). Of these, 168 patients had echocardiograms, and 68 patients had a cardiac magnetic resonance scan (CMR). A larger group (314) from 4 centers had brain natriuretic peptide (BNP) measured. Mean (SD) baseline oxygen desaturation index (ODI) and Epworth sleepiness score (ESS) were 13.5 (13.2), and 8.4 (4.0), respectively. CPAP significantly reduced ESS and ODI. Baseline LV ejection fraction (LVEF) was well preserved (60.4%). CPAP had no significant effect on echo-derived left atrial (LA) area (-1.0 cm2, 95% CI -2.6 to +0.6, p = 0.23) or early to late left ventricular filling velocity (E/A) ratio (-0.01, 95% CI -0.07 to +0.05, p = 0.79). There was a small change in echo-derived LV end diastolic volume (EDV) with CPAP (-5.9 mL, 95% CI -10.6 to -1.2, p = 0.015). No significant changes were detected by CMR on LV mass index (+1.1 g/m(2), 95% CI -5.9 to +8.0, p = 0.76) or LVEF (+0.8%, 95% CI -1.2 to +2.8, p = 0.41). CPAP did not affect BNP levels (p = 0.16). Six months of CPAP therapy does not change cardiac functional or structural parameters measured by echocardiogram or CMR in patients with minimally symptomatic mild-to-moderate OSA. ISRCTN 34164388 (http://isrctn.org). © 2015 American Academy of Sleep Medicine.

Effects of age on long-term outcomes after a routine invasive or selective invasive strategy in patients presenting with non-ST segment elevation acute coronary syndromes: a collaborative analysis of individual data from the FRISC II - ICTUS - RITA-3 (FIR) trials.

PubMed

Damman, Peter; Clayton, Tim; Wallentin, Lars; Lagerqvist, Bo; Fox, Keith A A; Hirsch, Alexander; Windhausen, Fons; Swahn, Eva; Pocock, Stuart J; Tijssen, Jan G P; de Winter, Robbert J

2012-02-01

To perform a patient-pooled analysis of a routine invasive versus a selective invasive strategy in elderly patients with non-ST segment elevation acute coronary syndrome. A meta-analysis was performed of patient-pooled data from the FRISC II-ICTUS-RITA-3 (FIR) studies. (Un)adjusted HRs were calculated by Cox regression, with adjustments for variables associated with age and outcomes. The main outcome was 5-year cardiovascular death or myocardial infarction (MI) following routine invasive versus selective invasive management. Regarding the 5-year composite of cardiovascular death or MI, the routine invasive strategy was associated with a lower hazard in patients aged 65-74 years (HR 0.72, 95% CI 0.58 to 0.90) and those aged ≥75 years (HR 0.71, 95% CI 0.55 to 0.91), but not in those aged <65 years (HR 1.11, 95% CI 0.90 to 1.38), p=0.001 for interaction between treatment strategy and age. The interaction was driven by an excess of early MIs in patients <65 years of age; there was no heterogeneity between age groups concerning cardiovascular death. The benefits were smaller for women than for men (p=0.009 for interaction). After adjustment for other clinical risk factors the HRs remained similar. The current analysis of the FIR dataset shows that the long-term benefit of the routine invasive strategy over the selective invasive strategy is attenuated in younger patients aged <65 years and in women by the increased risk of early events which seem to have no consequences for long-term cardiovascular mortality. No other clinical risk factors were able to identify patients with differential responses to a routine invasive strategy. Trial registration http://www.controlled-trials.com/ISRCTN82153174 (ICTUS), http://www.controlled-trials.com/ISRCTN07752711 (RITA-3).

A pilot randomised controlled trial of negative pressure wound therapy to treat grade III/IV pressure ulcers [ISRCTN69032034

PubMed Central

2012-01-01

Background Negative pressure wound therapy (NPWT) is widely promoted as a treatment for full thickness wounds; however, there is a lack of high-quality research evidence regarding its clinical and cost effectiveness. A trial of NPWT for the treatment of grade III/IV pressure ulcers would be worthwhile but premature without assessing whether such a trial is feasible. The aim of this pilot randomised controlled trial was to assess the feasibility of conducting a future full trial of NPWT for the treatment of grade III and IV pressure ulcers and to pilot all aspects of the trial. Methods This was a two-centre (acute and community), pilot randomised controlled trial. Eligible participants were randomised to receive either NPWT or standard care (SC) (spun hydrocolloid, alginate or foam dressings). Outcome measures were time to healing of the reference pressure ulcer, recruitment rates, frequency of treatment visits, resources used and duration of follow-up. Results Three hundred and twelve patients were screened for eligibility into this trial over a 12-month recruitment period and 12/312 participants (3.8%) were randomised: 6 to NPWT and 6 to SC. Only one reference pressure ulcer healed (NPWT group) during follow-up (time to healing 79 days). The mean number of treatment visits per week was 3.1 (NPWT) and 5.7 (SC); 6/6 NPWT and 1/6 SC participants withdrew from their allocated trial treatment. The mean duration of follow-up was 3.8 (NPWT) and 5.0 (SC) months. Conclusions This pilot trial yielded vital information for the planning of a future full study including projected recruitment rate, required duration of follow-up and extent of research nurse support required. Data were also used to inform the cost-effectiveness and value of information analyses, which were conducted alongside the pilot trial. Trial registration Current Controlled Trials ISRCTN69032034. PMID:22839453

The PD COMM trial: a protocol for the process evaluation of a randomised trial assessing the effectiveness of two types of SLT for people with Parkinson's disease.

PubMed

Masterson-Algar, Patricia; Burton, Christopher R; Brady, Marian C; Nicoll, Avril; Clarke, Carl E; Rick, Caroline; Hughes, Max; Au, Pui; Smith, Christina H; Sackley, Catherine M

2017-08-29

The PD COMM trial is a phase III multi-centre randomised controlled trial whose aim is to evaluate the effectiveness and cost-effectiveness of two approaches to speech and language therapy (SLT) compared with no SLT intervention (control) for people with Parkinson's disease who have self-reported or carer-reported problems with their speech or voice. Our protocol describes the process evaluation embedded within the outcome evaluation whose aim is to evaluate what happened at the time of the PD COMM intervention implementation and to provide findings that will assist in the interpretation of the PD COMM trial results. Furthermore, the aim of the PD COMM process evaluation is to investigate intervention complexity within a theoretical model of how the trialled interventions might work best and why. Drawing from the Normalization Process Theory and frameworks for implementation fidelity, a mixed method design will be used to address process evaluation research questions. Therapists' and participants' perceptions and experiences will be investigated via in-depth interviews. Critical incident reports, baseline survey data from therapists, treatment record forms and home practice diaries also will be collected at relevant time points throughout the running of the PD COMM trial. Process evaluation data will be analysed independently of the outcome evaluation before the two sets of data are then combined. To date, there are a limited number of published process evaluation protocols, and few are linked to trials investigating rehabilitation therapies. Providing a strong theoretical framework underpinning design choices and being tailored to meet the complex characteristics of the trialled interventions, our process evaluation has the potential to provide valuable insight into which components of the interventions being delivered in PD COMM worked best (and what did not), how they worked well and why. ISRCTN Registry, ISRCTN12421382 . Registered on 18 April 2016.

Limited Amount of Formula May Facilitate Breastfeeding: Randomized, Controlled Trial to Compare Standard Clinical Practice versus Limited Supplemental Feeding.

PubMed

Straňák, Zbyněk; Feyereislova, Simona; Černá, Marcela; Kollárová, Jana; Feyereisl, Jaroslav

2016-01-01

Breastfeeding is known to reduce infant morbidity and improve well-being. Nevertheless, breastfeeding rates remain low despite public health efforts. Our study aims to investigate the effect of controlled limited formula usage during birth hospitalisation on breastfeeding, using the primary hypothesis that early limited formula feeds in infants with early weight loss will not adversely affect the rate of exclusive or any breastfeeding as measured at discharge, 3 and 6 months of age. We randomly assigned 104 healthy term infants, 24 to 48 hours old, with ≥ 5% loss of birth weight to controlled limited formula (CLF) intervention (10 ml formula by syringe after each breastfeeding, discontinued at onset of lactation) or control group (standard approach, SA). Groups were compared for demographic data and breastfeeding rates at discharge, 3 months and 6 months of age (p-values adjusted for multiple testing). Fifty newborns were analysed in CLF and 50 in SA group. There were no differences in demographic data or clinical characteristics between groups. We found no evidence of difference between treatment groups in the rates of exclusive as well as any breastfeeding at discharge (p-value 0.2 and >0.99 respectively), 3 months (p-value 0.12 and 0.10) and 6 months of infants' age (p-value 0.45 and 0.34 respectively). The percentage weight loss during hospitalisation was significantly higher in the SA group (7.3% in CLF group, 8.4% in SA group, p = 0.002). The study shows that controlled limited formula use does not have an adverse effect on rates of breastfeeding in the short and long term. Larger studies are needed to confirm a possible potential in controlled limited formula use to support establishing breastfeeding and to help to improve the rates of breastfeeding overall. ISRCTN registry ISRCTN61915183.

Chuanhu Anti-Gout Mixture versus Colchicine for Acute Gouty Arthritis: A Randomized, Double-Blind, Double-Dummy, Non-Inferiority Trial

PubMed Central

Wang, YanGang; Wang, Luan; Li, EnZe; Li, Yang; Wang, ZhongChao; Sun, XiaoFang; Yu, XiaoLong; Ma, Lin; Wang, YunLong; Wang, YouXin

2014-01-01

Background The Chuanhu anti-gout mixture has been used for many years in the treatment of gout in Chinese Traditional Medicine, and current methods for treatments for acute gouty arthritis have been either less effective or have had serious side effects. Methods In this 12-week, double-blind, double-dummy, non-inferiority study, outpatient individuals with newly diagnosed acute gouty arthritis were randomly assigned to receive Chuanhu anti-gout mixture or colchicine. Both the study investigators and the participants were masked to the treatment assignments. The primary outcome was the recurrence rate of acute gouty arthritis, and the secondary outcomes were changes in white blood cells (WHC) and C-reactive protein (CRP). This trial is registered at ISRCTN.org as trial ISRCTN65219941. Results A total of 176 patients were randomly assigned to receive either the Chuanhu anti-gout mixture or Colchicine. The overall recurrence rates in the Chuanhu anti-gout mixture group (CH group) and the Colchicine group (Col group) were 12.50% vs 14.77% (difference -2.22%, 95% confidence interval (95% CI): -10.78%~6.23%), meeting the predefined non-inferiority criterion of 15%, as did the data for WHC and CRP. The incidence of adverse events (mainly diarrhea) was less in the Col group than in the CH group (2.27% vs 28.41%, 95% CI 0.01~0.26). In addition, changes in blood uric acid, alanine aminotransferase, aspartate aminotransferase and creatinine in the CH group were significantly larger compared to those in the Col group (P<0.05). Conclusions The Chuanhu anti-gout mixture was non-inferior to colchicine for the treatment of acute gouty arthritis. The study suggested that the Chuanhu anti-gout mixture can be considered an alternative choice for the treatment of acute gouty arthritis because of its lower incidence of adverse events and its protection of kidney and renal function. PMID:25013367

Accuracy of diagnostic tests to detect asymptomatic bacteriuria during pregnancy.

PubMed

Mignini, Luciano; Carroli, Guillermo; Abalos, Edgardo; Widmer, Mariana; Amigot, Susana; Nardin, Juan Manuel; Giordano, Daniel; Merialdi, Mario; Arciero, Graciela; Del Carmen Hourquescos, Maria

2009-02-01

A dipslide is a plastic paddle coated with agar that is attached to a plastic cap that screws onto a sterile plastic vial. Our objective was to estimate the diagnostic accuracy of the dipslide culture technique to detect asymptomatic bacteriuria during pregnancy and to evaluate the accuracy of nitrate and leucocyte esterase dipslides for screening. This was an ancillary study within a trial comparing single-day with 7-day therapy in treating asymptomatic bacteriuria. Clean-catch midstream samples were collected from pregnant women seeking routine care. Positive and negative likelihood ratios and sensitivity and specificity for the culture-based dipslide to detect and chemical dipsticks (nitrites, leukocyte esterase, or both) to screen were estimated using traditional urine culture as the "gold standard." : A total of 3,048 eligible pregnant women were screened. The prevalence of asymptomatic bacteriuria was 15%, with Escherichia coli the most prevalent organism. The likelihood ratio for detecting asymptomatic bacteriuria with a positive dipslide test was 225 (95% confidence interval [CI] 113-449), increasing the probability of asymptomatic bacteriuria to 98%; the likelihood ratio for a negative dipslide test was 0.02 (95% CI 0.01-0.05), reducing the probability of bacteriuria to less than 1%. The positive likelihood ratio of leukocyte esterase and nitrite dipsticks (when both or either one was positive) was 6.95 (95% CI 5.80-8.33), increasing the probability of bacteriuria to only 54%; the negative likelihood ratio was 0.50 (95% CI 0.45-0.57), reducing the probability to 8%. A pregnant woman with a positive dipslide test is very likely to have a definitive diagnosis of asymptomatic bacteriuria, whereas a negative result effectively rules out the presence of bacteriuria. Dipsticks that measure nitrites and leukocyte esterase have low sensitivity for use in screening for asymptomatic bacteriuria during gestation. ISRCTN, isrctn.org, 1196608 II.

Rationale, design and methods of the Study of Work and Pain (SWAP): a cluster randomised controlled trial testing the addition of a vocational advice service to best current primary care for patients with musculoskeletal pain (ISRCTN 52269669)

PubMed Central

2014-01-01

Background Musculoskeletal pain is a major contributor to short and long term work absence. Patients seek care from their general practitioner (GP) and yet GPs often feel ill-equipped to deal with work issues. Providing a vocational case management service in primary care, to support patients with musculoskeletal problems to remain at or return to work, is one potential solution but requires robust evaluation to test clinical and cost-effectiveness. Methods/Design This protocol describes a cluster randomised controlled trial, with linked qualitative interviews, to investigate the effect of introducing a vocational advice service into general practice, to provide a structured approach to managing work related issues in primary care patients with musculoskeletal pain who are absent from work or struggling to remain in work. General practices (n = 6) will be randomised to offer best current care or best current care plus a vocational advice service. Adults of working age who are absent from or struggling to remain in work due to a musculoskeletal pain problem will be invited to participate and 330 participants will be recruited. Data collection will be through patient completed questionnaires at baseline, 4 and 12 months. The primary outcome is self-reported work absence at 4 months. Incremental cost-utility analysis will be undertaken to calculate the cost per additional QALY gained and incremental net benefits. A linked interview study will explore the experiences of the vocational advice service from the perspectives of GPs, nurse practitioners (NPs), patients and vocational advisors. Discussion This paper presents the rationale, design, and methods of the Study of Work And Pain (SWAP) trial. The results of this trial will provide evidence to inform primary care practice and guide the development of services to provide support for musculoskeletal pain patients with work-related issues. Trial registration Current Controlled Trials ISRCTN52269669. PMID:25012813

Cost-effectiveness of the Australian Medical Sheepskin for the prevention of pressure ulcers in somatic nursing home patients: study protocol for a prospective multi-centre randomised controlled trial (ISRCTN17553857).

PubMed

Mistiaen, Patriek; Achterberg, Wilco; Ament, Andre; Halfens, Ruud; Huizinga, Janneke; Montgomery, Ken; Post, Henri; Francke, Anneke L

2008-01-07

Pressure ulcers are a major problem, especially in nursing home patients, although they are regarded as preventable and there are many pressure relieving methods and materials. One such pressure relieving material is the recently developed Australian Medical Sheepskin, which has been shown in two randomized controlled trials 12 to be an effective intervention in the prevention of sacral pressure ulcers in hospital patients. However, the use of sheepskins has been debated and in general discouraged by most pressure ulcer working groups and pressure ulcer guidelines, but these debates were based on old forms of sheepskins. Furthermore, nothing is yet known about the (cost-)effectiveness of the Australian Medical sheepskin in nursing home patients. The objective of this study is to assess the effects and costs of the use of the Australian Medical Sheepskin combined with usual care with regard to the prevention of sacral pressure ulcers in somatic nursing home patients, versus usual care only. In a multi-centre randomised controlled trial 750 patients admitted for a primarily somatic reason to one of the five participating nursing homes, and not having pressure ulcers on the sacrum at admission, will be randomized to either usual care only or usual care plus the use of the Australian Medical Sheepskin as an overlay on the mattress. Outcome measures are: incidence of sacral pressure ulcers in the first month after admission; sacrum pressure ulcer free days; costs; patient comfort; and ease of use. The skin of all the patients will be observed once a day from admission on for 30 days. Patient characteristics and pressure risk scores are assessed at admission and at day 30 after it. Additional to the empirical phase, systematic reviews will be performed in order to obtain data for economic weighting and modelling. The protocol is registered in the Controlled Trial Register as ISRCTN17553857.

Using the RE-AIM framework to evaluate a community-based summer camp for children with obesity: a prospective feasibility study.

PubMed

Burke, Shauna M; Shapiro, Sheree; Petrella, Robert J; Irwin, Jennifer D; Jackman, Michelle; Pearson, Erin S; Prapavessis, Harry; Shoemaker, Joel Kevin

2015-01-01

Increasing rates of childhood overweight and obesity highlight a need for the evaluation of lifestyle interventions. The purpose of the study was to determine the Reach, Effectiveness, Adoption, Implementation and Maintenance of a novel family-focused program targeting children with obesity (i.e., the Children's Health and Activity Modification Program [C.H.A.M.P.]) using the RE-AIM framework, an evaluation tool for community-based health interventions. A single-centre, single cohort interventional feasibility study was conducted over the course of two years. Children with obesity and their families completed a 4-week group-based lifestyle intervention in Year 1 (n = 15; M age = 10.6; 53% female) and/or Year 2 (n = 25; M age = 10.6; 56% female). Outcome variables were measured pre- and post-intervention, as well as 6- and 12-months following completion of the formal program. Overall, C.H.A.M.P. had high reach in terms of participant representativeness. In addition, participation in the program was associated with significantly improved standardized body mass index (BMI-z), body fat percentage, lean mass percentage, and child- and parent-proxy reported quality of life (QOL; effectiveness/individual maintenance). Furthermore, a number of community partnerships were built, strengthened, and maintained prior to, during, and following implementation of the two-year program (adoption/setting maintenance, respectively). Finally, the intervention was delivered as intended as evidenced by high adherence to the schedule, attendance rates, and cost effectiveness (implementation). Based on RE-AIM metrics, C.H.A.M.P. appears to be a promising childhood obesity program. The findings reported will inform researchers and practitioners on how to design and implement future community-based programs addressing pediatric obesity. ISRCTN Registry, Study ID ISRCTN13143236. Registered 27 March 2015.

Synthetic folic acid intakes and status in children living in Ireland exposed to voluntary fortification.

PubMed

Vaish, Shashi; White, Martin; Daly, Leslie; Molloy, Anne M; Staines, Anthony; Sweeney, Mary Rose

2016-02-01

In the context of mandatory and voluntary folic acid fortification, the exposure of children to folic acid has been a focus of concern, particularly regarding the possibility of whether any potentially adverse effects will emerge in the future. We explored concentrations of fasting unmetabolized folic acid (UFA) in the circulation of children living in Ireland who were exposed to the voluntary folic acid-fortification regimen in place in Ireland. Healthy children who were attending Our Lady's Children's Hospital, Crumlin, for routine minor surgery were recruited to provide a fasting 3-mL blood sample that was taken while a general anesthetic was administered. The samples were analyzed for plasma folate, red blood cell folate, and UFA concentrations. A short dietary questionnaire that captured recent and habitual intakes of folic acid, both as supplements and as fortified foods, was completed face to face with parents. We collected fasting samples (n = 68) and completed questionnaires that captured recent and habitual daily folic acid intakes of children grouped as follows: 0-5 y of age: 6 girls and 21 boys (27 children total); 6-10 y of age: 10 girls and 10 boys (20 children total); and 11-16 y of age: 10 girls and 11 boys (21 children total). UFA was detected in 10.3% of the samples tested (range: 0.5-1.3 nmol/L). Mean plasma folate and red blood cell folate concentrations were 35.1 nmol/L (range: 21-47 nmol/L) and 956 nmol/L (range: 305-2319 nmol/L), respectively. Mean daily intake of folic acid from fortified foods and supplements was 109 μg (range: 0-767 μg). We showed that there was UFA in the plasma of just >10% of the children sampled after an overnight fast. These findings should be considered by policy makers who are responsible for folic acid fortification. This trial was registered at www.isrctn.com as ISRCTN90038765. © 2016 American Society for Nutrition.

Preconceptional and gestational weight trajectories and risk of delivering a small-for-gestational-age baby in rural Gambia.

PubMed

Johnson, William; Elmrayed, Seham Aa; Sosseh, Fatou; Prentice, Andrew M; Moore, Sophie E

2017-06-01

Background: Maternal nutritional status is a key determinant of small for gestational age (SGA), but some knowledge gaps remain, particularly regarding the role of the energy balance entering pregnancy. Objective: We investigated how preconceptional and gestational weight trajectories (summarized by individual-level traits) are associated with SGA risk in rural Gambia. Design: The sample comprised 670 women in a trial with serial weight data (7310 observations) that were available before and during pregnancy. Individual trajectories from 6 mo before conception to 30 wk of gestation were produced with the use of multilevel modeling. Summary traits were expressed as weight z scores [weight z score at 3 mo preconception ( z wt -3 mo ), weight z score at conception, weight z score at 3 mo postconception, weight z score at 7 mo postconception ( z wt +7 mo ), and conditional measures that represented the change from the preceding time] and were related to SGA risk with the use of Poisson regression with confounder adjustment; linear splines were used to account for nonlinearity. Results: Maternal weight at each time point had a consistent nonlinear relation with SGA risk. For example, the z wt -3 mo estimate was stronger in women with values ≤0.5 (RR: 0.736; 95% CI: 0.594, 0.910) than in women with values >0.5 (RR: 0.920; 95% CI: 0.682, 1.241). The former group had the highest observed SGA prevalence. Focusing on weight change, only conditional z wt +7 mo was associated with SGA and only in women with values >-0.5 (RR: 0.579; 95% CI: 0.463, 0.724). Conclusions: Protection against delivering an SGA neonate offered by greater preconceptional or gestational weight may be most pronounced in more undernourished and vulnerable women. Independent of this possibility, greater second- and third-trimester weight gain beyond a threshold may be protective. This trial was registered at http://www.isrctn.com/ as ISRCTN49285450.

Four-year-old outcomes of a universal infant-toddler shared reading intervention: the let's read trial.

PubMed

Goldfeld, Sharon; Quach, Jon; Nicholls, Ruth; Reilly, Sheena; Ukoumunne, Obioha C; Wake, Melissa

2012-11-01

To determine the emergent literacy and language effects of a low-intensity literacy promotion program (Let's Read) provided via universal well-child services to parents during the first 4 years of their child's life. Population-based, cluster randomized controlled trial performed between March 1, 2006, and December 10, 2010. Maternal and child health centers (clusters) in 5 relatively disadvantaged local government areas in Melbourne, Australia. All parents attending their 4-week well-child appointments in participating centers were invited to take part in the study. The Let's Read program was delivered at 4, 12, 18, and 42 months during universal well-child care visits. Child emergent literacy skills (intrasyllabic, phonemic, and sound/letter knowledge) and language (core, receptive, and expressive), measured at 4 years of age. A total of 630 parents participated, with 365 children in 32 intervention clusters and 265 children in 33 control clusters; 563 children (89.4%) were retained in the study to 4 years of age. The adjusted mean differences (intervention minus control) for emergent literacy was 0.2 (95% CI, -0.2 to 0.6; P = .29) for intrasyllabic units, 0.05 (95% CI, -0.4 to 0.5; P = .85) for phonemic awareness, and 0.1 (95% CI, -1.5 to 1.6; P = .92) for letter knowledge. For language, the differences were 1.6 (95% CI, -1.1 to 4.3; P = .25) for core, 0.8 (95% CI, -2.0 to 3.7; P = .56) for receptive, and 1.4 (95% CI, -1.4 to 4.2; P = .32) for expressive scores. This population-wide primary care literacy promotion and book distribution program provided neither the anticipated benefits to literacy and language nor enhanced uptake of literacy activities at 4 years of age, even when targeted to relatively disadvantaged areas. isrctn.org Identifier: ISRCTN04602902.

Studying feasibility and effects of a two-stage nursing staff training in residential geriatric care using a 30 month mixed-methods design [ISRCTN24344776].

PubMed

Betschon, Elsbeth; Brach, Michael; Hantikainen, Virpi

2011-05-31

Transfer techniques and lifting weights often cause back pain and disorders for nurses in geriatric care. The Kinaesthetics care conception claims to be an alternative, yielding benefits for nurses as well as for clients.Starting a multi-step research program on the effects of Kinaesthetics, we assess the feasibility of a two-stage nursing staff training and a pre-post research design. Using quantitative and qualitative success criteria, we address mobilisation from the bed to a chair and backwards, walking with aid and positioning in bed on the staff level as well as on the resident level. In addition, effect estimates should help to decide on and to prepare a controlled trial. Standard basic and advanced Kinaesthetics courses (each comprising four subsequent days and an additional counselling day during the following four months) are offered to n = 36 out of 60 nurses in a residential geriatric care home, who are in charge of 76 residents. N = 22 residents needing movement support are participating to this study.On the staff level, measurements include focus group discussions, questionnaires, physical strain self-assessment (Borg scale), video recordings and external observation of patient assistance skills using a specialised instrument (SOPMAS). Questionnaires used on the resident level include safety, comfort, pain, and level of own participation during mobilisation. A functional mobility profile is assessed using a specialised test procedure (MOTPA).Measurements will take place at baseline (T0), after basic training (T1), and after the advanced course (T2). Follow-up focus groups will be offered at T1 and 10 months later (T3). Ten criteria for feasibility success are established before the trial, assigned to resources (missing data), processes (drop-out of nurses and residents) and science (minimum effects) criteria. This will help to make rational decision on entering the next stage of the research program. Current Controlled Trials ISRCTN24344776.

Labetalol Versus Nifedipine as Antihypertensive Treatment for Chronic Hypertension in Pregnancy: A Randomized Controlled Trial.

PubMed

Webster, Louise M; Myers, Jenny E; Nelson-Piercy, Catherine; Harding, Kate; Cruickshank, J Kennedy; Watt-Coote, Ingrid; Khalil, Asma; Wiesender, Cornelia; Seed, Paul T; Chappell, Lucy C

2017-11-01

Data from randomized controlled trials to guide antihypertensive agent choice for chronic hypertension in pregnancy are limited; this study aimed to compare labetalol and nifedipine, additionally assessing the impact of ethnicity on treatment efficacy. Pregnant women with chronic hypertension (12 +0 -27 +6 weeks' gestation) were enrolled at 4 UK centers (August 2014 to October 2015). Open-label first-line antihypertensive treatment was randomly assigned: labetalol- (200-1800 mg/d) or nifedipine-modified release (20-80 mg/d). Analysis included 112 women (98%) who completed the study (labetalol n=55, nifedipine n=57). Maximum blood pressure after randomization was 161/101 mm Hg with labetalol versus 163/105 mm Hg with nifedipine (mean difference systolic: 1.2 mm Hg [-4.9 to 7.2 mm Hg], diastolic: 3.3 mm Hg [-0.6 to 7.3 mm Hg]). Mean blood pressure was 134/84 mm Hg with labetalol and 134/85 mm Hg with nifedipine (mean difference systolic: 0.3 mm Hg [-2.8 to 3.4 mm Hg], and diastolic: -1.9 mm Hg [-4.1 to 0.3 mm Hg]). Nifedipine use was associated with a 7.4-mm Hg reduction (-14.4 to -0.4 mm Hg) in central aortic pressure, measured by pulse wave analysis. No difference in treatment effect was observed in black women (n=63), but a mean 4 mm Hg reduction (-6.6 to -0.8 mm Hg; P =0.015) in brachial diastolic blood pressure was observed with labetalol compared with nifedipine in non-black women (n=49). Labetalol and nifedipine control mean blood pressure to target in pregnant women with chronic hypertension. This study provides support for a larger definitive trial scrutinizing the benefits and side effects of first-line antihypertensive treatment. URL: https://www.isrctn.com. Unique identifier: ISRCTN40973936. © 2017 American Heart Association, Inc.

Increasing organ donation via anticipated regret (INORDAR): protocol for a randomised controlled trial

PubMed Central

2012-01-01

Background Throughout the world there is an insufficient supply of donor organs to meet the demand for organ transplantations. This paper presents a protocol for a randomised controlled trial, testing whether a simple, theory-based anticipated regret manipulation leads to a significant increase in posthumous organ donor registrations. Methods We will use a between-groups, prospective randomised controlled design. A random sample of 14,520 members of the adult Scottish general public will be contacted via post. These participants will be randomly allocated into 1 of the 4 conditions. The no questionnaire control (NQC) group will simply receive a letter and donor registration form. The questionnaire control (QC) arm will receive a questionnaire measuring their emotions and non-cognitive affective attitudes towards organ donation. The theory of planned behavior (TPB) group will complete the emotions and affective attitudes questionnaire plus additional items assessing their cognitive attitudes towards organ donation, perceived control over registration and how they think significant others view this action. Finally, the anticipated regret (AR) group will complete the same indices as the TPB group, plus two additional anticipated regret items. These items will assess the extent to which the participant anticipates regret for not registering as an organ donor in the near future. The outcome variable will be NHS Blood and Transplant verified registrations as an organ donor within 6 months of receiving our postal intervention. Discussion This study will assess whether simply asking people to reflect on the extent to which they may anticipate regret for not registering as an organ donor increases organ donor registration 6 months later. If successful, this simple and easy to administer theory-based intervention has the potential to save lives and money for the NHS by reducing the number of people receiving treatments such as dialysis. This intervention may also be incorporated into future organ donor campaigns. Trial registration number ISRCTN: ISRCTN92204897 PMID:22401534

Study protocol of cost-effectiveness and cost-utility of a biopsychosocial multidisciplinary intervention in the evolution of non-specific sub-acute low back pain in the working population: cluster randomised trial

PubMed Central

2011-01-01

Background Low back pain (LBP), with high incidence and prevalence rate, is one of the most common reasons to consult the health system and is responsible for a significant amount of sick leave, leading to high health and social costs. The objective of the study is to assess the cost-effectiveness and cost-utility analysis of a multidisciplinary biopsychosocial educational group intervention (MBEGI) of non-specific sub-acute LBP in comparison with the usual care in the working population recruited in primary healthcare centres. Methods/design The study design is a cost-effectiveness and cost-utility analysis of a MBEGI in comparison with the usual care of non-specific sub-acute LBP. Measures on effectiveness and costs of both interventions will be obtained from a cluster randomised controlled clinical trial carried out in 38 Catalan primary health care centres, enrolling 932 patients between 18 and 65 years old with a diagnosis of non-specific sub-acute LBP. Effectiveness measures are: pharmaceutical treatments, work sick leave (% and duration in days), Roland Morris disability, McGill pain intensity, Fear Avoidance Beliefs (FAB) and Golberg Questionnaires. Utility measures will be calculated from the SF-12. The analysis will be performed from a social perspective. The temporal horizon is at 3 months (change to chronic LBP) and 12 months (evaluate the outcomes at long term). Assessment of outcomes will be blinded and will follow the intention-to-treat principle. Discussion We hope to demonstrate the cost-effectiveness and cost-utility of MBEGI, see an improvement in the patients' quality of life, achieve a reduction in the duration of episodes and the chronicity of non-specific low back pain, and be able to report a decrease in the social costs. If the intervention is cost-effectiveness and cost-utility, it could be applied to Primary Health Care Centres. Trial registration ISRCTN: ISRCTN58719694 PMID:21859489

Use of Anticoagulants and Antiplatelet Agents in Stable Outpatients with Coronary Artery Disease and Atrial Fibrillation. International CLARIFY Registry

PubMed Central

Fauchier, Laurent; Greenlaw, Nicola; Ferrari, Roberto; Ford, Ian; Fox, Kim M.; Tardif, Jean-Claude; Tendera, Michal; Steg, Ph. Gabriel

2015-01-01

Background Few data are available regarding the use of antithrombotic strategies in coronary artery disease patients with atrial fibrillation (AF) in everyday practice. We sought to describe the prevalence of AF and its antithrombotic management in a contemporary population of patients with stable coronary artery disease. Methods and Findings CLARIFY is an international, prospective, longitudinal registry of outpatients with stable coronary artery disease, defined as prior (≥12 months) myocardial infarction, revascularization procedure, coronary stenosis >50%, or chest pain associated with evidence of myocardial ischemia. Overall, 33,428 patients were screened, of whom 32,954 had data available for analysis at baseline; of these 2,229 (6.7%) had a history of AF. Median (interquartile range) CHA2DS2-VASc score was 4 (3, 5). Oral anticoagulation alone was used in 25.7%, antiplatelet therapy alone in 52.8% (single 41.8%, dual 11.0%), and both in 21.5%. OAC use was independently associated with permanent AF (p<0.001), CHA2DS2-VASc score (p=0.006), pacemaker (p<0.001), stroke (p=0.04), absence of angina (p=0.004), decreased left ventricular ejection fraction (p<0.001), increased waist circumference (p=0.005), and longer history of coronary artery disease (p=0.008). History of percutaneous coronary intervention (p=0.004) and no/partial reimbursement for cardiovascular medication (p=0.01, p<0.001, respectively) were associated with reduced oral anticoagulant use. Conclusions In this contemporary cohort of patients with stable coronary artery disease and AF, most of whom are theoretical candidates for anticoagulation, oral anticoagulants were used in only 47.2%. Half of the patients received antiplatelet therapy alone and one-fifth received both antiplatelets and oral anticoagulants. Efforts are needed to improve adherence to guidelines in these patients. Trial Registration ISRCTN registry of clinical trials: ISRCTN43070564. PMID:25915904

Optimizing treatment with tumour necrosis factor inhibitors in rheumatoid arthritis—a proof of principle and exploratory trial: is dose tapering practical in good responders?

PubMed Central

Lorente-Cánovas, Beatriz; Doré, Caroline J; Bosworth, Ailsa; Ma, Margaret H; Galloway, James B; Cope, Andrew P; Pande, Ira; Walker, David; Scott, David L

2017-01-01

Abstract Objectives RA patients receiving TNF inhibitors (TNFi) usually maintain their initial doses. The aim of the Optimizing Treatment with Tumour Necrosis Factor Inhibitors in Rheumatoid Arthritis trial was to evaluate whether tapering TNFi doses causes loss of clinical response. Methods We enrolled RA patients receiving etanercept or adalimumab and a DMARD with DAS28 under 3.2 for over 3 months. Initially (months 0–6) patients were randomized to control (constant TNFi) or two experimental groups (tapering TNFi by 33 or 66%). Subsequently (months 6–12) control subjects were randomized to taper TNFi by 33 or 66%. Disease flares (DAS28 increasing ⩾0.6 with at least one additional swollen joint) were the primary outcome. Results Two hundred and forty-four patients were screened, 103 randomized and 97 treated. In months 0–6 there were 8/50 (16%) flares in controls, 3/26 (12%) with 33% tapering and 6/21 (29%) with 66% tapering. Multivariate Cox analysis showed time to flare was unchanged with 33% tapering but was reduced with 66% tapering compared with controls (adjusted hazard ratio 2.81, 95% CI: 0.99, 7.94; P = 0.051). Analysing all tapered patients after controls were re-randomized (months 6–12) showed differences between groups: there were 6/48 (13%) flares with 33% tapering and 14/39 (36%) with 66% tapering. Multivariate Cox analysis showed 66% tapering reduced time to flare (adjusted hazard ratio 3.47, 95% CI: 1.26, 9.58; P = 0.016). Conclusion Tapering TNFi by 33% has no impact on disease flares and appears practical in patients in sustained remission and low disease activity states. Trail registration EudraCT, https://www.clinicaltrialsregister.eu, 2010-020738-24; ISRCTN registry, https://www.isrctn.com, 28955701 PMID:28968858

Wordless intervention for epilepsy in learning disabilities (WIELD): study protocol for a randomized controlled feasibility trial.

PubMed

Durand, Marie-Anne; Gates, Bob; Parkes, Georgina; Zia, Asif; Friedli, Karin; Barton, Garry; Ring, Howard; Oostendorp, Linda; Wellsted, David

2014-11-20

Epilepsy is the most common neurological problem that affects people with learning disabilities. The high seizure frequency, resistance to treatments, associated skills deficit and co-morbidities make the management of epilepsy particularly challenging for people with learning disabilities. The Books Beyond Words booklet for epilepsy uses images to help people with learning disabilities manage their condition and improve quality of life. Our aim is to conduct a randomized controlled feasibility trial exploring key methodological, design and acceptability issues, in order to subsequently undertake a large-scale randomized controlled trial of the Books Beyond Words booklet for epilepsy. We will use a two-arm, single-centre randomized controlled feasibility design, over a 20-month period, across five epilepsy clinics in Hertfordshire, United Kingdom. We will recruit 40 eligible adults with learning disabilities and a confirmed diagnosis of epilepsy and will randomize them to use either the Books Beyond Words booklet plus usual care (intervention group) or to receive routine information and services (control group). We will collect quantitative data about the number of eligible participants, number of recruited participants, demographic data, discontinuation rates, variability of the primary outcome measure (quality of life: Epilepsy and Learning Disabilities Quality of Life scale), seizure severity, seizure control, intervention's patterns of use, use of other epilepsy-related information, resource use and the EQ-5D-5L health questionnaire. We will also gather qualitative data about the feasibility and acceptability of the study procedures and the Books Beyond Words booklet. Ethical approval for this study was granted on 28 April 2014, by the Wales Research Ethics Committee 5. Recruitment began on 1 July 2014. The outcomes of this feasibility study will be used to inform the design and methodology of a definitive study, adequately powered to determine the impact of the Books Beyond Words intervention to improve the management of epilepsy in people with learning disabilities. http://ISRCTN80067039 (Date of ISRCTN assignation: 23 April 2014).

Reproduction of overall spontaneous pain pattern by manual stimulation of active myofascial trigger points in fibromyalgia patients

PubMed Central

2011-01-01

Introduction It has previously been reported that local and referred pain from active myofascial trigger points (MTPs) in the neck and shoulder region contribute to fibromyalgia (FM) pain and that the pain pattern induced from active MTPs can reproduce parts of the spontaneous clinical FM pain pattern. The current study investigated whether the overall spontaneous FM pain pattern can be reproduced by local and referred pain from active MTPs located in different muscles. Methods A spontaneous pain pattern in FM was recorded in 30 FM patients and 30 healthy subjects served as controls. Local and referred pain patterns induced from active (patients) and latent (controls) MTPs were recorded following manual stimulation. The existence of MTPs was confirmed by intramuscular electromyographical registration of spontaneous electrical activity. Results Local and referred pain areas induced from key active MTPs in FM were larger than pain areas from latent MTPs in healthy controls (P < 0.001), but were similar to the overall spontaneous FM pain area in FM (P > 0.05). The induced pain area was positively associated with current spontaneous pain intensity in FM (P < 0.01). The locations of key active MTPs in FM patients were found to have latent MTPs in healthy subjects. The muscles containing key active MTPs in FM are often observed in the muscles of extensor digitorum, trapezius, infraspinatus in the upper part of the body and of quadratus lumborum, gluteus medius in the lower part of the body. Conclusions The overall spontaneous FM pain pattern can be reproduced by mechanical stimulation of active MTPs located in different muscles, suggesting that fibromyalgia pain is largely composed of pain arising from muscle pain and spasm. Targeting active MTPs and related perpetuating factors may be an important strategy in FM pain control. Trial registration ISRCTN ISRCTN43167547. PMID:21426569

A Randomized Controlled Trial of Storytelling as a Communication Tool

PubMed Central

Hartling, Lisa; Scott, Shannon D.; Johnson, David W.; Bishop, Ted; Klassen, Terry P.

2013-01-01

Introduction Stories may be an effective tool to communicate with patients because of their ability to engage the reader. Our objective was to evaluate the effectiveness of story booklets compared to standard information sheets for parents of children attending the emergency department (ED) with a child with croup. Methods Parents were randomized to receive story booklets (n=208) or standard information sheets (n=205) during their ED visit. The primary outcome was change in anxiety between triage to ED discharge as measured by the State-Trait Anxiety Inventory. Follow-up telephone interviews were conducted at 1 and 3 days after discharge, then every other day until 9 days (or until resolution of symptoms), and at 1 year. Secondary outcomes included: expected future anxiety, event impact, parental knowledge, satisfaction, decision regret, healthcare utilization, time to symptom resolution. Results There was no significant difference in the primary outcome of change in parental anxiety between recruitment and ED discharge (change of 5 points for the story group vs. 6 points for the comparison group, p=0.78). The story group showed significantly greater decision regret regarding their decision to go to the ED (p<0.001): 6.7% of the story group vs. 1.5% of the comparison group strongly disagreed with the statement “I would go for the same choice if I had to do it over again”. The story group reported shorter time to resolution of symptoms (mean 3.7 days story group vs. 4.0 days comparison group, median 3 days both groups; log rank test, p=0.04). No other outcomes were different between study groups. Conclusions Stories about parent experiences managing a child with croup did not reduce parental anxiety. The story group showed significantly greater decision regret and quicker time to resolution of symptoms. Further research is needed to better understand whether stories can be effective in improving patient-important outcomes. Trial Registration Current Controlled Trials, ISRCTN39642997 (http://www.controlled-trials.com/ISRCTN39642997) PMID:24204974

Case management to increase quality of life after cancer treatment: a randomized controlled trial.

PubMed

Scherz, Nathalie; Bachmann-Mettler, Irène; Chmiel, Corinne; Senn, Oliver; Boss, Nathalie; Bardheci, Katarina; Rosemann, Thomas

2017-03-28

Case management has been shown to be beneficial in phases of cancer screening and treatment. After treatment is completed, patients experience a loss of support due to reduced contact with medical professionals. Case management has the potential to offer continuity of care and ease re-entry to normal life. We therefore aim to investigate the effect of case management on quality of life in early cancer survivors. Between 06/2010 and 07/2012, we randomized 95 patients who had just completed cancer treatment in 11 cancer centres in the canton of Zurich, Switzerland. Patients in the case management group met with a case manager at least three times over 12 months. Patient-reported outcomes were assessed after 3, 6 and 12 months using the Functional Assessment of Cancer Therapy (FACT-G) scale, the Patient Assessment of Chronic Illness Care (PACIC) and the Self-Efficacy scale. The change in FACT-G over 12 months was significantly greater in the case management group than in the control group (16.2 (SE 2.0) vs. 9.2 (SE 1.5) points, P = 0.006). The PACIC score increased by 0.20 (SE 0.14) in the case management group and decreased by 0.29 (SE 0.12) points in the control group (P = 0.009). Self-Efficacy increased by 3.1 points (SE 0.9) in the case management group and by 0.7 (SE 0.8) points in the control group (P = 0.049). Case management has the potential to improve quality of life, to ease re-entry to normal life and to address needs for continuity of care in early cancer survivors. The study has been submitted to the ISRCTN register under the name "Case Management in Oncology Rehabilitation" on the 12th of October 2010 and retrospectively registered under the number ISRCTN41474586 on the 24th of November 2010.

B vitamin and/or ω-3 fatty acid supplementation and cancer: ancillary findings from the supplementation with folate, vitamins B6 and B12, and/or omega-3 fatty acids (SU.FOL.OM3) randomized trial.

PubMed

Andreeva, Valentina A; Touvier, Mathilde; Kesse-Guyot, Emmanuelle; Julia, Chantal; Galan, Pilar; Hercberg, Serge

2012-04-09

To advance knowledge about the cancer-chemopreventive potential of individual nutrients, we investigated the effects of B vitamin and/or ω-3 fatty acid supplements on cancer outcomes among survivors of cardiovascular disease. This was an ancillary study of the Supplementation With Folate, Vitamins B(6) and B(12) and/or Omega-3 Fatty Acids (SU.FOL.OM3) secondary prevention trial (2003-2009). In all, 2501 individuals aged 45 to 80 years were randomized in a 2 × 2 factorial design to one of the following 4 daily supplementation groups: (1) 5-methyltetrahydrofolate (0.56 mg), pyridoxine hydrochloride (vitamin B(6); 3 mg) and cyanocobalamin (vitamin B(12); 0.02 mg); (2) eicosapentaenoic and docosahexaenoic acid (600 mg) in a 2:1 ratio; (3) B vitamins and ω-3 fatty acids; or (4) placebo. Overall and sex-specific hazard ratios (HRs) and 95% CIs regarding the cancer outcomes were estimated with Cox proportional hazards models. After 5 years of supplementation, incident cancer was validated in 7.0% of the sample (145 events in men and 29 in women), and death from cancer occurred in 2.3% of the sample. There was no association between cancer outcomes and supplementation with B vitamins (HR, 1.15 [95% CI, 0.85-1.55]) and/or ω-3 fatty acids (HR, 1.17 [95% CI, 0.87-1.58]). There was a statistically significant interaction of treatment by sex, with no effect of treatment on cancer risk among men and increased cancer risk among women for ω-3 fatty acid supplementation (HR, 3.02 [95% CI, 1.33-6.89]). We found no beneficial effects of supplementation with relatively low doses of B vitamins and/or ω-3 fatty acids on cancer outcomes in individuals with prior cardiovascular disease. Trial Registration  isrctn.org Identifier: ISRCTN41926726.

Participants' preference for type of leaflet used to feed back the results of a randomised trial: a survey.

PubMed

Brealey, Stephen; Andronis, Lazaros; Dennis, Laura; Atwell, Christine; Bryan, Stirling; Coulton, Simon; Cox, Helen; Cross, Ben; Fylan, Fiona; Garratt, Andrew; Gilbert, Fiona; Gillan, Maureen; Hendry, Maggie; Hood, Kerenza; Houston, Helen; King, David; Morton, Veronica; Robling, Michael; Russell, Ian; Wilkinson, Clare

2010-12-01

Hundreds of thousands of volunteers take part in medical research, but many will never hear from researchers about what the study revealed. There is a growing demand for the results of randomised trials to be fed back to research participants both for ethical research practice and for ensuring their co-operation in a trial. This study aims to determine participants' preferences for type of leaflet (short versus long) used to summarise the findings of a randomised trial; and to test whether certain characteristics explained participants' preferences. 553 participants in a randomised trial about General Practitioners' access to Magnetic Resonance Imaging for patients presenting with suspected internal derangement of the knee were asked in the final follow-up questionnaire whether they would like to be fed back the results of the trial. Participants who agreed to this were included in a postal questionnaire survey asking about their preference, if any, between a short and a long leaflet and what it was about the leaflet that they preferred. Multinomial logistic regression was used to test whether certain demographics of responding participants along with treatment group explained whether a participant had a preference for type of leaflet or no preference. Of the participants who returned the final follow-up questionnaire, 416 (88%) agreed to receive the results of the trial. Subsequently 132 (32%) participants responded to the survey. Most participants preferred the longer leaflet (55%) and the main reasons for this were the use of technical information (94%) and diagrams (89%). There was weak evidence to suggest that gender might explain whether participants have a preference for type of leaflet or not (P = 0.084). Trial participants want to receive feed back about the results and appear to prefer a longer leaflet. Males and females might require information to be communicated to them differently and should be the focus of further research. The trial is registered with http://www.isrctn.org/ and ID is ISRCTN76616358.

Arterial Obstruction on Computed Tomographic or Magnetic Resonance Angiography and Response to Intravenous Thrombolytics in Ischemic Stroke.

PubMed

Mair, Grant; von Kummer, Rüdiger; Adami, Alessandro; White, Philip M; Adams, Matthew E; Yan, Bernard; Demchuk, Andrew M; Farrall, Andrew J; Sellar, Robin J; Sakka, Eleni; Palmer, Jeb; Perry, David; Lindley, Richard I; Sandercock, Peter A G; Wardlaw, Joanna M

2017-02-01

Computed tomographic angiography and magnetic resonance angiography are used increasingly to assess arterial patency in patients with ischemic stroke. We determined which baseline angiography features predict response to intravenous thrombolytics in ischemic stroke using randomized controlled trial data. We analyzed angiograms from the IST-3 (Third International Stroke Trial), an international, multicenter, prospective, randomized controlled trial of intravenous alteplase. Readers, masked to clinical, treatment, and outcome data, assessed prerandomization computed tomographic angiography and magnetic resonance angiography for presence, extent, location, and completeness of obstruction and collaterals. We compared angiography findings to 6-month functional outcome (Oxford Handicap Scale) and tested for interactions with alteplase, using ordinal regression in adjusted analyses. We also meta-analyzed all available angiography data from other randomized controlled trials of intravenous thrombolytics. In IST-3, 300 patients had prerandomization angiography (computed tomographic angiography=271 and magnetic resonance angiography=29). On multivariable analysis, more extensive angiographic obstruction and poor collaterals independently predicted poor outcome (P<0.01). We identified no significant interaction between angiography findings and alteplase effect on Oxford Handicap Scale (P≥0.075) in IST-3. In meta-analysis (5 trials of alteplase or desmoteplase, including IST-3, n=591), there was a significantly increased benefit of thrombolytics on outcome (odds ratio>1 indicates benefit) in patients with (odds ratio, 2.07; 95% confidence interval, 1.18-3.64; P=0.011) versus without (odds ratio, 0.88; 95% confidence interval, 0.58-1.35; P=0.566) arterial obstruction (P for interaction 0.017). Intravenous thrombolytics provide benefit to stroke patients with computed tomographic angiography or magnetic resonance angiography evidence of arterial obstruction, but the sample was underpowered to demonstrate significant treatment benefit or harm among patients with apparently patent arteries. URL: http://www.isrctn.com. Unique identifier: ISRCTN25765518. © 2016 The Authors.

A randomized controlled trial of storytelling as a communication tool.

PubMed

Hartling, Lisa; Scott, Shannon D; Johnson, David W; Bishop, Ted; Klassen, Terry P

2013-01-01

Stories may be an effective tool to communicate with patients because of their ability to engage the reader. Our objective was to evaluate the effectiveness of story booklets compared to standard information sheets for parents of children attending the emergency department (ED) with a child with croup. Parents were randomized to receive story booklets (n=208) or standard information sheets (n=205) during their ED visit. The primary outcome was change in anxiety between triage to ED discharge as measured by the State-Trait Anxiety Inventory. Follow-up telephone interviews were conducted at 1 and 3 days after discharge, then every other day until 9 days (or until resolution of symptoms), and at 1 year. Secondary outcomes included: expected future anxiety, event impact, parental knowledge, satisfaction, decision regret, healthcare utilization, time to symptom resolution. There was no significant difference in the primary outcome of change in parental anxiety between recruitment and ED discharge (change of 5 points for the story group vs. 6 points for the comparison group, p=0.78). The story group showed significantly greater decision regret regarding their decision to go to the ED (p<0.001): 6.7% of the story group vs. 1.5% of the comparison group strongly disagreed with the statement "I would go for the same choice if I had to do it over again". The story group reported shorter time to resolution of symptoms (mean 3.7 days story group vs. 4.0 days comparison group, median 3 days both groups; log rank test, p=0.04). No other outcomes were different between study groups. Stories about parent experiences managing a child with croup did not reduce parental anxiety. The story group showed significantly greater decision regret and quicker time to resolution of symptoms. Further research is needed to better understand whether stories can be effective in improving patient-important outcomes. Current Controlled Trials, ISRCTN39642997 (http://www.controlled-trials.com/ISRCTN39642997).

Satisfaction and safety using dexmedetomidine or propofol sedation during endoscopic oesophageal procedures: A randomised controlled trial.

PubMed

Eberl, Susanne; Preckel, Benedikt; Bergman, Jacques J; van Dieren, Susan; Hollmann, Markus W

2016-09-01

Dexmedetomidine possesses anxiolytic and hypnotic properties without respiratory side-effects, making it theoretically an ideal sedative agent for endoscopic procedures. We aimed to compare satisfaction and safety among outpatients receiving sedation with dexmedetomidine or propofol for endoscopic oesophageal procedures. A randomised controlled study. Endoscopic intervention suite at the Academic Medical Centre in Amsterdam, Netherlands. Patients aged at least 18 years, and American Society of Anesthesiologists' physical status 1 to 3. Total 63 patients were randomised to receive either dexmedetomidine (D) or propofol (P). Pain was treated with alfentanil in both groups. The primary outcomes were patients' and endoscopists' satisfaction levels measured by validated questionnaires (1 = very dissatisfied; 7 = highly satisfied). A secondary outcome was safety, determined by blood pressure, heart rate and oxygen saturation during and after the procedure, and respiratory rate and noninvasive cardiac output during the procedure. Satisfaction of patients [median (IQR); group D, 5.0 (3.75 to 5.75) vs. group P, 6.25 (5.3 to 6.5)] and satisfaction of gastroenterologists [group D, 5.0 (4.4 to 5.8) vs. group P, 6.0 (5.4 to 6.0)] were lower in group D (both P < 0.001). More patients in group D would not recommend this form of sedation to one of their friends (group D, 15 of 32 vs. group P, 1 of 31; P < 0.001). Total 30 min after the procedure, heart rate [group D, 60 bpm (52 to 69) vs. group P, 70 bpm (60 to 81), P = 0.031] and SBP group D, 112 mmHg (92 to 132) vs. group P, 120 mmHg (108 to 132); P = 0.013] were significantly lower after dexmedetomidine sedation. There were no other differences in safety between groups. Compared with propofol, sedation with dexmedetomidine resulted in less satisfaction, and caused prolonged haemodynamic depression after endoscopic oesophageal procedures. ISRCTN Register (ISRCTN 68599804).

The effects of housing stability on service use among homeless adults with mental illness in a randomized controlled trial of housing first.

PubMed

Kerman, Nick; Sylvestre, John; Aubry, Tim; Distasio, Jino

2018-03-20

Housing First is an effective intervention to stably house and alter service use patterns in a large proportion of homeless people with mental illness. However, it is unknown whether there are differences in the patterns of service use over time among those who do or do not become stably housed and what effect, if any, Housing First has on these differing service use patterns. This study explored changes in the service use of people with mental illness who received Housing First compared to standard care, and how patterns of use differed among people who did and did not become stably housed. The study design was a multi-site randomized controlled trial of Housing First, a supported housing intervention. 2039 participants (Housing First: n = 1131; standard care: n = 908) were included in this study. Outcome variables include nine types of self-reported service use over 24 months. Linear mixed models examined what effects the intervention and housing stability had on service use. Participants who achieved housing stability, across the two groups, had decreased use of inpatient psychiatric hospitals and increased use of food banks. Within the Housing First group, unstably housed participants spent more time in prison over the study period. The Housing First and standard care groups both had decreased use of emergency departments and homeless shelters. The temporal service use changes that occurred as homeless people with mental illness became stably housed are similar for those receiving Housing First or standard care, with the exception of time in prison. Service use patterns, particularly with regard to psychiatric hospitalizations and time in prison, may signify persons who are at-risk of recurrent homelessness. Housing support teams should be alert to the impacts of stay-based services, such as hospitalizations and incarcerations, on housing stability and offer an increased level of support to tenants during critical periods, such as discharges. ISRCTN. ISRCTN42520374 . Registered 18 August 2009.

Rationale, design and methods of the Study of Work and Pain (SWAP): a cluster randomised controlled trial testing the addition of a vocational advice service to best current primary care for patients with musculoskeletal pain (ISRCTN 52269669).

PubMed

Bishop, Annette; Wynne-Jones, Gwenllian; Lawton, Sarah A; van der Windt, Danielle; Main, Chris; Sowden, Gail; Burton, A Kim; Lewis, Martyn; Jowett, Sue; Sanders, Tom; Hay, Elaine M; Foster, Nadine E

2014-07-10

Musculoskeletal pain is a major contributor to short and long term work absence. Patients seek care from their general practitioner (GP) and yet GPs often feel ill-equipped to deal with work issues. Providing a vocational case management service in primary care, to support patients with musculoskeletal problems to remain at or return to work, is one potential solution but requires robust evaluation to test clinical and cost-effectiveness. This protocol describes a cluster randomised controlled trial, with linked qualitative interviews, to investigate the effect of introducing a vocational advice service into general practice, to provide a structured approach to managing work related issues in primary care patients with musculoskeletal pain who are absent from work or struggling to remain in work. General practices (n = 6) will be randomised to offer best current care or best current care plus a vocational advice service. Adults of working age who are absent from or struggling to remain in work due to a musculoskeletal pain problem will be invited to participate and 330 participants will be recruited. Data collection will be through patient completed questionnaires at baseline, 4 and 12 months. The primary outcome is self-reported work absence at 4 months. Incremental cost-utility analysis will be undertaken to calculate the cost per additional QALY gained and incremental net benefits. A linked interview study will explore the experiences of the vocational advice service from the perspectives of GPs, nurse practitioners (NPs), patients and vocational advisors. This paper presents the rationale, design, and methods of the Study of Work And Pain (SWAP) trial. The results of this trial will provide evidence to inform primary care practice and guide the development of services to provide support for musculoskeletal pain patients with work-related issues. Current Controlled Trials ISRCTN52269669.

The UK Cardiac and Vascular Surgery Interventional Anaemia Response (CAVIAR) Study: protocol for an observational cohort study to determine the impact and effect of preoperative anaemia management in cardiac and vascular surgical patients

PubMed Central

Chau, Marisa; Richards, Toby; Evans, Caroline; Butcher, Anna; Collier, Timothy; Klein, Andrew

2017-01-01

Introduction Preoperative anaemia is linked to poor postsurgical outcome, longer hospital stays, greater risk of complications and mortality. Currently in the UK, some sites have developed anaemia clinics or pathways that use intravenous iron to correct iron deficiency anaemia prior to surgery as their standard of care. Although intravenous iron has been observed to be effective in a variety of patient settings, there is insufficient evidence in its use in cardiac and vascular patients. The aim of this study is to observe the impact and effect of anaemia and its management in patients undergoing cardiac and vascular surgery. In addition, the UK Cardiac and Vascular Surgery Interventional Anaemia Response (CAVIAR) Study is also a feasibility study with the aim to establish anaemia management pathways in the preoperative setting to inform the design of future randomised controlled trials. Methods and analysis The UK CAVIAR Study is a multicentre, stepped, observational study, in patients awaiting major cardiac or vascular surgery. We will be examining different haematological variables (especially hepcidin), functional capacity and patient outcome. Patients will be compared based on their anaemia status, whether they received intravenous iron in accordance to their hospital’s preoperative pathway, and their disease group. The primary outcomes are the change in haemoglobin levels from baseline (before treatment) to before surgery; and the number of successful patients recruited and consented (feasibility). The secondary outcomes will include changes in biomarkers of iron deficiency, length of stay, quality of life and postoperative recovery. Ethics and dissemination The study protocol was approved by the London-Westminster Research Ethics Committee (15/LO/1569, 27 November 2015). NHS approval was also obtained with each hospital trust. The findings of the study will be published in peer-reviewed journals. Trial registration number Clinical Trials registry (NCT02637102) and the ISRCTN registry (ISRCTN55032357). PMID:28420664

Global abnormalities in lymphatic function following systemic therapy in patients with breast cancer.

PubMed

Bains, S K; Peters, A M; Zammit, C; Ryan, N; Ballinger, J; Glass, D M; Allen, S; Stanton, A W B; Mortimer, P S; Purushotham, A D

2015-04-01

Breast cancer-related lymphoedema (BCRL) is a result of interaction between several pathophysiological processes, and is not simply a 'stopcock' effect resulting from removal of axillary lymph nodes. The aim of this study was to test the hypothesis that there is a constitutional 'global' lymphatic dysfunction in patients who develop BCRL. Lower-limb lymphoscintigraphy was performed in 30 women who had undergone axillary lymph node dissection at least 3 years previously, of whom 15 had BCRL and 15 did not. No patient had any clinical abnormality of the lower limb. The control group comprised 24 women with no history of cancer or lower-limb lymphoedema. (99m) Tc-Nanocoll was injected subcutaneously into the first webspace of each foot, followed by whole-body imaging. Scans were reported as abnormal if there was delay in lymph transport or rerouting through skin or deep system. Quantification was expressed as the percentage injected activity accumulating in ilioinguinal nodes. Mean(s.d.) ilioinguinal nodal accumulation at 150 min was significantly lower in women with BCRL than in those without (2·7(2·5) versus 5·9(4·8) per cent respectively; P = 0·006). Abnormal findings on lower-limb lymphoscintigraphy were observed in 17 of the 30 patients: ten of the 15 women who had BCRL and seven of the 15 who did not. None of the 24 control subjects had abnormal scan findings. Women with BCRL had reduced lower-limb lymph drainage, supporting the hypothesis of a predisposition to BCRL. A surprisingly high proportion of patients with breast cancer also demonstrated lymphatic dysfunction, despite clinically normal lower limbs. Possible explanations could be a systemic effect of breast cancer or its treatment, or an unidentified association between breast cancer and lymphatic dysfunction. ISRCTN84866416 ( http://www.isrctn.com). © 2015 BJS Society Ltd Published by John Wiley & Sons Ltd.

Direct versus Indirect Treatment for Preschool Children who Stutter: The RESTART Randomized Trial.

PubMed

de Sonneville-Koedoot, Caroline; Stolk, Elly; Rietveld, Toni; Franken, Marie-Christine

2015-01-01

Stuttering is a common childhood disorder. There is limited high quality evidence regarding options for best treatment. The aim of the study was to compare the effectiveness of direct treatment with indirect treatment in preschool children who stutter. In this multicenter randomized controlled trial with an 18 month follow-up, preschool children who stutter who were referred for treatment were randomized to direct treatment (Lidcombe Program; n = 99) or indirect treatment (RESTART-DCM treatment; n = 100). Main inclusion criteria were age 3-6 years, ≥3% syllables stuttered (%SS), and time since onset ≥6 months. The primary outcome was the percentage of non-stuttering children at 18 months. Secondary outcomes included stuttering frequency (%SS), stuttering severity ratings by the parents and therapist, severity rating by the child, health-related quality of life, emotional and behavioral problems, and speech attitude. Percentage of non-stuttering children for direct treatment was 76.5% (65/85) versus 71.4% (65/91) for indirect treatment (Odds Ratio (OR), 0.6; 95% CI, 0.1-2.4, p = .42). At 3 months, children treated by direct treatment showed a greater decline in %SS (significant interaction time x therapy: β = -1.89; t(282.82) = -2.807, p = .005). At 18 months, stuttering frequency was 1.2% (SD 2.1) for direct treatment and 1.5% (SD 2.1) for indirect treatment. Direct treatment had slightly better scores on most other secondary outcome measures, but no differences between treatment approaches were significant. Direct treatment decreased stuttering more quickly during the first three months of treatment. At 18 months, however, clinical outcomes for direct and indirect treatment were comparable. These results imply that at 18 months post treatment onset, both treatments are roughly equal in treating developmental stuttering in ways that surpass expectations of natural recovery. Follow-up data are needed to confirm these findings in the longer term. isrctn.org ISRCTN24362190.

Auditory training changes temporal lobe connectivity in 'Wernicke's aphasia': a randomised trial.

PubMed

Woodhead, Zoe Vj; Crinion, Jennifer; Teki, Sundeep; Penny, Will; Price, Cathy J; Leff, Alexander P

2017-07-01

Aphasia is one of the most disabling sequelae after stroke, occurring in 25%-40% of stroke survivors. However, there remains a lack of good evidence for the efficacy or mechanisms of speech comprehension rehabilitation. This within-subjects trial tested two concurrent interventions in 20 patients with chronic aphasia with speech comprehension impairment following left hemisphere stroke: (1) phonological training using 'Earobics' software and (2) a pharmacological intervention using donepezil, an acetylcholinesterase inhibitor. Donepezil was tested in a double-blind, placebo-controlled, cross-over design using block randomisation with bias minimisation. The primary outcome measure was speech comprehension score on the comprehensive aphasia test. Magnetoencephalography (MEG) with an established index of auditory perception, the mismatch negativity response, tested whether the therapies altered effective connectivity at the lower (primary) or higher (secondary) level of the auditory network. Phonological training improved speech comprehension abilities and was particularly effective for patients with severe deficits. No major adverse effects of donepezil were observed, but it had an unpredicted negative effect on speech comprehension. The MEG analysis demonstrated that phonological training increased synaptic gain in the left superior temporal gyrus (STG). Patients with more severe speech comprehension impairments also showed strengthening of bidirectional connections between the left and right STG. Phonological training resulted in a small but significant improvement in speech comprehension, whereas donepezil had a negative effect. The connectivity results indicated that training reshaped higher order phonological representations in the left STG and (in more severe patients) induced stronger interhemispheric transfer of information between higher levels of auditory cortex.Clinical trial registrationThis trial was registered with EudraCT (2005-004215-30, https:// eudract .ema.europa.eu/) and ISRCTN (68939136, http://www.isrctn.com/). © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

The Impact of Supplemental Antioxidants on Visual Function in Nonadvanced Age-Related Macular Degeneration: A Head-to-Head Randomized Clinical Trial.

PubMed

Akuffo, Kwadwo Owusu; Beatty, Stephen; Peto, Tunde; Stack, Jim; Stringham, Jim; Kelly, David; Leung, Irene; Corcoran, Laura; Nolan, John M

2017-10-01

The purpose of this study was to evaluate the impact of supplemental macular carotenoids (including versus not including meso-zeaxanthin) in combination with coantioxidants on visual function in patients with nonadvanced age-related macular degeneration. In this study, 121 participants were randomly assigned to group 1 (Age-Related Eye Disease Study 2 formulation with a low dose [25 mg] of zinc and an addition of 10 mg meso-zeaxanthin; n = 60) or group 2 (Age-Related Eye Disease Study 2 formulation with a low dose [25 mg] of zinc; n = 61). Visual function was assessed using best-corrected visual acuity, contrast sensitivity (CS), glare disability, retinal straylight, photostress recovery time, reading performance, and the National Eye Institute Visual Function Questionnaire-25. Macular pigment was measured using customized heterochromatic flicker photometry. There was a statistically significant improvement in the primary outcome measure (letter CS at 6 cycles per degree [6 cpd]) over time (P = 0.013), and this observed improvement was statistically comparable between interventions (P = 0.881). Statistically significant improvements in several secondary outcome visual function measures (letter CS at 1.2 and 2.4 cpd; mesopic and photopic CS at all spatial frequencies; mesopic glare disability at 1.5, 3, and 6 cpd; photopic glare disability at 1.5, 3, 6, and 12 cpd; photostress recovery time; retinal straylight; mean and maximum reading speed) were also observed over time (P < 0.05, for all), and were statistically comparable between interventions (P > 0.05, for all). Statistically significant increases in macular pigment at all eccentricities were observed over time (P < 0.0005, for all), and the degree of augmentation was statistically comparable between interventions (P > 0.05). Antioxidant supplementation in patients with nonadvanced age-related macular degeneration results in significant increases in macular pigment and improvements in CS and other measures of visual function. (Clinical trial, http://www.isrctn.com/ISRCTN13894787).

Does Telehealth Monitoring Identify Exacerbations of Chronic Obstructive Pulmonary Disease and Reduce Hospitalisations? An Analysis of System Data

PubMed Central

Bentley, Claire L; Mountain, Gail A

2017-01-01

Background The increasing prevalence and associated cost of treating chronic obstructive pulmonary disease (COPD) is unsustainable. Health care organizations are focusing on ways to support self-management and prevent hospital admissions, including telehealth-monitoring services capturing physiological and health status data. This paper reports on data captured during a pilot randomized controlled trial of telehealth-supported care within a community-based service for patients discharged from hospital following an exacerbation of their COPD. Objective The aim was to undertake the first analysis of system data to determine whether telehealth monitoring can identify an exacerbation of COPD, providing clinicians with an opportunity to intervene with timely treatment and prevent hospital readmission. Methods A total of 23 participants received a telehealth-supported intervention. This paper reports on the analysis of data from a telehealth monitoring system that captured data from two sources: (1) data uploaded both manually and using Bluetooth peripheral devices by the 23 participants and (2) clinical records entered as nursing notes by the clinicians. Rules embedded in the telehealth monitoring system triggered system alerts to be reviewed by remote clinicians who determined whether clinical intervention was required. We also analyzed data on the frequency and length (bed days) of hospital admissions, frequency of hospital Accident and Emergency visits that did not lead to hospital admission, and frequency and type of community health care service contacts—other than the COPD discharge service—for all participants for the duration of the intervention and 6 months postintervention. Results Patients generated 512 alerts, 451 of which occurred during the first 42 days that all participants used the equipment. Patients generated fewer alerts over time with typically seven alerts per day within the first 10 days and four alerts per day thereafter. They also had three times more days without alerts than with alerts. Alerts were most commonly triggered by reports of being more tired, having difficulty with self-care, and blood pressure being out of range. During the 8-week intervention, and for 6-month follow-up, eight of the 23 patients were hospitalized. Hospital readmission rates (2/23, 9%) in the first 28 days of service were lower than the 20% UK norm. Conclusions It seems that the clinical team can identify exacerbations based on both an increase in alerts and the types of system-generated alerts as evidenced by their efforts to provided treatment interventions. There was some indication that telehealth monitoring potentially delayed hospitalizations until after patients had been discharged from the service. We suggest that telehealth-supported care can fulfill an important role in enabling patients with COPD to better manage their condition and remain out of hospital, but adequate resourcing and timely response to alerts is a critical factor in supporting patients to remain at home. Trial Registration International Standard Randomized Controlled Trial Number (ISRCTN): 68856013; http://www.isrctn.com/ISRCTN68856013 (Archived by WebCite at http://www.webcitation.org/6ofApNB2e) PMID:28330829

The impact of individual Cognitive Stimulation Therapy (iCST) on cognition, quality of life, caregiver health, and family relationships in dementia: A randomised controlled trial.

PubMed

Orrell, Martin; Yates, Lauren; Leung, Phuong; Kang, Sujin; Hoare, Zoe; Whitaker, Chris; Burns, Alistair; Knapp, Martin; Leroi, Iracema; Moniz-Cook, Esme; Pearson, Stephen; Simpson, Stephen; Spector, Aimee; Roberts, Steven; Russell, Ian; de Waal, Hugo; Woods, Robert T; Orgeta, Vasiliki

2017-03-01

Cognitive stimulation therapy (CST) is a well-established group psychosocial intervention for people with dementia. There is evidence that home-based programmes of cognitive stimulation delivered by family caregivers may benefit both the person and the caregiver. However, no previous studies have evaluated caregiver-delivered CST. This study aimed to evaluate the effectiveness of a home-based, caregiver-led individual cognitive stimulation therapy (iCST) program in (i) improving cognition and quality of life (QoL) for the person with dementia and (ii) mental and physical health (well-being) for the caregiver. A single-blind, pragmatic randomised controlled trial (RCT) was conducted at eight study sites across the United Kingdom. The intervention and blinded assessment of outcomes were conducted in participants' homes. Three hundred fifty-six people with mild to moderate dementia and their caregivers were recruited from memory services and community mental health teams (CMHTs). Participants were randomly assigned to iCST (75, 30-min sessions) or treatment as usual (TAU) control over 25 wk. iCST sessions consisted of themed activities designed to be mentally stimulating and enjoyable. Caregivers delivering iCST received training and support from an unblind researcher. Primary outcomes were cognition (Alzheimer's Disease Assessment Scale-cognitive [ADAS-Cog]) and self-reported QoL (Quality of Life Alzheimer's Disease [QoL-AD]) for the person with dementia and general health status (Short Form-12 health survey [SF-12]) for the caregiver. Secondary outcomes included quality of the caregiving relationship from the perspectives of the person and of the caregiver (Quality of the Carer Patient Relationship Scale) and health-related QoL (European Quality of Life-5 Dimensions [EQ-5D]) for the caregiver. Intention to treat (ITT) analyses were conducted. At the post-test (26 wk), there were no differences between the iCST and TAU groups in the outcomes of cognition (mean difference [MD] = -0.55, 95% CI -2.00-0.90; p = 0.45) and self-reported QoL (MD = -0.02, 95% CI -1.22-0.82; p = 0.97) for people with dementia, or caregivers' general health status (MD = 0.13, 95% CI -1.65-1.91; p = 0.89). However, people with dementia receiving iCST rated the relationship with their caregiver more positively (MD = 1.77, 95% CI 0.26-3.28; p = 0.02), and iCST improved QoL for caregivers (EQ-5D, MD = 0.06, 95% CI 0.02-0.10; p = 0.01). Forty percent (72/180) of dyads allocated to iCST completed at least two sessions per week, with 22% (39/180) completing no sessions at all. Study limitations include low adherence to the intervention. There was no evidence that iCST has an effect on cognition or QoL for people with dementia. However, participating in iCST appeared to enhance the quality of the caregiving relationship and caregivers' QoL. The iCST trial is registered with the ISRCTN registry (identified ISRCTN 65945963, URL: DOI 10.1186/ISRCTN65945963).

Evaluation of a Web-Based E-Learning Platform for Brief Motivational Interviewing by Nurses in Cardiovascular Care: A Pilot Study

PubMed Central

Cossette, Sylvie; Heppell, Sonia; Boyer, Louise; Mailhot, Tanya; Simard, Marie-Josée; Tanguay, Jean-Francois

2016-01-01

Background Brief motivational interviewing (MI) can contribute to reductions in morbidity and mortality related to coronary artery disease, through health behavior change. Brief MI, unlike more intensive interventions, was proposed to meet the needs of clinicians with little spare time. While the provision of face-to-face brief MI training on a large scale is complicated, Web-based e-learning is promising because of the flexibility it offers. Objective The primary objective of this pilot study was to examine the feasibility and acceptability of a Web-based e-learning platform for brief MI (MOTIV@CŒUR), which was evaluated by nurses in cardiovascular care. The secondary objective was to assess the preliminary effect of the training on nurses’ perceived brief MI skills and self-reported clinical use of brief MI. Methods We conducted a single-group, pre-post pilot study involving nurses working in a coronary care unit to evaluate MOTIV@CŒUR, which is a Web-based e-learning platform for brief MI, consisting of two sessions lasting 30 and 20 minutes. MOTIV@CŒUR covers 4 real-life clinical situations through role-modeling videos showing nurse-client interactions. A brief introduction to MI is followed by role playing, during which a nurse practitioner evaluates clients’ motivation to change and intervenes according to the principles of brief MI. The clinical situations target smoking, medication adherence, physical activity, and diet. Nurses were asked to complete both Web-based training sessions asynchronously within 20 days, which allowed assessment of the feasibility of the intervention. Data regarding acceptability and preliminary effects (perceived skills in brief MI, and self-reported clinical use of conviction and confidence interventions) were self-assessed through Web-based questionnaires 30 days (±5 days) after the first session. Results We enrolled 27 women and 4 men (mean age 37, SD 9 years) in March 2016. Of the 31 participants, 24 (77%, 95% CI 63%–91%) completed both sessions in ≤20 days. At 30 days, 28 of the 31 participants (90%) had completed at least one session. The training was rated as highly acceptable, with the highest scores observed for information quality (mean 6.26, SD 0.60; scale 0–7), perceived ease of use (mean 6.16, SD 0.78; scale 0–7), and system quality (mean 6.15, SD 0.58; scale 0–7). Posttraining scores for self-reported clinical use of confidence interventions were higher than pretraining scores (mean 34.72, SD 6.29 vs mean 31.48, SD 6.75, respectively; P=.03; scale 10–50). Other results were nonsignificant. Conclusions Brief MI training using a Web-based e-learning platform including role-modeling videos is both feasible and acceptable according to cardiovascular care nurses. Further research is required to evaluate the e-learning platform in a randomized controlled trial. Trial Registration International Standard Randomized Controlled Trial Number (ISRCTN): 16510888; http://www.isrctn.com/ISRCTN16510888 (Archived by WebCite at http://www.webcitation.org/6jf7dr7bx) PMID:27539960

Integrated Care in Prostate Cancer (ICARE-P): Nonrandomized Controlled Feasibility Study of Online Holistic Needs Assessment, Linking the Patient and the Health Care Team.

PubMed

Nanton, Veronica; Appleton, Rebecca; Dale, Jeremy; Roscoe, Julia; Hamborg, Thomas; Ahmedzai, Sam H; Arvanitis, Theodoros N; Badger, Douglas; James, Nicholas; Mendelsohn, Richard; Khan, Omar; Parashar, Deepak; Patel, Prashant

2017-07-28

The potential of technology to aid integration of care delivery systems is being explored in a range of contexts across a variety of conditions in the United Kingdom. Prostate cancer is the most common cancer in UK men. With a 10-year survival rate of 84%, there is a need to explore innovative methods of care that are integrated between primary health care providers and specialist teams in order to address long-term consequences of the disease and its treatment as well as to provide continued monitoring for recurrence. Our aim was to test the feasibility of a randomized controlled trial to compare a model of prostate cancer continuing and follow-up care integration, underpinned by digital technology, with usual care in terms of clinical and cost-effectiveness, patient-reported outcomes, and experience. A first phase of the study has included development of an online adaptive prostate specific Holistic Needs Assessment system (HNA), training for primary care-based nurses, training of an IT peer supporter, and interviews with health care professionals and men with prostate cancer to explore views of their care, experience of technology, and views of the proposed intervention. In Phase 2, men in the intervention arm will complete the HNA at home to help identify and articulate concerns and share them with their health care professionals, in both primary and specialist care. Participants in the control arm will receive usual care. Outcomes including quality of life and well-being, prostate-specific concerns, and patient enablement will be measured 3 times over a 9-month period. Findings from phase 1 indicated strong support for the intervention among men, including those who had had little experience of digital technology. Men expressed a range of views on ways that the online system might be used within a clinical pathway. Health care professionals gave valuable feedback on how the output of the assessment might be presented to encourage engagement and uptake by clinical teams. Recruitment to the second phase of the study, the feasibility trial, commenced March 2017. To our knowledge, this study is the first in the United Kingdom to trial an online holistic needs assessment for men with prostate cancer, with data shared between patients and primary and secondary care providers. This study addresses recommendations in recent policy documents promoting the importance of data sharing and enhanced communication between care providers as a basis for care integration. We anticipate that this model of care will ultimately provide important benefits for both patients and the National Health Service. International Standard Randomized Controlled Trial Number (ISRCTN): 31380482; http://www.isrctn.com/ISRCTN31380482 (Archived by WebCite at http://www.webcitation.org/6s8I42u5N). ©Veronica Nanton, Rebecca Appleton, Jeremy Dale, Julia Roscoe, Thomas Hamborg, Sam H Ahmedzai, Theodoros N Arvanitis, Douglas Badger, Nicholas James, Richard Mendelsohn, Omar Khan, Deepak Parashar, Prashant Patel. Originally published in JMIR Research Protocols (http://www.researchprotocols.org), 28.07.2017.

Effectiveness of a Web-based Intervention for Problem Drinkers and Reasons for Dropout: Randomized Controlled Trial

PubMed Central

de Haan, Hein A; ter Huurne, Elke D; Becker, Eni S; de Jong, Cor AJ

2010-01-01

Background Online self-help interventions for problem drinkers show promising results, but the effectiveness of online therapy with active involvement of a therapist via the Internet only has not been examined. Objective The objective of our study was to evaluate an e-therapy program with active therapeutic involvement for problem drinkers, with the hypotheses that e-therapy would (1) reduce weekly alcohol consumption, and (2) improve health status. Reasons for dropout were also systematically investigated. Method In an open randomized controlled trial, Dutch-speaking problem drinkers in the general population were randomly assigned (in blocks of 8, according to a computer-generated random list) to the 3-month e-therapy program (n = 78) or the waiting list control group (n = 78). The e-therapy program consisted of a structured 2-part online treatment program in which the participant and the therapist communicated asynchronously, via the Internet only. Participants in the waiting list control group received “no-reply” email messages once every 2 weeks. The primary outcome measures were (1) the difference in the score on weekly alcohol consumption, and (2) the proportion of participants drinking under the problem drinking limit. Intention-to-treat analyses were performed using multiple imputations to deal with loss to follow-up. A dropout questionnaire was sent to anyone who did not complete the 3-month assessment. Reasons for dropout were independently assessed by the first and third author. Results Of the 156 individuals who were randomly assigned, 102 (65%) completed assessment at 3 months. In the intention-to-treat analyses, the e-therapy group (n = 78) showed a significantly greater decrease in alcohol consumption than those in the control group (n = 78) at 3 months. The e-therapy group decreased their mean weekly alcohol consumption by 28.8 units compared with 3.1 units in the control group, a difference in means of 25.6 units on a weekly basis (95% confidence interval 15.69-35.80, P < .001). The between-group effect size (pooled SD) was large (d = 1.21). The results also showed that 68% (53/78) of the e-therapy group was drinking less than 15 (females) or 22 (males) units a week, compared with 15% (12/78) in the control group (OR 12.0, number needed to treat 1.9, P < .001). Dropout analysis showed that the main reasons for dropouts (n = 54) were personal reasons unrelated to the e-therapy program, discomfort with the treatment protocol, and satisfaction with the positive results achieved. Conclusions E-therapy for problem drinking is an effective intervention that can be delivered to a large population who otherwise do not seek help for their drinking problem. Insight into reasons for dropout can help improve e-therapy programs to decrease the number of dropouts. Additional research is needed to directly compare the effectiveness of the e-therapy program with a face-to-face treatment program. Trial registration ISRCTN39104853; http://controlled-trials.com/ISRCTN39104853/ISRCTN39104853 (Archived by WebCite at http://www.webcitation.org/5uX1R5xfW) PMID:21163776

Côte d'Ivoire Dual Burden of Disease (CoDuBu): Study Protocol to Investigate the Co-occurrence of Chronic Infections and Noncommunicable Diseases in Rural Settings of Epidemiological Transition.

PubMed

Eze, Ikenna C; Esse, Clémence; Bassa, Fidèle K; Koné, Siaka; Acka, Felix; Yao, Loukou; Imboden, Medea; Jaeger, Fabienne N; Schindler, Christian; Dosso, Mireille; Laubhouet-Koffi, Véronique; Kouassi, Dinard; N'Goran, Eliézer K; Utzinger, Jürg; Bonfoh, Bassirou; Probst-Hensch, Nicole

2017-10-27

Individual-level concomitance of infectious diseases and noncommunicable diseases (NCDs) is poorly studied, despite the reality of this dual disease burden for many low- and middle-income countries (LMICs). This study protocol describes the implementation of a cohort and biobank aiming for a better understanding of interrelation of helminth and Plasmodium infections with NCD phenotypes like metabolic syndrome, hypertension, and diabetes. A baseline cross-sectional population-based survey was conducted over one year, in the Taabo health and demographic surveillance system (HDSS) in south-central Côte d'Ivoire. We randomly identified 1020 consenting participants aged ≥18 years in three communities (Taabo-Cité, Amani-Ménou, and Tokohiri) reflecting varying stages of epidemiological transition. Participants underwent health examinations consisting of NCD phenotyping (anthropometry, blood pressure, renal function, glycemia, and lipids) and infectious disease testing (infections with soil-transmitted helminths, schistosomes, and Plasmodium). Individuals identified to have elevated blood pressure, glucose, lipids, or with infections were referred to the central/national health center for diagnostic confirmation and treatment. Aliquots of urine, stool, and venous blood were stored in a biobank for future exposome/phenome research. In-person interviews on sociodemographic attributes, risk factors for infectious diseases and NCDs, medication, vaccinations, and health care were also conducted. Appropriate statistical techniques will be applied in exploring the concomitance of infectious diseases and NCDs and their determinants. Participants' consent for follow-up contact was obtained. Key results from this baseline study, which will be published in peer-reviewed literature, will provide information on the prevalence and co-occurrence of infectious diseases, NCDs, and their risk factors. The Taabo HDSS consists of rural and somewhat more urbanized areas, allowing for comparative studies at different levels of epidemiological transition. An HDSS setting is ideal as a basis for longitudinal studies since their sustainable field work teams hold close contact with the local population. The collaboration between research institutions, public health organizations, health care providers, and staff from the Taabo HDSS in this study assures that the synthesized evidence will feed into health policy towards integrated infectious disease-NCD management. The preparation of health systems for the dual burden of disease is pressing in low- and middle-income countries. The established biobank will strengthen the local research capacity and offer opportunities for biomarker studies to deepen the understanding of the cross-talk between infectious diseases and NCDs. International Standard Randomized Controlled Trials Number (ISRCTN): 87099939; http://www.isrctn.com/ISRCTN87099939 (Archived by WebCite at http://www.webcitation.org/6uLEs1EsX). ©Ikenna C Eze, Clémence Esse, Fidèle K Bassa, Siaka Koné, Felix Acka, Loukou Yao, Medea Imboden, Fabienne N Jaeger, Christian Schindler, Mireille Dosso, Véronique Laubhouet-Koffi, Dinard Kouassi, Eliézer K N’Goran, Jürg Utzinger, Bassirou Bonfoh, Nicole Probst-Hensch. Originally published in JMIR Research Protocols (http://www.researchprotocols.org), 27.10.2017.

Assessing Feasibility and Acceptability of Web-Based Enhanced Relapse Prevention for Bipolar Disorder (ERPonline): A Randomized Controlled Trial

PubMed Central

Dodd, Alyson L; Sawczuk, Adam P; Asar, Ozgur; Dagnan, Dave; Diggle, Peter J; Griffiths, Martin; Honary, Mahsa; Knowles, Dawn; Long, Rita; Morriss, Richard; Parker, Rob; Jones, Steven

2017-01-01

Background Interventions that teach people with bipolar disorder (BD) to recognize and respond to early warning signs (EWS) of relapse are recommended but implementation in clinical practice is poor. Objectives The objective of this study was to test the feasibility and acceptability of a randomized controlled trial (RCT) to evaluate a Web-based enhanced relapse prevention intervention (ERPonline) and to report preliminary evidence of effectiveness. Methods A single-blind, parallel, primarily online RCT (n=96) over 48 weeks comparing ERPonline plus usual treatment with “waitlist (WL) control” plus usual treatment for people with BD recruited through National Health Services (NHSs), voluntary organizations, and media. Randomization was independent, minimized on number of previous episodes (<8, 8-20, 21+). Primary outcomes were recruitment and retention rates, levels of intervention use, adverse events, and participant feedback. Process and clinical outcomes were assessed by telephone and Web and compared using linear models with intention-to-treat analysis. Results A total of 280 people registered interest online, from which 96 met inclusion criteria, consented, and were randomized (49 to WL, 47 to ERPonline) over 17 months, with 80% retention in telephone and online follow-up at all time points, except at week 48 (76%). Acceptability was high for both ERPonline and trial methods. ERPonline cost approximately £19,340 to create, and £2176 per year to host and maintain the site. Qualitative data highlighted the importance of the relationship that the users have with Web-based interventions. Differences between the group means suggested that access to ERPonline was associated with: a more positive model of BD at 24 weeks (10.70, 95% CI 0.90 to 20.5) and 48 weeks (13.1, 95% CI 2.44 to 23.93); increased monitoring of EWS of depression at 48 weeks (−1.39, 95% CI −2.61 to −0.163) and of hypomania at 24 weeks (−1.72, 95% CI −2.98 to −0.47) and 48 weeks (−1.61, 95% CI −2.92 to −0.30), compared with WL. There was no evidence of impact of ERPonline on clinical outcomes or medication adherence, but relapse rates across both arms were low (15%) and the sample remained high functioning throughout. One person died by suicide before randomization and 5 people in ERPonline and 6 in WL reported ideas of suicide or self-harm. None were deemed study related by an independent Trial Steering Committee (TSC). Conclusions ERPonline offers a cheap accessible option for people seeking ongoing support following successful treatment. However, given high functioning and low relapse rates in this study, testing clinical effectiveness for this population would require very large sample sizes. Building in human support to use ERPonline should be considered. Trial registration International Standard Randomized Controlled Trial Number (ISRCTN): 56908625; http://www.isrctn.com/ISRCTN56908625 (Archived by WebCite at http://www.webcitation.org/6of1ON2S0) PMID:28341619

Evaluation of a Web-Based E-Learning Platform for Brief Motivational Interviewing by Nurses in Cardiovascular Care: A Pilot Study.

PubMed

Fontaine, Guillaume; Cossette, Sylvie; Heppell, Sonia; Boyer, Louise; Mailhot, Tanya; Simard, Marie-Josée; Tanguay, Jean-Francois

2016-08-18

Brief motivational interviewing (MI) can contribute to reductions in morbidity and mortality related to coronary artery disease, through health behavior change. Brief MI, unlike more intensive interventions, was proposed to meet the needs of clinicians with little spare time. While the provision of face-to-face brief MI training on a large scale is complicated, Web-based e-learning is promising because of the flexibility it offers. The primary objective of this pilot study was to examine the feasibility and acceptability of a Web-based e-learning platform for brief MI (MOTIV@CŒUR), which was evaluated by nurses in cardiovascular care. The secondary objective was to assess the preliminary effect of the training on nurses' perceived brief MI skills and self-reported clinical use of brief MI. We conducted a single-group, pre-post pilot study involving nurses working in a coronary care unit to evaluate MOTIV@CŒUR, which is a Web-based e-learning platform for brief MI, consisting of two sessions lasting 30 and 20 minutes. MOTIV@CŒUR covers 4 real-life clinical situations through role-modeling videos showing nurse-client interactions. A brief introduction to MI is followed by role playing, during which a nurse practitioner evaluates clients' motivation to change and intervenes according to the principles of brief MI. The clinical situations target smoking, medication adherence, physical activity, and diet. Nurses were asked to complete both Web-based training sessions asynchronously within 20 days, which allowed assessment of the feasibility of the intervention. Data regarding acceptability and preliminary effects (perceived skills in brief MI, and self-reported clinical use of conviction and confidence interventions) were self-assessed through Web-based questionnaires 30 days (±5 days) after the first session. We enrolled 27 women and 4 men (mean age 37, SD 9 years) in March 2016. Of the 31 participants, 24 (77%, 95% CI 63%-91%) completed both sessions in ≤20 days. At 30 days, 28 of the 31 participants (90%) had completed at least one session. The training was rated as highly acceptable, with the highest scores observed for information quality (mean 6.26, SD 0.60; scale 0-7), perceived ease of use (mean 6.16, SD 0.78; scale 0-7), and system quality (mean 6.15, SD 0.58; scale 0-7). Posttraining scores for self-reported clinical use of confidence interventions were higher than pretraining scores (mean 34.72, SD 6.29 vs mean 31.48, SD 6.75, respectively; P=.03; scale 10-50). Other results were nonsignificant. Brief MI training using a Web-based e-learning platform including role-modeling videos is both feasible and acceptable according to cardiovascular care nurses. Further research is required to evaluate the e-learning platform in a randomized controlled trial. International Standard Randomized Controlled Trial Number (ISRCTN): 16510888; http://www.isrctn.com/ISRCTN16510888 (Archived by WebCite at http://www.webcitation.org/6jf7dr7bx).

Cost analysis of in-home telerehabilitation for post-knee arthroplasty.

PubMed

Tousignant, Michel; Moffet, Hélène; Nadeau, Sylvie; Mérette, Chantal; Boissy, Patrick; Corriveau, Hélène; Marquis, François; Cabana, François; Ranger, Pierre; Belzile, Étienne L; Dimentberg, Ronald

2015-03-31

Rehabilitation provided through home visits is part of the continuum of care after discharge from hospital following total knee arthroplasty (TKA). As demands for rehabilitation at home are growing and becoming more difficult to meet, in-home telerehabilitation has been proposed as an alternate service delivery method. However, there is a need for robust data concerning both the effectiveness and the cost of dispensing in-home telerehabilitation. The objective of this study was to document, analyze, and compare real costs of two service delivery methods: in-home telerehabilitation and conventional home visits. The economic analysis was conducted as part of a multicenter randomized controlled trial (RCT) on telerehabilitation for TKA, and involved data from 197 patients, post-TKA. Twice a week for 8 weeks, participants received supervised physiotherapy via two delivery methods, depending on their study group allocation: in-home telerehabilitation (TELE) and home-visit rehabilitation (VISIT). Patients were recruited from eight hospitals in the province of Quebec, Canada. The TELE group intervention was delivered by videoconferencing over high-speed Internet. The VISIT group received the same intervention at home. Costs related to the delivery of the two services (TELE and VISIT) were calculated. Student's t tests were used to compare costs per treatment between the two groups. To take distance into account, the two treatment groups were compared within distance strata using two-way analyses of variance (ANOVAs). The mean cost of a single session was Can $93.08 for the VISIT group (SD $35.70) and $80.99 for the TELE group (SD $26.60). When comparing both groups, real total cost analysis showed a cost differential in favor of the TELE group (TELE minus VISIT: -$263, 95% CI -$382 to -$143). However, when the patient's home was located less than 30 km round-trip from the health care center, the difference in costs between TELE and VISIT treatments was not significant (P=.25, .26, and .11 for the <10, 10-19, and 20-29 km strata, respectively). The cost of TELE treatments was lower than VISIT treatments when the distance was 30 km or more (30-49 km: $81<$103, P=.002; ≥50 km: $90<$152, P<.001). To our knowledge, this is the first study of the actual costs of in-home telerehabilitation covering all subcosts of telerehabilitation and distance between the health care center and the patient's home. The cost for a single session of in-home telerehabilitation compared to conventional home-visit rehabilitation was lower or about the same, depending on the distance between the patient's home and health care center. Under the controlled conditions of an RCT, a favorable cost differential was observed when the patient was more than 30 km from the provider. Stakeholders and program planners can use these data to guide decisions regarding introducing telerehabilitation as a new service in their clinic. International Standard Registered Clinical Study Number (ISRCTN): 66285945; http://www.isrctn.com/ISRCTN66285945 (Archived by WebCite at http://www.webcitation.org/6WlT2nuX4).

Findings of the Chronic Obstructive Pulmonary Disease-Sitting and Exacerbations Trial (COPD-SEAT) in Reducing Sedentary Time Using Wearable and Mobile Technologies With Educational Support: Randomized Controlled Feasibility Trial.

PubMed

Orme, Mark W; Weedon, Amie E; Saukko, Paula M; Esliger, Dale W; Morgan, Mike D; Steiner, Michael C; Downey, John W; Sherar, Lauren B; Singh, Sally J

2018-04-11

Targeting sedentary time post exacerbation may be more relevant than targeting structured exercise for individuals with chronic obstructive pulmonary disease. Focusing interventions on sitting less and moving more after an exacerbation may act as a stepping stone to increase uptake to pulmonary rehabilitation. The aim of this paper was to conduct a randomized trial examining trial feasibility and the acceptability of an education and self-monitoring intervention using wearable technology to reduce sedentary behavior for individuals with chronic obstructive pulmonary disease admitted to hospital for an acute exacerbation. Participants were recruited and randomized in hospital into 3 groups, with the intervention lasting 2 weeks post discharge. The Education group received verbal and written information about reducing their time in sedentary behavior, sitting face-to-face with a study researcher. The Education+Feedback group received the same education component along with real-time feedback on their sitting time, stand-ups, and steps at home through a waist-worn inclinometer linked to an app. Patients were shown how to use the technology by the same study researcher. The inclinometer also provided vibration prompts to encourage movement at patient-defined intervals of time. Patients and health care professionals involved in chronic obstructive pulmonary disease exacerbation care were interviewed to investigate trial feasibility and acceptability of trial design and methods. Main quantitative outcomes of trial feasibility were eligibility, uptake, and retention, and for acceptability, were behavioral responses to the vibration prompts. In total, 111 patients were approached with 33 patients recruited (11 Control, 10 Education, and 12 Education+Feedback). Retention at 2-week follow-up was 52% (17/33; n=6 for Control, n=3 for Education, and n=8 for Education+Feedback). No study-related adverse events occurred. Collectively, patients responded to 106 out of 325 vibration prompts from the waist-worn inclinometer (32.62%). Within 5 min of the prompt, 41% of responses occurred, with patients standing for a mean 1.4 (SD 0.8) min and walking for 0.4 (SD 0.3) min (21, SD 11, steps). Interviews indicated that being unwell and overwhelmed after an exacerbation was the main reason for not engaging with the intervention. Health care staff considered reducing sedentary behavior potentially attractive for patients but suggested starting the intervention as an inpatient. Although the data support that it was feasible to conduct the trial, modifications are needed to improve participant retention. The intervention was acceptable to most patients and health care professionals. International Standard Randomized Controlled Trial Number (ISRCTN) 13790881; http://www.isrctn.com/ISRCTN13790881 (Archived by WebCite at http://www.webcitation.org/6xmnRGjFf). ©Mark W Orme, Amie E Weedon, Paula M Saukko, Dale W Esliger, Mike D Morgan, Michael C Steiner, John W Downey, Lauren B Sherar, Sally J Singh. Originally published in JMIR Mhealth and Uhealth (http://mhealth.jmir.org), 11.04.2018.

Effects on Engagement and Health Literacy Outcomes of Web-Based Materials Promoting Physical Activity in People With Diabetes: An International Randomized Trial

PubMed Central

Rowsell, Alison; Stuart, Beth; Hayter, Victoria; Little, Paul; Ganahl, Kristin; Müller, Gabriele; Doyle, Gerardine; Chang, Peter; Lyles, Courtney R; Nutbeam, Don; Yardley, Lucy

2017-01-01

Background Developing accessible Web-based materials to support diabetes self-management in people with lower levels of health literacy is a continuing challenge. Objective The objective of this international study was to develop a Web-based intervention promoting physical activity among people with type 2 diabetes to determine whether audiovisual presentation and interactivity (quizzes, planners, tailoring) could help to overcome the digital divide by making digital interventions accessible and effective for people with all levels of health literacy. This study also aimed to determine whether these materials can improve health literacy outcomes for people with lower levels of health literacy and also be effective for people with higher levels of health literacy. Methods To assess the impact of interactivity and audiovisual features on usage, engagement, and health literacy outcomes, we designed two versions of a Web-based intervention (one interactive and one plain-text version of the same content) to promote physical activity in people with type 2 diabetes. We randomly assigned participants from the United Kingdom, Austria, Germany, Ireland, and Taiwan to either an interactive or plain-text version of the intervention in English, German, or Mandarin. Intervention usage was objectively recorded by the intervention software. Self-report measures were taken at baseline and follow-up (immediately after participants viewed the intervention) and included measures of health literacy, engagement (website satisfaction and willingness to recommend the intervention to others), and health literacy outcomes (diabetes knowledge, enablement, attitude, perceived behavioral control, and intention to undertake physical activity). Results In total, 1041 people took part in this study. Of the 1005 who completed health literacy information, 268 (26.67%) had intermediate or low levels of health literacy. The interactive intervention overall did not produce better outcomes than did the plain-text version. Participants in the plain-text intervention group looked at significantly more sections of the intervention (mean difference –0.47, 95% CI –0.64 to –0.30, P<.001), but this did not lead to better outcomes. Health literacy outcomes, including attitudes and intentions to engage in physical activity, significantly improved following the intervention for participants in both intervention groups. These improvements were similar across higher and lower health literacy levels and in all countries. Participants in the interactive intervention group had acquired more diabetes knowledge (mean difference 0.80, 95% CI 0.65-0.94, P<.001). Participants from both groups reported high levels of website satisfaction and would recommend the website to others. Conclusions Following established practice for simple, clear design and presentation and using a person-based approach to intervention development, with in-depth iterative feedback from users, may be more important than interactivity and audiovisual presentations when developing accessible digital health interventions to improve health literacy outcomes. ClinicalTrial International Standard Randomized Controlled Trial Number (ISRCTN): 43587048; http://www.isrctn.com/ISRCTN43587048. (Archived by WebCite at http://www.webcitation.org/6nGhaP9bv) PMID:28115299

Integration of Dust Prediction Systems and Vegetation Phenology to Track Pollen for Asthma Alerts in Public Health

NASA Technical Reports Server (NTRS)

Luvall, Jeffrey C.; Sprigg, W. A.; Huete, A.; Nickovic, S.; Pejanovic, G.; Levetin, E.; Van de water, P.; Myers, O.; Budge, A. M.; Krapfl, H.;

L-Arginine Affects Aerobic Capacity and Muscle Metabolism in MELAS (Mitochondrial Encephalomyopathy, Lactic Acidosis and Stroke-Like Episodes) Syndrome

PubMed Central

Rodan, Lance H.; Wells, Greg D.; Banks, Laura; Thompson, Sara; Schneiderman, Jane E.; Tein, Ingrid

2015-01-01

Objective To study the effects of L-arginine (L-Arg) on total body aerobic capacity and muscle metabolism as assessed by 31Phosphorus Magnetic Resonance Spectroscopy (31P-MRS) in patients with MELAS (Mitochondrial Encephalomyopathy with Lactic Acidosis and Stroke-like episodes) syndrome. Methods We performed a case control study in 3 MELAS siblings (m.3243A>G tRNAleu(UUR) in MTTL1 gene) with different % blood mutant mtDNA to evaluate total body maximal aerobic capacity (VO2peak) using graded cycle ergometry and muscle metabolism using 31P-MRS. We then ran a clinical trial pilot study in MELAS sibs to assess response of these parameters to single dose and a 6-week steady-state trial of oral L-Arginine. Results At baseline (no L-Arg), MELAS had lower serum Arg (p = 0.001). On 31P-MRS muscle at rest, MELAS subjects had increased phosphocreatine (PCr) (p = 0.05), decreased ATP (p = 0.018), and decreased intracellular Mg2+ (p = 0.0002) when compared to matched controls. With L-arginine therapy, the following trends were noted in MELAS siblings on cycle ergometry: (1) increase in mean % maximum work at anaerobic threshold (AT) (2) increase in % maximum heart rate at AT (3) small increase in VO2peak. On 31P-MRS the following mean trends were noted: (1) A blunted decrease in pH after exercise (less acidosis) (2) increase in Pi/PCr ratio (ADP) suggesting increased work capacity (3) a faster half time of PCr recovery (marker of mitochondrial activity) following 5 minutes of moderate intensity exercise (4) increase in torque. Significance These results suggest an improvement in aerobic capacity and muscle metabolism in MELAS subjects in response to supplementation with L-Arg. Intramyocellular hypomagnesemia is a novel finding that warrants further study. Classification of Evidence Class III evidence that L-arginine improves aerobic capacity and muscle metabolism in MELAS subjects. Trial Registration ClinicalTrials.gov NCT01603446. PMID:25993630

[The transrectus sheath preperitoneal procedure: a safe, effective and cheap surgical approach to inguinal hernia?].

PubMed

Prins, M W Wiesje; Voropai, D A Dasha; van Laarhoven, C J H M Kees; Akkersdijk, Willem L

2013-01-01

The main complication of surgery for inguinal hernia is chronic postoperative pain. This is often reported following the Lichtenstein procedure. A new, open surgical technique for the repair of inguinal hernia has been developed. This procedure is called the transrectus sheath preperitoneal procedure (TREPP). At TREPP a lightweight mesh with a ring made of memory metal is introduced into the preperitoneal space through the transrectus sheath. The first results of this operative technique are very promising: short operation time, short learning curve and not many patients with chronic postoperative pain. In a randomised, multi-centre study which will start mid-2013 (ISRCTN18591339), the TREPP procedure is compared with the transinguinal preperitoneal procedure. The primary outcome measure of this study is chronic postoperative pain.

Effect Evaluation of a Web-Based Coaching Intervention to Support Implementation of Sex Education Among Secondary School Teachers: Randomized Controlled Trial.

PubMed

Schutte, Lisette; Mevissen, Fraukje E F; Meijer, Suzanne; Paulussen, Theo; van Empelen, Pepijn; Kok, Gerjo

2018-06-18

The quality of implementation is important to ensure the effectiveness of behavioral change interventions in practice. Implementing such programs with completeness and adherence is not an automatic process and may require additional support. In school settings, the support teachers receive during implementation is often limited and appears to fall short when attempting to preserve completeness and adherence in program delivery. With the aim to improve completeness and adherence of teachers' delivery of a sexual health promoting intervention ("Long Live Love" [LLL]) in secondary education, a Web-based e-coach was developed ("lesgevenindeliefde.nl"or"teachinglove.nl"). The effectiveness of the e-coach, as part of a broader implementation strategy, in influencing teachers' implementation was evaluated. This study aimed to report on the effect evaluation to determine the effect of the Web-based e-coach on teacher implementation of a school-based sex education program called LLL and on its determinants. A cluster randomized controlled trial (e-coaching vs waiting list control) was conducted with a baseline assessment (T0) and follow-up (T1) 2 weeks after completing the LLL program. A total of 43 schools with 83 teachers participated in the study. In the follow-up, 38 schools participated, 23 in the e-coaching condition with 41 teachers and 15 in the control condition with 26 teachers. Multilevel regression analysis was used to evaluate the effect of the e-coaching website on implementation behavior, namely, completeness and adherence to LLL implementation, and on its determinants. The e-coaching intervention was not found to have an effect on teachers' implementation behavior; teachers assigned to the experimental e-coaching website did not score higher on completeness (P=.60) or adherence (P=.67) as compared with teachers in the control condition. When comparing the 30 teachers who made actual use of the e-coaching website with the 37 teachers who did not, no significant differences were found either (P≥.54). In addition, there was no effect of e-coaching on the determinants of teacher implementation behavior (t 67-75 ≤0.69; P≥.22). E-coaching was not found to be effective in enhancing completeness of and adherence to LLL by teachers. The lack of effect may be attributed to the intervention content, the limited use, or the study design itself. The e-coaching intervention may not have adequately addressed adherence and completeness of LLL to bring about behavioral change. Furthermore, the e-coaching intervention was not or insufficiently used by teachers. A possible biased sample of motivated, able teachers may have agreed to participate in the study, and a possible "ceiling effect" may have been present because of the high implementation grade. This, however, does not imply that Web-based coaching in itself is an ineffective strategy to promote adherence and completeness of program implementation. A process evaluation is required as follow-up. International Standard Randomised Controlled Trial Number ISRCTN11754581; http://www.isrctn.com/ISRCTN11754581 (Archived by WebCite at http://www.webcitation.org/70C5TUOOh). ©Lisette Schutte, Fraukje E.F. Mevissen, Suzanne Meijer, Theo Paulussen, Pepijn van Empelen, Gerjo Kok. Originally published in the Journal of Medical Internet Research (http://www.jmir.org), 18.06.2018.

Assessing Therapeutic Alliance in the Context of mHealth Interventions for Mental Health Problems: Development of the Mobile Agnew Relationship Measure (mARM) Questionnaire.

PubMed

Berry, Katherine; Salter, Amy; Morris, Rohan; James, Susannah; Bucci, Sandra

2018-04-19

Digital health interventions in the form of smartphone apps aim to improve mental health and enable people access to support as and when needed without having to face the stigma they may experience in accessing services. If we are to evaluate mobile health (mHealth) apps and advance scientific understanding, we also need tools to help us understand in what ways mHealth interventions are effective or not. The concept of therapeutic alliance, a measure of the quality of the relationship between a health care provider and a service user, is a key factor in explaining the effects of mental health interventions. The Agnew Relationship Measure (ARM) is a well-validated measure of therapeutic alliance in face-to-face therapy. This study presented the first attempt to (1) explore service users' views of the concept of relationship within mHealth mental health interventions and (2) adapt a well-validated face-to-face measure of therapeutic alliance, the Agnew Relationship Measure (ARM), for use with mHealth interventions. In stage 1, we interviewed 9 mental health service users about the concept of therapeutic alliance in the context of a digital health intervention and derived key themes from interview transcripts using thematic analysis. In stage 2, we used rating scales and open-ended questions to elicit views from 14 service users and 10 mental health staff about the content and face validity of the scale, which replaced the word "therapist" with the word "app." In stage 3, we used the findings from stages 1 and 2 to adapt the measure with the support of a decision-making algorithm about which items to drop, retain, or adapt. Findings suggested that service users do identify relationship concepts when thinking about mHealth interventions, including forming a bond with an app and the ability to be open with an app. However, there were key differences between relationships with health professionals and relationships with apps. For example, apps were not as tailored and responsive to each person's unique needs. Furthermore, apps were not capable of portraying uniquely human-like qualities such as friendliness, collaboration, and agreement. We made a number of changes to the ARM that included revising 16 items; removing 4 items due to lack of suitable alternatives; and adding 1 item to capture a key theme derived from stage 1 of the study ("The app is like having a member of my care team in my pocket"). This study introduces the mHealth version of the ARM, the mARM, that has good face and content validity. We encourage researchers to include this easy-to-use tool in digital health intervention studies to gather further data about its psychometric properties and advance our understanding of how therapeutic alliance influences the efficacy of mHealth interventions. International Standard Randomized Controlled Trial Number (ISRCTN) 34966555; http://www.isrctn.com/ISRCTN34966555 (Archived by WebCite at http://www.webcitation.org/6ymBVwKif). ©Katherine Berry, Amy Salter, Rohan Morris, Susannah James, Sandra Bucci. Originally published in the Journal of Medical Internet Research (http://www.jmir.org), 19.04.2018.

Factors Associated With Dropout During Recruitment and Follow-Up Periods of a mHealth-Based Randomized Controlled Trial for Mobile.Net to Encourage Treatment Adherence for People With Serious Mental Health Problems.

PubMed

Kannisto, Kati Anneli; Korhonen, Joonas; Adams, Clive E; Koivunen, Marita Hannele; Vahlberg, Tero; Välimäki, Maritta Anneli

2017-02-21

Clinical trials are the gold standard of evidence-based practice. Still many papers inadequately report methodology in randomized controlled trials (RCTs), particularly for mHealth interventions for people with serious mental health problems. To ensure robust enough evidence, it is important to understand which study phases are the most vulnerable in the field of mental health care. We mapped the recruitment and the trial follow-up periods of participants to provide a picture of the dropout predictors from a mHealth-based trial. As an example, we used a mHealth-based multicenter RCT, titled "Mobile.Net," targeted at people with serious mental health problems. Recruitment and follow-up processes of the Mobile.Net trial were monitored and analyzed. Recruitment outcomes were recorded as screened, eligible, consent not asked, refused, and enrolled. Patient engagement was recorded as follow-up outcomes: (1) attrition during short message service (SMS) text message intervention and (2) attrition during the 12-month follow-up period. Multiple regression analysis was used to identify which demographic factors were related to recruitment and retention. We recruited 1139 patients during a 15-month period. Of 11,530 people screened, 36.31% (n=4186) were eligible. This eligible group tended to be significantly younger (mean 39.2, SD 13.2 years, P<.001) and more often women (2103/4181, 50.30%) than those who were not eligible (age: mean 43.7, SD 14.6 years; women: 3633/6514, 55.78%). At the point when potential participants were asked to give consent, a further 2278 refused. Those who refused were a little older (mean 40.2, SD 13.9 years) than those who agreed to participate (mean 38.3, SD 12.5 years; t1842=3.2, P<.001). We measured the outcomes after 12 months of the SMS text message intervention. Attrition from the SMS text message intervention was 4.8% (27/563). The patient dropout rate after 12 months was 0.36% (4/1123), as discovered from the register data. In all, 3.12% (35/1123) of the participants withdrew from the trial. However, dropout rates from the patient survey (either by paper or telephone interview) were 52.45% (589/1123) and 27.8% (155/558), respectively. Almost all participants (536/563, 95.2%) tolerated the intervention, but those who discontinued were more often women (21/27, 78%; P=.009). Finally, participants' age (P<.001), gender (P<.001), vocational education (P=.04), and employment status (P<.001) seemed to predict their risk of dropping out from the postal survey. Patient recruitment and engagement in the 12-month follow-up conducted with a postal survey were the most vulnerable phases in the SMS text message-based trial. People with serious mental health problems may need extra support during the recruitment process and in engaging them in SMS text message-based trials to ensure robust enough evidence for mental health care. International Standard Randomized Controlled Trial Number (ISRCTN): 27704027; http://www.isrctn.com/ISRCTN27704027 (Archived by WebCite at http://www.webcitation.org/6oHcU2SFp). ©Kati Anneli Kannisto, Joonas Korhonen, Clive E Adams, Marita Hannele Koivunen, Tero Vahlberg, Maritta Anneli Välimäki. Originally published in the Journal of Medical Internet Research (http://www.jmir.org), 21.02.2017.

The impact of individual Cognitive Stimulation Therapy (iCST) on cognition, quality of life, caregiver health, and family relationships in dementia: A randomised controlled trial

PubMed Central

Leung, Phuong; Whitaker, Chris; Burns, Alistair; Knapp, Martin; Leroi, Iracema; Spector, Aimee; Roberts, Steven; de Waal, Hugo; Orgeta, Vasiliki

2017-01-01

Background Cognitive stimulation therapy (CST) is a well-established group psychosocial intervention for people with dementia. There is evidence that home-based programmes of cognitive stimulation delivered by family caregivers may benefit both the person and the caregiver. However, no previous studies have evaluated caregiver-delivered CST. This study aimed to evaluate the effectiveness of a home-based, caregiver-led individual cognitive stimulation therapy (iCST) program in (i) improving cognition and quality of life (QoL) for the person with dementia and (ii) mental and physical health (well-being) for the caregiver. Methods and findings A single-blind, pragmatic randomised controlled trial (RCT) was conducted at eight study sites across the United Kingdom. The intervention and blinded assessment of outcomes were conducted in participants’ homes. Three hundred fifty-six people with mild to moderate dementia and their caregivers were recruited from memory services and community mental health teams (CMHTs). Participants were randomly assigned to iCST (75, 30-min sessions) or treatment as usual (TAU) control over 25 wk. iCST sessions consisted of themed activities designed to be mentally stimulating and enjoyable. Caregivers delivering iCST received training and support from an unblind researcher. Primary outcomes were cognition (Alzheimer’s Disease Assessment Scale–cognitive [ADAS-Cog]) and self-reported QoL (Quality of Life Alzheimer’s Disease [QoL-AD]) for the person with dementia and general health status (Short Form-12 health survey [SF-12]) for the caregiver. Secondary outcomes included quality of the caregiving relationship from the perspectives of the person and of the caregiver (Quality of the Carer Patient Relationship Scale) and health-related QoL (European Quality of Life–5 Dimensions [EQ-5D]) for the caregiver. Intention to treat (ITT) analyses were conducted. At the post-test (26 wk), there were no differences between the iCST and TAU groups in the outcomes of cognition (mean difference [MD] = −0.55, 95% CI −2.00–0.90; p = 0.45) and self-reported QoL (MD = −0.02, 95% CI −1.22–0.82; p = 0.97) for people with dementia, or caregivers’ general health status (MD = 0.13, 95% CI −1.65–1.91; p = 0.89). However, people with dementia receiving iCST rated the relationship with their caregiver more positively (MD = 1.77, 95% CI 0.26–3.28; p = 0.02), and iCST improved QoL for caregivers (EQ-5D, MD = 0.06, 95% CI 0.02–0.10; p = 0.01). Forty percent (72/180) of dyads allocated to iCST completed at least two sessions per week, with 22% (39/180) completing no sessions at all. Study limitations include low adherence to the intervention. Conclusions There was no evidence that iCST has an effect on cognition or QoL for people with dementia. However, participating in iCST appeared to enhance the quality of the caregiving relationship and caregivers’ QoL. Trial registration The iCST trial is registered with the ISRCTN registry (identified ISRCTN 65945963, URL: DOI 10.1186/ISRCTN65945963). PMID:28350796

Assessing Feasibility and Acceptability of Web-Based Enhanced Relapse Prevention for Bipolar Disorder (ERPonline): A Randomized Controlled Trial.

PubMed

Lobban, Fiona; Dodd, Alyson L; Sawczuk, Adam P; Asar, Ozgur; Dagnan, Dave; Diggle, Peter J; Griffiths, Martin; Honary, Mahsa; Knowles, Dawn; Long, Rita; Morriss, Richard; Parker, Rob; Jones, Steven

2017-03-24

Interventions that teach people with bipolar disorder (BD) to recognize and respond to early warning signs (EWS) of relapse are recommended but implementation in clinical practice is poor. The objective of this study was to test the feasibility and acceptability of a randomized controlled trial (RCT) to evaluate a Web-based enhanced relapse prevention intervention (ERPonline) and to report preliminary evidence of effectiveness. A single-blind, parallel, primarily online RCT (n=96) over 48 weeks comparing ERPonline plus usual treatment with "waitlist (WL) control" plus usual treatment for people with BD recruited through National Health Services (NHSs), voluntary organizations, and media. Randomization was independent, minimized on number of previous episodes (<8, 8-20, 21+). Primary outcomes were recruitment and retention rates, levels of intervention use, adverse events, and participant feedback. Process and clinical outcomes were assessed by telephone and Web and compared using linear models with intention-to-treat analysis. A total of 280 people registered interest online, from which 96 met inclusion criteria, consented, and were randomized (49 to WL, 47 to ERPonline) over 17 months, with 80% retention in telephone and online follow-up at all time points, except at week 48 (76%). Acceptability was high for both ERPonline and trial methods. ERPonline cost approximately £19,340 to create, and £2176 per year to host and maintain the site. Qualitative data highlighted the importance of the relationship that the users have with Web-based interventions. Differences between the group means suggested that access to ERPonline was associated with: a more positive model of BD at 24 weeks (10.70, 95% CI 0.90 to 20.5) and 48 weeks (13.1, 95% CI 2.44 to 23.93); increased monitoring of EWS of depression at 48 weeks (-1.39, 95% CI -2.61 to -0.163) and of hypomania at 24 weeks (-1.72, 95% CI -2.98 to -0.47) and 48 weeks (-1.61, 95% CI -2.92 to -0.30), compared with WL. There was no evidence of impact of ERPonline on clinical outcomes or medication adherence, but relapse rates across both arms were low (15%) and the sample remained high functioning throughout. One person died by suicide before randomization and 5 people in ERPonline and 6 in WL reported ideas of suicide or self-harm. None were deemed study related by an independent Trial Steering Committee (TSC). ERPonline offers a cheap accessible option for people seeking ongoing support following successful treatment. However, given high functioning and low relapse rates in this study, testing clinical effectiveness for this population would require very large sample sizes. Building in human support to use ERPonline should be considered. International Standard Randomized Controlled Trial Number (ISRCTN): 56908625; http://www.isrctn.com/ISRCTN56908625 (Archived by WebCite at http://www.webcitation.org/6of1ON2S0). ©Fiona Lobban, Alyson L Dodd, Adam P Sawczuk, Ozgur Asar, Dave Dagnan, Peter J Diggle, Martin Griffiths, Mahsa Honary, Dawn Knowles, Rita Long, Richard Morriss, Rob Parker, Steven Jones. Originally published in the Journal of Medical Internet Research (http://www.jmir.org), 24.03.2017.

Effects on Engagement and Health Literacy Outcomes of Web-Based Materials Promoting Physical Activity in People With Diabetes: An International Randomized Trial.

PubMed

Muller, Ingrid; Rowsell, Alison; Stuart, Beth; Hayter, Victoria; Little, Paul; Ganahl, Kristin; Müller, Gabriele; Doyle, Gerardine; Chang, Peter; Lyles, Courtney R; Nutbeam, Don; Yardley, Lucy

2017-01-23

Developing accessible Web-based materials to support diabetes self-management in people with lower levels of health literacy is a continuing challenge. The objective of this international study was to develop a Web-based intervention promoting physical activity among people with type 2 diabetes to determine whether audiovisual presentation and interactivity (quizzes, planners, tailoring) could help to overcome the digital divide by making digital interventions accessible and effective for people with all levels of health literacy. This study also aimed to determine whether these materials can improve health literacy outcomes for people with lower levels of health literacy and also be effective for people with higher levels of health literacy. To assess the impact of interactivity and audiovisual features on usage, engagement, and health literacy outcomes, we designed two versions of a Web-based intervention (one interactive and one plain-text version of the same content) to promote physical activity in people with type 2 diabetes. We randomly assigned participants from the United Kingdom, Austria, Germany, Ireland, and Taiwan to either an interactive or plain-text version of the intervention in English, German, or Mandarin. Intervention usage was objectively recorded by the intervention software. Self-report measures were taken at baseline and follow-up (immediately after participants viewed the intervention) and included measures of health literacy, engagement (website satisfaction and willingness to recommend the intervention to others), and health literacy outcomes (diabetes knowledge, enablement, attitude, perceived behavioral control, and intention to undertake physical activity). In total, 1041 people took part in this study. Of the 1005 who completed health literacy information, 268 (26.67%) had intermediate or low levels of health literacy. The interactive intervention overall did not produce better outcomes than did the plain-text version. Participants in the plain-text intervention group looked at significantly more sections of the intervention (mean difference -0.47, 95% CI -0.64 to -0.30, P<.001), but this did not lead to better outcomes. Health literacy outcomes, including attitudes and intentions to engage in physical activity, significantly improved following the intervention for participants in both intervention groups. These improvements were similar across higher and lower health literacy levels and in all countries. Participants in the interactive intervention group had acquired more diabetes knowledge (mean difference 0.80, 95% CI 0.65-0.94, P<.001). Participants from both groups reported high levels of website satisfaction and would recommend the website to others. Following established practice for simple, clear design and presentation and using a person-based approach to intervention development, with in-depth iterative feedback from users, may be more important than interactivity and audiovisual presentations when developing accessible digital health interventions to improve health literacy outcomes. International Standard Randomized Controlled Trial Number (ISRCTN): 43587048; http://www.isrctn.com/ISRCTN43587048. (Archived by WebCite at http://www.webcitation.org/6nGhaP9bv). ©Ingrid Muller, Alison Rowsell, Beth Stuart, Victoria Hayter, Paul Little, Kristin Ganahl, Gabriele Müller, Gerardine Doyle, Peter Chang, Courtney R Lyles, Don Nutbeam, Lucy Yardley. Originally published in the Journal of Medical Internet Research (http://www.jmir.org), 23.01.2017.

The Cool Little Kids randomised controlled trial: Population-level early prevention for anxiety disorders

PubMed Central

2011-01-01

Background The World Health Organization predicts that by 2030 internalising problems (e.g. depression and anxiety) will be second only to HIV/AIDS in international burden of disease. Internalising problems affect 1 in 7 school aged children, impacting on peer relations, school engagement, and later mental health, relationships and employment. The development of early childhood prevention for internalising problems is in its infancy. The current study follows two successful 'efficacy' trials of a parenting group intervention to reduce internalising disorders in temperamentally inhibited preschool children. Cool Little Kids is a population-level randomised trial to determine the impacts of systematically screening preschoolers for inhibition then offering a parenting group intervention, on child internalising problems and economic costs at school entry. Methods/Design This randomised trial will be conducted within the preschool service system, attended by more than 95% of Australian children in the year before starting school. In early 2011, preschool services in four local government areas in Melbourne, Australia, will distribute the screening tool. The ≈16% (n≈500) with temperamental inhibition will enter the trial. Intervention parents will be offered Cool Little Kids, a 6-session group program in the local community, focusing on ways to develop their child's bravery skills by reducing overprotective parenting interactions. Outcomes one and two years post-baseline will comprise child internalising diagnoses and symptoms, parenting interactions, and parent wellbeing. An economic evaluation (cost-consequences framework) will compare incremental differences in costs of the intervention versus control children to incremental differences in outcomes, from a societal perspective. Analyses will use the intention-to-treat principle, using logistic and linear regression models (binary and continuous outcomes respectively) to compare outcomes between the trial arms. Discussion This trial addresses gaps for internalising problems identified in the 2004 World Health Organization Prevention of Mental Disorders report. If effective and cost-effective, the intervention could readily be applied at a population level. Governments consider mental health to be a priority, enhancing the likelihood that an effective early prevention program would be adopted in Australia and internationally. Trial Registration ISRCTN: ISRCTN30996662 RCH Human Research Ethics Approval 30105A PMID:21208451

The causal role of breakfast in energy balance and health: a randomized controlled trial in obese adults.

PubMed

Chowdhury, Enhad A; Richardson, Judith D; Holman, Geoffrey D; Tsintzas, Kostas; Thompson, Dylan; Betts, James A

2016-03-01

The causal nature of associations between breakfast and health remain unclear in obese individuals. We sought to conduct a randomized controlled trial to examine causal links between breakfast habits and components of energy balance in free-living obese humans. The Bath Breakfast Project is a randomized controlled trial with repeated measures at baseline and follow-up among a cohort in South West England aged 21-60 y with dual-energy X-ray absorptiometry-derived fat mass indexes of ≥13 kg/m(2) for women (n = 15) and ≥9 kg/m(2) for men (n = 8). Components of energy balance (resting metabolic rate, physical activity thermogenesis, diet-induced thermogenesis, and energy intake) were measured under free-living conditions with random allocation to daily breakfast (≥700 kcal before 1100) or extended fasting (0 kcal until 1200) for 6 wk, with baseline and follow-up measures of health markers (e.g., hematology/adipose biopsies). Breakfast resulted in greater physical activity thermogenesis during the morning than when fasting during that period (difference: 188 kcal/d; 95% CI: 40, 335) but without any consistent effect on 24-h physical activity thermogenesis (difference: 272 kcal/d; 95% CI: -254, 798). Energy intake was not significantly greater with breakfast than fasting (difference: 338 kcal/d; 95% CI: -313, 988). Body mass increased across both groups over time but with no treatment effects on body composition or any change in resting metabolic rate (stable within 8 kcal/d). Metabolic/cardiovascular health also did not respond to treatments, except for a reduced insulinemic response to an oral-glucose-tolerance test over time with daily breakfast relative to an increase with daily fasting (P = 0.05). In obese adults, daily breakfast leads to greater physical activity during the morning, whereas morning fasting results in partial dietary compensation (i.e., greater energy intake) later in the day. There were no differences between groups in weight change and most health outcomes, but insulin sensitivity increased with breakfast relative to fasting. This trial was registered at www.isrctn.org as ISRCTN31521726.

Targeted prevention of common mental health disorders in university students: randomised controlled trial of a transdiagnostic trait-focused web-based intervention.

PubMed

Musiat, Peter; Conrod, Patricia; Treasure, Janet; Tylee, Andre; Williams, Chris; Schmidt, Ulrike

2014-01-01

A large proportion of university students show symptoms of common mental disorders, such as depression, anxiety, substance use disorders and eating disorders. Novel interventions are required that target underlying factors of multiple disorders. To evaluate the efficacy of a transdiagnostic trait-focused web-based intervention aimed at reducing symptoms of common mental disorders in university students. Students were recruited online (n=1047, age: M=21.8, SD=4.2) and categorised into being at high or low risk for mental disorders based on their personality traits. Participants were allocated to a cognitive-behavioural trait-focused (n=519) or a control intervention (n=528) using computerised simple randomisation. Both interventions were fully automated and delivered online (trial registration: ISRCTN14342225). Participants were blinded and outcomes were self-assessed at baseline, at 6 weeks and at 12 weeks after registration. Primary outcomes were current depression and anxiety, assessed on the Patient Health Questionnaire (PHQ9) and Generalised Anxiety Disorder Scale (GAD7). Secondary outcome measures focused on alcohol use, disordered eating, and other outcomes. Students at high risk were successfully identified using personality indicators and reported poorer mental health. A total of 520 students completed the 6-week follow-up and 401 students completed the 12-week follow-up. Attrition was high across intervention groups, but comparable to other web-based interventions. Mixed effects analyses revealed that at 12-week follow up the trait-focused intervention reduced depression scores by 3.58 (p<.001, 95%CI [5.19, 1.98]) and anxiety scores by 2.87 (p=.018, 95%CI [1.31, 4.43]) in students at high risk. In high-risk students, between group effect sizes were 0.58 (depression) and 0.42 (anxiety). In addition, self-esteem was improved. No changes were observed regarding the use of alcohol or disordered eating. This study suggests that a transdiagnostic web-based intervention for university students targeting underlying personality risk factors may be a promising way of preventing common mental disorders with a low-intensity intervention. ControlledTrials.com ISRCTN14342225.

Effects of homocysteine-lowering with folic acid plus vitamin B12 vs placebo on mortality and major morbidity in myocardial infarction survivors: a randomized trial.

PubMed

Armitage, Jane M; Bowman, Louise; Clarke, Robert J; Wallendszus, Karl; Bulbulia, Richard; Rahimi, Kazem; Haynes, Richard; Parish, Sarah; Sleight, Peter; Peto, Richard; Collins, Rory

2010-06-23

Blood homocysteine levels are positively associated with cardiovascular disease, but it is uncertain whether the association is causal. To assess the effects of reducing homocysteine levels with folic acid and vitamin B(12) on vascular and nonvascular outcomes. Double-blind randomized controlled trial of 12,064 survivors of myocardial infarction in secondary care hospitals in the United Kingdom between 1998 and 2008. 2 mg folic acid plus 1 mg vitamin B(12) daily vs matching placebo. First major vascular event, defined as major coronary event (coronary death, myocardial infarction, or coronary revascularization), fatal or nonfatal stroke, or noncoronary revascularization. Allocation to the study vitamins reduced homocysteine by a mean of 3.8 micromol/L (28%). During 6.7 years of follow-up, major vascular events occurred in 1537 of 6033 participants (25.5%) allocated folic acid plus vitamin B(12) vs 1493 of 6031 participants (24.8%) allocated placebo (risk ratio [RR], 1.04; 95% confidence interval [CI], 0.97-1.12; P = .28). There were no apparent effects on major coronary events (vitamins, 1229 [20.4%], vs placebo, 1185 [19.6%]; RR, 1.05; 95% CI, 0.97-1.13), stroke (vitamins, 269 [4.5%], vs placebo, 265 [4.4%]; RR, 1.02; 95% CI, 0.86-1.21), or noncoronary revascularizations (vitamins, 178 [3.0%], vs placebo, 152 [2.5%]; RR, 1.18; 95% CI, 0.95-1.46). Nor were there significant differences in the numbers of deaths attributed to vascular causes (vitamins, 578 [9.6%], vs placebo, 559 [9.3%]) or nonvascular causes (vitamins, 405 [6.7%], vs placebo, 392 [6.5%]) or in the incidence of any cancer (vitamins, 678 [11.2%], vs placebo, 639 [10.6%]). Substantial long-term reductions in blood homocysteine levels with folic acid and vitamin B(12) supplementation did not have beneficial effects on vascular outcomes but were also not associated with adverse effects on cancer incidence. isrctn.org Identifier: ISRCTN74348595.

Effect of mastication on lipid bioaccessibility of almonds in a randomized human study and its implications for digestion kinetics, metabolizable energy, and postprandial lipemia1234

PubMed Central

Grundy, Myriam ML; Grassby, Terri; Mandalari, Giuseppina; Waldron, Keith W; Butterworth, Peter J; Berry, Sarah EE

2015-01-01

Background: The particle size and structure of masticated almonds have a significant impact on nutrient release (bioaccessibility) and digestion kinetics. Objectives: The goals of this study were to quantify the effects of mastication on the bioaccessibility of intracellular lipid of almond tissue and examine microstructural characteristics of masticated almonds. Design: In a randomized, subject-blind, crossover trial, 17 healthy subjects chewed natural almonds (NAs) or roasted almonds (RAs) in 4 separate mastication sessions. Particle size distributions (PSDs) of the expectorated boluses were measured by using mechanical sieving and laser diffraction (primary outcome). The microstructure of masticated almonds, including the structural integrity of the cell walls (i.e., dietary fiber), was examined with microscopy. Lipid bioaccessibility was predicted by using a theoretical model, based on almond particle size and cell dimensions, and then compared with empirically derived release data. Results: Intersubject variations (n = 15; 2 subjects withdrew) in PSDs of both NA and RA samples were small (e.g., laser diffraction; CV: 12% and 9%, respectively). Significant differences in PSDs were found between these 2 almond forms (P < 0.05). A small proportion of lipid was released from ruptured cells on fractured surfaces of masticated particles, as predicted by using the mathematical model (8.5% and 11.3% for NAs and RAs, respectively). This low percentage of lipid bioaccessibility is attributable to the high proportion (35–40%) of large particles (>500 μm) in masticated almonds. Microstructural examination of the almonds indicated that most intracellular lipid remained undisturbed in intact cells after mastication. No adverse events were recorded. Conclusions: Following mastication, most of the almond cells remained intact with lipid encapsulated by cell walls. Thus, most of the lipid in masticated almonds is not immediately bioaccessible and remains unavailable for early stages of digestion. The lipid encapsulation mechanism provides a convincing explanation for why almonds have a low metabolizable energy content and an attenuated impact on postprandial lipemia. This trial was registered at isrctn.org as ISRCTN58438021. PMID:25527747

Support and Assessment for Fall Emergency Referrals (SAFER 1): Cluster Randomised Trial of Computerised Clinical Decision Support for Paramedics

PubMed Central

Snooks, Helen Anne; Carter, Ben; Dale, Jeremy; Foster, Theresa; Humphreys, Ioan; Logan, Philippa Anne; Lyons, Ronan Anthony; Mason, Suzanne Margaret; Phillips, Ceri James; Sanchez, Antonio; Wani, Mushtaq; Watkins, Alan; Wells, Bridget Elizabeth; Whitfield, Richard; Russell, Ian Trevor

2014-01-01

Objective To evaluate effectiveness, safety and cost-effectiveness of Computerised Clinical Decision Support (CCDS) for paramedics attending older people who fall. Design Cluster trial randomised by paramedic; modelling. Setting 13 ambulance stations in two UK emergency ambulance services. Participants 42 of 409 eligible paramedics, who attended 779 older patients for a reported fall. Interventions Intervention paramedics received CCDS on Tablet computers to guide patient care. Control paramedics provided care as usual. One service had already installed electronic data capture. Main Outcome Measures Effectiveness: patients referred to falls service, patient reported quality of life and satisfaction, processes of care. Safety Further emergency contacts or death within one month. Cost-Effectiveness Costs and quality of life. We used findings from published Community Falls Prevention Trial to model cost-effectiveness. Results 17 intervention paramedics used CCDS for 54 (12.4%) of 436 participants. They referred 42 (9.6%) to falls services, compared with 17 (5.0%) of 343 participants seen by 19 control paramedics [Odds ratio (OR) 2.04, 95% CI 1.12 to 3.72]. No adverse events were related to the intervention. Non-significant differences between groups included: subsequent emergency contacts (34.6% versus 29.1%; OR 1.27, 95% CI 0.93 to 1.72); quality of life (mean SF12 differences: MCS −0.74, 95% CI −2.83 to +1.28; PCS −0.13, 95% CI −1.65 to +1.39) and non-conveyance (42.0% versus 36.7%; OR 1.13, 95% CI 0.84 to 1.52). However ambulance job cycle time was 8.9 minutes longer for intervention patients (95% CI 2.3 to 15.3). Average net cost of implementing CCDS was £208 per patient with existing electronic data capture, and £308 without. Modelling estimated cost per quality-adjusted life-year at £15,000 with existing electronic data capture; and £22,200 without. Conclusions Intervention paramedics referred twice as many participants to falls services with no difference in safety. CCDS is potentially cost-effective, especially with existing electronic data capture. Trial Registration ISRCTN Register ISRCTN10538608 PMID:25216281

IMPROVDENT: improving dentures for patient benefit. A crossover randomised clinical trial comparing impression materials for complete dentures.

PubMed

Gray, Janine C; Navarro-Coy, Nuria; Pavitt, Sue H; Hulme, Claire; Godfrey, Mary; Craddock, Helen L; Brunton, Paul A; Brown, Sarah; Dillon, Sean; Dukanovic, Gillian; Fernandez, Catherine; Wright, Jonathan; Collier, Howard; Swithenbank, Shirley; Lee, Carol; Hyde, T Paul

2012-08-31

According to the UK Adult Dental Health Survey (2009) 15% of adults aged 65-74, 30% aged 75-84 and 47% aged >85 years are edentulous and require complete dentures. Patients' quality of life and nutrition status are affected by poor dentures. The quality of the dental impression is the most important issue for improving the fit and comfort of new dentures. There is paucity of RCT evidence for which impression material is best for complete dentures construction. This study aims to compare two impression materials for effectiveness and cost effectiveness. IMPROVDENT is a double-blind crossover trial comparing the use of alginate and silicone, two commonly used denture impression materials, in terms of patient preference and cost-effectiveness. Eighty five edentulous patients will be recruited and provided with two sets of dentures, similar in all aspects except for the impression material used (alginate or silicone). Patients will try both sets of dentures for a two-week period, unadjusted, to become accustomed to the feel of the new dentures (habituation period). Patients will then wear each set of dentures for a period of 8 weeks (in random order) during which time the dentures will be adjusted for optimum comfort. Finally, patients will be given both sets of dentures for a further two weeks to wear whichever denture they prefer (confirmation period).Patients will be asked about quality of life and to rate dentures on function and comfort at the end of each trial period and asked which set they prefer at the end of the habituation period (unadjusted denture preference) and confirmation period (adjusted denture preference). A health economic evaluation will estimate incremental cost-effectiveness ratios of producing dentures from the two materials. A qualitative study will investigate the impact of dentures on behaviour and quality of life. IMPROVDENT is funded by NIHR RfPB (PB-PG-0408-16300). This trial aims to provide evidence on the costs and quality of dentures cast from two different commonly used impression materials; the intention is to significantly impact on the quality of denture production within NHS dentistry. ISRCTN Register: ISRCTN01528038 UKCRN Portfolio ID: 8305.

Cohort Randomised Controlled Trial of a Multifaceted Podiatry Intervention for the Prevention of Falls in Older People (The REFORM Trial).

PubMed

Cockayne, Sarah; Adamson, Joy; Clarke, Arabella; Corbacho, Belen; Fairhurst, Caroline; Green, Lorraine; Hewitt, Catherine E; Hicks, Kate; Kenan, Anne-Maree; Lamb, Sarah E; McIntosh, Caroline; Menz, Hylton B; Redmond, Anthony C; Richardson, Zoe; Rodgers, Sara; Vernon, Wesley; Watson, Judith; Torgerson, David J

2017-01-01

Falls are a major cause of morbidity among older people. A multifaceted podiatry intervention may reduce the risk of falling. This study evaluated such an intervention. Pragmatic cohort randomised controlled trial in England and Ireland. 1010 participants were randomised (493 to the Intervention group and 517 to Usual Care) to either: a podiatry intervention, including foot and ankle exercises, foot orthoses and, if required, new footwear, and a falls prevention leaflet or usual podiatry treatment plus a falls prevention leaflet. The primary outcome was the incidence rate of self-reported falls per participant in the 12 months following randomisation. Secondary outcomes included: proportion of fallers and those reporting multiple falls, time to first fall, fear of falling, Frenchay Activities Index, Geriatric Depression Scale, foot pain, health related quality of life, and cost-effectiveness. In the primary analysis were 484 (98.2%) intervention and 507 (98.1%) control participants. There was a small, non statistically significant reduction in the incidence rate of falls in the intervention group (adjusted incidence rate ratio 0.88, 95% CI 0.73 to 1.05, p = 0.16). The proportion of participants experiencing a fall was lower (49.7 vs 54.9%, adjusted odds ratio 0.78, 95% CI 0.60 to 1.00, p = 0.05) as was the proportion experiencing two or more falls (27.6% vs 34.6%, adjusted odds ratio 0.69, 95% CI 0.52 to 0.90, p = 0.01). There was an increase (p = 0.02) in foot pain for the intervention group. There were no statistically significant differences in other outcomes. The intervention was more costly but marginally more beneficial in terms of health-related quality of life (mean quality adjusted life year (QALY) difference 0.0129, 95% CI -0.0050 to 0.0314) and had a 65% probability of being cost-effective at a threshold of £30,000 per QALY gained. There was a small reduction in falls. The intervention may be cost-effective. ISRCTN ISRCTN68240461.

Cohort Randomised Controlled Trial of a Multifaceted Podiatry Intervention for the Prevention of Falls in Older People (The REFORM Trial)

PubMed Central

Cockayne, Sarah; Adamson, Joy; Clarke, Arabella; Corbacho, Belen; Fairhurst, Caroline; Green, Lorraine; Hewitt, Catherine E.; Hicks, Kate; Kenan, Anne-Maree; Lamb, Sarah E.; McIntosh, Caroline; Menz, Hylton B.; Redmond, Anthony C.; Richardson, Zoe; Rodgers, Sara; Vernon, Wesley; Watson, Judith

2017-01-01

Background Falls are a major cause of morbidity among older people. A multifaceted podiatry intervention may reduce the risk of falling. This study evaluated such an intervention. Design Pragmatic cohort randomised controlled trial in England and Ireland. 1010 participants were randomised (493 to the Intervention group and 517 to Usual Care) to either: a podiatry intervention, including foot and ankle exercises, foot orthoses and, if required, new footwear, and a falls prevention leaflet or usual podiatry treatment plus a falls prevention leaflet. The primary outcome was the incidence rate of self-reported falls per participant in the 12 months following randomisation. Secondary outcomes included: proportion of fallers and those reporting multiple falls, time to first fall, fear of falling, Frenchay Activities Index, Geriatric Depression Scale, foot pain, health related quality of life, and cost-effectiveness. Results In the primary analysis were 484 (98.2%) intervention and 507 (98.1%) control participants. There was a small, non statistically significant reduction in the incidence rate of falls in the intervention group (adjusted incidence rate ratio 0.88, 95% CI 0.73 to 1.05, p = 0.16). The proportion of participants experiencing a fall was lower (49.7 vs 54.9%, adjusted odds ratio 0.78, 95% CI 0.60 to 1.00, p = 0.05) as was the proportion experiencing two or more falls (27.6% vs 34.6%, adjusted odds ratio 0.69, 95% CI 0.52 to 0.90, p = 0.01). There was an increase (p = 0.02) in foot pain for the intervention group. There were no statistically significant differences in other outcomes. The intervention was more costly but marginally more beneficial in terms of health-related quality of life (mean quality adjusted life year (QALY) difference 0.0129, 95% CI -0.0050 to 0.0314) and had a 65% probability of being cost-effective at a threshold of £30,000 per QALY gained. Conclusion There was a small reduction in falls. The intervention may be cost-effective. Trial Registration ISRCTN ISRCTN68240461 PMID:28107372

Bath Breakfast Project (BBP) - Examining the role of extended daily fasting in human energy balance and associated health outcomes: Study protocol for a randomised controlled trial [ISRCTN31521726

PubMed Central

2011-01-01

Background Current guidance regarding the role of daily breakfast in human health is largely grounded in cross-sectional observations. However, the causal nature of these relationships has not been fully explored and what limited information is emerging from controlled laboratory-based experiments appears inconsistent with much existing data. Further progress in our understanding therefore requires a direct examination of how daily breakfast impacts human health under free-living conditions. Methods/Design The Bath Breakfast Project (BBP) is a randomised controlled trial comparing the effects of daily breakfast consumption relative to extended fasting on energy balance and human health. Approximately 70 men and women will undergo extensive laboratory-based assessments of their acute metabolic responses under fasted and post-prandial conditions, to include: resting metabolic rate, substrate oxidation, dietary-induced thermogenesis and systemic concentrations of key metabolites/hormones. Physiological and psychological indices of appetite will also be monitored both over the first few hours of the day (i.e. whether fed or fasted) and also following a standardised test lunch used to assess voluntary energy intake under controlled conditions. Baseline measurements of participants' anthropometric characteristics (e.g. DEXA) will be recorded prior to intervention, along with an oral glucose tolerance test and acquisition of adipose tissue samples to determine expression of key genes and estimates of tissue-specific insulin action. Participants will then be randomly assigned either to a group prescribed an energy intake of ≥3000 kJ before 1100 each day or a group to extend their overnight fast by abstaining from ingestion of energy-providing nutrients until 1200 each day, with all laboratory-based measurements followed-up 6 weeks later. Free-living assessments of energy intake (via direct weighed food diaries) and energy expenditure (via combined heart-rate/accelerometry) will be made during the first and last week of intervention, with continuous glucose monitors worn both to document chronic glycaemic responses to the intervention and to verify compliance. Trial registration Current Controlled Trials ISRCTN31521726. PMID:21740575

The causal role of breakfast in energy balance and health: a randomized controlled trial in obese adults12

PubMed Central

Chowdhury, Enhad A; Richardson, Judith D; Holman, Geoffrey D; Tsintzas, Kostas; Thompson, Dylan; Betts, James A

2016-01-01

Background: The causal nature of associations between breakfast and health remain unclear in obese individuals. Objective: We sought to conduct a randomized controlled trial to examine causal links between breakfast habits and components of energy balance in free-living obese humans. Design: The Bath Breakfast Project is a randomized controlled trial with repeated measures at baseline and follow-up among a cohort in South West England aged 21–60 y with dual-energy X-ray absorptiometry–derived fat mass indexes of ≥13 kg/m2 for women (n = 15) and ≥9 kg/m2 for men (n = 8). Components of energy balance (resting metabolic rate, physical activity thermogenesis, diet-induced thermogenesis, and energy intake) were measured under free-living conditions with random allocation to daily breakfast (≥700 kcal before 1100) or extended fasting (0 kcal until 1200) for 6 wk, with baseline and follow-up measures of health markers (e.g., hematology/adipose biopsies). Results: Breakfast resulted in greater physical activity thermogenesis during the morning than when fasting during that period (difference: 188 kcal/d; 95% CI: 40, 335) but without any consistent effect on 24-h physical activity thermogenesis (difference: 272 kcal/d; 95% CI: −254, 798). Energy intake was not significantly greater with breakfast than fasting (difference: 338 kcal/d; 95% CI: −313, 988). Body mass increased across both groups over time but with no treatment effects on body composition or any change in resting metabolic rate (stable within 8 kcal/d). Metabolic/cardiovascular health also did not respond to treatments, except for a reduced insulinemic response to an oral-glucose-tolerance test over time with daily breakfast relative to an increase with daily fasting (P = 0.05). Conclusions: In obese adults, daily breakfast leads to greater physical activity during the morning, whereas morning fasting results in partial dietary compensation (i.e., greater energy intake) later in the day. There were no differences between groups in weight change and most health outcomes, but insulin sensitivity increased with breakfast relative to fasting. This trial was registered at www.isrctn.org as ISRCTN31521726. PMID:26864365

European COMPARative Effectiveness research on blended Depression treatment versus treatment-as-usual (E-COMPARED): study protocol for a randomized controlled, non-inferiority trial in eight European countries.

PubMed

Kleiboer, Annet; Smit, Jan; Bosmans, Judith; Ruwaard, Jeroen; Andersson, Gerhard; Topooco, Naira; Berger, Thomas; Krieger, Tobias; Botella, Cristina; Baños, Rosa; Chevreul, Karine; Araya, Ricardo; Cerga-Pashoja, Arlinda; Cieślak, Roman; Rogala, Anna; Vis, Christiaan; Draisma, Stasja; van Schaik, Anneke; Kemmeren, Lise; Ebert, David; Berking, Matthias; Funk, Burkhardt; Cuijpers, Pim; Riper, Heleen

2016-08-03

Effective, accessible, and affordable depression treatment is of high importance considering the large personal and economic burden of depression. Internet-based treatment is considered a promising clinical and cost-effective alternative to current routine depression treatment strategies such as face-to-face psychotherapy. However, it is not clear whether research findings translate to routine clinical practice such as primary or specialized mental health care. The E-COMPARED project aims to gain knowledge on the clinical and cost-effectiveness of blended depression treatment compared to treatment-as-usual in routine care. E-COMPARED will employ a pragmatic, multinational, randomized controlled, non-inferiority trial in eight European countries. Adults diagnosed with major depressive disorder (MDD) will be recruited in primary care (Germany, Poland, Spain, Sweden, and the United Kingdom) or specialized mental health care (France, The Netherlands, and Switzerland). Regular care for depression is compared to "blended" service delivery combining mobile and Internet technologies with face-to-face treatment in one treatment protocol. Participants will be followed up at 3, 6, and 12 months after baseline to determine clinical improvements in symptoms of depression (primary outcome: Patient Health Questionnaire-9), remission of depression, and cost-effectiveness. Main analyses will be conducted on the pooled data from the eight countries (n = 1200 in total, 150 participants in each country). The E-COMPARED project will provide mental health care stakeholders with evidence-based information and recommendations on the clinical and cost-effectiveness of blended depression treatment. France: ClinicalTrials.gov NCT02542891 . Registered on 4 September 2015; Germany: German Clinical Trials Register DRKS00006866 . Registered on 2 December 2014; The Netherlands: Netherlands Trials Register NTR4962 . Registered on 5 January 2015; Poland: ClinicalTrials.Gov NCT02389660 . Registered on 18 February 2015; Spain: ClinicalTrials.gov NCT02361684 . Registered on 8 January 2015; Sweden: ClinicalTrials.gov NCT02449447 . Registered on 30 March 2015; Switzerland: ClinicalTrials.gov NCT02410616 . Registered on 2 April 2015; United Kingdom: ISRCTN registry, ISRCTN12388725 . Registered on 20 March 2015.

Using mixed methods to assess fidelity of delivery and its influencing factors in a complex self-management intervention for people with osteoarthritis and low back pain.

PubMed

Toomey, Elaine; Matthews, James; Hurley, Deirdre A

2017-08-04

Despite an increasing awareness of the importance of fidelity of delivery within complex behaviour change interventions, it is often poorly assessed. This mixed methods study aimed to establish the fidelity of delivery of a complex self-management intervention and explore the reasons for these findings using a convergent/triangulation design. Feasibility trial of the Self-management of Osteoarthritis and Low back pain through Activity and Skills (SOLAS) intervention (ISRCTN49875385), delivered in primary care physiotherapy. 60 SOLAS sessions were delivered across seven sites by nine physiotherapists. Fidelity of delivery of prespecified intervention components was evaluated using (1) audio-recordings (n=60), direct observations (n=24) and self-report checklists (n=60) and (2) individual interviews with physiotherapists (n=9). Quantitatively, fidelity scores were calculated using percentage means and SD of components delivered. Associations between fidelity scores and physiotherapist variables were analysed using Spearman's correlations. Interviews were analysed using thematic analysis to explore potential reasons for fidelity scores. Integration of quantitative and qualitative data occurred at an interpretation level using triangulation. Quantitatively, fidelity scores were high for all assessment methods; with self-report (92.7%) consistently higher than direct observations (82.7%) or audio-recordings (81.7%). There was significant variation between physiotherapists' individual scores (69.8% - 100%). Both qualitative and quantitative data (from physiotherapist variables) found that physiotherapists' knowledge (Spearman's association at p=0.003) and previous experience (p=0.008) were factors that influenced their fidelity. The qualitative data also postulated participant-level (eg, individual needs) and programme-level factors (eg, resources) as additional elements that influenced fidelity. The intervention was delivered with high fidelity. This study contributes to the limited evidence regarding fidelity assessment methods within complex behaviour change interventions. The findings suggest a combination of quantitative methods is suitable for the assessment of fidelity of delivery. A mixed methods approach provided a more insightful understanding of fidelity and its influencing factors. ISRCTN49875385; Pre-results. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Intensive versus Guideline Blood Pressure and Lipid Lowering in Patients with Previous Stroke: Main Results from the Pilot 'Prevention of Decline in Cognition after Stroke Trial' (PODCAST) Randomised Controlled Trial.

PubMed

Bath, Philip M; Scutt, Polly; Blackburn, Daniel J; Ankolekar, Sandeep; Krishnan, Kailash; Ballard, Clive; Burns, Alistair; Mant, Jonathan; Passmore, Peter; Pocock, Stuart; Reckless, John; Sprigg, Nikola; Stewart, Rob; Wardlaw, Joanna M; Ford, Gary A

2017-01-01

Stroke is associated with the development of cognitive impairment and dementia. We assessed the effect of intensive blood pressure (BP) and/or lipid lowering on cognitive outcomes in patients with recent stroke in a pilot trial. In a multicentre, partial-factorial trial, patients with recent stroke, absence of dementia, and systolic BP (SBP) 125-170 mmHg were assigned randomly to at least 6 months of intensive (target SBP <125 mmHg) or guideline (target SBP <140 mmHg) BP lowering. The subset of patients with ischaemic stroke and total cholesterol 3.0-8.0 mmol/l were also assigned randomly to intensive (target LDL-cholesterol <1.3 mmol/l) or guideline (target LDL-c <3.0 mmol/l) lipid lowering. The primary outcome was the Addenbrooke's Cognitive Examination-Revised (ACE-R). We enrolled 83 patients, mean age 74.0 (6.8) years, and median 4.5 months after stroke. The median follow-up was 24 months (range 1-48). Mean BP was significantly reduced with intensive compared to guideline treatment (difference -10·6/-5·5 mmHg; p<0·01), as was total/LDL-cholesterol with intensive lipid lowering compared to guideline (difference -0·54/-0·44 mmol/l; p<0·01). The ACE-R score during treatment did not differ for either treatment comparison; mean difference for BP lowering -3.6 (95% CI -9.7 to 2.4), and lipid lowering 4.4 (95% CI -2.1 to 10.9). However, intensive lipid lowering therapy was significantly associated with improved scores for ACE-R at 6 months, trail making A, modified Rankin Scale and Euro-Qol Visual Analogue Scale. There was no difference in rates of dementia or serious adverse events for either comparison. In patients with recent stroke and normal cognition, intensive BP and lipid lowering were feasible and safe, but did not alter cognition over two years. The association between intensive lipid lowering and improved scores for some secondary outcomes suggests further trials are warranted. ISRCTN ISRCTN85562386.

Femoral nerve block Intervention in Neck of Femur fracture (FINOF): study protocol for a randomized controlled trial

PubMed Central

2014-01-01

Background Hip fractures are very painful leading to lengthy hospital stays. Conventional methods of treating pain are limited. Non-steroidal anti-inflammatories are relatively contraindicated and opioids have significant side effects.Regional anaesthesia holds promise but results from these techniques are inconsistent. Trials to date have been inconclusive with regard to which blocks to use and for how long. Interpatient variability remains a problem. Methods/Design This is a single centre study conducted at Queen’s Medical Centre, Nottingham; a large regional trauma centre in England. It is a pragmatic, parallel arm, randomized controlled trial. Sample size will be 150 participants (75 in each group). Randomization will be web-based, using computer generated concealed tables (service provided by Nottingham University Clinical Trials Unit). There is no blinding. Intervention will be a femoral nerve block (0.5 mls/kg 0.25% levo-bupivacaine) followed by ropivacaine (0.2% 5 ml/hr−1) infused via a femoral nerve catheter until 48 hours post-surgery. The control group will receive standard care. Participants will be aged over 70 years, cognitively intact (abbreviated mental score of seven or more), able to provide informed consent, and admitted directly through the Emergency Department from their place of residence. Primary outcomes will be cumulative ambulation score (from day 1 to 3 postoperatively) and cumulative dynamic pain scores (day 1 to 3 postoperatively). Secondary outcomes will be cumulative dynamic pain score preoperatively, cumulative side effects, cumulative calorific and protein intake, EUROQOL EQ-5D score, length of stay, and rehabilitation outcome (measured by mobility score). Discussion Many studies have shown the effectiveness of regional blockade in neck of femur fractures, but the techniques used have varied. This study aims to identify whether early and continuous femoral nerve block can be effective in relieving pain and enhancing mobilization.Trial registration. Trial registration The trial is registered with the European clinical trials database Eudract ref: 2010-023871-25. (17/02/2011). ISRCTN: ISRCTN92946117. Registered 26 October 2012. PMID:24885267

Comparison of midwife-led and consultant-led care of healthy women at low risk of childbirth complications in the Republic of Ireland: a randomised trial

PubMed Central

2011-01-01

Background No midwifery-led units existed in Ireland before 2004. The aim of this study was to compare midwife-led (MLU) versus consultant-led (CLU) care for healthy, pregnant women without risk factors for labour and delivery. Methods An unblinded, pragmatic randomised trial was designed, funded by the Health Service Executive (Dublin North-East). Following ethical approval, all women booking prior to 24 weeks of pregnancy at two maternity hospitals with 1,300-3,200 births annually in Ireland were assessed for trial eligibility.1,653 consenting women were centrally randomised on a 2:1 ratio to MLU or CLU care, (1101:552). 'Intention-to-treat' analysis was used to compare 9 key neonatal and maternal outcomes. Results No statistically significant difference was found between MLU and CLU in the seven key outcomes: caesarean birth (163 [14.8%] vs 84 [15.2%]; relative risk (RR) 0.97 [95% CI 0.76 to 1.24]), induction (248 [22.5%] vs 138 [25.0%]; RR 0.90 [0.75 to 1.08]), episiotomy (126 [11.4%] vs 68 [12.3%]; RR 0.93 [0.70 to 1.23]), instrumental birth (139 [12.6%] vs 79 [14.3%]; RR 0.88 [0.68 to 1.14]), Apgar scores < 8 (10 [0.9%] vs 9 [1.6%]; RR 0.56 [0.23 to 1.36]), postpartum haemorrhage (144 [13.1%] vs 75 [13.6%]; RR 0.96 [0.74 to 1.25]); breastfeeding initiation (616 [55.9%] vs 317 [57.4%]; RR 0.97 [0.89 to 1.06]). MLU women were significantly less likely to have continuous electronic fetal monitoring (397 [36.1%] vs 313 [56.7%]; RR 0.64 [0.57 to 0.71]), or augmentation of labour (436 [39.6%] vs 314 [56.9%]; RR 0.50 [0.40 to 0.61]). Conclusions Midwife-led care, as practised in this study, is as safe as consultant-led care and is associated with less intervention during labour and delivery. Trial registration number ISRCTN: ISRCTN14973283 PMID:22035427

A randomised active-controlled trial to examine the effects of an online mindfulness intervention on executive control, critical thinking and key thinking dispositions in a university student sample.

PubMed

Noone, Chris; Hogan, Michael J

2018-04-05

Arguments for including mindfulness instruction in higher education have included claims about the benefits of mindfulness practice for critical thinking. While there is theoretical support for this claim, empirical support is limited. The aim of this study was to test this claim by investigating the effects of an online mindfulness intervention on executive function, critical thinking skills and associated thinking dispositions. Participants recruited from a university were randomly allocated, following screening, to either a mindfulness meditation group or a sham meditation group. Both the researchers and the participants were blind to group allocation. The intervention content for both groups was delivered through the Headspace online application, an application which provides guided meditations to users. Both groups were requested to complete 30 guided mindfulness meditation sessions across a 6 week period. Primary outcome measures assessed mindfulness, executive functioning, critical thinking, actively open-minded thinking and need for cognition. Secondary outcome measures assessed wellbeing, positive and negative affect, and real-world outcomes. In a series of full-information maximum likelihood analyses, significant increases in mindfulness dispositions and critical thinking scores were observed in both the mindfulness meditation and sham meditation groups. However, no significant effects of group allocation were observed for either primary or secondary measures. Furthermore, mediation analyses testing the indirect effect of group allocation through executive functioning performance did not reveal a significant result and moderation analyses showed that the effect of the intervention did not depend on baseline levels of the key thinking dispositions, actively open-minded thinking and need for cognition. No evidence was found to suggest that engaging in guided mindfulness practice for 6 weeks using the online intervention method applied in this study improves critical thinking performance. While further research is warranted, claims regarding the benefits of mindfulness practice for critical thinking should be tempered in the meantime. The study was initially registered in the AEA Social Science Registry before the recruitment was initiated (RCT ID: AEARCTR-0000756; 14/11/2015) and retrospectively registered in the ISRCTN registry ( RCT ID: ISRCTN16588423 ) in line with requirements for publishing the study protocol.

Cognitive-Behavioral and Psychodynamic Therapy in Female Adolescents With Bulimia Nervosa: A Randomized Controlled Trial.

PubMed

Stefini, Annette; Salzer, Simone; Reich, Günter; Horn, Hildegard; Winkelmann, Klaus; Bents, Hinrich; Rutz, Ursula; Frost, Ulrike; von Boetticher, Antje; Ruhl, Uwe; Specht, Nicole; Kronmüller, Klaus-Thomas

2017-04-01

The authors compared cognitive-behavioral therapy (CBT) and psychodynamic therapy (PDT) for the treatment of bulimia nervosa (BN) in female adolescents. In this randomized controlled trial, 81 female adolescents with BN or partial BN according to the DSM-IV received a mean of 36.6 sessions of manualized disorder-oriented PDT or CBT. Trained psychologists blinded to treatment condition administered the outcome measures at baseline, during treatment, at the end of treatment, and 12 months after treatment. The primary outcome was the rate of remission, defined as a lack of DSM-IV diagnosis for BN or partial BN at the end of therapy. Several secondary outcome measures were evaluated. The remission rates for CBT and PDT were 33.3% and 31.0%, respectively, with no significant differences between them (odds ratio [OR] = 0.90, 95% CI = 0.35-2.28, p = .82). The within-group effect sizes were h = 1.22 for CBT and h = 1.18 for PDT. Significant improvements in all secondary outcome measures were found for both CBT (d = 0.51-0.82) and PDT (d = 0.24-1.10). The improvements remained stable at the 12-month follow-up in both groups. There were small between-group effect sizes for binge eating (d = 0.23) and purging (d = 0.26) in favor of CBT and for eating concern (d = -0.35) in favor of PDT. CBT and PDT were effective in promoting recovery from BN in female adolescents. The rates of remission for both therapies were similar to those in other studies evaluating CBT. This trial identified differences with small effects in binge eating, purging, and eating concern. Clinical trial registration information-Treating Bulimia Nervosa in Female Adolescents With Either Cognitive-Behavioral Therapy (CBT) or Psychodynamic Therapy (PDT). http://isrctn.com/; ISRCTN14806095. Copyright © 2017 American Academy of Child and Adolescent Psychiatry. Published by Elsevier Inc. All rights reserved.

Manipulation of starch bioaccessibility in wheat endosperm to regulate starch digestion, postprandial glycemia, insulinemia, and gut hormone responses: a randomized controlled trial in healthy ileostomy participants12

PubMed Central

Edwards, Cathrina H; Grundy, Myriam ML; Grassby, Terri; Vasilopoulou, Dafni; Frost, Gary S; Butterworth, Peter J; Berry, Sarah EE; Sanderson, Jeremy; Ellis, Peter R

2015-01-01

Background: Cereal crops, particularly wheat, are a major dietary source of starch, and the bioaccessibility of starch has implications for postprandial glycemia. The structure and properties of plant foods have been identified as critical factors in influencing nutrient bioaccessibility; however, the physical and biochemical disassembly of cereal food during digestion has not been widely studied. Objectives: The aims of this study were to compare the effects of 2 porridge meals prepared from wheat endosperm with different degrees of starch bioaccessibility on postprandial metabolism (e.g., glycemia) and to gain insight into the structural and biochemical breakdown of the test meals during gastroileal transit. Design: A randomized crossover trial in 9 healthy ileostomy participants was designed to compare the effects of 55 g starch, provided as coarse (2-mm particles) or smooth (<0.2-mm particles) wheat porridge, on postprandial changes in blood glucose, insulin, C-peptide, lipids, and gut hormones and on the resistant starch (RS) content of ileal effluent. Undigested food in the ileal output was examined microscopically to identify cell walls and encapsulated starch. Results: Blood glucose, insulin, C-peptide, and glucose-dependent insulinotropic polypeptide concentrations were significantly lower (i.e., 33%, 43%, 40%, and 50% lower 120-min incremental AUC, respectively) after consumption of the coarse porridge than after the smooth porridge (P < 0.01). In vitro, starch digestion was slower in the coarse porridge than in the smooth porridge (33% less starch digested at 90 min, P < 0.05, paired t test). In vivo, the structural integrity of coarse particles (∼2 mm) of wheat endosperm was retained during gastroileal transit. Microscopic examination revealed a progressive loss of starch from the periphery toward the particle core. The structure of the test meal had no effect on the amount or pattern of RS output. Conclusion: The structural integrity of wheat endosperm is largely retained during gastroileal digestion and has a primary role in influencing the rate of starch amylolysis and, consequently, postprandial metabolism. This trial was registered at isrctn.org as ISRCTN40517475. PMID:26333512

"CAN Stop"--implementation and evaluation of a secondary group prevention for adolescent and young adult cannabis users in various contexts--study protocol.

PubMed

Baldus, Christiane; Miranda, Alejandra; Weymann, Nina; Reis, Olaf; Moré, Kerstin; Thomasius, Rainer

2011-04-18

Current research shows that overall numbers for cannabis use among adolescents and young adults dropped in recent years. However, this trend is much less pronounced in continuous cannabis use. With regard to the heightened risk for detrimental health- and development-related outcomes, adolescents and young adults with continuous cannabis use need special attention. The health services structure for adolescents and young adults with substance related problems in Germany, is multifaceted, because different communal, medical and judicial agencies are involved. This results in a rather decentralized organizational structure of the help system. This and further system-inherent characteristics make the threshold for young cannabis users rather high. Because of this, there is a need to establish evidence-based low-threshold help options for young cannabis users, which can be easily disseminated. Therefore, a training programme for young cannabis users (age 14-21) was developed in the "CAN Stop" project. Within the project, we seek to implement and evaluate the training programme within different institutions of the help system. The evaluation is sensitive to the different help systems and their specific prerequisites. Moreover, within this study, we also test the practicability of a training provision through laypersons. The CAN Stop study is a four-armed randomized wait-list controlled trial. The four arms are needed for the different help system settings, in which the CAN Stop training programme is evaluated: (a) the drug addiction aid and youth welfare system, (b) the out-patient medical system, (c) the in-patient medical system and (d) prisons for juvenile offenders. Data are collected at three points, before and after the training or a treatment as usual, and six months after the end of either intervention. The CAN Stop study is expected to provide an evidence-based programme for young cannabis users seeking to reduce or quit their cannabis use. Moreover, we seek to gain knowledge about the programme's utility within different settings of the German help system for young cannabis users and information about the settings' specific clientele. The study protocol is discussed with regard to potential difficulties within the different settings. ISRCTN: ISRCTN57036983.

Modified high-intensity interval training reduces liver fat and improves cardiac function in non-alcoholic fatty liver disease: a randomized controlled trial.

PubMed

Hallsworth, Kate; Thoma, Christian; Hollingsworth, Kieren G; Cassidy, Sophie; Anstee, Quentin M; Day, Christopher P; Trenell, Michael I

2015-12-01

Although lifestyle changes encompassing weight loss and exercise remain the cornerstone of non-alcoholic fatty liver disease (NAFLD) management, the effect of different types of exercise on NAFLD is unknown. This study defines the effect of modified high-intensity interval training (HIIT) on liver fat, cardiac function and metabolic control in adults with NAFLD. Twenty-three patients with NAFLD [age 54±10 years, body mass index (BMI) 31±4 kg/m(2), intra-hepatic lipid >5%) were assigned to either 12 weeks HIIT or standard care (controls). HIIT involved thrice weekly cycle ergometry for 30-40 min. MRI and spectroscopy were used to assess liver fat, abdominal fat and cardiac structure/function/energetics. Glucose control was assessed by oral glucose tolerance test and body composition by air displacement plethysmography. Relative to control, HIIT decreased liver fat (11±5% to 8±2% compared with 10±4% to 10±4% P=0.019), whole-body fat mass (35±7 kg to 33±8 kg compared with 31±9 kg to 32±9 kg, P=0.013), alanine (52±29 units/l to 42±20 units/l compared with 47±22 units/l to 51±24 units/l, P=0.016) and aspartate aminotransferase (AST; 36±18 units/l to 33±15 units/l compared with 31±8 units/l to 35±8 units/l, P=0.017) and increased early diastolic filling rate (244±84 ml/s to 302±107 ml/s compared with 255±82 ml/s to 251±82 ml/s, P=0.018). There were no between groups differences in glucose control. Modified HIIT reduces liver fat and improves body composition alongside benefits to cardiac function in patients with NAFLD and should be considered as part of the broader treatment regimen by clinical care teams. ISRCTN trial ID: ISRCTN78698481. © 2015 Authors; published by Portland Press Limited.

Examining the effectiveness of consuming flour made from agronomically biofortified wheat (Zincol-2016/NR-421) for improving Zn status in women in a low-resource setting in Pakistan: study protocol for a randomised, double-blind, controlled cross-over trial (BiZiFED).

PubMed

Lowe, Nicola M; Khan, Muhammad Jaffar; Broadley, Martin R; Zia, Munir H; McArdle, Harry J; Joy, Edward J M; Ohly, Heather; Shahzad, Babar; Ullah, Ubaid; Kabana, Gul; Medhi, Rashid; Afridi, Mukhtiar Zaman

2018-04-17

Dietary zinc (Zn) deficiency is a global problem, particularly in low-income and middle-income countries where access to rich, animal-source foods of Zn is limited due to poverty. In Pakistan, Zn deficiency affects over 40% of the adult female population, resulting in suboptimal immune status and increased likelihood of complications during pregnancy. We are conducting a double-blind, randomised controlled feeding study with cross-over design in a low-resource setting in Pakistan. Households were provided with flour milled from genetically and agronomically biofortified grain (Zincol-2016/NR-421) or control grain (Galaxy-2013). Fifty households were recruited. Each household included a woman aged 16-49 years who is neither pregnant nor breastfeeding, and not currently consuming nutritional supplements. These women were the primary study participants. All households were provided with control flour for an initial 2-week baseline period, followed by an 8-week intervention period where 25 households receive biofortified flour (group A) and 25 households receive control flour (group B). After this 8-week period, groups A and B crossed over, receiving control and biofortified flour respectively for 8 weeks. Tissue (blood, hair and nails) have been collected from the women at five time points: baseline, middle and end of period 1, and middle and end of period 2. Ethical approval was granted from the lead university (reference no. STEMH 697 FR) and the collaborating institution in Pakistan. The final study methods (including any modifications) will be published in peer-reviewed journals, alongside the study outcomes on completion of the data analysis. In addition, findings will be disseminated to the scientific community via conference presentations and abstracts and communicated to the study participants through the village elders at an appropriate community forum. The trial has been registered with the ISRCTN registry, study ID ISRCTN83678069. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Impact of community based peer support in type 2 diabetes: a cluster randomised controlled trial of individual and/or group approaches.

PubMed

Simmons, David; Prevost, A Toby; Bunn, Chris; Holman, Daniel; Parker, Richard A; Cohn, Simon; Donald, Sarah; Paddison, Charlotte A M; Ward, Candice; Robins, Peter; Graffy, Jonathan

2015-01-01

Diabetes peer support, where one person with diabetes helps guide and support others, has been proposed as a way to improve diabetes management. We have tested whether different diabetes peer support strategies can improve metabolic and/or psychological outcomes. People with type 2 diabetes (n = 1,299) were invited to participate as either 'peer' or 'peer support facilitator' (PSF) in a 2x2 factorial randomised cluster controlled trial across rural communities (130 clusters) in England. Peer support was delivered over 8-12 months by trained PSFs, supported by monthly meetings with a diabetes educator. Primary end point was HbA1c. Secondary outcomes included quality of life, diabetes distress, blood pressure, waist, total cholesterol and weight. Outcome assessors and investigators were masked to arm allocation. Main factors were 1:1 or group intervention. Analysis was by intention-to-treat adjusting for baseline. The 4 arms were well matched (Group n = 330, 1:1(individual) n = 325, combined n = 322, control n = 322); 1035 (79·7%) completed the mid-point postal questionnaire and 1064 (81·9%) had a final HbA1c. A limitation was that although 92.6% PSFs and peers were in telephone contact, only 61.4% of intervention participants attended a face to face session. Mean baseline HbA1c was 57 mmol/mol (7·4%), with no significant change across arms. Follow up systolic blood pressure was 2·3 mm Hg (0.6 to 4.0) lower among those allocated group peer-support and 3·0 mm Hg (1.1 to 5.0) lower if the group support was attended at least once. There was no impact on other outcomes by intention to treat or significant differences between arms in self-reported adherence or medication. Group diabetes peer support over 8-12 months was associated with a small improvement in blood pressure but no other significant outcomes. Long term benefits should be investigated. ISRCTN.com ISRCTN6696362166963621.

Anemia Offers Stronger Protection Than Sickle Cell Trait Against the Erythrocytic Stage of Falciparum Malaria and This Protection Is Reversed by Iron Supplementation.

PubMed

Goheen, M M; Wegmüller, R; Bah, A; Darboe, B; Danso, E; Affara, M; Gardner, D; Patel, J C; Prentice, A M; Cerami, C

2016-12-01

Iron deficiency causes long-term adverse consequences for children and is the most common nutritional deficiency worldwide. Observational studies suggest that iron deficiency anemia protects against Plasmodium falciparum malaria and several intervention trials have indicated that iron supplementation increases malaria risk through unknown mechanism(s). This poses a major challenge for health policy. We investigated how anemia inhibits blood stage malaria infection and how iron supplementation abrogates this protection. This observational cohort study occurred in a malaria-endemic region where sickle-cell trait is also common. We studied fresh RBCs from anemic children (135 children; age 6-24months; hemoglobin <11g/dl) participating in an iron supplementation trial (ISRCTN registry, number ISRCTN07210906) in which they received iron (12mg/day) as part of a micronutrient powder for 84days. Children donated RBCs at baseline, Day 49, and Day 84 for use in flow cytometry-based in vitro growth and invasion assays with P. falciparum laboratory and field strains. In vitro parasite growth in subject RBCs was the primary endpoint. Anemia substantially reduced the invasion and growth of both laboratory and field strains of P. falciparum in vitro (~10% growth reduction per standard deviation shift in hemoglobin). The population level impact against erythrocytic stage malaria was 15.9% from anemia compared to 3.5% for sickle-cell trait. Parasite growth was 2.4 fold higher after 49days of iron supplementation relative to baseline (p<0.001), paralleling increases in erythropoiesis. These results confirm and quantify a plausible mechanism by which anemia protects African children against falciparum malaria, an effect that is substantially greater than the protection offered by sickle-cell trait. Iron supplementation completely reversed the observed protection and hence should be accompanied by malaria prophylaxis. Lower hemoglobin levels typically seen in populations of African descent may reflect past genetic selection by malaria. National Institute of Child Health and Development, Bill and Melinda Gates Foundation, UK Medical Research Council (MRC) and Department for International Development (DFID) under the MRC/DFID Concordat. Crown Copyright © 2016. Published by Elsevier B.V. All rights reserved.

Early motion and directed exercise (EMADE) versus usual care post ankle fracture fixation: study protocol for a pragmatic randomised controlled trial.

PubMed

Matthews, Paul A; Scammell, Brigitte E; Ali, Arfan; Coughlin, Timothy; Nightingale, Jessica; Khan, Tanvir; Ollivere, Ben J

2018-05-31

Following surgical fixation of ankle fractures, the traditional management has included immobilisation for 6 weeks in a below-knee cast. However, this can lead to disuse atrophy of the affected leg and joint stiffness. While early rehabilitation from 2 weeks post surgery is viewed as safe, controversy remains regarding its benefits. We will compare the effectiveness of early motion and directed exercise (EMADE) ankle rehabilitation, against usual care, i.e. 6 weeks' immobilisation in a below-knee cast. We have designed a pragmatic randomised controlled trial (p-RCT) to compare the EMADE intervention against usual care. We will recruit 144 independently living adult participants, absent of tissue-healing comorbidities, who have undergone surgical stabilisation of isolated Weber B ankle fractures. The EMADE intervention consists of a non-weight-bearing progressive home exercise programme, complemented with manual therapy and education. Usual care consists of immobilisation in a non-weight-bearing below-knee cast. The intervention period is between week 2 and week 6 post surgery. The primary outcome is the Olerud and Molander Ankle Score (OMAS) patient-reported outcome measure (PROM) at 12 weeks post surgery. Secondary PROMs include the EQ-5D-5 L questionnaire, return to work and return to driving, with objective outcomes including ankle range of motion. Analysis will be on an intention-to-treat basis. An economic evaluation will be included. The EMADE intervention is a package of care designed to address the detrimental effects of disuse atrophy and joint stiffness. An advantage of the OMAS is the potential of meta-analysis with other designs. Within the economic evaluation, the cost-utility analysis, may be used by commissioners, while the use of patient-relevant outcomes, such as return to work and driving, will ensure that the study remains pertinent to patients and their families. As it is being conducted in the clinical environment, this p-RCT has high external validity. Accordingly, if significant clinical benefits and cost-effectiveness are demonstrated, EMADE should become a worthwhile treatment option. A larger-scale, multicentre trial may be required to influence national guidelines. ISRCTN, ID: ISRCTN11212729 . Registered retrospectively on 20 March 2017.

Specialised teams or personal continuity across inpatient and outpatient mental healthcare? Study protocol for a natural experiment.

PubMed

Giacco, Domenico; Bird, Victoria Jane; McCrone, Paul; Lorant, Vincent; Nicaise, Pablo; Pfennig, Andrea; Bauer, Michael; Ruggeri, Mirella; Lasalvia, Antonio; Moskalewicz, Jacek; Welbel, Marta; Priebe, Stefan

2015-11-25

Mental healthcare organisation can either pursue specialisation, that is, distinct clinicians and teams for inpatient and outpatient care or personal continuity of care, that is, the same primary clinician for a patient across the two settings. Little systematic research has compared these approaches. Existing studies subject have serious methodological shortcomings. Yet, costly reorganisations of services have been carried out in different European countries, inconsistently aiming to achieve specialisation or personal continuity of care. More reliable evidence is required on whether specialisation or continuity of care is more effective and cost-effective, and whether this varies for different patient groups and contexts. In a natural experiment, we aim to recruit at least 6000 patients consecutively admitted to inpatient psychiatric care in Belgium, Germany, Italy, Poland, and the UK. In each country, care approaches supporting specialisation and personal continuity coexist. Patients will be followed up at 1 year to compare outcomes, costs and experiences. Inclusion criteria are: 18 years of age or older; clinical diagnosis of psychosis, affective disorder or anxiety/somatisation disorder; sufficient command of the language of the host country; absence of cognitive deterioration and/or organic brain disorders; and capacity to provide informed consent. Ethical approval was obtained in all countries: (1) England: NRES Committee North East-Newcastle & North Tyneside (ref: 14/NE/1017); (2) Belgium: Comité d'Ethique hospitalo-facultaire des Cliniques St-Luc; (3) Germany: Ethical Board, Technische Universität Dresden; (4) Italy: Comitati Etici per la sperimentazione clinica (CESC) delle provincie di Verona, Rovigo, Vicenza, Treviso, Padova; (5) Poland: Komisja Bioetyczna przy Instytucie Psychiatrii i Neurologii w Warszawie. We will disseminate the findings through scientific publications and a study-specific website. At the end of the study, we will develop recommendations for policy decision-making, and organise national and international workshops with stakeholders. ISRCTN registry: ISRCTN40256812. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

Assessment of a primary care-based telemonitoring intervention for home care patients with heart failure and chronic lung disease. The TELBIL study

PubMed Central

2011-01-01

Background Telemonitoring technology offers one of the most promising alternatives for the provision of health care services at the patient's home. The primary aim of this study is to evaluate the impact of a primary care-based telemonitoring intervention on the frequency of hospital admissions. Methods/design A primary care-based randomised controlled trial will be carried out to assess the impact of a telemonitoring intervention aimed at home care patients with heart failure (HF) and/or chronic lung disease (CLD). The results will be compared with those obtained with standard health care practice. The duration of the study will be of one year. Sixty patients will be recruited for the study. In-home patients, diagnosed with HF and/or CLD, aged 14 or above and with two or more hospital admissions in the previous year will be eligible. For the intervention group, telemonitoring will consist of daily patient self-measurements of respiratory-rate, heart-rate, blood pressure, oxygen saturation, weight and body temperature. Additionally, the patients will complete a qualitative symptom questionnaire daily using the telemonitoring system. Routine telephone contacts will be conducted every fortnight and additional telephone contacts will be carried out if the data received at the primary care centre are out of the established limits. The control group will receive usual care. The primary outcome measure is the number of hospital admissions due to any cause that occurred in a period of 12 months post-randomisation. The secondary outcome measures are: duration of hospital stay, hospital admissions due to HF or CLD, mortality rate, use of health care resources, quality of life, cost-effectiveness, compliance and patient and health care professional satisfaction with the new technology. Discussion The results of this study will shed some light on the effects of telemonitoring for the follow-up and management of chronic patients from a primary care setting. The study may contribute to enhance the understanding of alternative modes of health care provision for medically unstable elderly patients, who bear a high degree of physical and functional deterioration. Trial Registration ISRCTN: ISRCTN89041993 PMID:21385401

Identifying continence options after stroke (ICONS): a cluster randomised controlled feasibility trial.

PubMed

Thomas, Lois H; Watkins, Caroline L; Sutton, Christopher J; Forshaw, Denise; Leathley, Michael J; French, Beverley; Burton, Christopher R; Cheater, Francine; Roe, Brenda; Britt, David; Booth, Joanne; McColl, Elaine

2014-12-23

Urinary incontinence (UI) affects half of patients hospitalised after stroke and is often poorly managed. Cochrane systematic reviews have shown some positive impact of conservative interventions (such as bladder training) in reducing UI, but their effectiveness has not been demonstrated with stroke patients. We conducted a cluster randomised controlled feasibility trial of a systematic voiding programme (SVP) for the management of UI after stroke. Stroke services were randomised to receive SVP (n = 4), SVP plus supported implementation (SVP+, n = 4), or usual care (UC, n = 4).Feasibility outcomes were participant recruitment and retention. The main effectiveness outcome was presence or absence of UI at six and 12 weeks post-stroke. Additional effectiveness outcomes included were the effect of the intervention on different types of UI, continence status at discharge, UI severity, functional ability, quality of life, and death. It was possible to recruit patients (413; 164 SVP, 125 SVP+, and 124 UC) and participant retention was acceptable (85% and 88% at six and 12 weeks, respectively). There was no suggestion of a beneficial effect on the main outcome at six (SVP versus UC: odds ratio (OR) 0.94, 95% CI: 0.46 to 1.94; SVP+ versus UC: OR: 0.62, 95% CI: 0.28 to 1.37) or 12 weeks (SVP versus UC: OR: 1.02, 95% CI: 0.54 to 1.93; SVP+ versus UC: OR: 1.06, 95% CI: 0.54 to 2.09).No secondary outcomes showed a strong suggestion of clinically meaningful improvement in SVP and/or SVP+ arms relative to UC at six or 12 weeks. However, at 12 weeks both intervention arms had higher estimated odds of continence than UC for patients with urge incontinence. The trial has met feasibility outcomes of participant recruitment and retention. It was not powered to demonstrate effectiveness, but there is some evidence of a potential reduction in the odds of specific types of incontinence. A full trial should now be considered. ISRCTN Registry, ISRCTN08609907, date of registration: 7 July 2010.

Fermented dairy products consumption is associated with attenuated cortical bone loss independently of total calcium, protein, and energy intakes in healthy postmenopausal women.

PubMed

Biver, E; Durosier-Izart, C; Merminod, F; Chevalley, T; van Rietbergen, B; Ferrari, S L; Rizzoli, R

2018-05-03

A longitudinal analysis of bone microstructure in postmenopausal women of the Geneva Retirees Cohort indicates that age-related cortical bone loss is attenuated at non-bearing bone sites in fermented dairy products consumers, not in milk or ripened cheese consumers, independently of total energy, calcium, or protein intakes. Fermented dairy products (FDP), including yogurts, provide calcium, phosphorus, and proteins together with prebiotics and probiotics, all being potentially beneficial for bone. In this prospective cohort study, we investigated whether FDP, milk, or ripened cheese consumptions influence age-related changes of bone mineral density (BMD) and microstructure. Dietary intakes were assessed at baseline and after 3.0 ± 0.5 years with a food frequency questionnaire in 482 postmenopausal women enrolled in the Geneva Retirees Cohort. Cortical (Ct) and trabecular (Tb) volumetric (v) BMD and microstructure at the distal radius and tibia were assessed by high-resolution peripheral quantitative computerized tomography, in addition to areal (a) BMD and body composition by dual-energy X-ray absorptiometry, at the same time points. At baseline, FDP consumers had lower abdominal fat mass and larger bone size at the radius and tibia. Parathyroid hormone and β-carboxyterminal cross-linked telopeptide of type I collagen levels were inversely correlated with FDP consumption. In the longitudinal analysis, FDP consumption (mean of the two assessments) was associated with attenuated loss of radius total vBMD and of Ct vBMD, area, and thickness. There was no difference in aBMD and at the tibia. These associations were independent of total energy, calcium, or protein intakes. For other dairy products categories, only milk consumption was associated with lower decrease of aBMD and of failure load at the radius. In this prospective cohort of healthy postmenopausal women, age-related Ct bone loss was attenuated at non-bearing bone sites in FDP consumers, not in milk or ripened cheese consumers, independently of total energy, calcium, or protein intakes. ISRCTN11865958 ( http://www.isrctn.com ).

SFAs do not impair endothelial function and arterial stiffness123

PubMed Central

Sanders, Thomas AB; Lewis, Fiona J; Goff, Louise M; Chowienczyk, Philip J

2013-01-01

Background: It is uncertain whether saturated fatty acids (SFAs) impair endothelial function and contribute to arterial stiffening. Objective: We tested the effects of replacing SFAs with monounsaturated fatty acids (MUFAs) or carbohydrates on endothelial function and arterial stiffness. Design: With the use of a parallel-designed randomized controlled trial in 121 insulin-resistant men and women, we measured vascular function after 1 mo of consumption of a high-SFA (HS) diet and after 24 wk after random assignment to the HS diet or diets that contained <10% SFAs and were high in either MUFAs or carbohydrates. The primary outcome was a change in flow-mediated dilation (FMD), and secondary outcomes were changes in carotid to femoral pulse wave velocity (PWV) and plasma 8-isoprostane F2α-III concentrations. Results: For 112 participants with data available for analysis on the specified outcomes, no significant differences were shown. FMD with the HS reference diet was 6.7 ± 2.2%, and changes (95% CIs) after 6 mo of intervention were +0.3 (−0.4, 1.1), −0.2 (−0.8, 0.5), and −0.1 (−0.6, 0.7) with HS, high-MUFA (HM), and high-carbohydrate (HC) diets, respectively. After consumption of the HS reference diet, the geometric mean (±SD) PWV was 7.67 ± 1.62 m/s, and mean percentages of changes (95% CIs) were −1.0 (−6.2, 4.3) with the HS diet, 2.7 (−1.4, 6.9) with the HM diet, and −1.0 (−5.5, 3.4) with the HC diet. With the HS reference diet, the geometric mean (±SD) plasma 8-isoprostane F2α-III concentration was 176 ± 85 pmol/L, and mean percentage of changes (95% CIs) were 1 (−12, 14) with the HS diet, 6 (−5, 16) with the HM diet, and 4 (−7, 16) with the HC diet. Conclusion: The replacement of SFAs with MUFAs or carbohydrates in healthy subjects does not affect vascular function. This trial was registered at Current Controlled Trials (http://www.controlled-trials.com/ISRCTN) as ISRCTN 29111298. PMID:23964054

Impact of Personalised Feedback about Physical Activity on Change in Objectively Measured Physical Activity (the FAB Study): A Randomised Controlled Trial

PubMed Central

Godino, Job G.; Watkinson, Clare; Corder, Kirsten; Marteau, Theresa M.; Sutton, Stephen; Sharp, Stephen J.; Griffin, Simon J.; van Sluijs, Esther M. F.

2013-01-01

Background Low levels of physical activity are a major public health concern, and interventions to promote physical activity have had limited success. Whether or not personalised feedback about physical activity following objective measurement motivates behaviour change has yet to be rigorously examined. Methods And Findings: In a parallel group, open randomised controlled trial, 466 healthy adults aged 32 to 54 years were recruited from the ongoing population-based Fenland Study (Cambridgeshire, UK). Participants were randomised to receive either no feedback until the end of the trial (control group, n=120) or one of three different types of feedback: simple, visual, or contextualised (intervention groups, n=346). The primary outcome was physical activity (physical activity energy expenditure (PAEE) in kJ/kg/day and average body acceleration (ACC) in m/s2) measured objectively using a combined heart rate monitor and accelerometer (Actiheart®). The main secondary outcomes included self-reported physical activity, intention to increase physical activity, and awareness of physical activity (the agreement between self-rated and objectively measured physical activity). At 8 weeks, 391 (83.9%) participants had complete physical activity data. The intervention had no effect on objectively measured physical activity (PAEE: β=-0.92, 95% CI=-3.50 to 1.66, p=0.48 and ACC: β=0.01, 95% CI=-0.00 to 0.02, p=0.21), self-reported physical activity (β=-0.39, 95% CI=-1.59 to 0.81), or intention to increase physical activity (β=-0.05, 95% CI=-0.22 to 0.11). However, it was associated with an increase in awareness of physical activity (OR=1.74, 95% CI=1.05 to 2.89). Results did not differ according to the type of feedback. Conclusions Personalised feedback about physical activity following objective measurement increased awareness but did not result in changes in physical activity in the short term. Measurement and feedback may have a role in promoting behaviour change but are ineffective on their own. Trial Registration Current Controlled Trials ISRCTN92551397 http://www.controlled-trials.com/ISRCTN92551397 PMID:24066178

Online Cognitive Behavioral Therapy for Bulimic Type Disorders, Delivered in the Community by a Nonclinician: Qualitative Study

PubMed Central

McClay, Carrie-Anne; Waters, Louise; McHale, Ciaran; Schmidt, Ulrike

2013-01-01

Background Cognitive behavioral therapy is recommended in the National Institute for Clinical Excellence guidelines for the treatment of bulimia nervosa. In order to make this treatment option more accessible to patients, interactive online CBT programs have been developed that can be used in the user’s own home, in privacy, and at their convenience. Studies investigating online CBT for bulimic type eating disorders have provided promising results and indicate that, with regular support from a clinician or trained support worker, online CBT can be effective in reducing bulimic symptoms. Two main factors distinguish this study from previous research in this area. First, the current study recruited a wide range of adults with bulimic type symptoms from the community. Second, the participants in the current study had used cCBT with support from a nonclinical support worker rather than a specialist eating disorder clinician. Objective To investigate participants’ experiences of using an online self-help cognitive behavioral therapy (CBT) package (Overcoming Bulimia Online) for bulimia nervosa (BN) and eating disorders not otherwise specified (EDNOS). Methods Eight participants with a mean age of 33.9 years took part in semi-structured interviews. Interviews were transcribed and analyzed using a 6-step thematic analysis process. Results Saturation was achieved, and 7 themes were identified in the dataset. These were: (1) conceptualizing eating disorders, (2) help-seeking behavior, (3) aspects of the intervention, (4) motivation to use the online package, (5) privacy and secrecy with regard to their eating problems, (6) recovery and the future, and (7) participant engagement describing individuals’ thoughts on taking part in the online research study. Conclusions Participants suggested that online CBT self-help represented a generally desirable and acceptable treatment option for those with bulimic type eating problems, despite some difficulties with motivation and implementation of some elements of the package. Trial Registration International Standard Randomized Controlled Trial Number of the original RCT that this study is based on: ISRCTN41034162; http://www.controlled-trials.com/ISRCTN41034162 (Archived by WebCite at http://www.webcitation.org/6Ey9sBWTV) PMID:23502689

Safety of Perioperative Aprotinin Administration During Isolated Coronary Artery Bypass Graft Surgery: Insights From the ART (Arterial Revascularization Trial).

PubMed

Benedetto, Umberto; Altman, Douglas G; Gerry, Stephen; Gray, Alastair; Lees, Belinda; Angelini, Gianni D; Flather, Marcus; Taggart, David P

2018-03-03

There is still uncertainty about the safety of aprotinin for coronary artery bypass graft surgery. The ART (Arterial Revascularization Trial) was designed to compare survival after bilateral versus single internal thoracic artery grafting. Many of the ART patients (≈30%) received perioperative aprotinin. We investigated the association between perioperative aprotinin administration and short-term (in-hospital) and long-term outcomes by performing a post hoc analysis of the ART. Among patients enrolled in the ART (n=3102) from 2004 to 2007, we excluded those who did not undergo surgery (n=18) and those with no information about use of perioperative aprotinin (n=9). Finally, 836 of 3076 patients (27%) received aprotinin. Propensity matching was used to select 536 pairs for final comparison. Aprotinin was also associated with an increased risk of hospital mortality (9 [1.7%] versus 1 [0.2%]; odds ratio, 9.12; 95% confidence interval [CI], 1.15-72.2; P =0.03), intra-aortic balloon pump insertion (37 [6.9%] versus 17 [3.2%]; odds ratio, 2.26; 95% CI, 1.26-4.07; P =0.006), and acute kidney injury (102 [19.0%] versus 76 [14.2%]; odds ratio, 1.42; 95% CI, 1.03-1.97; P =0.03). Aprotinin was not associated with a lower incidence of transfusion (37 [6.9%] versus 28 [5.2%]; odds ratio, 1.34; 95% CI, 0.81-2.23; P =0.25) and reexploration (26 [4.9%] versus 19 [3.5%]; hazard ratio, 1.39; 95% CI, 0.76-2.53; P =0.28). At 5 years, all-cause mortality was significantly increased in the aprotinin group (56 [10.6%] versus 38 [7.3%]; hazard ratio, 1.51; 95% CI, 1.0-2.28; P =0.045). In the present post hoc ART analysis, aprotinin was associated with a significantly increased risk of early and late mortality. URL: http://www.isrctn.com. Unique identifier: ISRCTN46552265. © 2018 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley.

Predictive risk stratification model: a progressive cluster-randomised trial in chronic conditions management (PRISMATIC) research protocol

PubMed Central

2013-01-01

Background An ageing population increases demand on health and social care. New approaches are needed to shift care from hospital to community and general practice. A predictive risk stratification tool (Prism) has been developed for general practice that estimates risk of an emergency hospital admission in the following year. We present a protocol for the evaluation of Prism. Methods/Design We will undertake a mixed methods progressive cluster-randomised trial. Practices begin as controls, delivering usual care without Prism. Practices will receive Prism and training randomly, and thereafter be able to use Prism with clinical and technical support. We will compare costs, processes of care, satisfaction and patient outcomes at baseline, 6 and 18 months, using routine data and postal questionnaires. We will assess technical performance by comparing predicted against actual emergency admissions. Focus groups and interviews will be undertaken to understand how Prism is perceived and adopted by practitioners and policy makers. We will model data using generalised linear models and survival analysis techniques to determine whether any differences exist between intervention and control groups. We will take account of covariates and explanatory factors. In the economic evaluation we will carry out a cost-effectiveness analysis to examine incremental cost per emergency admission to hospital avoided and will examine costs versus changes in primary and secondary outcomes in a cost-consequence analysis. We will also examine changes in quality of life of patients across the risk spectrum. We will record and transcribe focus groups and interviews and analyse them thematically. We have received full ethical and R&D approvals for the study and Information Governance Review Panel (IGRP) permission for the use of routine data. We will comply with the CONSORT guidelines and will disseminate the findings at national and international conferences and in peer-reviewed journals. Discussion The proposed study will provide information on costs and effects of Prism; how it is used in practice, barriers and facilitators to its implementation; and its perceived value in supporting the management of patients with and at risk of developing chronic conditions. Trial registration Controlled Clinical Trials ISRCTN no. ISRCTN55538212. PMID:24330749

Study protocol for a multi-component kindergarten-based intervention to promote healthy diets in toddlers: a cluster randomized trial.

PubMed

Helland, Sissel H; Bere, Elling; Øverby, Nina Cecilie

2016-03-17

There is concern about the lack of diversity in children's diets, particularly low intakes of fruit and vegetables and high intakes of unhealthy processed food. This may be a factor in the rising prevalence of obesity. A reason for the lack of diversity in children's diets may be food neophobia. This study aimed to promote a healthy and varied diet among toddlers in kindergarten. The primary objectives were to reduce food neophobia in toddlers, and promote healthy feeding practices among kindergarten staff and parents. Secondary objectives were to increase food variety in toddlers' diets and reduce future overweight and obesity in these children. This is an ongoing, cluster randomized trial. The intervention finished in 2014, but follow-up data collection is not yet complete. Eighteen randomly selected kindergartens located in two counties in Norway with enrolled children born in 2012 participated in the intervention. The kindergartens were matched into pairs based on background information, and randomly assigned to the intervention or control groups. A 9-week multi-component intervention was implemented, with four main elements: 1) kindergarten staff implemented a pedagogical tool (Sapere method) in daily sessions to promote willingness to try new food; 2) kindergarten staff prepared and served the toddlers a cooked lunch from a menu corresponding to the pedagogical sessions; 3) kindergarten staff were encouraged to follow 10 meal principles on modeling, responsive feeding, repeated exposure, and enjoyable meals; and 4) parents were encouraged to read information and apply relevant feeding practices at home. The control group continued their usual practices. Preference taste tests were conducted to evaluate behavioral food neophobia, and children's height and weight were measured. Parents and staff completed questionnaires before and after the intervention. Data have not yet been analyzed. This study provides new knowledge about whether or not a Sapere-sensory education and healthy meal intervention targeting children, kindergarten staff, and parents will: reduce levels of food neophobia in toddlers; improve parental and kindergarten feeding practices; improve children's dietary variety; and reduce childhood overweight and obesity. ISRCTN74823448 DOI 10.1186/ISRCTN74823448.

Understanding influences on teachers' uptake and use of behaviour management strategies within the STARS trial: process evaluation protocol for a randomised controlled trial.

PubMed

Hansford, Lorraine; Sharkey, Siobhan; Edwards, Vanessa; Ukoumunne, Obioha; Byford, Sarah; Norwich, Brahm; Logan, Stuart; Ford, Tamsin

2015-02-10

The 'Supporting Teachers And childRen in Schools' (STARS) study is a cluster randomised controlled trial evaluating the Incredible Years Teacher Classroom Management (TCM) programme as a public health intervention. TCM is a 6 day training course delivered to groups of 8-12 teachers. The STARS trial will investigate whether TCM can improve children's behaviour, attainment and wellbeing, reduce teachers' stress and improve their self-efficacy. This protocol describes the methodology of the process evaluation embedded within the main trial, which aims to examine the uptake and implementation of TCM strategies within the classroom plus the wider school environment and improve the understanding of outcomes. The STARS trial will work with eighty teachers of children aged 4-9 years from eighty schools. Teachers will be randomised to attend the TCM course (intervention arm) or to "teach as normal" (control arm) and attend the course a year later. The process evaluation will use quantitative and qualitative approaches to assess fidelity to model, as well as explore headteachers' and teachers' experiences of TCM and investigate school factors that influence the translation of skills learnt to practice. Four of the eight groups of teachers (n = 40) will be invited to participate in focus groups within one month of completing the TCM course, and again a year later, while 45 of the 80 headteachers will be invited to take part in telephone interviews. Standardised checklists will be completed by group leaders and each training session will be videotaped to assess fidelity to model. Teachers will also complete standardised session evaluations. This study will provide important information about whether the Teacher Classroom Management course influences child and teacher mental health and well-being in both the short and long term. The process evaluation will provide valuable insights into factors that may facilitate or impede any impact. The trial has been registered with ISCTRN (Controlled Trials Ltd) and assigned an ISRCTN number ISRCTN84130388 . Date assigned: 15 May 2012.

Investigating the effectiveness and cost-effectiveness of FITNET-NHS (Fatigue In Teenagers on the interNET in the NHS) compared to Activity Management to treat paediatric chronic fatigue syndrome (CFS)/myalgic encephalomyelitis (ME): protocol for a randomised controlled trial.

PubMed

Baos, Sarah; Brigden, Amberly; Anderson, Emma; Hollingworth, William; Price, Simon; Mills, Nicola; Beasant, Lucy; Gaunt, Daisy; Garfield, Kirsty; Metcalfe, Chris; Parslow, Roxanne; Downing, Harriet; Kessler, David; Macleod, John; Stallard, Paul; Knoop, Hans; Van de Putte, Elise; Nijhof, Sanne; Bleijenberg, Gijs; Crawley, Esther

2018-02-22

Paediatric chronic fatigue syndrome or myalgic encephalomyelitis (CFS/ME) is a relatively common and disabling condition. The National Institute for Health and Clinical Excellence (NICE) recommends Cognitive Behavioural Therapy (CBT) as a treatment option for paediatric CFS/ME because there is good evidence that it is effective. Despite this, most young people in the UK are unable to access local specialist CBT for CFS/ME. A randomised controlled trial (RCT) showed FITNET was effective in the Netherlands but we do not know if it is effective in the National Health Service (NHS) or if it is cost-effective. This trial will investigate whether FITNET-NHS is clinically effective and cost-effective in the NHS. Seven hundred and thirty-four paediatric patients (aged 11-17 years) with CFS/ ME will be randomised (1:1) to receive either FITNET-NHS (online CBT) or Activity Management (delivered via video call). The internal pilot study will use integrated qualitative methods to examine the feasibility of recruitment and the acceptability of treatment. The full trial will assess whether FITNET-NHS is clinically effective and cost-effective. The primary outcome is disability at 6 months, measured using the SF-36-PFS (Physical Function Scale) questionnaire. Cost-effectiveness is measured via cost-utility analysis from an NHS perspective. Secondary subgroup analysis will investigate the effectiveness of FITNET-NHS in those with co-morbid mood disorders. If FITNET-NHS is found to be feasible and acceptable (internal pilot) and effective and cost-effective (full trial), its provision by the NHS has the potential to deliver substantial health gains for the large number of young people suffering from CFS/ME but unable to access treatment because there is no local specialist service. This trial will provide further evidence evaluating the delivery of online CBT to young people with chronic conditions. ISRCTN registry, registration number: ISRCTN18020851 . Registered on 4 August 2016.

Free breakfasts in schools: design and conduct of a cluster randomised controlled trial of the Primary School Free Breakfast Initiative in Wales [ISRCTN18336527

PubMed Central

Moore, Laurence; Moore, Graham F; Tapper, Katy; Lynch, Rebecca; Desousa, Carol; Hale, Janine; Roberts, Chris; Murphy, Simon

2007-01-01

Background School-based breakfast provision is increasingly being seen as a means of improving educational performance and dietary behaviour amongst children. Furthermore, recognition is growing that breakfast provision offers potential as a means of addressing social inequalities in these outcomes. At present however, the evidence base on the effectiveness of breakfast provision in bringing about these improvements is limited. Methods/Design This paper describes the research design of a large scale evaluation of the effectiveness of the Welsh Assembly Government's Primary School Free Breakfast Initiative. A cluster randomised trial, with school as the unit of randomisation was used for the outcome evaluation, with a nested qualitative process evaluation. Quantitative outcome measures included dietary habits, attitudes, cognitive function, classroom behaviour, and school attendance. The study recruited 111 primary schools in Wales, of which 56 were randomly assigned to control condition and 55 to intervention. Participants were Year 5 and 6 students (aged 9–11 years) in these schools. Data were collected for all 111 schools at each of three time points: baseline, 4 month and 12 month follow-up. This was achieved through a repeated cross-sectional survey of approximately 4350 students on each of these occasions. Of those students in Year 5 at baseline, 1975 provided data at one or both of the follow-ups, forming a nested cohort. The evaluation also included a nested process evaluation, using questionnaires, semi-structured interviews and case studies with students, school staff, and local authority scheme coordinators as key informants. Discussion An overview of the methods used for the evaluation is presented, providing an example of the feasibility of conducting robust evaluations of policy initiatives using a randomised trial design with nested process evaluation. Details are provided of response rates and the flow of participants. Reflection is offered on methodological issues encountered at various stages through the course of the study, focusing upon issues associated with conducting a randomised trial of a government policy initiative, and with conducting research in school settings. Trial registration Current Controlled Trials ISRCTN18336527 PMID:17888158

Improving Population-Level Maternal Health: A Hard Nut to Crack? Long Term Findings and Reflections on a 16-Community Randomised Trial in Australia to Improve Maternal Emotional and Physical Health after Birth [ISRCTN03464021

PubMed Central

Small, Rhonda; Watson, Lyndsey; Gunn, Jane; Mitchell, Creina; Brown, Stephanie

2014-01-01

Background Community level interventions to improve maternal and child health have been supported and well evaluated in resource poor settings, but less so in developed countries. PRISM - Program of Resources, Information and Support for Mothers - was a primary care and community-based cluster-randomised trial in sixteen municipalities in Victoria, Australia, which aimed to reduce depression in mothers and improve their physical health. The aim of this paper is to report the longer term outcomes of PRISM and to reflect on lessons learned from this universal community intervention to improve maternal health. Methods Maternal health outcome data in PRISM were collected by postal questionnaire at six months and two years. At two years, the main outcome measures included the Edinburgh Postnatal Depression Scale (EPDS) and the SF-36. Secondary outcome measures included the Experience of Motherhood Scale (EOM) and the Parenting Stress Index (PSI). A primary intention to treat analysis was conducted, adjusting for the randomisation by cluster. Results 7,169/18,424 (39%) women responded to the postal questionnaire at two years −3,894 (40%) in the intervention arm and 3,275 (38%) in the comparison arm. Respondents were mostly representative on available population data comparisons. There were no differences in depression prevalence (EPDS≥13) between the intervention and comparison arms (13.4% vs 13.1%; ORadj = 1.06, 95%CI 0.91–1.24). Nor did women's mental health (MCS: 48.6 vs 49.1) or physical health scores (PCS: 49.1 vs 49.0) on the SF-36 differ between the trial arms. Conclusion Improvement in maternal mental and physical health outcomes at the population level in the early years after childbirth remains a largely unmet challenge. Despite the lack of effectiveness of PRISM intervention strategies, important lessons about systems change, sustained investment and contextual understanding of the workability of intervention strategies can be drawn from the experience of PRISM. Trial Registration. Controlled-Trials.com ISRCTN03464021 PMID:24586327

Modulation of fecal Clostridiales bacteria and butyrate by probiotic intervention with Lactobacillus paracasei DG varies among healthy adults.

PubMed

Ferrario, Chiara; Taverniti, Valentina; Milani, Christian; Fiore, Walter; Laureati, Monica; De Noni, Ivano; Stuknyte, Milda; Chouaia, Bessem; Riso, Patrizia; Guglielmetti, Simone

2014-11-01

The modulation of gut microbiota is considered to be the first target to establish probiotic efficacy in a healthy population. This study was conducted to determine the impact of a probiotic on the intestinal microbial ecology of healthy volunteers. High-throughput 16S ribosomal RNA gene sequencing was used to characterize the fecal microbiota in healthy adults (23-55 y old) of both sexes, before and after 4 wk of daily consumption of a capsule containing at least 24 billion viable Lactobacillus paracasei DG cells, according to a randomized, double-blind, crossover placebo-controlled design. Probiotic intake induced an increase in Proteobacteria (P = 0.006) and in the Clostridiales genus Coprococcus (P = 0.009), whereas the Clostridiales genus Blautia (P = 0.036) was decreased; a trend of reduction was also observed for Anaerostipes (P = 0.05) and Clostridium (P = 0.06). We also found that the probiotic effect depended on the initial butyrate concentration. In fact, participants with butyrate >100 mmol/kg of wet feces had a mean butyrate reduction of 49 ± 21% and a concomitant decrease in the sum of 6 Clostridiales genera, namely Faecalibacterium, Blautia, Anaerostipes, Pseudobutyrivibrio, Clostridium, and Butyrivibrio (P = 0.021), after the probiotic intervention. In contrast, in participants with initial butyrate concentrations <25 mmol/kg of wet feces, the probiotic contributed to a 329 ± 255% (mean ± SD) increment in butyrate concomitantly with an ∼55% decrease in Ruminococcus (P = 0.016) and a 150% increase in an abundantly represented unclassified Bacteroidales genus (P = 0.05). The intake of L. paracasei DG increased the Blautia:Coprococcus ratio, which, according to the literature, can potentially confer a health benefit on the host. The probiotic impact on the microbiota and on short-chain fatty acids, however, seems to strictly depend on the initial characteristics of the intestinal microbial ecosystem. In particular, fecal butyrate concentrations could represent an important biomarker for identifying subjects who may benefit from probiotic treatment. This trial was registered at www.controlled-trials.com/isrctn as ISRCTN56945491. © 2014 American Society for Nutrition.

The UK Cardiac and Vascular Surgery Interventional Anaemia Response (CAVIAR) Study: protocol for an observational cohort study to determine the impact and effect of preoperative anaemia management in cardiac and vascular surgical patients.

PubMed

Chau, Marisa; Richards, Toby; Evans, Caroline; Butcher, Anna; Collier, Timothy; Klein, Andrew

2017-04-18

Preoperative anaemia is linked to poor postsurgical outcome, longer hospital stays, greater risk of complications and mortality. Currently in the UK, some sites have developed anaemia clinics or pathways that use intravenous iron to correct iron deficiency anaemia prior to surgery as their standard of care. Although intravenous iron has been observed to be effective in a variety of patient settings, there is insufficient evidence in its use in cardiac and vascular patients. The aim of this study is to observe the impact and effect of anaemia and its management in patients undergoing cardiac and vascular surgery. In addition, the UK Cardiac and Vascular Surgery Interventional Anaemia Response (CAVIAR) Study is also a feasibility study with the aim to establish anaemia management pathways in the preoperative setting to inform the design of future randomised controlled trials. The UK CAVIAR Study is a multicentre, stepped, observational study, in patients awaiting major cardiac or vascular surgery. We will be examining different haematological variables (especially hepcidin), functional capacity and patient outcome. Patients will be compared based on their anaemia status, whether they received intravenous iron in accordance to their hospital's preoperative pathway, and their disease group. The primary outcomes are the change in haemoglobin levels from baseline (before treatment) to before surgery; and the number of successful patients recruited and consented (feasibility). The secondary outcomes will include changes in biomarkers of iron deficiency, length of stay, quality of life and postoperative recovery. The study protocol was approved by the London-Westminster Research Ethics Committee (15/LO/1569, 27 November 2015). NHS approval was also obtained with each hospital trust. The findings of the study will be published in peer-reviewed journals. Clinical Trials registry (NCT02637102) and the ISRCTN registry (ISRCTN55032357). © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Research Exploring Physical Activity in Care Homes (REACH): study protocol for a randomised controlled trial.

PubMed

Forster, Anne; Airlie, Jennifer; Birch, Karen; Cicero, Robert; Cundill, Bonnie; Ellwood, Alison; Godfrey, Mary; Graham, Liz; Green, John; Hulme, Claire; Lawton, Rebecca; McLellan, Vicki; McMaster, Nicola; Farrin, Amanda

2017-04-19

As life expectancy increases and the number of older people, particularly those aged 85 years and over, expands there is an increase in demand for long-term care. A large proportion of people in a care home setting spend most of their time sedentary, and this is one of the leading preventable causes of death. Encouraging residents to engage in more physical activity could deliver benefits in terms of physical and psychological health, and quality of life. This study is the final stage of a programme of research to develop and preliminarily test an evidence-based intervention designed to enhance opportunities for movement amongst care home residents, thereby increasing levels of physical activity. This is a cluster randomised feasibility trial, aiming to recruit at least 8-12 residents at each of 12 residential care homes across Yorkshire, UK. Care homes will be randomly allocated on a 1:1 basis to receive either the intervention alongside usual care, or to continue to provide usual care alone. Assessment will be undertaken with participating residents at baseline (prior to care home randomisation) and at 3, 6, and 9 months post-randomisation. Data relating to changes in physical activity, physical function, level of cognitive impairment, mood, perceived health and wellbeing, and quality of life will be collected. Data at the level of the home will also be collected and will include staff experience of care, and changes in the numbers and types of adverse events residents experience (for example, hospital admissions, falls). Details of National Health Service (NHS) usage will be collected to inform the economic analysis. An embedded process evaluation will obtain information to test out the theory of change underpinning the intervention and its acceptability to staff and residents. This feasibility trial with embedded process evaluation and collection of health economic data will allow us to undertake detailed feasibility work to inform a future large-scale trial. It will provide valuable information to inform research procedures in this important but challenging area. ISRCTN registry, ISRCTN16076575 . Registered on 25 June 2015.

An effectiveness study of an integrated, community-based package for maternal, newborn, child and HIV care in South Africa: study protocol for a randomized controlled trial

PubMed Central

2011-01-01

Background Progress towards MDG4 in South Africa will depend largely on scaling up effective prevention against mother to child transmission (PMTCT) of HIV and also addressing neonatal mortality. This imperative drives increasing focus on the neonatal period and particularly on the development and testing of appropriate models of sustainable, community-based care in South Africa in order to reach the poor. A number of key implementation gaps affecting progress have been identified. Implementation gaps for HIV prevention in neonates; implementation gaps for neonatal care especially home postnatal care; and implementation gaps for maternal mental health support. We have developed and are evaluating and costing an integrated and scaleable home visit package delivered by community health workers targeting pregnant and postnatal women and their newborns to provide essential maternal/newborn care as well as interventions for Prevention of Mother to Child Transmission (PMTCT) of HIV. Methods The trial is a cluster randomized controlled trial that is being implemented in Umlazi which is a peri-urban settlement with a total population of 1 million close to Durban in KwaZulu Natal, South Africa. The trial consists of 30 randomized clusters (15 in each arm). A baseline survey established the homogeneity of clusters and neither stratification nor matching was performed. Sample size was based on increasing HIV-free survival from 74% to 84%, and calculated to be 120 pregnant women per cluster. Primary outcomes are higher levels of HIV free survival and levels of exclusive and appropriate infant feeding at 12 weeks postnatally. The intervention is home based with community health workers delivering two antenatal visits, a postnatal visit within 48 hours of birth, and a further four visits during the first two months of the infants life. We are undertaking programmatic and cost effectiveness analysis to cost the intervention. Discussion The question is not merely to develop an efficacious package but also to identify and test delivery strategies that enable scaling up, which requires effectiveness studies in a health systems context, adapting and testing Asian community-based studies in various African contexts. Trial registration ISRCTN: ISRCTN41046462 PMID:22044553