Multicentric primary extramammary Paget disease: a Toker cell disorder?

PubMed

Hashemi, Pantea; Kao, Grace F; Konia, Thomas; Kauffman, Lisa C; Tam, Christine C; Sina, Bahram

2014-07-01

Toker cells are epithelial clear cells found in the areolar and nipple areas of the breast, vulvar region, and other apocrine gland-bearing areas of the skin. Toker cells have been implicated in the pathogenesis of clear cell papulosis, cutaneous hamartoma with pagetoid cells, and rare cases of primary extramammary Paget disease (EMPD) but not in secondary EMPD with underlying adenocarcinoma. The pathogenesis of primary EMPD is not well defined. We report a case of multicentric primary EMPD with evidence of Toker cell proliferation and nonaggressive biologic behavior in a 63-year-old white man. A detailed description of the morphologic and biologic features of Toker cells and their possible carcinogenetic links also are discussed. Based on the observation and follow-up of our patient, we hypothesize that multicentric primary EMPD starts with Toker cell hyperplasia and can potentially evolve to carcinoma in the genital region.

Home safety measures and the risk of unintentional injury among young children: a multicentre case–control study

PubMed Central

LeBlanc, John C.; Pless, I. Barry; King, W. James; Bawden, Harry; Bernard-Bonnin, Anne-Claude; Klassen, Terry; Tenenbein, Milton

2006-01-01

Background Young children may sustain injuries when exposed to certain hazards in the home. To better understand the relation between several childproofing strategies and the risk of injuries to children in the home, we undertook a multicentre case–control study in which we compared hazards in the homes of children with and without injuries. Methods We conducted this case-control study using records from 5 pediatric hospital emergency departments for the 2-year period 1995–1996. The 351 case subjects were children aged 7 years and less who presented with injuries from falls, burns or scalds, ingestions or choking. The matched control subjects were children who presented during the same period with acute non-injury-related conditions. A home visitor, blinded to case-control status, assessed 19 injury hazards at the children's homes. Results Hazards found in the homes included baby walkers (21% of homes with infants), no functioning smoke alarm (17% of homes) and no fire extinguisher (51% of homes). Cases did not differ from controls in the mean proportion of home hazards. After controlling for siblings, maternal education and employment, we found that cases differed from controls for 5 hazards: the presence of a baby walker (odds ratio [OR] 9.0, 95% confidence interval [CI] 1.1–71.0), the presence of choking hazards within a child's reach (OR 2.0, 95% CI 1.0–3.7), no child-resistant lids in bathroom (OR 1.6, 95% CI 1.0–2.5), no smoke alarm (OR 3.2, 95% CI 1.4–7.7) and no functioning smoke alarm (OR 1.7, 95% CI 1.0–2.8). Interpretation Homes of children with injuries differed from those of children without injuries in the proportions of specific hazards for falls, choking, poisoning and burns, with a striking difference noted for the presence of a baby walker. In addition to counselling parents about specific hazards, clinicians should consider that the presence of some hazards may indicate an increased risk for home injuries beyond those directly related to the hazard found. Families with any home hazard may be candidates for interventions to childproof against other types of home hazards. PMID:16998079

Risk factors for acquisition of OXA-48-producing Klebsiella pneumonia among contact patients: a multicentre study.

PubMed

Hilliquin, D; Le Guern, R; Thepot Seegers, V; Neulier, C; Lomont, A; Marie, V; Legeay, C; Merrer, J; Lepelletier, D; Rogues, A M; Grandbastien, B; Lucet, J C; Zahar, J R

2018-03-01

Cohorting carbapenemase-producing Enterobacteriaceae (CPE) carriers during hospitalization limits in-hospital spreading. To identify risk factors for CPE acquisition among contacts of an index patient in non-cohorted populations. A multicentre retrospective matched case-control study was conducted in five hospitals. Each contact patient (case) who acquired Klebsiella pneumoniae (KP)-OXA-48 from an index patient was compared to three contact (controls) with the same index patients matched with hospitalization in the same unit and similar exposure times. Fifty-one secondary cases and 131 controls were included. By univariate analysis, exposure time (odds ratio: 1.06; 95% confidence interval: 1.02-1.1; P = 0.006), concomitant infection at admission (3.23; 1.42-7.35; P = 0.005), antimicrobial therapy within the last month before hospitalization (2.88; 1.34-6.2; P = 0.007), antimicrobial therapy during the exposure time (5.36; 2.28-12.6; P < 0.001), use of at least one invasive procedure (2.99; 1.25-7.15; P = 0.014), number of invasive procedures (1.52; 1.05-2.19; P = 0.025), and geographical proximity (2.84; 1.15-7.00; P = 0.023) were associated with CPE acquisition. By multivariate analysis, antimicrobial therapy during the exposure time (odds ratio: 6.36; 95% confidence interval: 2.46-16.44; P < 0.001), at least one invasive procedure (2.92; 1.04-8.17; P = 0.041), and geographical proximity (3.69; 1.15-11.86; P = 0.028) were associated with acquisition. In this study, geographical proximity, invasive procedure, and antimicrobial therapy during exposure time were significantly associated with KP-OXA-48 acquisition. Copyright © 2017 The Healthcare Infection Society. Published by Elsevier Ltd. All rights reserved.

Poison prevention practices and medically attended poisoning in young children: multicentre case-control study.

PubMed

Kendrick, Denise; Majsak-Newman, Gosia; Benford, Penny; Coupland, Carol; Timblin, Clare; Hayes, Mike; Goodenough, Trudy; Hawkins, Adrian; Reading, Richard

2017-04-01

Childhood poisonings are common, placing a substantial burden on health services. Case-control studies have found inconsistent evidence about modifiable risk factors for poisonings among children aged 0-4 years. This study quantifies associations between poison prevention practices and medically attended poisonings in children aged 0-4 years. Multicentre case-control study conducted at hospitals, minor injury units and family practices from four study centres in England between 2010 and 2013. Participants comprised 567 children presenting with unintentional poisoning occurring at home and 2320 community control participants matched on age, sex, date of event and study centre. Parents/caregivers provided data on safety practices, safety equipment use, home hazards and potential confounders by means of self-completion questionnaires. Data were analysed using conditional logistic regression. Compared with community controls, parents of poisoned children were significantly more likely not to store medicines out of reach (adjusted OR (AOR) 1.59; 95% CI 1.21 to 2.09; population attributable fraction (PAF) 15%), not to store medicines safely (locked or out of reach (AOR 1.83; 95% CI 1.38 to 2.42; PAF 16%) and not to have put all medicines (AOR 2.11; 95% CI 1.54 to 2.90; PAF 20%) or household products (AOR 1.79, 95% CI 1.29 to 2.48; PAF 11%) away immediately after use. Not storing medicines out of reach or locked away and not putting medicines and household products away immediately after use increased the odds of secondary care attended poisonings in children aged 0-4 years. If associations are causal, implementing these poison prevention practices could each prevent between 11% and 20% of poisonings. 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/.

Seroprevalence and risk factors for hepatitis C virus infection among blood donors in Serbia: A multicentre study.

PubMed

Mitrovic, Nikola; Delic, Dragan; Markovic-Denic, Ljiljana; Jovicic, Milica; Popovic, Natasa; Bojovic, Ksenija; Simonovic Babic, Jasmina; Svirtlih, Neda

2015-07-01

The epidemiological characteristics of hepatitis C virus (HCV) infection have not yet been described in Serbia. To determine the prevalence of anti-HCV-positive individuals among first-time blood donors and the risk factors for hepatitis C transmission. A multicentre case-control study nested within a prospective cohort study was conducted at 10 main transfusion centres in Serbia in 2013 and 27,160 blood donors who gave blood for the first time were included. Blood donors with confirmed anti-HCV positivity and seronegative controls were enrolled to determine the risk factors. Of 27,160 blood donors 52 were anti-HCV-positive; seroprevalence was 0.19%. By univariate analysis, marital status, educational level, drug use, previous transfusion, tattooing, non-use of condoms and number of sexual partners, were risk factors for hepatitis C. In the final multivariate analysis, three factors remained independently predictive: drug use, tattooing and previous blood transfusion. In total, 87.5% of cases had at least one of the risk factors for HCV transmission; 20.9% presumed that they knew when the infection occurred. HCV seroprevalence in Serbia is higher than in developed European countries. Preventive measures need to be directed towards drug use and tattooing facilities. The admission questionnaire for blood donors should be improved. Copyright © 2015 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.

EBV+ HHV-8+ Multicentric Castleman Disease With Plasmablastic Aggregates in an HIV+ Man: An Evolving Clinicopathologic Entity.

PubMed

Shivane, Aditya; Pearce, Amy; Khatib, Nadia; Smith, Mark E F

2018-06-01

We report a case of EBV+ and HHV-8+ multicentric Castleman disease with plasmablastic aggregates in an HIV-positive individual. A 41-year-old man presented in early 2015 with fevers, sweats, weight loss, intractable itching, and on subsequent testing was found to be HIV positive. Investigations showed cervical lymphadenopathy and splenomegaly. He was treated for HIV and his symptoms resolved. His symptoms recurred in January 2016, and a provisional diagnosis of multicentric Castleman disease was entertained. The HHV-8 (human herpesvirus-8) and EBV (Epstein-Barr virus) viral load was elevated. A left supraclavicular lymph node core biopsy was performed, which showed features of multicentric Castleman disease with plasmablastic aggregates that are EBV (EBER) and HHV-8 positive. He responded well to rituximab treatment and remains well with no symptoms at recent follow-up.

The British antibiotic and silver-impregnated catheters for ventriculoperitoneal shunts multi-centre randomised controlled trial (the BASICS trial): study protocol

PubMed Central

2014-01-01

Background Insertion of a ventriculoperitoneal shunt (VPS) for the treatment of hydrocephalus is one of the most common neurosurgical procedures in the UK, but failures caused by infection occur in approximately 8% of primary cases. VPS infection is associated with considerable morbidity and mortality and its management results in substantial cost to the health service. Antibiotic-impregnated (rifampicin and clindamycin) and silver-impregnated VPS have been developed to reduce infection rates. Whilst there is some evidence showing that such devices may lead to a reduction in VPS infection, there are no randomised controlled trials (RCTs) to support their routine use. Methods/design Overall, 1,200 patients will be recruited from 17 regional neurosurgical units in the UK and Ireland. Patients of any age undergoing insertion of their first VPS are eligible. Patients with previous indwelling VPS, active and on-going cerebrospinal fluid (CSF) or peritoneal infection, multiloculated hydrocephalus requiring multiple VPS or neuroendoscopy, and ventriculoatrial or ventriculopleural shunt planned will be excluded. Patients will be randomised 1:1:1 to either standard silicone (comparator), antibiotic-impregnated, or silver-impregnated VPS. The primary outcome measure is time to VPS infection. Secondary outcome measures include time to VPS failure of any cause, reason for VPS failure (infection, mechanical failure, or patient failure), types of bacterial VPS infection (organism type and antibiotic resistance), and incremental cost per VPS failure averted. Discussion The British antibiotic and silver-impregnated catheters for ventriculoperitoneal shunts multi-centre randomised controlled trial (the BASICS trial) is the first multi-centre RCT designed to determine whether antibiotic or silver-impregnated VPS reduce early shunt infection compared to standard silicone VPS. The results of this study will be used to inform current neurosurgical practice and may potentially benefit patients undergoing shunt surgery in the future. Trial registration International Standard Randomised Controlled Trial Number: ISRCTN49474281. PMID:24383496

Occupational risk factors for urothelial carcinoma: agent-specific results from a case-control study in Germany. MURC Study Group. Multicenter Urothelial and Renal Cancer.

PubMed

Pesch, B; Haerting, J; Ranft, U; Klimpel, A; Oelschlägel, B; Schill, W

2000-04-01

This multicentre population-based case-control study was conducted to estimate the urothelial cancer risk for occupational exposure to aromatic amines, polycyclic aromatic hydrocarbons (PAH), and chlorinated hydrocarbons besides other suspected risk factors. In a population-based multicentre study, 1035 incident urothelial cancer cases and 4298 controls matched for region, sex, and age were interviewed between 1991 and 1995 for their occupational history and lifestyle habits. Exposure to the agents under study was self-assessed as well as expert-rated with two job-exposure matrices and a job task-exposure matrix. Conditional logistic regression was used to calculate smoking adjusted odds ratios (OR) and to control for study centre and age. Urothelial cancer risk following exposure to aromatic amines was only slightly elevated. Among males, substantial exposures to PAH as well as to chlorinated solvents and their corresponding occupational settings were associated with significantly elevated risks after adjustment for smoking (PAH exposure, assessed with a job-exposure matrix: OR = 1.6, 95% CI: 1.1-2.3, exposure to chlorinated solvents, assessed with a job task-exposure matrix: OR = 1.8, 95% CI: 1.2-2.6). Metal degreasing showed an elevated urothelial cancer risk among males (OR = 2.3, 95% CI: 1.4-3.8). In females also, exposure to chlorinated solvents indicated a urothelial cancer risk. Because of small numbers the risk evaluation for females should be treated with caution. Occupational exposure to aromatic amines could not be shown to be as strong a risk factor for urothelial carcinomas as in the past. A possible explanation for this finding is the reduction in exposure over the last 50 years. Our results strengthen the evidence that PAH may have a carcinogenic potential for the urothelium. Furthermore, our results indicate a urothelial cancer risk for the use of chlorinated solvents.

The EuroNet paediatric hodgkin network - modern imaging data management for real time central review in multicentre trials.

PubMed

Kurch, L; Mauz-Körholz, C; Bertling, S; Wallinder, M; Kaminska, M; Marwede, D; Tchavdarova, L; Georgi, T W; Elsner, A; Barthel, A; Stoevesandt, D; Hasenclever, D; Sattler, B; Sabri, O; Körholz, D; Kluge, R

2013-11-01

Since 2007, children and adolescents with Hodgkin lymphomas are treated in the Europe-wide EuroNet-PHL trials. A real time central review process for stratification of the patients enhances quality control and efficient therapy management. This process includes reading of all cross-sectional-images. Since reference evaluation is time critical, a fast, easy to handle and safe data transfer is important. In addition, immediate and constant access to all the data has to be guaranteed in case of queries and for regulatory reasons. To meet the mentioned requirements the EuroNet Paediatric Hodgkin Data Network (funded by the European Union - Project Number: 2007108) was established between 2008 and 2011. A respective tailored data protection plan was formulated. The aim of this article is to describe the networks' mode of operation and the advantages for multi-centre trials that include centralized image review. © Georg Thieme Verlag KG Stuttgart · New York.

Reappraisal of known malaria resistance loci in a large multi-centre study

PubMed Central

Rockett, Kirk A.; Clarke, Geraldine M.; Fitzpatrick, Kathryn; Hubbart, Christina; Jeffreys, Anna E.; Rowlands, Kate; Craik, Rachel; Jallow, Muminatou; Conway, David J.; Bojang, Kalifa A.; Pinder, Margaret; Usen, Stanley; Sisay-Joof, Fatoumatta; Sirugo, Giorgio; Toure, Ousmane; Thera, Mahamadou A.; Konate, Salimata; Sissoko, Sibiry; Niangaly, Amadou; Poudiougou, Belco; Mangano, Valentina D.; Bougouma, Edith C.; Sirima, Sodiomon B.; Modiano, David; Amenga-Etego, Lucas N.; Ghansah, Anita; Koram, Kwadwo A.; Wilson, Michael D.; Enimil, Anthony; Evans, Jennifer; Amodu, Olukemi; Olaniyan, Subulade; Apinjoh, Tobias; Mugri, Regina; Ndi, Andre; Ndila, Carolyne M.; Uyoga, Sophie; Macharia, Alexander; Peshu, Norbert; Williams, Thomas N.; Manjurano, Alphaxard; Riley, Eleanor; Drakeley, Chris; Reyburn, Hugh; Nyirongo, Vysaul; Kachala, David; Molyneux, Malcolm; Dunstan, Sarah J.; Phu, Nguyen Hoan; Ngoc Quyen, Nguyen Thi; Thai, Cao Quang; Hien, Tran Tinh; Manning, Laurens; Laman, Moses; Siba, Peter; Karunajeewa, Harin; Allen, Steve; Allen, Angela; Davis, Timothy M. E.; Michon, Pascal; Mueller, Ivo; Green, Angie; Molloy, Sile; Johnson, Kimberly J.; Kerasidou, Angeliki; Cornelius, Victoria; Hart, Lee; Vanderwal, Aaron; SanJoaquin, Miguel; Band, Gavin; Le, Si Quang; Pirinen, Matti; Sepúlveda, Nuno; Spencer, Chris C.A.; Clark, Taane G.; Agbenyega, Tsiri; Achidi, Eric; Doumbo, Ogobara; Farrar, Jeremy; Marsh, Kevin; Taylor, Terrie; Kwiatkowski, Dominic P.

2015-01-01

Many human genetic associations with resistance to malaria have been reported but few have been reliably replicated. We collected data on 11,890 cases of severe malaria due to Plasmodium falciparum and 17,441 controls from 12 locations in Africa, Asia and Oceania. There was strong evidence of association with the HBB, ABO, ATP2B4, G6PD and CD40LG loci but previously reported associations at 22 other loci did not replicate in the multi-centre analysis. The large sample size made it possible to identify authentic genetic effects that are heterogeneous across populations or phenotypes, a striking example being the main African form of G6PD deficiency, which reduced the risk of cerebral malaria but increased the risk of severe malarial anaemia. The finding that G6PD deficiency has opposing effects on different fatal complications of P. falciparum infection indicates that the evolutionary origins of this common human genetic disorder are more complex than previously supposed. PMID:25261933

Multicentric Fibrosarcoma in a Cat and a Review of the Literature

PubMed Central

Harasen, G. L. G.

1984-01-01

A case of multicentric fibrosarcoma in a ten month old domestic short-haired cat is presented and discussed. Tumor tissue was found to involve the right distal forepaw, right shoulder area and a popliteal lymph node. This anaplastic neoplasm was concentrated primarily in subcutaneous tissues but also extended to muscle, bone and lung. The cat was found to be positive for feline leukemia virus by the ELISA test. Based on these findings, it is likely that the lesions in this case result from an interaction between the feline leukemia virus and feline sarcoma virus. ImagesFigures 1 and 2.Figure 3.Figure 4. PMID:17422403

[Two HHV8-related illnesses in a HIV-negative patient: Kaposi's sarcoma and multicentric Castleman's disease. Response to treatment with Rituximab and CHOP].

PubMed

Pastor, M A; Vasco, B; Mosquera, J M; Debén, G; Bautista, P; Requena, L

2006-01-01

Human herpes virus 8 (HHV8) was discovered in 1994 in the biopsy of a Kaposi's sarcoma in a patient with AIDS. Since then it has been identified in all variants of Kaposi's sarcoma and in another two rare disorders: multicentric Castleman's disease and primary body-cavity based lymphomas. The case discusses a 68 year old, HIV-negative male patient, presenting Kaposi's sarcoma for one year and being monitored by dermatology, who presented for weakness, anorexia and fever. On examination, he was found to have adenitis of the lymph nodes in his neck, underarm and groin. A biopsy on one of the swellings led to findings characteristic of multicentric plasma cell variant Castleman's disease. Blood tests for HHV8 and HIV were carried out, resulting positive and negative respectively (IgG anti-HHV8 positive, title 1/640, indirect immunofluorescence). PCR amplification showed HHV8 in peripheral blood. Patient received 8 cycles of CHOP and rituximab, leading to complete disappearance of the adenitis and general symptoms, with no worsening of his Kaposi's sarcoma. Patient remained in complete remission for 10 months after treatment. This paper discusses the case of a HIV-, HHV8+ patient, diagnosed with classic Kaposi's sarcoma, who developed multicentric plasma cell variant Castleman's disease. The coincidence of two or more HHV8-related illnesses in a HIV-negative patient has rarely been described in medical literature. Treatment with rituximab combined with CHOP chemotherapy was effective in this case, and no worsening of the patient's KS was observed.

Low social interactions in eating disorder patients in childhood and adulthood: a multi-centre European case control study.

PubMed

Krug, Isabel; Penelo, Eva; Fernandez-Aranda, Fernando; Anderluh, Marija; Bellodi, Laura; Cellini, Elena; di Bernardo, Milena; Granero, Roser; Karwautz, Andreas; Nacmias, Benedetta; Ricca, Valdo; Sorbi, Sandro; Tchanturia, Kate; Wagner, Gudrun; Collier, David; Treasure, Janet

2013-01-01

The objective of this article was to examine lifestyle behaviours in eating disorder (ED) patients and healthy controls. A total of 801 ED patients and 727 healthy controls from five European countries completed the questions related to lifestyle behaviours of the Cross-Cultural Questionnaire (CCQ). For children, the ED sample exhibited more solitary activities (rigorously doing homework [p<0.001] and watching TV [p<0.05] and less socializing with friends [p<0.05]) than the healthy control group and this continued in adulthood. There were minimal differences across ED sub-diagnoses and various cross-cultural differences emerged. Reduced social activities may be an important risk and maintaining factor for ED symptomatology.

[A national multicentre study on nosocomial infections in PICU].

PubMed

Jordan García, I; Arriourtúa, A Bustinza; Torre, J A Concha; Antón, J Gil; Vicente, J C de Carlos; González, C Téllez

2014-01-01

Nosocomial infection (NI) is a common complication in paediatric critical care units (PICU), with an associated mortality up to 11%. To describe NI epidemiology in the national PICU. To initiate an standard NI control measures to obtain paediatric incidence rates. Multicentre prospective study from 1 to 31 march 2007. Centre Disease Control diagnosis and methodological criteria were used. It was specially analyzed NI related to invasive devices: central venous catheter (CVC), mechanical ventilation (MV), urinary catheter (UC). There were recruited 300 patients from 6 PICU, with 17 NI episodes in 16 patients (5,3% from admitted). NI rates resulted in 13,8 infections/1000 patients-day. Middle age from infected patients was 2,31 years (± 3,43), 9 males. Risk factors were found in 7 cases. NI location was: catheter-related bloodstream infection in 7 patients (6,7/1000 days CVC), ventilator associated pneumonia in 4 (9,4/1000 MV days), urinary-tract infection associated with UC in 4 (5,5/1000 UC days), one case of primary bloodstream infection and one surgical site infection. Isolated microorganisms were: 9 gram negatives bacillus, 4 Candida, 2 plasmocoagulase negative staphylococcus, 1 Haemophilus and 1 Staphylococcus aureus. Seven isolations were resistant microorganisms. There weren't any died related to NI. NI epidemiology was similar to published data in our near countries. NI surveillance, with a standardized method of analysis is essential to the NI correct manage. Copyright © 2010 Asociación Española de Pediatría. Published by Elsevier Espana. All rights reserved.

A multicentre case control study on complicated coeliac disease: two different patterns of natural history, two different prognoses.

PubMed

Biagi, Federico; Marchese, Alessandra; Ferretti, Francesca; Ciccocioppo, Rachele; Schiepatti, Annalisa; Volta, Umberto; Caio, Giacomo; Ciacci, Carolina; Zingone, Fabiana; D'Odorico, Anna; Carroccio, Antonio; Ambrosiano, Giuseppe; Mansueto, Pasquale; Gasbarrini, Antonio; Piscaglia, Anna Chiara; Andrealli, Alida; Astegiano, Marco; Segato, Sergio; Neri, Matteo; Meggio, Alberto; de Pretis, Giovanni; De Vitis, Italo; Gobbi, Paolo; Corazza, Gino Roberto

2014-08-07

Coeliac disease is a common enteropathy characterized by an increased mortality mainly due to its complications. The natural history of complicated coeliac disease is characterised by two different types of course: patients with a new diagnosis of coeliac disease that do not improve despite a strict gluten-free diet (type A cases) and previously diagnosed coeliac patients that initially improved on a gluten-free diet but then relapsed despite a strict diet (type B cases). Our aim was to study the prognosis and survival of A and B cases. Clinical and laboratory data from coeliac patients who later developed complications (A and B cases) and sex- and age-matched coeliac patients who normally responded to a gluten-free diet (controls) were collected among 11 Italian centres. 87 cases and 136 controls were enrolled. Complications tended to occur rapidly after the diagnosis of coeliac disease and cumulative survival dropped in the first months after diagnosis of complicated coeliac disease. Thirty-seven cases died (30/59 in group A, 7/28 in group B). Type B cases presented an increased survival rate compared to A cases. Complicated coeliac disease is an extremely serious condition with a high mortality and a short survival. Survival depends on the type of natural history.

Multicentre validation of the bedside paediatric early warning system score: a severity of illness score to detect evolving critical illness in hospitalised children

PubMed Central

2011-01-01

Introduction The timely provision of critical care to hospitalised patients at risk for cardiopulmonary arrest is contingent upon identification and referral by frontline providers. Current approaches require improvement. In a single-centre study, we developed the Bedside Paediatric Early Warning System (Bedside PEWS) score to identify patients at risk. The objective of this study was to validate the Bedside PEWS score in a large patient population at multiple hospitals. Methods We performed an international, multicentre, case-control study of children admitted to hospital inpatient units with no limitations on care. Case patients had experienced a clinical deterioration event involving either an immediate call to a resuscitation team or urgent admission to a paediatric intensive care unit. Control patients had no events. The scores ranged from 0 to 26 and were assessed in the 24 hours prior to the clinical deterioration event. Score performance was assessed using the area under the receiver operating characteristic (AUCROC) curve by comparison with the retrospective rating of nurses and the temporal progression of scores in case patients. Results A total of 2,074 patients were evaluated at 4 participating hospitals. The median (interquartile range) maximum Bedside PEWS scores for the 12 hours ending 1 hour before the clinical deterioration event were 8 (5 to 12) in case patients and 2 (1 to 4) in control patients (P < 0.0001). The AUCROC curve (95% confidence interval) was 0.87 (0.85 to 0.89). In case patients, mean scores were 5.3 at 20 to 24 hours and 8.4 at 0 to 4 hours before the event (P < 0.0001). The AUCROC curve (95% CI) of the retrospective nurse ratings was 0.83 (0.81 to 0.86). This was significantly lower than that of the Bedside PEWS score (P < 0.0001). Conclusions The Bedside PEWS score identified children at risk for cardiopulmonary arrest. Scores were elevated and continued to increase in the 24 hours before the clinical deterioration event. Prospective clinical evaluation is needed to determine whether this score will improve the quality of care and patient outcomes. PMID:21812993

Anti-interleukin-6 receptor antibody (tocilizumab) treatment of multicentric Castleman's disease.

PubMed

Matsuyama, Masashi; Suzuki, Takeshi; Tsuboi, Hiroto; Ito, Satoshi; Mamura, Mizuko; Goto, Daisuke; Matsumoto, Isao; Tsutsumi, Akito; Sumida, Takayuki

2007-01-01

We report three cases of multicentric Castleman's disease (MCD) successfully treated with anti-interleukin-6 receptor antibody (tocilizumab). Tocilizumab was administered intravenously at a dose of 8 mg/kg every 2 weeks. In each case, tocilizumab alleviated symptoms, including generalized fatigue, pyrexia, and alleviated biochemical abnormalities, including anemia, hypoalbuminemia, hypergammaglobulinemia, and increased C-reactive protein (CRP). Side effects included hypercholesterolemia, acute pyelonephritis, mild inflammation of the parotid glands, and upper respiratory system inflammation. Other severe side effects were not observed. These results indicate that tocilizumab is effective for the treatment of MCD. This is the first report on tocilizumab efficacy for Castleman's disease after approval for use for Castleman's disease.

[Relevance of the sentinel lymph node biopsy in breast multifocal and multicentric cancer].

PubMed

Mosbah, R; Raimond, E; Pelissier, A; Hocedez, C; Graesslin, O

2015-05-01

The sentinel lymph node biopsy is a gold standard in the management of breast cancer. Its role in multifocal or multicentric tumors is still evolving. The aim of this study is to assess the feasibility and pertinence of sentinel lymph node biopsy in multifocal and multicentric tumors based on a systematic review of literature. A systematic review was conducted searching in the following electronic databases PubMed using "sentinel lymph node biopsy", "breast cancer", "multifocal tumor", "multicentric tumor" and "multiple tumor" as keywords. We included original articles published between 2000 and 2014, both French and English, studying feasibility of sentinel lymph node biopsy in invasive breast cancer, multicentric and/or multifocal tumors. The first end point was success rate and false negative rate. Twenty-six articles were included in this literature review, with 2212 cases (782 multifocal, 737 multicentric and 693 multiple tumors). Percentage of tumors whose stage was higher than stage T2 ranged from 0 to 86.3%. Success rate average was 83.1%. False negative average was 8.2%. False negative rate was less than 10% in 15 articles. Mean of sentinel lymph node biopsy was 2 (1-9). The average rate of sentinel lymph node positive was 50.6%. Axillary recurrence rate was 0.5%. Despite the methodological biases of the studies included in this review of literature, the false negative rate of sentinel node biopsy in multifocal and multicentric breast cancers are less than 10% with a low rate of axillary recurrence. Despite the lack of randomized study, this procedure can be routinely performed in accordance with rigorous technical process. Copyright © 2015 Elsevier Masson SAS. All rights reserved.

Spontaneous multicentric soft tissue sarcoma in a captive African pygmy hedgehog (Atelerix albiventris): case report and literature review.

PubMed

Díaz-Delgado, Josué; Pool, Roy; Hoppes, Sharman; Cerezo, Argine; Quesada-Canales, Óscar; Stoica, George

2017-05-18

This report describes the clinical, macroscopic, histopathological and immunohistochemical features of a spontaneous multicentric extraskeletal sarcoma in an adult male African hedgehog (Atelerix albiventris). It also provides a succinct up-to-date review on neoplasia in this species. On autopsy examination, main gross findings included a moderately demarcated cranial mass and a multilobulated, caudal intra-abdominal mass. The cranial mass had perforated the underlying temporal and occipital bones and had extended into the cranial vault and was compressing the surface of the cerebellum and cerebrum. Histologic, histochemical and immunohistochemical analyses supported a diagnosis of multicentric poorly differentiated spindle cell sarcoma with fibrosarcomatous, storiform and myxoid foci. The high incidence of neoplasia and cross similarities renders the African hedgehog a suitable species for comparative pathology studies.

A survey of contemporary opinions and practices of surgical and intensive care specialists towards peri-operative venous thromboembolism prophylaxis in Asia.

PubMed

Lee, L; Liew, N C; Gee, T

2012-12-01

This survey was conducted to determine the opinions and practices of peri-operative venous thromboembolism (VTE) prophylaxis among surgical and intensive care specialists in Asia. A set of questionnaire was distributed to surgeons and intensivists from different countries in Asia. The specialties included were general surgery and its sub-specialties, orthopaedic surgery, gynaecological surgery and intensive care unit. This survey involved teaching institutions, general hospitals and private hospitals. To gauge if the respondents were from hospitals that would likely encounter VTE cases, the hospital's bed-strength, intensive care facility and sub-specialty services were recorded. Over a period of six months, questionnaires and feedbacks were collected and analyzed. One hundred and ninety-one responses were received from 8 countries throughout Asia. Fifty-six percent of these were from large hospitals (800 bedded or more) and 62% of these hospitals have large intensive care facility (20 or more beds). Only half of the respondents practice routine thromboprophylaxis in moderate and high risk surgeries. Thirty six percent of them practices selective thromboprophylaxis and only 3% do not believe in any thromboprophylaxis. A third prescribed thromboprophylaxis for 3 to 5 days; another third extended it until patient is mobile. About 48.6% of the respondents do not have VTE guidelines in their institutions. Majority of the respondents agreed that more evidence is needed in the form of multi-centre randomized controlled trials to influence their decision on thromboprophylaxis. Despite the availability of strong epidemiological data, randomized controlled trials and multicentre case-controlled studies, perioperative VTE prophylactic practices are still suboptimal in Asia.

Adverse events associated with acupuncture: three multicentre randomized controlled trials of 1968 cases in China.

PubMed

Zhao, Ling; Zhang, Fu-wen; Li, Ying; Wu, Xi; Zheng, Hui; Cheng, Lin-hao; Liang, Fan-rong

2011-03-24

In order to evaluate the safety of acupuncture in China objectively, we investigated the adverse events associated with acupuncture based on three multicentre randomized controlled trials (RCTs) to assess the safety of acupuncture, identifying the common types of acupuncture adverse events, and analysing the related risk factors for their occurrence. This observational study included patients who received acupuncture from three multicentre RCTs respectively for migraine, functional dyspepsia and Bell's palsy. The 1968 patients and their acupuncturists documented adverse events associated with acupuncture after treatment. We collected data about adverse events due to acupuncture treatment from their case report forms. We analysed the incidence and details of the adverse effects, and studied the risk factors for acupuncture adverse events with non-conditional logistic regression analysis. Among the 1968 patients, 74 patients (3.76%) suffered at least one adverse event throughout the treatment period. We did not observe the occurrence of serious adverse events. 73 patients with adverse events recovered within 2 weeks through effective treatment such as physiotherapy or self-treatment. A total of 3 patients withdrew because of adverse events. There were 9 types of adverse events related to acupuncture, including subcutaneous haematoma, bleeding, skin bruising and needle site pain. Subcutaneous haematoma and haemorrhage in the needling points were the most common adverse events. Age and gender were related to the occurrence of acupuncture adverse events. The older the patients were, the higher the risk of adverse events was. In addition, male patients had slightly higher risk of an adverse event than female patients. Acupuncture is a safe therapy with low risk of adverse events in clinical practice. The risk factors for adverse events (AEs) were related to the patients' gender and age and the local anatomical structure of the acupoints. AEs could be reduced and mitigated by improving the medical environment, ensuring a high technical level of the acupuncture practitioners and establishing a good relationship of mutual trust between doctor and patient. ClinicalTrials.gov: NCT00599586, NCT00599677, NCT00608660.

Coronary CT angiography using 64 detector rows: methods and design of the multi-centre trial CORE-64.

PubMed

Miller, Julie M; Dewey, Marc; Vavere, Andrea L; Rochitte, Carlos E; Niinuma, Hiroyuki; Arbab-Zadeh, Armin; Paul, Narinder; Hoe, John; de Roos, Albert; Yoshioka, Kunihiro; Lemos, Pedro A; Bush, David E; Lardo, Albert C; Texter, John; Brinker, Jeffery; Cox, Christopher; Clouse, Melvin E; Lima, João A C

2009-04-01

Multislice computed tomography (MSCT) for the noninvasive detection of coronary artery stenoses is a promising candidate for widespread clinical application because of its non-invasive nature and high sensitivity and negative predictive value as found in several previous studies using 16 to 64 simultaneous detector rows. A multi-centre study of CT coronary angiography using 16 simultaneous detector rows has shown that 16-slice CT is limited by a high number of nondiagnostic cases and a high false-positive rate. A recent meta-analysis indicated a significant interaction between the size of the study sample and the diagnostic odds ratios suggestive of small study bias, highlighting the importance of evaluating MSCT using 64 simultaneous detector rows in a multi-centre approach with a larger sample size. In this manuscript we detail the objectives and methods of the prospective "CORE-64" trial ("Coronary Evaluation Using Multidetector Spiral Computed Tomography Angiography using 64 Detectors"). This multi-centre trial was unique in that it assessed the diagnostic performance of 64-slice CT coronary angiography in nine centres worldwide in comparison to conventional coronary angiography. In conclusion, the multi-centre, multi-institutional and multi-continental trial CORE-64 has great potential to ultimately assess the per-patient diagnostic performance of coronary CT angiography using 64 simultaneous detector rows.

Impact of rapid antigen detection testing on antibiotic prescription in acute pharyngitis in adults. FARINGOCAT STUDY: a multicentric randomized controlled trial

PubMed Central

2010-01-01

Background Acute pharyngitis is one of the most frequent consultations to the general practitioner and in most of the cases an antibiotic is prescribed in primary care in Spain. Bacterial etiology, mainly by group A beta-hemolytic streptococcus (GABHS), accounts for 10-20% of all these infections in adults. The purpose of this study is to assess the impact of rapid antigen detection testing (RADT) to identify GABHS in acute pharyngitis on the utilization of antibiotics in primary care. Methods/design Multicentric randomized controlled trial in which antibiotic prescription between two groups of patients with acute pharyngitis will be compared. The trial will include two arms, a control and an intervention group in which RADT will be performed. The primary outcome measure will be the proportion of inappropriate antibiotic prescription in each group. Two hundred seventy-six patients are required to detect a reduction in antibiotic prescription from 85% in the control group to 75% in the intervention group with a power of 90% and a level of significance of 5%. Secondary outcome measures will be specific antibiotic treatment, antibiotic resistance rates, secondary effects, days without working, medical visits during the first month and patient satisfaction. Discussion The implementation of RADT would allow a more rational use of antibiotics and would prevent adverse effects of antibiotics, emergence of antibiotic resistance and the growth of inefficient health expenses. Trial registration ISRCTN23587778 PMID:20331895

Effects of an alert system on implantable cardioverter defibrillator-related anxiety: rationale, design, and endpoints of the PANORAMIC multicentre trial.

PubMed

Duru, Firat; Dorian, Paul; Favale, Stefano; Perings, Christian; Pedersen, Susanne S; Willems, Vincent

2010-05-01

Implantable cardioverter defibrillators (ICD) can prevent sudden cardiac death by delivering high-energy shocks in patients at risk of life-threatening ventricular tachyarrhythmias. Patients may be anxious about receiving inappropriate shocks in case of device or lead system malfunction, or about failing to receive needed therapy for the same reason. New devices include programmable vibrating patient notifiers (PN), which, by warning patients of a possible device dysfunction, might lower device-related anxiety. PAtient NOtifier feature for Reduction of Anxiety: a Multicentre ICD study (PANORAMIC) is a multicentre, randomized, clinical trial designed to examine the effects of the awareness of an active vibrating alert system on device-related anxiety. The trial will randomly assign 356 patients in a 1:1 design to a control group (PN OFF) vs. a treatment group (PN ON). Patients will be followed for 12 months, with visits scheduled at 6 and 12 months. During clinical follow-up visits, the ICD will be interrogated, and all patients will complete the Hospital Anxiety and Depression Scale and a device-related anxiety questionnaire. The sensitivity and specificity of PN, the effect of personality on anxiety, using the Type D scale (DS14), the number of delivered appropriate and inappropriate ICD therapies, changes in anxiety related to the delivery of appropriate or inappropriate shocks, crossovers from the assigned group, the number of hospitalizations, and the mortality rate will also be assessed. ClinicalTrials.gov Identifier: NCT00559559.

Spatial analysis of county-based gonorrhoea incidence in mainland China, from 2004 to 2009.

PubMed

Yin, Fei; Feng, Zijian; Li, Xiaosong

2012-07-01

Gonorrhoea is one of the most common sexually transmissible infections in mainland China. Effective spatial monitoring of gonorrhoea incidence is important for successful implementation of control and prevention programs. The county-level gonorrhoea incidence rates for all of mainland China was monitored through examining spatial patterns. County-level data on gonorrhoea cases between 2004 and 2009 were obtained from the China Information System for Disease Control and Prevention. Bayesian smoothing and exploratory spatial data analysis (ESDA) methods were used to characterise the spatial distribution pattern of gonorrhoea cases. During the 6-year study period, the average annual gonorrhoea incidence was 12.41 cases per 100000 people. Using empirical Bayes smoothed rates, the local Moran test identified one significant single-centre cluster and two significant multi-centre clusters of high gonorrhoea risk (all P-values <0.01). Bayesian smoothing and ESDA methods can assist public health officials in using gonorrhoea surveillance data to identify high risk areas. Allocating more resources to such areas could effectively reduce gonorrhoea incidence.

Taking Control of Castleman Disease: Leveraging Precision Medicine Technologies to Accelerate Rare Disease Research.

PubMed

Newman, Samantha Kass; Jayanthan, Raj K; Mitchell, Grant W; Carreras Tartak, Jossie A; Croglio, Michael P; Suarez, Alexander; Liu, Amy Y; Razzo, Beatrice M; Oyeniran, Enny; Ruth, Jason R; Fajgenbaum, David C

2015-12-01

Castleman disease (CD) is a rare and heterogeneous disorder characterized by lymphadenopathy that may occur in a single lymph node (unicentric) or multiple lymph nodes (multicentric), the latter typically occurring secondary to excessive proinflammatory hypercytokinemia. While a cohort of multicentric Castleman disease (MCD) cases are caused by Human Herpes Virus-8 (HHV-8), the etiology of HHV-8 negative, idiopathic MCD (iMCD), remains unknown. Breakthroughs in "omics" technologies that have facilitated the development of precision medicine hold promise for elucidating disease pathogenesis and identifying novel therapies for iMCD. However, in order to leverage precision medicine approaches in rare diseases like CD, stakeholders need to overcome several challenges. To address these challenges, the Castleman Disease Collaborative Network (CDCN) was founded in 2012. In the past 3 years, the CDCN has worked to transform the understanding of the pathogenesis of CD, funded and initiated genomics and proteomics research, and united international experts in a collaborative effort to accelerate progress for CD patients. The CDCN's collaborative structure leverages the tools of precision medicine and serves as a model for both scientific discovery and advancing patient care.

Spontaneous multicentric soft tissue sarcoma in a captive African pygmy hedgehog (Atelerix albiventris): case report and literature review

PubMed Central

DÍAZ-DELGADO, Josué; POOL, Roy; HOPPES, Sharman; CEREZO, Argine; QUESADA-CANALES, Óscar; STOICA, George

2017-01-01

This report describes the clinical, macroscopic, histopathological and immunohistochemical features of a spontaneous multicentric extraskeletal sarcoma in an adult male African hedgehog (Atelerix albiventris). It also provides a succinct up-to-date review on neoplasia in this species. On autopsy examination, main gross findings included a moderately demarcated cranial mass and a multilobulated, caudal intra-abdominal mass. The cranial mass had perforated the underlying temporal and occipital bones and had extended into the cranial vault and was compressing the surface of the cerebellum and cerebrum. Histologic, histochemical and immunohistochemical analyses supported a diagnosis of multicentric poorly differentiated spindle cell sarcoma with fibrosarcomatous, storiform and myxoid foci. The high incidence of neoplasia and cross similarities renders the African hedgehog a suitable species for comparative pathology studies. PMID:28331115

A multicentre case control study on complicated coeliac disease: two different patterns of natural history, two different prognoses

PubMed Central

2014-01-01

Background Coeliac disease is a common enteropathy characterized by an increased mortality mainly due to its complications. The natural history of complicated coeliac disease is characterised by two different types of course: patients with a new diagnosis of coeliac disease that do not improve despite a strict gluten-free diet (type A cases) and previously diagnosed coeliac patients that initially improved on a gluten-free diet but then relapsed despite a strict diet (type B cases). Our aim was to study the prognosis and survival of A and B cases. Methods Clinical and laboratory data from coeliac patients who later developed complications (A and B cases) and sex- and age-matched coeliac patients who normally responded to a gluten-free diet (controls) were collected among 11 Italian centres. Results 87 cases and 136 controls were enrolled. Complications tended to occur rapidly after the diagnosis of coeliac disease and cumulative survival dropped in the first months after diagnosis of complicated coeliac disease. Thirty-seven cases died (30/59 in group A, 7/28 in group B). Type B cases presented an increased survival rate compared to A cases. Conclusions Complicated coeliac disease is an extremely serious condition with a high mortality and a short survival. Survival depends on the type of natural history. PMID:25103857

Going to sleep in the supine position is a modifiable risk factor for late pregnancy stillbirth; Findings from the New Zealand multicentre stillbirth case-control study

PubMed Central

Thompson, John M. D.; Cronin, Robin S.; Li, Minglan; Stacey, Tomasina; Stone, Peter R.; Lawton, Beverley A.; Ekeroma, Alec J.; Mitchell, Edwin A.

2017-01-01

Objective Our objective was to test the primary hypothesis that maternal non-left, in particular supine going-to-sleep position, would be a risk factor for late stillbirth (≥28 weeks of gestation). Methods A multicentre case-control study was conducted in seven New Zealand health regions, between February 2012 and December 2015. Cases (n = 164) were women with singleton pregnancies and late stillbirth, without congenital abnormality. Controls (n = 569) were women with on-going singleton pregnancies, randomly selected and frequency matched for health region and gestation. The primary outcome was adjusted odds of late stillbirth associated with self-reported going-to-sleep position, on the last night. The last night was the night before the late stillbirth was thought to have occurred or the night before interview for controls. Going-to-sleep position on the last night was categorised as: supine, left-side, right-side, propped or restless. Multivariable logistic regression adjusted for known confounders. Results Supine going-to-sleep position on the last night was associated with increased late stillbirth risk (adjusted odds ratios (aOR) 3.67, 95% confidence interval (CI) 1.74 to 7.78) with a population attributable risk of 9.4%. Other independent risk factors for late stillbirth (aOR, 95% CI) were: BMI (1.04, 1.01 to 1.08) per unit, maternal age ≥40 (2.88, 1.31 to 6.32), birthweight <10th customised centile (2.76, 1.59 to 4.80), and <6 hours sleep on the last night (1.81, 1.14 to 2.88). The risk associated with supine-going-to-sleep position was greater for term (aOR 10.26, 3.00 to 35.04) than preterm stillbirths (aOR 3.12, 0.97 to 10.05). Conclusions Supine going-to-sleep position is associated with a 3.7 fold increase in overall late stillbirth risk, independent of other common risk factors. A public health campaign encouraging women not to go-to-sleep supine in the third trimester has potential to reduce late stillbirth by approximately 9%. PMID:28609468

Evaluation of a multidrug chemotherapy protocol with mitoxantrone based maintenance (CHOP-MA) for the treatment of canine lymphoma.

PubMed

Daters, A T; Mauldin, G E; Mauldin, G N; Brodsky, E M; Post, G S

2010-03-01

The purpose of this study was to evaluate the efficacy of adding mitoxantrone to a cyclophosphamide, doxorubicin, vincristine, L-asparaginase and prednisone containing protocol. Sixty-five dogs with multicentric lymphoma were evaluated for overall remission and survival times. Remission and survival time versus stage, substage, pretreatment hypercalcaemia and pretreatment steroid administration were also evaluated. Overall median remission for dogs with multicentric lymphoma was 302 days and overall median survival was 622 days. Of the dogs with multicentric lymphoma, 23 (35%) received all scheduled mitoxantrone doses. Only median survival versus substage was found to be significant (substage a median survival was 679 days and substage b median survival was 302 days, P = 0.025). Increasing the total combined dose of doxorubicin and mitoxantrone may improve remission times when compared with historical controls, and further studies are needed to determine how best to utilize mitoxantrone in multidrug chemotherapy protocols for canine multicentric lymphoma.

[Multicentric hyaline vascular Castleman's disease. A POEMS type variant].

PubMed

Gracia-Ramos, Abraham Edgar; Cruz-Domínguez, María del Pilar; Vera-Lastra, Olga Lidia

2013-01-01

Castleman's disease is an atypical lymphoproliferative disorder which may be compatible with paraneoplastic manifestations of POEMS syndrome. a 53 year old man with a history of type 2 diabetes, hypothyroidism and Addison's disease presented with numbness and weakness in limbs, dyspnea, skin hardening, Raynaud's phenomenon, weight loss and fatigue. A physical exam showed tachypnea, generalized cutaneous hyperpigmentation and skin hardening of extremities, muscle weakness, hypoesthesia and hyporeflexia. Laboratory showed hyperprolactinemia, low testosterone, hypothyroidism and Addison's disease. Electrophoresis of proteins showed polyclonal hypergammaglobulinemia. Somatosensory evoked potentials reported peripheral neuropathy and severe axonal polyneuropathy by electromyography. Chest X-rays showed bilateral reticular infiltrates and mediastinal widening. An echocardiogram displayed moderate pulmonary hypertension. Skin biopsy had no evidence of scleroderma. CT reported axillar, mediastinal and retroperitoneal nodes. The mediastinal lesion biopsy reported hyaline vascular Castleman's disease, multicentric variety. He was treated with rituximab. the case meet criteria for multicentric hyaline vascular Castleman's disease, POEMS variant, treated with rituximab.

Conducting a paediatric multi-centre RCT with an industry partner: challenges and lessons learned.

PubMed

Maskell, Jessica; Newcombe, Peter; Martin, Graham; Kimble, Roy

2012-11-01

There are many benefits of multi-centred research including large sample sizes, statistical power, timely recruitment and generalisability of results. However, there are numerous considerations when planning and implementing a multi-centred study. This article reviews the challenges and successes of planning and implementing a multi-centred prospective randomised control trial involving an industry partner. The research investigated the impact on psychosocial functioning of a cosmetic camouflage product for children and adolescents with burn scarring. Multi-centred studies commonly have many stakeholders. Within this study, six Australian and New Zealand paediatric burn units as well as an industry partner were involved. The inclusion of an industry partner added complexities as they brought different priorities and expectations to the research. Further, multifaceted ethical and institutional approval processes needed to be negotiated. The challenges, successes, lessons learned and recommendations from this study regarding Australian and New Zealand ethics and research governance approval processes, collaboration with industry partners and the management of differing expectations will be outlined. Recommendations for future multi-centred research with industry partners include provision of regular written reports for the industry partner; continual monitoring and prompt resolution of concerns; basic research practices education for industry partners; minimisation of industry partner contact with participants; clear roles and responsibilities of all stakeholders and utilisation of single ethical review if available. © 2012 The Authors. Journal of Paediatrics and Child Health © 2012 Paediatrics and Child Health Division (Royal Australasian College of Physicians).

[PET-CT documented remission of multicentric Castleman disease after treatment with rituximab: case report and review].

PubMed

Adam, Zdeněk; Szturz, Petr; Koukalová, Renata; Řehák, Zdeněk; Pour, Luděk; Krejčí, Marta; Šmardová, Lenka; Eid, Michal; Volfová, Pavlína; Čermáková, Zdeňka; Křen, Leoš; Sokol, Filip; Hanke, Ivo; Michalková, Eva; Král, Zdeněk; Mayer, Jiří

2015-03-01

We describe a case of multicentric Castleman disease with generalized lymphadenopathy and splenomegaly, accompanied by typical B symptoms - loss of 15 kg, fever of non-infectious origin, night sweats, symptoms of anemia. Histological examination of the nodes with the highest accumulation of fluorodeoxyglucose, taken from mediastinum by thoracoscopy, revealed plasmocellular type of Castleman disease. Tests for HIV and human herpesvirus 8 (HHV-8) were negative. Three recurrences of herpes zoster indicating an alteration of immunity preceded the dia-gnosis of disease. Treatment was initiated with combination of thalidomide, dexamethasone, and cyclophosphamide. The response after 2 months therapy was not clear and patient doesn't tolerated the therapy well. Therefore, this treatment was terminated and R-CHOP (Mabthera - rituximab, cyclophosphamide, adriamycin, vincristine, and prednisone) was selected as a second-line therapy. Lymphadenopathy and splenomegaly were reduced during the 2 cycles of treatment, however, serious infectious complications accompanied the therapy. Therefore, only use of Mabthera monotherapy 375 mg /m2 was administered in 28-day intervals. This treatment has shown efficacy and tolerability. PET-CT scan has demonstrated disappearance of lymphadenopathy and splenomegaly, in addition, normalized accumulation of fluorodeoxyglucose. Monotherapy with Mabthera has proved to be effective and well tolerated drug in this case. Currently, there are more effective therapeutic alternatives in multicentric Castleman disease: treatment with monotherapy of rituximab or in combination therapy with immunomodulatory drugs (thalidomide or lenalidomide, treatment with anti-IL-6 (siltuximab) or against its receptor (tocilizumab). In the case of ineffectiveness of one treatment option must be tested other alternative. In this case the therapy based on thalidomide wasn't successful, whereas the treatment with Mabthera has achieved disappearance of disease symptoms.

A new social-family model for eating disorders: A European multicentre project using a case-control design.

PubMed

Krug, Isabel; Fuller-Tyszkiewicz, Matthew; Anderluh, Marija; Bellodi, Laura; Bagnoli, Silvia; Collier, David; Fernandez-Aranda, Fernando; Karwautz, Andreas; Mitchell, Sarah; Nacmias, Benedetta; Ricca, Valdo; Sorbi, Sandro; Tchanuria, Kate; Wagner, Gudrun; Treasure, Janet; Micali, Nadia

2015-12-01

To examine a new socio-family risk model of Eating Disorders (EDs) using path-analyses. The sample comprised 1264 (ED patients = 653; Healthy Controls = 611) participants, recruited into a multicentre European project. Socio-family factors assessed included: perceived maternal and parental parenting styles, family, peer and media influences, and body dissatisfaction. Two types of path-analyses were run to assess the socio-family model: 1.) a multinomial logistic path-model including ED sub-types [Anorexia Nervosa-Restrictive (AN-R), AN-Binge-Purging (AN-BP), Bulimia Nervosa (BN) and EDNOS)] as the key polychotomous categorical outcome and 2.) a path-model assessing whether the socio-family model differed across ED sub-types and healthy controls using body dissatisfaction as the outcome variable. The first path-analyses suggested that family and media (but not peers) were directly and indirectly associated (through body dissatisfaction) with all ED sub-types. There was a weak effect of perceived parenting directly on ED sub-types and indirectly through family influences and body dissatisfaction. For the second path-analyses, the socio-family model varied substantially across ED sub-types. Family and media influences were related to body dissatisfaction in the EDNOS and control sample, whereas perceived abusive parenting was related to AN-BP and BN. This is the first study providing support for this new socio-family model, which differed across ED sub-types. This suggests that prevention and early intervention might need to be tailored to diagnosis-specific ED profiles. Copyright © 2015 Elsevier Ltd. All rights reserved.

NEURAPRO-E study protocol: a multicentre randomized controlled trial of omega-3 fatty acids and cognitive-behavioural case management for patients at ultra high risk of schizophrenia and other psychotic disorders.

PubMed

Markulev, Connie; McGorry, Patrick D; Nelson, Barnaby; Yuen, Hok Pan; Schaefer, Miriam; Yung, Alison R; Thompson, Andrew; Berger, Gregor; Mossaheb, Nilufar; Schlögelhofer, Monika; Smesny, Stefan; de Haan, Lieuwe; Riecher-Rössler, Anita; Nordentoft, Merete; Chen, Eric Yu Hai; Verma, Swapna; Hickie, Ian; Amminger, G Paul

2017-10-01

Recent research has indicated that preventative intervention is likely to benefit patients 'at-risk' for psychosis, both in terms of symptom reduction and delay or prevention of onset of threshold psychotic disorder. The strong preliminary results for the effectiveness of omega-3 polyunsaturated fatty acids (PUFAs), coupled with the falling transition rate in ultra high-risk (UHR) samples, mean that further study of such benign, potentially neuroprotective interventions is clinically and ethically required. Employing a multicentre approach, enabling a large sample size, this study will provide important information with regard to the use of omega-3 PUFAs in the UHR group. This trial is a 6-month, double-blind, randomized placebo-controlled trial of 1.4 g day -1 omega-3 PUFAs in UHR patients aged between 13 and 40 years. The primary hypothesis is that UHR patients receiving omega-3 PUFAs plus cognitive-behavioural case management (CBCM) will be less likely to transition to psychosis over a 6-month period compared to treatment with placebo plus CBCM. Secondary outcomes will examine symptomatic and functional changes, as well as examine if candidate risk factors predict response to omega-3 PUFA treatment in the UHR group. This is the protocol of the NeuraproE study. Utilizing a large sample, results from this study will be important in informing indicated prevention strategies for schizophrenia and other psychotic disorders, which may be the strongest avenue for reducing the burden, stigmatization, disability and economic consequences of these disorders. © 2015 Wiley Publishing Asia Pty Ltd.

The European I-MOVE Multicentre 2013-2014 Case-Control Study. Homogeneous moderate influenza vaccine effectiveness against A(H1N1)pdm09 and heterogenous results by country against A(H3N2).

PubMed

Valenciano, Marta; Kissling, Esther; Reuss, Annicka; Jiménez-Jorge, Silvia; Horváth, Judit K; Donnell, Joan M O; Pitigoi, Daniela; Machado, Ausenda; Pozo, Francisco

2015-06-04

In the first five I-MOVE (Influenza Monitoring Vaccine Effectiveness in Europe) influenza seasons vaccine effectiveness (VE) results were relatively homogenous among participating study sites. In 2013-2014, we undertook a multicentre case-control study based on sentinel practitioner surveillance networks in six European Union (EU) countries to measure 2013-2014 influenza VE against medically-attended influenza-like illness (ILI) laboratory-confirmed as influenza. Influenza A(H3N2) and A(H1N1)pdm09 viruses co-circulated during the season. Practitioners systematically selected ILI patients to swab within eight days of symptom onset. We compared cases (ILI positive to influenza A(H3N2) or A(H1N1)pdm09) to influenza negative patients. We calculated VE for the two influenza A subtypes and adjusted for potential confounders. We calculated heterogeneity between sites using the I(2) index and Cochrane's Q test. If the I(2) was <50%, we estimated pooled VE as (1 minus the OR)×100 using a one-stage model with study site as a fixed effect. If the I(2) was >49% we used a two-stage random effects model. We included in the A(H1N1)pdm09 analysis 531 cases and 1712 controls and in the A(H3N2) analysis 623 cases and 1920 controls. For A(H1N1)pdm09, the Q test (p=0.695) and the I(2) index (0%) suggested no heterogeneity of adjusted VE between study sites. Using a one-stage model, the overall pooled adjusted VE against influenza A(H1N1)pdm2009 was 47.5% (95% CI: 16.4-67.0). For A(H3N2), the I(2) was 51.5% (p=0.067). Using a two-stage model for the pooled analysis, the adjusted VE against A(H3N2) was 29.7 (95% CI: -34.4-63.2). The results suggest a moderate 2013-2014 influenza VE against A(H1N1)pdm09 and a low VE against A(H3N2). The A(H3N2) estimates were heterogeneous among study sites. Larger sample sizes by study site are needed to prevent statistical heterogeneity, decrease variability and allow for two-stage pooled VE for all subgroup analyses. Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.

At-Risk Phenotype of Neurofibromatose-1 Patients: A Multicentre Case-Control Study

PubMed Central

2011-01-01

Objectives To assess associations between subcutaneous neurofibromas (SC-NFs) and internal neurofibromas in patients with neurofibromatosis type 1 (NF-1) and to determine whether the association between SC-NFs and peripheral neuropathy was ascribable to internal neurofibromas. Patients and methods Prospective multicentre case-control study. Between 2005 and 2008, 110 NF-1 adults having two or more SC-NFs were individually matched for age, sex and hospital with 110 controls who had no SC-NF. Patients underwent standardized MRI of the spinal cord, nerve roots and sciatic nerves and an electrophysiological study. Analyses used adjusted multinomial logistic regression (ORa) to estimate the risk of the presence of internal neurofibromas or peripheral neuropathies associated with patients presented 2 to 9 SC-NFs, at least 10 SC-NFs as compared to patients without any (referential category). Results Cases had a mean age of 41 (± 13) years; 85 (80%) had two to nine SC-NFs and 21 (19%) at least ten SC-NFs. SC-NFs were more strongly associated with internal neurofibromas in patients with ten or more SC-NFs than in patients with fewer NF-SCs (e.g., sciatic nerve, aOR = 29.1 [8.5 to 100] vs. 4.3 [2.1 to 9.0]). The association with SC-NFs was stronger for diffuse, intradural, and > 3 cm internal neurofibromas than with other internal neurofibromas. Axonal neuropathy with slowed conduction velocities (SCV) was more strongly associated with having at least ten SC-NFs (aOR = 29.9, 5.5 to 162.3) than with having fewer SC-NFs (aOR = 4.4, 0.9 to 22.0). Bivariate analyses showed that the association between axonal neuropathy with SCV and sciatic neurofibromas was mediated by the association between SC-NFs and sciatic neurofibromas. Conclusion The at-risk phenotype of NF-1 patients (i.e. NF-1 patients with SC-NFs) is ascribable to associations linking SC-NFs to internal neurofibromas at risk for malignant transformation and to axonal neuropathies with slowed conduction velocities. Axonal neuropathies with SCV are particularly common in patients with at least ten SC-NFs. Registration details ORPHA86301 PMID:21752287

At-risk phenotype of neurofibromatose-1 patients: a multicentre case-control study.

PubMed

Sbidian, Emilie; Bastuji-Garin, Sylvie; Valeyrie-Allanore, Laurence; Ferkal, Salah; Lefaucheur, Jean P; Drouet, Alain; Brugière, Pierre; Vialette, Cédric; Combemale, Patrick; Barbarot, Sébastien; Wolkenstein, Pierre

2011-07-13

To assess associations between subcutaneous neurofibromas (SC-NFs) and internal neurofibromas in patients with neurofibromatosis type 1 (NF-1) and to determine whether the association between SC-NFs and peripheral neuropathy was ascribable to internal neurofibromas. Prospective multicentre case-control study. Between 2005 and 2008, 110 NF-1 adults having two or more SC-NFs were individually matched for age, sex and hospital with 110 controls who had no SC-NF. Patients underwent standardized MRI of the spinal cord, nerve roots and sciatic nerves and an electrophysiological study. Analyses used adjusted multinomial logistic regression (ORa) to estimate the risk of the presence of internal neurofibromas or peripheral neuropathies associated with patients presented 2 to 9 SC-NFs, at least 10 SC-NFs as compared to patients without any (referential category). Cases had a mean age of 41 (± 13) years; 85 (80%) had two to nine SC-NFs and 21 (19%) at least ten SC-NFs. SC-NFs were more strongly associated with internal neurofibromas in patients with ten or more SC-NFs than in patients with fewer NF-SCs (e.g., sciatic nerve, aOR = 29.1 [8.5 to 100] vs. 4.3 [2.1 to 9.0]). The association with SC-NFs was stronger for diffuse, intradural, and > 3 cm internal neurofibromas than with other internal neurofibromas. Axonal neuropathy with slowed conduction velocities (SCV) was more strongly associated with having at least ten SC-NFs (aOR = 29.9, 5.5 to 162.3) than with having fewer SC-NFs (aOR = 4.4, 0.9 to 22.0). Bivariate analyses showed that the association between axonal neuropathy with SCV and sciatic neurofibromas was mediated by the association between SC-NFs and sciatic neurofibromas. The at-risk phenotype of NF-1 patients (i.e. NF-1 patients with SC-NFs) is ascribable to associations linking SC-NFs to internal neurofibromas at risk for malignant transformation and to axonal neuropathies with slowed conduction velocities. Axonal neuropathies with SCV are particularly common in patients with at least ten SC-NFs.

[Multicentric inflammatory pseudotumor with asynchronic presentation in meninges, liver, spleen and lymph nodes in a patient with seronegative spondiloarthropathy. Case report and review of the literature].

PubMed

Vicuña-González, R M; Rivera-Salgado, M I; García-Velarde, P M Pasquel; de León-Bojorge, B; Ortiz-Hidalgo, C

Inflammatory pseudotumor is a reactive process in which the etiology and pathogenesis are not well defined, that can be found in any location. The cases with central nervous system affection have been described in meninges, brain, choroid plexus and cranial and spinal nerves. Multicentric cases, synchronous and asynchronous have been described. A 45 years-old woman with a rheumatologic disease (a seronegative spondiloarthropathy) who developed an inflammatory pseudotumor in spleen, liver and abdominal lymph nodes in 1995, associated to fever of unknown origin, six years later she presented with an inflammatory pseudotumor of the meninges in the convexity of the right frontoparietal region, with fever, malaise, and increase of globular sedimentation rate, microcytic hypochromic anemia and thrombocytosis. The clinicopathologic features of this lesion are revised, including the different theories in regard to the etiology and pathogenesis, and the role of cytokines produced by inflammatory cells in the tumor.

Biliary intraductal papillary neoplasm with metachronous multiple tumors - true multicentric tumors or intrabiliary dissemination: A case report and review of the literature.

PubMed

Yokode, Masataka; Yamashita, Yukimasa; Zen, Yoh

2017-03-01

Intraductal papillary neoplasms of the bile duct (IPNBs) are recognized as a distinct type of biliary tumor. We herein discuss the possible mechanisms underlying the development of multiple tumors in patients with IPNBs through a case presentation and literature review. A 64-year-old woman initially underwent extended right hepatectomy for IPNB in the right hepatic duct. Although the surgical margin of the common bile duct was tumor-free, recurrence was detected in the intrapancreatic bile duct 26 months later. Both tumors had similar histopathological characteristics (intestinal-type IPNB with high-grade dysplasia, but no invasive cancer). A literature review identified 9 additional cases of multiple IPNBs. Unlike conventional IPNBs, which typically affect the intrahepatic or hilar bile duct, 80% of recurrent multiple tumors developed in the extrahepatic bile duct. Although multicentric tumors have been suggested in such cases, the intrabiliary dissemination of tumor cells appears to be more likely, as the majority of recurrent tumors develop in more distal parts of the bile duct compared with the primary tumor.

Intra-articular radioactive yttrium and triamcinolone hexacetonide: an inconclusive trial. Arthritis and Rheumatism Council Multicentre Radiosynoviorthesis Trial Group.

PubMed Central

1984-01-01

A restricted sequential design multicentre controlled trial of yttrium-90 against triamcinolone intra-articularly was undertaken in patients with rheumatoid arthritis with knee involvement. The trial had to be discontinued because of dwindling recruitment over time. The reasons for this and other features contributing to an inconclusive outcome are noted. This experience lends little encouragement to the idea that yttrium-90 therapy is more or less advantageous than triamcinolone hexacetonide. PMID:6383234

Intra-articular radioactive yttrium and triamcinolone hexacetonide: an inconclusive trial. Arthritis and Rheumatism Council Multicentre Radiosynoviorthesis Trial Group.

PubMed

1984-08-01

A restricted sequential design multicentre controlled trial of yttrium-90 against triamcinolone intra-articularly was undertaken in patients with rheumatoid arthritis with knee involvement. The trial had to be discontinued because of dwindling recruitment over time. The reasons for this and other features contributing to an inconclusive outcome are noted. This experience lends little encouragement to the idea that yttrium-90 therapy is more or less advantageous than triamcinolone hexacetonide.

Update and new approaches in the treatment of Castleman disease

PubMed Central

Chan, Kah-Lok; Lade, Stephen; Prince, H Miles; Harrison, Simon J

2016-01-01

First described 60 years ago, Castleman disease comprises a rare and heterogeneous cluster of disorders, characterized by lymphadenopathy with unique histological features and associated with cytokine-driven constitutional symptoms and biochemical disturbances. Although unicentric Castleman disease is curable with complete surgical excision, its multicentric counterpart is a considerable therapeutic challenge. The recent development of biological agents, particularly monoclonal antibodies to interleukin-6 and its receptor, allow for more targeted disease-specific intervention that promises improved response rates and more durable disease control; however, further work is required to fill knowledge gaps in terms of underlying pathophysiology and to facilitate alternative treatment options for refractory cases. PMID:27536166

Screening versus routine practice in detection of atrial fibrillation in patients aged 65 or over: cluster randomised controlled trial

PubMed Central

Fitzmaurice, David A; Jowett, Sue; Mant, Jonathon; Murray, Ellen T; Holder, Roger; Raftery, J P; Bryan, S; Davies, Michael; Lip, Gregory Y H; Allan, T F

2007-01-01

Objectives To assess whether screening improves the detection of atrial fibrillation (cluster randomisation) and to compare systematic and opportunistic screening. Design Multicentred cluster randomised controlled trial, with subsidiary trial embedded within the intervention arm. Setting 50 primary care centres in England, with further individual randomisation of patients in the intervention practices. Participants 14 802 patients aged 65 or over in 25 intervention and 25 control practices. Interventions Patients in intervention practices were randomly allocated to systematic screening (invitation for electrocardiography) or opportunistic screening (pulse taking and invitation for electrocardiography if the pulse was irregular). Screening took place over 12 months in each practice from October 2001 to February 2003. No active screening took place in control practices. Main outcome measure Newly identified atrial fibrillation. Results The detection rate of new cases of atrial fibrillation was 1.63% a year in the intervention practices and 1.04% in control practices (difference 0.59%, 95% confidence interval 0.20% to 0.98%). Systematic and opportunistic screening detected similar numbers of new cases (1.62% v 1.64%, difference 0.02%, −0.5% to 0.5%). Conclusion Active screening for atrial fibrillation detects additional cases over current practice. The preferred method of screening in patients aged 65 or over in primary care is opportunistic pulse taking with follow-up electrocardiography. Trial registration Current Controlled Trials ISRCTN19633732. PMID:17673732

External fixators in the treatment of midshaft clavicle non-unions: a systematic review.

PubMed

Barlow, Tim; Upadhyay, Piyush; Barlow, David

2014-02-01

Non- or mal-union of the clavicle is reported to occur in up to 15 % of conservatively treated fractures: the purpose of this systematic review is to examine the evidence for the use of external fixation in the treatment of clavicular non-union. We performed a search of MEDLINE and Embase, including all papers using external fixators for the treatment of clavicular non-union. Four papers satisfied our eligibility criteria: three case series and one case-control study. Level of evidence and quality assessment scoring were performed using published methods. Due to the heterogeneity of the study populations and interventions, no attempt at meta-analysis was made. External fixation in hypertrophic non-union of the clavicle, but not atrophic non-union, appears to be a reasonable treatment option. A pragmatic, multicentre, randomised controlled trial comparing external fixation and open reduction internal fixation in the treatment of hypertrophic non-union of the clavicle would be valuable.

Evaluation of sentinel lymph node biopsy prior to axillary lymph node dissection: the role of isolated tumor cells/micrometastases and multifocality/multicentricity-a retrospective study of 1214 breast cancer patients.

PubMed

Schröder, Lars; Fricker, Roland; Stein, Roland Gregor; Rink, Thomas; Fitz, Hartmut; Blasius, Sebastian; Wöckel, Achim; Müller, Thomas

2018-06-01

Sentinel lymph node biopsy (SLNB) alone has thus become an accepted surgical approach for patients with limited axillary metastatic disease. We investigated to what extent isolated tumor cells (ITC) or micrometastasis in SLNBs is associated with proven tumor cells or metastasis in non-sentinel lymph nodes. Furthermore, we investigated the feasibility of SLNB in multifocal and multicentric tumors as both entities have been considered a contraindication for this technique. 1214 women suffering from T1 and T2 invasive breast cancer, with clinically and sonographically insuspect axillary status and undergoing primary breast cancer surgery including SLNB and axillary staging in case of SLN (sentinel lymph node) metastases, were recruited into this multicentered study. ITC and micrometastases were found in 2.01 and 21.4% of patients with SLN metastases (n = 299). Among patients with sentinel micrometastases, 4.7% showed further axillary micrometastases, while only two patients (3.1%) had two axillary macrometastases. Multifocal and multicentric tumors were diagnosed in 9.3 and 2.6% of our patients who at least had one SLN resected, respectively. Detection rates of SLNs did not differ between the cohorts suffering from unicentric and multifocal or multicentric disease. Moreover, the portion of tumor-free SLNs, the number of SLNs with metastasis as well as the mean number of resected SLNs did not differ. No patient with sentinel node micrometastases showed more than two axillary macrometastases. Multifocal and multicentric disease is no contraindication for SLNB.

MULTICENTRIC T-CELL LYMPHOMA AND CUTANEOUS HEMANGIOSARCOMA IN A CAPTIVE CHEETAH (ACINONYX JUBATUS).

PubMed

Lindemann, Dana M; Carpenter, James W; Nietfeld, Jerome C; Gonzalez, Estehela; Hallman, Mackenzie; Hause, Ben M

2015-12-01

A 13-yr-old intact male cheetah (Acinonyx jubatus) presented for evaluation after a 4-mo history of intermittent lethargy and increased expiratory effort. The clinical signs were initially noted after the diagnosis and death of its 13-yr-old male sibling with solitary hepatic T-cell lymphoma. Physical examination findings included thin body condition, harsh lung sounds, peripheral lymphadenopathy, and a cutaneous mass on the right medial tarsus and scrotum. Excisional biopsies diagnosed well-differentiated cutaneous hemangiosarcomas. Thoracic radiographs revealed a cranial mediastinal mass. Complete blood count and serum biochemical analyses showed a leukocytosis with persistent lymphocytosis, progressive azotemia, and markedly elevated alkaline phosphatase. Because of the cheetah's declining quality of life, euthanasia was elected. Postmortem examination, histopathology, and immunohistochemical staining revealed multicentric T-cell lymphoma. Feline leukemia virus (FeLV) enzyme-linked immunosorbent assay, FeLV polymerase chain reaction (whole blood), and viral metagenomic analysis were negative. This is the first case of cutaneous hemangiosarcoma and multicentric T-cell lymphoma reported in a FeLV-negative cheetah.

Impact of tailored patient education on adherence of patients with chronic myeloid leukaemia to tyrosine kinase inhibitors: a randomized multicentre intervention study.

PubMed

Kekäle, Meri; Söderlund, Tim; Koskenvesa, Perttu; Talvensaari, Kimmo; Airaksinen, Marja

2016-09-01

The aim of this study was to evaluate the influence of tailored patient education on adherence to tyrosine kinase inhibitor medication among patients with chronic myeloid leukaemia. Management of chronic myeloid leukaemia has changed dramatically during the last decade. While medication adherence is crucial to clinical response, little is known about how to improve patients' adherence. Randomized multicentre intervention study. The study was conducted between June 2012-August 2014. Eighty-six patients with chronic myeloid leukaemia who had been on tyrosine kinase inhibitor medication for at least six months from eight hospitals were randomized into intervention and control groups. Intervention combined nurse-conducted medication counselling, an information booklet, video and website and text message reminders. Patients were interviewed to assess medication adherence using Morisky's 8-Item Medication Adherence Scale at baseline and nine months. Medication adherence improved with the adherence aids used. At nine months, 51% of patients were highly adherent in the intervention group, compared with 21% in the control group. Adherence improved for a higher proportion of patients in the intervention group than the control group (49% vs. 18%). Morisky's score decreased in almost half of control group cases. Patients were most satisfied with face-to-face counselling (86%) and the information booklet (83%) and least satisfied with text messages (9%). Tailored patient education improved the medication adherence of patients with chronic myeloid leukaemia. Without this, adherence behaviour tended to decline. Personal communication with a nurse proved to be an essential part of adherence support and should not be ignored. © 2016 John Wiley & Sons Ltd.

Delays in receiving obstetric care and poor maternal outcomes: results from a national multicentre cross-sectional study

PubMed Central

2014-01-01

Background The vast majority of maternal deaths in low-and middle-income countries are preventable. Delay in obtaining access to appropriate health care is a fairly common problem which can be improved. The objective of this study was to explore the association between delay in providing obstetric health care and severe maternal morbidity/death. Methods This was a multicentre cross-sectional study, involving 27 referral obstetric facilities in all Brazilian regions between 2009 and 2010. All women admitted to the hospital with a pregnancy-related cause were screened, searching for potentially life-threatening conditions (PLTC), maternal death (MD) and maternal near-miss (MNM) cases, according to the WHO criteria. Data on delays were collected by medical chart review and interview with the medical staff. The prevalence of the three different types of delays was estimated according to the level of care and outcome of the complication. For factors associated with any delay, the PR and 95%CI controlled for cluster design were estimated. Results A total of 82,144 live births were screened, with 9,555 PLTC, MNM or MD cases prospectively identified. Overall, any type of delay was observed in 53.8% of cases; delay related to user factors was observed in 10.2%, 34.6% of delays were related to health service accessibility and 25.7% were related to quality of medical care. The occurrence of any delay was associated with increasing severity of maternal outcome: 52% in PLTC, 68.4% in MNM and 84.1% in MD. Conclusions Although this was not a population-based study and the results could not be generalized, there was a very clear and significant association between frequency of delay and severity of outcome, suggesting that timely and proper management are related to survival. PMID:24886330

Delays in receiving obstetric care and poor maternal outcomes: results from a national multicentre cross-sectional study.

PubMed

Pacagnella, Rodolfo C; Cecatti, José G; Parpinelli, Mary A; Sousa, Maria H; Haddad, Samira M; Costa, Maria L; Souza, João P; Pattinson, Robert C

2014-05-05

The vast majority of maternal deaths in low-and middle-income countries are preventable. Delay in obtaining access to appropriate health care is a fairly common problem which can be improved. The objective of this study was to explore the association between delay in providing obstetric health care and severe maternal morbidity/death. This was a multicentre cross-sectional study, involving 27 referral obstetric facilities in all Brazilian regions between 2009 and 2010. All women admitted to the hospital with a pregnancy-related cause were screened, searching for potentially life-threatening conditions (PLTC), maternal death (MD) and maternal near-miss (MNM) cases, according to the WHO criteria. Data on delays were collected by medical chart review and interview with the medical staff. The prevalence of the three different types of delays was estimated according to the level of care and outcome of the complication. For factors associated with any delay, the PR and 95%CI controlled for cluster design were estimated. A total of 82,144 live births were screened, with 9,555 PLTC, MNM or MD cases prospectively identified. Overall, any type of delay was observed in 53.8% of cases; delay related to user factors was observed in 10.2%, 34.6% of delays were related to health service accessibility and 25.7% were related to quality of medical care. The occurrence of any delay was associated with increasing severity of maternal outcome: 52% in PLTC, 68.4% in MNM and 84.1% in MD. Although this was not a population-based study and the results could not be generalized, there was a very clear and significant association between frequency of delay and severity of outcome, suggesting that timely and proper management are related to survival.

Keeping children safe at home: protocol for three matched case–control studies of modifiable risk factors for falls

PubMed Central

Kendrick, Denise; Stewart, Jane; Clacy, Rose; Coffey, Frank; Cooper, Nicola; Coupland, Carol; Hayes, Mike; McColl, Elaine; Reading, Richard; Sutton, Alex; M L Towner, Elizabeth; Craig Watson, Michael

2012-01-01

Background Childhood falls result in considerable morbidity, mortality and health service use. Despite this, little evidence exists on protective factors or effective falls prevention interventions in young children. Objectives To estimate ORs for three types of medically attended fall injuries in young children in relation to safety equipment, safety behaviours and hazard reduction and explore differential effects by child and family factors and injury severity. Design Three multicentre case–control studies in UK hospitals with validation of parental reported exposures using home observations. Cases are aged 0–4 years with a medically attended fall injury occurring at home, matched on age and sex with community controls. Children attending hospital for other types of injury will serve as unmatched hospital controls. Matched analyses will use conditional logistic regression to adjust for potential confounding variables. Unmatched analyses will use unconditional logistic regression, adjusted for age, sex, deprivation and distance from hospital in addition to other confounders. Each study requires 496 cases and 1984 controls to detect an OR of 0.7, with 80% power, 5% significance level, a correlation between cases and controls of 0.1 and a range of exposure prevalences. Main outcome measures Falls on stairs, on one level and from furniture. Discussion As the largest in the field to date, these case control studies will adjust for potential confounders, validate measures of exposure and investigate modifiable risk factors for specific falls injury mechanisms. Findings should enhance the evidence base for falls prevention for young children. PMID:22628151

Lack of genetic association between the phospholipase A2 gene and bipolar mood disorder in a European multicentre case-control study.

PubMed

Dikeos, Dimitris G; Papadimitriou, George N; Souery, Daniel; Del-Favero, Jurgen; Massat, Isabelle; Blackwood, Douglas; Cichon, Sven; Daskalopoulou, Eugenia; Ivezic, Sladjana; Kaneva, Radka; Karadima, Georgia; Lorenzi, Cristina; Milanova, Vihra; Muir, Walter; Nöthen, Markus; Oruc, Lilijana; Rietschel, Marcella; Serretti, Alessandro; Van Broeckhoven, Christine; Soldatos, Constantin R; Stefanis, Costas N; Mendlewicz, Julien

2006-08-01

The possible association between phospholipase A2 gene and bipolar mood disorder was examined in 557 bipolar patients and 725 controls (all personally interviewed), recruited from seven countries (Belgium, Bulgaria, Croatia, Germany, Greece, Italy, and UK). The frequencies of the eight alleles that were identified did not differ between patients and control individuals in the whole population, while the power to detect an association based on our sample was relatively high. Some differences were noted among the various ethnic groups, but no significant trends existed, suggesting that population stratification by country may not be responsible for a type II error. On the basis of these results, mutations of the phospholipase A2 gene, at least in the region close to the polymorphism examined between exons 1 and 2, are not involved in the pathogenesis of bipolar mood disorder.

A Multi-centric, Double-blind, Placebo-controlled, Randomized, Prospective Study to Evaluate the Efficacy and Safety of Carica papaya Leaf Extract, as Empirical Therapy for Thrombocytopenia associated with Dengue Fever.

PubMed

Kasture, Prabhu Nagnathappa; Nagabhushan, K H; Kumar, Arun

2016-06-01

Dengue is a rapidly expanding global health problem. Approximately 2.5 billion people live in dengue-risk regions with about 100 million new cases each year worldwide. The cumulative dengue diseases burden has attained an unprecedented proportion in recent times with sharp increase in the size of human population at risk. The management of dengue virus infection is essentially supportive and symptomatic and no specific treatment is available for increasing the fallen platelets, which have a significant role in causing the mortality of dengue patient.This study was conducted to evaluate the platelet increasing efficacy of Carica papaya leaf extract (CPLE) in patients with dengue fever (DF). The administration of Carica papaya leaf extract should significantly increase the platelet count in cases of thrombocytopenia associated with dengue, preventing the patient to go in DHF or DSS conditions. A Multi-centric, Double blind, Placebo controlled, Randomized, prospective study was conducted in 300 patients across 5 centres', to evaluate the Efficacy and Safety of Carica Papaya Leaf Extract, as empirical therapy for thrombocytopenia associated with dengue fever. The subjects were randomized into two groups, as control and intervention group. Both the groups were managed by the standard management guidelines for dengue except steroid administration. In addition to this, the intervention group received CPLE tablet three times daily for five days. All of them were followed daily with platelet monitoring. This study has been registered in the clinical trial registry-India (CTRI Registration number: CTRI/2015/05/005806). The results indicate that CPLE had significant increase(p< 0.01) in the platelet count over the therapy duration, in dengue fever patients, confirming CPLE accelerates the increase in platelet count compared to the control group. There were few adverse events related to GI disturbance like nausea and vomiting which were similar in both groups. Thus this study concluded that Carica papaya leaf extract (CPLE) does significantly increase the platelet count in patients with thrombocytopenia associated with dengue with fewer side effects and good tolerability.

Behaviour-change intervention in a multicentre, randomised, placebo-controlled COPD study: methodological considerations and implementation.

PubMed

Bourbeau, Jean; Lavoie, Kim L; Sedeno, Maria; De Sousa, Dorothy; Erzen, Damijan; Hamilton, Alan; Maltais, François; Troosters, Thierry; Leidy, Nancy

2016-04-04

Chronic obstructive pulmonary disease is generally progressive and associated with reduced physical activity. Both pharmacological therapy and exercise training can improve exercise capacity; however, these are often not sufficient to change the amount of daily physical activity a patient undertakes. Behaviour-change self-management programmes are designed to address this, including setting motivational goals and providing social support. We present and discuss the necessary methodological considerations when integrating behaviour-change interventions into a multicentre study. PHYSACTO is a 12-week phase IIIb study assessing the effects on exercise capacity and physical activity of once-daily tiotropium+olodaterol 5/5 µg with exercise training, tiotropium+olodaterol 5/5 µg without exercise training, tiotropium 5 µg or placebo, with all pharmacological interventions administered via the Respimat inhaler. Patients in all intervention arms receive a behaviour-change self-management programme to provide an optimal environment for translating improvements in exercise capacity into increases in daily physical activity. To maximise the likelihood of success, special attention is given in the programme to: (1) the Site Case Manager, with careful monitoring of programme delivery; (2) the patient, incorporating patient-evaluation/programme-evaluation measures to guide the Site Case Manager in the self-management intervention; and (3) quality assurance, to help identify and correct any problems or shortcomings in programme delivery and ensure the effectiveness of any corrective steps. This paper documents the comprehensive methods used to optimise and standardise the behaviour-change self-management programme used in the study to facilitate dialogue on the inclusion of this type of programme in multicentre studies. The study has been approved by the relevant Institutional Review Boards, Independent Ethics Committee and Competent Authority according to national and international regulations. The results of this study will be disseminated through relevant, peer-reviewed journals and international conference presentations. NCT02085161. 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/

Surgical timing after chemoradiotherapy for rectal cancer, analysis of technique (STARRCAT): results of a feasibility multi-centre randomized controlled trial.

PubMed

Foster, J D; Ewings, P; Falk, S; Cooper, E J; Roach, H; West, N P; Williams-Yesson, B A; Hanna, G B; Francis, N K

2016-10-01

The optimal time of rectal resection after long-course chemoradiotherapy (CRT) remains unclear. A feasibility study was undertaken for a multi-centre randomized controlled trial evaluating the impact of the interval after chemoradiotherapy on the technical complexity of surgery. Patients with rectal cancer were randomized to either a 6- or 12-week interval between CRT and surgery between June 2012 and May 2014 (ISRCTN registration number: 88843062). For blinded technical complexity assessment, the Observational Clinical Human Reliability Analysis technique was used to quantify technical errors enacted within video recordings of operations. Other measured outcomes included resection completeness, specimen quality, radiological down-staging, tumour cell density down-staging and surgeon-reported technical complexity. Thirty-one patients were enrolled: 15 were randomized to 6 and 16-12 weeks across 7 centres. Fewer eligible patients were identified than had been predicted. Of 23 patients who underwent resection, mean 12.3 errors were observed per case at 6 weeks vs. 10.7 at 12 weeks (p = 0.401). Other measured outcomes were similar between groups. The feasibility of measurement of operative performance of rectal cancer surgery as an endpoint was confirmed in this exploratory study. Recruitment of sufficient numbers of patients represented a challenge, and a proportion of patients did not proceed to resection surgery. These results suggest that interval after CRT may not substantially impact upon surgical technical performance.

[Treatment of herpes zoster with cotton sheet moxibustion: multicentral randomized controlled trial].

PubMed

Yang, Jun-Xiong; Xiang, Kai-Wei; Zhang, Yu-Xue

2012-05-01

To compare the therapeutic effects and safety of herpes zoster treated by the cotton sheet moxibustion combined with the plum-blossom-needle tapping therapy to western medicine. The multicentral random controlled method was adopted, 120 cases of herpes zoster were randomly divided into a comprehensive treatment group and a western medication group, 60 cases in each one. In the comprehensive treatment group, the tapping therapy of plum blossom needle was applied to the foci, corresponding Jiaji (EX-B 2), Quchi (LI 11), Waiguan (TE 5), Zusanli (ST 36), Taichong (LR 3), etc. Afterward, the cotton sheet moxibustion was given. In western medication group, Acyclovir ointment for external application, Valaciclovir Hydrochloride tablets and Vitamin B1 for oral administration were prescribed. In 7 days of treatment, the clinical symptom score, effect time, efficacy and safety were observed before and after treatment between two groups. The recurrence of disease was followed up for 1 month. In the comprehensive treatment group, the cured rate and the total effective rate were 80.0% (48/60) and 98.3% (59/60) separately, which were significantly better than 45.0% (27/60) and 71.7% (43/60) in western medication group separately (P < 0.01, P < 0.05). After treatment, in either group, the scores of clinical symptoms such as pain rating index (PRI), Visual Analogue Scale (VAS), present pain intensity (PPI), skin lesion and sleeping score, etc. were all reduced significantly (P < 0.01, P < 0.05). The score reducing was much more obvious in the comprehensive treatment group (P < 0.01, P < 0.05). In the comprehensive treatment group, the time of pain stopping, the time of blister stopping, the time of scarring and the time of healing were all shorter tha tn those in western medication group (P < 0.01, P < 0.05). In the follow-up observation, 1 case (1.6%) was recurred in the comprehensive treatment group and 8 cases (13.3%) were in western medication group. In western medication group, 6 cases presented mild adverse reactions. The cotton sheet moxibustion combined with the plum-blossom-needle tapping therapy is advantageous at good efficacy, quick effect and short-time treatment for herpes zoster, which is apparently superior to the treatment with Acyclovir ointment for external application, Valaciclovir Hydrochloride tablets and Vitamin B1 for oral administration. It is the safe and effective therapy.

Sudden cardiac death in adults with congenital heart disease: does QRS-complex fragmentation discriminate in structurally abnormal hearts?

PubMed

Vehmeijer, Jim T; Koyak, Zeliha; Bokma, Jouke P; Budts, Werner; Harris, Louise; Mulder, Barbara J M; de Groot, Joris R

2018-06-01

Sudden cardiac death (SCD) causes a large portion of all mortality in adult congenital heart disease (ACHD) patients. However, identification of high-risk patients remains challenging. Fragmented QRS-complexes (fQRS) are a marker for SCD in patients with acquired heart disease but data in ACHD patients are lacking. We therefore aim to evaluate the prognostic value of fQRS for SCD in ACHD patients. From a multicentre cohort of 25 790 ACHD patients, we included tachyarrhythmic SCD cases (n = 147), and controls (n = 266) matched by age, gender, congenital defect and (surgical) intervention. fQRS was defined as ≥1 discontinuous deflection in narrow QRS-complexes, and ≥2 in wide QRS-complexes (>120 ms), in two contiguous ECG leads. We calculated odds ratios (OR) using univariable and multivariable conditional logistic regression models correcting for impaired systemic ventricular function, heart failure and QRS duration >120 ms. ECGs of 147 SCD cases (65% male, median age of death 34 years) and of 266 controls were assessed. fQRS was present in 51% of cases and 34% of controls (OR 2.0, P = 0.003). In multivariable analysis, fQRS was independently associated with SCD (OR 1.9, P = 0.01). The most common diagnose of SCD cases was tetralogy of Fallot (ToF, 34 cases). In ToF, fQRS was present in 71% of cases vs. 43% of controls (OR for SCD 2.8, P = 0.03). fQRS was independently associated with SCD in ACHD patients in a cohort of SCD patients and matched controls. fQRS may therefore contribute to the decision when evaluating ACHD patients for primary prevention of SCD.

Physiotherapy, and speech and language therapy intervention for patients with refractory chronic cough: a multicentre randomised control trial.

PubMed

Chamberlain Mitchell, Sarah A F; Garrod, Rachel; Clark, Lynne; Douiri, Abdel; Parker, Sean M; Ellis, Jenny; Fowler, Stephen J; Ludlow, Siobhan; Hull, James H; Chung, Kian Fan; Lee, Kai K; Bellas, H; Pandyan, Anand; Birring, Surinder S

2017-02-01

Physiotherapy, and speech and language therapy are emerging non-pharmacological treatments for refractory chronic cough. We aimed to investigate the efficacy of a physiotherapy, and speech and language therapy intervention (PSALTI) to improve health-related quality of life (HRQoL) and to reduce cough frequency in patients with refractory chronic cough. In this multicentre randomised controlled trial, patients with refractory chronic cough were randomised to four weekly 1:1 sessions of either PSALTI consisting of education, laryngeal hygiene and hydration, cough suppression techniques, breathing exercises and psychoeducational counselling or control intervention consisting of healthy lifestyle advice. We assessed the change in HRQoL at week 4 with the Leicester Cough Questionnaire (LCQ). Secondary efficacy outcomes included 24-hour objective cough frequency (Leicester Cough Monitor) and cough reflex sensitivity. The primary analysis used an analysis of covariance adjusted for baseline measurements with the intention-to-treat population. This study was registered at UK Clinical Research Network (UKCRN ID 10678). Between December 2011 and April 2014, we randomly assigned 75 participants who underwent baseline assessment (34 PSALTI and 41 controls). In the observed case analysis, HRQoL (LCQ) improved on average by 1.53 (95% CI 0.21 to 2.85) points more in PSALTI group than with control (p=0.024). Cough frequency decreased by 41% (95% CI 36% to 95%) in PSALTI group relative to control (p=0.030). The improvements within the PSALTI group were sustained up to 3 months. There was no significant difference between groups in the concentration of capsaicin causing five or more coughs. Greater improvements in HRQoL and cough frequency were observed with PSALTI intervention. Our findings support the use of PSALTI for patients with refractory chronic cough. UKCRN ID 10678 and ISRCTN 73039760; Results. 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 physical anthropometry, lifestyle habits and blood pressure of people presenting with a first clinical demyelinating event compared to controls: the Ausimmune study.

PubMed

Ponsonby, Anne-Louise; Lucas, Robyn M; Dear, Keith; van der Mei, Ingrid; Taylor, Bruce; Chapman, Caron; Coulthard, Alan; Dwyer, Terence; Kilpatrick, Trevor J; McMichael, Anthony J; Pender, Michael P; Valery, Patricia C; Williams, David

2013-11-01

Lifestyle factors prior to a first clinical demyelinating event (FCD), a disorder often preceding the development of clinically definite multiple sclerosis (MS), have not previously been examined in detail. Past tobacco smoking has been consistently associated with MS. This was a multicentre incident case-control study. Cases (n = 282) were aged 18-59 years with an FCD and resident within one of four Australian centres (from latitudes 27°S to 43°S), from 1 November 2003 to 31 December 2006. Controls (n = 558) were matched to cases on age, sex and study region, without CNS demyelination. Exposures measured included current and past tobacco and marijuana, alcohol and beverage use, physical activity patterns, blood pressure and physical anthropometry. A history of smoking ever was associated with FCD risk (AOR 1.89 (95%CL 1.82, 3.52)). Marijuana use was not associated with FCD risk after adjusting for confounders such as smoking ever but the estimates were imprecise because of a low prevalence of use. Alcohol consumption was common and not associated with FCD risk. No case-control differences in blood pressure or physical anthropometry were observed. Past tobacco smoking was positively associated with a risk of FCD but most other lifestyle factors were not. Prevention efforts against type 2 diabetes and cardiovascular disease by increasing physical activity and reducing obesity are unlikely to alter MS incidence, and more targeted campaigns will be required.

Autoantibodies and human immunodeficiency viruses infection: a case-control study.

PubMed

Chretien, P; Monier, J C; Oksman, F; San Marco, M; Escande, A; Goetz, J; Cohen, J; Baquey, A; Humbel, R L; Sibilia, J

2003-01-01

To determine the prevalence of organ-specific and non-specific autoantibodies in HIV-infected patients. A multicentric collaborative case-control study including 105 HIV patients and 100 sex- and age-matched HIV-negative healthy volunteers. Antinuclear, anti-ds DNA, anti-histone, anti-Sm, rheumatoid factor(IgM), anti-beta 2 glycoprotein 1, antineutrophil cytoplasmic, anti-LKM1, anti-LCA1, anti-gastric parietal cell, antiplatelet, anti-intermediate filament, anti-mitotic spindle apparatus, anti-Golgi, anti-ribosome and anti-thyroid autoantibodies were screened in six European laboratories. Only IgG and IgM anticardiolipin, IgG antiplatelet, anti-smooth muscle and anti-thyroglobulin antibodies were statistically more frequent in HIV patients. There was no correlation with the numbers of CD4+ cells except in the case of anti-smooth muscle antibodies. We were unable to find specific autoantibodies such as anti-ds DNA, anti-Sm, AMA, anti-LKM1, anti-LCA1 or anti-beta 2 GP1 antibodies in these patients. Our results indicate that the autoantibody profile of HIV infections is comparable to those of other chronic viral infections. HIV does not seem to be more autoimmunogenic than other viruses.

A pragmatic multi-centre randomised controlled trial of fluid loading and level of dependency in high-risk surgical patients undergoing major elective surgery: trial protocol

PubMed Central

2010-01-01

Background Patients undergoing major elective or urgent surgery are at high risk of death or significant morbidity. Measures to reduce this morbidity and mortality include pre-operative optimisation and use of higher levels of dependency care after surgery. We propose a pragmatic multi-centre randomised controlled trial of level of dependency and pre-operative fluid therapy in high-risk surgical patients undergoing major elective surgery. Methods/Design A multi-centre randomised controlled trial with a 2 * 2 factorial design. The first randomisation is to pre-operative fluid therapy or standard regimen and the second randomisation is to routine intensive care versus high dependency care during the early post-operative period. We intend to recruit 204 patients undergoing major elective and urgent abdominal and thoraco-abdominal surgery who fulfil high-risk surgical criteria. The primary outcome for the comparison of level of care is cost-effectiveness at six months and for the comparison of fluid optimisation is the number of hospital days after surgery. Discussion We believe that the results of this study will be invaluable in determining the future care and clinical resource utilisation for this group of patients and thus will have a major impact on clinical practice. Trial Registration Trial registration number - ISRCTN32188676 PMID:20398378

Improving patient recruitment to multicentre clinical trials: the case for employing a data manager in a district general hospital-based oncology centre.

PubMed

Street, A; Strong, J; Karp, S

2001-01-01

One of the most frequently cited reasons for poor recruitment to multicentre randomized clinical trials is the additional workload placed on clinical staff. We report the effect on patient recruitment of employing a data manager to support clinical staff in an English district general hospital (DGH). In addition, we explore the effect data managers have on the quality of data collected, proxied by the number of queries arising with the trial organizers. We estimate that the cost of employing a data manager on a full-time basis is 502 per patient recruited but may amount to 326 if the appointment is part-time. Data quality is high when full responsibility lies with a data manager but falls when responsibility is shared. Whether the costs of employing a data manager to recruit patients from a DGH are worth incurring depends on the value placed on the speed at which multicentre trials can be completed, how important it is to broaden the research base beyond the traditional setting of teaching hospitals, and the amount of evaluative data required.

Lower omega-3 fatty acids are associated with the presence of anti-cyclic citrullinated peptide autoantibodies in a population at risk for future rheumatoid arthritis: a nested case-control study

PubMed Central

Gan, Ryan W.; Young, Kendra A.; Zerbe, Gary O.; Demoruelle, M. Kristen; Weisman, Michael H.; Buckner, Jane H.; Gregersen, Peter K.; Mikuls, Ted R.; O’Dell, James R.; Keating, Richard M.; Clare-Salzler, Michael J.; Deane, Kevin D.; Holers, V. Michael

2016-01-01

Objective. The aim of this study was to investigate omega-3 fatty acid (FA) supplement use and omega-3 FAs in erythrocyte membranes [omega-3 FA % in erythrocyte membranes (RBC)] and their association with anti-CCP autoantibodies in a population without RA, but who are at genetic risk for RA. Methods. The multicentre Studies of the Etiology of RA (SERA) cohort includes RA-free subjects who are first-degree relatives of RA probands or are enriched with the HLA-DR4 allele. In a nested case-control study, 30 SERA cases were identified who were anti-CCP2 antibody positive. We further identified 47 autoantibody negative controls, frequency matched to cases on age at study visit, sex, race and study site. Anti-CCP2 status, self-reported omega-3 FA supplement use and omega-3 FA % in RBCs were obtained from a single visit. Results. Anti-CCP2 positive cases were less likely than controls to report omega-3 FA supplement use (odds ratio: 0.14; 95% CI 0.03, 0.68). In addition, the likelihood of anti-CCP2 positivity was inversely associated with total omega-3 FA % in RBCs (odds ratio: 0.47; 95% CI 0.24, 0.92, for a s.d. increase). Conclusion. The inverse association between anti-CCP2 positivity and self-reported omega-3 FA supplement use and omega-3 FA % in RBCs suggests that omega-3 FAs may protect against the development of RA-related autoimmunity in pre-clinical RA. PMID:26370400

Stressful life events and the risk of initial central nervous system demyelination.

PubMed

Saul, Alice; Ponsonby, Anne-Louise; Lucas, Robyn M; Taylor, Bruce V; Simpson, Steve; Valery, Patricia; Dwyer, Terence; Kilpatrick, Trevor J; Pender, Michael P; van der Mei, Ingrid Af

2017-06-01

There is substantial evidence that stress increases multiple sclerosis disease activity, but limited evidence on its association with the onset of multiple sclerosis. To examine the association between stressful life events and risk of first demyelinating event (FDE). This was a multicentre incident case-control study. Cases ( n = 282 with first diagnosis of central nervous system (CNS) demyelination, including n = 216 with 'classic FDE') were aged 18-59 years. Controls without CNS demyelination ( n = 558) were matched to cases on age, sex and study region. Stressful life events were assessed using a questionnaire based on the Social Readjustment Rating Scale. Those who suffered from a serious illness in the previous 12 months were more likely to have an FDE (odds ratio (OR) = 2.35 (1.36, 4.06), p = 0.002), and when we limited our reference group to those who had no stressful life events, the magnitude of effect became stronger (OR = 5.41 (1.80, 16.28)). The total stress number and stress load were not convincingly associated with the risk of an FDE. Cases were more likely to report a serious illness in the previous 12 months, which could suggest that a non-specific illness provides an additional strain to an already predisposed immune system.

Estimates of Pandemic Influenza Vaccine Effectiveness in Europe, 2009–2010: Results of Influenza Monitoring Vaccine Effectiveness in Europe (I-MOVE) Multicentre Case-Control Study

PubMed Central

Valenciano, Marta; Kissling, Esther; Cohen, Jean-Marie; Oroszi, Beatrix; Barret, Anne-Sophie; Rizzo, Caterina; Nunes, Baltazar; Pitigoi, Daniela; Larrauri Cámara, Amparro; Mosnier, Anne; Horvath, Judith K.; O'Donnell, Joan; Bella, Antonino; Guiomar, Raquel; Lupulescu, Emilia; Savulescu, Camelia; Ciancio, Bruno C.; Kramarz, Piotr; Moren, Alain

2011-01-01

Background A multicentre case-control study based on sentinel practitioner surveillance networks from seven European countries was undertaken to estimate the effectiveness of 2009–2010 pandemic and seasonal influenza vaccines against medically attended influenza-like illness (ILI) laboratory-confirmed as pandemic influenza A (H1N1) (pH1N1). Methods and Findings Sentinel practitioners swabbed ILI patients using systematic sampling. We included in the study patients meeting the European ILI case definition with onset of symptoms >14 days after the start of national pandemic vaccination campaigns. We compared pH1N1 cases to influenza laboratory-negative controls. A valid vaccination corresponded to >14 days between receiving a dose of vaccine and symptom onset. We estimated pooled vaccine effectiveness (VE) as 1 minus the odds ratio with the study site as a fixed effect. Using logistic regression, we adjusted VE for potential confounding factors (age group, sex, month of onset, chronic diseases and related hospitalizations, smoking history, seasonal influenza vaccinations, practitioner visits in previous year). We conducted a complete case analysis excluding individuals with missing values and a multiple multivariate imputation to estimate missing values. The multivariate imputation (n = 2902) adjusted pandemic VE (PIVE) estimates were 71.9% (95% confidence interval [CI] 45.6–85.5) overall; 78.4% (95% CI 54.4–89.8) in patients <65 years; and 72.9% (95% CI 39.8–87.8) in individuals without chronic disease. The complete case (n = 1,502) adjusted PIVE were 66.0% (95% CI 23.9–84.8), 71.3% (95% CI 29.1–88.4), and 70.2% (95% CI 19.4–89.0), respectively. The adjusted PIVE was 66.0% (95% CI −69.9 to 93.2) if vaccinated 8–14 days before ILI onset. The adjusted 2009–2010 seasonal influenza VE was 9.9% (95% CI −65.2 to 50.9). Conclusions Our results suggest good protection of the pandemic monovalent vaccine against medically attended pH1N1 and no effect of the 2009–2010 seasonal influenza vaccine. However, the late availability of the pandemic vaccine and subsequent limited coverage with this vaccine hampered our ability to study vaccine benefits during the outbreak period. Future studies should include estimation of the effectiveness of the new trivalent vaccine in the upcoming 2010–2011 season, when vaccination will occur before the influenza season starts. Please see later in the article for the Editors' Summary PMID:21379316

The cataract national data set electronic multi-centre audit of 55,567 operations: case-mix adjusted surgeon's outcomes for posterior capsule rupture.

PubMed

Sparrow, J M; Taylor, H; Qureshi, K; Smith, R; Johnston, R L

2011-08-01

To develop a methodology for case-mix adjustment of surgical outcomes for individual cataract surgeons using electronically collected multi-centre data conforming to the cataract national data set (CND). Routinely collected anonymised data were remotely extracted from electronic patient record (EPR) systems in 12 participating NHS Trusts undertaking cataract surgery. Following data checks and cleaning, analyses were carried out to risk adjust outcomes for posterior capsule rupture rates for individual surgeons, with stratification by surgical grade. A total of 406 surgeons from 12 NHS Trusts submitted data on 55,567 cataract operations between November 2001 and July 2006 (86% from January 2004). In all, 283 surgeons contributed data on >25 cases, providing 54,319 operations suitable for detailed analysis. Case-mix adjusted results of individual surgeons are presented as funnel plots for all surgeons together, and separately for three different grades of surgeon. Plots include 95 and 99.8% confidence limits around the case-mix adjusted outcomes for detection of surgical outliers. Routinely collected electronic data conforming to the CND provides sufficient detail for case-mix adjustment of cataract surgical outcomes. The validation of these risk indicators should be carried out using fresh data to confirm the validity of the risk model. Once validated this model should provide an equitable approach for peer-to-peer comparisons in the context of revalidation.

Intravesical administration of combined hyaluronic acid (HA) and chondroitin sulfate (CS) for the treatment of female recurrent urinary tract infections: a European multicentre nested case-control study.

PubMed

Ciani, Oriana; Arendsen, Erik; Romancik, Martin; Lunik, Richard; Costantini, Elisabetta; Di Biase, Manuel; Morgia, Giuseppe; Fragalà, Eugenia; Roman, Tomaskin; Bernat, Marian; Guazzoni, Giorgio; Tarricone, Rosanna; Lazzeri, Massimo

2016-03-31

To compare the clinical effectiveness of the intravesical administration of combined hyaluronic acid and chondroitin sulfate (HA+CS) versus current standard management in adult women with recurrent urinary tract infections (RUTIs). A European Union-based multicentre, retrospective nested case-control study. 276 adult women treated for RUTIs starting from 2009 to 2013. Patients treated with either intravesical administration of HA+CS or standard of care (antimicrobial/immunoactive prophylaxis/probiotics/cranberry). The primary outcome was occurrence of bacteriologically confirmed recurrence within 12 months. Secondary outcomes were time to recurrence, total number of recurrences, health-related quality of life and healthcare resource consumption. Crude and adjusted results for unbalanced characteristics are presented. 181 patients treated with HA+CS and 95 patients treated with standard of care from 7 centres were included. The crude and adjusted ORs (95% CI) for the primary end point were 0.77 (0.46 to 1.28) and 0.51 (0.27 to 0.96), respectively. However, no evidence of improvement in terms of total number of recurrences (incidence rate ratio (95% CI), 0.99 (0.69 to 1.43)) or time to first recurrence was seen (HR (95% CI), 0.99 (0.61 to 1.61)). The benefit of intravesical HA+CS therapy improves when the number of instillations is ≥ 5. Our results show that bladder instillations of combined HA+CS reduce the risk of bacteriologically confirmed recurrences compared with the current standard management of RUTIs. Total incidence rates and hazard rates were instead non-significantly different between the 2 groups after adjusting for unbalanced factors. In contrast to what happens with antibiotic prophylaxis, the effectiveness of the HA+CS reinstatement therapy improves over time. NCT02016118. 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/

A feasibility study investigating the acceptability and design of a multicentre randomised controlled trial of needle fasciotomy versus limited fasciectomy for the treatment of Dupuytren's contractures of the fingers (HAND-1): study protocol for a randomised controlled trial.

PubMed

Harrison, Eleanor; Tan, Wei; Mills, Nicola; Karantana, Alexia; Sprange, Kirsty; Duley, Lelia; Elliott, Daisy; Blazeby, Jane; Hollingworth, William; Montgomery, Alan A; Davis, Tim

2017-08-25

Dupuytren's contractures are fibrous cords under the skin of the palm of the hand. The contractures are painless but cause one or more fingers to curl into the palm, resulting in loss of function. Standard treatment within the NHS is surgery to remove (fasciectomy) or divide (fasciotomy) the contractures, and the treatment offered is frequently determined by surgeon preference. This study aims to determine the feasibility of conducting a large, multicentre randomised controlled trial to assess the clinical and cost-effectiveness of needle fasciotomy versus limited fasciectomy for the treatment of Dupuytren's contracture. HAND-1 is a parallel, two-arm, multicentre, randomised feasibility trial. Eligible patients aged 18 years or over who have one or more fingers with a Dupuytren's contracture of more than 30° in the metacarpophalangeal (MCP) and/or proximal interphalangeal (PIP) joints, well-defined cord(s) causing contracture, and have not undergone previous surgery for Dupuytren's on the same hand will be randomised (1:1) to treatment with either needle fasciotomy or limited fasciectomy. Participants will be followed-up for up to 6 months post surgery. Feasibility outcomes include number of patients screened, consented and randomised, adherence with treatment, completion of follow-up and identification of an appropriate patient-reported outcome measure (PROM) to use as primary outcome for a main trial. Embedded qualitative research, incorporating a QuinteT Recruitment Intervention, will focus on understanding and optimising the recruitment process, and exploring patients' experiences of trial participation and the interventions. This study will assess whether a large multicentre trial comparing the clinical and cost-effectiveness of needle fasciotomy and limited fasciectomy for the treatment of Dupuytren's contractures is feasible, and if so will provide data to inform its design and successful conduct. International Standard Registered Clinical/soCial sTudy Number: ISRCTN11164292 . Registered on 28 August 2015.

Appendectomy versus non-operative treatment for acute uncomplicated appendicitis in children: study protocol for a multicentre, open-label, non-inferiority, randomised controlled trial

PubMed Central

Eaton, Simon; Abbo, Olivier; Arnaud, Alexis P; Beaudin, Marianne; Brindle, Mary; Bütter, Andreana; Davies, Dafydd; Jancelewicz, Tim; Johnson, Kathy; Keijzer, Richard; Lapidus-Krol, Eveline; Offringa, Martin; Piché, Nelson; Rintala, Risto; Skarsgard, Erik; Svensson, Jan F; Ungar, Wendy J; Wester, Tomas; Willan, Andrew R; Zani, Augusto; St Peter, Shawn D; Pierro, Agostino

2017-01-01

Background Appendectomy is considered the gold standard treatment for acute appendicitis. Recently the need for surgery has been challenged in both adults and children. In children there is growing clinician, patient and parental interest in non-operative treatment of acute appendicitis with antibiotics as opposed to surgery. To date no multicentre randomised controlled trials that are appropriately powered to determine efficacy of non-operative treatment (antibiotics) for acute appendicitis in children compared with surgery (appendectomy) have been performed. Methods Multicentre, international, randomised controlled trial with a non-inferiority design. Children (age 5–16 years) with a clinical and/or radiological diagnosis of acute uncomplicated appendicitis will be randomised (1:1 ratio) to receive either laparoscopic appendectomy or treatment with intravenous (minimum 12 hours) followed by oral antibiotics (total course 10 days). Allocation to groups will be stratified by gender, duration of symptoms (> or <48 hours) and centre. Children in both treatment groups will follow a standardised treatment pathway. Primary outcome is treatment failure defined as additional intervention related to appendicitis requiring general anaesthesia within 1 year of randomisation (including recurrent appendicitis) or negative appendectomy. Important secondary outcomes will be reported and a cost-effectiveness analysis will be performed. The primary outcome will be analysed on a non-inferiority basis using a 20% non-inferiority margin. Planned sample size is 978 children. Discussion The APPY trial will be the first multicentre randomised trial comparing non-operative treatment with appendectomy for acute uncomplicated appendicitis in children. The results of this trial have the potential to revolutionise the treatment of this common gastrointestinal emergency. The randomised design will limit the effect of bias on outcomes seen in other studies. Trial registration number clinicaltrials.gov: NCT02687464. Registered on Jan 13th 2016. PMID:29637088

Individualised pelvic floor muscle training in women with pelvic organ prolapse (POPPY): a multicentre randomised controlled trial.

PubMed

Hagen, Suzanne; Stark, Diane; Glazener, Cathryn; Dickson, Sylvia; Barry, Sarah; Elders, Andrew; Frawley, Helena; Galea, Mary P; Logan, Janet; McDonald, Alison; McPherson, Gladys; Moore, Kate H; Norrie, John; Walker, Andrew; Wilson, Don

2014-03-01

Pelvic organ prolapse is common and is strongly associated with childbirth and increasing age. Women with prolapse are often advised to do pelvic floor muscle exercises, but evidence supporting the benefits of such exercises is scarce. We aimed to establish the effectiveness of one-to-one individualised pelvic floor muscle training for reducing prolapse symptoms. We did a parallel-group, multicentre, randomised controlled trial at 23 centres in the UK, one in New Zealand, and one in Australia, between June 22, 2007, and April 9, 2010. Female outpatients with newly-diagnosed, symptomatic stage I, II, or III prolapse were randomly assigned (1:1), by remote computer allocation with minimsation, to receive an individualised programme of pelvic floor muscle training or a prolapse lifestyle advice leaflet and no muscle training (control group). Outcome assessors, and investigators who were gynaecologists at trial sites, were masked to group allocation; the statistician was masked until after data analysis. Our primary endpoint was participants' self-report of prolapse symptoms at 12 months. Analysis was by intention-to-treat analysis. This trial is registered, number ISRCTN35911035. 447 eligible patients were randomised to the intervention group (n=225) or the control group (n=222). 377 (84%) participants completed follow-up for questionnaires at 6 months and 295 (66%) for questionnaires at 12 months. Women in the intervention group reported fewer prolapse symptoms (ie, a significantly greater reduction in the pelvic organ prolapse symptom score [POP-SS]) at 12 months than those in the control group (mean reduction in POP-SS from baseline 3.77 [SD 5.62] vs 2.09 [5.39]; adjusted difference 1.52, 95% CI 0.46-2.59; p=0.0053). Findings were robust to missing data. Eight adverse events (six vaginal symptoms, one case of back pain, and one case of abdominal pain) and one unexpected serious adverse event, all in women from the intervention group, were regarded as unrelated to the intervention or to participation in the study. One-to-one pelvic floor muscle training for prolapse is effective for improvement of prolapse symptoms. Long-term benefits should be investigated, as should the effects in specific subgroups. Chief Scientist Office of the Scottish Government Health and Social Care Directorates, New Zealand Lottery Board, and National Health and Medical Research Council (Australia). Copyright © 2014 Elsevier Ltd. All rights reserved.

Detection of Mycoplasma pneumoniae and Legionella pneumophila in Patients Having Community-Acquired Pneumonia: A Multicentric Study from New Delhi, India.

PubMed

Chaudhry, Rama; Valavane, Arvind; Sreenath, K; Choudhary, Mamta; Sagar, Tanu; Shende, Trupti; Varma-Basil, Mandira; Mohanty, Srujana; Kabra, S K; Dey, A B; Thakur, Bhaskar

2017-12-01

Atypical pathogens including Mycoplasma pneumoniae and Legionella pneumophila are increasingly recognized as important causes of community-acquired pneumonia (CAP). Mycoplasma pneumoniae accounts for 20-40% of all CAP and L. pneumophila is responsible for 3-15% of cases. The paucity of data from India in this regard prompted us to conduct this prospective multicentric analysis to detect the prevalence of M. pneumoniae and L. pneumophila in our geographical region. A total of 453 patients with symptoms of pneumonia and 90 controls with no history of lower respiratory tract infections were included in the study. A duplex polymerase chain reaction (PCR) targeting 543 bp region of P1 adhesin gene of M. pneumoniae and 375 bp region of macrophage infectivity potentiator (mip) gene of L. pneumophila was standardized for simultaneous detection of these atypical pathogens. Respiratory secretions, blood, and urine samples were collected from each patient and control and were subjected to duplex PCR, culture and serology for M. pneumoniae and L. pneumophila . Urine samples were subjected for detecting L. pneumophila antigen. Among the 453 patients investigated for M. pneumoniae , 52 (11.4%) were positive for IgM antibodies, 17 were positive by culture, and seven tested positive by PCR ( P1 gene). Similarly for L. pneumophila , 50 cases (11%) were serologically positive for IgM antibodies, one was positive by PCR ( mip gene) and urine antigen detection. A total of eight samples were positive by duplex PCR for M. pneumoniae P1 gene ( N = 7) and L. pneumophila mip gene ( N = 1). Of the 90 controls, two samples (2.2%) showed IgM positivity, and 15 (16.7%) showed IgG positivity for M. pneumoniae . For L. pneumophila , three samples (3.3%) tested positive for IgM, and 12 (13.3%) tested positive for IgG antibodies. The study findings indicate the presence of M. pneumoniae and L. pneumophila in our geographical region, and a combination of laboratory approaches including PCR, culture, and serology is required for effective detection of these agents.

The electrical heart axis and ST events in fetal monitoring: A post-hoc analysis following a multicentre randomised controlled trial.

PubMed

Vullings, Rik; Verdurmen, Kim M J; Hulsenboom, Alexandra D J; Scheffer, Stephanie; de Lau, Hinke; Kwee, Anneke; Wijn, Pieter F F; Amer-Wåhlin, Isis; van Laar, Judith O E H; Oei, S Guid

2017-01-01

Reducing perinatal morbidity and mortality is one of the major challenges in modern health care. Analysing the ST segment of the fetal electrocardiogram was thought to be the breakthrough in fetal monitoring during labour. However, its implementation in clinical practice yields many false alarms and ST monitoring is highly dependent on cardiotocogram assessment, limiting its value for the prediction of fetal distress during labour. This study aims to evaluate the relation between physiological variations in the orientation of the fetal electrical heart axis and the occurrence of ST events. A post-hoc analysis was performed following a multicentre randomised controlled trial, including 1097 patients from two participating centres. All women were monitored with ST analysis during labour. Cases of fetal metabolic acidosis, poor signal quality, missing blood gas analysis, and congenital heart disease were excluded. The orientation of the fetal electrical heart axis affects the height of the initial T/QRS baseline, and therefore the incidence of ST events. We grouped tracings with the same initial baseline T/QRS value. We depicted the number of ST events as a function of the initial baseline T/QRS value with a linear regression model. A significant increment of ST events was observed with increasing height of the initial T/QRS baseline, irrespective of the fetal condition; correlation coefficient 0.63, p<0.001. The most frequent T/QRS baseline is 0.12. The orientation of the fetal electrical heart axis and accordingly the height of the initial T/QRS baseline should be taken into account in fetal monitoring with ST analysis.

[Combination of acupuncture, cupping and medicine for treatment of fibromyalgia syndrome: a multi-central randomized controlled trial].

PubMed

Jang, Zhen-Ya; Li, Chang-Du; Qiu, Ling; Guo, Jun-Hua; He, Ling-Na; Yue, Yang; Li, Fang-Ze; Qin, Wen-Yi

2010-04-01

To evaluate the clinical effect of combination of acupuncture, cupping and medicine for treatment of fibromyalgia syndrome. By using multi-central randomized controlled method, 186 cases were randomly divided into an acupuncture combined with cupping and western medicine group (group A), an acupuncture combined with cupping group (group B) and a western medicine group (group C) and treated continuously for 4 weeks. The treatment of acupuncture combined with cupping was produced by acupuncture at five mental points and moving cupping on the Hechelu of the back, once evrey other day, thrice each week, and the western medicine therapy by oral administration of Amitriptyline, once each day. The scores of McGill Pain Questionnaire (MPQ), the amount of tenderness point and the time of producing effect were compared and the therapeutic effects were assessed with the Hamilton Depression Scale (HAMD). The cured and markedly effective rate was 65.0% (39/60) in the group A, which was superior to 15.9% (10/63) in the group B and 16.1% (9/56) in the group C (both P < 0.001). After treatment, the scores of MPQ and HAMD and the amount of tenderness point all decreased in the three groups, group A being significantly better than group B and group C, and the time of producing effect in the group A was more earlier than those in the group B and the group C. The therapeutic effect of combination of acupuncture, cupping and medicine on fibromyalgia syndrome is superior to that of the simple acupuncture combined with cupping or the simple medicine.

Distribution of causes of maternal mortality during delivery and post-partum: results of an African multicentre hospital-based study.

PubMed

Thonneau, Patrick F; Matsudai, Tomohiro; Alihonou, Eusèbe; De Souza, Jose; Faye, Ousseynou; Moreau, Jean-Charles; Djanhan, Yao; Welffens-Ekra, Christiane; Goyaux, Nathalie

2004-06-15

To assess the maternal mortality ratio in maternity units of reference hospitals in large west African cities, and to describe the distribution of complications and causes of maternal deaths. Prospective descriptive study in twelve reference maternities located in three African countries (Benin, Ivory Coast, Senegal). Data (clinical findings at hospital entry, medical history, complications, type of surgery, vital status of the women at discharge) were collected from obstetrical and surgical files and from admission hospital registers. All cases of maternal deaths were systematically reviewed by African and European staff. Of a total of 10,515 women, 1495 presented a major obstetric complication with dystocia or inappropriate management of the labour phase as the leading cause. Eighty-five maternal deaths were reported, giving a global hospital-based maternal mortality ratio of 800/100,000. Hypertensive disorders were involved in 25/85 cases (29%) and post-partum haemorrhage in 13/85 cases (15%). Relatively few cases (14) of major sepsis were reported, leading to three maternal deaths. The results of this multicentre study confirm the high rates of maternal mortality in maternity units of reference hospitals in large African cities, and in addition to dystocia the contribution of hypertensive disorders and post-partum haemorrhage to maternal deaths.

Treatments for somnambulism in adults: assessing the evidence.

PubMed

Harris, Melanie; Grunstein, Ronald R

2009-08-01

Somnambulism, or sleepwalking, is a parasomnia of non-rapid eye movement (NREM) sleep where movement behaviours usually confined to wakefulness are displayed during sleep. Generally, if sleepwalking is causing distress or danger in spite of safety measures, medical or psychological treatment is indicated. Clinicians will need to assess the evidence for treatment options. MEDLINE, EMBASE, PsycINFO and the Ovid Evidence-Based Medicine Reviews (EBM) multifile databases were searched. No properly powered rigorous controlled trials were found for treatment of sleepwalking in adults. Seven reports described small trials with some kind of control arm, or retrospective case series which included 30 or more patients. With no high quality evidence to underpin recommendations for treatments of somnambulism, full discussion with patients is advised. Adequately powered, well-designed clinical trials are now needed, and multi-centre collaborations may be required to obtain the sample sizes required.

An open source toolkit for medical imaging de-identification.

PubMed

González, David Rodríguez; Carpenter, Trevor; van Hemert, Jano I; Wardlaw, Joanna

2010-08-01

Medical imaging acquired for clinical purposes can have several legitimate secondary uses in research projects and teaching libraries. No commonly accepted solution for anonymising these images exists because the amount of personal data that should be preserved varies case by case. Our objective is to provide a flexible mechanism for anonymising Digital Imaging and Communications in Medicine (DICOM) data that meets the requirements for deployment in multicentre trials. We reviewed our current de-identification practices and defined the relevant use cases to extract the requirements for the de-identification process. We then used these requirements in the design and implementation of the toolkit. Finally, we tested the toolkit taking as a reference those requirements, including a multicentre deployment. The toolkit successfully anonymised DICOM data from various sources. Furthermore, it was shown that it could forward anonymous data to remote destinations, remove burned-in annotations, and add tracking information to the header. The toolkit also implements the DICOM standard confidentiality mechanism. A DICOM de-identification toolkit that facilitates the enforcement of privacy policies was developed. It is highly extensible, provides the necessary flexibility to account for different de-identification requirements and has a low adoption barrier for new users.

Higher intake of omega-3 polyunsaturated fatty acids is associated with a decreased risk of a first clinical diagnosis of central nervous system demyelination: Results from the Ausimmune Study.

PubMed

Hoare, Samuel; Lithander, Fiona; van der Mei, Ingrid; Ponsonby, Anne-Louise; Lucas, Robyn

2016-06-01

There is contradictory evidence for a role of dietary fat in risk of multiple sclerosis (MS). To examine the association between usual fat intake (total, saturated, monounsaturated (MUFA), polyunsaturated (PUFA), omega-3 and omega-6) and risk of a first clinical diagnosis of CNS demyelination (FCD). Multi-centre incident case-control study in four regions of Australia during 2003-2006. Cases were aged 18-59 years and had a FCD; controls were matched to a case on age, sex and location. Dietary data were collected using a validated food frequency questionnaire. In 267 cases and 517 controls with dietary data, higher intake (per g/day) of omega-3 PUFA (adjusted odds ratio, AOR=0.61 (95% CI 0.40-0.93)), and particularly that derived from fish (AOR=0.54 (95% CI 0.31-0.93)) rather than from plants (AOR=0.75 (95% CI 0.39-1.43)) was associated with a decreased risk of FCD. Total fat intake and intake of other types of fat were not associated with FCD risk. There was a significant decrease in FCD risk with higher intake of omega-3 PUFA, particularly that originating from fish. There was no evidence to indicate that the intake of other types of dietary fat or fat quantity in the previous 12 months was associated with an altered risk of FCD. © The Author(s), 2015.

HPV16 genetic variation and the development of cervical cancer worldwide

PubMed Central

Cornet, I; Gheit, T; Iannacone, M R; Vignat, J; Sylla, B S; Del Mistro, A; Franceschi, S; Tommasino, M; Clifford, G M

2013-01-01

Background: Factors that favour a small proportion of HPV16 infections to progress to cancer are still poorly understood, but several studies have implicated a role of HPV16 genetic variation. Methods: To evaluate the association between HPV16 genetic variants and cervical cancer risk, we designed a multicentre case–control study based on HPV16-positive cervical samples (1121 cervical cancer cases and 400 controls) from the International Agency for Research on Cancer biobank. By sequencing the E6 gene, HPV16 isolates were classified into variant lineages and the European (EUR)-lineage isolates were subclassified by the common polymorphism T350G. Results: Incidence of variant lineages differed between cases and controls in Europe/Central Asia (P=0.006, driven by an underrepresentation of African lineages in cases), and South/Central America (P=0.056, driven by an overrepresentation of Asian American/North American lineages in cases). EUR-350G isolates were significantly underrepresented in cervical cancer in East Asia (odds ratio (OR)=0.02 vs EUR-350T; 95% confidence interval (CI)=0.00–0.37) and Europe/Central Asia (OR=0.42; 95% CI=0.27–0.64), whereas the opposite was true in South/Central America (OR=4.69; 95% CI=2.07–10.66). Conclusion: We observed that the distribution of HPV16 variants worldwide, and their relative risks for cervical cancer appear to be population-dependent. PMID:23169278

Oxidative stress in dogs with multicentric lymphoma: Effect of chemotherapy on oxidative and antioxidant biomarkers.

PubMed

Bottari, Nathieli B; Munhoz, Thiago D; Torbitz, Vanessa D; Tonin, Alexandre A; Anai, Letícia A; Semolin, Lívia M S; Jark, Paulo C; Bollick, Yãnaí S; Moresco, Rafael N; França, Raqueli T; Lopes, Sonia T A; Stefani, Lenita M; Tinucci-Costa, Mirela; Da Silva, Aleksandro S

2015-01-01

Lymphoma is one of the most common types of cancer in dogs, characterized by the proliferation of lymphoid cells. The treatment of this type of cancer is usually based on drugs with high toxicity, which can cause severe side effects. Therefore, the aim of this study was to measure the levels of advanced oxidation protein products (AOPP), thiobarbituric acid reactive substances (TBARS), and ferric reducing antioxidant power (FRAP) in dogs with multicentric lymphoma before and after chemotherapy. For this purpose, serum samples of 25 dogs diagnosed with multicentric lymphoma and 15 healthy dogs were used. The animals were exposed to CHOP chemotherapy (cyclophosphamide, vincristine, doxorubicin, and prednisone) and serum samples were collected 5 weeks after treatment. High levels of TBARS, AOPP, and FRAP were observed in sera of dogs with multicentric lymphoma when compared to healthy dogs (P < 0.01), and even higher levels (TBARS and AOPP) were found after chemotherapy i.e. treatment exacerbated the oxidative stress levels. On the other hand, FRAP levels did not differ statistically between animals with lymphoma before and after treatment (P > 0.05). Exacerbated oxidative stress was observed in dogs with multicentric lymphoma Group II (Stage IV-V: involvement of lymph nodes and organs) compared to those in Group I (Stage I-III: only affected lymph nodes) of the disease, as well as the dogs with clinical signs and T immunophenotype. Another important result was observed after chemotherapy, where FRAP levels were higher in dogs that showed complete disease remission compared to animals with progressive disease. Therefore, dogs with lymphoma showed protein oxidation and lipid peroxidation, as well as increased total antioxidants before and after chemotherapy compared to the control group.

Is rectal indomethacin effective in preventing of post-endoscopic retrograde cholangiopancreatography pancreatitis?

PubMed Central

Döbrönte, Zoltán; Szepes, Zoltán; Izbéki, Ferenc; Gervain, Judit; Lakatos, László; Pécsi, Gyula; Ihász, Miklós; Lakner, Lilla; Toldy, Erzsébet; Czakó, László

2014-01-01

AIM: To investigate the effectiveness of rectally administered indomethacin in the prophylaxis of post-endoscopic retrograde cholangiopancreatography (ERCP) pancreatitis and hyperamylasaemia in a multicentre study. METHODS: A prospective, randomised, placebo-controlled multicentre study in five endoscopic units was conducted on 686 patients randomised to receive a suppository containing 100 mg indomethacin, or an inert placebo, 10-15 min before ERCP. Post-ERCP pancreatitis and hyperamylasaemia were evaluated 24 h following the procedure on the basis of clinical signs and laboratory parameters, and computed tomography/magnetic resonance imaging findings if required. RESULTS: Twenty-one patients were excluded because of incompleteness of their data or because of protocol violation. The results of 665 investigations were evaluated: 347 in the indomethacin group and 318 in the placebo group. The distributions of the risk factors in the two groups did not differ significantly. Pancreatitis developed in 42 patients (6.3%): it was mild in 34 (5.1%) and severe in eight (1.2%) cases. Hyperamylaesemia occurred in 160 patients (24.1%). There was no significant difference between the indomethacin and placebo groups in the incidence of either post-ERCP pancreatitis (5.8% vs 6.9%) or hyperamylasaemia (23.3% vs 24.8%). Similarly, subgroup analysis did not reveal any significant differences between the two groups. CONCLUSION: 100 mg rectal indomethacin administered before ERCP did not prove effective in preventing post-ERCP pancreatitis. PMID:25110443

Is rectal indomethacin effective in preventing of post-endoscopic retrograde cholangiopancreatography pancreatitis?

PubMed

Döbrönte, Zoltán; Szepes, Zoltán; Izbéki, Ferenc; Gervain, Judit; Lakatos, László; Pécsi, Gyula; Ihász, Miklós; Lakner, Lilla; Toldy, Erzsébet; Czakó, László

2014-08-07

To investigate the effectiveness of rectally administered indomethacin in the prophylaxis of post-endoscopic retrograde cholangiopancreatography (ERCP) pancreatitis and hyperamylasaemia in a multicentre study. A prospective, randomised, placebo-controlled multicentre study in five endoscopic units was conducted on 686 patients randomised to receive a suppository containing 100 mg indomethacin, or an inert placebo, 10-15 min before ERCP. Post-ERCP pancreatitis and hyperamylasaemia were evaluated 24 h following the procedure on the basis of clinical signs and laboratory parameters, and computed tomography/magnetic resonance imaging findings if required. Twenty-one patients were excluded because of incompleteness of their data or because of protocol violation. The results of 665 investigations were evaluated: 347 in the indomethacin group and 318 in the placebo group. The distributions of the risk factors in the two groups did not differ significantly. Pancreatitis developed in 42 patients (6.3%): it was mild in 34 (5.1%) and severe in eight (1.2%) cases. Hyperamylaesemia occurred in 160 patients (24.1%). There was no significant difference between the indomethacin and placebo groups in the incidence of either post-ERCP pancreatitis (5.8% vs 6.9%) or hyperamylasaemia (23.3% vs 24.8%). Similarly, subgroup analysis did not reveal any significant differences between the two groups. 100 mg rectal indomethacin administered before ERCP did not prove effective in preventing post-ERCP pancreatitis.

Icodextrin does not impact infectious and culture-negative peritonitis rates in peritoneal dialysis patients: a 2-year multicentre, comparative, prospective cohort study

PubMed Central

Vychytil, Andreas; Remón, César; Michel, Catherine; Williams, Paul; Rodríguez-Carmona, Ana; Marrón, Belén; Vonesh, Ed; van der Heyden, Synke; Filho, Jose C. Divino

2008-01-01

Background. Icodextrin is a glucose polymer derived by hydrolysis of cornstarch. The different biocompatibility profile of icodextrin-containing peritoneal dialysis (PD) solutions may have a positive influence on peritoneal host defence. Furthermore, cases of sterile peritonitis potentially associated with icodextrin have been reported. Methods. The primary objective of this multicentre, longitudinal, observational, non-interventional, prospective cohort study, which included 722 PD patients, was to evaluate the incidence of overall peritonitis in patients treated with icodextrin-containing PD solutions (Extraneal™) used during one long-dwell exchange/day compared with those treated with non-icodextrin-containing PD solutions. The secondary objective was to determine if culture-negative peritonitis rates differed between patients treated with icodextrin from two independent manufacturers. All peritonitis episodes were assessed by a Steering Committee in a blind manner. Results. There was no significant difference between icodextrin-treated and control patients in the adjusted overall, culture-positive or culture-negative peritonitis rates. When stratified by the icodextrin supplier, there was no significant difference in the adjusted rate of culture-negative peritonitis episodes between groups. Conclusion. Subjects receiving icodextrin as part of their PD regimen experienced neither a higher rate of culture-negative peritonitis nor a lower rate of infectious peritonitis compared with non-icodextrin users. There was no significant influence of the icodextrin raw material supplier on peritonitis rates. PMID:18556747

ALGOS: the development of a randomized controlled trial testing a case management algorithm designed to reduce suicide risk among suicide attempters

PubMed Central

2011-01-01

Background Suicide attempts (SA) constitute a serious clinical problem. People who attempt suicide are at high risk of further repetition. However, no interventions have been shown to be effective in reducing repetition in this group of patients. Methods/Design Multicentre randomized controlled trial. We examine the effectiveness of «ALGOS algorithm»: an intervention based in a decisional tree of contact type which aims at reducing the incidence of repeated suicide attempt during 6 months. This algorithm of case management comprises the two strategies of intervention that showed a significant reduction in the number of SA repeaters: systematic telephone contact (ineffective in first-attempters) and «Crisis card» (effective only in first-attempters). Participants who are lost from contact and those refusing healthcare, can then benefit from «short letters» or «postcards». Discussion ALGOS algorithm is easily reproducible and inexpensive intervention that will supply the guidelines for assessment and management of a population sometimes in difficulties with healthcare compliance. Furthermore, it will target some of these subgroups of patients by providing specific interventions for optimizing the benefits of case management strategy. Trial Registration The study was registered with the ClinicalTrials.gov Registry; number: NCT01123174. PMID:21194496

A multi-centre evaluation of oral cancer in Southern and Western Nigeria: an African oral pathology research consortium initiative.

PubMed

Omitola, Olufemi Gbenga; Soyele, Olujide Oladele; Sigbeku, Opeyemi; Okoh, Dickson; Akinshipo, Abdulwarith Olaitan; Butali, Azeez; Adeola, Henry Ademola

2017-01-01

Oral cancer is a leading cause of cancer deaths among African populations. Lack of standard cancer registries and under-reporting has inaccurately depicted its magnitude in Nigeria. Development of multi-centre collaborative oral pathology networks such as the African Oral Pathology Research Consortium (AOPRC) facilitates skill and expertise exchange and fosters a robust and systematic investigation of oral diseases across Africa. In this descriptive cross-sectional study, we have leveraged the auspices of the AOPRC to examine the burden of oral cancer in Nigeria, using a multi-centre approach. Data from 4 major tertiary health institutions in Western and Southern Nigeria was generated using a standardized data extraction format and analysed using the SPSS data analysis software (version 20.0; SPSS Inc. Chicago, IL). Of the 162 cases examined across the 4 centres, we observed that oral squamous cell carcinomas (OSCC) occurred mostly in the 6 th and 7 th decades of life and maxillary were more frequent than mandibular OSCC lesions. Regional variations were observed both for location, age group and gender distribution. Significant regional differences was found between poorly, moderately and well differentiated OSCC (p value = 0.0071). A multi-centre collaborative oral pathology research approach is an effective way to achieve better insight into the patterns and distribution of various oral diseases in men of African descent. The wider outlook for AOPRC is to employ similar approaches to drive intensive oral pathology research targeted at addressing the current morbidity and mortality of various oral diseases across Africa.

Managing multicentre clinical trials with open source.

PubMed

Raptis, Dimitri Aristotle; Mettler, Tobias; Fischer, Michael Alexander; Patak, Michael; Lesurtel, Mickael; Eshmuminov, Dilmurodjon; de Rougemont, Olivier; Graf, Rolf; Clavien, Pierre-Alain; Breitenstein, Stefan

2014-03-01

Multicentre clinical trials are challenged by high administrative burden, data management pitfalls and costs. This leads to a reduced enthusiasm and commitment of the physicians involved and thus to a reluctance in conducting multicentre clinical trials. The purpose of this study was to develop a web-based open source platform to support a multi-centre clinical trial. We developed on Drupal, an open source software distributed under the terms of the General Public License, a web-based, multi-centre clinical trial management system with the design science research approach. This system was evaluated by user-testing and well supported several completed and on-going clinical trials and is available for free download. Open source clinical trial management systems are capable in supporting multi-centre clinical trials by enhancing efficiency, quality of data management and collaboration.

Cyclosporin treatment for rheumatoid arthritis: a placebo controlled, double blind, multicentre study.

PubMed Central

van Rijthoven, A W; Dijkmans, B A; Goei The, H S; Hermans, J; Montnor-Beckers, Z L; Jacobs, P C; Cats, A

1986-01-01

The efficacy and safety of cyclosporin for patients with rheumatoid arthritis (RA) were assessed in a six month double blind, placebo controlled, multicentre study. The initial dosage of the drug was 10 mg/kg daily for two months. There were many discontinuations in both the cyclosporin group (eight out of 17) and the placebo group (six out of 19). Of the patients who completed the six months of therapy, those who had received cyclosporin showed a significant improvement in the number of swollen joints, the Ritchie articular index, and pain at active movement and at rest, compared not only with their condition at the start of the study, but also with the end results of the placebo group. Major adverse reactions to the drug were gastrointestinal disturbances and nephrotoxicity, which were probably due to the relatively high dosages of cyclosporin given in combination with non-steroidal anti-inflammatory drugs. PMID:3532966

Prenatal sonographic patterns in six cases of Wolf-Hirschhorn (4p-) syndrome.

PubMed

Boog, Georges; Le Vaillant, Claudine; Collet, Michel; Dupré, Pierre François; Parent, Philippe; Bongain, André; Benoit, Bernard; Trastour, Claire

2004-01-01

This multicentric study presents 6 cases of Wolf-Hirschhorn syndrome (deletion of 4p) detected after a sonographic prenatal diagnosis of early intrauterine growth retardation with fetal abnormalities. Standard karyotyping on regular G-banding during pregnancy was normal in half of the cases. Fortunately, the associated sonographic signs of a typical face, cystic cerebral lesions, midline fusion defects and bilateral renal hypoplasia may help to refine specific indications for high-resolution banding and molecular analysis by in situ hybridization. Copyright 2004 S. Karger AG, Basel

Ex post facto assessment of diffusion tensor imaging metrics from different MRI protocols: preparing for multicentre studies in ALS.

PubMed

Rosskopf, Johannes; Müller, Hans-Peter; Dreyhaupt, Jens; Gorges, Martin; Ludolph, Albert C; Kassubek, Jan

2015-03-01

Diffusion tensor imaging (DTI) for assessing ALS-associated white matter alterations has still not reached the level of a neuroimaging biomarker. Since large-scale multicentre DTI studies in ALS may be hampered by differences in scanning protocols, an approach for pooling of DTI data acquired with different protocols was investigated. Three hundred and nine datasets from 170 ALS patients and 139 controls were collected ex post facto from a monocentric database reflecting different scanning protocols. A 3D correction algorithm was introduced for a combined analysis of DTI metrics despite different acquisition protocols, with the focus on the CST as the tract correlate of ALS neuropathological stage 1. A homogenous set of data was obtained by application of 3D correction matrices. Results showed that a fractional anisotropy (FA) threshold of 0.41 could be defined to discriminate ALS patients from controls (sensitivity/specificity, 74%/72%). For the remaining test sample, sensitivity/specificity values of 68%/74% were obtained. In conclusion, the objective was to merge data recorded with different DTI protocols with 3D correction matrices for analyses at group level. These post processing tools might facilitate analysis of large study samples in a multicentre setting for DTI analysis at group level to aid in establishing DTI as a non-invasive biomarker for ALS.

Multicentre validation of IMRT pre-treatment verification: comparison of in-house and external audit.

PubMed

Jornet, Núria; Carrasco, Pablo; Beltrán, Mercè; Calvo, Juan Francisco; Escudé, Lluís; Hernández, Victor; Quera, Jaume; Sáez, Jordi

2014-09-01

We performed a multicentre intercomparison of IMRT optimisation and dose planning and IMRT pre-treatment verification methods and results. The aims were to check consistency between dose plans and to validate whether in-house pre-treatment verification results agreed with those of an external audit. Participating centres used two mock cases (prostate and head and neck) for the intercomparison and audit. Compliance to dosimetric goals and total number of MU per plan were collected. A simple quality index to compare the different plans was proposed. We compared gamma index pass rates using the centre's equipment and methodology to those of an external audit. While for the prostate case, all centres fulfilled the dosimetric goals and plan quality was homogeneous, that was not the case for the head and neck case. The number of MU did not correlate with the plan quality index. Pre-treatment verifications results of the external audit did not agree with those of the in-house measurements for two centres: being within tolerance for in-house measurements and unacceptable for the audit or the other way round. Although all plans fulfilled dosimetric constraints, plan quality is highly dependent on the planner expertise. External audits are an excellent tool to detect errors in IMRT implementation and cannot be replaced by intercomparison using results obtained by centres. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

Multicentre imaging measurements for oncology and in the brain

PubMed Central

Tofts, P S; Collins, D J

2011-01-01

Multicentre imaging studies of brain tumours (and other tumour and brain studies) can enable a large group of patients to be studied, yet they present challenging technical problems. Differences between centres can be characterised, understood and minimised by use of phantoms (test objects) and normal control subjects. Normal white matter forms an excellent standard for some MRI parameters (e.g. diffusion or magnetisation transfer) because the normal biological range is low (<2–3%) and the measurements will reflect this, provided the acquisition sequence is controlled. MR phantoms have benefits and they are necessary for some parameters (e.g. tumour volume). Techniques for temperature monitoring and control are given. In a multicentre study or treatment trial, between-centre variation should be minimised. In a cross-sectional study, all groups should be represented at each centre and the effect of centre added as a covariate in the statistical analysis. In a serial study of disease progression or treatment effect, individual patients should receive all of their scans at the same centre; the power is then limited by the within-subject reproducibility. Sources of variation that are generic to any imaging method and analysis parameters include MR sequence mismatch, B1 errors, CT effective tube potential, region of interest generation and segmentation procedure. Specific tissue parameters are analysed in detail to identify the major sources of variation and the most appropriate phantoms or normal studies. These include dynamic contrast-enhanced and dynamic susceptibility contrast gadolinium imaging, T1, diffusion, magnetisation transfer, spectroscopy, tumour volume, arterial spin labelling and CT perfusion. PMID:22433831

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 .

A Comparison of Functional Outcome in Patients Sustaining Major Trauma: A Multicentre, Prospective, International Study

PubMed Central

Rainer, Timothy H.; Yeung, Hiu Hung; Gabbe, Belinda J.; Yuen, Kai Y.; Ho, Hiu F.; Kam, Chak W.; Chang, Annice; Poon, Wai S.; Cameron, Peter A.; Graham, Colin A.

2014-01-01

Objectives To compare 6 month and 12 month health status and functional outcomes between regional major trauma registries in Hong Kong and Victoria, Australia. Summary Background Data Multicentres from trauma registries in Hong Kong and the Victorian State Trauma Registry (VSTR). Methods Multicentre, prospective cohort study. Major trauma patients and aged ≥18 years were included. The main outcome measures were Extended Glasgow Outcome Scale (GOSE) functional outcome and risk-adjusted Short-Form 12 (SF-12) health status at 6 and 12 months after injury. Results 261 cases from Hong Kong and 1955 cases from VSTR were included. Adjusting for age, sex, ISS, comorbid status, injury mechanism and GCS group, the odds of a better functional outcome for Hong Kong patients relative to Victorian patients at six months was 0.88 (95% CI: 0.66, 1.17), and at 12 months was 0.83 (95% CI: 0.60, 1.12). Adjusting for age, gender, ISS, GCS, injury mechanism and comorbid status, Hong Kong patients demonstrated comparable mean PCS-12 scores at 6-months (adjusted mean difference: 1.2, 95% CI: −1.2, 3.6) and 12-months (adjusted mean difference: −0.4, 95% CI: −3.2, 2.4) compared to Victorian patients. Keeping age, gender, ISS, GCS, injury mechanism and comorbid status, there was no difference in the MCS-12 scores of Hong Kong patients compared to Victorian patients at 6-months (adjusted mean difference: 0.4, 95% CI: −2.1, 2.8) or 12-months (adjusted mean difference: 1.8, 95% CI: −0.8, 4.5). Conclusion The unadjusted analyses showed better outcomes for Victorian cases compared to Hong Kong but after adjusting for key confounders, there was no difference in 6-month or 12-month functional outcomes between the jurisdictions. PMID:25157522

Induction of labour versus expectant monitoring for gestational hypertension or mild pre-eclampsia after 36 weeks' gestation (HYPITAT): a multicentre, open-label randomised controlled trial.

PubMed

Koopmans, Corine M; Bijlenga, Denise; Groen, Henk; Vijgen, Sylvia M C; Aarnoudse, Jan G; Bekedam, Dick J; van den Berg, Paul P; de Boer, Karin; Burggraaff, Jan M; Bloemenkamp, Kitty W M; Drogtrop, Addy P; Franx, Arie; de Groot, Christianne J M; Huisjes, Anjoke J M; Kwee, Anneke; van Loon, Aren J; Lub, Annemiek; Papatsonis, Dimitri N M; van der Post, Joris A M; Roumen, Frans J M E; Scheepers, Hubertina C J; Willekes, Christine; Mol, Ben W J; van Pampus, Maria G

2009-09-19

Robust evidence to direct management of pregnant women with mild hypertensive disease at term is scarce. We investigated whether induction of labour in women with a singleton pregnancy complicated by gestational hypertension or mild pre-eclampsia reduces severe maternal morbidity. We undertook a multicentre, parallel, open-label randomised controlled trial in six academic and 32 non-academic hospitals in the Netherlands between October, 2005, and March, 2008. We enrolled patients with a singleton pregnancy at 36-41 weeks' gestation, and who had gestational hypertension or mild pre-eclampsia. Participants were randomly allocated in a 1:1 ratio by block randomisation with a web-based application system to receive either induction of labour or expectant monitoring. Masking of intervention allocation was not possible. The primary outcome was a composite measure of poor maternal outcome--maternal mortality, maternal morbidity (eclampsia, HELLP syndrome, pulmonary oedema, thromboembolic disease, and placental abruption), progression to severe hypertension or proteinuria, and major post-partum haemorrhage (>1000 mL blood loss). Analysis was by intention to treat and treatment effect is presented as relative risk. This study is registered, number ISRCTN08132825. 756 patients were allocated to receive induction of labour (n=377 patients) or expectant monitoring (n=379). 397 patients refused randomisation but authorised use of their medical records. Of women who were randomised, 117 (31%) allocated to induction of labour developed poor maternal outcome compared with 166 (44%) allocated to expectant monitoring (relative risk 0.71, 95% CI 0.59-0.86, p<0.0001). No cases of maternal or neonatal death or eclampsia were recorded. Induction of labour is associated with improved maternal outcome and should be advised for women with mild hypertensive disease beyond 37 weeks' gestation. ZonMw.

Effect of timing and method of enteral tube feeding for dysphagic stroke patients (FOOD): a multicentre randomised controlled trial.

PubMed

Dennis, M S; Lewis, S C; Warlow, C

Undernutrition is common in patients admitted with stroke. We aimed to establish whether the timing and route of enteral tube feeding after stroke affected patients' outcomes at 6 months. The FOOD trials consist of three pragmatic multicentre randomised controlled trials, two of which included dysphagic stroke patients. In one trial, patients enrolled within 7 days of admission were randomly allocated to early enteral tube feeding or no tube feeding for more than 7 days (early versus avoid). In the other, patients were allocated percutaneous endoscopic gastrostomy (PEG) or nasogastric feeding. The primary outcome was death or poor outcome at 6 months. Analysis was by intention to treat. Between Nov 1, 1996, and July 31, 2003, 859 patients were enrolled by 83 hospitals in 15 countries into the early versus avoid trial. Early tube feeding was associated with an absolute reduction in risk of death of 5.8% (95% CI -0.8 to 12.5, p=0.09) and a reduction in death or poor outcome of 1.2% (-4.2 to 6.6, p=0.7). In the PEG versus nasogastric tube trial, 321 patients were enrolled by 47 hospitals in 11 countries. PEG feeding was associated with an absolute increase in risk of death of 1.0% (-10.0 to 11.9, p=0.9) and an increased risk of death or poor outcome of 7.8% (0.0 to 15.5, p=0.05). Early tube feeding might reduce case fatality, but at the expense of increasing the proportion surviving with poor outcome. Our data do not support a policy of early initiation of PEG feeding in dysphagic stroke patients.

The accuracy of colonoscopic localisation of colorectal tumours: a prospective, multi-centred observational study.

PubMed

Johnstone, M S; Moug, S J

2014-05-01

Colonoscopy is essential for accurate pre-operative colorectal tumour localisation, but its accuracy for localisation remains undetermined due to limitations of previous work. This study aimed to establish the accuracy of colonoscopic localisation and to determine how frequently inaccuracy results in altered surgical management. A prospective, multi-centred, powered observational study recruited 79 patients with colorectal tumours that underwent curative surgical resection. Patient and colonoscopic factors were recorded. Pre-operative colonoscopic and radiological lesion localisations were compared to intra-operative localisation using pre-defined anatomical bowel segments to determine accuracy, with changes in planned surgical management documented. Colonoscopy accurately located the colorectal tumour in 64/79 patients (81%). Five out of 15 inaccurately located patients required on-table alteration in planned surgical management. Pre-operative imaging was unable to visualise the primary tumour in 23.1% of cases, a finding that was more prevalent amongst bowel screener patients compared to symptomatic patients (45.8% vs. 13%; p = 0.003). Colonoscopic lesion localisation is inaccurate in 19.0% of cases and occurred throughout the colon with a change in on-table surgical management in 6.3%. With CT unable to visualise lesions in just under a quarter of cases, particularly in the screening population, preoperative localisation is heavily reliant on colonoscopy.

A multicenter, case-control study on risk factors for antepartum stillbirth.

PubMed

Facchinetti, Fabio; Alberico, Salvatore; Benedetto, Chiara; Cetin, Irene; Cozzolino, Sabrina; Di Renzo, Gian Carlo; Del Giovane, Cinzia; Ferrari, Francesca; Mecacci, Federico; Menato, Guido; Tranquilli, Andrea L; Baronciani, Dante

2011-03-01

As the influence of socio-demographic variables, lifestyle and medical conditions on the epidemiology of stillbirth (SB) is modified by population features, we aimed at investigating the role played by these factors on the incidence of SB in a developed country. Multivariate logistic regression analysis (OR with 95% CI) was utilized in a prospective multicentre nested case-control study to compare in a 1:2 ratio stillborn of >22 weeks gestation with matched for gestational age live-born (LB) infants. Intrapartum SB were excluded. Two hundred fifty-four consecutive SBs and 497 LBs were enrolled. Socio-demographic variables were equally distributed. Fetal malformations (7.96, 2.69-23.55), severe intrauterine growth restriction (IUGR) (birthweight ≤ 5(th) %ile) (4.32, 2.27?8.24), BMI > 25 (2.87, 1.90-4.33), and preeclampsia (PE, 0.40, 0.21-0.77) were recognized as independent predictors for SB. At term, only BMI > 25 was associated with SB (7.70, 2.9-20.5). Fetal malformations, severe IUGR and maternal BMI > 25 were associated with a significant increase in the risk of SB; PE presented instead a protective role. Maternal BMI > 25 was the only risk factor for SB identified in term pregnancies.

Risk factors for difficult peripheral venous cannulation in hospitalised patients. Protocol for a multicentre case-control study in 48 units of eight public hospitals in Spain.

PubMed

Rodriguez-Calero, Miguel Angel; Fernandez-Fernandez, Ismael; Molero-Ballester, Luis Javier; Matamalas-Massanet, Catalina; Moreno-Mejias, Luis; de Pedro-Gomez, Joan Ernest; Blanco-Mavillard, Ian; Morales-Asencio, Jose Miguel

2018-02-08

Patients with difficult venous access experience undesirable effects during healthcare, such as delayed diagnosis and initiation of treatment, stress and pain related to the technique and reduced satisfaction. This study aims to identify risk factors with which to model the appearance of difficulty in achieving peripheral venous puncture in hospital treatment. Case-control study. We will include adult patients requiring peripheral venous cannulation in eight public hospitals, excluding those in emergency situations and women in childbirth or during puerperium. The nurse who performs the technique will record in an anonymised register variables related to the intervention. Subsequently, a researcher will extract the health variables from the patient's medical history. Patients who present one of the following conditions will be assigned to the case group: two or more failed punctures, need for puncture support, need for central access after failure to achieve peripheral access, or decision to reject the technique. The control group will be obtained from records of patients who do not meet the above conditions. It has been stated a minimum sample size of 2070 patients, 207 cases and 1863 controls.A descriptive analysis will be made of the distribution of the phenomenon. The variables hypothesised to be risk factors for the appearance of difficult venous cannulation will be studied using a logistic regression model. The study was funded in January 2017 and obtained ethical approval from the Research Ethics Committee of the Balearic Islands. Informed consent will be obtained prior to data collection. Results will be published in a peer-reviewed scientific journal. © 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.

Iatrogenic facial nerve injuries during chronic otitis media surgery: a multicentre retrospective study.

PubMed

Linder, T; Mulazimoglu, S; El Hadi, T; Darrouzet, V; Ayache, D; Somers, T; Schmerber, S; Vincent, C; Mondain, M; Lescanne, E; Bonnard, D

2017-06-01

To give an insight into why, when and where iatrogenic facial nerve (FN) injuries may occur and to explain how to deal with them in an emergency setting. Multicentre retrospective study in eight tertiary referral hospitals over 17 years. Twenty patients with partial or total FN injury during surgery for chronic otitis media (COM) were revised. Indication and type of surgery, experience of the surgeon, intra- and postoperative findings, value of CT scanning, patient management and final FN outcome were recorded. In 12 cases, the nerve was completely transected, but the surgeon was unaware in 11 cases. A minority of cases occurred in academic teaching hospitals. Tympanic segment, second genu and proximal mastoid segments were the sites involved during injury. The FN was not deliberately identified in 18 patients at the time of injury, and nerve monitoring was only applied in one patient. Before revision surgery, CT scanning correctly identified the lesion site in 11 of 12 cases and depicted additional lesions such as damage to the lateral semicircular canal. A greater auricular nerve graft was interposed in 10 cases of total transection and in one partially lesioned nerve: seven of them resulted in an HB III functional outcome. In two of the transected nerves, rerouting and direct end-to-end anastomosis was applied. A simple FN decompression was used in four cases of superficially traumatised nerves. We suggest checklists for preoperative, intraoperative and postoperative management to prevent and treat iatrogenic FN injury during COM surgery. © 2016 John Wiley & Sons Ltd.

Network for Surveillance of Severe Maternal Morbidity: a powerful national collaboration generating data on maternal health outcomes and care.

PubMed

Cecatti, J G; Costa, M L; Haddad, S M; Parpinelli, M A; Souza, J P; Sousa, M H; Surita, F G; Pinto E Silva, J L; Pacagnella, R C; Passini, R

2016-05-01

To identify cases of severe maternal morbidity (SMM) during pregnancy and childbirth, their characteristics, and to test the feasibility of scaling up World Health Organization criteria for identifying women at risk of a worse outcome. Multicentre cross-sectional study. Twenty-seven referral maternity hospitals from all regions of Brazil. Cases of SMM identified among 82 388 delivering women over a 1-year period. Prospective surveillance using the World Health Organization's criteria for potentially life-threatening conditions (PLTC) and maternal near-miss (MNM) identified and assessed cases with severe morbidity or death. Indicators of maternal morbidity and mortality; sociodemographic, clinical and obstetric characteristics; gestational and perinatal outcomes; main causes of morbidity and delays in care. Among 9555 cases of SMM, there were 140 deaths and 770 cases of MNM. The main determining cause of maternal complication was hypertensive disease. Criteria for MNM conditions were more frequent as the severity of the outcome increased, all combined in over 75% of maternal deaths. This study identified around 9.5% of MNM or death among all cases developing any severe maternal complication. Multicentre studies on surveillance of SMM, with organised collaboration and adequate study protocols can be successfully implemented, even in low-income and middle-income settings, generating important information on maternal health and care to be used to implement appropriate health policies and interventions. Surveillance of severe maternal morbidity was proved to be possible in a hospital network in Brazil. © 2015 Royal College of Obstetricians and Gynaecologists.

Multifocal amelanotic conjunctival melanoma and acquired melanosis sine pigmento.

PubMed Central

Paridaens, A D; McCartney, A C; Hungerford, J L

1992-01-01

Clinical and histopathological features of four cases of multifocal amelanotic malignant melanoma of the conjunctiva in association with 'acquired melanosis sine pigmento' are reported. The absence of conjunctival pigmentation in this extremely rare combination of lesions prevented early diagnosis and clinical monitoring. As a result orbital exenteration was required in three cases. This multicentric non-pigmented variety of conjunctival malignant melanoma tends to present later than pigmented forms and may require exenteration of the orbit as a primary procedure. Images PMID:1540561

Multifocal amelanotic conjunctival melanoma and acquired melanosis sine pigmento.

PubMed

Paridaens, A D; McCartney, A C; Hungerford, J L

1992-03-01

Clinical and histopathological features of four cases of multifocal amelanotic malignant melanoma of the conjunctiva in association with 'acquired melanosis sine pigmento' are reported. The absence of conjunctival pigmentation in this extremely rare combination of lesions prevented early diagnosis and clinical monitoring. As a result orbital exenteration was required in three cases. This multicentric non-pigmented variety of conjunctival malignant melanoma tends to present later than pigmented forms and may require exenteration of the orbit as a primary procedure.

Efficacy and safety of high-dose baclofen for the treatment of alcohol dependence: A multicentre, randomised, double-blind controlled trial.

PubMed

Beraha, Esther M; Salemink, Elske; Goudriaan, Anna E; Bakker, Abraham; de Jong, David; Smits, Natasha; Zwart, Jan Willem; Geest, Dick van; Bodewits, Pieter; Schiphof, Tom; Defourny, Harma; van Tricht, Mirjam; van den Brink, Wim; Wiers, Reinout W

2016-12-01

Previous randomised placebo-controlled trials with low-to-medium doses of baclofen (30-60mg) showed inconsistent results, but case studies suggested a dose-response effect and positive outcomes in patients on high doses of baclofen (up to 270mg). Its prescription was temporary permitted for the treatment of alcohol dependence (AD) in France, and baclofen is now widely prescribed. Recently, a small RCT found a strong effect of a mean dose of 180mg baclofen. In the present study the efficacy and safety of high doses of baclofen was examined in a multicentre, double-blind, placebo-controlled trial. 151 patients were randomly assigned to either six weeks titration and ten weeks high-dose baclofen (N=58; up to 150mg), low-dose baclofen (N=31; 30mg), or placebo (N=62). The primary outcome measure was time to first relapse. Nine of the 58 patients (15.5%) in the high-dose group reached 150mg and the mean baclofen dose in this group was 93.6mg (SD=40.3). No differences between the survival distributions for the three groups were found in the time to first relapse during the ten-weeks high-dose phase (χ 2 =0.41; p=0.813) or the 16-weeks complete medication period (χ 2 =0.04; p=0.982). There were frequent dose-related adverse events in terms of fatigue, sleepiness, and dry mouth. One medication related serious adverse event occurred in the high-dose baclofen group. Neither low nor high doses of baclofen were effective in the treatment of AD. Adverse events were frequent, although generally mild and transient. Therefore, large-scale prescription of baclofen for the treatment of AD seems premature and should be reconsidered. Copyright © 2016 Elsevier B.V. and ECNP. All rights reserved.

The group-based social skills training SOSTA-FRA in children and adolescents with high functioning autism spectrum disorder - study protocol of the randomised, multi-centre controlled SOSTA - net trial

PubMed Central

2013-01-01

Background Group-based social skills training (SST) has repeatedly been recommended as treatment of choice in high-functioning autism spectrum disorder (HFASD). To date, no sufficiently powered randomised controlled trial has been performed to establish efficacy and safety of SST in children and adolescents with HFASD. In this randomised, multi-centre, controlled trial with 220 children and adolescents with HFASD it is hypothesized, that add-on group-based SST using the 12 weeks manualised SOSTA–FRA program will result in improved social responsiveness (measured by the parent rated social responsiveness scale, SRS) compared to treatment as usual (TAU). It is further expected, that parent and self reported anxiety and depressive symptoms will decline and pro-social behaviour will increase in the treatment group. A neurophysiological study in the Frankfurt HFASD subgroup will be performed pre- and post treatment to assess changes in neural function induced by SST versus TAU. Methods/design The SOSTA – net trial is designed as a prospective, randomised, multi-centre, controlled trial with two parallel groups. The primary outcome is change in SRS score directly after the intervention and at 3 months follow-up. Several secondary outcome measures are also obtained. The target sample consists of 220 individuals with ASD, included at the six study centres. Discussion This study is currently one of the largest trials on SST in children and adolescents with HFASD worldwide. Compared to recent randomised controlled studies, our study shows several advantages with regard to in- and exclusion criteria, study methods, and the therapeutic approach chosen, which can be easily implemented in non-university-based clinical settings. Trial registration ISRCTN94863788 – SOSTA – net: Group-based social skills training in children and adolescents with high functioning autism spectrum disorder. PMID:23289935

Effects of dietary sodium and the DASH diet on the occurrence of headaches: results from randomised multicentre DASH-Sodium clinical trial.

PubMed

Amer, Muhammad; Woodward, Mark; Appel, Lawrence J

2014-12-11

Headaches are a common medical problem, yet few studies, particularly trials, have evaluated therapies that might prevent or control headaches. We, thus, investigated the effects on the occurrence of headaches of three levels of dietary sodium intake and two diet patterns (the Dietary Approaches to Stop Hypertension (DASH) diet (rich in fruits, vegetables and low-fat dairy products with reduced saturated and total fat) and a control diet (typical of Western consumption patterns)). Randomised multicentre clinical trial. Post hoc analyses of the DASH-Sodium trial in the USA. In a multicentre feeding study with three 30 day periods, 390 participants were randomised to the DASH or control diet. On their assigned diet, participants ate food with high sodium during one period, intermediate sodium during another period and low sodium during another period, in random order. Occurrence and severity of headache were ascertained from self-administered questionnaires, completed at the end of each feeding period. The occurrence of headaches was similar in DASH versus control, at high (OR (95% CI)=0.65 (0.37 to 1.12); p=0.12), intermediate (0.57 (0.29 to 1.12); p=0.10) and low (0.64 (0.36 to 1.13); p=0.12) sodium levels. By contrast, there was a lower risk of headache on the low, compared with high, sodium level, both on the control (0.69 (0.49 to 0.99); p=0.05) and DASH (0.69 (0.49 to 0.98); p=0.04) diets. A reduced sodium intake was associated with a significantly lower risk of headache, while dietary patterns had no effect on the risk of headaches in adults. Reduced dietary sodium intake offers a novel approach to prevent headaches. NCT00000608. 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.

Effects of dietary sodium and the DASH diet on the occurrence of headaches: results from randomised multicentre DASH-Sodium clinical trial

PubMed Central

Amer, Muhammad; Woodward, Mark; Appel, Lawrence J

2014-01-01

Objectives Headaches are a common medical problem, yet few studies, particularly trials, have evaluated therapies that might prevent or control headaches. We, thus, investigated the effects on the occurrence of headaches of three levels of dietary sodium intake and two diet patterns (the Dietary Approaches to Stop Hypertension (DASH) diet (rich in fruits, vegetables and low-fat dairy products with reduced saturated and total fat) and a control diet (typical of Western consumption patterns)). Design Randomised multicentre clinical trial. Setting Post hoc analyses of the DASH-Sodium trial in the USA. Participants In a multicentre feeding study with three 30 day periods, 390 participants were randomised to the DASH or control diet. On their assigned diet, participants ate food with high sodium during one period, intermediate sodium during another period and low sodium during another period, in random order. Outcome measures Occurrence and severity of headache were ascertained from self-administered questionnaires, completed at the end of each feeding period. Results The occurrence of headaches was similar in DASH versus control, at high (OR (95% CI)=0.65 (0.37 to 1.12); p=0.12), intermediate (0.57 (0.29 to 1.12); p=0.10) and low (0.64 (0.36 to 1.13); p=0.12) sodium levels. By contrast, there was a lower risk of headache on the low, compared with high, sodium level, both on the control (0.69 (0.49 to 0.99); p=0.05) and DASH (0.69 (0.49 to 0.98); p=0.04) diets. Conclusions A reduced sodium intake was associated with a significantly lower risk of headache, while dietary patterns had no effect on the risk of headaches in adults. Reduced dietary sodium intake offers a novel approach to prevent headaches. Trial registration number NCT00000608. PMID:25500372

Multicentric study on malignant pleural mesothelioma and non-occupational exposure to asbestos.

PubMed

Magnani, C; Agudo, A; González, C A; Andrion, A; Calleja, A; Chellini, E; Dalmasso, P; Escolar, A; Hernandez, S; Ivaldi, C; Mirabelli, D; Ramirez, J; Turuguet, D; Usel, M; Terracini, B

2000-07-01

Insufficient evidence exists on the risk of pleural mesothelioma from non-occupational exposure to asbestos. A population-based case-control study was carried out in six areas from Italy, Spain and Switzerland. Information was collected for 215 new histologically confirmed cases and 448 controls. A panel of industrial hygienists assessed asbestos exposure separately for occupational, domestic and environmental sources. Classification of domestic and environmental exposure was based on a complete residential history, presence and use of asbestos at home, asbestos industrial activities in the surrounding area, and their distance from the dwelling. In 53 cases and 232 controls without evidence of occupational exposure to asbestos, moderate or high probability of domestic exposure was associated with an increased risk adjusted by age and sex: odds ratio (OR) 4.81, 95% confidence interval (CI) 1.8-13.1. This corresponds to three situations: cleaning asbestos-contaminated clothes, handling asbestos material and presence of asbestos material susceptible to damage. The estimated OR for high probability of environmental exposure (living within 2000 m of asbestos mines, asbestos cement plants, asbestos textiles, shipyards, or brakes factories) was 11.5 (95% CI 3.5-38.2). Living between 2000 and 5000 m from asbestos industries or within 500 m of industries using asbestos could also be associated with an increased risk. A dose-response pattern appeared with intensity of both sources of exposure. It is suggested that low-dose exposure to asbestos at home or in the general environment carries a measurable risk of malignant pleural mesothelioma.

The effectiveness of telemedicine for paediatric retrieval consultations: rationale and study design for a pragmatic multicentre randomised controlled trial.

PubMed

Armfield, Nigel R; Coulthard, Mark G; Slater, Anthony; McEniery, Julie; Elcock, Mark; Ware, Robert S; Scuffham, Paul A; Bensink, Mark E; Smith, Anthony C

2014-11-11

In many health systems, specialist services for critically ill children are typically regionalised or centralised. Studies have shown that high-risk paediatric patients have improved survival when managed in specialist centres and that volume of cases is a predictor of care quality. In acute cases where distance and time impede access to specialist care, clinical advice may be provided remotely by telephone. Emergency retrieval services, attended by medical and nursing staff may be used to transport patients to specialist centres. Even with the best quality retrieval services, stabilisation of the patient and transport logistics may delay evacuation to definitive care. Several studies have examined the use of telemedicine for providing specialist consultations for critically ill children. However, no studies have yet formally examined the clinical effectiveness and economic implications of using telemedicine in the context of paediatric patient retrieval. The study is a pragmatic, multicentre randomised controlled trial running over 24 months which will compare the use of telemedicine with the use of the telephone for paediatric retrieval consultations between four referring hospitals and a tertiary paediatric intensive care unit. We aim to recruit 160 children for whom a specialist retrieval consultation is required. The primary outcome measure is stabilisation time (time spent on site at the referring hospital by the retrieval team) adjusted for initial risk. Secondary outcome measures are change in patient's physiological status (repeated measure, two time points) scored using the Children's Emergency Warning Tool; change in diagnosis (repeated measure taken at three time points); change in destination of retrieved patients at the tertiary hospital (general ward or paediatric intensive care unit); retrieval decision, and length of stay in the Paediatric Intensive Care Unit for retrieved patients. The trial has been approved by the Human Research Ethics Committees of Children's Health Services Queensland and The University of Queensland, Australia. Health services are adopting telemedicine, however formal evidence to support its use in paediatric acute care is limited. Generalisable evidence is required to inform clinical use and health system policy relating to the effectiveness and economic implications of the use in telemedicine in paediatric retrieval. Australian and New Zealand Clinical Trials Registry ACTRN12612000156886 .

Catheter ablation in patients with persistent atrial fibrillation

PubMed Central

Kirchhof, Paulus; Calkins, Hugh

2017-01-01

Catheter ablation is increasingly offered to patients who suffer from symptoms due to atrial fibrillation (AF), based on a growing body of evidence illustrating its efficacy compared with antiarrhythmic drug therapy. Approximately one-third of AF ablation procedures are currently performed in patients with persistent or long-standing persistent AF. Here, we review the available information to guide catheter ablation in these more chronic forms of AF. We identify the following principles: Our clinical ability to discriminate paroxysmal and persistent AF is limited. Pulmonary vein isolation is a reasonable and effective first approach for catheter ablation of persistent AF. Other ablation strategies are being developed and need to be properly evaluated in controlled, multicentre trials. Treatment of concomitant conditions promoting recurrent AF by life style interventions and medical therapy should be a routine adjunct to catheter ablation of persistent AF. Early rhythm control therapy has a biological rationale and trials evaluating its value are underway. There is a clear need to generate more evidence for the best approach to ablation of persistent AF beyond pulmonary vein isolation in the form of adequately powered controlled multi-centre trials. PMID:27389907

[Clinical-caring epidemiology of pain at the hospital--the ECAD-O project].

PubMed

Sichetti, Daniela; Fosco, Beatrice; Romero, Marilena; Tognoni, Gianni

2007-01-01

Pain continues to be underreported and undertreated, and resistances to the administration of morphine and opioids are one of the major drawbacks. a. to activate a surveillance as part of routine care; b. to produce periodical reports to follow-up any improvement or changes in oppioid and specifically treatment of pain; c. to the groups of patients whose pain is undertreated; d. to create a multicentre network of hospitals willing and able to promote a permanent surveillance on pain and its treatment. A cross sectional survey will be conducted in index days to collect data on the number of patients exposed to analgesics; the perception of health workers on the effectiveness of treatments administered; patients' satisfaction on pain control. A prospective surveillance on: a. adverse events; b. incident difficult cases (patients whose pain is not controlled or difficult to treat, e.g. because of comorbidities or contraindications to opioids). Data produced will be analysed and presented for each participating centre and will be used for education, audit and quality improvement.

Zolpidem efficacy and safety in disorders of consciousness.

PubMed

Machado, Calixto; Estévez, Mario; Rodriguez-Rojas, Rafael

2018-01-01

Sutton and Clauss presented a detailed review about the effectiveness of zolpidem, discussing recoveries from brain damage due to strokes, trauma and hypoxia. A significant finding has been the unexpected and paradoxical increment of brain activity in vegetative state/unresponsive wakefulness syndrome (VS/UWS). On the contrary, zolpidem is considered one of the best sleep inducers in normal subjects. We have studied series of VS/UWS cases after zolpidem intake. We have demonstrated EEG activation, increment of BOLD signal in different brain regions, and an autonomic influence, mainly characterized by a vagolytic chronotropic effect without a significant increment of the vasomotor sympathetic tone. As this autonomic imbalance might induce cardio- circulatory complications, which we didn't find in any of our patients, we suggest developing future trials under control of physiological indices by bedside monitoring. However, considering that the paradoxical arousing zolpidem effect might be certainly related to brain function improvement, we agree with Sutton and Clauss that future multicentre and multinational clinical trials should be developed, but under control of physiological indices.

Cognitive and emotional factors affecting avoidable decision-making delay in acute myocardial infarction male adults.

PubMed

Vidotto, Giulio; Bertolotti, Giorgio; Zotti, AnnaMaria; Marchi, Stefano; Tavazzi, Luigi

2013-01-01

To study the potentially avoidable decision-making delay in acute myocardial infarction (AMI) adults male with different psychological characteristics a nationwide multicentre study was conducted in Italy by the 118 Coronary Care Units (CCUs). 929 AMI patients consecutively presented to the CCU in a conscious condition less than two hours, 2-6 hours, 6-12 hours, and more than 12 hours after symptom onset and completing the Disease Distress Questionnaire (DDQ) were enrolled in a multicentre case-control study. The DDQ collects information regarding the decision time to seek help, and includes a set of items assessing psychological factors and pain-related symptoms. The relationship between the perceived threat and the delay due to decision-making was evaluated by means of a multivariate model using LISREL 8 structural equation modelling. The delay significantly correlated with perceived threat, which was mainly related to somatic awareness. It was only slightly related to pain and was not associated with any of the other variables. Perceived threat was also related to psychological upset, fear and health worries, the first of which was considerably influenced by emotional instability. Somatic awareness is the main dimension affecting perceived threat, but subjective pain intensity affects the delay both directly and indirectly. The core of the model is the relationship between perceived threat and the delay due to decision-making. The importance of subjective pain intensity is well documented, but it is still not clear how subjective and objective pain interact.

Comparison of a CHOP-LAsp-based protocol with and without maintenance for canine multicentric lymphoma.

PubMed

Lautscham, E M; Kessler, M; Ernst, T; Willimzig, L; Neiger, R

2017-03-25

The recommendation to treat canine lymphoma with a discontinuous protocol is based on small case numbers and mostly historic controls. This study compares duration of first remission (DFR) and overall survival time (ST) with a discontinuous protocol to the same protocol with maintenance phase. 408 dogs were treated with a CHOP-LAsp (C=cyclophosphamide; H=hydroxydaunorubicin; O=Oncovin; P=prednisolone; LAsp=l-asparaginase)-based 28-week induction protocol. In 75 dogs (cohort 1), this was followed by a maintenance phase consisting of vincristine, chlorambucil and actinomycin-D with a total treatment duration of two years. In the subsequent 333 dogs, therapy was discontinued after induction (cohort 2). Median DFR and ST in cohort 1 were 216 and 375 days and 184 and 304 days in cohort 2. 6-Month, 1-year and 2-year survival rates in cohort 1 were 73 per cent, 50 per cent, 24 per cent and 67 per cent, 39 per cent, 21 per cent in cohort 2. There was no significant difference between the two protocols (P=0.291 for ST, P=0.071 for DFR). On multivariate analysis, corticosteroid pretreatment (P=0.005), thrombocytopenia at diagnosis (P=0.019), stage (P=0.009), substage b at relapse (P<0.001), age (P=0.002) and incomplete or unstable remission necessitating intensification of therapy (P=0.004) were negatively correlated with ST in both groups. This study supports the use of a discontinuous protocol for canine multicentric lymphoma. British Veterinary Association.

Effects of continuous positive airway pressure on neurocognitive architecture and function in patients with obstructive sleep apnoea: study protocol for a multicentre randomised controlled trial

PubMed Central

Xu, Huajun; Wang, Hui; Guan, Jian; Yi, Hongliang; Qian, Yingjun; Zou, Jianyin; Xia, Yunyan; Fu, Yiqun; Li, Xinyi; Jiao, Xiao; Huang, Hengye; Dong, Pin; Yu, Ziwei; Yang, Jun; Xiang, Mingliang; Li, Jiping; Chen, Yanqing; Wang, Peihua; Sun, Yizhou; Li, Yuehua; Zheng, Xiaojian; Jia, Wei; Yin, Shankai

2017-01-01

Objectives Many clinical studies have indicated that obstructive sleep apnoea (OSA), the most common chronic sleep disorder, may affect neurocognitive function, and that treatment for continuous positive airway pressure (CPAP) has some neurocognitive protective effects against the adverse effects of OSA. However, the effects of CPAP treatment on neurocognitive architecture and function remain unclear. Therefore, this multicentre trial was designed to investigate whether and when neurocognitive architecture and function in patients with OSA can be improved by CPAP treatment and to explore the role of gut microbiota in improving neurocognitive function during treatment. Methods/design This study will be a multicentre, randomised, controlled trial with allocation concealment and assessor blinding. A total of 148 eligible patients with moderate to severe OSA will be enrolled from five sleep centres and randomised to receive CPAP with best supportive care (BSC) intervention or BSC intervention alone. Cognitive function, structure and function of brain regions, gut microbiota, metabolites, biochemical variables, electrocardiography, echocardiography, pulmonary function and arterial stiffness will be assessed at baseline before randomisation and at 3, 6 and 12 months. Ethics and dissemination This study has been approved by the Medical Ethics Committee of Shanghai Jiao Tong University Affiliated Sixth People’s Hospital (approval number 2015-79). The results from this study will be published in peer-reviewed journals and at relevant conferences. Trial registration number NCT02886156; pre-results. PMID:28550021

A large-scale multicentre cerebral diffusion tensor imaging study in amyotrophic lateral sclerosis.

PubMed

Müller, Hans-Peter; Turner, Martin R; Grosskreutz, Julian; Abrahams, Sharon; Bede, Peter; Govind, Varan; Prudlo, Johannes; Ludolph, Albert C; Filippi, Massimo; Kassubek, Jan

2016-06-01

Damage to the cerebral tissue structural connectivity associated with amyotrophic lateral sclerosis (ALS), which extends beyond the motor pathways, can be visualised by diffusion tensor imaging (DTI). The effective translation of DTI metrics as biomarker requires its application across multiple MRI scanners and patient cohorts. A multicentre study was undertaken to assess structural connectivity in ALS within a large sample size. 442 DTI data sets from patients with ALS (N=253) and controls (N=189) were collected for this retrospective study, from eight international ALS-specialist clinic sites. Equipment and DTI protocols varied across the centres. Fractional anisotropy (FA) maps of the control participants were used to establish correction matrices to pool data, and correction algorithms were applied to the FA maps of the control and ALS patient groups. Analysis of data pooled from all centres, using whole-brain-based statistical analysis of FA maps, confirmed the most significant alterations in the corticospinal tracts, and captured additional significant white matter tract changes in the frontal lobe, brainstem and hippocampal regions of the ALS group that coincided with postmortem neuropathological stages. Stratification of the ALS group for disease severity (ALS functional rating scale) confirmed these findings. This large-scale study overcomes the challenges associated with processing and analysis of multiplatform, multicentre DTI data, and effectively demonstrates the anatomical fingerprint patterns of changes in a DTI metric that reflect distinct ALS disease stages. This success paves the way for the use of DTI-based metrics as read-out in natural history, prognostic stratification and multisite disease-modifying studies in ALS. 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/

Laser in Glaucoma and Ocular Hypertension (LiGHT) trial. A multicentre, randomised controlled trial: design and methodology.

PubMed

Gazzard, Gus; Konstantakopoulou, Evgenia; Garway-Heath, David; Barton, Keith; Wormald, Richard; Morris, Stephen; Hunter, Rachael; Rubin, Gary; Buszewicz, Marta; Ambler, Gareth; Bunce, Catey

2018-05-01

The Laser in Glaucoma and Ocular Hypertension (LiGHT) Trial aims to establish whether initial treatment with selective laser trabeculoplasty (SLT) is superior to initial treatment with topical medication for primary open-angle glaucoma (POAG) or ocular hypertension (OHT). The LiGHT Trial is a prospective, unmasked, multicentre, pragmatic, randomised controlled trial. 718 previously untreated patients with POAG or OHT were recruited at six collaborating centres in the UK between 2012 and 2014. The trial comprises two treatment arms: initial SLT followed by conventional medical therapy as required, and medical therapy without laser therapy. Randomisation was provided online by a web-based randomisation service. Participants will be monitored for 3 years, according to routine clinical practice. The target intraocular pressure (IOP) was set at baseline according to an algorithm, based on disease severity and lifetime risk of loss of vision at recruitment, and subsequently adjusted on the basis of IOP control, optic disc and visual field. The primary outcome measure is health-related quality of life (HRQL) (EQ-5D five-level). Secondary outcomes are treatment pathway cost and cost-effectiveness, Glaucoma Utility Index, Glaucoma Symptom Scale, Glaucoma Quality of Life, objective measures of pathway effectiveness, visual function and safety profiles and concordance. A single main analysis will be performed at the end of the trial on an intention-to-treat basis. The LiGHT Trial is a multicentre, pragmatic, randomised clinical trial that will provide valuable data on the relative HRQL, clinical effectiveness and cost-effectiveness of SLT and topical IOP-lowering medication. ISRCTN32038223, Pre-results. © 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.

Overall survival and clinical characteristics of BRCA mutation carriers with stage I/II pancreatic cancer.

PubMed

Golan, Talia; Sella, Tal; O'Reilly, Eileen M; Katz, Matthew H G; Epelbaum, Ron; Kelsen, David P; Borgida, Ayelet; Maynard, Hannah; Kindler, Hedy; Friedmen, Eitan; Javle, Milind; Gallinger, Steven

2017-03-14

BRCA1/BRCA2 germ line (GL) mutation carriers with pancreatic adenocarcinoma (PDAC) may have distinct outcomes. We recently described an apparent more favourable prognosis of surgically resected BRCA-associated PDAC patients in a single-arm, uncontrolled, retrospective study. However, the prognostic impact of GL BRCA1/2 mutations in surgically resected PDAC has not been compared with a matched control population. A larger multi-centre, case-control retrospective analysis was performed. Cases were patients with surgically resected, BRCA1/2-associated PDAC from 2004 to 2013. Controls included surgically resected PDAC cases treated during the same time period that were either BRCA non-carriers, or had no family history of breast, ovarian or pancreatic cancers. Cases and controls were matched by: age at diagnosis (within ±5-year period) and institution. Demographics, clinical history, overall survival (OS) and disease-free survival (DFS) were abstracted from patient records. Statistical comparisons were assessed using χ 2 - and Fisher's exact test, and median DFS/OS using Kaplan-Meier method and log-rank testing. Twenty-five patients with BRCA1-(n=4) or BRCA2 (N=21)-associated resectable PDAC were identified. Mean age was 55.7 years (range, 34-78 years), 48% (n=12) were females and 76% (n=19) were Jewish. Cases were compared (1 : 2) with 49 resectable PDAC controls, and were balanced for age, ethnicity and other relevant clinical and pathological features. BRCA-associated PDAC patients received neoadjuvant, or adjuvant platinum-based treatment more frequently than controls (7 out of 8 vs 6 out of 14) and (7 out of 21 vs 3 out of 44), respectively. No significant difference in median OS (37.06 vs 38.77 months, P=0.838) and in DFS (14.3 vs 12.0 months, P=0.303) could be demonstrated between cases and controls. A trend to increased DFS was observed among BRCA-positive cases treated with neoadjuvant/adjuvant platinum-containing regimens (n=10) compared with similarly treated controls (n=7) (39.1 vs 12.4 months, P=0.255). In this retrospective analysis, the prognosis of surgically resectable BRCA-associated PDAC is no different than that of sporadic PDAC from the same institution. The role of platinum-based adjuvant therapy in this setting requires prospective investigation.

Results of a multicentre randomised controlled trial of statistical process control charts and structured diagnostic tools to reduce ward-acquired meticillin-resistant Staphylococcus aureus: the CHART Project.

PubMed

Curran, E; Harper, P; Loveday, H; Gilmour, H; Jones, S; Benneyan, J; Hood, J; Pratt, R

2008-10-01

Statistical process control (SPC) charts have previously been advocated for infection control quality improvement. To determine their effectiveness, a multicentre randomised controlled trial was undertaken to explore whether monthly SPC feedback from infection control nurses (ICNs) to healthcare workers of ward-acquired meticillin-resistant Staphylococcus aureus (WA-MRSA) colonisation or infection rates would produce any reductions in incidence. Seventy-five wards in 24 hospitals in the UK were randomised into three arms: (1) wards receiving SPC chart feedback; (2) wards receiving SPC chart feedback in conjunction with structured diagnostic tools; and (3) control wards receiving neither type of feedback. Twenty-five months of pre-intervention WA-MRSA data were compared with 24 months of post-intervention data. Statistically significant and sustained decreases in WA-MRSA rates were identified in all three arms (P<0.001; P=0.015; P<0.001). The mean percentage reduction was 32.3% for wards receiving SPC feedback, 19.6% for wards receiving SPC and diagnostic feedback, and 23.1% for control wards, but with no significant difference between the control and intervention arms (P=0.23). There were significantly more post-intervention 'out-of-control' episodes (P=0.021) in the control arm (averages of 0.60, 0.28, and 0.28 for Control, SPC and SPC+Tools wards, respectively). Participants identified SPC charts as an effective communication tool and valuable for disseminating WA-MRSA data.

[Antimicrobial susceptibility testing of anaerobic bacteria].

PubMed

García-Sánchez, José E; García-Sánchez, Enrique; García-García, María Inmaculada

2014-02-01

The anaerobic bacteria resistance to antibiotics is increasing, and even has appeared against the most active of those, like metronidazol and carbapenems. This fact forces to make and periodical sensibility tests -at least in the most aggressive and virulent species, in cases that they are isolated from life locations and in the absence of therapeutic response- to check the local sensibility and to establish suitable empiric therapies, all based on multicentric studies carried out in order to this or well to check the activity of new antibiotics. For the laboratory routine, the easiest sensibility method is the E-test/MIC evaluator. Another alternative is microdilution, that's only normalized for Bacteroides. There are preliminary facts that allow the use of disc diffusion method in some species of Bacteroides and Clostridium. For the temporal and multicentric studies, the procedure is dilution in agar plate, the reference method. Copyright © 2014 Elsevier España, S.L. All rights reserved.

[Candidemias: multicentre analysis in 16 hospitals in Andalusia (Spain)].

PubMed

Rodríguez-Hernández, M Jesús; Ruiz-Pérez de Pipaon, Maite; Márquez-Solero, Manuel; Martín-Rico, Patricia; Castón-Osorio, Juan José; Guerrero-Sánchez, Francisca M; Vidal-Verdú, Elisa; García-Figueras, Carolina; Del Arco-Jiménez, Alfonso; Rodríguez-Baño, Jesús; Martín-Mazuelos, Estrella; Cisneros-Herreros, José Miguel

2011-05-01

Candidemia is a nosocomial infection with high associated mortality. There have been changes in microbiology, epidemiology and treatment over the last few years, which has led us to analyse our own situation. Prospective, multicentre and observational study. All episodes of candidemia in adult patients seen in 17 Andalusian hospitals from 1 October 2005 to 30 September 2006 were included. Were detected 220 cases, the incidence was 0.58 cases/1,000 hospital discharges. Candida albicans was the most frecuent species (53% of cases). The majority of isolates (89%) was susceptibility to fluconazole. Sepsis was the most frequent clinical manifestation (65.7%). The treatment was inadequate in 38.7% of cases. Overall mortality was 40%. On univarite analysis death was found to be significantly associated with: aged > 60 years, unknown candidemia focus, Pitt score ≥ 2, APACHE II, shock at onset, persistents positive second blood cultures, non-removal of the central venous catheter and Candida species different of C. parasilopsis, among others. In the multivariate analysis death was found to be significantly associated with: aged > 60 years, Pitt score ≥ 2, Candida species different of C.parasilopsis and inadequate treatment. The candidemia clinical epidemiology in our region is similar to other areas and receiving inadequate treatment is the only modifiable risk factor associated with higher odds of mortality. Therefore, this modifiable factor needs to be improved to reduce the mortality. Copyright © 2010 Elsevier España, S.L. All rights reserved.

Xpert MTB/RIF assay for diagnosis of pulmonary tuberculosis in children: a prospective, multi-centre evaluation.

PubMed

Reither, Klaus; Manyama, Christina; Clowes, Petra; Rachow, Andrea; Mapamba, Daniel; Steiner, Andreas; Ross, Amanda; Mfinanga, Elirehema; Sasamalo, Mohamed; Nsubuga, Martin; Aloi, Francesco; Cirillo, Daniela; Jugheli, Levan; Lwilla, Fred

2015-04-01

Following endorsement by the World Health Organisation, the Xpert MTB/RIF assay has been widely incorporated into algorithms for the diagnosis of adult tuberculosis (TB). However, data on its performance in children remain scarce. This prospective, multi-centre study evaluated the performance of Xpert MTB/RIF to diagnose pulmonary tuberculosis in children. Children older than eight weeks and younger than 16 years with suspected pulmonary tuberculosis were enrolled at three TB endemic settings in Tanzania and Uganda, and assigned to five well-defined case definition categories: culture-confirmed TB, highly probable TB, probable TB, not TB, or indeterminate. The diagnostic accuracy of Xpert MTB/RIF was assessed using culture-confirmed TB cases as reference standard. In total, 451 children were enrolled. 37 (8%) had culture-confirmed TB, 48 (11%) highly probably TB and 62 probable TB (13%). The Xpert MTB/RIF assay had a sensitivity of 68% (95% CI, 50%-82%) and specificity of 100% (95% CI, 97%-100%); detecting 1.7 times more culture-confirmed cases than smear microscopy with a similar time to detection. Xpert MTB/RIF was positive in 2% (1/48) of highly probable and in 3% (2/62) of probable TB cases. Xpert MTB/RIF provided timely results with moderate sensitivity and excellent specificity compared to culture. Low yields in children with highly probable and probable TB remain problematic. Copyright © 2014 The British Infection Association. Published by Elsevier Ltd. All rights reserved.

A Multi-Centre Audit of the Use of Medication for the Management of Behavioural Problems in Adults with Intellectual Disabilities

ERIC Educational Resources Information Center

Unwin, Gemma L.; Deb, Shoumitro

2008-01-01

The aim was to investigate prescribing practices surrounding the use of medication for the management of behavioural problems in adults with intellectual disabilities with reference to a national guideline development project. A case note review methodology was employed to explore adherence to the audit criteria that were derived from the…

Castleman's disease of the spleen.

PubMed

Mantas, Dimitrios; Damaskos, Christos; Dailiani, Panagiota; Samarkos, Michael; Korkolopoulou, Penelope

2017-06-01

Castleman's disease (CD), also known as giant or angiofolicular lymphoid hyperplasia or lymphoid hamartoma, is a group of atypical lymphoproliferative disorders that share common lymph node histological features and may be localized either to a single lymph node (unicentric) or occur systemically (multicentric). Herein, we present a rare case of a of 75-year-old female patient who was referred to our department and after a thorough work-up, underwent splenectomy with synchronous resection of an accessory spleen, splenic artery lymph nodes, and splenic hilar lymph nodes due to splenic involvement in a multicentric CD. The pathology of the specimens led to the conclusion that it was a case of polycentric HHV-8-positive CD, affecting the spleen, the accessory spleen, and the lymph nodes. Incidence of this rare condition is believed to be approximately 0.001-0.05%. CD has been linked to the human immunodeficiency virus (HIV), human herpes virus 8 (HHV-8), and is associated with malignancies. The pathogenesis mechanism is considered to be a dysregulation and hypersecretion of cytokines, either idiopathic or secondary to a viral infection, with the latter considered the most frequent. Solid organ involvement is very rare as is splenic involvement.

A case of multicentric low-grade neuroendocrine breast tumor with an unusual histological pattern.

PubMed

D'Antonio, Antonio; Addesso, Maria; Memoli, Domenico; Cascone, Annamaria; Cremone, Luigi

2016-01-01

Neuroendocrine features are detectable in carcinomas of the breast either as scattered cells, that are recognized by their expression of neuroendocrine cell markers. Instead, pure breast carcinomas with neuroendocrine features (NEBC) are very rare and represent <1% of all breast cancer. Usually NEBC may be well or poorly differentiated and more frequent in older woman. These tumors showed variable histological pattern but a common feature is represented by expression of neuroendocrine markers. Here we report a case of a primary multicentric low-grade neuroendocrine carcinoma of the breast presented because of its rarity and for the unusual tubular and cribriform pattern resembling a well-differentiated conventional breast carcinoma. The tumor was treated with left quadrantectomy with concomitant wide excisional biopsy of other two nodules and lymph node sentinel biopsy. No recurrence was observed during 1-year follow-up. Because of its rarity and variability of morphologic features, there exist diagnostic challenges for pathologists to differentiate primary NEBC to some conventional breast carcinomas and to the breast metastasis from neuroendocrine tumor of the lung or gastrointestinal tract. It is important to be able recognize this tumor in order to avoid potential misdiagnosis and improper management of afflicted patients.

Multicentre study of allergic contact cheilitis from toothpastes.

PubMed

Francalanci, S; Sertoli, A; Giorgini, S; Pigatto, P; Santucci, B; Valsecchi, R

2000-10-01

The present work reports the results of a multicentre study of toothpaste allergic contact cheilitis (TACC) conducted by GIRDCA (Gruppo Italiano Ricerca Dermatiti da Contatto e Ambientali). The study examined 54 patients with eczematous lesions on the lips, the possible cause of which was suspected to be the use of toothpastes. Patch tests were conducted with a standard series, a specially-targeted series (toothpaste cheilitis series, TCS), and with suspected toothpaste(s). A stop-restart test (SRT) was carried out with these, together with a use test to identify possible alternative products. The TCS produced 17 positive reactions in 13 patients, the most frequent being to spearmint oil. Of the 54 patients, 5 displayed positive reactions only to the TCS. The patch tests with toothpaste produced positive reactions in 11/32 patients, the SRT a positive response in 10/12 cases. The diagnosis of TACC was confirmed in 15/54 patients. Alternative products were identified for 5 patients. In conclusion, the allergens most frequently responsible for TACC were the flavourings, and the additional series proved to be useful in many cases (together with patch tests with toothpastes and the SRT) for correct diagnosis and to initiate effective prevention.

Ultrasonography of the medial iliac lymph nodes in the dog.

PubMed

Llabrés-Díaz, Francisco J

2004-01-01

Sixty-one medial iliac lymph nodes of 38 different dogs (eight with adenocarcinoma of the apocrine glands of the anal sac, 13 with multicentric lymphoma, six with multicentric lymphoma but in clinical remission, and 11 control dogs) were evaluated to assess the ability of ultrasound to identify and interrogate these lymph nodes across the different groups and to differentiate these groups using different sonographic parameters. Ultrasound proved to be useful to assess canine medial iliac lymph nodes. An increase in size or number of detected lymph nodes or finding rounder or heterogeneous lymph nodes could differentiate lymph nodes of dogs of the control group from lymph nodes of dogs with lymphoma or an adenocarcinoma of the apocrine glands of the anal sac. Subcategories of malignancy could not be differentiated. More studies need to be performed, both with patients with reactive lymph nodes and also focusing on other canine superficial lymph nodes, before generalizing the results of this study to other areas or diseases.

Attachment Styles of Dermatological Patients in Europe: A Multi-centre Study in 13 Countries.

PubMed

Szabó, Csanád; Altmayer, Anita; Lien, Lars; Poot, Françoise; Gieler, Uwe; Tomas-Aragones, Lucía; Kupfer, Jörg; Jemec, Gregor B E; Misery, Laurent; Linder, M Dennis; Sampogna, Francesca; van Middendorp, Henriët; Halvorsen, Jon Anders; Balieva, Flora; Szepietowski, Jacek C; Romanov, Dmitry; Marron, Servando E; Altunay, Ilknur K; Finlay, Andrew Y; Salek, Sam S; Dalgard, Florence

2017-07-06

Attachment styles of dermatological outpatients and satisfaction with their dermatologists were investigated within the framework of a multicentre study conducted in 13 European countries, organized by the European Society for Dermatology and Psychiatry. Attachment style was assessed with the Adult Attachment Scale. Patient satisfaction with the dermatologist was assessed with an 11-degree scale. A total of 3,635 adult outpatients and 1,359 controls participated in the study. Dermatological outpatients were less able to depend on others, were less comfortable with closeness and intimacy, and experienced similar rates of anxiety in relationships as did the controls. Participants who had secure attachment styles reported stressful life events during the last 6 months significantly less often than those who had insecure attachment styles. Patients with secure attachment styles tended to be more satisfied with their dermatologist than did insecure patients. These results suggest that secure attachment of dermatological outpatients may be a protective factor in the management of stress.

Effectiveness of assertive case management on repeat self-harm in patients admitted for suicide attempt: Findings from ACTION-J study.

PubMed

Furuno, Taku; Nakagawa, Makiko; Hino, Kosuke; Yamada, Tomoki; Kawashima, Yoshitaka; Matsuoka, Yutaka; Shirakawa, Osamu; Ishizuka, Naoki; Yonemoto, Naohiro; Kawanishi, Chiaki; Hirayasu, Yoshio

2018-01-01

Self-harm is an important risk factor for subsequent suicide and repetition of self-harm, and a common cause of emergency department presentations. However, there still remains limited evidence on intervention in emergency department settings for individuals who self-harm. This multicentre, randomised controlled trial was conducted at 17 general hospitals in Japan. In total, 914 adult patients admitted to emergency departments for a suicide attempt and had a DSM-IV-TR axis I disorder were randomly assigned to two groups, to receive either assertive case management (intervention) or enhanced usual care (control). Assertive case management was introduced by the case manager during emergency department admissions for suicide attempts, and continued after discharge. Interventions were provided until the end of the study period (for at least 18 months and up to 5 years). The number of overall self-harm episodes per person-year was significantly lower in the intervention group (adjusted incidence risk ratio (IRR) 0.88, 95%CI 0.80-0.96, p=0.0031). Subgroup analysis showed a greater reduction of overall self-harm episodes among patients with no previous suicide attempt at baseline (adjusted IRR 0.73, 95% CI 0.53-0.98, p=0.037). Patients younger than 20 years and patients who self-harmed but were not admitted to an emergency department were excluded. The present study showed that assertive case management following emergency admission for a suicide attempt reduced the incident rate of repeat overall self-harm. Copyright © 2017 Elsevier B.V. All rights reserved.

Seven-year survey of classical and pleomorphic invasive lobular breast carcinomas in women from southeastern Serbia: Differences in clinicopathological and immunohistochemical features.

PubMed

Ilic, Ivan R; Djordjevic, Nebojsa P; Randjelovic, Pavle J; Stojanovic, Nikola M; Radulovic, Niko S; Ilic, Ratko S

2016-01-01

The occurrence of different variants of invasive lobular carcinoma (ILC) of the breast is variable. For example, the pleomorphic variant of ILC has an incidence of around 5%; however, the number of analyzed cases of ILC is shadowed by the number of ductal type carcinoma (IDC). Thus, we aimed to analyze the classical and pleomorphic ILCs in women from southeastern Serbia. Analyzed were 296 cases (11.91%) diagnosed with ILC, out of 2486 cases of all breast cancers (BCs), during a 7-year period (2005-2011) from southeastern Serbia. The differences in clinicopathological and immunohistochemical features (estrogen receptor/ER, progesterone receptor/ PR, HER-2, Ki-67, BRCA-1, p53 and E-cadherin) of these cases of ILCs were assessed and compared. Pleomorphic ILC occurred relatively rarely compared to other variants, however almost one fifth of the ILC cases were pleomorphic. No statistically significant correlation was found between patient age, tumor stage and the presence/absence of multifocality (MFC), multicentricity (MCC) and bilaterality (BL) on one side, and ILC variant on the other. Only the expression of two prognostic and predictive immunohistochemical markers, important for endocrine therapy, ER and PR, showed significant correlation with the ILC variant. Although higher tumor stage, incidence of multicentricity, overexpression of HER2 and higher p53 positivity were deemed to be characteristic of pleomorphic ILC, in our study that included a much larger number of cases than previous studies did, such correlations were not observed. Thus, it appears that the only two features of pleomorphic ILCs is absence of ER and PR positivity.

A guide to multi-centre ethics for surgical research in Australia and New Zealand.

PubMed

Boult, Maggi; Fitzpatrick, Kate; Maddern, Guy; Fitridge, Robert

2011-03-01

This paper describes existing inconsistencies as well as the disparate processes and logistics required when obtaining ethics approval in Australia and New Zealand in order to initiate a multi-centre bi-national surgical trial. The endovascular aortic aneurysm repair trial is a large multi-centre trial that aims to obtain pre- and post-operative data from patients in hospitals across Australia and New Zealand. As the trial was research based, ethics applications were submitted to all hospitals where surgeons wished to be involved in the trial. Few ethics committees have embraced attempts to simplify the application process for multi-centre trials. There was limited mutual review between Human Research Ethics Committees necessitating the submission of multiple applications. Though the use of the National Ethics Application Form in ethical review is increasing, some Human Research Ethics Committees do not accept it in its entirety; many require site-specific applications or sections of the Common Application Form modules. Queensland, New South Wales and New Zealand were the easiest systems to prepare, submit and lodge ethics applications because of their understanding and accommodation of reviewing multi-centred trials. The time, expense and complexity of obtaining ethics approval for multi-centre research projects are impediments to their establishment and reduce the time available for research. Australia is working to implement a system named the Harmonisation of Multi-centre Ethical Review to ease the process of obtaining multi-centre ethics clearance. Our experience suggests there will be some teething problems with implementation and acceptance. © 2010 The Authors. ANZ Journal of Surgery © 2010 Royal Australasian College of Surgeons.

The LIPPSMAck POP (Lung Infection Prevention Post Surgery - Major Abdominal - with Pre-Operative Physiotherapy) trial: study protocol for a multi-centre randomised controlled trial.

PubMed

Boden, Ianthe; Browning, Laura; Skinner, Elizabeth H; Reeve, Julie; El-Ansary, Doa; Robertson, Iain K; Denehy, Linda

2015-12-15

Post-operative pulmonary complications are a significant problem following open upper abdominal surgery. Preliminary evidence suggests that a single pre-operative physiotherapy education and preparatory lung expansion training session alone may prevent respiratory complications more effectively than supervised post-operative breathing and coughing exercises. However, the evidence is inconclusive due to methodological limitations. No well-designed, adequately powered, randomised controlled trial has investigated the effect of pre-operative education and training on post-operative respiratory complications, hospital length of stay, and health-related quality of life following upper abdominal surgery. The Lung Infection Prevention Post Surgery - Major Abdominal- with Pre-Operative Physiotherapy (LIPPSMAck POP) trial is a pragmatic, investigator-initiated, bi-national, multi-centre, patient- and assessor-blinded, parallel group, randomised controlled trial, powered for superiority. Four hundred and forty-one patients scheduled for elective open upper abdominal surgery at two Australian and one New Zealand hospital will be randomised using concealed allocation to receive either i) an information booklet or ii) an information booklet, plus one additional pre-operative physiotherapy education and training session. The primary outcome is respiratory complication incidence using standardised diagnostic criteria. Secondary outcomes include hospital length of stay and costs, pneumonia diagnosis, intensive care unit readmission and length of stay, days/h to mobilise >1 min and >10 min, and, at 6 weeks post-surgery, patient reported complications, health-related quality of life, and physical capacity. The LIPPSMAck POP trial is a multi-centre randomised controlled trial powered and designed to investigate whether a single pre-operative physiotherapy session prevents post-operative respiratory complications. This trial standardises post-operative assisted ambulation and physiotherapy, measures many known confounders, and includes a post-discharge follow-up of complication rates, functional capacity, and health-related quality of life. This trial is currently recruiting. Australian New Zealand Clinical Trials Registry number: ACTRN12613000664741 , 19 June 2013.

PIMS (Positioning In Macular hole Surgery) trial - a multicentre interventional comparative randomised controlled clinical trial comparing face-down positioning, with an inactive face-forward position on the outcome of surgery for large macular holes: study protocol for a randomised controlled trial.

PubMed

Pasu, Saruban; Bunce, Catey; Hooper, Richard; Thomson, Ann; Bainbridge, James

2015-11-17

Idiopathic macular holes are an important cause of blindness. They have an annual incidence of 8 per 100,000 individuals, and prevalence of 0.2 to 3.3 per 1000 individuals with visual impairment. The condition occurs more frequently in adults aged 75 years or older. Macular holes can be repaired by surgery in which the causative tractional forces in the eye are released and a temporary bubble of gas is injected. To promote successful hole closure individuals may be advised to maintain a face-down position for up to 10 days following surgery. The aim of this study is to determine whether advice to position face-down improves the surgical success rate of closure of large (>400 μm) macular holes, and thereby reduces the need for further surgery. This will be a multicentre interventional, comparative randomised controlled clinical trial comparing face-down positioning with face-forward positioning. At the conclusion of standardised surgery across all sites, participants still eligible for inclusion will be allocated randomly 1:1 to 1 of the 2 treatment arms stratified by site, using random permuted blocks of size 4 or 6 in equal proportions. We will recruit 192 participants having surgery for large macular holes (>400 μm); 96 in each of the 2 arms of the study. The primary objective is to determine the impact of face-down positioning on the likelihood of closure of large (≥400 μm) full-thickness macular holes following surgery. This will be the first multicentre randomised control trial to investigate the value of face-down positioning following macular hole standardised surgery. UK CRN: 17966 (date of registration 26 November 2014).

High prevalence of psychiatric disorders in patients with skin-restricted lupus: a case-control study.

PubMed

Jalenques, I; Rondepierre, F; Massoubre, C; Haffen, E; Grand, J P; Labeille, B; Perrot, J L; Aubin, F; Skowron, F; Mulliez, A; D'Incan, M

2016-05-01

Psychiatric disorders have been extensively documented in patients with systemic lupus erythematosus (SLE). However, the prevalence of psychiatric disorders in patients with skin-restricted lupus (SRL) remains unknown, although SRL is more common than SLE. To assess current and lifetime prevalence of Axis I psychiatric disorders among outpatients with SRL and to examine the factors associated with psychiatric disorders among such patients. A multicentre case-control study involving outpatients with SRL and controls matched for sex, age and education level. The Mini International Neuropsychiatric Interview was used for psychiatric evaluation. We evaluated 75 patients and 150 controls. Of these, 49% of patients vs. 13% of controls fulfilled the criteria for at least one current psychiatric disorder (P < 0·001). The following disorders were significantly more frequent among patients than controls: current and lifetime major depressive disorder (9% vs. 0%, P < 0·001 and 44% vs. 26%, P = 0·01), generalized anxiety disorder (23% vs. 3%, P < 0·001 and 35% vs. 19%, P = 0·03), panic disorder (7% vs. 0%, P = 0·004 and 21% vs. 3%, P < 0·001), current suicide risk (24% vs. 7%, P = 0·003), alcohol dependence (7% vs. 0%, P = 0·004) and lifetime agoraphobia (20% vs. 9%, P = 0·01). Lupus duration and lupus past treatment by thalidomide were significantly higher among patients with current psychiatric disorders. This study demonstrates a high prevalence of several psychiatric disorders (anxiety, depression, suicide risk, alcohol dependence) in patients with SRL. © 2016 British Association of Dermatologists.

Improved quality monitoring of multi-center acupuncture clinical trials in China

PubMed Central

2009-01-01

Background In 2007, the Chinese Science Division of the State Administration of Traditional Chinese Medicine(TCM) convened a special conference to discuss quality control for TCM clinical research. Control and assurance standards were established to guarantee the quality of clinical research. This paper provides practical guidelines for implementing strict and reproducible quality control for acupuncture randomized controlled trials (RCTs). Methods A standard quality control program (QCP) was established to monitor the quality of acupuncture trials. Case report forms were designed; qualified investigators, study personnel and data management personnel were trained. Monitors, who were directly appointed by the project leader, completed the quality control programs. They guaranteed data accuracy and prevented or detected protocol violations. Clinical centers and clinicians were audited, the randomization system of the centers was inspected, and the treatment processes were audited as well. In addition, the case report forms were reviewed for completeness and internal consistency, the eligibility and validity of the patients in the study was verified, and data was monitored for compliance and accuracy. Results and discussion The monitors complete their reports and submit it to quality assurance and the sponsors. Recommendations and suggestions are made for improving performance. By holding regular meetings to discuss improvements in monitoring standards, the monitors can improve quality and efficiency. Conclusions Supplementing and improving the existed guidelines for quality monitoring will ensure that large multi-centre acupuncture clinical trials will be considered as valid and scientifically stringent as pharmaceutical clinical trials. It will also develop academic excellence and further promote the international recognition of acupuncture. PMID:20035630

Novel ways to explore surgical interventions in randomised controlled trials: applying case study methodology in the operating theatre.

PubMed

Blencowe, Natalie S; Blazeby, Jane M; Donovan, Jenny L; Mills, Nicola

2015-12-28

Multi-centre randomised controlled trials (RCTs) in surgery are challenging. It is particularly difficult to establish standards of surgery and ensure that interventions are delivered as intended. This study developed and tested methods for identifying the key components of surgical interventions and standardising interventions within RCTs. Qualitative case studies of surgical interventions were undertaken within the internal pilot phase of a surgical RCT for obesity (the By-Band study). Each case study involved video data capture and non-participant observation of gastric bypass surgery in the operating theatre and interviews with surgeons. Methods were developed to transcribe and synchronise data from video recordings with observational data to identify key intervention components, which were then explored in the interviews with surgeons. Eight qualitative case studies were undertaken. A novel combination of video data capture, observation and interview data identified variations in intervention delivery between surgeons and centres. Although surgeons agreed that the most critical intervention component was the size and shape of the gastric pouch, there was no consensus regarding other aspects of the procedure. They conceded that evidence about the 'best way' to perform bypass was lacking and, combined with the pragmatic nature of the By-Band study, agreed that strict standardisation of bypass might not be required. This study has developed and tested methods for understanding how surgical interventions are designed and delivered delivered in RCTs. Applying these methods more widely may help identify key components of interventions to be delivered by surgeons in trials, enabling monitoring of key components and adherence to the protocol. These methods are now being tested in the context of other surgical RCTs. Current Controlled Trials ISRCTN00786323 , 05/09/2011.

Multicenter external validation of two malignancy risk prediction models in patients undergoing 18F-FDG-PET for solitary pulmonary nodule evaluation.

PubMed

Perandini, Simone; Soardi, G A; Larici, A R; Del Ciello, A; Rizzardi, G; Solazzo, A; Mancino, L; Zeraj, F; Bernhart, M; Signorini, M; Motton, M; Montemezzi, S

2017-05-01

To achieve multicentre external validation of the Herder and Bayesian Inference Malignancy Calculator (BIMC) models. Two hundred and fifty-nine solitary pulmonary nodules (SPNs) collected from four major hospitals which underwent 18-FDG-PET characterization were included in this multicentre retrospective study. The Herder model was tested on all available lesions (group A). A subgroup of 180 SPNs (group B) was used to provide unbiased comparison between the Herder and BIMC models. Receiver operating characteristic (ROC) area under the curve (AUC) analysis was performed to assess diagnostic accuracy. Decision analysis was performed by adopting the risk threshold stated in British Thoracic Society (BTS) guidelines. Unbiased comparison performed In Group B showed a ROC AUC for the Herder model of 0.807 (95 % CI 0.742-0.862) and for the BIMC model of 0.822 (95 % CI 0.758-0.875). Both the Herder and the BIMC models were proven to accurately predict the risk of malignancy when tested on a large multicentre external case series. The BIMC model seems advantageous on the basis of a more favourable decision analysis. • The Herder model showed a ROC AUC of 0.807 on 180 SPNs. • The BIMC model showed a ROC AUC of 0.822 on 180 SPNs. • Decision analysis is more favourable to the BIMC model.

Determining Surgical Complications in the Overweight (DISCOVER): a multicentre observational cohort study to evaluate the role of obesity as a risk factor for postoperative complications in general surgery.

PubMed

Nepogodiev, Dmitri; Chapman, Stephen J; Glasbey, James; Kelly, Michael; Khatri, Chetan; Drake, Thomas M; Kong, Chia Yew; Mitchell, Harriet; Harrison, Ewen M; Fitzgerald, J Edward; Bhangu, Aneel

2015-07-20

Obesity is increasingly prevalent among patients undergoing surgery. Conflicting evidence exists regarding the impact of obesity on postoperative complications. This multicentre study aims to determine whether obesity is associated with increased postoperative complications following general surgery. This prospective, multicentre cohort study will be performed utilising a collaborative methodology. Consecutive adults undergoing open or laparoscopic, elective or emergency, gastrointestinal, bariatric or hepatobiliary surgery will be included. Day case patients will be excluded. The primary end point will be the overall 30-day major complication rate (Clavien-Dindo grade III-V complications). Data will be collected to risk-adjust outcomes for potential confounding factors, such as preoperative cardiac risk. This study will be disseminated through structured medical student networks using established collaborative methodology. The study will be powered to detect a two-percentage point increase in the major postoperative complication rate in obese versus non-obese patients. Following appropriate assessment, an exemption from full ethics committee review has been received, and the study will be registered as a clinical audit or service evaluation at each participating hospital. Dissemination will take place through national and local research collaborative networks. 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.

Painful bone metastasis in elderly treated with radiation therapy: Single- or multiple-fraction regimen? A multicentre retrospective observational analysis.

PubMed

Falivene, S; Pezzulla, D; Di Franco, R; Giugliano, F M; Esposito, E; Scoglio, C; Amato, B; Borzillo, V; D'Aiuto, M; Muto, P

2017-02-01

Bone metastases are a frequent complication of advanced oncologic disease. Pain associated to bone metastasis is a major cause of morbidity in cancer patients, especially in elderly. The aim of this multicentric retrospective observational study is to evaluate the efficacy of different schedules of radiation therapy in elderly patients in terms of pain relief. 206 patients over the age of 60 were enrolled in 1 year time for a multicentre retrospective observational study. Patients were treated with palliative purposes for painful bone metastases. Pain intensity difference (PID) was found in 72% of patients. Reported PID was statistically significant for p < 0.01. Pain intensity measured by a point numeric rating scale was statistically significant reduced for p < 0.05 by one-fraction regimen compared to other two regimens. In recent years, numerous studies have evaluated the most appropriate regimen of fractionation in individual cases, despite this, a consensus about the best schedule is still debated. On our analysis, single-fractionation scheme (8 Gy) confirmed to be statistical significant effective in providing pain reduction due to bone metastases. Radiation therapy provides significant pain relief of symptomatic bone metastases, but appropriate radiotherapy scheduled is needed in order to get significant response to treatment. Multidisciplinary approach is warranted to value the balance between the therapeutic objectives and the patient quality of life.

Harmonization Process and Reliability Assessment of Anthropometric Measurements in the Elderly EXERNET Multi-Centre Study

PubMed Central

Gómez-Cabello, Alba; Vicente-Rodríguez, Germán; Albers, Ulrike; Mata, Esmeralda; Rodriguez-Marroyo, Jose A.; Olivares, Pedro R.; Gusi, Narcis; Villa, Gerardo; Aznar, Susana; Gonzalez-Gross, Marcela; Casajús, Jose A.; Ara, Ignacio

2012-01-01

Background The elderly EXERNET multi-centre study aims to collect normative anthropometric data for old functionally independent adults living in Spain. Purpose To describe the standardization process and reliability of the anthropometric measurements carried out in the pilot study and during the final workshop, examining both intra- and inter-rater errors for measurements. Materials and Methods A total of 98 elderly from five different regions participated in the intra-rater error assessment, and 10 different seniors living in the city of Toledo (Spain) participated in the inter-rater assessment. We examined both intra- and inter-rater errors for heights and circumferences. Results For height, intra-rater technical errors of measurement (TEMs) were smaller than 0.25 cm. For circumferences and knee height, TEMs were smaller than 1 cm, except for waist circumference in the city of Cáceres. Reliability for heights and circumferences was greater than 98% in all cases. Inter-rater TEMs were 0.61 cm for height, 0.75 cm for knee-height and ranged between 2.70 and 3.09 cm for the circumferences measured. Inter-rater reliabilities for anthropometric measurements were always higher than 90%. Conclusion The harmonization process, including the workshop and pilot study, guarantee the quality of the anthropometric measurements in the elderly EXERNET multi-centre study. High reliability and low TEM may be expected when assessing anthropometry in elderly population. PMID:22860013

[Pearson syndrome. Case report].

PubMed

Cammarata-Scalisi, Francisco; López-Gallardo, Ester; Emperador, Sonia; Ruiz-Pesini, Eduardo; Da Silva, Gloria; Camacho, Nolis; Montoya, Julio

2011-09-01

Among the etiologies of anemia in the infancy, the mitochondrial cytopathies are infrequent. Pearson syndrome is diagnosed principally during the initial stages of life and it is characterized by refractory sideroblastic anemia with vacuolization of marrow progenitor cells, exocrine pancreatic dysfunction and variable neurologic, hepatic, renal and endocrine failures. We report the case of a 14 month-old girl evaluated by a multicentric study, with clinic and molecular diagnosis of Pearson syndrome, with the 4,977-base pair common deletion of mitochondrial DNA. This entity has been associated to diverse phenotypes within the broad clinical spectrum of mitochondrial disease.

Overall survival and clinical characteristics of BRCA mutation carriers with stage I/II pancreatic cancer

PubMed Central

Golan, Talia; Sella, Tal; O'Reilly, Eileen M; Katz, Matthew H G; Epelbaum, Ron; Kelsen, David P; Borgida, Ayelet; Maynard, Hannah; Kindler, Hedy; Friedmen, Eitan; Javle, Milind; Gallinger, Steven

2017-01-01

Background: BRCA1/BRCA2 germ line (GL) mutation carriers with pancreatic adenocarcinoma (PDAC) may have distinct outcomes. We recently described an apparent more favourable prognosis of surgically resected BRCA-associated PDAC patients in a single-arm, uncontrolled, retrospective study. However, the prognostic impact of GL BRCA1/2 mutations in surgically resected PDAC has not been compared with a matched control population. Methods: A larger multi-centre, case–control retrospective analysis was performed. Cases were patients with surgically resected, BRCA1/2-associated PDAC from 2004 to 2013. Controls included surgically resected PDAC cases treated during the same time period that were either BRCA non-carriers, or had no family history of breast, ovarian or pancreatic cancers. Cases and controls were matched by: age at diagnosis (within ±5-year period) and institution. Demographics, clinical history, overall survival (OS) and disease-free survival (DFS) were abstracted from patient records. Statistical comparisons were assessed using χ2- and Fisher's exact test, and median DFS/OS using Kaplan–Meier method and log-rank testing. Results: Twenty-five patients with BRCA1-(n=4) or BRCA2 (N=21)-associated resectable PDAC were identified. Mean age was 55.7 years (range, 34–78 years), 48% (n=12) were females and 76% (n=19) were Jewish. Cases were compared (1 : 2) with 49 resectable PDAC controls, and were balanced for age, ethnicity and other relevant clinical and pathological features. BRCA-associated PDAC patients received neoadjuvant, or adjuvant platinum-based treatment more frequently than controls (7 out of 8 vs 6 out of 14) and (7 out of 21 vs 3 out of 44), respectively. No significant difference in median OS (37.06 vs 38.77 months, P=0.838) and in DFS (14.3 vs 12.0 months, P=0.303) could be demonstrated between cases and controls. A trend to increased DFS was observed among BRCA-positive cases treated with neoadjuvant/adjuvant platinum-containing regimens (n=10) compared with similarly treated controls (n=7) (39.1 vs 12.4 months, P=0.255). Conclusions: In this retrospective analysis, the prognosis of surgically resectable BRCA-associated PDAC is no different than that of sporadic PDAC from the same institution. The role of platinum-based adjuvant therapy in this setting requires prospective investigation. PMID:28183138

Assessing treatment-as-usual provided to control groups in adherence trials: Exploring the use of an open-ended questionnaire for identifying behaviour change techniques.

PubMed

Oberjé, Edwin J M; Dima, Alexandra L; Pijnappel, Frank J; Prins, Jan M; de Bruin, Marijn

2015-01-01

Reporting guidelines call for descriptions of control group support in equal detail as for interventions. However, how to assess the active content (behaviour change techniques (BCTs)) of treatment-as-usual (TAU) delivered to control groups in trials remains unclear. The objective of this study is to pre-test a method of assessing TAU in a multicentre cost-effectiveness trial of an HIV-treatment adherence intervention. HIV-nurses (N = 21) completed a semi-structured open-ended questionnaire enquiring about TAU adherence counselling. Two coders independently coded BCTs. Completeness and clarity of nurse responses, inter-coder reliabilities and the type of BCTs reported were examined. The clarity and completeness of nurse responses were adequate. Twenty-three of the 26 identified BCTs could be reliably coded (mean κ = .79; mean agreement rate = 96%) and three BCTs scored below κ = .60. Total number of BCTs reported per nurse ranged between 7 and 19 (M = 13.86, SD = 3.35). This study suggests that the TAU open-ended questionnaire is a feasible and reliable tool to capture active content of support provided to control participants in a multicentre adherence intervention trial. Considerable variability in the number of BCTs provided to control patients was observed, illustrating the importance of reliably collecting and accurately reporting control group support.

Evaluation of the McGrath MAC and Macintosh laryngoscope for tracheal intubation in 2000 patients undergoing general anaesthesia: the randomised multicentre EMMA trial study protocol

PubMed Central

Kriege, Marc; Alflen, Christian; Tzanova, Irene; Schmidtmann, Irene; Piepho, Tim; Noppens, Ruediger R

2017-01-01

Introduction The direct laryngoscopy technique using a Macintosh blade is the first choice globally for most anaesthetists. In case of an unanticipated difficult airway, the complication rate increases with the number of intubation attempts. Recently, McGrath MAC (McGrath) video laryngoscopy has become a widely accepted method for securing an airway by tracheal intubation because it allows the visualisation of the glottis without a direct line of sight. Several studies and case reports have highlighted the benefit of the video laryngoscope in the visualisation of the glottis and found it to be superior in difficult intubation situations. The aim of this study was to compare the first-pass intubation success rate using the (McGrath) video laryngoscope compared with conventional direct laryngoscopy in surgical patients. Methods and analysis The EMMA trial is a multicentre, open-label, patient-blinded, randomised controlled trial. Consecutive patients requiring tracheal intubation are randomly allocated to either the McGrath video laryngoscope or direct laryngoscopy using the Macintosh laryngoscope. The expected rate of successful first-pass intubation is 95% in the McGrath group and 90% in the Macintosh group. Each group must include a total of 1000 patients to achieve 96% power for detecting a difference at the 5% significance level. Successful intubation with the first attempt is the primary endpoint. The secondary endpoints are the time to intubation, attempts for successful intubation, the necessity of alternatives, visualisation of the glottis using the Cormack & Lehane score and percentage of glottic opening score and definite complications. Ethics and dissemination The project was approved by the local ethics committee of the Medical Association of the Rhineland Palatine state and Westphalia-Lippe. The results of this study will be made available in the form of manuscripts for publication and presentations at national and international meetings. Trial registration number ClinicalTrials.gov NCT 02611986; pre-results. PMID:28827261

Synchronic nasopharyngeal and intraparotid warthin tumors: A case report and literature review.

PubMed

Yáñez-Barraza, Karina-Lizbeth; Domínguez-Malagon, Hugo-Ricardo; Mosqueda-Taylor, Adalberto; Cano-Valdez, Ana-María; Luna-Ortiz, Kuauhyama

2014-10-01

Warthin tumor is the second most frequent benign salivary gland tumor after pleomorphic adenoma; it occurs almost exclusively in the parotid gland and peri-parotideal lymph nodes, although it may rarely present in other locations. It may be multicentric and bilateral in a small percentage of cases. Nasopharyngeal Warthin tumor is very rare, and the presence of a synchronic WT involving nasopharynx and parotid is an exceptional event, as it has been described only twice in the literature. In this article we report an additional case of a synchronic Warthin tumor and review the related literature. Key words:Warthin tumor, synchronic WT, multicéntrico, nasopharynx.

Experience from a multicentre stroke register: a preliminary report

PubMed Central

Hatano, S.

1976-01-01

In collaboration with 15 centres in 10 countries of Africa, Asia, and Europe, WHO started a pilot study of a community-based stroke register, with standardized methods. Preliminary data were obtained on 6395 new cases of stroke in defined study communities, from May 1971 to September 1974. Information on incidence rates, clinical profiles, diagnosis, management, and course and prognosis for these patients is given. PMID:1088404

Castleman's Disease with Paraneoplastic Pemphigus

PubMed Central

Dinesha; Padyana, Mahesha; Nayak, Kashinath; Nirupama, M; Pai, D Shivanand

2014-01-01

Castleman's disease is a rare autoimmune disorder with varied clinical presentations. Castleman's commonly involves mediastinum and hence it is thoracic in most of the reported cases. Paraneoplastic pemphigus (PNP) and myasthenia gravis can be associated with multicentric Castleman's disease. Its association with HIV, Kaposi sarcoma, and lymphoma is also well known. We report a rare combination of unicentric, extrathoracic Castleman's disease with PNP and myasthenia gravis. PMID:25071278

Occupation and malignant lymphoma: a population based case control study in Germany

PubMed Central

Mester, B; Nieters, A; Deeg, E; Elsner, G; Becker, N; Seidler, A

2006-01-01

Aims To identify occupations suspected to be associated with malignant lymphoma and to generate new hypotheses about occupational risks in a multicentre, population based case control study. Methods Male and female patients with malignant lymphoma (n = 710) aged 18–80 years of age were prospectively recruited in six study regions in Germany. For each newly recruited lymphoma case, a sex, region, and age matched control was drawn from the population registers. Odds ratios and 95% confidence intervals for major occupations and industries were calculated using conditional logistic regression analysis, adjusted for smoking (in pack‐years) and alcohol consumption. Patients with specific lymphoma subentities were additionally compared with the entire control group using unconditional logistic regression analysis. Results The following economic/industrial sectors were positively associated with lymphoma: food products, beverages, tobacco; paper products, publishing and printing; and metals. Chemicals; real estate, renting, and business activities were negatively associated with lymphoma diagnosis. The authors observed an increased overall lymphoma risk among architects; maids; farmers; glass formers; and construction workers. Shoemaking and leather goods making was negatively associated with the lymphoma diagnosis (although based on small numbers). In the occupational group analysis of lymphoma subentities, Hodgkin's lymphoma was significantly associated only with rubber and plastic products making; diffuse large B cell lymphoma risk was considerably increased among metal processors; follicular lymphoma showed highly significant risk increases for several occupational groups (medical, dental, and veterinary workers; sales workers; machinery fitters; and electrical fitters); and multiple myeloma showed a particularly pronounced risk increase for farmers as well as for agriculture and animal husbandry workers. Conclusions The results partly confirm previously defined occupational risks. Occupational risk factors for follicular lymphomas might differ from the overall risk factors for malignant lymphoma. PMID:16361401

Automatic segmentation of male pelvic anatomy on computed tomography images: a comparison with multiple observers in the context of a multicentre clinical trial.

PubMed

Geraghty, John P; Grogan, Garry; Ebert, Martin A

2013-04-30

This study investigates the variation in segmentation of several pelvic anatomical structures on computed tomography (CT) between multiple observers and a commercial automatic segmentation method, in the context of quality assurance and evaluation during a multicentre clinical trial. CT scans of two prostate cancer patients ('benchmarking cases'), one high risk (HR) and one intermediate risk (IR), were sent to multiple radiotherapy centres for segmentation of prostate, rectum and bladder structures according to the TROG 03.04 "RADAR" trial protocol definitions. The same structures were automatically segmented using iPlan software for the same two patients, allowing structures defined by automatic segmentation to be quantitatively compared with those defined by multiple observers. A sample of twenty trial patient datasets were also used to automatically generate anatomical structures for quantitative comparison with structures defined by individual observers for the same datasets. There was considerable agreement amongst all observers and automatic segmentation of the benchmarking cases for bladder (mean spatial variations < 0.4 cm across the majority of image slices). Although there was some variation in interpretation of the superior-inferior (cranio-caudal) extent of rectum, human-observer contours were typically within a mean 0.6 cm of automatically-defined contours. Prostate structures were more consistent for the HR case than the IR case with all human observers segmenting a prostate with considerably more volume (mean +113.3%) than that automatically segmented. Similar results were seen across the twenty sample datasets, with disagreement between iPlan and observers dominant at the prostatic apex and superior part of the rectum, which is consistent with observations made during quality assurance reviews during the trial. This study has demonstrated quantitative analysis for comparison of multi-observer segmentation studies. For automatic segmentation algorithms based on image-registration as in iPlan, it is apparent that agreement between observer and automatic segmentation will be a function of patient-specific image characteristics, particularly for anatomy with poor contrast definition. For this reason, it is suggested that automatic registration based on transformation of a single reference dataset adds a significant systematic bias to the resulting volumes and their use in the context of a multicentre trial should be carefully considered.

Association between androgenetic alopecia and coronary artery disease in young male patients.

PubMed

Sharma, Kamal H; Jindal, Anchal

2014-01-01

Several studies have demonstrated an association between androgenetic alopecia (AGA) and cardiovascular disease. Still controversies exist regarding the association. Are they truly associated? The purpose of the present study was to assess the prevalence of AGA and establish its association in young (<45 years) Asian Indian Gujarati male patients having coronary artery disease (CAD). Case-control prospective multicentric study was carried out on 424 men. Case group consisted of 212 male subjects having CAD (Group 1) and another 212, either sibling or first degree male relative of the case subjects (having no evidence of CAD) were considered as the control group (Group 2). Age, total cholesterol, incidence of diabetes mellitus, and hypertension were similar in both groups. The degree of alopecia was assessed using the Norwood-Hamilton scale for men. Statistical analysis was performed using Chi-square test. AGA was found in 80 (37.73%) young CAD patients (Group 1), whereas 44 (20.7%) of patients had alopecia in the control group (Group 2). There was statistically significant association between male AGA and CAD (P = 0.001). Odds ratio was 2.70 (95% confidence interval [CI], 1.72 ± 4.26). Statistically significant association was found between high grade baldness (Grades IV-VII) and CAD in young men (P < 0.05). Odds ratio = 2.36 (95% CI, 1.108 ± 5.033). There is statistically significant association of AGA in young Asian Gujarati male with CAD and the prevalence of AGA in young CAD patient is 37.73%. This study implies early onset AGA in male is independently associated with CAD, though mechanisms need to be investigated.

Multicentre hospital-based case-control study of diffuse large B-cell lymphoma in Shanghai, China.

PubMed

Fan, Rong; Zhang, Lu-Yao; Wang, Hong; Yang, Bo; Han, Tao; Zhao, Xiao-Li; Wang, Wei; Wang, Xiao-Qin; Lin, Guo-Wei

2012-01-01

Several potential risk factors have been identified for diffuse large B-cell lymphoma (DLBCL); however, epidemiological studies investigating the association between these risk factors and DLBCL have yielded inconsistent results. To investigate potential medical, lifestyle, and environmental risk factors of DLBCL in Shanghai, China through a hospital-based case-control study. One-hundred- and-forty-seven newly diagnosed DLBCL patients and 294 sex- and age-matched controls were recruited from 11 hospitals in Shanghai between 2003 and 2007. A standardized structured questionnaire was used to obtain patient data on demographics, medical history, family history, lifestyle, and environmental exposures. Conditional logistic regression models were used to estimate odds ratios (ORs), with 95% confidence intervals (CIs), for risk associated with each data category. History of tuberculosis (TB) infection and "living on a farm" were positively associated with DLBCL (TB: OR=3.05, 95% CI: 1.19-7.80; farm: OR=1.82, 95% CI: 1.21-2.73). In contrast, taking traditional Chinese medicine was negatively associated with DLBCL (OR=0.36, 95% CI: 0.14- 0.89). No significant correlation with DLBCL risk was found for any of the other potential risk factors (p>0.05), including but not limited to hair dyes, alcohol drinking, smoking, and home/workplace renovation within one year. Consistent with results from previous studies in other DLBCL case populations, traditional Chinese medicine appeared to have a direct or indirect protective effect against DLBCL. However, this study also identified a possible predisposition for DLBCL in TB sufferers and farmers.

Effects of continuous positive airway pressure on neurocognitive architecture and function in patients with obstructive sleep apnoea: study protocol for a multicentre randomised controlled trial.

PubMed

Xu, Huajun; Wang, Hui; Guan, Jian; Yi, Hongliang; Qian, Yingjun; Zou, Jianyin; Xia, Yunyan; Fu, Yiqun; Li, Xinyi; Jiao, Xiao; Huang, Hengye; Dong, Pin; Yu, Ziwei; Yang, Jun; Xiang, Mingliang; Li, Jiping; Chen, Yanqing; Wang, Peihua; Sun, Yizhou; Li, Yuehua; Zheng, Xiaojian; Jia, Wei; Yin, Shankai

2017-05-25

Many clinical studies have indicated that obstructive sleep apnoea (OSA), the most common chronic sleep disorder, may affect neurocognitive function, and that treatment for continuous positive airway pressure (CPAP) has some neurocognitive protective effects against the adverse effects of OSA. However, the effects of CPAP treatment on neurocognitive architecture and function remain unclear. Therefore, this multicentre trial was designed to investigate whether and when neurocognitive architecture and function in patients with OSA can be improved by CPAP treatment and to explore the role of gut microbiota in improving neurocognitive function during treatment. This study will be a multicentre, randomised, controlled trial with allocation concealment and assessor blinding. A total of 148 eligible patients with moderate to severe OSA will be enrolled from five sleep centres and randomised to receive CPAP with best supportive care (BSC) intervention or BSC intervention alone. Cognitive function, structure and function of brain regions, gut microbiota, metabolites, biochemical variables, electrocardiography, echocardiography, pulmonary function and arterial stiffness will be assessed at baseline before randomisation and at 3, 6 and 12 months. This study has been approved by the Medical Ethics Committee of Shanghai Jiao Tong University Affiliated Sixth People's Hospital (approval number 2015-79). The results from this study will be published in peer-reviewed journals and at relevant conferences. NCT02886156; 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.

pRotective vEntilation with veno-venouS lung assisT in respiratory failure: A protocol for a multicentre randomised controlled trial of extracorporeal carbon dioxide removal in patients with acute hypoxaemic respiratory failure.

PubMed

McNamee, J J; Gillies, M A; Barrett, N A; Agus, A M; Beale, R; Bentley, A; Bodenham, A; Brett, S J; Brodie, D; Finney, S J; Gordon, A J; Griffiths, M; Harrison, D; Jackson, C; McDowell, C; McNally, C; Perkins, G D; Tunnicliffe, W; Vuylsteke, A; Walsh, T S; Wise, M P; Young, D; McAuley, D F

2017-05-01

One of the few interventions to demonstrate improved outcomes for acute hypoxaemic respiratory failure is reducing tidal volumes when using mechanical ventilation, often termed lung protective ventilation. Veno-venous extracorporeal carbon dioxide removal (vv-ECCO 2 R) can facilitate reducing tidal volumes. pRotective vEntilation with veno-venouS lung assisT (REST) is a randomised, allocation concealed, controlled, open, multicentre pragmatic trial to determine the clinical and cost-effectiveness of lower tidal volume mechanical ventilation facilitated by vv-ECCO 2 R in patients with acute hypoxaemic respiratory failure. Patients requiring intubation and mechanical ventilation for acute hypoxaemic respiratory failure will be randomly allocated to receive either vv-ECCO 2 R and lower tidal volume mechanical ventilation or standard care with stratification by recruitment centre. There is a need for a large randomised controlled trial to establish whether vv-ECCO 2 R in acute hypoxaemic respiratory failure can allow the use of a more protective lung ventilation strategy and is associated with improved patient outcomes.

Energy and nutrient intake of patients with mild-to-moderate chronic renal failure compared with healthy children: an Italian multicentre study.

PubMed

Rätsch, I M; Catassi, C; Verrina, E; Gusmano, R; Appiani, A; Bettinelli, A; Picca, S; Rizzoni, G; Fabian-Bach, C; Wingen, A M

1992-09-01

Nutritional counselling is important in the management of children with chronic renal failure (CRF). In 1988, a controlled European multicentre study was started to evaluate the effects of a low-protein diet on the progression of CRF in children. To assess the energy, macro- and micronutrient intake, 4-day weighed dietary records were obtained from 50 children with low to moderate CRF (creatinine clearance 65 to 15 ml/min per 1.73 m2) and from 93 healthy children. The mean energy intake was 90%-93% of the recommended dietary allowance for Italian children in controls and 76%-88% in CRF patients. The mean protein intake was 2.1-3.1 g/kg per day in controls and 1.6-2.7 g/kg per day in CRF patients. Overall, the energy intake was 10% and the protein intake 33% lower in CRF patients than in healthy children. Children with CRF consumed less cholesterol, calcium and phosphorus than healthy children. The lower spontaneous intake of energy, protein and other nutrients should be taken into account when planning the nutrition of children with CRF.

Feasibility of the AML profiler (Skyline™ Array) for patient risk stratification in a multicentre trial: a preliminary comparison with the conventional approach.

PubMed

Nomdedéu, Josep F; Puigdecanet, Eulalia; Bussaglia, Elena; Hernández, Juan José; Carricondo, Maite; Estivill, Camino; Martí-Tutusaus, Josep Maria; Tormo, Mar; Zamora, Lurdes; Serrano, Elena; Perea, Granada; de Llano, Maria Paz Queipo; García, Antoni; Sánchez-Ortega, Isabel; Ribera, Josep Maria; Nonell, Lara; Aventin, Anna; Solé, Francesc; Brunet, Maria Salut; Sierra, Jorge

2017-12-01

Deoxyribonucleic acid microarrays allow researchers to measure mRNA levels of thousands of genes in a single experiment and could be useful for diagnostic purposes in patients with acute myeloid leukaemia (AML). We assessed the feasibility of the AML profiler (Skyline™ Array) in genetic stratification of patients with de novo AML and compared the results with those obtained using the standard cytogenetic and molecular approach. Diagnostic bone marrow from 31 consecutive de novo AML cases was used to test MLL-PTD, FLT3-ITD and TKD, NPM1 and CEBPAdm mutations. Purified RNA was used to assess RUNX1-RUNX1T1, PML-RARα and CBFβ-MYH11 rearrangements. RNA remnants underwent gene expression profiling analysis using the AML profiler, which detects chromosomal aberrations: t(8;21), t(15;17), inv(16), mutations (CEBPAdm, ABD-NPM1) and BAALC and EVI1 expression. Thirty cases were successfully analysed with both methods. Five cases had FLT3-ITD. In one case, a t(8;21) was correctly detected by both methods. Four cases had inv(16); in one, the RNA quality was unsatisfactory and it was not hybridized, and in the other three, the AML profiler detected the genetic lesion - this being a rare type I translocation in one case. Two cases with acute promyelocytic leukaemia were diagnosed by both methods. Results for NPM1 mutations were concordant in all but two cases (2/11, non-ABD mutations). Analysis of costs and turnaround times showed that the AML profiler was no more expensive than the conventional molecular approach. These results suggest that the AML profiler could be useful in multicentre trials to rapidly identify patients with AML with a good prognosis. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

Long-acting chloramphenicol versus intravenous ampicillin for treatment of bacterial meningitis.

PubMed

Pécoul, B; Varaine, F; Keita, M; Soga, G; Djibo, A; Soula, G; Abdou, A; Etienne, J; Rey, M

1991-10-05

In most developing countries, bacterial meningitis (BM) is associated with a high case-fatality rate. The search for a simple, convenient, and inexpensive antibiotic treatment remains a priority. In this study, a non-blinded, multicentre, randomised clinical trial of 528 cases of BM was done in two hospitals in Mali and Niger, between March, 1989, and May, 1990, to see whether a double injection of long-acting chloramphenicol (on admission to hospital and 48 h later) is as effective as a course of intravenous ampicillin (8 days, 4 times a day). The cumulative case-fatality rate on day 4 (principal end-point) among the chloramphenicol (254 patients) and ampicillin (274) groups were, respectively, 28% and 24.5% (relative risk 1.14, 95% confidence interval 0.86-1.52). No outbreak occurred during the study period. The hospital case-fatality rate was 33.1%. Main risk factors for death were associated with clinical condition on admission--ie, altered consciousness, convulsions, or dehydration. The case-fatality rates were 13% (21/161) for Neisseria meningitidis, 36.1% (48/133) for Haemophilus influenzae, and 67% (77/115) for Streptococcus pneumoniae. In a multiple logistic regression model, controlling for the differential distribution of potential risk factors (including bacterial species), there was no difference between treatment groups. Our findings suggest that long-acting chloramphenicol is a useful first-line presumptive treatment for BM in high-incidence countries.

Myositis in primary Sjögren's syndrome: data from a multicentre cohort.

PubMed

Colafrancesco, Serena; Priori, Roberta; Gattamelata, Angelica; Picarelli, Giovanna; Minniti, Antonina; Brancatisano, Filippo; D'Amati, Giulia; Giordano, Carla; Cerbelli, Bruna; Maset, Marta; Quartuccio, Luca; Bartoloni, Elena; Carubbi, Francesco; Cipriani, Paola; Baldini, Chiara; Luciano, Nicoletta; De Vita, Salvatore; Gerli, Roberto; Giacomelli, Roberto; Bombardieri, Stefano; Valesini, Guido

2015-01-01

In primary Sjögren's syndrome (pSS), muscle pain and/or muscular weakness is relatively frequent while myositis has been reported in 3% of patients. The aim of this study was to describe the prevalence of myositis in a multicentre Italian pSS cohort and to address the clinical manifestations, histological findings and therapeutic strategies. Clinical, serological and therapeutic data from a pSS cohort of patients were retrospectively collected. According to Bohan and Peter's criteria, inflammatory myopathy (IM) was suspected in case of muscular weakness associated with increased creatine-phosphokinase (CPK) or abnormal electromyography (EMG). When performed, muscle biopsies were analysed. In a cohort of 1320 patients, 17 (1.28%) presented muscular weakness [in some cases myalgias (7/17, 41.1%)], accompanied by increased CPK [13/17, (76.4%)] and/or abnormal EMG [13/14, (92.8%)]. Ten out of 17 (58.8%) fulfilled at least three diagnostic criteria for IM. Muscular biopsy was performed in 13/17 (76.4%) cases with histologically confirmed myositis in 6/13 (46.1%) (1"IBM-like"-5"PM-like"). In two "PM-like" cases, several fibres showed a decreased histochemical cytochrome C oxidase (COX) stain. Two biopsies tested "negative", four showed "non-specific" findings. All patients were treated with corticosteroids followed by different DMARDs. Our retrospective analysis shows a prevalence of myositis in pSS lower than previously reported, mainly appearing as an overlapping syndrome. Histological findings confirm the possible presence of an IBM or of a myopathy more similar to PM with a decreased COX activity. Classical immunosuppressants are effective although in most difficult cases IVIg or RTX may be used with benefit.

Integrative radiogenomic analysis for multicentric radiophenotype in glioblastoma

PubMed Central

Kong, Doo-Sik; Kim, Jinkuk; Lee, In-Hee; Kim, Sung Tae; Seol, Ho Jun; Lee, Jung-Il; Park, Woong-Yang; Ryu, Gyuha; Wang, Zichen; Ma'ayan, Avi; Nam, Do-Hyun

2016-01-01

We postulated that multicentric glioblastoma (GBM) represents more invasiveness form than solitary GBM and has their own genomic characteristics. From May 2004 to June 2010 we retrospectively identified 51 treatment-naïve GBM patients with available clinical information from the Samsung Medical Center data registry. Multicentricity of the tumor was defined as the presence of multiple foci on the T1 contrast enhancement of MR images or having high signal for multiple lesions without contiguity of each other on the FLAIR image. Kaplan-Meier survival analysis demonstrated that multicentric GBM had worse prognosis than solitary GBM (median, 16.03 vs. 20.57 months, p < 0.05). Copy number variation (CNV) analysis revealed there was an increase in 11 regions, and a decrease in 17 regions, in the multicentric GBM. Gene expression profiling identified 738 genes to be increased and 623 genes to be decreased in the multicentric radiophenotype (p < 0.001). Integration of the CNV and expression datasets identified twelve representative genes: CPM, LANCL2, LAMP1, GAS6, DCUN1D2, CDK4, AGAP2, TSPAN33, PDLIM1, CLDN12, and GTPBP10 having high correlation across CNV, gene expression and patient outcome. Network and enrichment analyses showed that the multicentric tumor had elevated fibrotic signaling pathways compared with a more proliferative and mitogenic signal in the solitary tumors. Noninvasive radiological imaging together with integrative radiogenomic analysis can provide an important tool in helping to advance personalized therapy for the more clinically aggressive subset of GBM. PMID:26863628

A multicentre randomised controlled trial to evaluate the efficacy, morbidity and functional outcome of endoscopic transanal proctectomy versus laparoscopic proctectomy for low-lying rectal cancer (ETAP-GRECCAR 11 TRIAL): rationale and design.

PubMed

Lelong, Bernard; de Chaisemartin, Cécile; Meillat, Helene; Cournier, Sandra; Boher, Jean Marie; Genre, Dominique; Karoui, Mehdi; Tuech, Jean Jacques; Delpero, Jean Robert

2017-04-11

Total mesorectal excision is the standard surgical treatment for mid- and low-rectal cancer. Laparoscopy represents a clear leap forward in the management of rectal cancer patients, offering significant improvements in post-operative measures such as pain, first bowel movement, and hospital length of stay. However, there are still some limits to its applications, especially in difficult cases. Such cases may entail either conversion to an open procedure or positive resection margins. Transanal endoscopic proctectomy (ETAP) was recently described and could address the difficulties of approaching the lower third of the rectum. Early series and case-control studies have shown favourable short-term results, such as a low conversion rate, reduced hospital length of stay and oncological outcomes comparable to laparoscopic surgery. The aim of the proposed study is to compare the rate of positive resection margins (R1 resection) with ETAP versus laparoscopic proctectomy (LAP), with patients randomly assigned to each arm. The proposed study is a multicentre randomised trial using two parallel groups to compare ETAP and LAP. Patients with T3 lower-third rectal adenocarcinomas for whom conservative surgery with manual coloanal anastomosis is planned will be recruited. Randomisation will be performed immediately prior to surgery after ensuring that the patient meets the inclusion criteria and completing the baseline functional and quality of life tests. The study is designed as a non-inferiority trial with a main criterion of R0/R1 resection. Secondary endpoints will include the conversion rate, the minimal invasiveness of the abdominal approach, postoperative morbidity, the length of hospital stay, mesorectal macroscopic assessment, functional urologic and sexual results, faecal continence, global quality of life, stoma-free survival, and disease-free survival at 3 years. The inclusion period will be 3 years, and every patient will be followed for 3 years. The number of patients needed is 226. There is a strong need for optimal evaluation of the ETAP because of substancial changes in the operative technique. Assessment of oncological safety and septic risk, as well as digestive and urological functional results, is particularily mandatory. Moreover, benefits of the ETAP technique could be demonstrated  in post-operative outcome. ClinicalTrial.gov: NCT02584985 . Date and version identifier: Version n°2 - 2015 July 6.

2015/16 I-MOVE/I-MOVE+ multicentre case-control study in Europe: Moderate vaccine effectiveness estimates against influenza A(H1N1)pdm09 and low estimates against lineage-mismatched influenza B among children.

PubMed

Kissling, Esther; Valenciano, Marta; Pozo, Francisco; Vilcu, Ana-Maria; Reuss, Annicka; Rizzo, Caterina; Larrauri, Amparo; Horváth, Judit Krisztina; Brytting, Mia; Domegan, Lisa; Korczyńska, Monika; Meijer, Adam; Machado, Ausenda; Ivanciuc, Alina; Višekruna Vučina, Vesna; van der Werf, Sylvie; Schweiger, Brunhilde; Bella, Antonino; Gherasim, Alin; Ferenczi, Annamária; Zakikhany, Katherina; O Donnell, Joan; Paradowska-Stankiewicz, Iwona; Dijkstra, Frederika; Guiomar, Raquel; Lazar, Mihaela; Kurečić Filipović, Sanja; Johansen, Kari; Moren, Alain

2018-07-01

During the 2015/16 influenza season in Europe, the cocirculating influenza viruses were A(H1N1)pdm09 and B/Victoria, which was antigenically distinct from the B/Yamagata component in the trivalent influenza vaccine. We used the test-negative design in a multicentre case-control study in twelve European countries to measure 2015/16 influenza vaccine effectiveness (VE) against medically attended influenza-like illness (ILI) laboratory-confirmed as influenza. General practitioners swabbed a systematic sample of consulting ILI patients and a random sample of influenza-positive swabs was sequenced. We calculated adjusted VE against influenza A(H1N1)pdm09, A(H1N1)pdm09 genetic group 6B.1 and influenza B overall and by age group. We included 11 430 ILI patients, of which 2272 were influenza A(H1N1)pdm09 and 2901 were influenza B cases. Overall VE against influenza A(H1N1)pdm09 was 32.9% (95% CI: 15.5-46.7). Among those aged 0-14, 15-64 and ≥65 years, VE against A(H1N1)pdm09 was 31.9% (95% CI: -32.3 to 65.0), 41.4% (95% CI: 20.5-56.7) and 13.2% (95% CI: -38.0 to 45.3), respectively. Overall VE against influenza A(H1N1)pdm09 genetic group 6B.1 was 32.8% (95% CI: -4.1 to 56.7). Among those aged 0-14, 15-64 and ≥65 years, VE against influenza B was -47.6% (95% CI: -124.9 to 3.1), 27.3% (95% CI: -4.6 to 49.4) and 9.3% (95% CI: -44.1 to 42.9), respectively. Vaccine effectiveness (VE) against influenza A(H1N1)pdm09 and its genetic group 6B.1 was moderate in children and adults, and low among individuals ≥65 years. Vaccine effectiveness (VE) against influenza B was low and heterogeneous among age groups. More information on effects of previous vaccination and previous infection is needed to understand the VE results against influenza B in the context of a mismatched vaccine. © 2017 The Authors. Influenza and Other Respiratory Viruses Published by John Wiley & Sons Ltd.

Diet and Pre-eclampsia: A Prospective Multicentre Case-Control Study in Ethiopia.

PubMed

Endeshaw, Mulualem; Abebe, Fantu; Bedimo, Melkamu; Asart, Anemaw

2015-06-01

Pre-eclampsia is one of the most commonly encountered hypertensive disorders of pregnancy that accounts for 20-80% of maternal mortality in developing countries, including Ethiopia. For many years, diet has been suggested to play a role in pre-eclampsia. However, the hypotheses have been diverse with inconsistent results across studies, and this has not been studied in Ethiopia. The objective of this study was to determine the effect of dietary habits on the incidence of pre-eclampsia in Bahir Dar, Ethiopia A prospective multicentre unmatched case-control study was conducted among 453 (151 cases and 302 controls) pregnant women attending antepartum or intrapartum care in public health facilities of Bahir Dar City from June to September 2014. The interviewer conducted a face-to-face interview, measured the mid-upper arm circumference (MUAC) and collected the mid-pregnancy haemoglobin level from clinical notes using a standardized and pretested questionnaire. Epi Info 3.5.3 was used for data entry and cleaning, while IBM SPSS Statistics 20 was used for data analysis. Backward stepwise unconditional logistic regression analysis was employed to determine the strength of association of predictive variables with the outcome variable and to control for the effect of confounding variables. A P-value ≤0.05 was considered statistically significant. For every 1-cm increase of MUAC, there was an increase in the incidence rate of pre-eclampsia by a factor of 1.35 (adjusted odds ratio (AOR)=1.35, 95% confidence interval (CI): 1.21, 1.51). A higher incidence of pre-eclampsia was found in women who reported to have consumed coffee daily during pregnancy (AOR=1.78, 95% CI: 1.20, 3.05). Similarly, for women who had anaemia during the first trimester, the incidence of pre-eclampsia was 2.5 times higher than their counterparts (AOR=2.47, 95% CI: 1.12, 7.61). This study also revealed consumption of fruit or vegetables at least three times a week during pregnancy to be protective against pre-eclampsia (AOR=0.51, 95% CI: 0.29, 0.91; AOR=0.46, 95% CI: 0.24, 0.90, respectively). In addition, compliance with folate intake during pregnancy has shown a significant independent effect on the prevention of pre-eclampsia in this study (AOR=0.16, 95% CI: 0.08, 0.29). Adequate vegetable and fruit consumption and compliance with folate intake during pregnancy are independent protective factors against pre-eclampsia. On the other hand, higher MUAC, anaemia and daily coffee intake during pregnancy are risk factors for the development of pre-eclampsia. Audience-specific education and promotion of the use of the protective factors identified in this study should be prioritized. The risk factors identified can be used for prediction and early diagnoses of pre-eclampsia allowing timely interventions to be performed to minimize deaths associated with severe pre-eclampsia/eclampsia. Copyright © 2015 Elsevier Ltd. All rights reserved.

Social class based on occupation is associated with hospitalization for A(H1N1)pdm09 infection. Comparison between hospitalized and ambulatory cases.

PubMed

Pujol, J; Godoy, P; Soldevila, N; Castilla, J; González-Candelas, F; Mayoral, J M; Astray, J; Garcia, S; Martin, V; Tamames, S; Delgado, M; Domínguez, A

2016-03-01

This study aimed to analyse the existence of an association between social class (categorized by type of occupation) and the occurrence of A(H1N1)pmd09 infection and hospitalization for two seasons (2009-2010 and 2010-2011). This multicentre study compared ambulatory A(H1N1)pmd09 confirmed cases with ambulatory controls to measure risk of infection, and with hospitalized A(H1N1)pmd09 confirmed cases to asses hospitalization risk. Study variables were: age, marital status, tobacco and alcohol use, pregnancy, chronic obstructive pulmonary disease, chronic respiratory failure, cardiovascular disease, diabetes, chronic liver disease, body mass index >40, systemic corticosteroid treatment and influenza vaccination status. Occupation was registered literally and coded into manual and non-manual worker occupational social class groups. A conditional logistic regression analysis was performed. There were 720 hospitalized cases, 996 ambulatory cases and 1062 ambulatory controls included in the study. No relationship between occupational social class and A(H1N1)pmd09 infection was found [adjusted odds ratio (aOR) 0·97, 95% confidence interval (CI) 0·74-1·27], but an association (aOR 1·53, 95% CI 1·01-2·31) between occupational class and hospitalization for A(H1N1)pmd09 was observed. Influenza vaccination was a protective factor for A(H1N1)pmd09 infection (aOR 0·41, 95% CI 0·23-0·73) but not for hospitalization. We conclude that manual workers have the highest risk of hospitalization when infected by influenza than other occupations but they do not have a different probability of being infected by influenza.

Mutation status of the mediator complex subunit 12 (MED12) in uterine leiomyomas and concurrent/metachronous multifocal peritoneal smooth muscle nodules (leiomyomatosis peritonealis disseminata).

PubMed

Rieker, Ralf J; Agaimy, Abbas; Moskalev, Evgeny A; Hebele, Simone; Hein, Alexander; Mehlhorn, Grit; Beckmann, Matthias W; Hartmann, Arndt; Haller, Florian

2013-06-01

The pathogenesis and classification of multicentric smooth muscle tumours with benign appearance and concurrent/metachronous uterine and peritoneal involvement is controversial and may on occasion be diagnostically challenging. Leiomyomatosis peritonealis disseminata (LPD) is a rare condition affecting women of reproductive age, characterised by the occurrence of multiple small peritoneal smooth muscle nodules with bland histology. We investigated a total of 12 uterine and seven concurrent/metachronous peritoneal smooth muscle nodules with benign appearance from two females for mutations in the mediator complex subunit 12 (MED12), which has recently been identified as the most frequent genetic aberration in uterine leiomyomas. The first case harboured different MED12 mutations in the peritoneal nodules. Mutational status of peritoneal nodules was discordant with that of the uterine leiomyomas. The second case displayed the same MED12 mutation in all five peritoneal nodules, but this mutation was not detected in her current uterine leiomyomas. Our results suggest that smooth muscle neoplasms with benign appearance of the primary and secondary müllerian system share a similar genetic background of MED12 mutation in combination with oestrogen dependency. Analysis of MED12 mutation status might be a valuable adjunct tool for the future classification of these sometimes diagnostically challenging multicentric tumours.

Multicentric GISCoR Study "intensive clinical follow-up versus surgical radicalization after complete endoscopic polypectomy of a malignant adenoma" (SEC-GISCoR).

PubMed

Andreoni, Bruno; Camellini, Lorenzo; Sonzogni, Angelica; Crosta, Cristiano; Pirola, Maria Elena; Corbellini, Carlo

2011-09-01

Colorectal cancer screening programs result in an early diagnosis of the disease. In 2007, 250 malignant polyps were identified in Lombardy, out of 1,329 screen-detected colorectal carcinomas. The Italian Group for Colorectal Cancer (GISCoR) promoted the multicentric study "Endoscopic Follow-up versus Surgical Radicalization of Malignant Polyps after Complete Endoscopic Polypectomy" (SEC-GISCoR). The protocol was a multicentric, prospective, observational, non-randomized study. It included patients diagnosed a colorectal malignant adenoma, after complete endoscopic removal. From November 2005 to September 2009, three participating centers enrolled 120 patients with malignant polyps after "complete" endoscopic polypectomy; malignant polyps were classified as "low risk" or "high risk". The study had two arms: "Intensive follow-up" (42 patients: 32 with low-risk and 10 with high-risk polyps) and "Surgical radicalization" (78 patients: 5 with low-risk and 73 with high-risk polyps). Data were collected using an online CRF. Overall, 37/120 polyps (30.8%) were low risk and 83/120 (69.2%) were high risk. 42 out of 120 patients (35%) were enrolled in the "clinical follow-up" arm, while 78/120 (65%) entered the surgery arm. In 15 cases, patients were not enrolled in the correct arm, according to the criteria agreed upon before starting the study. There still is a high incidence (11.5%) of pathological mismatches. No clinical event was reported in 2.9 years of follow-up. In conclusion, some differences emerged in the management of patients with malignant polyps among participating centers (p < 0.001), mismatches can be explained by high surgical risk or patient's choice. Only in 5 cases (4.2%), did data analysis not allow to exactly determine the reason for a choice different from protocol criteria. The availability of new risk factors and the evidence of pathological mismatches confirmed the need for future studies on this issue.

Overcoming the Barriers Experienced in Conducting a Medication Trial in Adults with Aggressive Challenging Behaviour and Intellectual Disabilities

ERIC Educational Resources Information Center

Oliver-Africano, P.; Dickens, S.; Ahmed, Z.; Bouras, N.; Cooray, S.; Deb, S.; Knapp, M.; Hare, M.; Meade, M.; Reece, B.; Bhaumik, S.; Harley, D.; Piachaud, J.; Regan, A.; Ade Thomas, D.; Karatela, S.; Rao, B.; Dzendrowskyj, T.; Lenotre, L.; Watson, J.; Tyrer, P.

2010-01-01

Background: Aggressive challenging behaviour in people with intellectual disability (ID) is frequently treated with antipsychotic drugs, despite a limited evidence base. Method: A multi-centre randomised controlled trial was undertaken to investigate the efficacy, adverse effects and costs of two commonly prescribed antipsychotic drugs…

Multicentre experience with the BridgePoint devices to facilitate recanalisation of chronic total coronary occlusions through controlled subintimal re-entry.

PubMed

Werner, Gerald S; Schofer, Joachim; Sievert, Horst; Kugler, Chad; Reifart, Nicolaus J

2011-06-01

The major challenge for the interventional treatment of chronic total coronary occlusion (CTO) is a low primary success rate. A common problem is the passage of the recanalisation wire into a subintimal position. New devices, which were evaluated in the first multicentre study in CTOs resistant to a conventional wire approach, may help to facilitate a controlled re-entry into the true lumen. The aim of this study was to assess the safety and efficacy of this approach, with successful true lumen distal wire passage as the primary endpoint. Forty-two patients were enrolled in four centres with high expertise in PCI for CTOs. All CTOs were of at least three months duration, and were initially attempted with dedicated recanalisation wires. After failure to pass or creation of a subintimal dissection, the BridgePoint devices were applied, consisting of a ball-tipped catheter (CrossBoss) to pass the proximal occlusion cap, and a flat-shaped balloon catheter (Stingray catheter) to be inflated within the subintimal space to guide the re-entry into the true vessel lumen with a special wire (Stingray guidewire). The primary endpoint was met in 67% of all patients. A higher success rate seemed to be possible when all devices were used in sequenced beginning with the CrossBoss, and in the case of a subintimal passage, followed by the Stingray. True lumen re-entry failed because of the loss of distally contrast filling and thus loss of a target for re-entry, and by a failure to advance the Stingray balloon far enough distal and parallel to the distal lumen. There were no severe device related complications. In patients with complex CTOs referred to dedicated centres with high experience in CTOs, these results demonstrate the potential of a guided re-entry from a subintimal wire position by use of the BridgePoint devices.

Long-term response to hydroxychloroquine in patients with discoid lupus erythematosus.

PubMed

Wahie, S; Meggitt, S J

2013-09-01

The recommended first-line oral therapy for discoid lupus erythematosus (DLE) is the antimalarial hydroxychloroquine. To the best of our knowledge, there is no published information regarding the long-term (i.e. > 6 months) response of DLE to hydroxychloroquine in clinical practice. To describe the long-term clinical response of DLE to hydroxychloroquine after 6 months of use. A multicentre retrospective cohort study was conducted in patients with DLE who had received treatment with hydroxychloroquine. All patients were recruited and interviewed by a single investigator and response to hydroxychloroquine assessed by the same individual through a retrospective review of case notes using a specified protocol. A total of 200 patients with DLE were recruited (F:M = 4 : 1) with a median age at diagnosis of 40 years (range 16-81) and median follow-up of 8 years (range 0·5-37). An adequate clinical response to hydroxychloroquine was recorded in 91 patients (45·5%) but nonresponse occurred in 85 patients (42·5%). The remainder of patients either had partial response or withdrew from therapy due to toxicity or were unclassifiable. Importantly, of those individuals that did respond to hydroxychloroquine within the first 6 months of use, almost one in five eventually lost their response, despite continued administration, after a median interval of 2 years. These patients often regained disease control if treated with a combination of hydroxychloroquine and mepacrine. Of those that did not respond to hydroxychloroquine within the first 6 months of use, almost one in 10 became eventual responders either after continued administration for up to 2 years or when rechallenged on hydroxychloroquine. The remaining nonresponders relied frequently on oral corticosteroid. In this cohort of patients with DLE, long-term clinical response to hydroxychloroquine occurred in less than 50% of patients. Nonresponders to hydroxychloroquine frequently required oral steroid to achieve disease control. These findings merit further investigation through a multicentre prospective study using a validated disease activity measure. © 2013 British Association of Dermatologists.

Primaquine treatment and relapse in Plasmodium vivax malaria

PubMed Central

2016-01-01

The relapsing peculiarity of Plasmodium vivax is one of the prime reasons for sustained global malaria transmission. Global containment of P. vivax is more challenging and crucial compared to other species for achieving total malaria control/elimination. Primaquine (PQ) failure and P. vivax relapse is a major global public health concern. Identification and characterization of different relapse strains of P. vivax prevalent across the globe should be one of the thrust areas in malaria research. Despite renewed and rising global concern by researchers on this once ‘neglected’ species, research and development on the very topic of P. vivax reappearance remains inadequate. Many malaria endemic countries have not mandated routine glucose-6-phosphate dehydrogenase (G6PD) testing before initiating PQ radical cure in P. vivax malaria. This results in either no PQ prescription or thoughtless prescription and administration of PQ to P. vivax patients by healthcare providers without being concerned about patients’ G6PD status and associated complications. It is imperative to ascertain the G6PD status and optimum dissemination of PQ radical cure in all cases of P. vivax malaria across the globe. There persists a compelling need to develop/validate a rapid, easy-to-perform, easy-to-interpret, quality controllable, robust, and cost-effective G6PD assay. High-dose PQ of both standard and short duration appears to be safe and more effective for preventing relapses and should be practiced among patients with normal G6PD activity. Multicentric studies involving adequately representative populations across the globe with reference PQ dose must be carried out to determine the true distribution of PQ failure. Study proving role of cytochrome P450-2D6 gene in PQ metabolism and association of CYP2D6 metabolizer phenotypes and P. vivax relapse is of prime importance and should be carried forward in multicentric systems across the globe. PMID:27077309

Vitamin K antagonists and pregnancy outcome. A multi-centre prospective study.

PubMed

Schaefer, Christof; Hannemann, Doreen; Meister, Reinhard; Eléfant, Elisabeth; Paulus, Wolfgang; Vial, Thierry; Reuvers, Minke; Robert-Gnansia, Elisabeth; Arnon, Judy; De Santis, Marco; Clementi, Maurizio; Rodriguez-Pinilla, Elvira; Dolivo, Alla; Merlob, Paul

2006-06-01

Vitamin K antagonists (VKA) are known to act as teratogens; however, there is still uncertainty about the relative risk for birth defects and the most sensitive period. In a multi-centre (n = 12), observational, prospective study we compared 666 pregnant women exposed to phenprocoumon (n = 280), acenocoumarol (n = 226), fluindione (n = 99), warfarin (n = 63) and phenindione (n = 2) to a non-exposed control group (n = 1,094). Data were collected by institutes collaborating in the European Network of Teratology Information Services (ENTIS) during individual risk counselling between 1988 and 2004. Main outcome measures were coumarin embryopathy and other birth defects, miscarriage rate, birth-weight, and prematurity. The rate of major birth defects after 1st trimester exposure was significantly increased (OR 3.86, 95% CI 1.86-8.00). However, there were only two coumarin embryopathies (0.6%; both phenprocoumon). Prematurity was more frequent (16.0% vs. 7.6%, OR 2.61, 95% CI 1.76-3.86), mean gestational age at delivery (37.9 vs.39.4, p<0.001), and mean birth weight of term infants (3,166 g vs. 3,411 g; p < 0.001) were lower compared to the controls. Using the methodology of survival analysis, miscarriage rate reached 42% vs. 14% (hazard ratio 3.36; 95% CI 2.28-4.93). In conclusion, use of VKA during pregnancy increases the risk of structural defects and other adverse pregnancy outcomes. The risk for coumarin embryopathy is, however, very small, in particular when therapy during the 1(st) trimester did not take place later than week 8 after the 1(st) day of the last menstrual period. Therefore, elective termination of a wanted pregnancy is not recommended if (inadvertent) exposure took place in early pregnancy. Close follow-up by the obstetrician including level II ultrasound should be recommended in any case of VKA exposure during pregnancy.

Cost-Effectiveness Analysis of a Transparent Antimicrobial Dressing for Managing Central Venous and Arterial Catheters in Intensive Care Units

PubMed Central

Bernatchez, Stéphanie F.; Ruckly, Stéphane; Timsit, Jean-François

2015-01-01

Objective To model the cost-effectiveness impact of routine use of an antimicrobial chlorhexidine gluconate-containing securement dressing compared to non-antimicrobial transparent dressings for the protection of central vascular lines in intensive care unit patients. Design This study uses a novel health economic model to estimate the cost-effectiveness of using the chlorhexidine gluconate dressing versus transparent dressings in a French intensive care unit scenario. The 30-day time non-homogeneous markovian model comprises eight health states. The probabilities of events derive from a multicentre (12 French intensive care units) randomized controlled trial. 1,000 Monte Carlo simulations of 1,000 patients per dressing strategy are used for probabilistic sensitivity analysis and 95% confidence intervals calculations. The outcome is the number of catheter-related bloodstream infections avoided. Costs of intensive care unit stay are based on a recent French multicentre study and the cost-effectiveness criterion is the cost per catheter-related bloodstream infections avoided. The incremental net monetary benefit per patient is also estimated. Patients 1000 patients per group simulated based on the source randomized controlled trial involving 1,879 adults expected to require intravascular catheterization for 48 hours. Intervention Chlorhexidine Gluconate-containing securement dressing compared to non-antimicrobial transparent dressings. Results The chlorhexidine gluconate dressing prevents 11.8 infections /1,000 patients (95% confidence interval: [3.85; 19.64]) with a number needed to treat of 85 patients. The mean cost difference per patient of €141 is not statistically significant (95% confidence interval: [€-975; €1,258]). The incremental cost-effectiveness ratio is of €12,046 per catheter-related bloodstream infection prevented, and the incremental net monetary benefit per patient is of €344.88. Conclusions According to the base case scenario, the chlorhexidine gluconate dressing is more cost-effective than the reference dressing. Trial Registration This model is based on the data from the RCT registered with www.clinicaltrials.gov (NCT01189682). PMID:26086783

Summary Protocol for a Multi-Centre Randomised Controlled Trial of Enteral Lactoferrin Supplementation in Newborn Very Preterm Infants (ELFIN).

PubMed

2018-06-11

In a multi-centre randomised controlled trial (RCT), we are assessing whether giving very preterm (i.e., born at < 32 weeks' gestation) infants prophylactic enteral bovine lactoferrin supplementation (150 mg/kg/day) from shortly after birth until 34 weeks' post-menstrual age reduces the incidence of late-onset invasive infection (primary outcome), all-cause mortality, bronchopulmonary dysplasia, necrotising enterocolitis, retinopathy of prematurity, and the duration of antibiotic exposure, intensive care, and hospital admission. The trial is recruiting 2,200 participants from 37 neonatal care centres in the UK over 4 years. We will undertake an economic evaluation within the RCT to evaluate cost-effectiveness and provide an estimate of incremental costs for differences in the pre-specified outcomes in primary and subgroup analyses. If a statistically significant and clinically important effect on the primary outcome is detected, we will seek further funding and approval to assess the impact of enteral lactoferrin supplementation on rates of adverse neuro-developmental outcomes in the participating infants when they are 5 years old. © 2018 S. Karger AG, Basel.

PATCH: platelet transfusion in cerebral haemorrhage: study protocol for a multicentre, randomised, controlled trial.

PubMed

de Gans, Koen; de Haan, Rob J; Majoie, Charles B; Koopman, Maria M; Brand, Anneke; Dijkgraaf, Marcel G; Vermeulen, Marinus; Roos, Yvo B

2010-03-18

Patients suffering from intracerebral haemorrhage have a poor prognosis, especially if they are using antiplatelet therapy. Currently, no effective acute treatment option for intracerebral haemorrhage exists. Limiting the early growth of intracerebral haemorrhage volume which continues the first hours after admission seems a promising strategy. Because intracerebral haemorrhage patients who are on antiplatelet therapy have been shown to be particularly at risk of early haematoma growth, platelet transfusion may have a beneficial effect. The primary objective is to investigate whether platelet transfusion improves outcome in intracerebral haemorrhage patients who are on antiplatelet treatment. The PATCH study is a prospective, randomised, multi-centre study with open treatment and blind endpoint evaluation. Patients will be randomised to receive platelet transfusion within six hours or standard care. The primary endpoint is functional health after three months. The main secondary endpoints are safety of platelet transfusion and the occurrence of haematoma growth. To detect an absolute poor outcome reduction of 20%, a total of 190 patients will be included. To our knowledge this is the first randomised controlled trial of platelet transfusion for an acute haemorrhagic disease.

Multicentric Castleman Disease: Where are we now?

PubMed Central

Wang, Hao-Wei; Pittaluga, Stefania; Jaffe, Elaine S.

2016-01-01

Multicentric Castleman disease (MCD) encompasses a spectrum of conditions that give rise to overlapping clinicopathological manifestations. The fundamental pathogenetic mechanism involves dysregulated cytokine activity, which causes systemic inflammatory symptoms as well as lymphadenopathy. The histological changes in lymph nodes resemble in part the findings originally described in the unicentric forms Castleman disease, both hyaline vascular and plasma cell variants. In MCD caused by Kaposi sarcoma-associated herpesvirus/human herpesvirus-8 (KSHV/HHV8), the cytokine over activity is caused by viral products, which can also lead to atypical lymphoproliferations and potential progression to lymphoma. In cases negative for KSHV/HHV8, so-called idiopathic MCD, the hypercytokinemia can result from various mechanisms, which ultimately lead to different constellations of clinical presentations and varied pathology in lymphoid tissues. In this article, we review the evolving concepts and definitions of the various conditions under the eponym of Castleman disease, and summarize current knowledge regarding the histopathology and pathogenesis of lesions within the MCD spectrum. PMID:27296355

Doxycycline in the treatment of respiratory tract infections. Results of a pan-European multi-centre trial.

PubMed

Pestel, M

1975-01-01

In the winter of 1973-4, general practitioners from seven European countries took part in a multi-centre trial of doxycycline in the treatment of infections of the respiratory tract. The carefully designed protocol was observed by all participants. A total of 1,747 patients were admitted to the trial; their ages ranged from 6 years to over 80. The commonest diagnoses (50%) were acute bronchitis and acute exacerbations of chronic bronchitis. On the recommended dosage of 200 mg doxycycline on the first day, followed by 100 mg daily thereafter (though 200 mg could be continued daily in severe cases), 87% of patients achieved good or very good results. Both subjective (pain) and objective (sputum volume and viscosity, temperature, cough) measures showed rapid improvement, usually by the third to fifth days. Side-effects were minimal and mainly gastrointestinal and caused only 4 patients to discontinue treatment. Overall, doxycycline proved its effectiveness and rapidity of action.

Radiofrequency-induced thermal therapy: results of a European multicentre study of resistive ablation of incompetent truncal varicose veins.

PubMed

Braithwaite, B; Hnatek, L; Zierau, U; Camci, M; Akkersdijk, Gjm; Nio, D; Sarlija, M; Ajduk, M; Santoro, P; Roche, E

2013-02-01

To investigate the effectiveness of bipolar radiofrequency-induced thermal therapy (RFITT) in a multicentre non-randomized study. Some 672 incompetent saphenous veins (85% great saphenous varicose vein, 15% short saphenous vein) in 462 patients (56.5% CEAP [clinical, aetiological, anatomical and pathological elements] class 3 or worse) were treated in eight European centres. Patients were assessed between 180 and 360 days postoperatively. Occlusion rates were determined by duplex ultrasound and compared with the power used for treatment, pull back rate and experience of the operating surgeon. Complete occlusion rates of 98.4% were achieved when treatments were performed by an experienced operator (more than 20 cases), when the maximum power setting on the RFITT generator was between 18 and 20 W and the applicator was withdrawn at a rate slower than 1.5 second/cm RFITT is efficacious, well tolerated by patients and has a low incidence of procedure-related post-operative complications.

Performance of the TB-LAMP diagnostic assay in reference laboratories: Results from a multicentre study.

PubMed

Pham, Thu Hang; Peter, Jonathan; Mello, Fernanda C Q; Parraga, Tommy; Lan, Nguyen Thi Ngoc; Nabeta, Pamela; Valli, Eloise; Caceres, Tatiana; Dheda, Keertan; Dorman, Susan E; Hillemann, Doris; Gray, Christen M; Perkins, Mark D

2018-03-01

To evaluate the diagnostic performance of TB-LAMP, a manual molecular tuberculosis (TB) detection method, and provide comparison to the Xpert MTB/RIF assay. In a large multicentre study, two sputum samples were collected from participants with TB symptoms in reference laboratories in Peru, South Africa, Brazil, and Vietnam. Each sample was tested with TB-LAMP. The reference standard consisted of four direct smears, four cultures, and clinical and radiological findings. Individuals negative on conventional tests were followed up after 8 weeks. The Xpert MTB/RIF assay was performed on fresh or frozen samples as a molecular test comparison. A total of 1036 adults with suspected TB were enrolled. Among 375 culture-confirmed TB cases with 750 sputum samples, TB-LAMP detected 75.6% (95% confidence interval (CI) 71.8-79.4%), including 97.9% (95% CI 96.4-99.4%) of smear-positive TB samples and 46.6% (95% CI 40.6-52.7%) of smear-negative TB samples. Specificity in 477 culture-negative participants not treated for TB (954 sputum samples) was 98.7% (95% CI 97.9-99.6%). TB-LAMP test results were indeterminate in 0.3% of cases. TB-LAMP detects nearly all smear-positive and half of smear-negative TB cases and has a high specificity when performed in reference laboratories. Performance was similar to the Xpert MTB/RIF assay. Copyright © 2018 The Author(s). Published by Elsevier Ltd.. All rights reserved.

A hinting strategy for online learning of radiograph interpretation by medical students.

PubMed

Boutis, Kathy; Pecaric, Martin; Shiau, Maria; Ridley, Jane; P Gladding, Sophie; S Andrews, John; V Pusic, Martin

2013-09-01

We examined whether a 'hint' manoeuvre increases the time novice medical learners spend on reviewing a radiograph, thereby potentially increasing their interpretation accuracy. Senior year medical students were recruited into a randomised control, three-arm, multicentre trial. Students reviewed an online 50-case learning set that varied in degree of 'hint' intervention. The 'hint' was a dialogue box that appeared after a student submitted an answer, encouraging the student to re-evaluate their interpretation. The students in the control group received no hints. In the weak intervention group, students received 'hints' with 66% of their incorrect interpretations and 33% of those that were correct. In the strong intervention group, the incorrect interpretation hint frequency was 80%, whereas for correct responses it was 20%. All students completed a 20-case post-test immediately and 2 weeks after the 50 cases. The primary outcome was student performance on the immediate post-test, measured as the ability to discriminate between normal and abnormal films (dPrime). Secondary outcomes included the probability of considering the hint, time spent on learning cases and knowledge retention at 2 weeks. We enrolled 117 medical students from three sites into the three study groups: control (36), weak intervention (40) and strong intervention (41) groups. The mean (standard deviation) dPrime in the control, weak and strong groups were 0.4 (1.1), 0.7 (1.1) and 0.4 (0.9), respectively (P = 0.4). In the weak and strong groups, participants reconsidered answers in 556 of 1944 (28.6%) hinting opportunities, and those who reconsidered their answers spent a mean (95% confidence interval) of 13.9 (11.9, 16.0) seconds longer on each case. There were no significant differences in knowledge retention at 2 weeks between the groups (P = 0.2). Although the implemented hinting strategy did result in students spending more time considering a proportion of the cases, overall it was not effective in improving student performance. © John Wiley & Sons Ltd.

Treatment of canine parvoviral enteritis with interferon-omega in a placebo-controlled field trial.

PubMed

de Mari, K; Maynard, L; Eun, H M; Lebreux, B

2003-01-25

The clinical efficacy of a recombinant feline interferon (IFN) (type omega) was evaluated under field conditions for the treatment of dogs with parvoviral enteritis. In this multicentric, double-blind, placebo-controlled trial, 94 dogs from one to 28 months old were randomly assigned to two groups which were treated intravenously either with IFN (2.5 million units/kg) or placebo once a day for three consecutive days, and monitored for clinical signs and mortality for 10 days. Each dog received individual supportive treatment The data from 92 interpretable cases (43 IFN-treated and 49 placebo) showed that the clinical signs of the IFN-treated animals improved significantly in comparison with the control animals, and that there were only three deaths in the IFN group compared with 14 deaths in the placebo group (P = 0.0096) corresponding to a 4.4-fold reduction. Alternative analyses of the data taking into account the prior vaccination status of the dogs against canine parvovirus suggested that the IFN therapy resulted in a 6.4-fold reduction in mortality (P = 0.044) in the unvaccinated cohort, a significant reduction when compared with the vaccinated cohort.

Multicentric intraepithelial neoplasia involving the vulva. Clinical features and association with human papillomavirus and herpes simplex virus.

PubMed

Bornstein, J; Kaufman, R H; Adam, E; Adler-Storthz, K

1988-10-15

Sixteen of 46 patients (35%) with Grade 3 vulvar intraepithelial neoplasia (VIN 3) were found to have an additional site of lower genital tract squamous cell neoplasia, primarily in the cervix. The frequency of multicentricity decreased significantly with age. In addition, patients with multicentric disease (involving the vagina and/or cervix in addition to the vulva) had a significantly higher frequency of multifocal disease involving the vulva (involving more than one location on the vulva) and of recurrence than patients without multicentric disease. Human papillomavirus (HPV) DNA was detected by in situ hybridization in 81% of the women with multicentric squamous cell neoplasia. No significant difference was noticed between patients with multicentric and unicentric squamous cell neoplasia in the detection rate of papillomavirus antigen, HPV DNA, the various HPV types, herpes simplex virus Type 2 (HSV2)-related antigen, type-specific antibodies to HSV, and dual HPV and HSV2 infections. These findings suggest that HPV and HSV2, although strongly associated with VIN 3, do not influence the development pattern of squamous cell neoplasia, and that all patients with VIN 3, especially if they are younger than 50 years of age, should be evaluated periodically for additional centers of lower genital tract squamous cell neoplasia.

Intracavitary irradiation of renal pyelocalyceal transitional cell carcinoma with iridium-192

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

Kadish, S.P.; Danford, R.; Felton, L.M.

1981-11-01

A case of multicentric urothelial transitional cell carcinoma is presented, in which the patient underwent a left ureteronephrectomy and in the remaining right kidney recurrent transitional cell carcinoma was found in the inferior calyx. Because this area was accessible via a cutaneous nephrostomy, it is treated with a combination of external beam radiation and intracavitary implantation with iridium-192. The iridium was placed in the vicinity of the tumor using an angiographic procedure. The technique successfully preserved remaining renal parenchyma. The case illustrates how angiography skills and procedures can be applied in a novel brachytherapy application.

Does sensory relearning improve tactile function after carpal tunnel decompression? A pragmatic, assessor-blinded, randomized clinical trial

PubMed Central

Jerosch-Herold, C.; Houghton, J.; Miller, L.; Shepstone, L.

2016-01-01

Despite surgery for carpal tunnel syndrome being effective in 80%–90% of cases, chronic numbness and hand disability can occur. The aim of this study was to investigate whether sensory relearning improves tactile discrimination and hand function after decompression. In a multi-centre, pragmatic, randomized, controlled trial, 104 patients were randomized to a sensory relearning (n = 52) or control (n = 52) group. A total of 93 patients completed a 12-week follow-up. Primary outcome was the shape-texture identification test at 6 weeks. Secondary outcomes were touch threshold, touch localization, dexterity and self-reported hand function. No significant group differences were seen for the primary outcome (Shape-Texture Identification) at 6 weeks or 12 weeks. Similarly, no significant group differences were observed on secondary outcomes, with the exception of self-reported hand function. A secondary complier-averaged-causal-effects analysis showed no statistically significant treatment effect on the primary outcome. Sensory relearning for tactile sensory and functional deficits after carpal tunnel decompression is not effective. Level of Evidence: II PMID:27402282

Synchronic nasopharyngeal and intraparotid warthin tumors: A case report and literature review

PubMed Central

Domínguez-Malagon, Hugo-Ricardo; Mosqueda-Taylor, Adalberto; Cano-Valdez, Ana-María; Luna-Ortiz, Kuauhyama

2014-01-01

Warthin tumor is the second most frequent benign salivary gland tumor after pleomorphic adenoma; it occurs almost exclusively in the parotid gland and peri-parotideal lymph nodes, although it may rarely present in other locations. It may be multicentric and bilateral in a small percentage of cases. Nasopharyngeal Warthin tumor is very rare, and the presence of a synchronic WT involving nasopharynx and parotid is an exceptional event, as it has been described only twice in the literature. In this article we report an additional case of a synchronic Warthin tumor and review the related literature. Key words:Warthin tumor, synchronic WT, multicéntrico, nasopharynx. PMID:25593670

Risk factors for rectal lymphogranuloma venereum in gay men: results of a multicentre case-control study in the U.K.

PubMed

Macdonald, N; Sullivan, A K; French, P; White, J A; Dean, G; Smith, A; Winter, A J; Alexander, S; Ison, C; Ward, H

2014-06-01

To identify risk factors for rectal lymphogranuloma venereum (rLGV) in men who have sex with men (MSM). A case-control study at 6 U.K. hospitals compared MSM with rLGV (cases) with rLGV-negative controls: MSM without potential rLGV symptoms (CGa) and separately, MSM with such symptoms (CGs). Between 2008 and 2010, there were 90 rLGV cases, 74 CGa and 69 CGs recruited. Lifestyles and sexual behaviours in the previous 3 months were reported using internet-based computer-assisted self-interviews. Logistic regression was used to investigate factors associated with rLGV. Cases were significantly more likely to be HIV-positive (89%) compared with CGa (46%) and CGs (64%). Independent behavioural risks for rLGV were: unprotected receptive anal intercourse (adjusted OR (AOR)10.7, 95% CI 3.5 to 32.8), fisting another (AOR=6.7, CI 1.8 to 25.3), sex under the influence of gamma-hydroxybutyrate (AOR=3.1, CI 1.3 to 7.4) and anonymous sexual contacts (AOR=2.7, CI 1.2 to 6.3), compared with CGa; unprotected insertive anal intercourse (AOR=4.7, CI 2.0 to 10.9) and rectal douching (AOR=2.9 CI 1.3 to 6.6), compared with CGs. An incubation period from exposure to symptoms of 30 days was indicated. Unprotected receptive anal intercourse is a key risk factor for rectal LGV with the likelihood that rectal-to-rectal transmission is facilitated where insertive anal sex also occurs. The association between HIV and rLGV appears linked to HIV-positive men seeking unprotected sex with others with the same HIV status, sexual and drug interests. Such men should be targeted for frequent STI screening and interventions to minimise associated risks. 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.

Risk factors for rectal lymphogranuloma venereum in gay men: results of a multicentre case-control study in the UK

PubMed Central

Macdonald, N; Sullivan, A K; French, P; White, J A; Dean, G; Smith, A; Winter, A J; Alexander, S; Ison, C; Ward, H

2014-01-01

Objective To identify risk factors for rectal lymphogranuloma venereum (rLGV) in men who have sex with men (MSM). Design A case-control study at 6 UK hospitals compared MSM with rLGV (cases) with rLGV-negative controls: MSM without potential rLGV symptoms (CGa) and separately, MSM with such symptoms (CGs). Methods Between 2008 and 2010, there were 90 rLGV cases, 74 CGa and 69 CGs recruited. Lifestyles and sexual behaviours in the previous 3 months were reported using internet-based computer-assisted self-interviews. Logistic regression was used to investigate factors associated with rLGV. Results Cases were significantly more likely to be HIV-positive (89%) compared with CGa (46%) and CGs (64%). Independent behavioural risks for rLGV were: unprotected receptive anal intercourse (adjusted OR (AOR)10.7, 95% CI 3.5 to 32.8), fisting another (AOR=6.7, CI 1.8 to 25.3), sex under the influence of gamma-hydroxybutyrate (AOR=3.1, CI 1.3 to 7.4) and anonymous sexual contacts (AOR=2.7, CI 1.2 to 6.3), compared with CGa; unprotected insertive anal intercourse (AOR=4.7, CI 2.0 to 10.9) and rectal douching (AOR=2.9 CI 1.3 to 6.6), compared with CGs. An incubation period from exposure to symptoms of 30 days was indicated. Conclusions Unprotected receptive anal intercourse is a key risk factor for rectal LGV with the likelihood that rectal-to-rectal transmission is facilitated where insertive anal sex also occurs. The association between HIV and rLGV appears linked to HIV-positive men seeking unprotected sex with others with the same HIV status, sexual and drug interests. Such men should be targeted for frequent STI screening and interventions to minimise associated risks. PMID:24493859

Securing All intraVenous devices Effectively in hospitalised patients--the SAVE trial: study protocol for a multicentre randomised controlled trial.

PubMed

Rickard, Claire M; Marsh, Nicole; Webster, Joan; Playford, E Geoffrey; McGrail, Matthew R; Larsen, Emily; Keogh, Samantha; McMillan, David; Whitty, Jennifer A; Choudhury, Md Abu; Dunster, Kimble R; Reynolds, Heather; Marshall, Andrea; Crilly, Julia; Young, Jeanine; Thom, Ogilvie; Gowardman, John; Corley, Amanda; Fraser, John F

2015-09-23

Over 70% of all hospital admissions have a peripheral intravenous device (PIV) inserted; however, the failure rate of PIVs is unacceptably high, with up to 69% of these devices failing before treatment is complete. Failure can be due to dislodgement, phlebitis, occlusion/infiltration and/or infection. This results in interrupted medical therapy; painful phlebitis and reinsertions; increased hospital length of stay, morbidity and mortality from infections; and wasted medical/nursing time. Appropriate PIV dressing and securement may prevent many cases of PIV failure, but little comparative data exist regarding the efficacy of various PIV dressing and securement methods. This trial will investigate the clinical and cost-effectiveness of 4 methods of PIV dressing and securement in preventing PIV failure. A multicentre, parallel group, superiority randomised controlled trial with 4 arms, 3 experimental groups (tissue adhesive, bordered polyurethane dressing, sutureless securement device) and 1 control (standard polyurethane dressing) is planned. There will be a 3-year recruitment of 1708 adult patients, with allocation concealment until randomisation by a centralised web-based service. The primary outcome is PIV failure which includes any of: dislodgement, occlusion/infiltration, phlebitis and infection. Secondary outcomes include: types of PIV failure, PIV dwell time, costs, device colonisation, skin colonisation, patient and staff satisfaction. Relative incidence rates of device failure per 100 devices and per 1000 device days with 95% CIs will summarise the impact of each dressing, and test differences between groups. Kaplan-Meier survival curves (with log-rank Mantel-Cox test) will compare device failure over time. p Values of <0.05 will be considered significant. Secondary end points will be compared between groups using parametric or non-parametric techniques appropriate to level of measurement. Ethical approval has been received from Queensland Health (HREC/11/QRCH/152) and Griffith University (NRS/46/11/HREC). Results will be published according to the CONSORT statement and presented at relevant conferences. Australian New Zealand Clinical Trial Registry (ACTRN); 12611000769987. 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.

Securing All intraVenous devices Effectively in hospitalised patients—the SAVE trial: study protocol for a multicentre randomised controlled trial

PubMed Central

Rickard, Claire M; Marsh, Nicole; Webster, Joan; Playford, E Geoffrey; McGrail, Matthew R; Larsen, Emily; Keogh, Samantha; McMillan, David; Whitty, Jennifer A; Choudhury, Md Abu; Dunster, Kimble R; Reynolds, Heather; Marshall, Andrea; Crilly, Julia; Young, Jeanine; Thom, Ogilvie; Gowardman, John; Corley, Amanda; Fraser, John F

2015-01-01

Introduction Over 70% of all hospital admissions have a peripheral intravenous device (PIV) inserted; however, the failure rate of PIVs is unacceptably high, with up to 69% of these devices failing before treatment is complete. Failure can be due to dislodgement, phlebitis, occlusion/infiltration and/or infection. This results in interrupted medical therapy; painful phlebitis and reinsertions; increased hospital length of stay, morbidity and mortality from infections; and wasted medical/nursing time. Appropriate PIV dressing and securement may prevent many cases of PIV failure, but little comparative data exist regarding the efficacy of various PIV dressing and securement methods. This trial will investigate the clinical and cost-effectiveness of 4 methods of PIV dressing and securement in preventing PIV failure. Methods and analysis A multicentre, parallel group, superiority randomised controlled trial with 4 arms, 3 experimental groups (tissue adhesive, bordered polyurethane dressing, sutureless securement device) and 1 control (standard polyurethane dressing) is planned. There will be a 3-year recruitment of 1708 adult patients, with allocation concealment until randomisation by a centralised web-based service. The primary outcome is PIV failure which includes any of: dislodgement, occlusion/infiltration, phlebitis and infection. Secondary outcomes include: types of PIV failure, PIV dwell time, costs, device colonisation, skin colonisation, patient and staff satisfaction. Relative incidence rates of device failure per 100 devices and per 1000 device days with 95% CIs will summarise the impact of each dressing, and test differences between groups. Kaplan-Meier survival curves (with log-rank Mantel-Cox test) will compare device failure over time. p Values of <0.05 will be considered significant. Secondary end points will be compared between groups using parametric or non-parametric techniques appropriate to level of measurement. Ethics and dissemination Ethical approval has been received from Queensland Health (HREC/11/QRCH/152) and Griffith University (NRS/46/11/HREC). Results will be published according to the CONSORT statement and presented at relevant conferences. Trial registration number Australian New Zealand Clinical Trial Registry (ACTRN); 12611000769987. PMID:26399574

DupuytrEn Treatment EffeCtiveness Trial (DETECT): a protocol for prospective, randomised, controlled, outcome assessor-blinded, three-armed parallel 1:1:1, multicentre trial comparing the effectiveness and cost of collagenase clostridium histolyticum, percutaneous needle fasciotomy and limited fasciectomy as short-term and long-term treatment strategies in Dupuytren's contracture.

PubMed

Räisänen, Mikko P; Karjalainen, Teemu; Göransson, Harry; Reito, Aleksi; Kautiainen, Hannu; Malmivaara, Antti; Leppänen, Olli V

2018-03-28

Dupuytren's contracture (DC) is a chronic fibroproliferative disorder of the palmar fascia which leads to flexion contracture in one or more fingers. There is no definitive cure for DC, and treatment aims at relieving symptoms by releasing the contracture using percutaneous or operative techniques. We planned a prospective, randomised, controlled, outcome assessor-blinded, three-armed parallel 1:1:1, multicentre trial comparing the effectiveness and cost of (1) collagenase clostridium histolyticum injection followed by limited fasciectomy in non-responsive cases, (2) percutaneous needle fasciotomy followed by limited fasciectomy in non-responsive cases and (3) primary limited fasciectomy during short-term and long-term follow-up for Tubiana I-III stages DC. We will recruit participants from seven national centres in Finland. Primary outcome is the rate of success in the treatment arm at 5 years after recruitment. Success is a composite outcome comprising (1) at least 50% contracture release from the date of recruitment and (2) participants in a patient-accepted symptom state (PASS). Secondary outcomes are (1) angle of contracture, (2) quick disabilities of the arm, a shoulder and hand outcome measure (QuickDASH), (3) perceived hand function, (4) EQ-5D-3L, (5) rate of major adverse events, (6) patient's trust of the treatment, (7) global rating, (8) rate of PASS, (9) rate of minimal clinically important improvement, (10) expenses, (11) progression of disease, (12) progression-free survival, (13) favoured treatment modality, (14) patients achieving full contracture release and >50% improvement and (15) patient satisfaction with the treatment effect. Predictive factors for achieving the PASS will also be analysed. The protocol was approved by the Tampere University Hospital Institutional Review Board and Finnish Medicine Agency. The study will be performed according to the principles of good clinical practice. The results of the trial will be disseminated as published articles in peer-reviewed journals. NCT03192020; Pre-results. © 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.

Early-life hygiene-related factors affect risk of central nervous system demyelination and asthma differentially

PubMed Central

Hughes, A-M; Lucas, R M; McMichael, A J; Dwyer, T; Pender, M P; Mei, I; Taylor, B V; Valery, P; Chapman, C; Coulthard, A; Dear, K; Kilpatrick, T J; Williams, D; Ponsonby, A-L

2013-01-01

The increasing prevalence of immune-related diseases, including multiple sclerosis, may be partly explained by reduced microbial burden during childhood. Within a multi-centre case–control study population, we examined: (i) the co-morbid immune diseases profile of adults with a first clinical diagnosis of central nervous system demyelination (FCD) and (ii) sibship structure in relation to an autoimmune (FCD) and an allergic (asthma) disease. FCD cases (n = 282) were aged 18–59 years; controls (n = 558) were matched on age, sex and region. Measures include: history of doctor-diagnosed asthma; sibling profile (number; dates of birth); and regular childcare attendance. FCD cases did not differ from controls with regard to personal or family history of allergy, but had a greater likelihood of chronic fatigue syndrome [odds ratio (OR) = 3·11; 95% confidence interval (CI) 1·11, 8·71]. Having any younger siblings showed reduced odds of FCD (OR = 0·68; 95% CI: 0·49, 0·95) but not asthma (OR = 1·47; 95% CI: 0·91, 2·38). In contrast, an increasing number of older siblings was associated with reduced risk of asthma (P trend = 0·04) but not FCD (P trend = 0·66). Allergies were not over-represented among people presenting with FCD. Sibship characteristics influence both FCD and asthma risk but the underlying mechanisms differ, possibly due to the timing of the putative ‘sibling effect’. PMID:23600835

Clinical and cost effectiveness of mobile phone supported self monitoring of asthma: multicentre randomised controlled trial.

PubMed

Ryan, Dermot; Price, David; Musgrave, Stan D; Malhotra, Shweta; Lee, Amanda J; Ayansina, Dolapo; Sheikh, Aziz; Tarassenko, Lionel; Pagliari, Claudia; Pinnock, Hilary

2012-03-23

To determine whether mobile phone based monitoring improves asthma control compared with standard paper based monitoring strategies. Multicentre randomised controlled trial with cost effectiveness analysis. UK primary care. 288 adolescents and adults with poorly controlled asthma (asthma control questionnaire (ACQ) score ≥ 1.5) from 32 practices. Participants were centrally randomised to twice daily recording and mobile phone based transmission of symptoms, drug use, and peak flow with immediate feedback prompting action according to an agreed plan or paper based monitoring. Changes in scores on asthma control questionnaire and self efficacy (knowledge, attitude, and self efficacy asthma questionnaire (KASE-AQ)) at six months after randomisation. Assessment of outcomes was blinded. Analysis was on an intention to treat basis. There was no significant difference in the change in asthma control or self efficacy between the two groups (ACQ: mean change 0.75 in mobile group v 0.73 in paper group, mean difference in change -0.02 (95% confidence interval -0.23 to 0.19); KASE-AQ score: mean change -4.4 v -2.4, mean difference 2.0 (-0.3 to 4.2)). The numbers of patients who had acute exacerbations, steroid courses, and unscheduled consultations were similar in both groups, with similar healthcare costs. Overall, the mobile phone service was more expensive because of the expenses of telemonitoring. Mobile technology does not improve asthma control or increase self efficacy compared with paper based monitoring when both groups received clinical care to guidelines standards. The mobile technology was not cost effective. Clinical Trials NCT00512837.

Immunotherapy safety: a prospective multi-centric monitoring study of biologically standardized therapeutic vaccines for allergic diseases.

PubMed

Moreno, C; Cuesta-Herranz, J; Fernández-Távora, L; Alvarez-Cuesta, E

2004-04-01

The fear of side-effects has led to strict regulations preventing a more widespread use of specific immunotherapy (SIT) in some countries, in spite of the low risk of systemic reactions (SRs) reported in well-controlled studies. The goal of the study was to carry out a prospective and multi-centric trial to evaluate the safety, risk factors and compliance degree of commercially available SIT. The study was carried out in 14 allergy departments from Spain. Four-hundred and eighty-eight patients with rhinitis and/or asthma were submitted to treatment with biologically standardized allergen extracts commercially available. They were administered following the European Academy of Allergy and Clinical Immunology guidelines. Four hundred and twenty-three patients (86.7%) completed the treatment and remained under control at the end of the trial. Out of 17,526 administered doses, 17,368 doses (99.1%) were not associated with a reaction. Eighteen patients (3.7%) experienced 53 (0.3% of the doses) SRs. All immediate SRs were mild or moderate and responded well to ordinary treatment measures. There were no fatal reactions, anaphylactic shock or life-threatening reactions. A higher ratio of SRs was found among asthmatic and dust mite allergic patients, although multi-variable logistic analysis did not demonstrate any risk factor associated with SRs. There was also a subgroup of patients at risk for recurrent reactions, and therefore 40% of SRs had been avoided if the maximal number of SRs had been previously limited to only three SRs. This multi-centric study showed that SIT was a safe treatment with a very good compliance. Future guidelines of SIT should limit the maximal number of SRs.

Efficacy of a standardized herbal preparation (Roidosanal®) in the treatment of hemorrhoids: A randomized, controlled, open-label multicentre study

PubMed Central

Aggrawal, Kapil; Satija, Naveen; Dasgupta, Gita; Dasgupta, Partha; Nain, Parul; Sahu, Aditya R.

2014-01-01

Background: Catechins and epicatechins are monomers of naturally occurring proanthocyanidins, which have been reported with free radical scavenging, antioxidant, antiinflammatory, antiallergic, and vasodilatory properties. Plant parts rich in proanthocyanidins have been used for years in treatment of various ano-rectal diseases. This study compares the efficacy of two herbal preparations, Daflon® 500 mg and Roidosanal®, in ameliorating the signs and symptoms associated with hemorrhoids. Objective: To evaluate the safety and to compare the efficacy of a herbal preparation, Roidosanal® versus Daflon® 500 mg, on signs and symptoms of hemorrhoidal disease. Materials and Methods: In this pilot, active controlled, open-labeled multicentre study, 73 patients with proctoscopy proven hemorrhoids (Grade I to III) were randomly assigned to receive either Roidosanal® (Gr R; n = 37) or Daflon® 500 mg (Gr D; n = 36), for 15 days, at three centers in India. Assessment of hemorrhoidal symptoms was carried out in all patients at different time points. Intent-to-treat analysis was performed for both primary and secondary endpoints. Results: Baseline characteristics were comparable between the two groups. Both products were found to be equally effective in improving the ano-rectal conditions in Grade I and Grade II hemorrhoids; however, Roidosanal® demonstrated better efficacy in patients with Grade III hemorrhoids. Hemorrhoids associated symptoms like bleeding, pain, etc., improved in both groups, although intergroup comparisons were comparable. Conclusion: Both Roidosanal® and Daflon® 500 mg were equally effective in resolving signs and symptoms of hemorrhoids. Roidosanal® can be tried as a safe and effective treatment option for treatment of hemorrhoids. Further randomized, double-blind and large multicentre studies are recommended. PMID:24948863

Involving older people in a multi-centre randomised trial of a complex intervention in pre-hospital emergency care: implementation of a collaborative model.

PubMed

Koniotou, Marina; Evans, Bridie Angela; Chatters, Robin; Fothergill, Rachael; Garnsworthy, Christopher; Gaze, Sarah; Halter, Mary; Mason, Suzanne; Peconi, Julie; Porter, Alison; Siriwardena, A Niroshan; Toghill, Alun; Snooks, Helen

2015-07-10

Health services research is expected to involve service users as active partners in the research process, but few examples report how this has been achieved in practice in trials. We implemented a model to involve service users in a multi-centre randomised controlled trial in pre-hospital emergency care. We used the generic Standard Operating Procedure (SOP) from our Clinical Trials Unit (CTU) as the basis for creating a model to fit the context and population of the SAFER 2 trial. In our model, we planned to involve service users at all stages in the trial through decision-making forums at 3 levels: 1) strategic; 2) site (e.g. Wales; London; East Midlands); 3) local. We linked with charities and community groups to recruit people with experience of our study population. We collected notes of meetings alongside other documentary evidence such as attendance records and study documentation to track how we implemented our model. We involved service users at strategic, site and local level. We also added additional strategic level forums (Task and Finish Groups and Writing Days) where we included service users. Service user involvement varied in frequency and type across meetings, research stages and locations but stabilised and increased as the trial progressed. Involving service users in the SAFER 2 trial showed how it is feasible and achievable for patients, carers and potential patients sharing the demographic characteristics of our study population to collaborate in a multi-centre trial at the level which suited their health, location, skills and expertise. A standard model of involvement can be tailored by adopting a flexible approach to take account of the context and complexities of a multi-site trial. Current Controlled Trials ISRCTN60481756. Registered: 13 March 2009.

Genetic ancestry is associated with colorectal adenomas and adenocarcinomas in Latino populations.

PubMed

Hernandez-Suarez, Gustavo; Sanabria, Maria Carolina; Serrano, Marta; Herran, Oscar F; Perez, Jesus; Plata, Jose L; Zabaleta, Jovanny; Tenesa, Albert

2014-10-01

Colorectal cancer rates in Latin American countries are less than half of those observed in the United States. Latin Americans are the resultant of generations of an admixture of Native American, European, and African individuals. The potential role of genetic admixture in colorectal carcinogenesis has not been examined. We evaluate the association of genetic ancestry with colorectal neoplasms in 190 adenocarcinomas, 113 sporadic adenomas and 243 age- and sex-matched controls enrolled in a multicentric case-control study in Colombia. Individual ancestral genetic fractions were estimated using the STRUCTURE software, based on allele frequencies and assuming three distinct population origins. We used the Illumina Cancer Panel to genotype 1,421 sparse single-nucleotide polymorphisms (SNPs), and Northern and Western European ancestry, LWJ and Han Chinese in Beijing, China populations from the HapMap project as references. A total of 678 autosomal SNPs overlapped with the HapMap data set SNPs and were used for ancestry estimations. African mean ancestry fraction was higher in adenomas (0.13, 95% confidence interval (95% CI)=0.11-0.15) and cancer cases (0.14, 95% CI=0.12-0.16) compared with controls (0.11, 95% CI=0.10-0.12). Conditional logistic regression analysis, controlling for known risk factors, showed a positive association of African ancestry per 10% increase with both colorectal adenoma (odds ratio (OR)=1.12, 95% CI=0.97-1.30) and adenocarcinoma (OR=1.19, 95% CI=1.05-1.35). In conclusion, increased African ancestry (or variants linked to it) contributes to the increased susceptibility of colorectal cancer in admixed Latin American population.

Genetic association between the phospholipase A2 gene and unipolar affective disorder: a multicentre case-control study.

PubMed

Papadimitriou, George N; Dikeos, Dimitris G; Souery, Daniel; Del-Favero, Jurgen; Massat, Isabelle; Avramopoulos, Dimitrios; Blairy, Sylvie; Cichon, Sven; Ivezic, Sladjana; Kaneva, Radka; Karadima, Georgia; Lilli, Roberta; Milanova, Vihra; Nöthen, Markus; Oruc, Lilijana; Rietschel, Marcella; Serretti, Alessandro; Van Broeckhoven, Christine; Stefanis, Costas N; Mendlewicz, Julien

2003-12-01

The co-segregation in one pedigree of bipolar affective disorder with Darier's disease whose gene is on chromosome 12q23-q24.1, and findings from linkage and association studies with the neighbouring gene of phospholipase A2 (PLA2) indicate that PLA2 may be considered as a candidate gene for affective disorders. All relevant genetic association studies, however, were conducted on bipolar patients. In the present study, the possible association between the PLA2 gene and unipolar affective disorder was examined on 321 unipolar patients and 604 controls (all personally interviewed), recruited from six countries (Belgium, Bulgaria, Croatia, Germany, Greece, and Italy) participating in the European Collaborative Project on Affective Disorders. After controlling for population group and gender, one of the eight alleles of the investigated marker (allele 7) was found to be more frequent among unipolar patients with more than three major depressive episodes than among controls (P<0.01); genotypic association was also observed, under the dominant model of genetic transmission (P<0.02). In addition, presence of allele 7 was correlated with a higher frequency of depressive episodes (P<0.02). These findings suggest that structural variations at the PLA2 gene or the chromosomal region around it may confer susceptibility for unipolar affective disorder.

Glomus Tumor of the Larynx: A Rare Synchronous Paraganglioma in a Patient with Bilateral Carotid Body Tumor Detected on 68Ga-DOTANOC PET/CT.

PubMed

Tripathy, Sarthak; Mukherjee, Anirban; Singh, Chirom A; Jat, Bhinyaram; Bal, Chandrasekhar; Shamim, Shamim Ahmed

2017-01-01

Paragangliomas are neoplasms arising from extra-adrenal chromaffin tissue. They frequently cause symptoms by overproduction of catecholamines with known predilection to multicentricity. We describe the case of a patient with bilateral carotid body tumor who underwent a baseline 68 Gallium labeled [1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid]-1-NaI3-Octreotide.

Glomus Tumor of the Larynx: A Rare Synchronous Paraganglioma in a Patient with Bilateral Carotid Body Tumor Detected on 68Ga-DOTANOC PET/CT

PubMed Central

Tripathy, Sarthak; Mukherjee, Anirban; Singh, Chirom A; Jat, Bhinyaram; Bal, Chandrasekhar; Shamim, Shamim Ahmed

2017-01-01

Paragangliomas are neoplasms arising from extra-adrenal chromaffin tissue. They frequently cause symptoms by overproduction of catecholamines with known predilection to multicentricity. We describe the case of a patient with bilateral carotid body tumor who underwent a baseline 68 Gallium labeled [1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid]-1-NaI3-Octreotide PMID:28680217

Osteoblastic and fibroblastic multicentric osteosarcoma

PubMed Central

Cabello, Raúl Romero; Sánchez, Carlos J.; Padilla, Marco A. Duran; De la Garza Navarro, José M.; Feregrino, Raul Romero; Vázquez, Avissai Alcántara; González, Mercedes Hernández; Feregrino, Rodrigo Romero

2011-01-01

Bone sarcomas are uncommon tumours, of which osteosarcoma is the least rare, as well as the third most common malignant tumour in childhood, appearing usually between the 10 and 20 years of age. The case the authors present in this work is of a patient suffering from a long-standing condition encompassing skin and soft tissue lesions. After multiple medical treatments, the patient was diagnosed with squamous osteosarcoma, which required aggressive surgical management and chemotherapy. PMID:22674697

Is ultraviolet exposure acquired at work the most important risk factor for cutaneous squamous cell carcinoma? Results of the population-based case-control study FB-181.

PubMed

Schmitt, J; Haufe, E; Trautmann, F; Schulze, H-J; Elsner, P; Drexler, H; Bauer, A; Letzel, S; John, S M; Fartasch, M; Brüning, T; Seidler, A; Dugas-Breit, S; Gina, M; Weistenhöfer, W; Bachmann, K; Bruhn, I; Lang, B M; Bonness, S; Allam, J P; Grobe, W; Stange, T; Westerhausen, S; Knuschke, P; Wittlich, M; Diepgen, T L

2018-02-01

Squamous cell carcinoma (SCC) is one of the most frequent types of cancer constituting a significant public health burden. Prevention strategies focus on limiting ultraviolet (UV) exposure during leisure time. However, the relative impact of occupational and nonoccupational UV exposure for SCC occurrence is unclear. To investigate the association between occupational and nonoccupational UV exposure for SCC in a multicentre population-based case-control study hypothesizing that high occupational UV exposure increases the risk of SCC. Consecutive patients with incident SCC (n = 632) were recruited from a German national dermatology network. Population-based controls (n = 996) without history of skin cancer were recruited from corresponding residents' registration offices and propensity score matched to cases. Lifetime UV exposure, sociodemographic and clinical characteristics were assessed by trained physicians. Occupational and nonoccupational UV exposure doses were estimated by masked investigators using established reference values. Odds ratios (ORs) and corresponding 95% confidence intervals (CIs) were assessed using conditional logistic regression adjusting for relevant confounders. Total solar UV exposure was significantly associated with increased SCC. The OR for high (> 90th percentile) vs. low (< 40th percentile) and high vs, moderate (40-59th percentile) occupational UV exposure was 1·95 (95% CI 1·19-3·18) and 2·44 (95% CI 1·47-4·06) for SCC. Adjusting for occupational UV exposure, nonoccupational UV exposure was not significantly related to SCC incidence. Dose-response relationships were observed for occupational but not for nonoccupational solar UV exposure. Solar occupational UV exposure is a major determinant of incident SCC. Our findings indicate that prevention strategies should be further expanded to the occupational setting. © 2017 British Association of Dermatologists.

Association Between Androgenetic Alopecia and Coronary Artery Disease in Young Male Patients

PubMed Central

Sharma, Kamal H; Jindal, Anchal

2014-01-01

Background: Several studies have demonstrated an association between androgenetic alopecia (AGA) and cardiovascular disease. Still controversies exist regarding the association. Are they truly associated? Objective: The purpose of the present study was to assess the prevalence of AGA and establish its association in young (<45 years) Asian Indian Gujarati male patients having coronary artery disease (CAD). Materials and Methods: Case-control prospective multicentric study was carried out on 424 men. Case group consisted of 212 male subjects having CAD (Group 1) and another 212, either sibling or first degree male relative of the case subjects (having no evidence of CAD) were considered as the control group (Group 2). Age, total cholesterol, incidence of diabetes mellitus, and hypertension were similar in both groups. The degree of alopecia was assessed using the Norwood-Hamilton scale for men. Statistical analysis was performed using Chi-square test. Results: AGA was found in 80 (37.73%) young CAD patients (Group 1), whereas 44 (20.7%) of patients had alopecia in the control group (Group 2). There was statistically significant association between male AGA and CAD (P = 0.001). Odds ratio was 2.70 (95% confidence interval [CI], 1.72 ± 4.26). Statistically significant association was found between high grade baldness (Grades IV-VII) and CAD in young men (P < 0.05). Odds ratio = 2.36 (95% CI, 1.108 ± 5.033). There is statistically significant association of AGA in young Asian Gujarati male with CAD and the prevalence of AGA in young CAD patient is 37.73%. Conclusion: This study implies early onset AGA in male is independently associated with CAD, though mechanisms need to be investigated. PMID:25114445

Occupational risk factors for renal cell carcinoma: agent-specific results from a case-control study in Germany. MURC Study Group. Multicenter urothelial and renal cancer study.

PubMed

Pesch, B; Haerting, J; Ranft, U; Klimpel, A; Oelschlägel, B; Schill, W

2000-12-01

This case-control study was conducted to estimate the renal cell cancer (RCC) risk for exposure to occupation-related agents, besides other suspected risk factors. In a population-based multicentre study, 935 incident RCC cases and 4298 controls matched for region, sex, and age were interviewed between 1991 and 1995 for their occupational history and lifestyle habits. Agent-specific exposure was expert-rated with two job-exposure matrices and a job task-exposure matrix. Conditional logistic regression was used to calculate smoking adjusted odds ratios (OR). Very long exposures in the chemical, rubber, and printing industries were associated with risk for RCC. Males considered as 'substantially exposed to organic solvents' showed a significant excess risk (OR = 1.6, 95% CI : 1.1-2.3). In females substantial exposure to solvents was also a significant risk factor (OR = 2.1, 95% CI : 1.0-4.4). Excess risks were shown for high exposure to cadmium (OR = 1.4, 95% CI : 1.1-1.8, in men, OR = 2.5, 95% CI : 1.2-5.3 in women), for substantial exposure to lead (OR = 1.5, 95% CI : 1.0-2.3, in men, OR = 2.6, 95% CI : 1.2-5.5, in women) and to solder fumes (OR = 1.5, 95% CI : 1.0-2.4, in men). In females, an excess risk for the task 'soldering, welding, milling' was found (OR = 3.0, 95% CI : 1.1-7.8). Exposure to paints, mineral oils, cutting fluids, benzene, polycyclic aromatic hydrocarbons, and asbestos showed an association with RCC development. Our results indicate that substantial exposure to metals and solvents may be nephrocarcinogenic. There is evidence for a gender-specific susceptibility of the kidneys.

Coffee and tea consumption and risk of leukaemia in an adult population: A reanalysis of the Italian multicentre case-control study.

PubMed

Parodi, Stefano; Merlo, Domenico Franco; Stagnaro, Emanuele

2017-04-01

Coffee and tea are the most frequently consumed beverages in the world. Their potential effect on the risk of developing different types of malignancies has been largely investigated, but studies on leukaemia in adults are scarce. The present investigation is aimed at evaluating the potential role of regular coffee and tea intake on the risk of adult leukaemia by reanalysing a large population based case-control study carried out in Italy, a country with a high coffee consumption and a low use of green tea. Interviewed subjects, recruited between 1990 and 1993 in 11 Italian areas, included 1771 controls and 651 leukaemia cases. Association between Acute Myeloid Leukaemia (AML), Acute Lymphoid Leukaemia, Chronic Myeloid Leukaemia, Chronic Lymphoid Leukaemia, and use of coffee and tea was evaluated by standard logistic regression. Odds Ratios (OR) were estimated adjusting for the following potential confounders: gender, age, residence area, smoking habit, educational level, previous chemotherapy treatment, alcohol consumption and exposure to electromagnetic fields, radiation, pesticides and aromatic hydrocarbons. No association was observed between regular use of coffee and any type of leukaemia. A small protective effect of tea intake was found among myeloid malignancies, which was more evident among AML (OR=0.68, 95%CI: 0.49-0.94). However, no clear dose-response relation was found. The lower risk of leukaemia among regular coffee consumers, reported by a few of previous small studies, was not confirmed. The protective effect of tea on the AML risk is only partly consistent with results from other investigations. Copyright © 2017 Elsevier Ltd. All rights reserved.

Inflammatory potential of diet and risk for hepatocellular cancer in a case-control study from Italy.

PubMed

Shivappa, Nitin; Hébert, James R; Polesel, Jerry; Zucchetto, Antonella; Crispo, Anna; Montella, Maurizio; Franceschi, Silvia; Rossi, Marta; La Vecchia, Carlo; Serraino, Diego

2016-01-28

Inflammation and diet have been suggested to be important risk factors for hepatocellular cancer (HCC). This Italian multicentre hospital-based case-control study conducted between 1999 and 2002 and including 185 cases with incident, histologically confirmed HCC, and 404 controls hospitalised for acute non-neoplastic diseases provided an opportunity to investigate the association between HCC and the dietary inflammatory index (DII). The DII was computed on the basis of dietary intake assessed 2 years before the date of interview by a validated sixty-three-item FFQ. Logistic regression models were used to estimate OR adjusted for age, sex, study centre, education, BMI, smoking, physical activity, serum markers of hepatitis B and C infection and energy intake. Energy adjustment for DII was performed using the residual method. Participants in the highest tertile of DII scores (i.e. with a more pro-inflammatory diet) had a higher risk for HCC (ORtertile 3 v, 1 2·43; 95 % CI 1·27, 4·68; P trend=0·03). When stratified by the presence or absence of hepatitis B/C infection and sex, DII was strongly associated with HCC in hepatitis B- and C-negative participants (ORtertile 3 v. 1 4·18; 95 % CI 1·53, 11·39; P trend=0·02) and among males (ORtertile 3 v. 1 3·60; 95 % CI 1·65, 7·87; P trend=0·001). These results indicate that a pro-inflammatory diet is associated with increased risk for HCC, in those without a history of hepatitis B/C infection and among males.

Variations in colonoscopy practice in Europe: a multicentre descriptive study (EPAGE).

PubMed

Harris, Jennifer K; Vader, John-Paul; Wietlisbach, Vincent; Burnand, Bernard; Gonvers, Jean-Jacques; Froehlich, Florian

2007-01-01

The volume of colonoscopies performed is increasing and differences in colonoscopy practice over time and between centres have been reported. Examination of current practice is important for bench-marking quality. The objective of this study was to examine variations in colonoscopy practice in endoscopy centres internationally. This observational study prospectively included consecutive patients referred for colonoscopy from 21 centres in 11 countries. Patient, procedure and centre characteristics were collected through questionnaires. Descriptive statistics were performed and the variation between centres while controlling for case-mix was examined. A total of 6004 patients were included in the study. Most colonoscopies (93%; range between centres 70-100%) were performed for diagnostic purposes. The proportion of main indications for colonoscopy showed wide variations between centres, the two most common indications, surveillance and haematochezia, ranging between 7-24% and 5-38%, respectively. High-quality cleansing occurred in 74% (range 51-94%) of patients, and 30% (range 0-100%) of patients received deep sedation. Three-quarters (range 0-100%) of the patients were monitored during colonoscopy, and one-quarter (range 14-35%) underwent polypectomy. Colonoscopy was complete in 89% (range 69-98%) of patients and the median total duration was 20 min (range of centre medians 15-30 min). The variation between centres was not reduced when case-mix was controlled for. This study documented wide variations in colonoscopy practice between centres. Controlling for case-mix did not remove these variations, indicating that centre and procedure characteristics play a role. Centres generally were within the existing guidelines, although there is still some work to be done to ensure that all centres attain the goal of providing high-quality colonoscopy.

Acute uncomplicated appendicitis study: rationale and protocol for a multicentre, prospective randomised controlled non-inferiority study to evaluate the safety and effectiveness of non-operative management in children with acute uncomplicated appendicitis.

PubMed

Xu, Jane; Liu, Yingrui Cyril; Adams, Susan; Karpelowsky, Jonathan

2016-12-21

This article presents an overview of a prospective randomised controlled non-inferiority study designed to evaluate the safety and effectiveness of non-operative management (NOM) with operative management in children with acute uncomplicated appendicitis (AUA). Here, we present the study protocol for this APRES study, a multicentre Australian study. The rationale and details of future analysis, in particular, non-inferiority calculations, cost-effectiveness, feasibility and acceptability of each intervention. A multicentre, prospective randomised controlled clinical trial, conducted in 2 Australian tertiary paediatric hospitals. Children who meet the inclusion criteria of an age between 5 and 15 years and a clinical diagnosis of AUA will be invited to participate, and after consent will be randomised via a computer-based program into treatment groups. The study started in June 2016, and the target recruitment is 220 patients. Children in the control group will be treated with prophylactic antibiotics and appendicectomy, and those in the intervention group will be treated with antibiotic therapy alone. Primary outcome measures include unplanned or unnecessary operation and complications at 30 days. Secondary outcomes include longer term complications within 1 year, length of stay, time off work and school analgesic requirements and cost. Data analyses will be on the intention-to-treat principle using non-inferiority analysis. Analysis will include the Pearson χ 2 test for categorical variables and independent sample t-test or Mann-Whitney test for continuous variables. Non-inferiority for NOM will be tested using 1-sided Wald tests with an α level of 0.05. The research has been approved by the Human Research Ethics Committee of the Sydney Children's Hospital Network. In addition, results will be reported through academic journals, seminars and conference presentations. NCT02795793; ACTRN12616000788471. 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/.

Randomized controlled multicentre study comparing biological mesh closure of the pelvic floor with primary perineal wound closure after extralevator abdominoperineal resection for rectal cancer (BIOPEX-study)

PubMed Central

2014-01-01

Background Primary perineal wound closure after conventional abdominoperineal resection (cAPR) for rectal cancer has been the standard of care for many years. Since the introduction of neo-adjuvant radiotherapy and the extralevator APR (eAPR), oncological outcome has been improved, but at the cost of increased rates of perineal wound healing problems and perineal hernia. This has progressively increased the use of biological meshes, although not supported by sufficient evidence. The aim of this study is to determine the effectiveness of pelvic floor reconstruction using a biological mesh after standardized eAPR with neo-adjuvant (chemo)radiotherapy compared to primary perineal wound closure. Methods/Design In this multicentre randomized controlled trial, patients with a clinical diagnosis of primary rectal cancer who are scheduled for eAPR after neo-adjuvant (chemo)radiotherapy will be considered eligible. Exclusion criteria are prior radiotherapy, sacral resection above S4/S5, allergy to pig products or polysorbate, collagen disorders, and severe systemic diseases affecting wound healing, except for diabetes. After informed consent, 104 patients will be randomized between standard care using primary wound closure of the perineum and the experimental arm consisting of suturing a biological mesh derived from porcine dermis in the pelvic floor defect, followed by perineal closure similar to the control arm. Patients will be followed for one year after the intervention and outcome assessors and patients will be blinded for the study treatment. The primary endpoint is the percentage of uncomplicated perineal wound healing, defined as a Southampton wound score of less than II on day 30. Secondary endpoints are hospital stay, incidence of perineal hernia, quality of life, and costs. Discussion The BIOPEX-study is the first randomized controlled multicentre study to determine the additive value of using a biological mesh for perineal wound closure after eAPR with neo-adjuvant radiotherapy compared to primary perineal wound closure with regard to perineal wound healing and the occurrence of perineal hernia. Trail registration number NCT01927497 (Clinicaltrial.gov). PMID:25163547

The new system of review by multicentre research ethics committees: prospective study

PubMed Central

Tully, Joanna; Ninis, Nelly; Booy, Robert; Viner, Russell

2000-01-01

Objective To assess the function of the new system of review by multicentre research ethics committees and to highlight areas where improvement is still needed. Design Prospectively collected data from a multicentre study was examined with respect to the ethics review process. Administrative, financial, and time elements of the review process were audited. Setting A single multicentre research ethics committee and 125 local ethics committees from six regions of England. Main outcome measures Time to reply, time to approval, and number of non-local changes to the application requested. Results Only 40% of local ethics committees considered our study in the manner specified in the 1998 directive. Less than a third of committees replied within the 21 day period stipulated, although committees acting by executive subcommittee replied more quickly than those not acting by executive subcommittee. There was a tendency for executive subcommittees to approve studies in a shorter time. Local ethics committees asked for a large number of non-local changes to the application. The financial cost of applying to multiple ethics committees remains high, mainly because multiple copies of research applications are being requested. Conclusions The new system of approval by multicentre research ethics committee for multicentre studies was introduced to reduce administrative costs, speed up the process of reviews by multiple research ethics committees, and standardise the conclusions of the local research ethics committees. Since its introduction an improvement has been seen, but the system is not yet universally functioning as intended. Ethics review still remains a hindrance to the financial resources and commencement of national studies. We strongly support the structure of review by multicentre research ethics committees but suggest that the system has yet to achieve its aims. PMID:10784541

Efficacy and safety of acarbose in the treatment of Type 1 diabetes mellitus: a placebo-controlled, double-blind, multicentre study.

PubMed

Riccardi, G; Giacco, R; Parillo, M; Turco, S; Rivellese, A A; Ventura, M R; Contadini, S; Marra, G; Monteduro, M; Santeusanio, F; Brunetti, P; Librenti, M C; Pontiroli, A E; Vedani, P; Pozza, G; Bergamini, L; Bianchi, C

1999-03-01

The aim of the study was to evaluate the efficacy and safety of acarbose in patients with Type 1 diabetes mellitus (DM). A multicentre double-blind, randomized, placebo-controlled study was performed. After a 6-week run-in, 121 patients were randomized to acarbose or placebo and to high- or low-fibre diet for 24 weeks. Acarbose dose was 50 mg t.d.s. for the first 2 weeks and 100 mg t.d.s. for the subsequent weeks. At the end of 24 weeks of treatment the intention to treat analysis showed that acarbose compared with placebo decreased 2 h postprandial plasma glucose levels (12.23 +/- 0.83 vs. 14.93 +/- 0.87 mmol/l; F = 6.1, P < 0.02) (least square means +/- SEM). No significant effect of acarbose was recorded on HbA1c or on the number of hypoglycaemic episodes. The effect of acarbose on blood glucose control was not influenced by the amount of carbohydrate and/or fibre intake. The incidence of adverse events were 75% and 39% in acarbose and placebo groups, respectively; they were mild and confined to the gastrointestinal tract. The use of acarbose in combination with insulin reduces postprandial plasma glucose levels in Type 1 diabetic patients who are not satisfactorily controlled with insulin alone but without significant effect on HbA1c.

Analysis of GPR101 and AIP genes mutations in acromegaly: a multicentric study.

PubMed

Ferraù, Francesco; Romeo, P D; Puglisi, S; Ragonese, M; Torre, M L; Scaroni, C; Occhi, G; De Menis, E; Arnaldi, G; Trimarchi, F; Cannavò, S

2016-12-01

This multicentric study aimed to investigate the prevalence of the G protein-coupled receptor 101 (GPR101) p.E308D variant and aryl hydrocarbon receptor interacting protein (AIP) gene mutations in a representative cohort of Italian patients with acromegaly. 215 patients with GH-secreting pituitary adenomas, referred to 4 Italian referral centres for pituitary diseases, have been included. Three cases of gigantism were present. Five cases were classified as FIPA. All the patients have been screened for germline AIP gene mutations and GPR101 gene p.E308D variant. Heterozygous AIP gene variants have been found in 7 patients (3.2 %). Five patients carried an AIP mutation (2.3 %; 4 females): 3 patients harboured the p.R3O4Q mutation, one had the p.R304* mutation and the last one the IVS3+1G>A mutation. The prevalence of AIP mutations was 3.3 % and 2.8 % when considering only the patients diagnosed when they were <30 or <40-year old, respectively. Furthermore, 2.0 % of the patients with a pituitary macroadenoma and 4.2 % of patients resistant to somatostatin analogues treatment were found to harbour an AIP gene mutation. None of the patients was found to carry the GPR101 p.E308D variant. The prevalence of AIP gene mutations among our sporadic and familial acromegaly cases was similar to that one reported in previous studies, but lower when considering only the cases diagnosed before 40 years of age. The GPR101 p.E308D change is unlikely to have a role in somatotroph adenomas tumorigenesis, since none of our sporadic or familial patients tested positive for this variant.

Frequency of genetic defects in combined pituitary hormone deficiency: a systematic review and analysis of a multicentre Italian cohort.

PubMed

De Rienzo, Francesca; Mellone, Simona; Bellone, Simonetta; Babu, Deepak; Fusco, Ileana; Prodam, Flavia; Petri, Antonella; Muniswamy, Ranjith; De Luca, Filippo; Salerno, Mariacarolina; Momigliano-Richardi, Patricia; Bona, Gianni; Giordano, Mara

2015-12-01

Combined pituitary hormonal deficiency (CPHD) can result from mutations within genes that encode transcription factors. This study evaluated the frequency of mutations in these genes in a cohort of 144 unrelated Italian patients with CPHD and estimated the overall prevalence of mutations across different populations using a systematic literature review. A multicentre study of adult and paediatric patients with CPHD was performed. The PROP1, POU1F1, HESX1, LHX3 and LHX4 genes were analysed for the presence of mutations using direct sequencing. We systematically searched PubMed with no date restrictions for studies that reported genetic screening of CPHD cohorts. We only considered genetic screenings with at least 10 individuals. Data extraction was conducted in accordance with the guidelines set by the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). Global mutation frequency in Italian patients with CPHD was 2·9% (4/136) in sporadic cases and 12·5% (1/8) in familial cases. The worldwide mutation frequency for the five genes calculated from 21 studies was 12·4%, which ranged from 11·2% in sporadic to 63% in familial cases. PROP1 was the most frequently mutated gene in sporadic (6·7%) and familial cases (48·5%). The frequency of defects in genes encoding pituitary transcription factors is quite low in Italian patients with CPHD and other western European countries, especially in sporadic patients. The decision of which genes should be tested and in which order should be guided by hormonal and imaging phenotype, the presence of extrapituitary abnormalities and the frequency of mutation for each gene in the patient-referring population. © 2015 John Wiley & Sons Ltd.

The prevalence of lymphogranuloma venereum infection in men who have sex with men: results of a multicentre case finding study

PubMed Central

Ward, H; Alexander, S; Carder, C; Dean, G; French, P; Ivens, D; Ling, C; Paul, J; Tong, W; White, J; Ison, C A

2009-01-01

Objective: To determine the prevalence of lymphogranuloma venereum (LGV) and non-LGV associated serovars of urethral and rectal Chlamydia trachomatis (CT) infection in men who have sex with men (MSM). Design: Multicentre cross-sectional survey. Setting: Four genitourinary medicine clinics in the United Kingdom from 2006–7. Subjects: 4825 urethral and 6778 rectal samples from consecutive MSM attending for sexual health screening. Methods: Urethral swabs or urine and rectal swabs were tested for CT using standard nucleic acid amplification tests. Chlamydia-positive specimens were sent to the reference laboratory for serovar determination. Main outcome: Positivity for both LGV and non-LGV associated CT serovars; proportion of cases that were symptomatic. Results: The positivity (with 95% confidence intervals) in rectal samples was 6.06% (5.51% to 6.66%) for non-LGV CT and 0.90% (0.69% to 1.16%) for LGV; for urethral samples 3.21% (2.74% to 3.76%) for non-LGV CT and 0.04% (0.01% to 0.16%) for LGV. The majority of LGV was symptomatic (95% of rectal, one of two urethral cases); non-LGV chlamydia was mostly symptomatic in the urethra (68%) but not in the rectum (16%). Conclusions: Chlamydial infections are common in MSM attending for sexual health screening, and the majority are non-LGV associated serovars. We did not identify a large reservoir of asymptomatic LGV in the rectum or urethra. Testing for chlamydia from the rectum and urethra should be included for MSM requesting a sexual health screen, but serovar-typing is not indicated in the absence of symptoms. We have yet to identify the source of most cases of LGV in the UK. PMID:19221105

Nipple sparing mastectomy: Surgical and oncological outcomes from a national multicentric registry with 913 patients (1006 cases) over a six year period.

PubMed

Orzalesi, Lorenzo; Casella, Donato; Santi, Caterina; Cecconi, Lorenzo; Murgo, Roberto; Rinaldi, Stefano; Regolo, Lea; Amanti, Claudio; Roncella, Manuela; Serra, Margherita; Meneghini, Graziano; Bortolini, Massimiliano; Altomare, Vittorio; Cabula, Carlo; Catalano, Francesca; Cirilli, Alfredo; Caruso, Francesco; Lazzaretti, Maria Grazia; Cataliotti, Luigi; Bernini, Marco

2016-02-01

Nipple sparing mastectomy is deemed surgically and oncologically safe based on a long lasting literature data from reviews of single institution series. This study aims at evaluating surgical and oncological outcomes of NSM on a large multi-institutional scale, by means of the Italian National registry. In July 2011 a panel of Italian specialists agreed upon and designed a National database of NSM. Centers with at least 150 cancers per year and following the National follow-up schedule guidelines could participate inserting any NSM case performed, retrospectively and prospectively from that moment on. In March 2015 analysis of data was accomplished. Dataset for this study consists of cases performed in the period between January 1st 2009 and December 31st 2014. 913 Women were included in the analysis, for a total of 1006 procedures. Prophylactic mastectomies were 124 (12.3%). MRI utilization increased over time. NSM failure rate, with NAC removal for any reason was 11.5%. NAC necrosis rate was 4.8%. Larger skin-flap necrosis rate was 2.3%. Major surgical complications rate was 4.4%. Oncological outcomes were calculated among primitive EBC cases only: locoregional recurrences rate was 2.9%, NAC recurrence 0.7%. Systemic recurrence rate was 1.0%. Five deaths (0.7%) were registered. More than 10% of NSM procedures are prophylactic mastectomies. MRI is gaining more importance over time. Surgical and oncological results show that NSM is effective. This National multicentric analysis enables a comparison of results with no geographical differences and a "safe" state of the art of NSM in Italy. Copyright © 2015 Elsevier Ltd. All rights reserved.

[Diagnosis and surgical treatment of Castleman's disease].

PubMed

Ma, Shi-hong; Liu, Qin-jiang; Zhang, You-cheng; Yang, Rong

2011-04-26

To explore the clinical features and surgical treatment of tumors associated with Castleman's disease (CD). The clinical profiles of 19 patients with neck giant lymph node hyperplasia were analyzed retrospectively. There were 8 males and 11 females with a median age of 40 years old (range: 7 - 74). The tumor locations were neck (n = 12), neck & mediastinal cavity (n = 2), axillary fossa (n = 2), retroperitoneal area (n = 2) and abdominal cavity (n = 1). Eighteen of them underwent surgical resection of tumor or lymph nodes. All were diagnosed as CD by pathological examinations. There were 16 localized CD (LCD) including hyaline vascular type (HV type, n = 11), mixed type (mix type, n = 4) and plasma cell type-Hodgkin's disease (n = 1). Among 3 multicentric CD (MCD), there were 2 case of plasma cell type (PC type) and 1 case of mixed type (mix type). Long-term survival was achieved in 19 cases among which 1 case of plasma cell type MCD survived for 5 years and underwent a second operation and postoperative chemotherapy of CVP (cyclophosphamide, vincristine & prednisone) regimen for 3 cycles due to recurrence in 2 years and 1 case of plasma cell type LCD-Hodgkin's disease survived for 15 months and underwent a second operation and postoperative chemotherapy of ABVD (adriamycin, bleomycin, vinblastine & dacarbazine)regimen for 6 cycles due to recurrence in 6 months. One case of plasma cell type MCD in abdominal cavity on chemotherapy of CHOP (cyclophosphamide, hydroxydaunorubicin, vincristine & prednisone) regimen for 6 cycles was discharged after a successful management of intestinal obstruction. The major clinical symptom of CD is a gradually enlarging painless mass. Surgical resection of tumor remains the first-line treatment for localized CD and the prognosis is excellent. Multicentric and plasma cell type CDs are prone to recurrence and transformation to lymphoma. And their first-line therapeutic should encompass multi-modality regimens of surgery and adjuvant chemotherapy. However, the clinical prognosis is still poor.

[Comparative evaluation of ultrasonography, computerized tomography, angiography and lipiodol CT in defining extent of hepatocarcinoma. A multicenter study].

PubMed

Dalla Palma, L; Pozzi Mucelli, R; Sponza, M; Bartolozzi, C; De Santis, M; Gandini, G; Mannella, P; Matricardi, L; Rossi, C; Simonetti, G

1995-03-01

The authors report the results of a multicentric trial on hepatocellular carcinoma (HCC) patients, whose lesions were confirmed with biopsy or by high (> 400 ng/ml) alpha-fetoprotein levels. The series consisted of 149 patients examined in 8 different centers and submitted to ultrasonography (US), Computed Tomography (CT) before and after contrast agent administration, angiography and Lipiodol CT. According to lesion size and number, the patients were divided with each imaging modality into three groups: a) group 1: unifocal HCC < 5 cm diameter; b) group 2: multifocal HCC with 2-3 nodules and/or tumor mass < 80 ml; c) multifocal HCC with more than 3 nodules (with total tumor mass not exceeding 40% of liver volume) or with total tumor mass > 80 ml. In 77 patients all the examinations were available for comparison. US and CT diagnosed more patients as belonging to group 1 than angiography and Lipiodol CT, while more patients were classified as groups 2 and 3 with angiography and Lipiodol CT, meaning that US and CT may understage some HCC cases (about 15%) because they show a lower number of nodules. This observation was confirmed by the direct comparison between US and Lipiodol CT (in 114 patients), CT and Lipiodol CT (in 103 patients) and angiography and Lipiodol CT (in 116 patients). US and Lipiodol CT were in disagreement in 18 cases, CT and Lipiodol CT in 16 cases and angiography and Lipiodol CT in 13 cases. In most of these cases, Lipiodol CT showed more lesions than the other techniques. The size of the undetected lesions was small, ranging few mm to 2 cm in nearly all cases. To conclude, the results of this multicentric trial show that Lipiodol CT is a fundamental tool to evaluate HCC extent. In contrast, conventional CT appeared not to add any significant piece of information and can therefore be excluded from the diagnostic protocol of HCC.

[Generalized eruptive histiocytoma. Apropos of a case. Review of the literature].

PubMed

Bobin, P; Carsuzaa, F; Seurat, P; Lucas, D

1983-01-01

About one case of generalized eruptive histiocytoma (G.E.H.) (the second French case) and about thirteen others cases mentioned in literature, the authors remind the clinical, histological, immuno-histochemical and evolutive aspects of this misunderstanding disease, described by Winkelmann in 1963. After having classed it, in the group of nodular, non X, non lipidique, benign histiocytosis, they expose the imprecision of this nosological limits of the G.E.H., in comparison to the bordering diseases. At last, they insist upon the fact that the few number of cases published up to this time, the lack of stand back and the casual transformation into a multicentric reticulo-histiocytosis must induce to watchfulness by requiring for each patient affected by G. E. H. and for a long time, a regular, clinical, radiological and hematological supervision.

Improvement in late renal allograft survival between 1990 and 2002 in Spain: results from a multicentre case-control study.

PubMed

Moreso, Francesc; Alonso, Angel; Gentil, Miguel A; González-Molina, Miguel; Capdevila, Lluis; Marcén, Roberto; Pascual, Julio; Serón, Daniel

2010-09-01

Epidemiological studies have failed to show an improvement in graft survival beyond 1 year after kidney transplantation possibly because of an increased number of expanded donors and older recipients. Thus, we performed a case-control study matching patients transplanted in different eras by donor and recipient characteristics. We considered renal transplant recipients included in the database of the Spanish Chronic Allograft Dysfunction Study Group in 1990, 1994, 1998 and 2002 (n = 4842). We matched patients from these cohorts considering the following variables: donor and recipient age, cause of donor death, hepatitis C virus, panel reactive antibodies and re-transplantation. We identified a total of 896 patients distributed in four cohorts of 224 matched patients. Between 1990 and 2002, the use of cyclosporin decreased (96%, 94%, 80% and 23% respectively, P = 0.001), while the use of tacrolimus increased (0%, 1%, 15% and 63% respectively, P = 0.001) and the prevalence of acute rejection decreased (46%, 37.9%, 20.6% and 15.8% respectively, P < 0.001). One-year serum creatinine was 1.63 +/- 0.66, 1.64 +/- 0.70, 1.44 +/- 0.52 and 1.38 +/- 0.75 respectively, P = 0.001. Graft survival beyond the first year between 1990 and 2002 significantly improved while patient survival did not. Transplant outcome has improved between 1990 and 2002 when donors and recipients of similar characteristics are compared.

PubMed Central

Petithory, J. C.; Ambroise-Thomas, P.; De Loye, J.; Pelloux, H.; Goullier-Fleuret, A.; Milgram, M.; Buffard, C.; Garin, J. P.

1996-01-01

Reported are the results of a multicentre study involving 40 laboratories that was carried out in France to assess all the currently available methods used for the serodiagnosis of toxoplasmosis. For this purpose 10 batches of control sera were prepared with titres in the range 0-260 IU per ml. These sera were tested in nine laboratories using immunofluorescence methods; in three laboratories using dye tests; in forty laboratories using enzyme-linked immunosorbent assay; in four laboratories using direct agglutination and haemagglutination; in seven laboratories using the high-sensitivity IgG agglutination test; and in three laboratories using the latex agglutination test. In this way, 70 series of titrations were carried out using seven procedures and the results were compared with those obtained using the WHO reference serum in 15 cases, with the French national E6 serum in 16 other cases, and in 39 cases using 15 reference sera supplied by the reagent manufacturers. Rigorous comparison of the tests was not possible in all cases because one aim of the study was to ensure that the tests were carried out under the usual working conditions that prevailed in the participating laboratories. The results obtained indicate that the serological tests currently available for toxoplasmosis are acceptable for its serodiagnosis. Presentation of the titres in IU has advantages; however, caution is required since the definition of IU varies according to the test and reagents used. It is therefore essential that the conditions and limits for a positive reaction be carefully defined in each case, especially for commercially available kits. PMID:8829878

Early prognostic value of an Algorithm based on spectral Variables of Ventricular fibrillAtion from the EKG of patients with suddEn cardiac death: A multicentre observational study (AWAKE).

PubMed

Palacios-Rubio, Julián; Marina-Breysse, Manuel; Quintanilla, Jorge G; Gil-Perdomo, José Miguel; Juárez-Fernández, Miriam; Garcia-Gonzalez, Inés; Rial-Bastón, Verónica; Corcobado, María Carmen; Espinosa, María Carmen; Ruiz, Francisco; Gómez-Mascaraque Pérez, Francisco; Bringas-Bollada, María; Lillo-Castellano, José María; Pérez-Castellano, Nicasio; Martínez-Sellés, Manuel; López de Sá, Esteban; Martín-Benítez, Juan Carlos; Perez-Villacastín, Julián; Filgueiras-Rama, David

2018-06-06

Ventricular fibrillation (VF)-related sudden cardiac death (SCD) is a leading cause of mortality and morbidity. Current biological and imaging parameters show significant limitations on predicting cerebral performance at hospital admission. The AWAKE study (NCT03248557) is a multicentre observational study to validate a model based on spectral ECG analysis to early predict cerebral performance and survival in resuscitated comatose survivors. Data from VF ECG tracings of patients resuscitated from SCD will be collected using an electronic Case Report Form. Patients can be either comatose (Glasgow Coma Scale - GCS - ≤8) survivors undergoing temperature control after return of spontaneous circulation (RoSC), or those who regain consciousness (GCS=15) after RoSC; all admitted to Intensive Cardiac Care Units in 4 major university hospitals. VF tracings prior to the first direct current shock will be digitized and analyzed to derive spectral data and feed a predictive model to estimate favorable neurological performance (FNP). The results of the model will be compared to the actual prognosis. The primary clinical outcome is FNP during hospitalization. Patients will be categorized into 4 subsets of neurological prognosis according to the risk score obtained from the predictive model. The secondary clinical outcomes are survival to hospital discharge, and FNP and survival after 6 months of follow-up. The model-derived categorisation will be also compared with clinical variables to assess model sensitivity, specificity, and accuracy. A model based on spectral analysis of VF tracings is a promising tool to obtain early prognostic data after SCD. Copyright © 2018 Instituto Nacional de Cardiología Ignacio Chávez. Publicado por Masson Doyma México S.A. All rights reserved.

Cohort profile: the German ClinSurv HIV project--a multicentre open clinical cohort study supplementing national HIV surveillance.

PubMed

Bätzing-Feigenbaum, J; Kollan, C; Kühne, A; Matysiak-Klose, D; Gunsenheimer-Bartmeyer, B; Hamouda, O

2011-05-01

New forms of HIV/AIDS therapy require new surveillance instruments to meet shifting public health demands. The Clinical Surveillance of HIV Disease (ClinSurv HIV) project was established in 1999 as a collaboration between major HIV treatment centres in Germany and the Robert Koch Institute (RKI). The project contributes to national HIV surveillance and focuses on the changing epidemiology of HIV/AIDS after the introduction of new therapies in 1995. ClinSurv HIV is designed as an open multicentre observational cohort study of HIV-infected patients. Anonymized data on diagnoses, treatment and laboratory parameters are collected in a standardized format. Data are currently sampled biannually via 11 centres specializing in HIV diagnosis and care within the legal framework of the German Protection against Infection Act [Infektionsschutzgesetz (IfSG)]. A total of 14874 patients were enrolled in the study by 30 June 2009. Of these, 10221 patients (68.7%) were enrolled after 1 January 1999 and 6006 patients (40.4%) were known to have been diagnosed as positive for HIV before 1999. Evaluation indicators, such as the number of newly enrolled patients per half-year period, loss to follow-up, completeness of data per case, availability of data per possible clinical contact, and internal quality control parameters, show a very stable evolution in the cohort, which although open, can be observed. Comparison with the national HIV surveillance data suggests a high degree of representativeness according to major demographic variables. Bearing in mind the obvious strengths and weaknesses discussed, the German ClinSurv HIV cohort provides a broad range of research opportunities in the field of HIV/AIDS both within Germany and in international collaborative research.

Performance of a lateral flow immunochromatography test for the rapid diagnosis of active tuberculosis in a large multicentre study in areas with different clinical settings and tuberculosis exposure levels.

PubMed

Manga, Selene; Perales, Rocio; Reaño, Maria; D'Ambrosio, Lia; Migliori, Giovanni Battista; Amicosante, Massimo

2016-11-01

Tuberculosis (TB) continues to cause an outsized burden of morbidity and mortality worldwide, still missing efficient and largely accessible diagnostic tools determining an appropriate control of the disease. Serological tests have the potentially to impact TB diagnosis, in particular in extreme clinical settings. The diagnostic performances of the TB-XT HEMA EXPRESS (HEMA-EXPRESS) immunochromatographic rapid test for active TB diagnosis, based on use of multiple Mycobacterium tuberculosis (MTB) specific antigens, have been evaluated in a large study multicentre TB case-finding study, in populations with different exposure level to TB. A total of 1,386 subjects were enrolled in the six participating centres in Peru: 290 active-TB and 1,096 unaffected subjects. The TB prevalence (overall 20.5%) varied between 4.0% and 41.1% in the different study groups. Overall, the HEMA-EXPRESS test had 30.6% sensitivity (range 3.9-77.9%) and 84.6% specificity (range 51.6-97.3%). A significant inverse correlation between test accuracy (overall 73.5%, range 40.4-96.4%) and TB prevalence in the various study populations was observed (Pearson's r=-0.7985; P=0.05). HEMA-EXPRESS, is rapid and relatively inexpensive test suitable for routine use in TB diagnosis. In low TB prevalence conditions, test performance appears in line with WHO Target Product Profile for TB diagnostics. Performances appear suboptimal in high TB prevalence settings. Appropriate set-up in operative clinical settings has to be considered for novel serological tests for TB diagnosis, particularly for formats suitable for point-of-care use.

Ventricular enlargement as a possible measure of Alzheimer's disease progression validated using the Alzheimer's disease neuroimaging initiative database

PubMed Central

Nestor, Sean M.; Rupsingh, Raul; Borrie, Michael; Smith, Matthew; Accomazzi, Vittorio; Wells, Jennie L.; Fogarty, Jennifer

2008-01-01

Ventricular enlargement may be an objective and sensitive measure of neuropathological change associated with mild cognitive impairment (MCI) and Alzheimer's disease (AD), suitable to assess disease progression for multi-centre studies. This study compared (i) ventricular enlargement after six months in subjects with MCI, AD and normal elderly controls (NEC) in a multi-centre study, (ii) volumetric and cognitive changes between Apolipoprotein E genotypes, (iii) ventricular enlargement in subjects who progressed from MCI to AD, and (iv) sample sizes for multi-centre MCI and AD studies based on measures of ventricular enlargement. Three dimensional T1-weighted MRI and cognitive measures were acquired from 504 subjects (NEC n = 152, MCI n = 247 and AD n = 105) participating in the multi-centre Alzheimer's Disease Neuroimaging Initiative. Cerebral ventricular volume was quantified at baseline and after six months using semi-automated software. For the primary analysis of ventricle and neurocognitive measures, between group differences were evaluated using an analysis of covariance, and repeated measures t-tests were used for within group comparisons. For secondary analyses, all groups were dichotomized for Apolipoprotein E genotype based on the presence of an ε4 polymorphism. In addition, the MCI group was dichotomized into those individuals who progressed to a clinical diagnosis of AD, and those subjects that remained stable with MCI after six months. Group differences on neurocognitive and ventricle measures were evaluated by independent t-tests. General sample size calculations were computed for all groups derived from ventricle measurements and neurocognitive scores. The AD group had greater ventricular enlargement compared to both subjects with MCI (P = 0.0004) and NEC (P < 0.0001), and subjects with MCI had a greater rate of ventricular enlargement compared to NEC (P = 0.0001). MCI subjects that progressed to clinical AD after six months had greater ventricular enlargement than stable MCI subjects (P = 0.0270). Ventricular enlargement was different between Apolipoprotein E genotypes within the AD group (P = 0.010). The number of subjects required to demonstrate a 20% change in ventricular enlargement was substantially lower than that required to demonstrate a 20% change in cognitive scores. Ventricular enlargement represents a feasible short-term marker of disease progression in subjects with MCI and subjects with AD for multi-centre studies. PMID:18669512

Measurement of HbA1c in multicentre diabetes trials - should blood samples be tested locally or sent to a central laboratory: an agreement analysis.

PubMed

Arch, Barbara N; Blair, Joanne; McKay, Andrew; Gregory, John W; Newland, Paul; Gamble, Carrol

2016-10-24

Glycated haemoglobin (HbA1c) is an important outcome measure in diabetes clinical trials. For multicentre designs, HbA1c can be measured locally at participating centres or by sending blood samples to a central laboratory. This study analyses the agreement between local and central measurements, using 1-year follow-up data collected in a multicentre randomised controlled trial (RCT) of newly diagnosed children with type I diabetes. HbA1c measurements were routinely analysed both locally and centrally at baseline and then at 3, 6, 9 and 12 months and the data reported in mmol/mol. Agreement was assessed by calculating the bias and 95 % limits of agreement, using the Bland-Altman analysis method. A predetermined benchmark for clinically acceptable margin of error between measurements was subjectively set as ±10 % for HbA1c. The percentage of pairs of measurements that were classified as clinically acceptable was calculated. Descriptive statistics were used to examine the agreement within centres. Treatment group was not considered. Five hundred and ninety pairs of measurement, representing 255 children and 15 trial centres across four follow-up time points, were compared. There was no significant bias: local measurements were an average of 0.16 mmol/mol (SD = 4.5, 95 % CI -0.2 to 0.5) higher than central. The 95 % limits of agreement were -8.6 to 9.0 mmol/mol (local minus central). Eighty percent of local measurements were within ±10 % of corresponding central measurements. Some trial centres were more varied in the differences observed between local and central measurements: IQRs ranging from 3 to 9 mmol/mol; none indicated systematic bias. Variation in agreement between HbA1c measurements was greater than had been expected although no overall bias was detected and standard deviations were similar. Discrepancies were present across all participating centres. These findings have implications for the comparison of standards of clinical care between centres, the design of future multicentre RCTs and existing quality assurance processes for HbA1c measurements. We recommend that centralised HbA1c measurement is preferable in the multicentre clinical trial setting. Eudract No. 2010-023792-25 , registered on 4 November 2010.

Multiple Myeloma and Epidural Spinal Cord Compression : Case Presentation and a Spine Surgeon's Perspective

PubMed Central

Ha, Kee-Yong; Kim, Hyun-Woo

2013-01-01

Multiple myeloma, a multicentric hematological malignancy, is the most common primary tumor of the spine. As epidural myeloma causing spinal cord compression is a rare condition, its therapeutic approach and clinical results have been reported to be diverse, and no clear guidelines for therapeutic decision have been established. Three patients presented with progressive paraplegia and sensory disturbance. Image and serological studies revealed multiple myeloma and spinal cord compression caused by epidural myeloma. Emergency radiotherapy and steroid therapy were performed in all three cases. However, their clinical courses and results were distinctly different. Following review of our cases and the related literature, we suggest a systematic therapeutic approach for these patients to achieve better clinical results. PMID:24175035

Prognostic significance of clinical presentation, induction and rescue treatment in 42 cases of canine centroblastic diffuse large B-cell multicentric lymphoma in the United Kingdom.

PubMed

Davies, O; Szladovits, B; Polton, G; Garden, O A; Leo, C; Lara-Garcia, A

2018-06-01

Canine lymphoma is a heterogeneous group of diseases and many previous studies have evaluated the response of a mixed population of lymphoma cases to one specific treatment protocol. The aim of this retrospective study was to describe the outcome and prognostic factors in 42 cases of multicentric centroblastic diffuse large B-cell lymphoma treated with either a COP-type (35%) or CHOP-type (64%) induction chemotherapy. The objective response rate to induction therapy was 94%; entire dogs had a greater rate of complete vs partial remissions than neutered dogs (P = .017). Median progression-free survival for the first remission (PFS1) was 182 days; absence of anaemia at diagnosis (P = .002) and pretreatment neutrophil:lymphocyte ratio (NLR) below 9.44 (P = .015) were independently predictive of longer PFS1. Fifty-eight percent of dogs received rescue protocols with an objective response rate of 81%; 31% of dogs received further rescue protocols (up to a total of 5) and the median number of protocols administered were 2. Median overall survival (OS) was 322 days, the 1-year survival rate was 38% and the 2-year survival rate was 9%. Lymphocyte:monocyte ratio above 1.43 (P = .031), NLR below 11.44 (P = .009), the combination of induction and rescue therapy (P = .030) and the total number of doxorubicin doses used (P = .002) were independently predictive of longer OS. Use of a COP-type protocol induction compared with CHOP did not undermine OS providing doxorubicin was used as rescue therapy. © 2017 John Wiley & Sons Ltd.

Revisiting the Robustness of PET-Based Textural Features in the Context of Multi-Centric Trials.

PubMed

Bailly, Clément; Bodet-Milin, Caroline; Couespel, Solène; Necib, Hatem; Kraeber-Bodéré, Françoise; Ansquer, Catherine; Carlier, Thomas

2016-01-01

This study aimed to investigate the variability of textural features (TF) as a function of acquisition and reconstruction parameters within the context of multi-centric trials. The robustness of 15 selected TFs were studied as a function of the number of iterations, the post-filtering level, input data noise, the reconstruction algorithm and the matrix size. A combination of several reconstruction and acquisition settings was devised to mimic multi-centric conditions. We retrospectively studied data from 26 patients enrolled in a diagnostic study that aimed to evaluate the performance of PET/CT 68Ga-DOTANOC in gastro-entero-pancreatic neuroendocrine tumors. Forty-one tumors were extracted and served as the database. The coefficient of variation (COV) or the absolute deviation (for the noise study) was derived and compared statistically with SUVmax and SUVmean results. The majority of investigated TFs can be used in a multi-centric context when each parameter is considered individually. The impact of voxel size and noise in the input data were predominant as only 4 TFs presented a high/intermediate robustness against SUV-based metrics (Entropy, Homogeneity, RP and ZP). When combining several reconstruction settings to mimic multi-centric conditions, most of the investigated TFs were robust enough against SUVmax except Correlation, Contrast, LGRE, LGZE and LZLGE. Considering previously published results on either reproducibility or sensitivity against delineation approach and our findings, it is feasible to consider Homogeneity, Entropy, Dissimilarity, HGRE, HGZE and ZP as relevant for being used in multi-centric trials.

Geriatric assessment of older patients with cancer in Australia--a multicentre audit.

PubMed

Lakhanpal, Roopa; Yoong, Jaclyn; Joshi, Sachin; Yip, Desmond; Mileshkin, Linda; Marx, Gavin M; Dunlop, Tracey; Hovey, Elizabeth J; Della Fiorentina, Stephen A; Venkateswaran, Lakshmi; Tattersall, Martin H N; Liew, Sem; Field, Kathryn; Singhal, Nimit; Steer, Christopher B

2015-05-01

The aim of this study is to determine the frequency of geriatric assessment in patients aged over 70 years in Australian medical oncology clinics. This was a multicentre audit in two parts: a retrospective file review of initial consultations with an oncologist and prospective audit of case presentations at multidisciplinary meetings (MDMs). Patients aged over 70 years presenting to a medical oncology clinic or being discussed at an MDM were eligible. Data was collected at six oncology centres in Victoria, NSW and Canberra from October 2009 to March 2010. Data was collected from 251 file reviews and 108 MDM discussions in a total of 304 patients. Median age was 76 years (range 70-95). The geriatric assessment (GA) domains most frequently assessed during an initial consultation were the presence of comorbidities (92%), social situation-living alone or with someone (80%), social supports (63%), any mention of at least one Activity of Daily Living (ADL) (50%) and performance status (49%). Less frequently assessed were any Instrumental Activity of Daily Living (IADL) (26%), presence of a geriatric syndrome (24%), polypharmacy (29%) and creatinine clearance (11%). Only one patient had all components of ADLs and IADLs assessed. During MDMs all the geriatric domains were comparatively less frequently assessed. No patients had all ADL and IADL components discussed formally in an MDM. This is the first multicentre audit that reveals the low rates of GA in Australian medical oncology practice and describes the GA domains considered important by oncology clinicians. Copyright © 2015 Elsevier Inc. All rights reserved.

Local epidemiology and resistance profiles in acute uncomplicated cystitis (AUC) in women: a prospective cohort study in an urban urological ambulatory setting.

PubMed

Seitz, Michael; Stief, Christian; Waidelich, Raphaela

2017-10-16

Acute uncomplicated cystitis (AUC) is a common ailment in the urological setting. Guidelines for urinary tract infections are based on large-scale multi-centre, epidemiological and international studies. The objective of this observational study was to establish whether the results of a multi-centre study on the resistance profile of Escherichia coli (E. coli) in patients with AUC could be directly applied to an urological practice in a major European city or whether there are divergences in the resistance profile. An observational study was applied prospectively to 502 patients with AUC between January 2015 and January 2017). Personal data were anonymised. Exclusion criteria were the patient's age (<18) and treatment with an antibiotic in the week preceding examination. The average age was 32 (range 18-56). The most commonly detected bacteria was E. coli with 86%, followed by Enterococcus faecalis with 10% and Klebsiella pneumoniae with 4%. Resistance tests showed E. coli to be highly sensitive to fosfomycin (99.2%), nitrofurantoin (98.1%) and cefpodoxime (92.9%). E. coli exhibited resistance to ciprofloxacin (CIP) in 15.1%, to trimethoprim/sulfamethoxazole (TRS) in 25.2% and to amoxicillin/clavulanic acid (AMC) in 34% of cases. The comparison between data from this study and data from a multi-centre European (ECO-SENSI, ECO-SENSII and the 2014 update) showed relatively good sensitivity rates for fosfomycin and nitrofurantoin but significant differences in respect of resistance levels to TRS, CIP and AMC. AUC should therefore only be treated with TRS, CIP and AMC after a susceptibility test has been carried out.

Development of a web-based register for the Dutch national study on biologicals in JIA: www.ABC-register.nl.

PubMed

Prince, F H M; Ferket, I S; Kamphuis, S; Armbrust, W; Ten Cate, R; Hoppenreijs, E P A H; Koopman-Keemink, Y; van Rossum, M A J; van Santen-Hoeufft, M; Twilt, M; van Suijlekom-Smit, L W A

2008-09-01

Most clinical studies use paper case record forms (CRFs) to collect data. In the Dutch multi-centre observational study on biologicals we encountered several disadvantages of using the paper CRFs. These are delay in data collection, lack of overview in collected data and difficulties in obtaining up-to-date interim reports. Therefore, we wanted to create a more effective method of data collection compared with CRFs on paper in a multi-centre study. We designed a web-based register with the intention to make it easy to use for participating physicians and at the same time accurate and up-to-date. Security demands were taken into account to secure the safety of the patient data. The web-based register was tested with data from 161 juvenile idiopathic arthritis patients from nine different centres. Internal validity was obtained and user-friendliness guaranteed. To secure the completeness of the data automatically generated e-mail alerts were implemented into the web-based register. More transparency of data was achieved by including the option to automatically generate interim reports of data in the web-based register. The safety was tested and approved. By digitalizing the CRF we achieved our aim to provide easy, rapid and safe access to the database and contributed to a new way of data collection. Although the web-based register was designed for the current multi-centre observational study, this type of instrument can also be applied to other types of studies. We expect that especially collaborative study groups will find it an efficient tool to collect data.

Maternal dental caries and pre-term birth: results from the EPIPAP study.

PubMed

Vergnes, Jean-Noel; Kaminski, Monique; Lelong, Nathalie; Musset, Anne-Marie; Sixou, Michel; Nabet, Cathy

2011-07-01

OBJECTIVE. The aim of this study was to analyse the association between maternal dental caries and pre-term birth (PTB), with a particular focus on the infection-suspected causes of pre-term births. MATERIALS AND METHODS. A secondary analysis was performed on data from the EPIPAP study, a French multi-centre case-control study. Cases were 1107 women giving birth to a singleton live-born infant before 37 weeks of gestation and controls were 1094 women delivering at 37 weeks or more. A sub-group of cases was defined as women with spontaneous labour and/or pre-term premature rupture of membranes (PPROM, n = 620). A full-mouth dental examination was performed after delivery. The main factor of interest was the presence of decay on at least one tooth. RESULTS. Crude associations between presence of tooth decay and PTB or spontaneous PTB/PPROM were significant (OR = 1.21 [1.01-1.45] and OR = 1.25 [1.01-1.55], respectively). After adjustment for two sets of potential confounders (four pre-term birth risk factors and four social characteristics), for periodontitis status and for inter-examiner variability, tooth decay was not significantly associated with either PTB or spontaneous PTB/PPROM (aOR = 1.10 [0.91-1.32] and aOR = 1.14 [0.91-1.42], respectively). CONCLUSIONS. This study failed to demonstrate a significant association between tooth decay and pre-term birth. However, future well-designed studies are needed to further assess the link between dental caries and adverse pregnancy outcomes.

Maternal Psychological Distress in the First Two Years after Very Preterm Birth and Early Intervention

ERIC Educational Resources Information Center

Meijssen, Dominique; Wolf, Marie-Jeanne; Koldewijn, Karen; van Baar, Anneloes; Kok, Joke

2011-01-01

Preterm delivery may have a strong impact on mothers. In a multicentre randomised controlled trial, including very preterm infants (less than 32 weeks and/or less than 1500 g), the effect of the Infant Behavioral Assessment and Intervention Program (IBAIP) on maternal psychological distress at 6, 12 and 24 (corrected) months after preterm birth…

Glutamine--from conditionally essential to totally dispensable?

PubMed

Wernerman, Jan

2014-07-02

Recently a large multicentre randomised controlled trial in critically ill patients reported harm to the patients given supplementary glutamine. In the original publication, no explanation was offered for why this result was obtained; a large number of studies have reported beneficial effects or no effect, but never before reported harm. These results have been commented upon in a number of communications. Now some of the authors of the multicentre randomised controlled trial present a review and meta-analysis of glutamine supplementation, and the discrepancy of results is suggested to relate to intravenous administration to patients of supplementary glutamine via parenteral nutrition or a combination of enteral and parenteral nutrition in contrast to enteral administration of supplementation or a combination of enteral and parenteral supplementation. To explain results by epidemiological means only, by combining results into a meta-analysis, is perhaps not the best way to explain mechanisms behind results. Meta-analyses are primarily hypothesis generating. Launching treatment without a solid mechanistic explanation is always risky. Glutamine supplementation of the critically ill comes into that category. Now we will all have to do our homework and try to understand whether supplementation or omission of glutamine for patients fed parenterally is a good idea or not.

Resolving controversies in hip fracture care: the need for large collaborative trials in hip fractures.

PubMed

Bhandari, Mohit; Sprague, Sheila; Schemitsch, Emil H

2009-07-01

Hip fractures are a significant cause of morbidity and mortality worldwide and the burden of disability associated with hip fractures globally vindicate the need for high-quality research to advance the care of patients with hip fractures. Historically, large, multi-centre randomized controlled trials have been rare in the orthopaedic trauma literature. Similar to other medical specialties, orthopaedic research is currently undergoing a paradigm shift from single centre initiatives to larger collaborative groups. This is evident with the establishment of several collaborative groups in Canada, in the United States, and in Europe, which has proven that multi-centre trials can be extremely successful in orthopaedic trauma research.Despite ever increasing literature on the topic of his fractures, the optimal treatment of hip fractures remains unknown and controversial. To resolve this controversy large multi-national collaborative randomized controlled trials are required. In 2005, the International Hip Fracture Research Collaborative was officially established following funding from the Canadian Institute of Health Research International Opportunity Program with the mandate of resolving controversies in hip fracture management. This manuscript will describe the need, the information, the organization, and the accomplishments to date of the International Hip Fracture Research Collaborative.

Functional variants in the sucrase-isomaltase gene associate with increased risk of irritable bowel syndrome.

PubMed

Henström, Maria; Diekmann, Lena; Bonfiglio, Ferdinando; Hadizadeh, Fatemeh; Kuech, Eva-Maria; von Köckritz-Blickwede, Maren; Thingholm, Louise B; Zheng, Tenghao; Assadi, Ghazaleh; Dierks, Claudia; Heine, Martin; Philipp, Ute; Distl, Ottmar; Money, Mary E; Belheouane, Meriem; Heinsen, Femke-Anouska; Rafter, Joseph; Nardone, Gerardo; Cuomo, Rosario; Usai-Satta, Paolo; Galeazzi, Francesca; Neri, Matteo; Walter, Susanna; Simrén, Magnus; Karling, Pontus; Ohlsson, Bodil; Schmidt, Peter T; Lindberg, Greger; Dlugosz, Aldona; Agreus, Lars; Andreasson, Anna; Mayer, Emeran; Baines, John F; Engstrand, Lars; Portincasa, Piero; Bellini, Massimo; Stanghellini, Vincenzo; Barbara, Giovanni; Chang, Lin; Camilleri, Michael; Franke, Andre; Naim, Hassan Y; D'Amato, Mauro

2018-02-01

IBS is a common gut disorder of uncertain pathogenesis. Among other factors, genetics and certain foods are proposed to contribute. Congenital sucrase-isomaltase deficiency (CSID) is a rare genetic form of disaccharide malabsorption characterised by diarrhoea, abdominal pain and bloating, which are features common to IBS. We tested sucrase-isomaltase ( SI ) gene variants for their potential relevance in IBS. We sequenced SI exons in seven familial cases, and screened four CSID mutations (p.Val557Gly, p.Gly1073Asp, p.Arg1124Ter and p.Phe1745Cys) and a common SI coding polymorphism (p.Val15Phe) in a multicentre cohort of 1887 cases and controls. We studied the effect of the 15Val to 15Phe substitution on SI function in vitro. We analysed p.Val15Phe genotype in relation to IBS status, stool frequency and faecal microbiota composition in 250 individuals from the general population. CSID mutations were more common in patients than asymptomatic controls (p=0.074; OR=1.84) and Exome Aggregation Consortium reference sequenced individuals (p=0.020; OR=1.57). 15Phe was detected in 6/7 sequenced familial cases, and increased IBS risk in case-control and population-based cohorts, with best evidence for diarrhoea phenotypes (combined p=0.00012; OR=1.36). In the population-based sample, 15Phe allele dosage correlated with stool frequency (p=0.026) and Parabacteroides faecal microbiota abundance (p=0.0024). The SI protein with 15Phe exhibited 35% reduced enzymatic activity in vitro compared with 15Val (p<0.05). SI gene variants coding for disaccharidases with defective or reduced enzymatic activity predispose to IBS. This may help the identification of individuals at risk, and contribute to personalising treatment options in a subset of patients. 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/.

Description and process evaluation of pharmacists' interventions in a pharmacist-led information technology-enabled multicentre cluster randomised controlled trial for reducing medication errors in general practice (PINCER trial).

PubMed

Howard, Rachel; Rodgers, Sarah; Avery, Anthony J; Sheikh, Aziz

2014-02-01

To undertake a process evaluation of pharmacists' recommendations arising in the context of a complex IT-enabled pharmacist-delivered randomised controlled trial (PINCER trial) to reduce the risk of hazardous medicines management in general practices. PINCER pharmacists manually recorded patients' demographics, details of interventions recommended, actions undertaken by practice staff and time taken to manage individual cases of hazardous medicines management. Data were coded, double-entered into SPSS version 15 and then summarised using percentages for categorical data (with 95% confidence interval (CI)) and, as appropriate, means (± standard deviation) or medians (interquartile range) for continuous data. Pharmacists spent a median of 20 min (interquartile range 10, 30) reviewing medical records, recommending interventions and completing actions in each case of hazardous medicines management. Pharmacists judged 72% (95% CI 70, 74; 1463/2026) of cases of hazardous medicines management to be clinically relevant. Pharmacists recommended 2105 interventions in 74% (95% CI 73, 76; 1516/2038) of cases and 1685 actions were taken in 61% (95% CI 59, 63; 1246/2038) of cases; 66% (95% CI 64, 68; 1383/2105) of interventions recommended by pharmacists were completed and 5% (95% CI 4, 6; 104/2105) of recommendations were accepted by general practitioners (GPs), but not completed at the end of the pharmacists' placement; the remaining recommendations were rejected or considered not relevant by GPs. The outcome measures were used to target pharmacist activity in general practice towards patients at risk from hazardous medicines management. Recommendations from trained PINCER pharmacists were found to be broadly acceptable to GPs and led to ameliorative action in the majority of cases. It seems likely that the approach used by the PINCER pharmacists could be employed by other practice pharmacists following appropriate training. © 2013 The Authors. International Journal of Pharmacy Practice published by John Wiley & Sons Ltd on behalf of Royal Pharmaceutical Society.

Multicentric T-cell lymphoma associated with feline leukemia virus infection in a captive namibian cheetah (Acinonyx jubatus).

PubMed

Marker, Laurie; Munson, Linda; Basson, Peter A; Quackenbush, Sandra

2003-07-01

This case report describes a multicentric lymphoma in a 4 yr old female wildborn captive cheetah (Acinonyx jubatus) in Namibia after being housed in an enclosure adjacent to a feline leukemia virus (FeLV) infected cheetah that had previously been in contact with domestic cats. The year prior to the onset of clinical signs, the wild-born cheetah was FeLV antigen negative. The cheetah subsequently developed lymphoma, was found to be infected with FeLV, and then rapidly deteriorated and died. At necropsy, the liver, spleen, lymph nodes, and multiple other organs were extensively infiltrated with neoplastic T-lymphocytes. Feline leukemia virus DNA was identified in neoplastic lymphocytes from multiple organs by polymerase chain reaction and Southern blot analysis. Although the outcome of infection in this cheetah resembles that of FeLV infections in domestic cats, the transmission across an enclosure fence was unusual and may indicate a heightened susceptibility to infection in cheetahs. Caution should be exercised in holding and translocating cheetahs where contact could be made with FeLV-infected domestic, feral, or wild felids.

Fracture of the medial intercondylar eminence of the tibia in horses treated by arthroscopic fragment removal (21 horses).

PubMed

Rubio-Martínez, L M; Redding, W R; Bladon, B; Wilderjans, H; Payne, R J; Tessier, C; Geffroy, O; Parker, R; Bell, C; Collingwood, F A

2018-01-01

Fractures of the medial intercondylar eminence of the tibia (MICET) are scarcely reported in horses. To report the clinical and diagnostic findings, surgical treatment and outcome in a series of horses presented with MICET fracture and treated with arthroscopic fragment removal. Multicentre retrospective case series. Case records of horses diagnosed with MICET fractures that had undergone surgical treatment were reviewed. Follow-up information was obtained from re-examination visits and/or owners. Twenty-one cases were identified at 9 equine hospitals between 2004 and 2016. A history of trauma and acute onset of lameness was reported in 12 horses. All cases underwent fracture removal via arthroscopy of the medial femorotibial joint. The cranial cruciate ligament was intact in 6 horses and damaged in 15 horses (damage was ≤25% [n = 9], 25-50% [n = 4] or ≥50% [n = 2] of the cross-sectional area). The cranial ligament of the medial meniscus was damaged in 11 horses (≤25% [n = 8], 25-50% [n = 3]). The medial meniscus was damaged in 5 horses and articular cartilage damage was identified in 14 horses (mild [n = 8], moderate [n = 6]). Follow-up information (median 14 months; 4 months-6 years) was available for 20 cases; 2 horses were sound but convalescing; 13 horses were sound and returned to their previous or expected use. Of the 4 horses with the most severe changes to the articular soft tissue structures, 2 remained lame and 2 were subjected to euthanasia because of persistent lameness. The retrospective, multicentre nature of this study and the limited number of horses are the main limitations. Fractures of the MICET are commonly associated with a traumatic event. Prompt diagnosis and early arthroscopic removal of the fracture are recommended. © 2017 The Authors. Equine Veterinary Journal published by John Wiley & Sons Ltd on behalf of EVJ Ltd.

Factors associated with survival of epiploic foramen entrapment colic: a multicentre, international study.

PubMed

Archer, D C; Pinchbeck, G L; Proudman, C J

2011-08-01

Epiploic foramen entrapment (EFE) has been associated with reduced post operative survival compared to other types of colic but specific factors associated with reduced long-term survival of these cases have not been evaluated in a large number of horses using survival analysis. To describe post operative survival of EFE cases and to identify factors associated with long-term survival. A prospective, multicentre, international study was conducted using clinical data and long-term follow-up information for 126 horses diagnosed with EFE during exploratory laparotomy at 15 clinics in the UK, Ireland and USA. Descriptive data were generated and survival analysis performed to identify factors associated with reduced post operative survival. For the EFE cohort that recovered following anaesthesia, survival to hospital discharge was 78.5%. Survival to 1 and 2 years post operatively was 50.6 and 34.3%, respectively. The median survival time of EFE cases undergoing surgery was 397 days. Increased packed cell volume (PCV) and increased length of small intestine (SI) resected were significantly associated with increased likelihood of mortality when multivariable analysis of pre- and intraoperative variables were analysed. When all pre-, intra- and post operative variables were analysed separately, only horses that developed post operative ileus (POI) were shown to be at increased likelihood of mortality. Increased PCV, increased length of SI resected and POI are all associated with increased likelihood of mortality of EFE cases. This emphasises the importance of early diagnosis and treatment and the need for improved strategies in the management of POI in order to reduce post operative mortality in these cases. The present study provides evidence-based information to clinicians and owners of horses undergoing surgery for EFE about long-term survival. These results are applicable to university and large private clinics over a wide geographical area. © 2011 EVJ Ltd.

Magnetic Resonance Enterography to Assess Multifocal and Multicentric Bowel Endometriosis.

PubMed

Nyangoh Timoh, Krystel; Stewart, Zelda; Benjoar, Mikhael; Beldjord, Selma; Ballester, Marcos; Bazot, Marc; Thomassin-Naggara, Isabelle; Darai, Emile

To prospectively determine the accuracy of magnetic resonance enterography (MRE) compared with conventional magnetic resonance imaging (MRI) for multifocal (i.e., multiple lesions affecting the same digestive segment) and multicentric (i.e., multiple lesions affecting several digestive segments) bowel endometriosis. A prospective study (Canadian Task Force classification II-2). Tenon University Hospital, Paris, France. Patients with MRI-suspected colorectal endometriosis scheduled for colorectal resection from April 2014 to February 2016 were included. Patients underwent both 1.5-Tesla MRI and MRE as well as laparoscopically assisted and open colorectal resections. The diagnostic performance of MRI and MRE was evaluated for sensitivity, specificity, positive and negative predictive values, accuracy, and positive and negative likelihood ratios (LRs). The interobserver variability of the experienced and junior radiologists was quantified using weighted statistics. Forty-seven patients were included. Twenty-two (46.8%) patients had unifocal lesions, 14 (30%) had multifocal lesions, and 11 (23.4%) had multicentric lesions. The sensitivity, specificity, positive LR, and negative LR for the diagnosis of multifocal lesions were 0.29 (6/21), 1.00 (23/24), 15.36, and 0.71 for MRI and 0.57 (12/21), 0.89 (23/25), 4.95, and 0.58 for MRE. The sensitivity, specificity, positive LR, and negative LR for the diagnosis of multicentric lesions were 0.18 (1/11), 1.00 (1/1), 15, and 0.80 for MRI and 0.46 (5/11), 0.92 (33/36), 5.45, and 0.60 for MRE. Lower accuracies for MRI compared with MRE to diagnose multicentric (p = .01) and multifocal lesions (p = .004) were noted. The interobserver agreement for MRE was good for both multifocality (κ = 0.80) and multicentricity (κ = 0.61). MRE has better accuracy for diagnosing multifocal and multicentric bowel endometriosis than conventional MRI. Copyright © 2018. Published by Elsevier Inc.

Cytological surveillance compared with immediate referral for colposcopy in management of women with low grade cervical abnormalities: multicentre randomised controlled trial.

PubMed

2009-07-28

To examine the effectiveness of cytological surveillance in primary care compared with immediate referral for colposcopic examination in women with low grade abnormal results on cervical cytology tests. Multicentre individually randomised controlled trial. NHS cervical screening programmes in Grampian, Tayside, and Nottingham. 4439 women, aged 20-59, with a cytology result showing borderline nuclear abnormalities or mild dyskaryosis, October 1999-October 2002. Cytological screening every six months in primary care (n=2223) or referral for colposcopy and related interventions (n=2216). All women were followed for three years, concluding with an exit appointment at which colposcopic examination was undertaken. Colposcopists assessing outcome at this appointment were blinded to randomisation. Primary end point: cumulative incidence of cervical intraepithelial neoplasia grade II or more severe disease. Other end points: cervical intraepithelial neoplasia grade III or worse, clinically significant anxiety and depression, other self reported after effects, and rates of non-attendance. Analysis was by intention to treat; all those randomised were included. The cumulative incidence of cervical intraepithelial neoplasia grade II or worse was 79 per 1000 person years in the colposcopy arm and 58 per 1000 person years in the cytological surveillance arm (relative risk 1.37, 95% confidence interval 1.19 to 1.57). This difference was less marked for cervical intraepithelial neoplasia grade III or more severe disease, but the incidence was still higher in the colposcopy arm (relative risk 1.26, 1.04 to 1.53). Among women randomised to immediate colposcopy, 79% (74.9% to 82.5%) of cases of cervical intraepithelial neoplasia grade II or worse were diagnosed at the time of the immediate colposcopy, while among women randomised to cytological surveillance, 77% (72.1% to 81.2%) of cases were detected by surveillance cytology and related interventions. Similar proportions of women were anxious or depressed in the two arms. A higher proportion of women in the colposcopy arm reported after effects, and these were of longer duration and more severe. Non-attendance was low in both arms. The more marked difference between the arms in the occurrence of cervical intraepithelial neoplasia grade II or worse than in the occurrence of grade III or worse can probably be accounted for by the spontaneous regression of some cases of grade II neoplasia. Compared with cytological surveillance, a policy of immediate colposcopy detects more cervical intraepithelial neoplasia grade II or worse, and some more grade III or worse, but might lead to overtreatment. Such a policy is associated with a higher rate of reported after effects, which are more severe and of longer duration than those associated with cytological surveillance. ISRCTN 34841617.

Treating KSHV-Associated Multicentric Castleman Disease

Cancer.gov

In this study, patients with KSHV-associated multicentric Castleman disease will receive IV tocilizumab every other week for up to 12 weeks. Patients who do not benefit may go on to receive high-dose AZT and valganciclovir as well.

Multi-Centrality Graph Spectral Decompositions and Their Application to Cyber Intrusion Detection

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

Chen, Pin-Yu; Choudhury, Sutanay; Hero, Alfred

Many modern datasets can be represented as graphs and hence spectral decompositions such as graph principal component analysis (PCA) can be useful. Distinct from previous graph decomposition approaches based on subspace projection of a single topological feature, e.g., the centered graph adjacency matrix (graph Laplacian), we propose spectral decomposition approaches to graph PCA and graph dictionary learning that integrate multiple features, including graph walk statistics, centrality measures and graph distances to reference nodes. In this paper we propose a new PCA method for single graph analysis, called multi-centrality graph PCA (MC-GPCA), and a new dictionary learning method for ensembles ofmore » graphs, called multi-centrality graph dictionary learning (MC-GDL), both based on spectral decomposition of multi-centrality matrices. As an application to cyber intrusion detection, MC-GPCA can be an effective indicator of anomalous connectivity pattern and MC-GDL can provide discriminative basis for attack classification.« less

Cognitive profile of children and adolescents with anorexia nervosa.

PubMed

Kjaersdam Telléus, Gry; Jepsen, Jens Richardt; Bentz, Mette; Christiansen, Eva; Jensen, Signe O W; Fagerlund, Birgitte; Thomsen, Per Hove

2015-01-01

Few studies of cognitive functioning in children and adolescents with anorexia nervosa (AN) have been conducted. The aim of this study was to examine the neurocognitive and intelligence profile of this clinical group. The study was a matched case-control (N = 188), multi-centre study including children and adolescents with AN (N = 94) and healthy control participants (N = 94). The results suggest that Full Scale Intelligence Quotient (Wechsler Intelligence Scale for Children-III/Wechsler Adult Intelligence Scale-III) in this patient group is close to the normal population mean of 100. Individuals with AN exhibited significantly worse performance in nonverbal intelligence functions (i.e. Wechsler Intelligence Scale for Children-III/Wechsler Adult Intelligence Scale-III, Perceptual Organization Index) and in verbal memory (Test of Memory and Learning-Second Edition, Memory for Stories) and motor speed (Cambridge Neuropsychological Test Automated Battery, Simple and Choice Reaction Time) compared with healthy control participants. No significant difference in set-shifting ability (Cambridge Neuropsychological Test Automated Battery, Intra-Extra Dimensional Set Shift and Trail Making Test B) was found. Inefficiency in nonverbal intelligence functions and in specific cognitive functions was found in this study of children and adolescents with AN. © 2014 The Authors. European Eating Disorders Review published by John Wiley & Sons, Ltd.

Multicentric study on malignant pleural mesothelioma and non-occupational exposure to asbestos

PubMed Central

Magnani, C; Agudo, A; González, C A; Andrion, A; Calleja, A; Chellini, E; Dalmasso, P; Escolar, A; Hernandez, S; Ivaldi, C; Mirabelli, D; Ramirez, J; Turuguet, D; Usel, M; Terracini, B

2000-01-01

Insufficient evidence exists on the risk of pleural mesothelioma from non-occupational exposure to asbestos. A population-based case–control study was carried out in six areas from Italy, Spain and Switzerland. Information was collected for 215 new histologically confirmed cases and 448 controls. A panel of industrial hygienists assessed asbestos exposure separately for occupational, domestic and environmental sources. Classification of domestic and environmental exposure was based on a complete residential history, presence and use of asbestos at home, asbestos industrial activities in the surrounding area, and their distance from the dwelling. In 53 cases and 232 controls without evidence of occupational exposure to asbestos, moderate or high probability of domestic exposure was associated with an increased risk adjusted by age and sex: odds ratio (OR) 4.81, 95% confidence interval (CI) 1.8–13.1. This corresponds to three situations: cleaning asbestos-contaminated clothes, handling asbestos material and presence of asbestos material susceptible to damage. The estimated OR for high probability of environmental exposure (living within 2000 m of asbestos mines, asbestos cement plants, asbestos textiles, shipyards, or brakes factories) was 11.5 (95% CI 3.5–38.2). Living between 2000 and 5000 m from asbestos industries or within 500 m of industries using asbestos could also be associated with an increased risk. A dose–response pattern appeared with intensity of both sources of exposure. It is suggested that low-dose exposure to asbestos at home or in the general environment carries a measurable risk of malignant pleural mesothelioma. © 2000 Cancer Research Campaign PMID:10883677

Combination antiemetic therapy with aprepitant/fosaprepitant in patients with colorectal cancer receiving oxaliplatin-based chemotherapy (SENRI trial): a multicentre, randomised, controlled phase 3 trial.

PubMed

Nishimura, Junichi; Satoh, Taroh; Fukunaga, Mutsumi; Takemoto, Hiroyoshi; Nakata, Ken; Ide, Yoshihito; Fukuzaki, Takayuki; Kudo, Toshihiro; Miyake, Yasuhiro; Yasui, Masayoshi; Morita, Shunji; Sakai, Daisuke; Uemura, Mamoru; Hata, Taishi; Takemasa, Ichiro; Mizushima, Tsunekazu; Ohno, Yuko; Yamamoto, Hirofumi; Sekimoto, Mitsugu; Nezu, Riichiro; Doki, Yuichiro; Mori, Masaki

2015-07-01

The oral neurokinin-1 antagonist aprepitant is recommended in several guidelines for preventing chemotherapy-induced nausea & vomiting (CINV) due to highly emetogenic cancer chemotherapy. Little is known about the feasibility and safety of aprepitant in patients treated with oxaliplatin. In this multicentre, open label, randomised, phase 3 trial, we recruited patients with colorectal cancer who underwent an oxaliplatin-based chemotherapy. Patients were centrally randomised in a 1:1 ratio to the control group (5-HT3-receptor antagonist+dexamethasone) or aprepitant group (5-HT3-receptor antagonist+dexamethasone+aprepitant or fosaprepitant) in the first course. All patients were treated with aprepitant/fosaprepitant therapy in the second course. The primary end-point was the proportion of patients with no emesis. A total of 413 patients entered this clinical trial from 25 centres in Japan. Significantly more patients in the aprepitant group achieved no vomiting overall and delayed phase than those in the control group (95.7% versus 83.6%, and 95.7% versus 84.7%, respectively). The aprepitant group also had statistically significantly higher percentages of no significant nausea, complete response and complete protection than the control group overall. In the control group, the percentages of no vomiting were higher in the second cycle than in the first cycle. The incidence of vomiting occurred day 7 or later was significantly higher in the control group compared with the aprepitant group. Other adverse events were not significant between the groups. The aprepitant therapy was more effective than the control therapy for prevention of CINV in colorectal cancer patients receiving an oxaliplatin-based regimen. Copyright © 2015 Elsevier Ltd. All rights reserved.

A possible genetic association with chronic fatigue in primary Sjögren's syndrome: a candidate gene study.

PubMed

Norheim, Katrine Brække; Le Hellard, Stephanie; Nordmark, Gunnel; Harboe, Erna; Gøransson, Lasse; Brun, Johan G; Wahren-Herlenius, Marie; Jonsson, Roland; Omdal, Roald

2014-02-01

Fatigue is prevalent and disabling in primary Sjögren's syndrome (pSS). Results from studies in chronic fatigue syndrome (CFS) indicate that genetic variation may influence fatigue. The aim of this study was to investigate single nucleotide polymorphism (SNP) variations in pSS patients with high and low fatigue. A panel of 85 SNPs in 12 genes was selected based on previous studies in CFS. A total of 207 pSS patients and 376 healthy controls were genotyped. One-hundred and ninety-three patients and 70 SNPs in 11 genes were available for analysis after quality control. Patients were dichotomized based on fatigue visual analogue scale (VAS) scores, with VAS <50 denominated "low fatigue" (n = 53) and VAS ≥50 denominated "high fatigue" (n = 140). We detected signals of association with pSS for one SNP in SLC25A40 (unadjusted p = 0.007) and two SNPs in PKN1 (both p = 0.03) in our pSS case versus control analysis. The association with SLC25A40 was stronger when only pSS high fatigue patients were analysed versus controls (p = 0.002). One SNP in PKN1 displayed an association in the case-only analysis of pSS high fatigue versus pSS low fatigue (p = 0.005). This candidate gene study in pSS did reveal a trend for associations between genetic variation in candidate genes and fatigue. The results will need to be replicated. More research on genetic associations with fatigue is warranted, and future trials should include larger cohorts and multicentre collaborations with sharing of genetic material to increase the statistical power.

Work productivity and activity impairment in gastroesophageal reflux disease in Korean full-time employees: a multicentre study.

PubMed

Shin, Woon Geon; Kim, Heung Up; Kim, Sang Gyun; Kim, Gwang Ha; Shim, Ki-Nam; Kim, Jeong Wook; Kim, Jin Il; Kim, Jae Gyu; Kim, Jae J; Yim, Da-Hae; Park, Sue K; Park, Soo-Heon

2012-04-01

The costs of gastroesophageal reflux disease have not been assessed in Asia, even though the prevalence of gastroesophageal reflux disease is gradually increasing. We evaluated work presenteeism and absenteeism as indirect costs of gastroesophageal reflux disease in Korea. This was a cross-sectional and multicentre study using patient-reported outcome instruments. A total of 1009 full-time employees who visited the gastrointestinal department for any reason (281 patients with gastroesophageal reflux disease and 728 controls) were included. Main outcomes were presenteeism and absenteeism measured as work productivity loss and monetary cost per week. Absenteeism and presenteeism were significantly higher in the gastroesophageal reflux disease than the control group (1.49% vs. 0.46%, P=0.0010; 34.13% vs. 9.23%, P<0.0001). Loss of work productivity was significantly greater in the gastroesophageal reflux disease than the control group (33.09% vs. 9.02%; P<0.0001). This loss of work productivity difference between the two groups represented an additional productivity loss of 11.7h/week in the gastroesophageal reflux disease group compared with the control group. Assuming average hourly wages of $14.12, the weekly burden of gastroesophageal reflux disease reached $165.07 per person. Gastroesophageal reflux disease was associated with substantial work productivity loss, mainly due to presenteeism rather than absenteeism, in Korean full-time employees. Copyright © 2011 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.

Efficacy and safety of teneligliptin, a novel dipeptidyl peptidase-4 inhibitor, in Korean patients with type 2 diabetes mellitus: a 24-week multicentre, randomized, double-blind, placebo-controlled phase III trial.

PubMed

Hong, S; Park, C-Y; Han, K A; Chung, C H; Ku, B J; Jang, H C; Ahn, C W; Lee, M-K; Moon, M K; Son, H S; Lee, C B; Cho, Y-W; Park, S-W

2016-05-01

We assessed the 24-week efficacy and safety of teneligliptin, a novel dipeptidyl peptidase-4 inhibitor, in Korean patients with type 2 diabetes mellitus (T2DM) that was inadequately controlled with diet and exercise. The present study was designed as a multicentre, randomized, double-blind, placebo-controlled, parallel-group, phase III study. Patients (n = 142) were randomized 2 : 1 into two different treatment groups as follows: 99 received teneligliptin (20 mg) and 43 received placebo. The primary endpoint was change in glycated haemoglobin (HbA1c) level from baseline to week 24. Teneligliptin significantly reduced the HbA1c level from baseline compared with placebo after 24 weeks. At week 24, the differences between changes in HbA1c and fasting plasma glucose (FBG) in the teneligliptin and placebo groups were -0.94% [least-squares (LS) mean -1.22, -0.65] and -1.21 mmol/l (-1.72, -0.70), respectively (all p < 0.001). The incidence of hypoglycaemia and adverse events were not significantly different between the two groups. This phase III, randomized, placebo-controlled study provides evidence of the safety and efficacy of 24 weeks of treatment with teneligliptin as a monotherapy in Korean patients with T2DM. © 2016 The Authors. Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd.

Thromboembolism in Dogs with Protein-Losing Enteropathy with Non-Neoplastic Chronic Small Intestinal Disease.

PubMed

Jacinto, Ana M L; Ridyard, Alison E; Aroch, Itamar; Watson, Penny J; Morrison, Linda R; Chandler, Marge L; Kuzi, Sharon

Dogs with protein-losing enteropathy (PLE) are suggested to be at increased risk of developing thromboembolic events. However, with some exceptions, there are very few reports of thromboembolism in such dogs. This multicentre retrospective observational study describes a case series of thromboembolism (TE) in eight dogs with PLE secondary to non-neoplastic, chronic small intestinal disease. Seven dogs had poorly controlled PLE when the thromboembolic event occurred. Pulmonary thromboembolism (PTE) occurred in six dogs, while one dog developed splenic vein thrombosis and another had concurrent splenic vein and aortic TE. Six dogs died, all with PTE. Antithrombin activity was decreased in one of two dogs in which it was measured. Serum cobalamin and folate concentrations were measured in three dogs and cobalamin was subnormal in all three. Serum magnesium, measured in two dogs, was low in both. Dogs with uncontrolled chronic small intestinal disease and PLE are at risk for developing serious life-threatening TE, mostly PTE.

Association between smoking status and the parameters of vascular structure and function in adults: results from the EVIDENT study.

PubMed

Recio-Rodriguez, Jose I; Gomez-Marcos, Manuel A; Patino Alonso, Maria C; Martin-Cantera, Carlos; Ibañez-Jalon, Elisa; Melguizo-Bejar, Amor; Garcia-Ortiz, Luis

2013-12-01

The present study analyses the relation between smoking status and the parameters used to assess vascular structure and function. This cross-sectional, multi-centre study involved a random sample of 1553 participants from the EVIDENT study. The smoking status, peripheral augmentation index and ankle-brachial index were measured in all participants. In a small subset of the main population (265 participants), the carotid intima-media thickness and pulse wave velocity were also measured. After controlling for the effect of age, sex and other risk factors, present smokers have higher values of carotid intima-media thickness (p = 0.011). Along the same lines, current smokers have higher values of pulse wave velocity and lower mean values of ankle-brachial index but without statistical significance in both cases. Among the parameters of vascular structure and function analysed, only the IMT shows association with the smoking status, after adjusting for confounders.

Association between smoking status and the parameters of vascular structure and function in adults: results from the EVIDENT study

PubMed Central

2013-01-01

Background The present study analyses the relation between smoking status and the parameters used to assess vascular structure and function. Methods This cross-sectional, multi-centre study involved a random sample of 1553 participants from the EVIDENT study. Measurements: The smoking status, peripheral augmentation index and ankle-brachial index were measured in all participants. In a small subset of the main population (265 participants), the carotid intima-media thickness and pulse wave velocity were also measured. Results After controlling for the effect of age, sex and other risk factors, present smokers have higher values of carotid intima-media thickness (p = 0.011). Along the same lines, current smokers have higher values of pulse wave velocity and lower mean values of ankle-brachial index but without statistical significance in both cases. Conclusions Among the parameters of vascular structure and function analysed, only the IMT shows association with the smoking status, after adjusting for confounders. PMID:24289208

[Sentinel node biopsy in patients with multifocal and multicentric breast cancer: A 5-year follow-up].

PubMed

Blanco Saiz, I; López Carballo, M T; Martínez Fernández, J; Carrión Maldonado, J; Cabrera Pereira, A; Moral Alvarez, S; Santamaría Girón, L; Cantero Cerquella, F; López Secades, A; Díaz González, D; Llaneza Folgueras, A; Aira Delgado, F J

2014-01-01

Sentinel lymph node biopsy (SLNB) as a staging procedure in multiple breast cancer is a controversial issue. We have aimed to evaluate the efficacy of sentinel node (SN) detection in patients with multifocal or multicentric breast cancer as well as the safety of its clinical application after a long follow-up. A prospective descriptive study was performed. Eighty-nine patients diagnosed of multiple breast cancer (73 multifocal; 16 multicentric) underwent SLNB. These patients were compared to those with unifocal neoplasia. Periareolar radiocolloid administration was performed in most of the patients. Evaluation was made at an average of 67.2 months of follow-up (32-126 months). Scintigraphic and surgical SN localization in patients with multiple breast cancer were 95.5% and 92.1%, respectively. A higher percentage of extra-axillary nodes was observed than in the unifocal group (11.7% vs 5.4%) as well as a significantly higher number of SN per patient (1.70 vs 1.38). The rate of SN localization in multicentric cancer was slightly lower than in multifocal cancer (87.5% vs 93.1%), and the finding of extra-axillary drainages was higher (20% vs 10%). Number of SN per patient was significantly higher in multicentric breast cancer (2.33 vs 1.57). No axillary relapses have been demonstrated in the follow-up in multiple breast cancer patients group. SLNB performed by periareolar injection is a reliable and accurate staging procedure of patients with multiple breast cancer, including those with multicentric processes. Copyright © 2013 Elsevier España, S.L. and SEMNIM. All rights reserved.

Revisiting the Robustness of PET-Based Textural Features in the Context of Multi-Centric Trials

PubMed Central

Bailly, Clément; Bodet-Milin, Caroline; Couespel, Solène; Necib, Hatem; Kraeber-Bodéré, Françoise; Ansquer, Catherine; Carlier, Thomas

2016-01-01

Purpose This study aimed to investigate the variability of textural features (TF) as a function of acquisition and reconstruction parameters within the context of multi-centric trials. Methods The robustness of 15 selected TFs were studied as a function of the number of iterations, the post-filtering level, input data noise, the reconstruction algorithm and the matrix size. A combination of several reconstruction and acquisition settings was devised to mimic multi-centric conditions. We retrospectively studied data from 26 patients enrolled in a diagnostic study that aimed to evaluate the performance of PET/CT 68Ga-DOTANOC in gastro-entero-pancreatic neuroendocrine tumors. Forty-one tumors were extracted and served as the database. The coefficient of variation (COV) or the absolute deviation (for the noise study) was derived and compared statistically with SUVmax and SUVmean results. Results The majority of investigated TFs can be used in a multi-centric context when each parameter is considered individually. The impact of voxel size and noise in the input data were predominant as only 4 TFs presented a high/intermediate robustness against SUV-based metrics (Entropy, Homogeneity, RP and ZP). When combining several reconstruction settings to mimic multi-centric conditions, most of the investigated TFs were robust enough against SUVmax except Correlation, Contrast, LGRE, LGZE and LZLGE. Conclusion Considering previously published results on either reproducibility or sensitivity against delineation approach and our findings, it is feasible to consider Homogeneity, Entropy, Dissimilarity, HGRE, HGZE and ZP as relevant for being used in multi-centric trials. PMID:27467882

Is screening for fetal anomalies reliable in HIV-infected pregnant women? A multicentre study.

PubMed

Brossard, Philippe; Boulvain, Michel; Coll, Oriol; Barlow, Patricia; Aebi-Popp, Karoline; Bischof, Paul; Martinez de Tejada, Begoña

2008-10-01

To assess the impact of HIV infection on the reliability of the first-trimester screening for Down syndrome, using free beta-human chorionic gonadotrophin, pregnancy-associated plasma protein-A and fetal nuchal translucency, and of the second-trimester screening for neural tube defects, using alpha-fetoprotein. Multicentre study comparing the multiples of the median of markers for Down syndrome and neural tube defect screening among 214 HIV-infected pregnant women and 856 HIV-negative controls undergoing a first-trimester Down syndrome screening test, and 209 HIV-positive women and 836 HIV-negative controls with a risk evaluation for neural tube defect. The influence of treatment, chronic hepatitis and HIV disease characteristics were also evaluated. Multiples of the median medians for pregnancy-associated plasma protein-A and beta-human chorionic gonadotrophin were lower in HIV-positive women than controls (0.88 vs. 1.05 and 0.84 vs. 1.09, respectively; P < 0.005), but these differences had no impact on risk estimation; no differences were observed for the other markers. No association was found between HIV disease characteristics, antiretroviral treatment use at the time of screening or chronic hepatitis and marker levels. Screening for Down syndrome during the first trimester and for neural tube defect during the second trimester is accurate for HIV-infected women and should be offered, similar to HIV-negative women.

Intravenous thrombolysis guided by a telemedicine consultation system for acute ischaemic stroke patients in China: the protocol of a multicentre historically controlled study

PubMed Central

Yuan, Ziwen; Wang, Bo; Li, Feijiang; Wang, Jing; Zhi, Jin; Luo, Erping; Liu, Zhirong; Zhao, Gang

2015-01-01

Introduction The rate of intravenous thrombolysis with tissue-type plasminogen activator or urokinase for stroke patients is extremely low in China. It has been demonstrated that a telestroke service may help to increase the rate of intravenous thrombolysis and improve stroke care quality in local hospitals. The aim of this study, also called the Acute Stroke Advancing Program, is to evaluate the effectiveness and safety of decision-making concerning intravenous thrombolysis via a telemedicine consultation system for acute ischaemic stroke patients in China. Methods and analysis This is a multicentre historically controlled study with a planned enrolment of 300 participants in each of two groups. The telestroke network consists of one hub hospital and 14 spoke hospitals in underserved regions of China. The usual stroke care quality in the spoke hospitals without guidance from the hub hospital will be used as the historical control. The telemedicine consultation system is an interactive, two-way, wireless, audiovisual system accessed on portable devices. The primary outcome is the percentage of patients treated with intravenous thrombolysis within 4.5 h of stroke onset. Ethics and dissemination The project has been approved by the Institutional Review Board of Xijing Hospital. The results will be published in scientific journals and presented to local government and relevant institutes. Trial registration number NCT02088346 (12 March 2014). PMID:25979867

CoDuSe group exercise programme improves balance and reduces falls in people with multiple sclerosis: A multi-centre, randomized, controlled pilot study.

PubMed

Carling, Anna; Forsberg, Anette; Gunnarsson, Martin; Nilsagård, Ylva

2017-09-01

Imbalance leading to falls is common in people with multiple sclerosis (PwMS). To evaluate the effects of a balance group exercise programme (CoDuSe) on balance and walking in PwMS (Expanded Disability Status Scale, 4.0-7.5). A multi-centre, randomized, controlled single-blinded pilot study with random allocation to early or late start of exercise, with the latter group serving as control group for the physical function measures. In total, 14 supervised 60-minute exercise sessions were delivered over 7 weeks. Pretest-posttest analyses were conducted for self-reported near falls and falls in the group starting late. Primary outcome was Berg Balance Scale (BBS). A total of 51 participants were initially enrolled; three were lost to follow-up. Post-intervention, the exercise group showed statistically significant improvement ( p = 0.015) in BBS and borderline significant improvement in MS Walking Scale ( p = 0.051), both with large effect sizes (3.66; -2.89). No other significant differences were found between groups. In the group starting late, numbers of falls and near falls were statistically significantly reduced after exercise compared to before ( p < 0.001; p < 0.004). This pilot study suggests that the CoDuSe exercise improved balance and reduced perceived walking limitations, compared to no exercise. The intervention reduced falls and near falls frequency.

Positive and cost-effectiveness effect of spa therapy on the resumption of occupational and non-occupational activities in women in breast cancer remission: a French multicentre randomised controlled trial.

PubMed

Mourgues, Charline; Gerbaud, Laurent; Leger, Stéphanie; Auclair, Candy; Peyrol, Fleur; Blanquet, Marie; Kwiatkowski, Fabrice; Leger-Enreille, Anne; Bignon, Yves-Jean

2014-10-01

The main aim was to assess the effects of a spa treatment on the resumption of occupational and non-occupational activities and the abilities of women in breast cancer remission. A cost-effectiveness analysis (CEA) was also performed. A multicentre randomised controlled trial was carried out between 2008 and 2010 in the University Hospital of Auvergne and two private hospitals in Clermont-Ferrand, France. Eligible patients were women in complete breast cancer remission without contraindication for physical activities or cognitive disorders and a body mass index between 18.5 and 40 kg/m(2). The intervention group underwent spa treatment combined with consultation with dietician whereas the control underwent consultations with the dietician only. Of the 181 patients randomised, 92 and 89 were included in the intervention and the control groups, respectively. The CEA involved 90 patients, 42 from the intervention group and 48 from the control group. The main results showed a higher rate of resumption of occupational activities in the intervention group (p = 0.0025) and a positive effect of the intervention on the women's ability to perform occupational activities 12 months after the beginning of the study (p = 0.0014), and on their ability to perform family activities (p = 0.033). The stay in a thermal centre was cost-effective at 12 months. Spa treatment is a cost-effective strategy to improve resumption of occupational and non-occupational activities and the abilities of women in breast cancer remission. Copyright © 2014 Elsevier Ltd. All rights reserved.

[Effectiveness of a micronized purified flavonoid fraction (MPFF) in the healing process of lower limb ulcers. An open multicentre study, controlled and randomized].

PubMed

Glinski, W; Chodynicka, B; Roszkiewicz, J; Bogdanowski, T; Lecewicz-Torun, B; Kaszuba, A; Bowszyc, J; Nowak, A; Wnorowski, J; Wasik, F; Glinska-Ferenz, M; Blaszczyk, M; Strzyga, P; Pachocki, R

2001-04-01

To determine the increase in healing rate of venous ulcer in patients receiving a micronised purified flavonoid fraction (MPFF) as supplementation to standard local care. A randomised, open, controlled, multicentre study. Departments of Dermatology and University Outpatients Clinics. One hundred and forty patients with chronic venous insufficiency and venous ulcers. PATIENTS received standard compressive therapy plus external treatment alone or 2 tablets of MPFF daily in addition to the above treatment for 24 weeks. Healing of ulcers and their reduction in size after 24 weeks of treatment. The percentage of patients whose ulcers healed completely was found to be markedly higher in those receiving MPFF in addition to standard external and compressive treatment than in those treated with conventional therapy alone (46.5% vs 27.5%; p<0.05. OR=2.3, 95% CI 1.1-4.6). Ulcers with diameters <3 cm were cured in 71% of patients in the MPFF group and in 50% of patients in the control group, whereas ulcers between 3 and 6 cm in diameter were cured in 60% and 32% of patients (p<0.05), respectively. The mean reduction in ulcer size was also found to be greater in patients treated with MPFF (80%) than in the control group (65%) (p<0.05). The cost-effectiveness ratio (cost per healed ulcer) in the MPFF group was 1026.2 compared with 1871.8 in the control group. These results indicate that MPFF significantly improves the cure rate in patients with chronic venous insufficiency.

Socioeconomic status and exposure to disinfection by-products in drinking water in Spain.

PubMed

Castaño-Vinyals, Gemma; Cantor, Kenneth P; Villanueva, Cristina M; Tardon, Adonina; Garcia-Closas, Reina; Serra, Consol; Carrato, Alfredo; Malats, Núria; Rothman, Nathaniel; Silverman, Debra; Kogevinas, Manolis

2011-03-16

Disinfection by-products in drinking water are chemical contaminants that have been associated with cancer and other adverse effects. Exposure occurs from consumption of tap water, inhalation and dermal absorption. We determined the relationship between socioeconomic status and exposure to disinfection by-products in 1271 controls from a multicentric bladder cancer case-control study in Spain. Information on lifetime drinking water sources, swimming pool attendance, showering-bathing practices, and socioeconomic status (education, income) was collected through personal interviews. The most highly educated subjects consumed less tap water (57%) and more bottled water (33%) than illiterate subjects (69% and 17% respectively, p-value = 0.003). These differences became wider in recent time periods. The time spent bathing or showering was positively correlated with attained educational level (p < 0.001). Swimming pool attendance was more frequent among highly educated subjects compared to the illiterate (odds ratio = 3.4; 95% confidence interval 1.6-7.3). The most highly educated subjects were less exposed to chlorination by-products through ingestion but more exposed through dermal contact and inhalation in pools and showers/baths. Health risk perceptions and economic capacity may affect patterns of water consumption that can result in differences in exposure to water contaminants.

[Local approval procedures act as a brake on RCTs].

PubMed

van der Stok, E P; Huiskens, J; Hemmes, B; Grünhagen, D J; van Gulik, T M; Verhoef, C; Punt, C J A

2016-01-01

Large multicentre randomised controlled trials (RCTs) in the Netherlands are increasingly being impeded by major differences between local approval procedures. However, no national agenda exists as yet to improve this situation. The existence of major local differences in processing time and documentation required has been reported previously but little is known about the costs incurred and whether or not specific certifications and research contracts are mandatory. The current study evaluated these aspects of local procedures for obtaining approval of two oncological multicentre RCTs. Retrospective, descriptive. All local procedures for obtaining approval of two randomised clinical trials were evaluated: the CAIRO5 and CHARISMA trials initiated by the Dutch Colorectal Cancer Group (DCCG). We objectified time between approval by the Medical Ethics Review Committee (METC) and final approval by the Board of Directors (RvB), the type and number of documents needed, and costs charged. The median time interval between the approval by the Medical Ethics Review Committee and the approval by the Board of Directors was 90 days (range 4-312). The number of documents required per centre ranged from 6-20. The costs charged ranged from € 0-€ 1750, and amounted to € 8575 for all procedures combined. No costs were charged by the majority of the centres. The approval procedures for multicentre clinical trials in the Netherlands demonstrate major differences. Processing times, documentation required and costs are unpredictable; greater uniformity is highly desirable in this context.

CADASIL: Treatment and Management Options.

PubMed

Bersano, Anna; Bedini, Gloria; Oskam, Joshua; Mariotti, Caterina; Taroni, Franco; Baratta, Silvia; Parati, Eugenio Agostino

2017-09-01

CADASIL is a life-threatening and disabling disease. Despite the progress achieved so far, no therapies able to limit the disease progression have been found and only empiric treatments can be employed to relieve the main disease symptoms. Further in vivo studies as well as data aggregation and multi-centre controlled clinical trials are needed to confirm the emerging findings in order to identify evidence-based therapies for CADASIL.

Maintenance Cognitive Stimulation Therapy (CST) for dementia: A single-blind, multi-centre, randomized controlled trial of Maintenance CST vs. CST for dementia

PubMed Central

2010-01-01

Background Psychological treatments for dementia are widely used in the UK and internationally, but only rarely have they been standardised, adequately evaluated or systematically implemented. There is increasing recognition that psychosocial interventions may have similar levels of effectiveness to medication, and both can be used in combination. Cognitive Stimulation Therapy (CST) is a 7-week cognitive-based approach for dementia that has been shown to be beneficial for cognition and quality of life and is cost-effective, but there is less conclusive evidence for the effects of CST over an extended period. Methods/Design This multi-centre, pragmatic randomised controlled trial (RCT) to assess the effectiveness and cost-effectiveness of Maintenance CST groups for dementia compares a intervention group who receive CST for 7 weeks followed by the Maintenance CST programme once a week for 24 weeks with the control group who receive CST for 7 weeks, followed by treatment as usual for 24 weeks. The primary outcome measures are quality of life of people with dementia assessed by the QoL-AD and cognition assessed by the ADAS-Cog. Secondary outcomes include the person with dementia's mood, behaviour, activities of daily living, ability to communicate and costs; as well as caregiver health-related quality of life. Using a 5% significance level, comparison of 230 participants will yield 80% power to detect a standardised difference of 0.39 on the ADAS-Cog between the groups. The trial includes a cost-effectiveness analysis from a public sector perspective. Discussion A pilot study of longer-term Maintenance CST, offering 16 weekly sessions of maintenance following the initial CST programme, previously found a significant improvement in cognitive function (MMSE) for those on the intervention group. The study identified the need for a large-scale, multi-centre RCT to define the potential longer-term benefits of continuing the therapy. This study aims to provide definitive evidence of the potential efficacy of maintenance CST and establish how far the long-term benefits can be compared with antidementia drugs such as cholinesterase inhibitors. Trial Registration ISRCTN26286067 PMID:20426866

Does the effect of one-day simulation team training in obstetric emergencies decline within one year? A post-hoc analysis of a multicentre cluster randomised controlled trial.

PubMed

van de Ven, J; Fransen, A F; Schuit, E; van Runnard Heimel, P J; Mol, B W; Oei, S G

2017-09-01

Does the effect of one-day simulation team training in obstetric emergencies decline within one year? A post-hoc analysis of a multicentre cluster randomised controlled trial. J van de Ven, AF Fransen, E Schuit, PJ van Runnard Heimel, BW Mol, SG Oei OBJECTIVE: To investigate whether the effect of a one-day simulation-based obstetric team training on patient outcome changes over time. Post-hoc analysis of a multicentre, open, randomised controlled trial that evaluated team training in obstetrics (TOSTI study).We studied women with a singleton pregnancy beyond 24 weeks of gestation in 24 obstetric units. Included obstetric units were randomised to either a one-day, multi-professional simulation-based team training focusing on crew resource management in a medical simulation centre (12 units) or to no team training (12 units). We assessed whether outcomes differed between both groups in each of the first four quarters following the team training and compared the effect of team training over quarters. Primary outcome was a composite outcome of low Apgar score, severe postpartum haemorrhage, trauma due to shoulder dystocia, eclampsia and hypoxic-ischemic encephalopathy. During a one year period after the team training the rate of obstetric complications, both on the composite level and the individual component level, did not differ between any of the quarters. For trauma due to shoulder dystocia team training led to a significant decrease in the first quarter (0.06% versus 0.26%, OR 0.19, 95% CI 0.03 to 0.98) but in the subsequent quarters no significant reductions were observed. Similar results were found for invasive treatment for severe postpartum haemorrhage where a significant increase was only seen in the first quarter (0.4% versus 0.03%, OR 19, 95% CI 2.5-147), and not thereafter. The beneficial effect of a one-day, simulation-based, multiprofessional, obstetric team training seems to decline after three months. If team training is further evaluated or implemented, repetitive training sessions every three months seem therefore recommended. Copyright © 2017 Elsevier B.V. All rights reserved.

Maintenance Cognitive Stimulation Therapy (CST) for dementia: a single-blind, multi-centre, randomized controlled trial of Maintenance CST vs. CST for dementia.

PubMed

Aguirre, Elisa; Spector, Aimee; Hoe, Juanita; Russell, Ian T; Knapp, Martin; Woods, Robert T; Orrell, Martin

2010-04-28

Psychological treatments for dementia are widely used in the UK and internationally, but only rarely have they been standardised, adequately evaluated or systematically implemented. There is increasing recognition that psychosocial interventions may have similar levels of effectiveness to medication, and both can be used in combination. Cognitive Stimulation Therapy (CST) is a 7-week cognitive-based approach for dementia that has been shown to be beneficial for cognition and quality of life and is cost-effective, but there is less conclusive evidence for the effects of CST over an extended period. This multi-centre, pragmatic randomised controlled trial (RCT) to assess the effectiveness and cost-effectiveness of Maintenance CST groups for dementia compares a intervention group who receive CST for 7 weeks followed by the Maintenance CST programme once a week for 24 weeks with the control group who receive CST for 7 weeks, followed by treatment as usual for 24 weeks.The primary outcome measures are quality of life of people with dementia assessed by the QoL-AD and cognition assessed by the ADAS-Cog. Secondary outcomes include the person with dementia's mood, behaviour, activities of daily living, ability to communicate and costs; as well as caregiver health-related quality of life. Using a 5% significance level, comparison of 230 participants will yield 80% power to detect a standardised difference of 0.39 on the ADAS-Cog between the groups. The trial includes a cost-effectiveness analysis from a public sector perspective. A pilot study of longer-term Maintenance CST, offering 16 weekly sessions of maintenance following the initial CST programme, previously found a significant improvement in cognitive function (MMSE) for those on the intervention group. The study identified the need for a large-scale, multi-centre RCT to define the potential longer-term benefits of continuing the therapy. This study aims to provide definitive evidence of the potential efficacy of maintenance CST and establish how far the long-term benefits can be compared with antidementia drugs such as cholinesterase inhibitors.

Ankle Injury Management (AIM): design of a pragmatic multi-centre equivalence randomised controlled trial comparing Close Contact Casting (CCC) to Open surgical Reduction and Internal Fixation (ORIF) in the treatment of unstable ankle fractures in patients over 60 years.

PubMed

Willett, Keith; Keene, David J; Morgan, Lesley; Gray, Bridget; Handley, Robert; Chesser, Tim; Pallister, Ian; Tutton, Elizabeth; Knox, Christopher; Lall, Ranjit; Briggs, Andrew; Lamb, Sarah E

2014-03-12

Ankle fractures account for 9% of all fractures with a quarter of these occurring in adults over 60 years. The short term disability and long-term consequences of this injury can be considerable. Current opinion favours open reduction and internal fixation (ORIF) over non-operative treatment (fracture manipulation and the application of a standard moulded cast) for older people. Both techniques are associated with complications but the limited published research indicates higher complication rates of fracture malunion (poor position at healing) with casting. The aim of this study is to compare ORIF with a modification of existing casting techniques, Close Contact Casting (CCC). We propose that CCC may offer an equivalent functional outcome to ORIF and avoid the risks associated with surgery. This study is a pragmatic multi-centre equivalence randomised controlled trial. 620 participants will be randomised to receive ORIF or CCC after sustaining an isolated displaced unstable ankle fracture. Participants will be recruited from a minimum of 20 National Health Service (NHS) acute hospitals throughout England and Wales. Participants will be aged over 60 years and be ambulatory prior to injury. Follow-up will be at six weeks and six months after randomisation. The primary outcome is the Olerud & Molander Ankle Score, a functional patient reported outcome measure, at 6 months. Follow-up will also include assessments of mobility, ankle range of movement, health related quality of life and complications. The six-month follow-up will be conducted face-to-face by an assessor blinded to the allocated intervention. A parallel economic evaluation will consider both a health service and a broader societal perspective including the individual and their family. In order to explore patient experience of their treatment and recovery, a purposive sample of 40 patients will also be interviewed using a semi-structured interview schedule between 6-10 weeks post treatment. This multicentre study was open to recruitment July 2010 and recruitment is due to be completed in December 2013. Current Controlled Trials ISRCTN04180738.

A Phase IIIb, Multicentre, Randomised, Parallel-Group, Placebo-Controlled, Double-Blind Study to Investigate the Efficacy and Safety of OROS Hydromorphone in Subjects with Moderate-to-Severe Chronic Pain Induced by Osteoarthritis of the Hip or the Knee

PubMed Central

Vojtaššák, Jozef; Vojtaššák, Jozef; Jacobs, Adam; Rynn, Leonie; Waechter, Sandra; Richarz, Ute

2011-01-01

Background. Opioid analgesics are included in treatment guidelines for the symptomatic management of osteoarthritis (OA). Starting with a low dose of opioid and slowly titrating to a higher dose may help avoid intolerable side effects. Methods. Subjects aged ≥40 years, with moderate to severe pain induced by OA of the hip or knee not adequately controlled by previous non-steroidal anti-inflammatory drugs (NSAIDs) or paracetamol treatment, were enrolled. Subjects received OROS hydromorphone 4 mg or placebo once-daily. The dose was titrated every 3-4 days in case of unsatisfactory pain control during the 4-week titration phase. A 12 week maintenance phase followed. The primary efficacy endpoint was the change in “pain on average” measured on the Brief Pain Inventory (BPI) scale from baseline to the end of the maintenance phase. Results. 139 subjects received OROS hydromorphone and 149 subjects received placebo. All efficacy endpoints showed similar improvements from baseline to end of study in the 2 groups. The safety results were consistent with the safety profile of OROS hydromorphone. Conclusion.The study did not meet the primary endpoint; although many subjects' pain was not adequately controlled at inclusion, their pain may have improved with continued paracetamol or NSAID treatment. PMID:22110921

Authorship issues in multi-centre clinical trials: the importance of making an authorship contract.

PubMed

Rosenberg, Jacob; Burcharth, Jakob; Pommergaard, Hans-Christian; Vinther, Siri

2015-02-01

Discussions about authorship often arise in multi-centre clinical trials. Such trials may involve up to hundreds of contributors of whom some will eventually co-author the final publication. It is, however, often impossible to involve all contributors in the manuscript process sufficiently for them to qualify for authorship as defined by the International Committee of Medical Journal Editors. Therefore, rules for authorship in multi-centre trials are strongly recommended. We propose two contracts to prevent conflicts regarding authorship; both are freely available for use without pay but with reference to the original source.

Conducting a multicentre and multinational qualitative study on patient transitions.

PubMed

Johnson, Julie K; Barach, Paul; Vernooij-Dassen, Myrra

2012-12-01

A multicentre, multinational research study requires careful planning and coordination to accomplish the aims of the study and to ensure systematic and rigorous examination of all project methods and data collected. The aim of this paper is to describe the approach we used during the HANDOVER Project to develop a multicentre, multinational research project for studying transitions of patient care while creating a community of practice for the researchers. We highlight the process used to assure the quality of a multicentre qualitative study and to create a codebook for data analysis as examples of attending to the community of practice while conducting rigorous qualitative research. Essential elements for the success of this multinational, multilanguage research project included recruiting a strong research team, explicit planning for decision-making processes to be used throughout the project, acknowledging the differences among the study settings and planning the protocols to capitalise upon those differences. Although not commonly discussed in reports of large research projects, there is an underlying, concurrent stream of activities to develop a cohesive team that trusts and respects one another's skills and that engage independent researchers in a group process that contributes to achieving study goals. We discuss other lessons learned and offer recommendations for other teams planning multicentre research.

Non-commercial vs. commercial clinical trials: a retrospective study of the applications submitted to a research ethics committee.

PubMed

Fuentes Camps, Inmaculada; Rodríguez, Alexis; Agustí, Antonia

2018-06-01

There are many difficulties in undertaking independent clinical research without support from the pharmaceutical industry. In this retrospective observational study, some design characteristics, the clinical trial public register and the publication rate of noncommercial clinical trials were compared to those of commercial clinical trials. A total of 809 applications of drug-evaluation clinical trials were submitted from May 2004 to May 2009 to the research ethics committee of a tertiary hospital, and 16.3% of trials were noncommercial. They were mainly phase IV, multicentre national, and unmasked controlled trials, compared to the commercial trials that were mainly phase II or III, multicentre international, and double-blind masked trials. The commercial trials were registered and published more often than noncommercial trials. More funding for noncommercial research is still needed. The results of the research, commercial or noncommercial, should be disseminated in order not to compromise either its scientific or its social value. © 2018 The British Pharmacological Society.

Strengthening Data Confidentiality and Integrity Protection in the Context of a Multi-Centric Information System Dedicated to Autism Spectrum Disorder.

PubMed

Ben Said, Mohamed; Robel, Laurence; Golse, Bernard; Jais, Jean Philippe

2017-01-01

Autism spectrum disorders (ASD) are complex neuro-developmental disorders affecting children in early age. Diagnosis relies on multidisciplinary investigations, in psychiatry, neurology, genetics, electrophysiology, neuro-imagery, audiology, and ophthalmology. To support clinicians, researchers, and public health decision makers, we developed an information system dedicated to ASD, called TEDIS. It was designed to manage systematic, exhaustive and continuous multi-centric patient data collection via secured internet connections. TEDIS will be deployed in nine ASD expert assessment centers in Ile-DeFrance district. We present security policy and infrastructure developed in context of TEDIS to protect patient privacy and clinical information. TEDIS security policy was organized around governance, ethical and organisational chart-agreement, patients consents, controlled user access, patients' privacy protection, constrained patients' data access. Security infrastructure was enriched by further technical solutions to reinforce ASD patients' privacy protection. Solutions were tested on local secured intranet environment and showed fluid functionality with consistent, transparent and safe encrypting-decrypting results.

Reflecting on the methodological challenges of recruiting to a United Kingdom-wide, multi-centre, randomised controlled trial in gynaecology outpatient settings.

PubMed

Dickson, Sylvia; Logan, Janet; Hagen, Suzanne; Stark, Diane; Glazener, Cathryn; McDonald, Alison M; McPherson, Gladys

2013-11-15

Successful recruitment of participants to any trial is central to its success. Trial results are routinely published, and recruitment is often cited to be slower and more difficult than anticipated. This article reflects on the methodological challenges of recruiting women with prolapse attending United Kingdom (UK) gynaecology outpatient clinics to a multi-centre randomised controlled trial (RCT) of physiotherapy, and the systems put in place in an attempt to address them. Gynaecology outpatients with symptomatic prolapse were to be recruited over a 16-month period from 14 UK hospitals and one New Zealand hospital. Eligible women were informed about the trial by their gynaecologist and informed consent was obtained by the central trial office. Recruitment difficulties were encountered early on, and a number of strategies were employed to try to improve recruitment. Some strategies were more successful than others and they differed in the resources required. Actions that facilitated recruitment included increasing recruiting centres to 23 UK and two international hospitals, good centre support, using processes embedded in clinical practice, and good communication between the trial office, collaborators and participants. Collaborator incentives, whereby staff involved received the benefit immediately, were more successful than a nominal monetary payment per woman randomised. Barriers to recruitment included fewer eligible women than anticipated, patient's preference to receive active treatment rather than allocation to the control group, lack of support staff and high staff turnover. Geographical variations in Primary Care Trust Research Management and Governance approval systems and general practitioner (GP) referral procedures also impacted negatively on recruitment. Our article reflects on the methodological challenges of recruiting to a multi-centre RCT in a UK gynaecology setting. Effective interventions included increasing the number of recruiting centres and providing collaborator incentives. Barriers to recruitment included fewer eligible women than anticipated, patient's preference to be allocated to the treatment group, lack of support staff, and variations in approval systems and GP referral procedures. To improve the evidence base on clinical trial recruitment, trialists need to publish their experiences and lessons learned. Future RCTs should evaluate, where possible, the effect of strategies designed to improve recruitment and retention. Current Controlled Trials ISRCTN35911035.

Reflecting on the methodological challenges of recruiting to a United Kingdom-wide, multi-centre, randomised controlled trial in gynaecology outpatient settings

PubMed Central

2013-01-01

Background Successful recruitment of participants to any trial is central to its success. Trial results are routinely published, and recruitment is often cited to be slower and more difficult than anticipated. This article reflects on the methodological challenges of recruiting women with prolapse attending United Kingdom (UK) gynaecology outpatient clinics to a multi-centre randomised controlled trial (RCT) of physiotherapy, and the systems put in place in an attempt to address them. Methods Gynaecology outpatients with symptomatic prolapse were to be recruited over a 16-month period from 14 UK hospitals and one New Zealand hospital. Eligible women were informed about the trial by their gynaecologist and informed consent was obtained by the central trial office. Recruitment difficulties were encountered early on, and a number of strategies were employed to try to improve recruitment. Results Some strategies were more successful than others and they differed in the resources required. Actions that facilitated recruitment included increasing recruiting centres to 23 UK and two international hospitals, good centre support, using processes embedded in clinical practice, and good communication between the trial office, collaborators and participants. Collaborator incentives, whereby staff involved received the benefit immediately, were more successful than a nominal monetary payment per woman randomised. Barriers to recruitment included fewer eligible women than anticipated, patient’s preference to receive active treatment rather than allocation to the control group, lack of support staff and high staff turnover. Geographical variations in Primary Care Trust Research Management and Governance approval systems and general practitioner (GP) referral procedures also impacted negatively on recruitment. Conclusions Our article reflects on the methodological challenges of recruiting to a multi-centre RCT in a UK gynaecology setting. Effective interventions included increasing the number of recruiting centres and providing collaborator incentives. Barriers to recruitment included fewer eligible women than anticipated, patient’s preference to be allocated to the treatment group, lack of support staff, and variations in approval systems and GP referral procedures. To improve the evidence base on clinical trial recruitment, trialists need to publish their experiences and lessons learned. Future RCTs should evaluate, where possible, the effect of strategies designed to improve recruitment and retention. Trial registration Current Controlled Trials ISRCTN35911035 PMID:24228935

Reduced live-birth rates after IVF/ICSI in women with previous unilateral oophorectomy: results of a multicentre cohort study.

PubMed

Lind, Tekla; Holte, Jan; Olofsson, Jan I; Hadziosmanovic, Nermin; Gudmundsson, Johannes; Nedstrand, Elizabeth; Lood, Mikael; Berglund, Lars; Rodriguez-Wallberg, Kenny

2018-02-01

Is there a reduced live-birth rate (LBR) after IVF/ICSI treatment in women with a previous unilateral oophorectomy (UO)? A significantly reduced LBR after IVF/ICSI was found in women with previous UO when compared with women with intact ovaries in this large multicentre cohort, both crudely and after adjustment for age, BMI, fertility centre and calendar period and regardless of whether the analysis was based on transfer of embryos in the fresh cycle only or on cumulative results including transfers using frozen-thawed embryos. Similar pregnancy rates after IVF/ICSI have been previously reported in case-control studies and small cohort studies of women with previous UO versus women without ovarian surgery. In all previous studies multiple embryos were transferred. No study has previously evaluated LBR in a large cohort of women with a history of UO. This research was a multicentre cohort study, including five reproductive medicine centres in Sweden: Carl von Linné Clinic (A), Karolinska University Hospital (B), Uppsala University Hospital (C), Linköping University Hospital (D) and Örebro University Hospital (E). The women underwent IVF/ICSI between January 1999 and November 2015. Single embryo transfer (SET) was performed in approximately 70% of all treatments, without any significant difference between UO exposed women versus controls (68% versus 71%), respectively (P = 0.32), and a maximum of two embryos were transferred in the remaining cases. The dataset included all consecutive treatments and fresh and frozen-thawed cycles. The exposed cohort included 154 women with UO who underwent 301 IVF/ICSI cycles and the unexposed control cohort consisted of 22 693 women who underwent 41 545 IVF/ICSI cycles. Overall, at the five centres (A-E), the exposed cohort underwent 151, 34, 35, 41 and 40 treatments, respectively, and they were compared with controls of the same centre (18 484, 8371, 5575, 4670 and 4445, respectively). The primary outcome was LBR, which was analysed per started cycle, per ovum pick-up (OPU) and per embryo transfer (ET). Secondary outcomes included the numbers of oocytes retrieved and supernumerary embryos obtained, the Ovarian Sensitivity Index (OSI), embryo quality scores and cumulative pregnancy rates. We used a Generalized Estimating Equation (GEE) model for statistical analysis in order to account for repeated treatments. The exposed (UO) and control women's groups were comparable with regard to age and performance of IVF or ICSI. Significant differences in LBR, both crude and age-adjusted, were observed between the UO and control groups: LBR per started cycle (18.6% versus 25.4%, P = 0.007 and P = 0.014, respectively), LBR/OPU (20.3% versus 27.1%, P = 0.012 and P = 0.015, respectively) and LBR/ET (23.0% versus 29.7%, P = 0.022 and P = 0.025, respectively). The differences in LBR remained significant after inclusion of both fresh and frozen-thawed transfers (both crude and age-adjusted data): LBR/OPU (26.1% versus 34.4%, P = 0.005 and P = 0.006, respectively) and LBR/ET (28.3% versus 37.1%, P = 0.006 and P = 0.006, respectively). The crude cancellation rate was significantly higher among women with a history of UO than in controls (18.9% versus 14.5%, P = 0.034 and age-adjusted, P = 0.178). In a multivariate GEE model, the cumulative odds ratios for LBR (fresh and frozen-thawed)/OPU (OR 0.70, 95% CI 0.52-0.94, P = 0.016) and LBR (fresh and frozen-thawed)/ET (OR 0.68, 95% CI 0.51-0.92, P = 0.012) were approximately 30% lower in the group of women with UO when adjusted for age, BMI, reproductive centre, calendar period and number of embryos transferred when appropriate. The OSI was significantly lower in women with a history of UO than in controls (3.6 versus 6.0) and the difference was significant for both crude and age-adjusted data (P = <0.001 for both). Significantly fewer oocytes were retrieved in treatments of women with UO than in controls (7.2 versus 9.9, P = <0.001, respectively). Due to the nature of the topic, this is a retrospective analysis, with all its inherent limitations. Furthermore, the cause for UO was not possible to obtain in all cases. A diagnosis of endometriosis was also more common in the UO group, i.e. a selection bias in terms of poorer patient characteristics in the UO group cannot be completely ruled out. However, adjustment for all known confounders did not affect the general results. To date, this is the largest cohort investigated and the first study indicating an association of achieving reduced live birth after IVF/ICSI in women with previous UO. These findings are novel and contradict the earlier notion that IVF/ICSI treatment is not affected, or is only marginally affected by previous UO. None. Not applicable. © The Author 2017. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com

Efficacy and safety of acarbose chewable tablet in patients with type 2 diabetes: a multicentre, randomized, double-blinded, double-dummy positive controlled trial.

PubMed

Wu, Qian Lin; Liu, Yu Ping; Lu, Ju Ming; Wang, Chang Jiang; Yang, Tao; Dong, Ji Xiang; Li, Cheng Jiang; Ma, Jian Hua; Xue, Yao Ming; Sun, Rui Hua; Wei, Dong; Tian, Hao Ming

2012-08-01

To evaluate the effect and safety of HbA1c and glycemic control of acarbose chewable tablets in patients with type 2 diabetic. A multicentre, randomized, double-blinded, double-dummy, positive controlled clinical trial was conducted. Two hundred thirty-four Chinese patients with type 2 diabetic were enrolled in eight clinical centres, who were divided randomly into the acarbose chewable tablet group (experimental group, n = 116) and the acarbose treatment group (control group, n = 118). Two hundred seven patients (88.5%) took part in the 12-week trial. At the beginning and end of the clinical trial, HbA1c and blood glucose as well as safety indexes were measured. After the treatment, the level of finger two-hour postprandial blood glucose (PPBG) was decreased 4.15 mmol/L (26.82%) and 3.54 mmol/L (22.77%), respectively, in the experiment group and the control group. The levels of venous two-hour PPBG in the experiment group and the control group were decreased 4.04 mmol/L (25.38%) and 2.75 mmol/L (17.26%), respectively, with the means of HbA1c lowering 11.67% and 12.44%, respectively. Fasting blood glucose (FBG) also was reduced significantly in both groups. Patients in both groups showed obvious weight reduction (P < 0.0001). There were no significant differences in the incidence of adverse events between the two groups. In summary, acarbose chewable tablets have a definite curative effect in treating type 2 diabetic patients as HbA1c and blood glucose levels decreased significantly after the 12-week treatment. © 2012 Wiley Publishing Asia Pty Ltd and Chinese Cochrane Center, West China Hospital of Sichuan University.

Short-term outcome of treatment limitation discussions for newborn infants, a multicentre prospective observational cohort study.

PubMed

Aladangady, Narendra; Shaw, Chloe; Gallagher, Katie; Stokoe, Elizabeth; Marlow, Neil

2017-03-01

To determine the short-term outcomes of babies for whom clinicians or parents discussed the limitation of life-sustaining treatment (LST). Prospective multicentre observational study. Two level 3, six level 2 and one level 1 neonatal units in the North-East London Neonatal Network. A total of 87 babies including 68 for whom limiting LST was discussed with parents and 19 babies died without discussion of limiting LST in the labour ward or neonatal unit. Final decision reached after discussions about limiting LST and neonatal unit outcomes (death or survived to discharge) for babies. Withdrawing LST, withholding LST and do not resuscitate (DNR) order was discussed with 48, 16 and 4 parents, respectively. In 49/68 (72%) cases decisions occurred in level 3 and 19 cases in level 2 units. Following the initial discussions, 34/68 parents made the decision to continue LST. In 33/68 cases, a second opinion was obtained. The parents of 14/48 and 2/16 babies did not agree to withdraw and withhold LST, respectively. Forty-seven out of 87 babies (54%) died following limitation of LST, 28/87 (32%) died receiving full intensive care support, 5/87 (6%) survived following a decision to limit LST and 7/87 (8%) babies survived following decision to continue LST. A significant proportion of parents chose to continue treatment following discussions regarding limiting LST for their babies, and a proportion of these babies survived to neonatal unit discharge. The long-term outcomes of babies who survive following limiting LST discussion need to be investigated. 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/.

Sale of antibiotics without a prescription at community pharmacies in urban China: a multicentre cross-sectional survey.

PubMed

Chang, Jie; Ye, Dan; Lv, Bing; Jiang, Minghuan; Zhu, Shan; Yan, Kangkang; Tian, Yun; Fang, Yu

2017-04-01

To quantify sales of antibiotics without a medical prescription and to assess the quality of pharmacy services in relation to the antibiotics sold in community pharmacies in urban China. A multicentre cross-sectional survey of community pharmacies was undertaken in 2015 using the simulated client method. Two clinical case scenarios (paediatric diarrhoea and adult acute upper respiratory infection) were presented at systematically sampled community pharmacies in Eastern (Nanjing), Central (Changsha) and Western China (Xi'an). Of 256 pharmacies, antibiotics were obtained without a prescription from 55.9% (95% CI: 49.5%-62.0%) when paediatric diarrhoea was simulated and from 77.7% (95% CI: 72.1%-82.7%) when adult respiratory infection was simulated. Of the pharmacies where antibiotics were dispensed, 83.9% and 66.3% dispensed after the simulated clients requested or insisted in the case of paediatric diarrhoea and adult respiratory infection, respectively. Significant differences ( P  < 0.001, χ 2 test) in inappropriate antibiotic dispensing were found among cities, with 57.7%, 37.3% and 73.7% in the case of paediatric diarrhoea and 60.8%, 80.7% and 96.1% in adult respiratory infection in Nanjing, Changsha and Xi'an, respectively. Pharmacists were available in only 14.8% (95% CI: 10.7%-19.8%) of the pharmacies. The performance of pharmacy staff regarding the provision of information and advice was unsatisfactory. Antibiotics were easily obtained without a prescription in community pharmacies in urban China. Measures to enhance the enforcement of prescription-only regulations and training programmes for pharmacy staff to promote the appropriate use of antibiotics are warranted. © The Author 2017. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Validation of sentinel lymph node biopsy in breast cancer women N1-N2 with complete axillary response after neoadjuvant chemotherapy. Multicentre study in Tarragona.

PubMed

Carrera, D; de la Flor, M; Galera, J; Amillano, K; Gomez, M; Izquierdo, V; Aguilar, E; López, S; Martínez, M; Martínez, S; Serra, J M; Pérez, M; Martin, L

2016-01-01

The aim of our study was to evaluate sentinel lymph node biopsy as a diagnostic test for assessing the presence of residual metastatic axillary lymph nodes after neoadjuvant chemotherapy, replacing the need for a lymphadenectomy in negative selective lymph node biopsy patients. A multicentre, diagnostic validation study was conducted in the province of Tarragona, on women with T1-T3, N1-N2 breast cancer, who presented with a complete axillary response after neoadjuvant chemotherapy. Study procedures consisted of performing an selective lymph node biopsy followed by lymphadenectomy. A total of 53 women were included in the study. Surgical detection rate was 90.5% (no sentinel node found in 5 patients). Histopathological analysis of the lymphadenectomy showed complete disease regression of axillary nodes in 35.4% (17/48) of the patients, and residual axillary node involvement in 64.6% (31/48) of them. In lymphadenectomy positive patients, 28 had a positive selective lymph node biopsy (true positive), while 3 had a negative selective lymph node biopsy (false negative). Of the 28 true selective lymph node biopsy positives, the sentinel node was the only positive node in 10 cases. All lymphadenectomy negative cases were selective lymph node biopsy negative. These data yield a sensitivity of 93.5%, a false negative rate of 9.7%, and a global test efficiency of 93.7%. Selective lymph node biopsy after chemotherapy in patients with a complete axillary response provides valid and reliable information regarding axillary status after neoadjuvant treatment, and might prevent lymphadenectomy in cases with negative selective lymph node biopsy. Copyright © 2016 Elsevier España, S.L.U. and SEMNIM. All rights reserved.

A Retrospective Multicentre Cohort Review of Patient Characteristics and Surgical Aspects versus the Long-Term Outcomes for Recipients of a Fully Implantable Active Middle Ear Implant

PubMed Central

Lefebvre, Philippe P.; Gisbert, Javier; Cuda, Domenico; Tringali, Stéphane; Deveze, Arnaud

2017-01-01

Objective To summarise treatment outcomes compared to surgical and patient variables for a multicentre recipient cohort using a fully implantable active middle ear implant for hearing impairment. To describe the authors' preferred surgical technique to determine microphone placement. Study Design Multicentre retrospective, observational survey. Setting Five tertiary referral centres. Patients Carina recipients (66 ears, 62 subjects) using the current Cochlear® Carina® System or the legacy device, the Otologics® Fully Implantable Middle Ear, with a T2 transducer. Methods Patient file review and routine clinical review. Patient outcomes assessed were satisfaction, daily use and feedback reports at the first fitting and ≥12 months after implantation. Descriptive and statistical analysis of correlations of variables and their influence on outcomes was performed. Independently reported preferred methods for microphone placement are collectively summarised. Results The average implant experience was 3.5 years. Satisfaction increased significantly over time (p < 0.05). No correlation with covariates examined was observed. Feedback significantly decreased over time, showing a significant correlation with microphone location, primary motivation, gender, age at implantation, and contralateral hearing aid use (p < 0.05). Patient satisfaction was inversely correlated with reports of system feedback (p < 0.05). The implantable microphone was most commonly on the posterior inferior mastoid line, in 42/66 (65%) cases, correlating with less likelihood for feedback and consistent with author surgical preference. Conclusion Carina recipients in this study present as satisfied consistent daily users with very few reports of persistent feedback. As microphone location is an influencing factor, a careful surgical consideration of microphone placement is required. The authors prefer a posterior inferior mastoid line position whenever possible. PMID:28052264

Elective frozen elephant trunk procedure using the E-Vita Open Plus prosthesis in 94 patients: a multicentre French registry.

PubMed

Verhoye, Jean-Philippe; Belhaj Soulami, Reda; Fouquet, Olivier; Ruggieri, Vito Giovanni; Kaladji, Adrien; Tomasi, Jacques; Sellin, Michel; Farhat, Fadi; Anselmi, Amedeo

2017-10-01

Our goal was to evaluate the operative outcomes of the frozen elephant trunk technique using the E-Vita Open Plus® hybrid prosthesis in chronic aortic arch diseases and report clinical and radiological outcomes at the 1-year follow-up. As determined from a prospective multicentre registry, 94 patients underwent frozen elephant trunk procedures using the E-Vita Open Plus hybrid device for the treatment of chronic aortic conditions, including 50% chronic aortic dissections, 40% degenerative aneurysms and 10% miscellaneous indications. Fifty percent of the cases were reoperations. The perioperative mortality rate was 11.7%. Spinal cord ischaemia and stroke rates were 4% and 9.6%, respectively. The mean cardiopulmonary bypass time was 252 ± 97 min, cardiac ischaemia time was 152 ± 53 min and cerebral perfusion time was 82 ± 22 min. Concomitant procedures were observed in 15% of patients. Among the 83 surviving patients, the survival rate after the 1-year follow-up was 98%. Eleven percent of patients underwent endovascular completion, whereas 4% of patients required aortic reintervention at 1 year. The E-Vita Open Plus hybrid device confirms the favourable short- and mid-term outcomes offered by its predecessor in frozen elephant trunk procedures in patients with chronic aortic arch disease. Implantation of the E-Vita Open Plus is associated with good 1-year survival rates, good rates of favourable aortic remodelling in both chronic dissection and degenerative aneurysms and a reproducible technique in a multicentre registry. Continued follow-up is required due to the risk of evolution at the downstream aorta. © The Author 2017. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.

Financial considerations in the conduct of multi-centre randomised controlled trials: evidence from a qualitative study.

PubMed

Snowdon, Claire; Elbourne, Diana R; Garcia, Jo; Campbell, Marion K; Entwistle, Vikki A; Francis, David; Grant, Adrian M; Knight, Rosemary C; McDonald, Alison M; Roberts, Ian

2006-12-21

Securing and managing finances for multicentre randomised controlled trials is a highly complex activity which is rarely considered in the research literature. This paper describes the process of financial negotiation and the impact of financial considerations in four UK multicentre trials. These trials had met, or were on schedule to meet, recruitment targets agreed with their public-sector funders. The trials were considered within a larger study examining factors which might be associated with trial recruitment (STEPS). In-depth semi-structured telephone interviews were conducted in 2003-04 with 45 individuals with various responsibilities to one of the four trials. Interviewees were recruited through purposive and then snowball sampling. Interview transcripts were analysed with the assistance of the qualitative package Atlas-ti. The data suggest that the UK system of dividing funds into research, treatment and NHS support costs brought the trial teams into complicated negotiations with multiple funders. The divisions were somewhat malleable and the funding system was used differently in each trial. The fact that all funders had the potential to influence and shape the trials considered here was an important issue as the perspectives of applicants and funders could diverge. The extent and range of industry involvement in non-industry-led trials was striking. Three broad periods of financial work (foundation, maintenance, and resourcing completion) were identified. From development to completion of a trial, the trialists had to be resourceful and flexible, adapting to changing internal and external circumstances. In each period, trialists and collaborators could face changing costs and challenges. Each trial extended the recruitment period; three required funding extensions from MRC or HTA. This study highlights complex financial aspects of planning and conducting trials, especially where multiple funders are involved. Recognition of the importance of financial stability and of the need for appropriate training in this area should be paralleled by further similar research with a broader range of trials, aimed at understanding and facilitating the conduct of clinical research.

Clinical performance of the Prostate Health Index (PHI) for the prediction of prostate cancer in obese men: data from the PROMEtheuS project, a multicentre European prospective study.

PubMed

Abrate, Alberto; Lazzeri, Massimo; Lughezzani, Giovanni; Buffi, Nicolòmaria; Bini, Vittorio; Haese, Alexander; de la Taille, Alexandre; McNicholas, Thomas; Redorta, Joan Palou; Gadda, Giulio M; Lista, Giuliana; Kinzikeeva, Ella; Fossati, Nicola; Larcher, Alessandro; Dell'Oglio, Paolo; Mistretta, Francesco; Freschi, Massimo; Guazzoni, Giorgio

2015-04-01

To test serum prostate-specific antigen (PSA) isoform [-2]proPSA (p2PSA), p2PSA/free PSA (%p2PSA) and Prostate Health Index (PHI) accuracy in predicting prostate cancer in obese men and to test whether PHI is more accurate than PSA in predicting prostate cancer in obese patients. The analysis consisted of a nested case-control study from the pro-PSA Multicentric European Study (PROMEtheuS) project. The study is registered at http://www.controlled-trials.com/ISRCTN04707454. The primary outcome was to test sensitivity, specificity and accuracy (clinical validity) of serum p2PSA, %p2PSA and PHI, in determining prostate cancer at prostate biopsy in obese men [body mass index (BMI) ≥30 kg/m(2) ], compared with total PSA (tPSA), free PSA (fPSA) and fPSA/tPSA ratio (%fPSA). The number of avoidable prostate biopsies (clinical utility) was also assessed. Multivariable logistic regression models were complemented by predictive accuracy analysis and decision-curve analysis. Of the 965 patients, 383 (39.7%) were normal weight (BMI <25 kg/m(2) ), 440 (45.6%) were overweight (BMI 25-29.9 kg/m(2) ) and 142 (14.7%) were obese (BMI ≥30 kg/m(2) ). Among obese patients, prostate cancer was found in 65 patients (45.8%), with a higher percentage of Gleason score ≥7 diseases (67.7%). PSA, p2PSA, %p2PSA and PHI were significantly higher, and %fPSA significantly lower in patients with prostate cancer (P < 0.001). In multivariable logistic regression models, PHI significantly increased accuracy of the base multivariable model by 8.8% (P = 0.007). At a PHI threshold of 35.7, 46 (32.4%) biopsies could have been avoided. In obese patients, PHI is significantly more accurate than current tests in predicting prostate cancer. © 2014 The Authors. BJU International © 2014 BJU International.

Does 3-Day Course of Oral Amoxycillin Benefit Children of Non-Severe Pneumonia with Wheeze: A Multicentric Randomised Controlled Trial

PubMed Central

Awasthi, Shally; Agarwal, Girdhar; Kabra, Sushil K.; Singhi, Sunit; Kulkarni, Madhuri; More, Vaishali; Niswade, Abhimanyu; Pillai, Raj Mohan; Luke, Ravi; Srivastava, Neeraj M.; Suresh, Saradha; Verghese, Valsan P.; Raghupathy, P.; Lodha, R.; Walter, Stephen D.

2008-01-01

Background WHO-defined pneumonias, treated with antibiotics, are responsible for a significant proportion of childhood morbidity and mortality in the developing countries. Since substantial proportion pneumonias have a viral etiology, where children are more likely to present with wheeze, there is a concern that currently antibiotics are being over-prescribed for it. Hence the current trial was conducted with the objective to show the therapeutic equivalence of two treatments (placebo and amoxycillin) for children presenting with non-severe pneumonia with wheeze, who have persistent fast breathing after nebulisation with salbutamol, and have normal chest radiograph. Methodology This multi-centric, randomised placebo controlled double blind clinical trial intended to investigate equivalent efficacy of placebo and amoxicillin and was conducted in ambulatory care settings in eight government hospitals in India. Participants were children aged 2–59 months of age, who received either oral amoxycillin (31–54 mg/Kg/day, in three divided doses for three days) or placebo, and standard bronchodilator therapy. Primary outcome was clinical failure on or before day- 4. Principal Findings We randomized 836 cases in placebo and 835 in amoxycillin group. Clinical failures occurred in 201 (24.0%) on placebo and 166 (19.9%) on amoxycillin (risk difference 4.2% in favour of antibiotic, 95% CI: 0.2 to 8.1). Adherence for both placebo and amoxycillin was >96% and 98.9% subjects were followed up on day- 4. Clinical failure was associated with (i) placebo treatment (adjusted OR = 1.28, 95% CI: 1.01 to1.62), (ii) excess respiratory rate of >10 breaths per minute (adjusted OR = 1.51, 95% CI: 1.19, 1.92), (iii) vomiting at enrolment (adjusted OR = 1.49, 95% CI: 1.13, 1.96), (iv) history of use of broncho-dilators (adjusted OR = 1.71, 95% CI: 1.30, 2.24) and (v) non-adherence (adjusted OR = 8.06, 95% CI: 4.36, 14.92). Conclusions Treating children with non-severe pneumonia and wheeze with a placebo is not equivalent to treatment with oral amoxycillin. Trial Registration ClinicalTrials.gov NCT00407394 PMID:18431478

Exploring the effect of previous inactivated influenza vaccination on seasonal influenza vaccine effectiveness against medically attended influenza: Results of the European I-MOVE multicentre test-negative case-control study, 2011/2012-2016/2017.

PubMed

Valenciano, Marta; Kissling, Esther; Larrauri, Amparo; Nunes, Baltazar; Pitigoi, Daniela; O'Donnell, Joan; Reuss, Annicka; Horváth, Judit Krisztina; Paradowska-Stankiewicz, Iwona; Rizzo, Caterina; Falchi, Alessandra; Daviaud, Isabelle; Brytting, Mia; Meijer, Adam; Kaic, Bernard; Gherasim, Alin; Machado, Ausenda; Ivanciuc, Alina; Domegan, Lisa; Schweiger, Brunhilde; Ferenczi, Annamária; Korczyńska, Monika; Bella, Antonino; Vilcu, Ana-Maria; Mosnier, Anne; Zakikhany, Katherina; de Lange, Marit; Kurečić Filipovićović, Sanja; Johansen, Kari; Moren, Alain

2018-04-16

Results of previous influenza vaccination effects on current season influenza vaccine effectiveness (VE) are inconsistent. To explore previous influenza vaccination effects on current season VE among population targeted for vaccination. We used 2011/2012 to 2016/2017 I-MOVE primary care multicentre test-negative data. For each season, we compared current season adjusted VE (aVE) between individuals vaccinated and unvaccinated in previous season. Using unvaccinated in both seasons as a reference, we then compared aVE between vaccinated in both seasons, current only, and previous only. We included 941, 2645 and 959 influenza-like illness patients positive for influenza A(H1N1)pdm09, A(H3N2) and B, respectively, and 5532 controls. In 2011/2012, 2014/2015 and 2016/2017, A(H3N2) aVE point estimates among those vaccinated in previous season were -68%, -21% and -19%, respectively; among unvaccinated in previous season, these were 33%, 48% and 46%, respectively (aVE not computable for influenza A(H1N1)pdm09 and B). Compared to current season vaccination only, VE for both seasons' vaccination was (i) similar in two of four seasons for A(H3N2) (absolute difference [ad] 6% and 8%); (ii) lower in three of four seasons for influenza A(H1N1)pdm09 (ad 18%, 26% and 29%), in two seasons for influenza A(H3N2) (ad 27% and 39%) and in two of three seasons for influenza B (ad 26% and 37%); (iii) higher in one season for influenza A(H1N1)pdm09 (ad 20%) and influenza B (ad 24%). We did not identify any pattern of previous influenza vaccination effect. Prospective cohort studies documenting influenza infections, vaccinations and vaccine types are needed to understand previous influenza vaccinations' effects. © 2018 The Authors. Influenza and Other Respiratory Viruses Published by John Wiley & Sons Ltd.

Comparing meta-analysis and ecological-longitudinal analysis in time-series studies. A case study of the effects of air pollution on mortality in three Spanish cities.

PubMed

Saez, M; Figueiras, A; Ballester, F; Pérez-Hoyos, S; Ocaña, R; Tobías, A

2001-06-01

The objective of this paper is to introduce a different approach, called the ecological-longitudinal, to carrying out pooled analysis in time series ecological studies. Because it gives a larger number of data points and, hence, increases the statistical power of the analysis, this approach, unlike conventional ones, allows the complementation of aspects such as accommodation of random effect models, of lags, of interaction between pollutants and between pollutants and meteorological variables, that are hardly implemented in conventional approaches. The approach is illustrated by providing quantitative estimates of the short-term effects of air pollution on mortality in three Spanish cities, Barcelona, Valencia and Vigo, for the period 1992-1994. Because the dependent variable was a count, a Poisson generalised linear model was first specified. Several modelling issues are worth mentioning. Firstly, because the relations between mortality and explanatory variables were non-linear, cubic splines were used for covariate control, leading to a generalised additive model, GAM. Secondly, the effects of the predictors on the response were allowed to occur with some lag. Thirdly, the residual autocorrelation, because of imperfect control, was controlled for by means of an autoregressive Poisson GAM. Finally, the longitudinal design demanded the consideration of the existence of individual heterogeneity, requiring the consideration of mixed models. The estimates of the relative risks obtained from the individual analyses varied across cities, particularly those associated with sulphur dioxide. The highest relative risks corresponded to black smoke in Valencia. These estimates were higher than those obtained from the ecological-longitudinal analysis. Relative risks estimated from this latter analysis were practically identical across cities, 1.00638 (95% confidence intervals 1.0002, 1.0011) for a black smoke increase of 10 microg/m(3) and 1.00415 (95% CI 1.0001, 1.0007) for a increase of 10 microg/m(3) of sulphur dioxide. Because the statistical power is higher than in the individual analysis more interactions were statistically significant, especially those among air pollutants and meteorological variables. Air pollutant levels were related to mortality in the three cities of the study, Barcelona, Valencia and Vigo. These results were consistent with similar studies in other cities, with other multicentric studies and coherent with both, previous individual, for each city, and multicentric studies for all three cities.

Use of drug therapy in the management of symptomatic ureteric stones in hospitalized adults (SUSPEND), a multicentre, placebo-controlled, randomized trial of a calcium-channel blocker (nifedipine) and an α-blocker (tamsulosin): study protocol for a randomized controlled trial

PubMed Central

2014-01-01

Background Urinary stone disease is common, with an estimated prevalence among the general population of 2% to 3%. Ureteric stones can cause severe pain and have a significant impact on quality of life, accounting for over 15,000 hospital admissions in England annually. Uncomplicated cases of smaller stones in the lower ureter are traditionally treated expectantly. Those who fail standard care or develop complications undergo active treatment, such as extracorporeal shock wave lithotripsy or ureteroscopy with stone retrieval. Such interventions are expensive, require urological expertise and carry a risk of complications. Growing understanding of ureteric function and pathophysiology has led to the hypothesis that drugs causing relaxation of ureteric smooth muscle, such as the selective α-blocker tamsulosin and the calcium-channel blocker nifedipine, can enhance the spontaneous passage of ureteric stones. The use of drugs in augmenting stone passage, reducing the morbidity and costs associated with ureteric stone disease, is promising. However, the majority of clinical trials conducted to date have been small, poor to moderate quality and lacking in comprehensive economic evaluation. This trial aims to determine the clinical and cost-effectiveness of tamsulosin and nifedipine in the management of symptomatic urinary stones. Methods/design The SUSPEND (Spontaneous Urinary Stone Passage ENabled by Drugs) trial is a multicentre, double-blind, randomized controlled trial evaluating two medical expulsive therapy strategies (nifedipine or tamsulosin) versus placebo. Patients aged 18 to 65 with a ureteric stone confirmed by non-contrast computed tomography of the kidney, ureter and bladder will be randomized to receive nifedipine, tamsulosin or placebo (400 participants per arm) for a maximum of 28 days. The primary clinical outcome is spontaneous passage of ureteric stones at 4 weeks (defined as no further intervention required to facilitate stone passage). The primary economic outcome is a reduction in the incremental cost per quality-adjusted life years, determined at 12 weeks. The analysis will be based on all participants as randomized (intention to treat). The trial has 90% power with a type I error rate of 5% to detect a 10% increase in primary outcome between the tamsulosin and nifedipine treatment groups. Trial registration ISRCTN69423238; EudraCT number: 2010-019469-26 PMID:24947817

Use of drug therapy in the management of symptomatic ureteric stones in hospitalized adults (SUSPEND), a multicentre, placebo-controlled, randomized trial of a calcium-channel blocker (nifedipine) and an α-blocker (tamsulosin): study protocol for a randomized controlled trial.

PubMed

McClinton, Sam; Starr, Kathryn; Thomas, Ruth; McLennan, Graeme; McPherson, Gladys; McDonald, Alison; Lam, Thomas; N'Dow, James; Kilonzo, Mary; Pickard, Robert; Anson, Ken; Burr, Jennifer

2014-06-20

Urinary stone disease is common, with an estimated prevalence among the general population of 2% to 3%. Ureteric stones can cause severe pain and have a significant impact on quality of life, accounting for over 15,000 hospital admissions in England annually. Uncomplicated cases of smaller stones in the lower ureter are traditionally treated expectantly. Those who fail standard care or develop complications undergo active treatment, such as extracorporeal shock wave lithotripsy or ureteroscopy with stone retrieval. Such interventions are expensive, require urological expertise and carry a risk of complications.Growing understanding of ureteric function and pathophysiology has led to the hypothesis that drugs causing relaxation of ureteric smooth muscle, such as the selective α-blocker tamsulosin and the calcium-channel blocker nifedipine, can enhance the spontaneous passage of ureteric stones. The use of drugs in augmenting stone passage, reducing the morbidity and costs associated with ureteric stone disease, is promising. However, the majority of clinical trials conducted to date have been small, poor to moderate quality and lacking in comprehensive economic evaluation.This trial aims to determine the clinical and cost-effectiveness of tamsulosin and nifedipine in the management of symptomatic urinary stones. The SUSPEND (Spontaneous Urinary Stone Passage ENabled by Drugs) trial is a multicentre, double-blind, randomized controlled trial evaluating two medical expulsive therapy strategies (nifedipine or tamsulosin) versus placebo.Patients aged 18 to 65 with a ureteric stone confirmed by non-contrast computed tomography of the kidney, ureter and bladder will be randomized to receive nifedipine, tamsulosin or placebo (400 participants per arm) for a maximum of 28 days. The primary clinical outcome is spontaneous passage of ureteric stones at 4 weeks (defined as no further intervention required to facilitate stone passage). The primary economic outcome is a reduction in the incremental cost per quality-adjusted life years, determined at 12 weeks. The analysis will be based on all participants as randomized (intention to treat). The trial has 90% power with a type I error rate of 5% to detect a 10% increase in primary outcome between the tamsulosin and nifedipine treatment groups. ISRCTN69423238; EudraCT number: 2010-019469-26.

CD56‐positive haematological neoplasms of the skin: a multicentre study of the Cutaneous Lymphoma Project Group of the European Organisation for Research and Treatment of Cancer

PubMed Central

Assaf, Chalid; Gellrich, Sylke; Whittaker, Sean; Robson, Alistair; Cerroni, Lorenzo; Massone, Cesare; Kerl, Helmut; Rose, Christian; Chott, Andreas; Chimenti, Sergio; Hallermann, Christian; Petrella, Tony; Wechsler, Janine; Bagot, Martine; Hummel, Michael; Bullani‐Kerl, Katrin; Bekkenk, Marcel W; Kempf, Werner; Meijer, Chris J L M; Willemze, Rein; Sterry, Wolfram

2007-01-01

Background Cutaneous lymphomas expressing CD56, a neural cell adhesion molecule, are characterised in most cases by a highly aggressive clinical course and a poor prognosis. However, prognostic subsets within the CD56+ group have been difficult to identify due to the lack of uniform clinicopathological and immunophenotypical criteria. Methods A multicentre study was conducted by the Cutaneous Lymphoma Task Force of the European Organisation for Research and Treatment of Cancer to define prognostic parameters and establish diagnostic and therapeutic guidelines for CD56+ haematological neoplasms presenting primarily in the skin. Results Four different subtypes of lymphoproliferations with CD56 expression were identified: (1) haematodermic neoplasm; (2) skin infiltration as the first manifestation of CD56+ acute myeloid leukaemia; (3) nasal‐type extranodal natural killer/T‐cell lymphoma; and (4) “classical” cases of cutaneous T‐cell lymphoma (CTCL) with co‐expression of the CD56 molecule. Patients in the first three groups had a poor outcome (93% died) with a median survival rate of 11 months (95% CI 2–72 months), whereas all patients with CD56+ CTCL were alive at the last follow‐up. Conclusion Results show that CD56+ cutaneous lymphoproliferative disorders, with the exception of CD56+ CTCL have a very poor prognosis. It is therefore clinically important to separate CD56+ CTCL from the remaining CD56+ haematological disorders. PMID:17018683

Multi-centre audit of VMAT planning and pre-treatment verification.

PubMed

Jurado-Bruggeman, Diego; Hernández, Victor; Sáez, Jordi; Navarro, David; Pino, Francisco; Martínez, Tatiana; Alayrach, Maria-Elena; Ailleres, Norbert; Melero, Alejandro; Jornet, Núria

2017-08-01

We performed a multi-centre intercomparison of VMAT dose planning and pre-treatment verification. The aims were to analyse the dose plans in terms of dosimetric quality and deliverability, and to validate whether in-house pre-treatment verification results agreed with those of an external audit. The nine participating centres encompassed different machines, equipment, and methodologies. Two mock cases (prostate and head and neck) were planned using one and two arcs. A plan quality index was defined to compare the plans and different complexity indices were calculated to check their deliverability. We compared gamma index pass rates using the centre's equipment and methodology to those of an external audit (global 3D gamma, absolute dose differences, 10% of maximum dose threshold). Log-file analysis was performed to look for delivery errors. All centres fulfilled the dosimetric goals but plan quality and delivery complexity were heterogeneous and uncorrelated, depending on the manufacturer and the planner's methodology. Pre-treatment verifications results were within tolerance in all cases for gamma 3%-3mm evaluation. Nevertheless, differences between the external audit and in-house measurements arose due to different equipment or methodology, especially for 2%-2mm criteria with differences up to 20%. No correlation was found between complexity indices and verification results amongst centres. All plans fulfilled dosimetric constraints, but plan quality and complexity did not correlate and were strongly dependent on the planner and the vendor. In-house measurements cannot completely replace external audits for credentialing. Copyright © 2017 Elsevier B.V. All rights reserved.

Prognostic value of baseline absolute lymphocyte concentration and neutrophil/lymphocyte ratio in dogs with newly diagnosed multi-centric lymphoma.

PubMed

Mutz, M; Boudreaux, B; Kearney, M; Stroda, K; Gaunt, S; Shiomitsu, K

2015-12-01

Canine multi-centric B-cell lymphoma shares similarities with diffuse large B-cell (Non-Hodgkin's) lymphoma (NHL) in people. In people with NHL, lymphopenia at diagnosis and first relapse and neutrophil/lymphocyte ratio (N:L) > 3.5 are negative prognostic factors for survival. The objective of this study was to determine if lymphocyte concentration at diagnosis and first relapse and N:L were prognostic for survival in dogs with newly diagnosed multi-centric lymphoma. Medical records of 77 dogs with multi-centric lymphoma treated with a CHOP-based chemotherapy protocol were retrospectively evaluated. Absolute lymphocyte concentration and N:L ratio at presentation of dogs pre-treated with steroids was not significantly different from dogs who had not received steroids. On multivariate analysis, only immunophenotype remained significant for progression-free survival (PFS), whereas no variables remained significant for ST. A prospective study of these haematologic variables is warranted to assess their true significance. © 2013 John Wiley & Sons Ltd.

Balance exercise for persons with multiple sclerosis using Wii games: a randomised, controlled multi-centre study.

PubMed

Nilsagård, Ylva E; Forsberg, Anette S; von Koch, Lena

2013-02-01

The use of interactive video games is expanding within rehabilitation. The evidence base is, however, limited. Our aim was to evaluate the effects of a Nintendo Wii Fit® balance exercise programme on balance function and walking ability in people with multiple sclerosis (MS). A multi-centre, randomised, controlled single-blinded trial with random allocation to exercise or no exercise. The exercise group participated in a programme of 12 supervised 30-min sessions of balance exercises using Wii games, twice a week for 6-7 weeks. Primary outcome was the Timed Up and Go test (TUG). In total, 84 participants were enrolled; four were lost to follow-up. After the intervention, there were no statistically significant differences between groups but effect sizes for the TUG, TUGcognitive and, the Dynamic Gait Index (DGI) were moderate and small for all other measures. Statistically significant improvements within the exercise group were present for all measures (large to moderate effect sizes) except in walking speed and balance confidence. The non-exercise group showed statistically significant improvements for the Four Square Step Test and the DGI. In comparison with no intervention, a programme of supervised balance exercise using Nintendo Wii Fit® did not render statistically significant differences, but presented moderate effect sizes for several measures of balance performance.

Efficacy and safety of rasagiline as an adjunct to levodopa treatment in Chinese patients with Parkinson's disease: a randomized, double-blind, parallel-controlled, multi-centre trial.

PubMed

Zhang, Lina; Zhang, Zhiqin; Chen, Yangmei; Qin, Xinyue; Zhou, Huadong; Zhang, Chaodong; Sun, Hongbin; Tang, Ronghua; Zheng, Jinou; Yi, Lin; Deng, Liying; Li, Jinfang

2013-08-01

Rasagiline mesylate is a highly potent, selective and irreversible monoamine oxidase type B (MAOB) inhibitor and is effective as monotherapy or adjunct to levodopa for patients with Parkinson's disease (PD). However, few studies have evaluated the efficacy and safety of rasagiline in the Chinese population. This study was designed to investigate the safety and efficacy of rasagiline as adjunctive therapy to levodopa treatment in Chinese PD patients. This was a randomized, double-blind, placebo-controlled, parallel-group, multi-centre trial conducted over a 12-wk period that enrolled 244 PD patients with motor fluctuations. Participants were randomly assigned to oral rasagiline mesylate (1 mg) or placebo, once daily. Altogether, 219 patients completed the trial. Rasagiline showed significantly greater efficacy compared with placebo. During the treatment period, the primary efficacy variable--mean adjusted total daily off time--decreased from baseline by 1.7 h in patients treated with 1.0 mg/d rasagiline compared to placebo (p < 0.05). Scores using the Unified Parkinson's Disease Rating Scale also improved during rasagiline treatment. Rasagiline was well tolerated. This study demonstrated that rasagiline mesylate is effective and well tolerated as an adjunct to levodopa treatment in Chinese PD patients with fluctuations.

Haptic-Based Neurorehabilitation in Poststroke Patients: A Feasibility Prospective Multicentre Trial for Robotics Hand Rehabilitation

PubMed Central

Daud Albasini, Omar A.; Oboe, Roberto; Tonin, Paolo; Paolucci, Stefano; Sandrini, Giorgio; Piron, Lamberto

2013-01-01

Background. Haptic robots allow the exploitation of known motor learning mechanisms, representing a valuable option for motor treatment after stroke. The aim of this feasibility multicentre study was to test the clinical efficacy of a haptic prototype, for the recovery of hand function after stroke. Methods. A prospective pilot clinical trial was planned on 15 consecutive patients enrolled in 3 rehabilitation centre in Italy. All the framework features of the haptic robot (e.g., control loop, external communication, and graphic rendering for virtual reality) were implemented into a real-time MATLAB/Simulink environment, controlling a five-bar linkage able to provide forces up to 20 [N] at the end effector, used for finger and hand rehabilitation therapies. Clinical (i.e., Fugl-Meyer upper extremity scale; nine hold pegboard test) and kinematics (i.e., time; velocity; jerk metric; normalized jerk of standard movements) outcomes were assessed before and after treatment to detect changes in patients' motor performance. Reorganization of cortical activation was detected in one patient by fMRI. Results and Conclusions. All patients showed significant improvements in both clinical and kinematic outcomes. Additionally, fMRI results suggest that the proposed approach may promote a better cortical activation in the brain. PMID:24319496

Haptic-based neurorehabilitation in poststroke patients: a feasibility prospective multicentre trial for robotics hand rehabilitation.

PubMed

Turolla, Andrea; Daud Albasini, Omar A; Oboe, Roberto; Agostini, Michela; Tonin, Paolo; Paolucci, Stefano; Sandrini, Giorgio; Venneri, Annalena; Piron, Lamberto

2013-01-01

Background. Haptic robots allow the exploitation of known motor learning mechanisms, representing a valuable option for motor treatment after stroke. The aim of this feasibility multicentre study was to test the clinical efficacy of a haptic prototype, for the recovery of hand function after stroke. Methods. A prospective pilot clinical trial was planned on 15 consecutive patients enrolled in 3 rehabilitation centre in Italy. All the framework features of the haptic robot (e.g., control loop, external communication, and graphic rendering for virtual reality) were implemented into a real-time MATLAB/Simulink environment, controlling a five-bar linkage able to provide forces up to 20 [N] at the end effector, used for finger and hand rehabilitation therapies. Clinical (i.e., Fugl-Meyer upper extremity scale; nine hold pegboard test) and kinematics (i.e., time; velocity; jerk metric; normalized jerk of standard movements) outcomes were assessed before and after treatment to detect changes in patients' motor performance. Reorganization of cortical activation was detected in one patient by fMRI. Results and Conclusions. All patients showed significant improvements in both clinical and kinematic outcomes. Additionally, fMRI results suggest that the proposed approach may promote a better cortical activation in the brain.

Exposure to non‐arsenic pesticides is associated with lymphoma among farmers in Spain

PubMed Central

van Balen, E; Font, R; Cavallé, N; Font, L; Garcia‐Villanueva, M; Benavente, Y; Brennan, P; de Sanjose, S

2006-01-01

Objectives To estimate the risk of lymphoma among farmers in Spain. Methods This is a multicentre case control study conducted in Spain. Cases were subjects diagnosed with lymphoma according to the World Health Organization (WHO) classification in four hospitals between 1998–2002. Hospital controls were frequency matched to the cases by sex, age, and centre. All subjects were interviewed about jobs ever held in lifetime for at least one year and the exposures in those jobs were recorded. The risk of lymphomas among subjects ever having had a job as a farmer was compared with all other occupations. Farmers were analysed according to the type of farming job performed: crop farming, animal farming, and general farming. Occupational exposure was summarised into 15 main categories: organic dust, radiation, contact with animals, PAH, non‐arsenic pesticides (carbamates, organophosphates, chlorinated hydrocarbons, triazines and triazoles, phenoxy herbicides, chlorophenols, dibenzodioxin, and dibenzofuran), arsenic pesticides, contact with meat, contact with children, solvents, asbestos, soldering fumes, organic colourants, polychlorinated biphenyls, ethylene oxide, and hair dyes. Results Although farmers were not at an increased risk of lymphoma as compared with all other occupations, farmers exposed to non‐arsenic pesticides were found to be at increased risk of lymphoma (OR = 1.8, 95% CI 1.1 to 2). This increased risk was observed among farmers working exclusively either as crop farmers or as animal farmers (OR = 2.8, 95% CI 1.3 to 5.8). Risk was highest for exposure to non‐arsenic pesticides for over nine years (OR = 2.4, 95% CI 1.2 to 2.8). Conclusions Long term exposure to non‐arsenic pesticides may induce lymphomagenesis among farmers. PMID:16757510

The medical value and cost-effectiveness of an exercise test for sport preparticipation evaluation in asymptomatic middle-aged white male and female athletes.

PubMed

Chevalier, Laurent; Kervio, Gaelle; Doutreleau, Stephane; Mathieu, Jean-Philippe; Guy, Jean-Michel; Mignot, Aude; Corneloup, Luc; Passard, François; Laporte, Thierry; Girard-Girod, Aude; Hennebert, Olivier; Bernadet, Philippe; Vincent-Chevalier, Marie-Pierre; Gencel, Laurent; Carré, François

2017-03-01

Cardiovascular events related to high-intensity sport practice are rare but dramatic. Coronary artery disease (CAD) is the leading cause of these events after the age of 35 years. The value of a maximal exercise test (ET) for detection of athletes at risk remains a matter of debate. The aim of this prospective multicentre study was to clarify the medical value and cost-effectiveness of an ET in middle-aged white asymptomatic athletes who participate in high-intensity sport. All athletes had a physical examination, assessment of cardiovascular risk factors, a resting electrocardiogram and an ET. In case of abnormal ET, complementary cardiovascular evaluation was performed, when requested, to detect potential cardiovascular disease. 1361 asymptomatic athletes (mean age 50.4±9.6 years; mean training 5.1±3.2h/week; 10.4% women) with a normal resting electrocardiogram and without cardiovascular disease were consecutively included. An abnormal ET was reported in 144 subjects (94% men); this was positively related to the subject's age and cardiovascular risk level. Cardiac arrhythmias (48%) and CAD symptoms (33.3%) were mainly reported. Cardiovascular disease was confirmed in 24 cases (1.7% from the whole population; 16.7% from those with an abnormal ET) - mainly CAD (n=12) and arterial hypertension (n=8). Seventy athletes presented significant unexplained arrhythmias. The cost was approximately €8450 for every confirmed case of cardiovascular disease. In this multicentre study in middle-aged athletes, a systematic ET was abnormal in 10.6% of cases. About 2% of subjects had cardiovascular disease, mainly arrhythmias and CAD. From these results, it seems that in a trained population aged >35 years, ET should be targeted at men with at least two cardiovascular risk factors, with acceptable cost-effectiveness. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

Colonoscopic full-thickness resection using an over-the-scope device: a prospective multicentre study in various indications.

PubMed

Schmidt, Arthur; Beyna, Torsten; Schumacher, Brigitte; Meining, Alexander; Richter-Schrag, Hans-Juergen; Messmann, Helmut; Neuhaus, Horst; Albers, David; Birk, Michael; Thimme, Robert; Probst, Andreas; Faehndrich, Martin; Frieling, Thomas; Goetz, Martin; Riecken, Bettina; Caca, Karel

2017-08-10

Endoscopic full-thickness resection (EFTR) is a novel treatment of colorectal lesions not amenable to conventional endoscopic resection. The aim of this prospective multicentre study was to assess the efficacy and safety of the full-thickness resection device. 181 patients were recruited in 9 centres with the indication of difficult adenomas (non-lifting and/or at difficult locations), early cancers and subepithelial tumours (SET). Primary endpoint was complete en bloc and R0 resection. EFTR was technically successful in 89.5%, R0 resection rate was 76.9%. In 127 patients with difficult adenomas and benign histology, R0 resection rate was 77.7%. In 14 cases, lesions harboured unsuspected cancer, another 15 lesions were primarily known as cancers. Of these 29 cases, R0 resection was achieved in 72.4%; 8 further cases had deep submucosal infiltration >1000 µm. Therefore, curative resection could only be achieved in 13/29 (44.8%). In the subgroup with SET (n=23), R0 resection rate was 87.0%. In general, R0 resection rate was higher with lesions ≤2 cm vs >2 cm (81.2% vs 58.1%, p=0.0038). Adverse event rate was 9.9% with a 2.2% rate of emergency surgery. Three-month follow-up was available from 154 cases and recurrent/residual tumour was evident in 15.3%. EFTR has a reasonable technical efficacy especially in lesions ≤2 cm with acceptable complication rates. Curative resection rate for early cancers was too low to recommend its primary use in this indication. Further comparative studies have to show the clinical value and long-term outcome of EFTR in benign colorectal lesions. NCT02362126; 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.

Cost-effectiveness of cryotherapy versus salicylic acid for the treatment of plantar warts: economic evaluation alongside a randomised controlled trial (EVerT trial)

PubMed Central

2012-01-01

Abstract Background Plantar warts (verrucae) are extremely common. Although many will spontaneously disappear without treatment, treatment may be sought for a variety of reasons such as discomfort. There are a number of different treatments for cutaneous warts, with salicylic acid and cryotherapy using liquid nitrogen being two of the most common forms of treatment. To date, no full economic evaluation of either salicylic acid or cryotherapy has been conducted based on the use of primary data in a pragmatic setting. This paper describes the cost-effectiveness analysis which was conducted alongside a pragmatic multicentre, randomised trial evaluating the clinical effectiveness of cryotherapy versus 50% salicylic acid of the treatment of plantar warts. Methods A cost-effectiveness analysis was undertaken alongside a pragmatic multicentre, randomised controlled trial assessing the clinical effectiveness of 50% salicylic acid and cryotherapy using liquid nitrogen at 12 weeks after randomisation of patients. Cost-effectiveness outcomes were expressed as the additional cost required to completely cure the plantar warts of one additional patient. A NHS perspective was taken for the analysis. Results Cryotherapy costs on average £101.17 (bias corrected and accelerated (BCA) 95% CI: 85.09-117.26) more per participant over the 12 week time-frame, while there is no additional benefit, in terms of proportion of patients healed compared with salicylic acid. Conclusions Cryotherapy is more costly and no more effective than salicylic acid. Trial registration Current Controlled Trials ISRCTN18994246 [controlled-trials.com] and National Research Register N0484189151. PMID:22369511

CA27.29: a valuable marker for breast cancer management. A confirmatory multicentric study on 603 cases.

PubMed

Gion, M; Mione, R; Leon, A E; Lüftner, D; Molina, R; Possinger, K; Robertson, J F

2001-02-01

Recently, a fully automated method has become commercially available to measure the MUC-1-associated antigen CA27.29. The present investigation was performed in order to compare CA27.29 and CA15.3 in a wide series of patients affected with breast cancer. Overall, 603 cases with breast cancer and 194 healthy controls were investigated. Patients were enrolled in 4 institutions, while assays were performed in one laboratory. CA27.29 was measured by the ACS:180 BR assay (Bayer Diagnostics) and CA15.3 by the AxSYM (Abbott Laboratories). An excellent correlation was found between the results obtained by the two methods. The two markers showed comparable results in healthy controls, with higher levels in post-menopausal than in pre-menopausal subjects. The markers were significantly higher in primary breast cancer than in controls. The areas under the receiver operating characteristics (ROC) curves of the two tests were comparable, but CA27.29 showed better sensitivity in cases with low antigen concentrations (below the cut-off point). Accordingly, when comparing each test in different stage categories, significance levels of the differences were higher for CA27.29 than for CA15.3 for all T categories versus healthy controls, for pT1 versus pT2, for all N categories versus healthy controls and for node-negative versus N1-3 patients. From the results of the present study, that has been performed on samples taken at diagnosis and prior to any treatment from the widest series of patients with primary breast cancer reported so far, we can draw the following conclusions: CA27.29 provides comparable results to CA15.3; CA27.29 seems more sensitive than CA15.3 to limited variations of tumour extension; however, it cannot help clinicians in distinguishing stage I patients from stage II patients. However, from the point of view of clinical decision making, CA27.29 provides comparable results to CA15.3. CA27.29 is therefore suitable for routine use in the management of patients with breast cancer.

Glucose-6-phosphate dehydrogenase deficiency, chlorproguanil-dapsone with artesunate and post-treatment haemolysis in African children treated for uncomplicated malaria.

PubMed

Van Malderen, Carine; Van Geertruyden, Jean-Pierre; Machevo, Sonia; González, Raquel; Bassat, Quique; Talisuna, Ambrose; Yeka, Adoke; Nabasumba, Carolyn; Piola, Patrice; Daniel, Atwine; Turyakira, Eleanor; Forret, Pascale; Van Overmeir, Chantal; van Loen, Harry; Robert, Annie; D' Alessandro, Umberto

2012-07-10

Malaria is a leading cause of mortality, particularly in sub-Saharan African children. Prompt and efficacious treatment is important as patients may progress within a few hours to severe and possibly fatal disease. Chlorproguanil-dapsone-artesunate (CDA) was a promising artemisinin-based combination therapy (ACT), but its development was prematurely stopped because of safety concerns secondary to its associated risk of haemolytic anaemia in glucose-6-phosphate dehydrogenase (G6PD)-deficient individuals. The objective of the study was to assess whether CDA treatment and G6PD deficiency are risk factors for a post-treatment haemoglobin drop in African children<5 years of age with uncomplicated malaria. This case-control study was performed in the context of a larger multicentre randomized clinical trial comparing safety and efficacy of four different ACT in children with uncomplicated malaria. Children, who after treatment experienced a haemoglobin drop≥2 g/dl (cases) within the first four days (days 0, 1, 2, and 3), were compared with those without an Hb drop (controls). Cases and controls were matched for study site, sex, age and baseline haemoglobin measurements. Data were analysed using a conditional logistic regression model. G6PD deficiency prevalence, homo- or hemizygous, was 8.5% (10/117) in cases and 6.8% (16/234) in controls (p=0.56). The risk of a Hb drop≥2 g/dl was not associated with either G6PD deficiency (adjusted odds ratio (AOR): 0.81; p=0.76) or CDA treatment (AOR: 1.28; p=0.37) alone. However, patients having both risk factors tended to have higher odds (AOR: 11.13; p=0.25) of experiencing a Hb drop≥2 g/dl within the first four days after treatment, however this finding was not statistically significant, mainly because G6PD deficient patients treated with CDA were very few. In non-G6PD deficient individuals, the proportion of cases was similar between treatment groups while in G6PD-deficient individuals, haemolytic anaemia occurred more frequently in children treated with CDA (56%) than in those treated with other ACT (29%), though the difference was not significant (p=0.49). The use of CDA for treating uncomplicated malaria may increase the risk of haemolytic anaemia in G6PD-deficient children.

Management of patients with ocular manifestations in vesiculobullous disorders affecting the mouth.

PubMed

Hansen, M S; Klefter, O N; Julian, H O; Lynge Pedersen, A M; Heegaard, S

2017-10-01

Pemphigoid and pemphigus diseases as well as Stevens-Johnson syndrome present as vesiculobullous disorders of the skin and may additionally involve both the oral cavity and the ocular surface. Ocular involvement ranges from mild irritation and dry eye disease to chronic conjunctivitis, symblepharon, eyelid malposition, ocular surface scarring and severe visual loss. In addition to diagnostic assessments, ophthalmologists must treat the dry eye and meibomian gland dysfunction components of these diseases using a stepladder approach, including eyelid hygiene and lubricants. Topical anti-inflammatory therapy is used to treat acute inflammatory exacerbations of the ocular surface, but it cannot prevent scarring alone. Intralesional antimetabolite therapy can cause regression of conjunctival pathology in selected cases. Hence, patients with vesiculobullous disorders should be managed by a multidisciplinary team representing ophthalmology, dermatology, otolaryngology, oral medicine and pathology, internal medicine and intensive care. Systemic treatments including corticosteroids, azathioprine, cyclophosphamide, cyclosporine and mycophenolate mofetil help control inflammation. Intravenous immunoglobulins, plasmapheresis and targeted antibody therapy can be used in selected, severe and treatment-resistant cases. Local surgical management may include debridement of pseudomembranes, lysis of symblepharon, amniotic and mucous membrane grafting as well as reconstructive procedures. Prospective, multicentre, international studies are recommended to further support evidence-based practice. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Association of dietary soy genistein intake with lung function and asthma control: a post-hoc analysis of patients enrolled in a prospective multicentre clinical trial

PubMed Central

Bime, Christian; Wei, Christine Y; Holbrook, Janet; Smith, Lewis J; Wise, Robert A

2013-01-01

Background Broad dietary patterns have been linked to asthma but the relative contribution of specific nutrients is unclear. Soy genistein has important anti-inflammatory and other biological effects that might be beneficial in asthma. A positive association was previously reported between soy genistein intake and lung function but not with asthma exacerbations. Aims To conduct a post-hoc analysis of patients with inadequately controlled asthma enrolled in a prospective multicentre clinical trial to replicate this association. Methods A total of 300 study participants were included in the analysis. Dietary soy genistein intake was measured using the Block Soy Foods Screener. The level of soy genistein intake (little or no intake, moderate intake, or high intake) was compared with baseline lung function (pre-bronchodilator forced expiratory volume in 1 second (FEV1)) and asthma control (proportion of participants with an episode of poor asthma control (EPAC) and annualised rates of EPACs over a 6-month follow-up period. Results Participants with little or no genistein intake had a lower baseline FEV1 than those with a moderate or high intake (2.26L vs. 2.53L and 2.47L, respectively; p=0.01). EPACs were more common among those with no genistein intake than in those with a moderate or high intake (54% vs. 35% vs. 40%, respectively; p<0.001). These findings remained significant after adjustment for patient demographics and body mass index. Conclusions In patients with asthma, consumption of a diet with moderate to high amounts of soy genistein is associated with better lung function and better asthma control. PMID:22885561

The burden of common skin diseases assessed with the EQ5D™: a European multicentre study in 13 countries.

PubMed

Balieva, F; Kupfer, J; Lien, L; Gieler, U; Finlay, A Y; Tomás-Aragonés, L; Poot, F; Misery, L; Sampogna, F; van Middendorp, H; Halvorsen, J A; Szepietowski, J C; Lvov, A; Marrón, S E; Salek, M S; Dalgard, F J

2017-05-01

Generic instruments measuring health-related quality of life (HRQoL), like EQ5D™, enable comparison of skin diseases with healthy populations and nondermatological medical conditions, as well as calculation of utility data. To measure HRQoL in patients with common skin diseases and healthy controls across Europe using the EQ5D. This multicentre observational cross-sectional study was conducted in 13 European countries. Each dermatology clinic recruited at least 250 consecutive adult outpatients to complete questionnaires, including the EQ5D. There were 5369 participants (4010 patients and 1359 controls). Mean ± SD self-rated health state reported by patients was 69·9 ± 19·7; for controls it was 82·2 ± 15·5. When adjusted for confounding factors, including comorbidity, mean patient EQ visual analogue scores were 10·5 points lower than for controls (standardized β = -0·23). Odds ratio with 95% confidence interval for impairment in all five dimensions of EQ5D adjusted for confounders was doubled for patients compared with controls. Patients with hidradenitis suppurativa (HS), blistering conditions, leg ulcers, psoriasis and eczemas had the highest risk for reduction in HRQoL in most dimensions (2-10-fold). Data on differences of impairment by dimensions offer new insights. This study confirms the large impact skin conditions have on patients' well-being, differentiating between aspects of HRQoL. Patients with HS, blistering diseases, leg ulcers, infections and most chronic skin diseases reported reduced HRQoL compared with patients with chronic obstructive lung disease, diabetes mellitus, cardiovascular disease and cancers. These findings are important in the prioritization of resource allocation between medical fields and within dermatological subspecialities. © 2016 British Association of Dermatologists.

Spinal cord stimulation in patients with painful diabetic neuropathy: a multicentre randomized clinical trial.

PubMed

de Vos, Cecile C; Meier, Kaare; Zaalberg, Paul Brocades; Nijhuis, Harold J A; Duyvendak, Wim; Vesper, Jan; Enggaard, Thomas P; Lenders, Mathieu W P M

2014-11-01

Painful diabetic neuropathy (PDN) is a peripheral neuropathic pain condition that is often difficult to relieve. Spinal cord stimulation (SCS) is a proven effective therapy for various types of mixed neuropathic conditions, yet effectiveness of SCS treatment for PDN is not well established. To our knowledge, ours is the first multicentre randomized controlled trial investigating the effectiveness of SCS in patients with PDN. Sixty patients with PDN in the lower extremities refractory to conventional medical therapy were enrolled and followed for 6 months. They were randomized 2:1 to best conventional medical practice with (SCS group) or without (control group) additional SCS therapy, and both groups were assessed at regular intervals. At each follow-up visit, the EuroQoL 5D, the short form McGill Pain Questionnaire (SF-MPQ) and a visual analogue scale (VAS, ranging 0-100) to measure pain intensity were recorded. The average VAS score for pain intensity was 73 in the SCS group and 67 in the control group at baseline. After 6 months of treatment, the average VAS score was significantly reduced to 31 in the SCS group (P<.001) and remained 67 (P=.97) in the control group. The SF-MPQ and EuroQoL 5D questionnaires also showed that patients in the SCS group, unlike those in the control group, experienced reduced pain and improved health and quality of life after 6 months of treatment. In patients with refractory painful diabetic neuropathy, spinal cord stimulation therapy significantly reduced pain and improved quality of life. Copyright © 2014 International Association for the Study of Pain. Published by Elsevier B.V. All rights reserved.

The effect of Helicobacter pylori infection and eradication in patients with gastro-oesophageal reflux disease: A parallel-group, double-blind, placebo-controlled multicentre study.

PubMed

Schwizer, Werner; Menne, Dieter; Schütze, Kurt; Vieth, Michael; Goergens, Reiner; Malfertheiner, Peter; Leodolter, Andreas; Fried, Michael; Fox, Mark R

2013-08-01

This study aimed to resolve controversy regarding the effects of Helicobacter pylori eradication therapy and H. pylori infection in gastro-oesophageal reflux disease. A randomized, double-blind, multicentre trial was performed in patients presenting with reflux symptoms. H. pylori-positive patients were randomized to receive either antibiotics or placebo for 7 days. H. pylori-negative patient controls received placebo. All received esomeprazole 20 mg b.d. for 7 days, followed by 40 mg o.d. to complete an 8-week course, and were followed up for 32 weeks by telephone. In this study, 198/589 (34%) patients were H. pylori-positive and 113 H. pylori-negative patients served as controls. Baseline endoscopy revealed 63% Los Angeles grade 0A and 37% Los Angeles grade BCD oesophagitis with no difference between patient groups. Symptom improvement on esomeprazole was seen in 89%. H. pylori eradication was successful in 82%. H. pylori eradication had no effect on symptomatic relapse (hazard ratio 1.15, 95% CI 0.74-1.8; p = 0.5). Overall, H. pylori-positive patients had a lower probability of relapse compared to H. pylori-negative controls (hazard ratio 0.6, 95% CI 0.43-0.85; p = 0.004). Relapse hazard was modulated also by oesophagitis grade (BCD vs. 0A, hazard ratio 2.1, 95% CI 1.5-3.0). Relapse of gastro-oesophageal reflux disease symptoms after a course of high dose acid suppression took longer for H. pylori-positive patients than H. pylori-negative controls; however eradication therapy had no effect on the risk of relapse; ClincialTrials.gov number, NCT00574925.

The effect of Helicobacter pylori infection and eradication in patients with gastro-oesophageal reflux disease: A parallel-group, double-blind, placebo-controlled multicentre study

PubMed Central

Menne, Dieter; Schütze, Kurt; Vieth, Michael; Goergens, Reiner; Malfertheiner, Peter; Leodolter, Andreas; Fried, Michael; Fox, Mark R

2013-01-01

Objectives This study aimed to resolve controversy regarding the effects of Helicobacter pylori eradication therapy and H. pylori infection in gastro-oesophageal reflux disease. Design A randomized, double-blind, multicentre trial was performed in patients presenting with reflux symptoms. H. pylori-positive patients were randomized to receive either antibiotics or placebo for 7 days. H. pylori-negative patient controls received placebo. All received esomeprazole 20 mg b.d. for 7 days, followed by 40 mg o.d. to complete an 8-week course, and were followed up for 32 weeks by telephone. Results In this study, 198/589 (34%) patients were H. pylori-positive and 113 H. pylori-negative patients served as controls. Baseline endoscopy revealed 63% Los Angeles grade 0A and 37% Los Angeles grade BCD oesophagitis with no difference between patient groups. Symptom improvement on esomeprazole was seen in 89%. H. pylori eradication was successful in 82%. H. pylori eradication had no effect on symptomatic relapse (hazard ratio 1.15, 95% CI 0.74–1.8; p = 0.5). Overall, H. pylori-positive patients had a lower probability of relapse compared to H. pylori-negative controls (hazard ratio 0.6, 95% CI 0.43–0.85; p = 0.004). Relapse hazard was modulated also by oesophagitis grade (BCD vs. 0A, hazard ratio 2.1, 95% CI 1.5–3.0). Conclusion Relapse of gastro-oesophageal reflux disease symptoms after a course of high dose acid suppression took longer for H. pylori-positive patients than H. pylori-negative controls; however eradication therapy had no effect on the risk of relapse; ClincialTrials.gov number, NCT00574925. PMID:24917966

Asparaginase and MOPP treatment of dogs with lymphoma.

PubMed

Brodsky, E M; Maudlin, G N; Lachowicz, J L; Post, G S

2009-01-01

Dogs with multicentric lymphoma are treated with various cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP)-based chemotherapy protocols with variable success. To describe the progression-free survival (PFS) time and overall survival time (OST) of dogs with T-cell lymphoma or hypercalcemic lymphoma treated with L-asparaginase and mechlorethamine, vincristine, prednisone, procarbazine (MOPP). Fifty dogs with T-cell lymphoma, hypercalcemic lymphoma, or both treated at 3 referral veterinary hospitals. Retrospective study. Case were selected based on histologic or cytologic diagnosis of lymphoma; presence of the T-cell phenotype, presence of hypercalcemia or both; and absence of previous chemotherapy. The T-cell phenotype was determined by flow cytometry, immunocytochemistry, immunohistochemistry, or polymerase chain reaction of antigen receptor rearrangement. The overall response rate was 98% (78% complete response, 20% partial response). The median PFS for the entire study population was 189 days with 25% PFS at 939 days. The median OST for the entire study population was 270 days with 25% surviving 939 days. Twenty percent of the dogs required hospitalization for treatment related complications. L-Asp/MOPP chemotherapy might result in longer PFS and OST for dogs with multicentric T-cell lymphoma, dogs with hypercalcemic lymphoma or both, than achieved with CHOP.

Management of renal transplant urolithiasis: a multicentre study by the French Urology Association Transplantation Committee.

PubMed

Branchereau, J; Timsit, M O; Neuzillet, Y; Bessède, T; Thuret, R; Gigante, M; Tillou, X; Codas, R; Boutin, J; Doerfler, A; Sallusto, F; Culty, T; Delaporte, V; Brichart, N; Barrou, B; Salomon, L; Karam, G; Rigaud, J; Badet, L; Kleinklauss, F

2018-01-01

Urolithiasis is rare among renal transplant recipients and its management has not been clearly defined. This multicentre retrospective study was organised by the Comité de Transplantation de l'Association Française d'Urologie (French Urology Association transplantation committee). Statistical analysis was performed with SPSS 19 software. Ninety-five patients were included in this study. Renal transplant urolithiasis was an incidental finding in 55% of cases, mostly on a routine follow-up ultrasound examination. One half of symptomatic stones were due to urinary tract infection and the other half were due to an episode of acute renal failure. The initial management following diagnosis of urolithiasis was double J stenting (27%), nephrostomy tube placement (21%), or watchful waiting (52%). Definitive management consisted of: watchful waiting (48%), extracorporeal lithotripsy (13%), rigid or flexible ureteroscopy (26%), percutaneous nephrolithotomy (11%) and surgical pyelotomy (2%). All transplants remained functional following treatment of the stone. The main limitation is the retrospective design. The incidence of lithiasis could be higher in kidney transplanted patients due to a possible anatomical or metabolical abnormalities. The therapeutic management of renal transplant urolithiasis appears to be comparable to that of native kidney urolithiasis.

Ethical approval for research involving geographically dispersed subjects: unsuitability of the UK MREC/LREC system and relevance to uncommon genetic disorders.

PubMed

Lewis, J C; Tomkins, S; Sampson, J R

2001-10-01

To assess the process involved in obtaining ethical approval for a single-centre study involving geographically dispersed subjects with an uncommon genetic disorder. Observational data of the application process to 53 local research ethics committees (LRECs) throughout Wales, England and Scotland. The Multicentre Research Ethics Committee (MREC) for Wales had already granted approval. Application to the 53 LRECs required 24,552 sheets of paper and took two months of the researcher's time. The median time taken for approval was 39 days with only seven (13%) of committees responding within the recommended 21 days. In at least nineteen cases (36%) a subcommittee considered the application. Thirty-three committees (62%) accepted the proposal without amendments but, of the remainder, four (8%) requested changes outside of the remit of LRECs. Difficulties still exist with the system for obtaining ethical approval for studies involving a single centre but with patients at multiple sites, as is often required for genetic observational research. As such studies differ from true multicentre studies, it may be advantageous to develop a separate and specific process of application to ensure that resources are not unnecessarily expended in the quest for ethical approval.

Efficacy of nurse-led and general practitioner-led comprehensive geriatric assessment in primary care: protocol of a pragmatic three-arm cluster randomised controlled trial (CEpiA study)

PubMed Central

Ferrat, Emilie; Bastuji-Garin, Sylvie; Paillaud, Elena; Caillet, Philippe; Clerc, Pascal; Moscova, Laura; Gouja, Amel; Renard, Vincent; Attali, Claude; Breton, Julien Le; Audureau, Etienne

2018-01-01

Introduction Older patients raise therapeutic challenges, because they constitute a heterogeneous population with multimorbidity. To appraise this complexity, geriatricians have developed a multidimensional comprehensive geriatric assessment (CGA), which may be difficult to apply in primary care settings. Our primary objective was to compare the effect on morbimortality of usual care compared with two complex interventions combining educational seminars about CGA: a dedicated geriatric hotline for general practitioners (GPs) and CGA by trained nurses or GPs. Methods and analysis The Clinical Epidemiology and Ageing study is an open-label, pragmatic, multicentre, three-arm, cluster randomised controlled trial comparing two intervention groups and one control group. Patients must be 70 years or older with a long-term illness or with unscheduled hospitalisation in the past 3 months (750 patients planned). This study involves volunteering GPs practising in French primary care centres, with randomisation at the practice level. The multifaceted interventions for interventional arms comprise an educational interactive multiprofessional seminar for GPs and nurses, a geriatric hotline dedicated to GPs in case of difficulties and the performance of a CGA updated to primary care. The CGA is systematically performed by a nurse in arm 1 but is GP-led on a case-by-case basis in arm 2. The primary endpoint is a composite criterion comprising overall death, unscheduled hospitalisations, emergency admissions and institutionalisation within 12 months after inclusion. Intention-to-treat analysis will be performed using mixed-effects logistic regression models, with adjustment for potential confounders. Ethics and dissemination The protocol was approved by an appropriate ethics committee (CPP Ile-de-France IV, Paris, France, approval April 2015;15 664). This study is conducted according to principles of good clinical practice in the context of current care and will provide useful knowledge on the clinical benefits achievable by CGA in primary care. Trial registration number NCT02664454; Pre-results. PMID:29654038

Functional variants in the sucrase–isomaltase gene associate with increased risk of irritable bowel syndrome

PubMed Central

Henström, Maria; Diekmann, Lena; Bonfiglio, Ferdinando; Hadizadeh, Fatemeh; Kuech, Eva-Maria; von Köckritz-Blickwede, Maren; Thingholm, Louise B; Zheng, Tenghao; Assadi, Ghazaleh; Dierks, Claudia; Heine, Martin; Philipp, Ute; Distl, Ottmar; Money, Mary E; Belheouane, Meriem; Heinsen, Femke-Anouska; Rafter, Joseph; Nardone, Gerardo; Cuomo, Rosario; Usai-Satta, Paolo; Galeazzi, Francesca; Neri, Matteo; Walter, Susanna; Simrén, Magnus; Karling, Pontus; Ohlsson, Bodil; Schmidt, Peter T; Lindberg, Greger; Dlugosz, Aldona; Agreus, Lars; Andreasson, Anna; Mayer, Emeran; Baines, John F; Engstrand, Lars; Portincasa, Piero; Bellini, Massimo; Stanghellini, Vincenzo; Barbara, Giovanni; Chang, Lin; Camilleri, Michael; Franke, Andre; Naim, Hassan Y

2018-01-01

Objective IBS is a common gut disorder of uncertain pathogenesis. Among other factors, genetics and certain foods are proposed to contribute. Congenital sucrase–isomaltase deficiency (CSID) is a rare genetic form of disaccharide malabsorption characterised by diarrhoea, abdominal pain and bloating, which are features common to IBS. We tested sucrase–isomaltase (SI) gene variants for their potential relevance in IBS. Design We sequenced SI exons in seven familial cases, and screened four CSID mutations (p.Val557Gly, p.Gly1073Asp, p.Arg1124Ter and p.Phe1745Cys) and a common SI coding polymorphism (p.Val15Phe) in a multicentre cohort of 1887 cases and controls. We studied the effect of the 15Val to 15Phe substitution on SI function in vitro. We analysed p.Val15Phe genotype in relation to IBS status, stool frequency and faecal microbiota composition in 250 individuals from the general population. Results CSID mutations were more common in patients than asymptomatic controls (p=0.074; OR=1.84) and Exome Aggregation Consortium reference sequenced individuals (p=0.020; OR=1.57). 15Phe was detected in 6/7 sequenced familial cases, and increased IBS risk in case–control and population-based cohorts, with best evidence for diarrhoea phenotypes (combined p=0.00012; OR=1.36). In the population-based sample, 15Phe allele dosage correlated with stool frequency (p=0.026) and Parabacteroides faecal microbiota abundance (p=0.0024). The SI protein with 15Phe exhibited 35% reduced enzymatic activity in vitro compared with 15Val (p<0.05). Conclusions SI gene variants coding for disaccharidases with defective or reduced enzymatic activity predispose to IBS. This may help the identification of individuals at risk, and contribute to personalising treatment options in a subset of patients. PMID:27872184

Medicine in spine exercise (MiSpEx) for nonspecific low back pain patients: study protocol for a multicentre, single-blind randomized controlled trial.

PubMed

Niederer, Daniel; Vogt, Lutz; Wippert, Pia-Maria; Puschmann, Anne-Katrin; Pfeifer, Ann-Christin; Schiltenwolf, Marcus; Banzer, Winfried; Mayer, Frank

2016-10-20

Arising from the relevance of sensorimotor training in the therapy of nonspecific low back pain patients and from the value of individualized therapy, the present trial aims to test the feasibility and efficacy of individualized sensorimotor training interventions in patients suffering from nonspecific low back pain. A multicentre, single-blind two-armed randomized controlled trial to evaluate the effects of a 12-week (3 weeks supervised centre-based and 9 weeks home-based) individualized sensorimotor exercise program is performed. The control group stays inactive during this period. Outcomes are pain, and pain-associated function as well as motor function in adults with nonspecific low back pain. Each participant is scheduled to five measurement dates: baseline (M1), following centre-based training (M2), following home-based training (M3) and at two follow-up time points 6 months (M4) and 12 months (M5) after M1. All investigations and the assessment of the primary and secondary outcomes are performed in a standardized order: questionnaires - clinical examination - biomechanics (motor function). Subsequent statistical procedures are executed after the examination of underlying assumptions for parametric or rather non-parametric testing. The results and practical relevance of the study will be of clinical and practical relevance not only for researchers and policy makers but also for the general population suffering from nonspecific low back pain. Identification number DRKS00010129. German Clinical Trial registered on 3 March 2016.

Reliability of intra-oral quantitative sensory testing (QST) in patients with atypical odontalgia and healthy controls - a multicentre study.

PubMed

Baad-Hansen, L; Pigg, M; Yang, G; List, T; Svensson, P; Drangsholt, M

2015-02-01

The reliability of comprehensive intra-oral quantitative sensory testing (QST) protocol has not been examined systematically in patients with chronic oro-facial pain. The aim of the present multicentre study was to examine test-retest and interexaminer reliability of intra-oral QST measures in terms of absolute values and z-scores as well as within-session coefficients of variation (CV) values in patients with atypical odontalgia (AO) and healthy pain-free controls. Forty-five patients with AO and 68 healthy controls were subjected to bilateral intra-oral gingival QST and unilateral extratrigeminal QST (thenar) on three occasions (twice on 1 day by two different examiners and once approximately 1 week later by one of the examiners). Intra-class correlation coefficients and kappa values for interexaminer and test-retest reliability were computed. Most of the standardised intra-oral QST measures showed fair to excellent interexaminer (9-12 of 13 measures) and test-retest (7-11 of 13 measures) reliability. Furthermore, no robust differences in reliability measures or within-session variability (CV) were detected between patients with AO and the healthy reference group. These reliability results in chronic orofacial pain patients support earlier suggestions based on data from healthy subjects that intra-oral QST is sufficiently reliable for use as a part of a comprehensive evaluation of patients with somatosensory disturbances or neuropathic pain in the trigeminal region. © 2014 John Wiley & Sons Ltd.

The psychosocial burden of hand eczema: Data from a European dermatological multicentre study.

PubMed

Marron, Servando E; Tomas-Aragones, Lucia; Navarro-Lopez, Jorge; Gieler, Uwe; Kupfer, Jörg; Dalgard, Florence J; Lien, Lars; Finlay, Andrew Y; Poot, Françoise; Linder, Dennis; Szepietowski, Jacek C; Misery, Laurent; Jemec, Gregor B E; Romanov, Dmitry; Sampogna, Francesca; Szabo, Csanad; Altunay, Ilknur K; Spillekom-van Koulil, Saskia; Balieva, Flora; Ali, Faraz M; Halvorsen, Jon A; Marijuan, Pedro C

2018-06-01

The essential physical role, visibility and social importance of the hands place a major psychological burden on patients with hand eczema. The aim of this study was to identify the psychological, social and clinical characteristics of patients with hand eczema, in particular the prevalences of depression, anxiety, suicidal ideation, and comorbidities. Data on patients with hand eczema were analysed from a large European multicentre study conducted with dermatology outpatients from 13 countries. Groups of patients and controls were compared to analyse the psychological burden of hand eczema. Female patients with hand eczema had higher Hospital Anxiety and Depression Scale (HADS) scores for anxiety (n = 86, median = 7.0) than controls (n = 900, median = 5.0, P = .02), and for depression (median = 4.0) than controls (3.0, P < .001). Patients with high suicidal ideation, with low socioeconomic status and who were widowed or divorced were more likely to fulfil the HADS criteria for anxiety [odds ratio (OR) > 1, P = .038, P < .001, and P < .001, respectively]. The median Dermatology Life Quality Index score was 7.0 (n = 68). This study identifies a specific psychological burden experienced by hand eczema patients, highlighting the need for focused psychosocial interventions. Physicians in particular should be aware of the need to identify anxiety and depression in female patients. © 2018 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

[Second primary cancers of the bronchi treated surgically (recurrence excluded). Results of a national survey (1987)].

PubMed

Levasseur, P; Delambre, J F

1989-01-01

A multicentre study conducted by a number of French Thoracic Surgery centres has collected a total of 88 cases of operated metachronous cancers. After defining the concept of metachronous cancer, the reporters of this survey successively analyse the frequency, histological type and clinical course of such lesions. The various types of resection and the results (postoperative course and long-term acturial survival) are also examined in detail. The good long-term survival of such metachronous cancers justifies a deliberately "aggressive" surgical approach.

Body mass index kinetics around adiposity rebound in Anorexia nervosa: A case-control study.

PubMed

Neveu, Rémi; Neveu, Dorine; Carrier, Edouard; Ourrad, Nadia; Perroud, Alain; Nicolas, Alain

2016-10-01

Anorexia nervosa (AN) is associated with parameters involved in body mass index (BMI) regulation. Contrary to obesity, BMI kinetics around the adiposity rebound is not documented in AN. This study aimed at investigating which characteristics of BMI kinetics around the adiposity rebound are associated with AN. Multicentre case-control study with 101 inpatient women with AN onset after 10 years of age, and 101 healthy women, all free of overweight history and matched for age, level of education and fathers' socio-professional status. Age at adiposity rebound, pre- and post-adiposity rebound BMI velocities and accelerations (change in velocity over time) were estimated with linear mixed models using data recorded between 2 and 10 years of age. Patients had an earlier adiposity rebound (mean (standard deviation (SD)): 5.3 (1.3) vs 5.7 (1.1) years), a larger BMI at adiposity rebound (mean (SD): 15.3 [1] vs 14.9 (0.9) kg/m 2 ) and 29% lower BMI acceleration after adiposity rebound than controls. After adjustment, only BMI at adiposity rebound and BMI acceleration after adiposity rebound were associated with a higher risk of AN (Odds ratio [95% confidence interval]: 2.15 [1.41-3.46] for an increase of 1 kg/m 2 and 2.44 [1.56-4.02] for an increase of 0.1 kg/(m 2 *years 2 ) respectively). These two factors were not correlated in patients (r = 0.007, p = 0.96). A flattened evolution of BMI after adiposity rebound and higher BMI at adiposity rebound were associated with AN. Further prospective study is needed to confirm these findings. Copyright © 2016 European Society for Clinical Nutrition and Metabolism. Published by Elsevier Ltd. All rights reserved.

Family history and lung cancer risk: international multicentre case-control study in Eastern and Central Europe and meta-analyses.

PubMed

Lissowska, Jolanta; Foretova, Lenka; Dabek, Joanna; Zaridze, David; Szeszenia-Dabrowska, Neonila; Rudnai, Peter; Fabianova, Eleonora; Cassidy, Adrian; Mates, Dana; Bencko, Vladimir; Janout, Vladimir; Hung, Rayjean J; Brennan, Paul; Boffetta, Paolo

2010-07-01

Lung cancer is the most common neoplastic disease in Eastern and Central Europe. The role of hereditary factors in lung carcinogenesis is not fully understood. Family history (FH) of lung cancer and other tobacco-related cancers might be a strong predictor of the lung cancer risk. We investigated family history of cancer among first-degree relatives of 2,861 patients with lung cancer and 3,118 controls from the Czech Republic, Hungary, Poland, Romania, Russia, Slovakia, and United Kingdom within the IARC Multicenter Case-Control Study. Odds ratios (ORs) and 95% CI were calculated using logistic regression, adjusting for age, gender, study center, education, tobacco smoking, and number of first-degree relatives. In addition, we conducted a meta-analysis of 41 studies on FH of cancer and lung cancer risk. Positive FH of lung cancer increased risk of lung cancer with OR of 1.63 (95%CI: 1.31-2.01), and having two or more affected relatives with lung cancer further increased the risk of lung cancer with OR 3.60 (95%CI: 1.56-8.31). Among subjects aged less than 50, the OR for FH of lung cancer was 2.08 (95%CI: 1.18-3.63). The associations were generally stronger for squamous cell carcinoma and large cell carcinoma subtypes. Heterogeneity in results was not found with respect to smoking status and gender. A significant association was not observed for FH of other smoking-related tumors. The results of meta-analysis were consistent with that of our study with regard to young onset, non-smokers and histology. FH of lung cancer is a predictor of an increased risk of lung cancer, especially in subjects aged less than 50.

Four Cases of Spontaneous Neoplasia in the Naked Mole-Rat (Heterocephalus glaber), A Putative Cancer-Resistant Species.

PubMed

Taylor, Kyle R; Milone, Nicholas A; Rodriguez, Carlos E

2017-01-01

The naked mole-rat (Heterocephalus glaber) is widely acclaimed to be cancer-resistant and of considerable research interest based on a paucity of reports of neoplasia in this species. We have, however, encountered four spontaneous cases of neoplasia and one presumptive case of neoplasia through routine necropsy and biopsy of individuals in a zoo collection of nonhybrid naked mole-rats bred from a single pair. One case each of metastasizing hepatocellular carcinoma, nephroblastoma (Wilms' tumor), and multicentric lymphosarcoma, as well as presumptive esophageal adenocarcinoma (Barrett's esophagus-like) was identified postmortem among 37 nonautolyzed necropsy submissions of naked mole-rats over 1-year-old that were submitted for necropsy between 1998 and August 2015. One incidental case of cutaneous hemangioma was also identified antemortem by skin biopsy from one naked mole-rat examined for trauma. © The Author 2016. Published by Oxford University Press on behalf of The Gerontological Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

[Establishment and Management of Multicentral Collection Bio-sample Banks of Malignant Tumors from Digestive System].

PubMed

Shen, Si; Shen, Junwei; Zhu, Liang; Wu, Chaoqun; Li, Dongliang; Yu, Hongyu; Qiu, Yuanyuan; Zhou, Yi

2015-11-01

To establish and manage of multicentral collection bio-sample banks of malignant tumors from digestive system, the paper designed a multicentral management system, established the standard operation procedures (SOPs) and leaded ten hospitals nationwide to collect tumor samples. The biobank has been established for half a year, and has collected 695 samples from patients with digestive system malignant tumor. The clinical data is full and complete, labeled in a unified way and classified to be managed. The clinical and molecular biology researches were based on the biobank, and obtained achievements. The biobank provides a research platform for malignant tumor of digestive system from different regions and of different types.

Multifocal synchronous ipsilateral Warthin tumors: case report and review of the literature.

PubMed

Hall, Joseph E; Statham, Melissa McCarty; Sheridan, Rachel M; Wilson, Keith M

2010-09-01

We report a case of a 73-year-old woman who presented with an enlarging superficial parotid mass, a concomitant ipsilateral deep-lobe parotid mass, and associated upper jugular lymphadenopathy. The clinical presentation and radiographic imaging were suggestive of malignancy, and the patient was treated with total parotidectomy with upper jugular lymph node sampling. Pathologic examination revealed two distinct masses, one in the superficial lobe and one in the deep lobe of the parotid gland, both consistent with synchronous Warthin tumors. Analysis of the upper jugular lymph nodes was consistent with reactive lymphoid hyperplasia. Although the true incidence of multicentricity in ipsilateral Warthin tumors may be underappreciated and underreported, this entity should remain in the differential diagnosis for unilateral parotid masses.

Enzootic leucosis in a flock of sheep in Rhodesia.

PubMed

Boyt, W P; Mackenzie, P K; Emslie, V W

1976-02-07

Fourteen cases of lymphosarcoma occurred in a small experimental flock of sheep in Rhodesia. There appeared to be horizontal spread and the ages of the affected animals varied from one to more than 10 years. Thirteen of the cases so far diagnosed were leucaemic with a high lymphocyte count. Eleven of the sheep demonstrated multicentric lesions and two alimentary mesenteric; the remaining animal is still alive. Transmission attempts in four neonates resulted in one showing a high white cell count after 25 months. Electron microscope studies failed to demonstrate C-type virus-like particles. This appears to be the first recorded example of an outbreak of lymphosarcoma in a flock of sheep in Southern Africa and the descriptive term "enzootic leucosis" has been adopted.

Should medical students learn to develop a personal formulary?

PubMed Central

Daniels, J. M. A.; Mulder, C. W.; Groot, O. A.; Wewerinke, L.; Barnes, K. I.; Bakathir, H. A.; Hassan, N. A. G. M.; Van Bortel, L.; Kriska, M.; Santoso, B.; Sanz, E. J.; Thomas, M.; Ziganshina, L. E.; Bezemer, P. D.; Van Kan, C.; Richir, M. C.; Hogerzeil, H. V.

2008-01-01

Objective This study was performed to determine whether students who are trained in developing a personal formulary become more competent in rational prescribing than students who have only learned to use existing formularies. Methods This was a multicentre, randomised, controlled study conducted in eight universities in India, Indonesia, the Netherlands, the Russian Federation, Slovakia, South Africa, Spain and Yemen. Five hundred and eighty-three medical students were randomised into three groups: the personal formulary group (PF; 94), the existing formulary group (EF; 98) and the control group (C; 191). The PF group was taught how to develop and use a personal formulary, whereas e the EF group was taught how to review and use an existing formulary. The C group received no additional training and participated only in the tests. Student’s prescribing skills were measured by scoring their treatment plans for written patient cases. Results The mean PF group score increased by 23% compared with 19% for the EF group (p < 0.05) and 6% for controls (p < 0.05). The positive effect of PF training was only significant in universities that had a mainly classic curriculum. Conclusion Training in development and use of a personal formulary was particularly effective in universities with a classic curriculum and with traditional pharmacology teaching. In universities with a general problem-based curriculum, pharmacotherapy teaching can be based on either existing or personal formularies. PMID:18338161

Role of capsule endoscopy in suspected celiac disease: A European multi-centre study

PubMed Central

Luján-Sanchis, Marisol; Pérez-Cuadrado-Robles, Enrique; García-Lledó, Javier; Juanmartiñena Fernández, José-Francisco; Elli, Luca; Jiménez-García, Victoria-Alejandra; Egea-Valenzuela, Juan; Valle-Muñoz, Julio; Carretero-Ribón, Cristina; Fernández-Urién-Sainz, Ignacio; López-Higueras, Antonio; Alonso-Lázaro, Noelia; Sanjuan-Acosta, Mileidis; Sánchez-Ceballos, Francisco; Rosa, Bruno; González-Vázquez, Santiago; Branchi, Federica; Ruano-Díaz, Lucía; Prieto-de-Frías, César; Pons-Beltrán, Vicente; Borque-Barrera, Pilar; González-Suárez, Begoña; Xavier, Sofía; Argüelles-Arias, Federico; Herrerías-Gutiérrez, Juan-Manuel; Pérez-Cuadrado-Martínez, Enrique; Sempere-García-Argüelles, Javier

2017-01-01

AIM To analyze the diagnostic yield (DY), therapeutic impact (TI) and safety of capsule endoscopy (CE). METHODS This is a multi-centre, observational, analytical, retrospective study. A total of 163 patients with suspicion of celiac disease (CD) (mean age = 46.4 ± 17.3 years, 68.1% women) who underwent CE from 2003 to 2015 were included. Patients were divided into four groups: seronegative CD with atrophy (Group-I, n = 19), seropositive CD without atrophy (Group-II, n = 39), contraindication to gastroscopy (Group-III, n = 6), seronegative CD without atrophy, but with a compatible context (Group-IV, n = 99). DY, TI and the safety of CE were analysed. RESULTS The overall DY was 54% and the final diagnosis was villous atrophy (n = 65, 39.9%), complicated CD (n = 12, 7.4%) and other enteropathies (n = 11, 6.8%; 8 Crohn’s). DY for groups I to IV was 73.7%, 69.2%, 50% and 44.4%, respectively. Atrophy was located in duodenum in 24 cases (36.9%), diffuse in 19 (29.2%), jejunal in 11 (16.9%), and patchy in 10 cases (15.4%). Factors associated with a greater DY were positive serology (68.3% vs 49.2%, P = 0.034) and older age (P = 0.008). On the other hand, neither sex nor clinical presentation, family background, positive histology or HLA status were associated with DY. CE results changed the therapeutic approach in 71.8% of the cases. Atrophy was associated with a greater TI (92.3% vs 45.3%, P < 0.001) and 81.9% of the patients responded to diet. There was one case of capsule retention (0.6%). Agreement between CE findings and subsequent histology was 100% for diagnosing normal/other conditions, 70% for suspected CD and 50% for complicated CD. CONCLUSION CE has a high DY in cases of suspicion of CD and it leads to changes in the clinical course of the disease. CE is safe procedure with a high degree of concordance with histology and it helps in the differential diagnosis of CD. PMID:28216978

Virtual patients design and its effect on clinical reasoning and student experience: a protocol for a randomised factorial multi-centre study.

PubMed

Bateman, James; Allen, Maggie E; Kidd, Jane; Parsons, Nick; Davies, David

2012-08-01

Virtual Patients (VPs) are web-based representations of realistic clinical cases. They are proposed as being an optimal method for teaching clinical reasoning skills. International standards exist which define precisely what constitutes a VP. There are multiple design possibilities for VPs, however there is little formal evidence to support individual design features. The purpose of this trial is to explore the effect of two different potentially important design features on clinical reasoning skills and the student experience. These are the branching case pathways (present or absent) and structured clinical reasoning feedback (present or absent). This is a multi-centre randomised 2 x 2 factorial design study evaluating two independent variables of VP design, branching (present or absent), and structured clinical reasoning feedback (present or absent).The study will be carried out in medical student volunteers in one year group from three university medical schools in the United Kingdom, Warwick, Keele and Birmingham. There are four core musculoskeletal topics. Each case can be designed in four different ways, equating to 16 VPs required for the research. Students will be randomised to four groups, completing the four VP topics in the same order, but with each group exposed to a different VP design sequentially. All students will be exposed to the four designs. Primary outcomes are performance for each case design in a standardized fifteen item clinical reasoning assessment, integrated into each VP, which is identical for each topic. Additionally a 15-item self-reported evaluation is completed for each VP, based on a widely used EViP tool. Student patterns of use of the VPs will be recorded.In one centre, formative clinical and examination performance will be recorded, along with a self reported pre and post-intervention reasoning score, the DTI. Our power calculations indicate a sample size of 112 is required for both primary outcomes. This trial will provide robust evidence to support the effectiveness of different designs of virtual patients, based on student performance and evaluation. The cases and all learning materials will be open access and available on a Creative Commons Attribution-Share-Alike license.

Treatment of unicentric and multicentric Castleman disease and the role of radiotherapy.

PubMed

Chronowski, G M; Ha, C S; Wilder, R B; Cabanillas, F; Manning, J; Cox, J D

2001-08-01

Although surgery is considered standard therapy for unicentric Castleman disease, favorable responses to radiotherapy also have been documented. The authors undertook this study to analyze the clinical factors, treatment approaches, and outcomes of patients with unicentric or multicentric Castleman disease, and to report the outcomes of patients with unicentric Castleman disease treated with radiotherapy. The authors reviewed the medical records of 22 patients who had received a histologic diagnosis of Castleman disease at the University of Texas M. D. Anderson Cancer Center between 1988 and 1999. One patient with a concurrent histopathologic diagnosis of nonsecretory multiple myeloma was excluded from the study. In all patients, the diagnosis of Castleman disease was based on the results of lymph node biopsies. Disease was categorized as being either unicentric or multicentric and further subdivided into hyaline vascular, plasma cell, or mixed variant histologic types. Clinical variables and outcomes were analyzed according to treatment, which consisted of surgery, chemotherapy, or radiotherapy. Records from 21 patients were analyzed: 12 had unicentric disease, and 9 had multicentric disease. The mean follow-up time for the entire series was 51 months (median, 40 months). Four patients with unicentric disease were treated with radiotherapy alone: 2 remain alive and symptom free, 2 died of causes unrelated to Castleman disease and had no evidence of disease at last follow-up. Eight patients with unicentric disease were treated with complete or partial surgical resection, and all are alive and asymptomatic. All nine patients with multicentric disease were treated with combination chemotherapy: five are alive with no evidence of disease, and four are alive with progressive disease. Surgery results in excellent rates of cure in patients with unicentric Castleman disease; radiotherapy can also achieve clinical response and cure in selected patients. Multicentric Castleman disease is a more aggressive clinical entity and is most effectively treated with combination chemotherapy, whereas the role of radiotherapy in its treatment remains unclear. Copyright 2001 American Cancer Society.

Usefulness and applicability of the revised dengue case classification by disease: multi-centre study in 18 countries

PubMed Central

2011-01-01

Background In view of the long term discussion on the appropriateness of the dengue classification into dengue fever (DF), dengue haemorrhagic fever (DHF) and dengue shock syndrome (DSS), the World Health Organization (WHO) has outlined in its new global dengue guidelines a revised classification into levels of severity: dengue fever with an intermediary group of "dengue fever with warning sings", and severe dengue. The objective of this paper was to compare the two classification systems regarding applicability in clinical practice and surveillance, as well as user-friendliness and acceptance by health staff. Methods A mix of quantitative (prospective and retrospective review of medical charts by expert reviewers, formal staff interviews), semi-quantitative (open questions in staff interviews) and qualitative methods (focus group discussions) were used in 18 countries. Quality control of data collected was undertaken by external monitors. Results The applicability of the DF/DHF/DSS classification was limited, even when strict DHF criteria were not applied (13.7% of dengue cases could not be classified using the DF/DHF/DSS classification by experienced reviewers, compared to only 1.6% with the revised classification). The fact that some severe dengue cases could not be classified in the DF/DHF/DSS system was of particular concern. Both acceptance and perceived user-friendliness of the revised system were high, particularly in relation to triage and case management. The applicability of the revised classification to retrospective data sets (of importance for dengue surveillance) was also favourable. However, the need for training, dissemination and further research on the warning signs was highlighted. Conclusions The revised dengue classification has a high potential for facilitating dengue case management and surveillance. PMID:21510901

Reduced susceptibility to penicillin among pneumococci causing invasive infection in children - Canada, 1991 to 1998

PubMed Central

Scheifele, David; Halperin, Scott; Pelletier, Louise; Talbot, James; Lovgren, Marguerite; Vaudry, Wendy; Jadavji, Taj; Law, Barbara; MacDonald, Noni; Gold, Ron; Wang, Elaine; Mills, Elaine; Lebel, Marc; Déry, Pierre; Morris, Rob

2001-01-01

OBJECTIVE: To determine, over time, the rate and serotypes of pneumococci with reduced penicillin susceptibility obtained from children with invasive infection. DESIGN: Active, hospital-based, multicentre surveillance spanning from 1991 to 1998. SETTING: Eleven Canadian tertiary care paediatric facilities located from coast to coast. POPULATION STUDIED: 1847 children with invasive pneumococcal infection whose isolates (from a normally sterile site) were available for serotyping and standardized testing for penicillin susceptibility at the National Centre for Streptococcus. MAIN RESULTS: The prevalence of reduced penicillin susceptibility increased from 2.5% of 197 cases in 1991 to 13.0% of 276 cases in 1998. In the latter year, 8.7% of isolates had intermediate level resistance, and 4.3% had high level resistance. Since they were first detected in 1992, strains with high level resistance have been encountered only sporadically at most centres, but by 1998, all centres but two had encountered examples. Of 40 isolates with high level resistance and 101 isolates with intermediate level resistance, serotypes matched those included in new seven-valent conjugate vaccines for children in 97.5% and 79.2% of cases, respectively. CONCLUSIONS: Pneumococci with reduced susceptibility to penicillin are increasing in frequency across Canada among children with invasive infection. The Immunization Monitoring Program, Active data indicate that new conjugate vaccines could help to curb infections due to pneumococci with reduced susceptibility to penicillin but are unlikely to control completely the problem of antibiotic resistance. PMID:18159346

Evaluation of Cobas Integra 800 under simulated routine conditions in six laboratories.

PubMed

Redondo, Francisco L; Bermudez, Pilar; Cocco, Claudio; Colella, Francesca; Graziani, Maria Stella; Fiehn, Walter; Hierla, Thomas; Lemoël, Gisèle; Belliard, AnneMarie; Manene, Dieudonne; Meziani, Mourad; Liebel, Maryann; McQueen, Matthew J; Stockmann, Wolfgang

2003-03-01

The new selective access analyser Cobas Integra 800 from Roche Diagnostics was evaluated in an international multicentre study at six sites. Routine simulation experiments showed good performance and full functionality of the instrument and provocation of anomalous situations generated no problems. The new features on Cobas Integra 800, namely clot detection and dispensing control, worked according to specifications. The imprecision of Cobas Integra 800 fulfilled the proposed quality specifications regarding imprecision of analytical systems for clinical chemistry with few exceptions. Claims for linearity, drift, and carry-over were all within the defined specifications, except urea linearity. Interference exists in some cases, as could be expected due to the chemistries applied. Accuracy met the proposed quality specifications, except in some special cases. Method comparisons with Cobas Integra 700 showed good agreement; comparisons with other analysis systems yielded in several cases explicable deviations. Practicability of Cobas Integra 800 met or exceeded the requirements for more than 95% of all attributes rated. The strong points of the new analysis system were reagent handling, long stability of calibration curves, high number of tests on board, compatibility of the sample carrier to other Roche systems, and the sample integrity check for more reliable analytical results. The improvement of the workflow offered by the 5-position rack and STAT handling like on Cobas Integra 800 makes the instrument attractive for further consolidation in the medium-sized laboratory, for dedicated use of special analytes, and/or as back-up in the large routine laboratory.

What can patients tell us about the quality and safety of hospital care? Findings from a UK multicentre survey study.

PubMed

O'Hara, Jane K; Reynolds, Caroline; Moore, Sally; Armitage, Gerry; Sheard, Laura; Marsh, Claire; Watt, Ian; Wright, John; Lawton, Rebecca

2018-03-15

Patient safety measurement remains a global challenge. Patients are an important but neglected source of learning; however, little is known about what patients can add to our understanding of safety. We sought to understand the incidence and nature of patient-reported safety concerns in hospital. Feedback about the experience of safety within hospital was gathered from 2471 inpatients as part of a multicentre, waitlist cluster randomised controlled trial of an intervention, undertaken within 33 wards across three English NHS Trusts, between May 2013 and September 2014. Patient volunteers, supported by researchers, developed a classification framework of patient-reported safety concerns from a random sample of 231 reports. All reports were then classified using the patient-developed categories. Following this, all patient-reported safety concerns underwent a two-stage clinical review process for identification of patient safety incidents. Of the 2471 inpatients recruited, 579 provided 1155 patient-reported incident reports. 14 categories were developed for classification of reports, with communication the most frequently occurring (22%), followed by staffing issues (13%) and problems with the care environment (12%). 406 of the total 1155 patient incident reports (35%) were classified by clinicians as a patient safety incident according to the standard definition. 1 in 10 patients (264 patients) identified a patient safety incident, with medication errors the most frequently reported incident. Our findings suggest that patients can provide insight about safety that complements existing patient safety measurement, with a frequency of reported patient safety incidents that is similar to those obtained via case note review. However, patients provide a unique perspective about hospital safety which differs from and adds to current definitions of patient safety incidents. ISRCTN07689702; 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.

A UK NEQAS ICC and ISH multicentre study using the Kreatech Poseidon HER2 FISH probe: intersite variation can be rigorously controlled using FISH.

PubMed

Bartlett, John M S; Campbell, Fiona M; Ibrahim, Merdol; Thomas, Jeremy; Wencyk, Pete; Ellis, Ian; Kay, Elaine; Connolly, Yvonne; O'Grady, Anthony; Barnett, Sarah; Starczynski, Jane; Cunningham, Paul; Miller, Keith

2010-02-01

To assess a new HER2 fluorescence in situ hybridization (FISH) test and report on multicentre intrasite and intersite variation. HER2 results were scored from 45 breast cancers in eight laboratories using the Kreatech Poseidon HER2 FISH probe (Kreatech Diagnostics, Amsterdam, the Netherlands). Overall, 80.9% of cores were successfully analysed. Mean intrasite variation for HER2 ratio assessment was low (4.74%). Intersite variation in ratio was in line with previous reports (11.9+/-0.8%) for both reference and non-reference laboratories; only one laboratory displayed significantly higher intersite variation (P=0.009) than the remaining seven laboratories. The overall incidence of misclassification of cores was <1.3%, demonstrating an excellent level of concordance (>98.7%) across all eight laboratories, irrespective of whether they were 'reference' or 'routine diagnostic' laboratories. The Kreatech Poseidon HER2 FISH test is robust and reproducible. Highly quantitatively reproducible FISH results were obtained from eight 'diagnostic' and 'reference' laboratories; however, continued quality assessments are essential to good performance.

MAFB Determines Human Macrophage Anti-Inflammatory Polarization: Relevance for the Pathogenic Mechanisms Operating in Multicentric Carpotarsal Osteolysis.

PubMed

Cuevas, Víctor D; Anta, Laura; Samaniego, Rafael; Orta-Zavalza, Emmanuel; Vladimir de la Rosa, Juan; Baujat, Geneviève; Domínguez-Soto, Ángeles; Sánchez-Mateos, Paloma; Escribese, María M; Castrillo, Antonio; Cormier-Daire, Valérie; Vega, Miguel A; Corbí, Ángel L

2017-03-01

Macrophage phenotypic and functional heterogeneity derives from tissue-specific transcriptional signatures shaped by the local microenvironment. Most studies addressing the molecular basis for macrophage heterogeneity have focused on murine cells, whereas the factors controlling the functional specialization of human macrophages are less known. M-CSF drives the generation of human monocyte-derived macrophages with a potent anti-inflammatory activity upon stimulation. We now report that knockdown of MAFB impairs the acquisition of the anti-inflammatory profile of human macrophages, identify the MAFB-dependent gene signature in human macrophages and illustrate the coexpression of MAFB and MAFB-target genes in CD163 + tissue-resident and tumor-associated macrophages. The contribution of MAFB to the homeostatic/anti-inflammatory macrophage profile is further supported by the skewed polarization of monocyte-derived macrophages from multicentric carpotarsal osteolysis (Online Mendelian Inheritance in Man #166300), a pathology caused by mutations in the MAFB gene. Our results demonstrate that MAFB critically determines the acquisition of the anti-inflammatory transcriptional and functional profiles of human macrophages. Copyright © 2017 by The American Association of Immunologists, Inc.

[Multicenter randomized trial of amnioinfusion].

PubMed

Fraser, W; Marcoux, S; Prendiville, W; Petrou, S; Hofmeyr, J; Reinharz, D; Goulet, C; Ohlsson, A

2000-05-01

Meconium staining of the amniotic fluid in labor is a frequent problem that is associated with an increase in the risk of neonatal and maternal morbidity. Amnioinfusion is a simple technique that is designed to prevent neonatal and maternal morbidity associated with meconium. Preliminary studies indicate that amnioinfusion is a promising approach to the prevention of such complications of labor. However, further research is required. The primary objective of this multi-centre randomized controlled study is to determine if amnioinfusion for thick meconium stained amniotic fluid results in a reduction in perinatal death or moderate to severe meconium aspiration syndrome. We will also assess the effects of amnioinfusion on other indicators of neonatal morbidity and on cesarean section. The study includes an evaluation of womens views on their childbirth experience and an economic evaluation of a policy of amnioinfusion The study will be achieved with the collaboration of approximately 50 obstetrical centres from across Canada, US, Europe, South America and South Africa. This multicentre trial will provide urgently needed information on the efficacy and effectiveness of amniofusion for the indication of meconium stained amniotic fluid.

Moral imperialism and multi-centric clinical trials in peripheral countries.

PubMed

Garrafa, Volnei; Lorenzo, Claudio

2008-10-01

Moral imperialism is expressed in attempts to impose moral standards from one particular culture, geopolitical region or culture onto other cultures, regions or countries. Examples of Direct Moral Imperialism can be seen in various recurrent events involving multi-centric clinical trials promoted by developed (central) countries in poor and developing (peripheral) countries, particularly projects related to the theory of double standards in research. After the WMA General Assembly refused to change the Helsinki Declaration - which would have given moral recognition to the above mentioned theory - the USA abandoned the declaration and began to promote regional seminars in peripheral countries with the aim of "training" researchers on ethical perspectives that reflect America's best interests. Individuals who received such training became transmitters of these central countries' ideas across the peripheral countries, representing a form of Indirect Moral Imperialism. The paper proposes the establishment of regulatory and social control systems for clinical trials implemented in peripheral countries, through the formulation of ethical norms that reflect the specific contexts of these countries, along with the drawing up and validation of their own national norms.

Screening colonoscopy in 40- to 50-year-old first-degree relatives of patients with colorectal cancer is efficient: a controlled multicentre study.

PubMed

Menges, Markus; Fischinger, Johannes; Gärtner, Barbara; Georg, Thomas; Woerdehoff, Dietrich; Maier, Matthias; Harloff, Matthias; Stegmaier, Christa; Raedle, Jochen; Zeitz, Martin

2006-05-01

Persons with a familial risk of colorectal cancer (CRC) account for about 25% of all CRC cases. The adenoma prevalence in relatives of CRC patients 50-60 years of age is 17-34%; data on younger individuals are scarce. Our aim was to prospectively define the adenoma prevalence in 40- to 50-year-old first-degree relatives of CRC patients compared to controls. CRC patients were identified via the regional cancer registry, and their 40- to 50-year-old first-degree relatives (risk group) were invited for screening colonoscopy. Additional probands and controls of the same age were recruited by newspaper articles and radio or television broadcastings. Using high-resolution video colonoscopy, each detected polyp was removed and histopathologically assessed. Each participant completed demographic and epidemiological questionnaires. Of 228 subjects in the risk group 36.4% had polypoid lesions compared to 20.9% of 220 controls (p<0.001). Forty-three (18.9%) subjects in the risk group had adenomas compared to 18 (8.2%) in the control group (p=0.001). High-risk adenomas (>10 mm and/or of villous type) were found in 12 persons in the risk group compared to 5 controls (not significant). In the risk group most lesions (52%) were located proximal to the sigmoid colon compared to 29% in controls. Subjects between 40-50 years with first-degree relatives with CRC demonstrate a significantly higher prevalence of adenomas than controls, with a tendency towards a more proximal location. These data support a screening colonoscopy in persons with familial risk already between 40 and 50 years.

A multicentre prospective study of Guillain-Barré syndrome in Japan: a focus on the incidence of subtypes.

PubMed

Mitsui, Yoshiyuki; Kusunoki, Susumu; Arimura, Kimiyoshi; Kaji, Ryuji; Kanda, Takashi; Kuwabara, Satoshi; Sonoo, Masahiro; Takada, Kazuo

2015-01-01

Guillain-Barré Syndrome (GBS) is classified into the two major subtypes; acute inflammatory demyelinating polyneuropathy (AIDP) and acute motor axonal neuropathy (AMAN). Previous studies have suggested that AIDP is predominant and AMAN is rare in Western countries, whereas AMAN is not always uncommon in East Asia. We aimed to clarify the incidence of the subtypes of GBS in Japan. We performed a prospective multicentre survey over 3 years (2007-2010). Clinical and electrophysiological findings were collected from 184 patients with GBS in 23 tertiary neurology institutes. Anti-ganglioside antibodies were measured by ELISA. We also surveyed the incidence of Fisher syndrome (FS). By electrodiagnostic criteria of Ho et al, patients were classified as having AIDP (40%), or AMAN (22%), or unclassified (38%). Anti-GM1 IgG antibodies were found for 47% of AMAN patients, and 18% of AIDP patients (p<0.001). There were no specific regional trends of the electrodiagnosis and anti-GM1 positivity. During the same study period, 79 patients with FS were identified; the percentage of FS cases out of all cases (FS/(GBS+FS)) was 26%. The frequency of GBS patients with the electrodiagnosis of AMAN by single nerve conduction studies is approximately 20% in Japan, and the AMAN pattern is closely associated with anti-GM1 antibodies. The incidence of FS appears to be much higher in Japan than in Western countries. 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.

Blunt traumatic aortic injuries of the ascending aorta and aortic arch: a clinical multicentre study.

PubMed

Mosquera, Victor X; Marini, Milagros; Muñiz, Javier; Gulias, Daniel; Asorey-Veiga, Vanesa; Adrio-Nazar, Belen; Herrera, José M; Pradas-Montilla, Gonzalo; Cuenca, José J

2013-09-01

To report the clinical and radiological characteristics, management and outcomes of traumatic ascending aorta and aortic arch injuries. Historic cohort multicentre study including 17 major trauma patients with traumatic aortic injury from January 2000 to January 2011. The most common mechanism of blunt trauma was motor-vehicle crash (47%) followed by motorcycle crash (41%). Patients sustaining traumatic ascending aorta or aortic arch injuries presented a high proportion of myocardial contusion (41%); moderate or greater aortic valve regurgitation (12%); haemopericardium (35%); severe head injuries (65%) and spinal cord injury (23%). The 58.8% of the patients presented a high degree aortic injury (types III and IV). Expected in-hospital mortality was over 50% as defined by mean TRISS 59.7 (SD 38.6) and mean ISS 48.2 (SD 21.6) on admission. Observed in-hospital mortality was 53%. The cause of death was directly related to the ATAI in 45% of cases, head and abdominal injuries being the cause of death in the remaining 55% cases. Long-term survival was 46% at 1 year, 39% at 5 years, and 19% at 10 years. Traumatic aortic injuries of the ascending aorta/arch should be considered in any major thoracic trauma patient presenting cardiac tamponade, aortic valve regurgitation and/or myocardial contusion. These aortic injuries are also associated with a high incidence of neurological injuries, which can be just as lethal as the aortic injury, so treatment priorities should be modulated on an individual basis. Copyright © 2012 Elsevier Ltd. All rights reserved.

Ultrasound-guided breast-sparing surgery to improve cosmetic outcomes and quality of life. A prospective multicentre randomised controlled clinical trial comparing ultrasound-guided surgery to traditional palpation-guided surgery (COBALT trial)

PubMed Central

2011-01-01

Background Breast-conserving surgery for breast cancer was developed as a method to preserve healthy breast tissue, thereby improving cosmetic outcomes. Thus far, the primary aim of breast-conserving surgery has been the achievement of tumour-free resection margins and prevention of local recurrence, whereas the cosmetic outcome has been considered less important. Large studies have reported poor cosmetic outcomes in 20-40% of patients after breast-conserving surgery, with the volume of the resected breast tissue being the major determinant. There is clear evidence for the efficacy of ultrasonography in the resection of nonpalpable tumours. Surgical resection of palpable breast cancer is performed with guidance by intra-operative palpation. These palpation-guided excisions often result in an unnecessarily wide resection of adjacent healthy breast tissue, while the rate of tumour-involved resection margins is still high. It is hypothesised that the use of intra-operative ultrasonography in the excision of palpable breast cancer will improve the ability to spare healthy breast tissue while maintaining or even improving the oncological margin status. The aim of this study is to compare ultrasound-guided surgery for palpable tumours with the standard palpation-guided surgery in terms of the extent of healthy breast tissue resection, the percentage of tumour-free margins, cosmetic outcomes and quality of life. Methods/design In this prospective multicentre randomised controlled clinical trial, 120 women who have been diagnosed with palpable early-stage (T1-2N0-1) primary invasive breast cancer and deemed suitable for breast-conserving surgery will be randomised between ultrasound-guided surgery and palpation-guided surgery. With this sample size, an expected 20% reduction of resected breast tissue and an 18% difference in tumour-free margins can be detected with a power of 80%. Secondary endpoints include cosmetic outcomes and quality of life. The rationale, study design and planned analyses are described. Conclusion The COBALT trial is a prospective, multicentre, randomised controlled study to assess the efficacy of ultrasound-guided breast-conserving surgery in patients with palpable early-stage primary invasive breast cancer in terms of the sparing of breast tissue, oncological margin status, cosmetic outcomes and quality of life. Trial Registration Number Netherlands Trial Register (NTR): NTR2579 PMID:21410949

Ankle Injury Management (AIM): design of a pragmatic multi-centre equivalence randomised controlled trial comparing Close Contact Casting (CCC) to Open surgical Reduction and Internal Fixation (ORIF) in the treatment of unstable ankle fractures in patients over 60 years

PubMed Central

2014-01-01

Background Ankle fractures account for 9% of all fractures with a quarter of these occurring in adults over 60 years. The short term disability and long-term consequences of this injury can be considerable. Current opinion favours open reduction and internal fixation (ORIF) over non-operative treatment (fracture manipulation and the application of a standard moulded cast) for older people. Both techniques are associated with complications but the limited published research indicates higher complication rates of fracture malunion (poor position at healing) with casting. The aim of this study is to compare ORIF with a modification of existing casting techniques, Close Contact Casting (CCC). We propose that CCC may offer an equivalent functional outcome to ORIF and avoid the risks associated with surgery. Methods/Design This study is a pragmatic multi-centre equivalence randomised controlled trial. 620 participants will be randomised to receive ORIF or CCC after sustaining an isolated displaced unstable ankle fracture. Participants will be recruited from a minimum of 20 National Health Service (NHS) acute hospitals throughout England and Wales. Participants will be aged over 60 years and be ambulatory prior to injury. Follow-up will be at six weeks and six months after randomisation. The primary outcome is the Olerud & Molander Ankle Score, a functional patient reported outcome measure, at 6 months. Follow-up will also include assessments of mobility, ankle range of movement, health related quality of life and complications. The six-month follow-up will be conducted face-to-face by an assessor blinded to the allocated intervention. A parallel economic evaluation will consider both a health service and a broader societal perspective including the individual and their family. In order to explore patient experience of their treatment and recovery, a purposive sample of 40 patients will also be interviewed using a semi-structured interview schedule between 6-10 weeks post treatment. Discussion This multicentre study was open to recruitment July 2010 and recruitment is due to be completed in December 2013. Trial registration Current Controlled Trials ISRCTN04180738. PMID:24621174

Case management in oncology rehabilitation (CAMON): the effect of case management on the quality of life in patients with cancer after one year of ambulant rehabilitation. a study protocol for a randomized controlled clinical trial in oncology rehabilitation.

PubMed

Bachmann-Mettler, Irene; Steurer-Stey, Claudia; Senn, Oliver; Wang, Mathyas; Bardheci, Katarina; Rosemann, Thomas

2011-04-28

Cancer diseases and their therapies have negative effects on the quality of life. The aim of this study is to assess the effectiveness of case management in a sample of oncological outpatients with the intent of rehabilitation after cancer treatment. Case management wants to support the complex information needs of the patients in addition to the segmented structure of the health care system. Emphasis is put on support for self-management in order to enhance health - conscious behaviour, learning to deal with the burden of the illness and providing the opportunity for regular contacts with care providers. We present a study protocol to investigate the efficacy of a case management in patients following oncology rehabilitation after cancer treatment. The trial is a multicentre, two-arm randomised controlled study. Patients are randomised parallel in either 'usual care' plus case management or 'usual care' alone. Patients with all types of cancer can be included in the study, if they have completed the therapy with chemo- and/or radiotherapy/surgery with curative intention and are expected to have a survival time >1 year. To determine the health-related quality of life the general questionnaire FACT G is used. The direct correlation between self-management and perceived self-efficacy is measured with the Jerusalem & Schwarzer questionnaire. Patients satisfaction with the care received is measured using the Patient Assessment of Chronic Illness Care 5 As (PACIC-5A). Data are collected at the beginning of the trial and after 3, 6 and 12 months. The power analysis revealed a sample size of 102 patients. The recruitment of the centres began in 2009. The inclusion of patients began in May 2010. Case management has proved to be effective regarding quality of life of patients with chronic diseases. When it comes to oncology, case management is mainly used in cancer treatment, but it is not yet common in the rehabilitation of cancer patients. Case management in oncology rehabilitation is not well-established in Switzerland. A major challenge of the study will therefore probably be the recruitment of the patients due to the physicians' and patients' scarcely existing awareness of this issue. Trial registrationISRCTN41474586

Comparative randomised controlled clinical trial of a herbal eye drop with artificial tear and placebo in computer vision syndrome.

PubMed

Biswas, N R; Nainiwal, S K; Das, G K; Langan, U; Dadeya, S C; Mongre, P K; Ravi, A K; Baidya, P

2003-03-01

A comparative randomised double masked multicentric clinical trial has been conducted to find out the efficacy and safety of a herbal eye drop preparation, itone eye drops with artificial tear and placebo in 120 patients with computer vision syndrome. Patients using computer for at least 2 hours continuosly per day having symptoms of irritation, foreign body sensation, watering, redness, headache, eyeache and signs of conjunctival congestion, mucous/debris, corneal filaments, corneal staining or lacrimal lake were included in this study. Every patient was instructed to put two drops of either herbal drugs or placebo or artificial tear in the eyes regularly four times for 6 weeks. Objective and subjective findings were recorded at bi-weekly intervals up to six weeks. Side-effects, if any, were also noted. In computer vision syndrome the herbal eye drop preparation was found significantly better than artificial tear (p < 0.01). No side-effects were noted by any of the drugs. Both subjective and objective improvements were observed in itone treated cases. So, itone can be considered as a useful drug in computer vision syndrome.

The short term fetal cardiovascular effects of corticosteroids used in obstetrics

PubMed Central

Shand, Antonia; Welsh, Alec

2015-01-01

Abstract Background: Corticosteroids are widely used in obstetrics due to their striking effect on perinatal morbidity and mortality of premature neonates. Despite this, relatively few studies have explored short term fetal effects of corticosteroids as measured by ultrasound. Objectives: 1) To present a literature review of short term fetal cardiovascular effects of corticosteroids 2) To describe the protocol of a current observational study (SUPER‐A*STEROID) of cardiovascular effects of dexamethasone and betamethasone in the first week after their administration. This trial is nested within the A*STEROID blinded multicentre randomised controlled trial of the two steroid preparations. Findings: Existing data suggest corticosteroids have little effect on the major measured fetal blood vessels when the baseline ultrasound is normal. In the compromised fetus, where the umbilical artery end‐diastolic flow is abnormal prior to maternal corticosteroids, flow is temporarily restored in approximately 50% of cases. Whether such changes are beneficial is uncertain. Very little data exist that directly compare the short‐term effects of betamethasone and dexamethasone. The SUPER‐ A*STEROID study described will help provide this information. PMID:28191187

Characterisation of the opposing effects of G6PD deficiency on cerebral malaria and severe malarial anaemia.

PubMed

Clarke, Geraldine M; Rockett, Kirk; Kivinen, Katja; Hubbart, Christina; Jeffreys, Anna E; Rowlands, Kate; Jallow, Muminatou; Conway, David J; Bojang, Kalifa A; Pinder, Margaret; Usen, Stanley; Sisay-Joof, Fatoumatta; Sirugo, Giorgio; Toure, Ousmane; Thera, Mahamadou A; Konate, Salimata; Sissoko, Sibiry; Niangaly, Amadou; Poudiougou, Belco; Mangano, Valentina D; Bougouma, Edith C; Sirima, Sodiomon B; Modiano, David; Amenga-Etego, Lucas N; Ghansah, Anita; Koram, Kwadwo A; Wilson, Michael D; Enimil, Anthony; Evans, Jennifer; Amodu, Olukemi K; Olaniyan, Subulade; Apinjoh, Tobias; Mugri, Regina; Ndi, Andre; Ndila, Carolyne M; Uyoga, Sophie; Macharia, Alexander; Peshu, Norbert; Williams, Thomas N; Manjurano, Alphaxard; Sepúlveda, Nuno; Clark, Taane G; Riley, Eleanor; Drakeley, Chris; Reyburn, Hugh; Nyirongo, Vysaul; Kachala, David; Molyneux, Malcolm; Dunstan, Sarah J; Phu, Nguyen Hoan; Quyen, Nguyen Ngoc; Thai, Cao Quang; Hien, Tran Tinh; Manning, Laurens; Laman, Moses; Siba, Peter; Karunajeewa, Harin; Allen, Steve; Allen, Angela; Davis, Timothy Me; Michon, Pascal; Mueller, Ivo; Molloy, Síle F; Campino, Susana; Kerasidou, Angeliki; Cornelius, Victoria J; Hart, Lee; Shah, Shivang S; Band, Gavin; Spencer, Chris Ca; Agbenyega, Tsiri; Achidi, Eric; Doumbo, Ogobara K; Farrar, Jeremy; Marsh, Kevin; Taylor, Terrie; Kwiatkowski, Dominic P

2017-01-09

Glucose-6-phosphate dehydrogenase (G6PD) deficiency is believed to confer protection against Plasmodium falciparum malaria, but the precise nature of the protective effecthas proved difficult to define as G6PD deficiency has multiple allelic variants with different effects in males and females, and it has heterogeneous effects on the clinical outcome of P. falciparum infection. Here we report an analysis of multiple allelic forms of G6PD deficiency in a large multi-centre case-control study of severe malaria, using the WHO classification of G6PD mutations to estimate each individual's level of enzyme activity from their genotype. Aggregated across all genotypes, we find that increasing levels of G6PD deficiency are associated with decreasing risk of cerebral malaria, but with increased risk of severe malarial anaemia. Models of balancing selection based on these findings indicate that an evolutionary trade-off between different clinical outcomes of P. falciparum infection could have been a major cause of the high levels of G6PD polymorphism seen in human populations.

Leptin Receptor Gene Variant rs11804091 Is Associated with BMI and Insulin Resistance in Spanish Female Obese Children: A Case-Control Study

PubMed Central

Rupérez, Azahara I.; Gil-Campos, Mercedes; Leis, Rosaura; Cañete, Ramón; Tojo, Rafael

2017-01-01

Leptin is an endocrine hormone that has a critical role in body weight homoeostasis and mediates its effects via the leptin receptor (LEPR). Common polymorphisms in the genes coding leptin receptors have been associated with metabolic abnormalities. We assessed the association of 28 LEPR polymorphisms with body mass index (BMI) and their relationship with obesity-related phenotypes, inflammation and cardiovascular disease risk biomarkers. A multicentre case-control study was conducted in 522 children (286 with obesity and 236 with normal-BMI). All anthropometric, metabolic factors and biomarkers were higher in children with obesity except apolipoprotein (Apo)-AI, cholesterol, high-density lipoprotein cholesterol (HDL-c), and adiponectin, which were lower in the obesity group; and glucose, low-density lipoprotein cholesterol (LDL-c), and matrix metalloproteinase-9 that did not differ between groups. We identified the associations between rs11208659, rs11804091, rs10157275, rs9436303 and rs1627238, and BMI in the whole population, as well as the association of rs11804091, rs10157275, and rs1327118 with BMI in the female group, although only the rs11804091 remained associated after Bonferroni correction (p = 0.038). This single nucleotide polymorphisms (SNP) was also associated with insulin (p = 0.004), homeostasis model assessment for insulin resistance (HOMA-IR) (p = 0.006), quantitative insulin sensitivity check index (QUICKI) (p = 0.005) and adiponectin (p = 0.046) after adjusting for age, Tanner stage and BMI. Our results show a sex-specific association between the rs11804091 and obesity suggesting an influence of this SNP on insulin resistance. PMID:28771179

[Cognitive impairment in earthquake brain injury treated with comprehensive program of acupuncture and rehabilitation: a randomized controlled trial].

PubMed

Zhou, Jian-Wei; Zhang, An-Ren; Qiu, Ling; Huang, Shu; Wang, Wen-Chun; Hu, Yong-He; Zhang, Zhao; Xie, Hui-Jun; Zhao, Jing-Jing; Zhai, Jia-Li; Jiang, Yue; Tian, Tian; Liu, Di; Zheng, Xu; Wang, Min

2014-02-01

To explore the comprehensive program of integrated Chinese and western medicine in the treatment of cognitive impairment in earthquake brain injury. The multi-central randomized controlled trial was adopted. The qualified subjects were randomized into an acupuncture + rehabilitation group (38 cases) and a rehabilitation group (35 cases). In the acupuncture + rehabilitation group, acupuncture, hyperbaric oxygen (HBO) and cognitive rehabilitation training were combined as the comprehensive program of integrated Chinese and western medicine in the treatment. In the rehabilitation group, HBO and cognitive rehabilitation training were adopted. The efficacy and safety were assessed. (1) After treatment of 2 months, the intelligent state, cognitive function and activity of daily life of patients were improved in the both groups (all P < 0.01). (2) After treatment of 2 months, the score of MMSE and the score of activity of daily life were (24.11 +/- 4.08) and (75.45 +/- 13.95) in the acupuncture + rehabilitation group, which were more significant as compared with (17.05 +/- 43.84), (66.06 +/- 12.75) in the rehabilitation group, respectively (both P < 0.01). In 6-month follow-up visit after treatment, the cognitive function and activity of daily life were improved continuously in the acupuncture + rehabilitation group, which was more significant as compared with the rehabilitation group (P < 0.01, P < 0.05). The integrated Chinese and western medicine of acupuncture, HBO and cognitive rehabilitation training is safe and effective in the treatment of cognitive impairment in earthquake brain injury. The therapeutic effect is more advantageous as compared with the simple rehabilitation program of western medicine.

2015/16 seasonal vaccine effectiveness against hospitalisation with influenza A(H1N1)pdm09 and B among elderly people in Europe: results from the I-MOVE+ project

PubMed Central

Rondy, Marc; Larrauri, Amparo; Casado, Itziar; Alfonsi, Valeria; Pitigoi, Daniela; Launay, Odile; Syrjänen, Ritva K; Gefenaite, Giedre; Machado, Ausenda; Vučina, Vesna Višekruna; Horváth, Judith Krisztina; Paradowska-Stankiewicz, Iwona; Marbus, Sierk D; Gherasim, Alin; Díaz-González, Jorge Alberto; Rizzo, Caterina; Ivanciuc, Alina E; Galtier, Florence; Ikonen, Niina; Mickiene, Aukse; Gomez, Veronica; Kurečić Filipović, Sanja; Ferenczi, Annamária; Korcinska, Monika R; van Gageldonk-Lafeber, Rianne; Valenciano, Marta

2017-01-01

We conducted a multicentre test-negative case–control study in 27 hospitals of 11 European countries to measure 2015/16 influenza vaccine effectiveness (IVE) against hospitalised influenza A(H1N1)pdm09 and B among people aged ≥ 65 years. Patients swabbed within 7 days after onset of symptoms compatible with severe acute respiratory infection were included. Information on demographics, vaccination and underlying conditions was collected. Using logistic regression, we measured IVE adjusted for potential confounders. We included 355 influenza A(H1N1)pdm09 cases, 110 influenza B cases, and 1,274 controls. Adjusted IVE against influenza A(H1N1)pdm09 was 42% (95% confidence interval (CI): 22 to 57). It was 59% (95% CI: 23 to 78), 48% (95% CI: 5 to 71), 43% (95% CI: 8 to 65) and 39% (95% CI: 7 to 60) in patients with diabetes mellitus, cancer, lung and heart disease, respectively. Adjusted IVE against influenza B was 52% (95% CI: 24 to 70). It was 62% (95% CI: 5 to 85), 60% (95% CI: 18 to 80) and 36% (95% CI: -23 to 67) in patients with diabetes mellitus, lung and heart disease, respectively. 2015/16 IVE estimates against hospitalised influenza in elderly people was moderate against influenza A(H1N1)pdm09 and B, including among those with diabetes mellitus, cancer, lung or heart diseases. PMID:28797322

Longitudinal analysis of meta-analysis literatures in the database of ISI Web of Science.

PubMed

Zhu, Changtai; Jiang, Ting; Cao, Hao; Sun, Wenguang; Chen, Zhong; Liu, Jinming

2015-01-01

The meta-analysis is regarded as an important evidence for making scientific decision. The database of ISI Web of Science collected a great number of high quality literatures including meta-analysis literatures. However, it is significant to understand the general characteristics of meta-analysis literatures to outline the perspective of meta-analysis. In this present study, we summarized and clarified some features on these literatures in the database of ISI Web of Science. We retrieved the meta-analysis literatures in the database of ISI Web of Science including SCI-E, SSCI, A&HCI, CPCI-S, CPCI-SSH, CCR-E, and IC. The annual growth rate, literature category, language, funding, index citation, agencies and countries/territories of the meta-analysis literatures were analyzed, respectively. A total of 95,719 records, which account for 0.38% (99% CI: 0.38%-0.39%) of all literatures, were found in the database. From 1997 to 2012, the annual growth rate of meta-analysis literatures was 18.18%. The literatures involved in many categories, languages, fundings, citations, publication agencies, and countries/territories. Interestingly, the index citation frequencies of the meta-analysis were significantly higher than that of other type literatures such as multi-centre study, randomize controlled trial, cohort study, case control study, and cases report (P<0.0001). The increasing numbers, intensively global influence and high citations revealed that the meta-analysis has been becoming more and more prominent in recent years. In future, in order to promote the validity of meta-analysis, the CONSORT and PRISMA standard should be continuously popularized in the field of evidence-based medicine.

[Multicentre study of infection incidence in knee prosthesis].

PubMed

Jaén, F; Sanz-Gallardo, M I; Arrazola, M P; García de Codes, A; de Juanes, A; Resines, C

2012-01-01

To determine the incidence of surgical site infection in knee prosthesis surgical procedure for a follow-up period of one year in twelve hospitals in Madrid region. A prospective study was carried out from January to December 2009 using a national surveillance system called Indicadores Clínicos de Mejora Continua de Calidad. Primary and revision knee joint replacements in patients operated on in the previous year were included. Criteria used to define surgical site infection and patient risk index categories were those established by the Centers for Disease Control and Prevention and National Nosocomial Infections Surveillance. The incidence rates were worked out crude and adjusted by hazard ratio. 2,088 knee prosthesis procedures were analyzed. The overall incidence of surgical site infection was 2.1%. Sixty-five percent of the infections were organ/space. Sixty percent of the infections were identified in the early postoperative period. Of all surgical site infections, 41.9% were microbiologically confirmed. Antibiotic prophylaxis was implemented correctly in 63.3% of the cases. The most important cause of inappropriate prophylaxis was an unsuitable duration in 85.7% of the cases. The presurgical preparation was carried out correctly in 50.3% of surgical operations. The incidence of knee arthroplasty infection was twice as high as in the National Healthcare Safety Network and similar to national rates. In this study, the incidence of infection was within the range of infection rates in other published European studies. Surveillance and control strategies of health care for associated infections allow us to assess trends and the impact of preventive measures. Copyright © 2011 SECOT. Published by Elsevier Espana. All rights reserved.

Comparison between point-of-care dermatophyte test medium and mycology laboratory culture for diagnosis of dermatophytosis in dogs and cats.

PubMed

Kaufmann, Ronnie; Blum, Shlomo E; Elad, Daniel; Zur, Gila

2016-08-01

Point-of-care Dermatophyte Test Medium (PoC-DTM) is a diagnostic procedure to rule in/rule out dermatophytosis in veterinary clinics. To evaluate the performance of PoC-DTM in the clinic compared to DTM plate culture in a mycology laboratory and to compare results obtained by general practitioners and referral clinicians. Hair samples were collected from 47 cats and 54 dogs with suspected dermatophytosis and from nine healthy controls (seven cats and two dogs). This was a multicentre blinded study. In one group (65 suspected cases, 9 healthy controls), PoC-DTM results were evaluated by clinicians in a referral clinic (SP group) who examined the colony morphology macroscopically and microscopically. In the other group (36 suspected cases) PoC-DTM results were evaluated by clinicians from general practice for colour change only, with no macroscopic or microscopic examination (GP group). All hair samples were also cultured on DTM plates in a mycology laboratory. Laboratory culture was considered the gold standard for comparison. Agreements between tests were 97% (two false positive; κ = 0.839) and 80.6% (five false positives and two false negatives; κ = 0.466) in the SP and GP groups, respectively. This difference between groups was significant (P = 0.024). When applying macroscopic and microscopic evaluation of the colony, PoC-DTM is accurate for diagnosing dermatophytes with only a 3% chance of error. However, when macroscopic and microscopic examination is not included there is significant (19.4%) chance for an incorrect diagnosis. © 2016 ESVD and ACVD.

Sources of Pre-Analytical Variations in Yield of DNA Extracted from Blood Samples: Analysis of 50,000 DNA Samples in EPIC

PubMed Central

Caboux, Elodie; Lallemand, Christophe; Ferro, Gilles; Hémon, Bertrand; Mendy, Maimuna; Biessy, Carine; Sims, Matt; Wareham, Nick; Britten, Abigail; Boland, Anne; Hutchinson, Amy; Siddiq, Afshan; Vineis, Paolo; Riboli, Elio; Romieu, Isabelle; Rinaldi, Sabina; Gunter, Marc J.; Peeters, Petra H. M.; van der Schouw, Yvonne T.; Travis, Ruth; Bueno-de-Mesquita, H. Bas; Canzian, Federico; Sánchez, Maria-José; Skeie, Guri; Olsen, Karina Standahl; Lund, Eiliv; Bilbao, Roberto; Sala, Núria; Barricarte, Aurelio; Palli, Domenico; Navarro, Carmen; Panico, Salvatore; Redondo, Maria Luisa; Polidoro, Silvia; Dossus, Laure; Boutron-Ruault, Marie Christine; Clavel-Chapelon, Françoise; Trichopoulou, Antonia; Trichopoulos, Dimitrios; Lagiou, Pagona; Boeing, Heiner; Fisher, Eva; Tumino, Rosario; Agnoli, Claudia; Hainaut, Pierre

2012-01-01

The European Prospective Investigation into Cancer and nutrition (EPIC) is a long-term, multi-centric prospective study in Europe investigating the relationships between cancer and nutrition. This study has served as a basis for a number of Genome-Wide Association Studies (GWAS) and other types of genetic analyses. Over a period of 5 years, 52,256 EPIC DNA samples have been extracted using an automated DNA extraction platform. Here we have evaluated the pre-analytical factors affecting DNA yield, including anthropometric, epidemiological and technical factors such as center of subject recruitment, age, gender, body-mass index, disease case or control status, tobacco consumption, number of aliquots of buffy coat used for DNA extraction, extraction machine or procedure, DNA quantification method, degree of haemolysis and variations in the timing of sample processing. We show that the largest significant variations in DNA yield were observed with degree of haemolysis and with center of subject recruitment. Age, gender, body-mass index, cancer case or control status and tobacco consumption also significantly impacted DNA yield. Feedback from laboratories which have analyzed DNA with different SNP genotyping technologies demonstrate that the vast majority of samples (approximately 88%) performed adequately in different types of assays. To our knowledge this study is the largest to date to evaluate the sources of pre-analytical variations in DNA extracted from peripheral leucocytes. The results provide a strong evidence-based rationale for standardized recommendations on blood collection and processing protocols for large-scale genetic studies. PMID:22808065

[Management of the Legionella-link risk in a multicentre area's hospital: lessons learned of a six-year experience].

PubMed

Lecointe, D; Fagundez, E; Pierron, P; Musset, J-P; Brissé, P; Vollereau, D; Breton, D; Théodora, C; Beauvais, R; Malbrunot, C; Crine, L; Fèvre, C

2010-04-01

To reduce the Legionella-linked risk in the several sites of Sud-Francilien Hospital, following a hospital-acquired legionellosis case, a multidisciplinary working group performed an action plan monitored through Legionella pneumophila counts in hot water supply. From 2003 to the first half year 2009, positive points for Legionella pneumophila in the main sites of the hospital decreased from 85.71 to 28.00%, representing a significant reduction of 67.33%. Similar results were observed for three of the four establishments, whereas the last did not describe a pronounced reduction of Legionella pneumophila counts and showed constantly serogroup 1 strains. During this period, investigations of additional cases of legionellosis demonstrated a nosocomial transmission in one case in this last site. Multidisciplinary mobilization in management of Legionella-linked risk contributed to these results. Copyright 2009 Elsevier Masson SAS. All rights reserved.

Solitary Rectal Ulcer Syndrome: A Paediatric Case Report

PubMed Central

Abreu, Marlene; Azevedo Alves, Raquel; Pinto, João; Campos, Miguel; Aroso, Sofia

2017-01-01

Introduction Solitary rectal ulcer syndrome (SRUS) is an uncommon benign rectal disease. Mostly young adults are affected, and it is rare in paediatric populations. Clinical Case We present a 12-year-old girl with a 6-month history of tenesmus, frequent defaecation, and bloody stools with mucus. There was no previous history of constipation or other symptoms. At the first visit, physical examination and routine laboratory test results were normal. A stool examination for bacteria and parasites was negative. Colonoscopy revealed a single ulcer in the distal rectum 6 cm from the anal margin. SRUS was confirmed by biopsy. Despite conservative measures, the symptoms persisted. A defaecation proctography showed a small rectocele with no rectal mucosal prolapse. Because of its proximity to the anal sphincter, no surgical intervention was performed. Conclusion The present case illustrates how difficult the management of SRUS is. Multicentre studies are needed to establish treatment protocols for children. PMID:28848799

Inflammatory potential of diet and risk of laryngeal cancer in a case-control study from Italy.

PubMed

Shivappa, Nitin; Hébert, James R; Rosato, Valentina; Serraino, Diego; La Vecchia, Carlo

2016-08-01

Besides tobacco and alcohol, diet and inflammation have been suggested to be important risk factors for laryngeal cancer. In this study, we examined the role of diet-associated inflammation, as estimated by dietary inflammatory index (DII) scores, in laryngeal cancer in a multicentre case-control study conducted between 1992 and 2000 in Italy. This study included 460 cases with incident, histologically confirmed laryngeal cancer, and 1,088 controls hospitalized for acute non-neoplastic diseases unrelated to tobacco and alcohol consumption. DII scores were computed from a reproducible and valid 78-item food-frequency questionnaire. Logistic regression models controlling for age, sex, study center, education, body mass index, tobacco smoking, alcohol drinking, and non-alcohol energy intake were used to estimate odds ratios (ORs) and the corresponding 95 % confidence intervals (CIs). Subjects with higher DII scores (i.e., with a more pro-inflammatory diet) had a higher risk of laryngeal cancer. The OR was 3.30 (95 % CI 2.06, 5.28; p for trend <0.0001) for the highest versus the lowest DII quartile. When DII was considered as a continuous variable, the OR was 1.27 (95 % CI 1.15, 1.40) for a one-unit (9 % of the DII range) increase. Stratified analyses produced slightly stronger associations between DII and laryngeal cancer risk among Subjects <60 years old (ORquartile4vs1 = 4.68), overweight subjects (ORQuartile4vs1 = 3.62), and among those with higher education (ORQuartile4vs1 = 3.92). We also observed a strong combined effect of higher DII and tobacco smoking or alcohol consumption on risk of laryngeal cancer. Compared with non-smokers having low DII scores, the OR was 6.64 for smokers with high DII scores. Likewise, compared with non/moderate drinkers with low DII, the OR was 5.82 for heavy drinkers with high DII. These results indicate that a pro-inflammatory diet is associated with increased risk of laryngeal cancer.

Epidemiological multicentre study on the education provided to patients with type 2 diabetes mellitus in the Spanish Health Care System. The Forma2 study.

PubMed

García-Donaire, J A; Franch-Nadal, J; Rodríguez-Fortúnez, P; Labrador-Barba, E; Orera-Peña, M L; Rodríguez de Miguel, M

The purpose of the present study was to characterize the education that patients with type 2 diabetes mellitus receive, and to identify differences as regards the presence of insulin therapy or not. This crossover, multicentre and descriptive study involved 1066 Spanish physicians who completed a questionnaire on Internet. The physicians that responded had a mean of 26.0 years of experience in healthcare, and mainly worked in a walk-in clinic in an urban area. Physicians rated the level of patient knowledge about their disease on a 5.0 point-scale. Fifty percent of them indicated that they spent between 15 and 30min in educating patients at the time of diagnosis. Previous control with HbA1c>9%, presence of microvascular complications, and a low socio-cultural level, were factors associated with spending more time in education. This is the first study designed to evaluate the education provided to patients with type 2 diabetes mellitus from Spain. The time spent and the individualization of the education are important factors associated with better long-term control of the disease, and thus with the effectiveness of the clinical management. Copyright © 2017 Sociedad Española de Médicos de Atención Primaria (SEMERGEN). Publicado por Elsevier España, S.L.U. All rights reserved.

Psychological and psychosocial functioning of children with burn scarring using cosmetic camouflage: a multi-centre prospective randomised controlled trial.

PubMed

Maskell, Jessica; Newcombe, Peter; Martin, Graham; Kimble, Roy

2014-02-01

Burns leave patients with long-term physical scarring. Children with scarring are required to face challenges of reintegration into their community, including acceptance of an altered appearance and acceptance by others. This can be difficult given society's preoccupation with physical appearance. Limited research exists investigating validity of cosmetic camouflage as a psychosocial intervention for children with scarring. This study investigated whether using cosmetic camouflage (Microskin™) had a positive impact on health-related quality of life, self-concept and psychopathology for children and adolescents (8-17 years) with burn scarring. A prospective multi-centre randomised controlled trial was conducted across Australian and New Zealand paediatric hospitals. 63 participants (49 females, mean age 12.7 ± 2.1 years) were enrolled. Data points were baseline (Time 1) and at 8 weeks (Time 2) using reliable and valid psychometric measures. Findings indicate there were significant improvements in socialisation, school and appearance scales on the Paediatric Quality of Life Inventory and psychopathology scores particularly peer problems decreased. However self-concept remained stable from baseline throughout intervention use. Cosmetic camouflage appears to have a positive impact on quality of life particularly socialisation. Cosmetic camouflage is a valid tool to assist children with scarring to actively participate socially within their communities. Copyright © 2013 Elsevier Ltd and ISBI. All rights reserved.

The Plasma-Lyte 148 v Saline (PLUS) study protocol: a multicentre, randomised controlled trial of the effect of intensive care fluid therapy on mortality.

PubMed

Hammond, Naomi E; Bellomo, Rinaldo; Gallagher, Martin; Gattas, David; Glass, Parisa; Mackle, Diane; Micallef, Sharon; Myburgh, John; Saxena, Manoj; Taylor, Colman; Young, Paul; Finfer, Simon

2017-09-01

0.9% sodium chloride (saline) is the most commonly administered resuscitation fluid on a global basis but emerging evidence suggests that its high chloride content may have important adverse effects. To describe the study protocol for the Plasma- Lyte 148 v Saline study, which will test the hypothesis that in critically ill adult patients the use of Plasma-Lyte 148 (a buffered crystalloid solution) for fluid therapy results in different 90-day all-cause mortality when compared with saline. We will conduct this multicentre, blinded, randomised controlled trial in approximately 50 intensive care units in Australia and New Zealand. We will randomly assign 8800 patients to either Plasma-Lyte 148 or saline for all resuscitation fluid, maintenance fluid and compatible drug dilution therapy while in the ICU for up to 90 days after randomisation. The primary outcome is 90-day all-cause mortality; secondary outcomes include mean and peak creatinine concentration, incidence of renal replacement therapy, incidence and duration of vasoactive drug treatment, duration of mechanical ventilation, ICU and hospital length of stay, and quality of life and health services use at 6 months. The PLUS study will provide high-quality data on the comparative safety and efficacy of Plasma-Lyte 148 compared with saline for resuscitation and compatible crystalloid fluid therapy in critically ill adult patients.

Effect of family nursing therapeutic conversations on health-related quality of life, self-care and depression among outpatients with heart failure: A randomized multi-centre trial.

PubMed

Østergaard, Birte; Mahrer-Imhof, Romy; Wagner, Lis; Barington, Torben; Videbæk, Lars; Lauridsen, Jørgen

2018-03-07

To evaluate the short-term (3 months) effects of family nursing therapeutic conversations (FNTC) on health-related quality of life, self-care and depression in outpatients with Heart failure (HF). A randomised multi-centre trial was conducted in three Danish HF clinics. The control group (n = 167) received usual care, and the intervention group (n = 180) received FNTCs as supplement to usual care. Primary outcome was clinically significant changes (6 points) in Kansas City Cardiomyopathy Questionnaire (KCCQ) summary score between groups. Secondary outcomes were changes in self-care behaviour and depression scores. Data were assessed before first consultation and repeated after three months. No statistically significant difference was found in the change of KCCQ, self-care and depression scores between the groups. KCCQ scores of patients in the FNTC group changed clinically significant in seven domains, compared to one domain in the control group, with the highest improvement in self-efficacy, social limitation and symptom burden. FNTC was not superior to standard care of patients with HF regarding health-related quality of life, self-care and depression. Addressing the impact of the disease on the family, might improve self-efficacy, social limitation and symptom burden in patients with heart failure. Copyright © 2018 Elsevier B.V. All rights reserved.

Live birth after artificial oocyte activation using a ready-to-use ionophore: a prospective multicentre study.

PubMed

Ebner, Thomas; Montag, Markus; Montag, M; Van der Ven, K; Van der Ven, H; Ebner, T; Shebl, O; Oppelt, P; Hirchenhain, J; Krüssel, J; Maxrath, B; Gnoth, C; Friol, K; Tigges, J; Wünsch, E; Luckhaus, J; Beerkotte, A; Weiss, D; Grunwald, K; Struller, D; Etien, C

2015-04-01

Artificial oocyte activation has been proposed as a suitable means to overcome the problem of failed or impaired fertilization after intracytoplasmic sperm injection (ICSI). In a multicentre setting artificial oocyte activation was applied to 101 patients who were diagnosed with fertilization abnormalities (e.g. less than 50% fertilized oocytes) in a previous conventional ICSI cycle. Female gametes were activated for 15 min immediately after ICSI using a ready-to-use Ca(2+)-ionophore solution (A23187). Fertilization, pregnancy and live birth rates were compared with the preceding cycle without activation. The fertilization rate of 48% in the study cycles was significantly higher compared with the 25% in the control cycles (P < 0.001). Further splitting of the historical control group into failed (0%), low (1-30%) and moderate fertilization rate (31-50%) showed that all groups significantly benefitted (P < 0.001) in the ionophore cycle. Fewer patients had their embryo transfer cancelled compared with their previous treatments (1/101 versus 15/101). In total, 99% of the patients had an improved outcome with A23187 application resulting in a 28% live birth rate (35 babies). These data suggest that artificial oocyte activation using a ready-to-use compound is an efficient method. Copyright © 2014 Reproductive Healthcare Ltd. Published by Elsevier Ltd. All rights reserved.

A randomised, double blind, multicentre trial of octreotide in moderate to severe acute pancreatitis

PubMed Central

Uhl, W; Buchler, M; Malfertheiner, P; Beger, H; Adler, G; Gaus, W; the, G

1999-01-01

BACKGROUND—The pharmacological inhibition of exocrine pancreatic secretion with the somatostatin analogue octreotide has been advocated as a specific treatment of acute pancreatitis.
AIM—To investigate the efficacy of octreotide in acute pancreatitis in a randomised, placebo controlled trial.
METHODS—302 patients from 32 hospitals, fulfilling the criteria for moderate to severe acute pancreatitis within 96 hours of the onset of symptoms, were randomly assigned to one of three treatment groups: group P (n=103) received placebo, while groups O1 (n=98) and O2 (n=101) received 100 and 200 µg of octreotide, respectively, by subcutaneous injection three times daily for seven days. The primary outcome variable was a score composed of mortality and 15 typical complications of acute pancreatitis.
RESULTS—The three groups were well matched with respect to pretreatment characteristics. An intent to treat analysis of all 302 patients revealed no significant differences among treatment groups with respect to mortality (P: 16%; O1: 15%; O2: 12%), the rate of newly developed complications, the duration of pain, surgical interventions, or the length of the hospital stay. A valid for efficacy analysis (251 patients) also revealed no significant differences.
CONCLUSIONS—This trial shows no benefit of octreotide in the treatment of acute pancreatitis.


Keywords: acute pancreatitis; somatostatin; octreotide; randomised controlled multicentre trial PMID:10369711

Study design and rationale for Optimal aNtiplatelet pharmacotherapy guided by bedSIDE genetic or functional TESTing in elective percutaneous coronary intervention patients (ONSIDE TEST): a prospective, open-label, randomised parallel-group multicentre trial (NCT01930773).

PubMed

Kołtowski, Łukasz; Aradi, Daniel; Huczek, Zenon; Tomaniak, Mariusz; Sibbing, Dirk; Filipiak, Krzysztof J; Kochman, Janusz; Balsam, Paweł; Opolski, Grzegorz

2016-01-01

High platelet reactivity (HPR) and presence of CYP2C19 loss-of-function alleles are associated with higher risk for periprocedural myocardial infarction in clopidogrel-treated patients undergoing percutaneous coronary intervention (PCI). It is unknown whether personalised treatment based on platelet function testing or genotyping can prevent such complications. The ONSIDE-TEST is a multicentre, prospective, open-label, randomised controlled clinical trial aiming to assess if optimisation of antiplatelet therapy based on either phenotyping or genotyping is superior to conventional care. Patients will be randomised into phenotyping, genotyping, or control arms. In the phenotyping group, patients will be tested with the VerifyNow P2Y12 assay before PCI, and patients with a platelet reactivity unit greater than 208 will be switched over to prasugrel, while others will continue on clopidogrel therapy. In the genotyping group, carriers of the *2 loss-of-function allele will receive prasugrel for PCI, while wild-type subjects will be treated with clopidogrel. Patients in the control arm will be treated with standard-dose clopidogrel. The primary endpoint of the study is the prevalence of periprocedural myocardial injury within 24 h after PCI in the controls as compared to the phenotyping and genotyping group. Secondary endpoints include cardiac death, myocardial infarction, definite or probable stent thrombosis, or urgent repeat revascularisation within 30 days of PCI. Primary safety outcome is Bleeding Academic Research Consortium (BARC) type 3 and 5 bleeding during 30 days of PCI. The ONSIDE TEST trial is expected to verify the clinical utility of an individualised antiplatelet strategy in preventing periprocedural myocardial injury by either phenotyping or genotyping. ClinicalTrials.gov: NCT01930773.

The Prevalence and Characteristics of Primary Headache and Dream-Enacting Behaviour in Japanese Patients with Narcolepsy or Idiopathic Hypersomnia: A Multi-Centre Cross-Sectional Study.

PubMed

Suzuki, Keisuke; Miyamoto, Masayuki; Miyamoto, Tomoyuki; Inoue, Yuichi; Matsui, Kentaro; Nishida, Shingo; Hayashida, Kenichi; Usui, Akira; Ueki, Yoichiro; Nakamura, Masaki; Murata, Momoyo; Numao, Ayaka; Watanabe, Yuji; Suzuki, Shiho; Hirata, Koichi

2015-01-01

Because the prevalence and characteristics of primary headache have yet to be thoroughly studied in patients with hypersomnia disorders, including narcolepsy and idiopathic hypersomnia, we examined these parameters in the Japanese population. In a multicentre cross-sectional survey, among 576 consecutive outpatients with sleep disorders, 68 narcolepsy patients and 35 idiopathic hypersomnia patients were included. Additionally, 61 healthy control subjects participated. Semi-structured headache questionnaires were administered to all participants. The patients with narcolepsy (52.9%) and idiopathic hypersomnia (77.1%) more frequently experienced headache than the healthy controls (24.6%; p<0.0001). The prevalence rates were 23.5%, 41.2% and 4.9% for migraine (p<0.0001) and 16.2%, 23.5% and 14.8% (p = 0.58) for tension-type headache among the narcolepsy patients, the idiopathic hypersomnia patients and the control subjects, respectively. Those who experienced migraine more frequently experienced excessive daytime sleepiness, defined as an Epworth Sleepiness Scale score of ≥10, than those who did not experience headache among the patients with narcolepsy (93.8% vs. 65.6%, p = 0.040) and idiopathic hypersomnia (86.7% vs. 37.5%, p = 0.026). Dream-enacting behaviour (DEB), as evaluated by the rapid eye movement sleep disorders questionnaire, was more frequently observed in the narcolepsy patients than in the idiopathic hypersomnia patients and the control subjects. An increased DEB frequency was observed in the narcolepsy patients with migraines compared to those without headache. Migraines were frequently observed in patients with narcolepsy and idiopathic hypersomnia. DEB is a characteristic of narcolepsy patients. Further studies are required to assess the factors that contribute to migraines in narcolepsy and idiopathic hypersomnia patients.

The Prevalence and Characteristics of Primary Headache and Dream-Enacting Behaviour in Japanese Patients with Narcolepsy or Idiopathic Hypersomnia: A Multi-Centre Cross-Sectional Study

PubMed Central

Suzuki, Keisuke; Miyamoto, Masayuki; Miyamoto, Tomoyuki; Inoue, Yuichi; Matsui, Kentaro; Nishida, Shingo; Hayashida, Kenichi; Usui, Akira; Ueki, Yoichiro; Nakamura, Masaki; Murata, Momoyo; Numao, Ayaka; Watanabe, Yuji; Suzuki, Shiho; Hirata, Koichi

2015-01-01

Background Because the prevalence and characteristics of primary headache have yet to be thoroughly studied in patients with hypersomnia disorders, including narcolepsy and idiopathic hypersomnia, we examined these parameters in the Japanese population. Methods In a multicentre cross-sectional survey, among 576 consecutive outpatients with sleep disorders, 68 narcolepsy patients and 35 idiopathic hypersomnia patients were included. Additionally, 61 healthy control subjects participated. Semi-structured headache questionnaires were administered to all participants. Results The patients with narcolepsy (52.9%) and idiopathic hypersomnia (77.1%) more frequently experienced headache than the healthy controls (24.6%; p<0.0001). The prevalence rates were 23.5%, 41.2% and 4.9% for migraine (p<0.0001) and 16.2%, 23.5% and 14.8% (p = 0.58) for tension-type headache among the narcolepsy patients, the idiopathic hypersomnia patients and the control subjects, respectively. Those who experienced migraine more frequently experienced excessive daytime sleepiness, defined as an Epworth Sleepiness Scale score of ≥10, than those who did not experience headache among the patients with narcolepsy (93.8% vs. 65.6%, p = 0.040) and idiopathic hypersomnia (86.7% vs. 37.5%, p = 0.026). Dream-enacting behaviour (DEB), as evaluated by the rapid eye movement sleep disorders questionnaire, was more frequently observed in the narcolepsy patients than in the idiopathic hypersomnia patients and the control subjects. An increased DEB frequency was observed in the narcolepsy patients with migraines compared to those without headache. Conclusions Migraines were frequently observed in patients with narcolepsy and idiopathic hypersomnia. DEB is a characteristic of narcolepsy patients. Further studies are required to assess the factors that contribute to migraines in narcolepsy and idiopathic hypersomnia patients. PMID:26418536

[Introduction of capillary glycosylated haemoglobin determination in a Primary Care Health Area: Multicentre study of the evolution of patients with type 2 diabetes mellitus].

PubMed

Núñez-Sánchez, M Á; Cervantes-Cuesta, M Á; Brocal-Ibañez, P; Salmeron-Arjona, E; León-Martínez, L P; Cerezo-Sanmartin, M

The aim of this study was to evaluate the efficiency of a joint intervention that included educational components, self-assessment, and information to optimise diabetes control through the introduction of instant capillary glycosylated haemoglobin (HbA1c) determination in Primary Care. A multicentre prospective descriptive study was carried out over 3years in 10Primary Care Centres of the Area VII Murcia East. At the end of the study there were 804 patients with type 2 diabetes (DM2). Patients were divided into 4 groups based on initial values of HbA1c, and if changes in their treatment were needed. HbA1c, body mass index, and blood pressure were monitored. A financial assessment was also performed on the impact of the implementation of a protocol to measure instant capillary RESULTS: A significant reduction was observed in HbA1c values. The initial HbA1c mean value was 7.4±1.4%, which decreased to a final value of 6.9±1.0% (P<.001). At the end of the study, 71.4% of patients included reached diabetic control objectives. In addition, the financial assessment demonstrated that the implementation of this diabetes control system led to a decrease of the 24.7% in spending on glucose strips after the first year of study in Area VII Murcia Health Service. The introduction of capillary HbA1c determination in Primary Care has demonstrated to improve diabetes control and the efficiency of the health personnel. Furthermore, a reduction in the health costs of patients with DM2 was also shown. Copyright © 2016 SECA. Publicado por Elsevier España, S.L.U. All rights reserved.

Design of a multicentre randomized controlled trial to assess the safety and efficacy of dose titration by specialized nurses in patients with heart failure. ETIFIC study protocol

PubMed Central

García‐Garrido, LLuisa; Nebot Margalef, Magdalena; Lekuona, Iñaki; Comin‐Colet, Josep; Manito, Nicolás; Roure, Julia; Ruiz Rodriguez, Pilar; Enjuanes, Cristina; Latorre, Pedro; Torcal Laguna, Jesús; García‐Gutiérrez, Susana

2017-01-01

Abstract Aims Heart failure (HF) is associated with many hospital admissions and relatively high mortality, rates decreasing with administration of beta‐blockers (BBs), angiotensin‐converting‐enzyme inhibitors, angiotensin II receptor blockers, and mineralocorticoid receptor antagonists. The effect is dose dependent, suboptimal doses being common in clinical practice. The 2012 European guidelines recommend close monitoring and dose titration by HF nurses. Our main aim is to compare BB doses achieved by patients after 4 months in intervention (HF nurse‐managed) and control (cardiologist‐managed) groups. Secondary aims include comparing doses of the other aforementioned drugs achieved after 4 months, adverse events, and outcomes at 6 months in the two groups. Methods We have designed a multicentre (20 hospitals) non‐inferiority randomized controlled trial, including patients with new‐onset HF, left ventricular ejection fraction ≤40%, and New York Heart Association class II–III, with no contraindications to BBs. We will also conduct qualitative analysis to explore potential barriers to and facilitators of dose titration by HF nurses. In the intervention group, HF nurses will implement titration as prescribed by cardiologists, following a protocol. In controls, cardiologists will both prescribe and titrate doses. The study variables are doses of each of the drugs after 4 months relative to the target dose (%), New York Heart Association class, left ventricular ejection fraction, N‐terminal pro B‐type natriuretic peptide levels, 6 min walk distance, comorbidities, renal function, readmissions, mortality, quality of life, and psychosocial characteristics. Conclusions The trial seeks to assess whether titration by HF nurses of drugs recommended in practice guidelines is safe and not inferior to direct management by cardiologists. The results could have an impact on clinical practice. PMID:29154427

Moxibustion for the treatment of pressure ulcers: study protocol for a pilot, multicentre, randomised controlled trial.

PubMed

Zhang, Qin-hong; Yue, Jin-huan; Li, Chao-ran; Sun, Zhong-ren

2014-12-30

Pressure ulcers are common in the elderly and immobile. Currently, there are few proven effective treatments for pressure ulcers. This trial aims to evaluate the feasibility, efficacy and safety of moxibustion for pressure ulcers. This is a multicentre, two-armed, parallel-design randomised controlled trial (RCT). 30 eligible patients with pressure ulcers will be randomised in a ratio of 1:1 to the treatment group and control group. The participants in the treatment group will undergo indirect moxibustion for 30 min before application of a dressing, one session daily, five sessions weekly for 4 weeks. The patients in the control group will only receive a dressing, applied in the same way as in the treatment group. Both groups will be followed up for 3 months. The primary outcome measures will be wound surface area (WSA) and proportion of ulcers healed within trial period (PUHTP). The secondary outcomes will be the Pressure Ulcer Scale for Healing (PUSH Tool), visual analogue scale (VAS) and adverse events. All outcomes will be evaluated at the beginning of the study, at the end of the second week, at 4 weeks after randomisation and at 1 and 3 months after treatment cessation. This trial has undergone ethical scrutiny and been approved by the ethics review boards of First Affiliated Hospital of Heilongjiang University of Chinese Medicine and Second Affiliated Hospital of Heilongjiang University of Chinese Medicine (Permission number: HZYEYLP2014). The results of this study will provide clinical evidence for the feasibility, efficacy and safety of moxibustion for pressure ulcers. ChiCTR-TRC-13003959. 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.

Knocked by the shuttlecock: twelve sight-threatening blunt-eye injuries in Australian badminton players.

PubMed

Jao, Kathy K; Atik, Alp; Jamieson, Michael P; Sheales, Mariana P; Lee, Matthew H; Porter, Ashley; Roufas, Athena; Goldberg, Ivan; Zamir, Ehud; White, Andrew; Skalicky, Simon E

2017-07-01

Non-penetrating ocular injuries from badminton shuttlecocks can result in severe damage and life-long complications. This case series highlights the morbidity of such injuries, particularly in regard to post-traumatic glaucoma. This is a retrospective case series of 12 patients with shuttlecock-related blunt eye injuries sustained during badminton play without eye protection. By approaching colleagues through conference presentations and networking, the authors have attempted to gather all known cases of shuttlecock ocular injury managed in tertiary ocular emergency departments or private ophthalmological clinics in Victoria and New South Wales, Australia in 2015. This is the first multicentre case series to describe badminton-related ocular injuries in Australia. Our case series demonstrates, in particular, long-term glaucoma-related morbidity for patients over a large age range (16 to 77 years), with one patient requiring ongoing management 26 years following their initial injury. The cases reported further add to the literature promoting awareness of badminton-related ocular injury. We encourage player education and advocacy on badminton-related eye injuries and appropriate use of eye protection to reduce associated morbidity. © 2016 Optometry Australia.

[Blood pressure control in a population of hypertensive diabetic patients treated in primary care: PRESCAP-Diabetes Study 2010].

PubMed

Barquilla García, A; Llisterri Caro, J L; Prieto Díaz, M A; Alonso Moreno, F J; García Matarín, L; Galgo Nafría, A; Mediavilla Bravo, J J

2015-01-01

To determine the level of blood pressure (BP) control in hypertensive diabetic patients treated in primary care and to determine the factors associated with poor control. A cross-sectional, multicentre study that enrolled hypertensive diabetics recruited by consecutive sampling by family doctors in Spain in June 2010. A mean BP of less than 140/90mmHg was considered as good control of arterial hypertension. The percentages of patients with<130/80mmHg PA, 140/80mmHg, and 140/85mmHg, respectively, were also determined. Sociodemographic, clinical, cardiovascular risk factors, and pharmacological treatments were recorded. A total of 3,993 patients were enrolled (50.1% female) with a mean age (standard deviation) of 68.2 (10.2) years, of whom 73.9% received combination therapy. The figures showed good control of both blood pressure values (<140/90mmHg) in 56.4% (95% CI: 54.3 to 58.4) of the cases, with 58.5% (95% CI: 57.0-60.0) only in systolic BP, and 84.6% (95% CI, 83.2 to 85.8) only in diastolic BP. The variables with strongest association with poor control were the presence of albuminuria, elevated total cholesterol, physical inactivity, and not taking the medication on the day of the interview. The PRESCAP-Diabetes 2010 study results indicate that 43.6% of diabetics with hypertension seen in primary care have a poorly controlled BP, in particular, systolic BP. Copyright © 2013 Sociedad Española de Médicos de Atención Primaria (SEMERGEN). Publicado por Elsevier España. All rights reserved.

Lymphatic and local spread of T1 and T2 pancreatic cancer. A study of autopsy material.

PubMed Central

Nagai, H; Kuroda, A; Morioka, Y

1986-01-01

Eight autopsy cases of pancreatic cancer (duct cell adenocarcinoma) with T1 and T2 primary tumors were studied histologically to examine the exact extent of lymphatic and local spread. Six of them had microscopic metastasis in grossly negative lymph nodes near the primary tumor. In addition, four of them had a few metastatic nodes in the para-aortic region. In cases with lymphatic metastases, the extent of cancer infiltration within lymphatic vessels, nerves, and/or connective tissues was almost the same as that of lymph node metastasis. Major vascular involvement was found in four cases. There was no case in which multicentricity or marked intraductal spread of cancer cells was observed in the pancreas. It has been suggested that most of T1 and T2 pancreatic cancers have a fairly widespread microscopic extension, although extremely small T1 cancers have a very limited extension. Images FIG. 2. FIGS. 4a-c. FIGS. 5a-c. PMID:3015059

Zika virus infection in 18 travellers returning from Surinam and the Dominican Republic, The Netherlands, November 2015-March 2016.

PubMed

Duijster, Janneke W; Goorhuis, Abraham; van Genderen, Perry J J; Visser, Leo G; Koopmans, Marion P; Reimerink, Johan H; Grobusch, Martin P; van der Eijk, Annemiek A; van den Kerkhof, Johannes H C T; Reusken, Chantal B; Hahné, Susan J M

2016-12-01

We report 18 cases of confirmed Zika virus (ZIKV) infection in travellers returning to the Netherlands from Surinam (South America, bordering northern Brazil) and the Dominican Republic. In a multi-centre study, we collected epidemiological, virological and clinical characteristics, as well as data on travel history, underlying illness and laboratory results of the 18 imported ZIKV infection cases using a standardised form. Most cases had a self-limiting course of disease, two patients developed complications, one had Guillain-Barré and another had severe thrombocytopenia. Four patients had underlying illness. One of the reported cases was pregnant. Three of 13 patients tested had a weak-positive result for dengue IgM. The majority of patients were born in Suriname and/or visiting friends and relatives (VFR). Providing pre-travel advice among travellers, especially VFR travellers, is needed to enhance the use of preventive measures against ZIKV infection. Further evidence on health risks associated with ZIKV infection is urgently needed.

Prevalence of β-thalassemia and other haemoglobinopathies in six cities in India: a multicentre study.

PubMed

Mohanty, D; Colah, R B; Gorakshakar, A C; Patel, R Z; Master, D C; Mahanta, J; Sharma, S K; Chaudhari, U; Ghosh, M; Das, S; Britt, R P; Singh, S; Ross, C; Jagannathan, L; Kaul, R; Shukla, D K; Muthuswamy, V

2013-01-01

The population of India is extremely diverse comprising of more than 3,000 ethnic groups who still follow endogamy. Haemoglobinopathies are the commonest hereditary disorders in India and pose a major health problem. The data on the prevalence of β-thalassemias and other haemoglobinopathies in different caste/ethnic groups of India is scarce. Therefore the present multicentre study was undertaken in six cities of six states of India (Maharashtra, Gujarat, West Bengal, Assam, Karnataka and Punjab) to determine the prevalence of haemoglobinopathies in different caste/ethnic groups using uniform methodology. Fifty-six thousand seven hundred eighty individuals (college students and pregnant women) from different caste/ethnic groups were screened. RBC indices were measured on an automated haematology counter while the percentage of HbA(2), HbF and other abnormal Hb variants were estimated by HPLC on the Variant Hemoglobin Testing System. The overall prevalence of β-thalassemia trait was 2.78 % and varied from 1.48 to 3.64 % in different states, while the prevalence of β-thalassemia trait in 59 ethnic groups varied from 0 to 9.3 %. HbE trait was mainly seen in Dibrugarh in Assam (23.9 %) and Kolkata in West Bengal (3.92 %). In six ethnic groups from Assam, the prevalence of HbE trait varied from 41.1 to 66.7 %. Few subjects with δβ-thalassemia, HPFH, HbS trait, HbD trait, HbE homozygous and HbE β-thalassemia as well as HbS homozygous and HbS-β-thalassemia (<1 %) were also identified. This is the first large multicentre study covering cities from different regions of the country for screening for β-thalassemia carriers and other haemoglobinopathies where uniform protocols and methodology was followed and quality control ensured by the co-ordinating centre. This study also shows that establishment of centres for screening for β-thalassemia and other haemoglobinopathies is possible in medical colleges. Creating awareness, screening and counselling can be done at these centres. This experience will help to formulate a national thalassemia control programme in India.

Feasibility randomised multicentre, double-blind, double-dummy controlled trial of anakinra, an interleukin-1 receptor antagonist versus intramuscular methylprednisolone for acute gout attacks in patients with chronic kidney disease (ASGARD): protocol study.

PubMed

Balasubramaniam, Gowrie; Parker, Trisha; Turner, David; Parker, Mike; Scales, Jonathan; Harnett, Patrick; Harrison, Michael; Ahmed, Khalid; Bhagat, Sweta; Marianayagam, Thiraupathy; Pitzalis, Costantino; Mallen, Christian; Roddy, Edward; Almond, Mike; Dasgupta, Bhaskar

2017-09-05

Acute gout occurs in people with chronic kidney disease, who are commonly older people with comorbidities such as hypertension, heart disease and diabetes. Potentially harmful treatments are administered to these vulnerable patients due to a lack of clear evidence. Newly available treatment that targets a key inflammatory pathway in acute gout attacks provides an opportunity to undertake the first-ever trial specifically looking treating people with kidney disease. This paper describes the protocol for a feasibility randomised controlled trial (RCT) comparing anakinra, a novel interleukin-1 antagonist versus steroids in people with chronic kidney disease (ASGARD). ASGARD is a two-parallel group double-blind, double-dummy multicentre RCT comparing anakinra 100 mg, an interleukin-1 antagonist, subcutaneous for 5 days against intramuscular methylprednisolone 120 mg. The primary objective is to assess the feasibility of the trial design and procedures for a definitive RCT. The specific aims are: (1) test recruitment and retention rates and willingness to be randomised; (2) test eligibility criteria; (3) collect and analyse outcome data to inform sample and power calculations for a trial of efficacy; (4) collect economic data to inform a future economic evaluation estimating costs of treatment and (5) assess capacity of the project to scale up to a national multicentre trial. We will also gather qualitative insights from participants. It aims to recruit 32 patients with a 1:1 randomisation. Information from this feasibility study will help design a definitive trial and provide general information in designing acute gout studies. The London-Central Ethics Committee approved the protocol. The results will be disseminated in peer-reviewed journals and at scientific conferences. EudraCT No. 2015-001787-19, NCT/Clinicalstrials.gov No. NCT02578394, pre-results, WHO Universal Trials Reference No. U1111-1175-1977. NIHR Grant PB-PG-0614-34090. © 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.

Financial considerations in the conduct of multi-centre randomised controlled trials: evidence from a qualitative study

PubMed Central

Snowdon, Claire; Elbourne, Diana R; Garcia, Jo; Campbell, Marion K; Entwistle, Vikki A; Francis, David; Grant, Adrian M; Knight, Rosemary C; McDonald, Alison M; Roberts, Ian

2006-01-01

Background Securing and managing finances for multicentre randomised controlled trials is a highly complex activity which is rarely considered in the research literature. This paper describes the process of financial negotiation and the impact of financial considerations in four UK multicentre trials. These trials had met, or were on schedule to meet, recruitment targets agreed with their public-sector funders. The trials were considered within a larger study examining factors which might be associated with trial recruitment (STEPS). Methods In-depth semi-structured telephone interviews were conducted in 2003–04 with 45 individuals with various responsibilities to one of the four trials. Interviewees were recruited through purposive and then snowball sampling. Interview transcripts were analysed with the assistance of the qualitative package Atlas-ti. Results The data suggest that the UK system of dividing funds into research, treatment and NHS support costs brought the trial teams into complicated negotiations with multiple funders. The divisions were somewhat malleable and the funding system was used differently in each trial. The fact that all funders had the potential to influence and shape the trials considered here was an important issue as the perspectives of applicants and funders could diverge. The extent and range of industry involvement in non-industry-led trials was striking. Three broad periods of financial work (foundation, maintenance, and resourcing completion) were identified. From development to completion of a trial, the trialists had to be resourceful and flexible, adapting to changing internal and external circumstances. In each period, trialists and collaborators could face changing costs and challenges. Each trial extended the recruitment period; three required funding extensions from MRC or HTA. Conclusion This study highlights complex financial aspects of planning and conducting trials, especially where multiple funders are involved. Recognition of the importance of financial stability and of the need for appropriate training in this area should be paralleled by further similar research with a broader range of trials, aimed at understanding and facilitating the conduct of clinical research. PMID:17184521

Effects of pimecrolimus cream 1% in the treatment of patients with atopic dermatitis who demonstrate a clinical insensitivity to topical corticosteroids: a randomized, multicentre vehicle-controlled trial.

PubMed

Leung, D Y M; Hanifin, J M; Pariser, D M; Barber, K A; Langley, R G; Schlievert, P M; Abrams, B; Hultsch, T

2009-08-01

Colonization with Staphylococcus aureus in atopic dermatitis (AD) is often associated with worsening of clinical symptoms. Staphylococcus aureus produces superantigens that contribute to cutaneous inflammation and corticosteroid (CS) resistance. To investigate the relationship between CS insensitivity, S. aureus colonization and superantigen production in AD, and to explore the efficacy of pimecrolimus cream in CS-insensitive AD. This was a randomized, double-blind, vehicle-controlled, multicentre, parallel-group study. Seventy-three patients with AD, aged 2-49 years, who had a documented clinical insensitivity to topical CS, were recruited. The primary efficacy parameters combined laboratory (including S. aureus colonization, superantigens) and clinical assessments [including Eczema Area and Severity Index (EASI), whole body Investigator's Global Assessment (IGA), pruritus assessment score, patient's assessment score of disease control]. An increase in S. aureus counts correlated with worsening of clinical score (week 6 vs. baseline) when assessed by IGA, pruritus severity and patient assessment. The presence of superantigens correlated with this worsening. During the 6-week double-blind phase, disease improvement in the pimecrolimus cream group was demonstrated by decreasing EASI scores compared with vehicle. Mean EASI scores for the head and neck showed greater improvement in the pimecrolimus cream group than in the vehicle group at all observed time points. In a cohort of patients with clinical insensitivity to CS there was a significant positive correlation between S. aureus and disease severity. Results suggest that for some of these patients, treatment with pimecrolimus cream 1% is useful, especially in the head/neck area.

Electroacupuncture for insomnia disorder: study protocol for a randomized controlled trial.

PubMed

Kim, Sung-Phil; Kim, Joo-Hee; Kim, Bo-Kyung; Kim, Hyeong-Jun; Jung, In Chul; Cho, Jung Hyo; Kim, Jung-Eun; Kim, Mi-Kyung; Kwon, O-Jin; Kim, Ae-Ran; Park, Hyo-Ju; Seo, Bok-Nam

2017-04-13

Insomnia is a common sleep disorder that affects many adults either transiently or chronically. The societal cost of insomnia is on the rise, while long-term use of current drug treatments can involve adverse effects. Recently, electroacupuncture (EA) has been used to treat various conditions including insomnia. The objective of this study is to provide scientific evidence for the effect and safety of using EA to treat insomnia. In this multicentre, assessor-blind, three-arm, parallel-design, randomised controlled trial, 150 participants will be assigned to the EA group, the sham EA (SEA) group, or the usual care group. The EA and SEA groups will receive the specific treatments 2-3 times a week for 4 weeks, for a total of 10 sessions, whereas the usual care group will not receive EA and will continue with usual care during the same time period. The primary outcome measure will be changes in the Insomnia Severity Index 5 weeks after randomisation. The secondary outcomes will include the Pittsburgh Sleep Quality Index, the Hospital Anxiety and Depression Scale, a sleep diary, the EuroQoL-5 dimension questionnaire, the levels of melatonin and cortisol, and the Patient Global Impression of Change. Safety will be assessed at each visit. The results of this multicentre randomised controlled trial will contribute to provide rigorous clinical evidence for the effects and safety of EA for insomnia disorder. Korean Clinical Trial Registry, CRIS, KCT0001685 . Registered on 2 November 2015 (retrospectively registered). Date of enrolment of the first participant to the trial 13 October 2015.

Feasibility and Preliminary Efficacy of Visual Cue Training to Improve Adaptability of Walking after Stroke: Multi-Centre, Single-Blind Randomised Control Pilot Trial.

PubMed

Hollands, Kristen L; Pelton, Trudy A; Wimperis, Andrew; Whitham, Diane; Tan, Wei; Jowett, Sue; Sackley, Catherine M; Wing, Alan M; Tyson, Sarah F; Mathias, Jonathan; Hensman, Marianne; van Vliet, Paulette M

2015-01-01

Given the importance of vision in the control of walking and evidence indicating varied practice of walking improves mobility outcomes, this study sought to examine the feasibility and preliminary efficacy of varied walking practice in response to visual cues, for the rehabilitation of walking following stroke. This 3 arm parallel, multi-centre, assessor blind, randomised control trial was conducted within outpatient neurorehabilitation services. Community dwelling stroke survivors with walking speed <0.8m/s, lower limb paresis and no severe visual impairments. Over-ground visual cue training (O-VCT), Treadmill based visual cue training (T-VCT), and Usual care (UC) delivered by physiotherapists twice weekly for 8 weeks. Participants were randomised using computer generated random permutated balanced blocks of randomly varying size. Recruitment, retention, adherence, adverse events and mobility and balance were measured before randomisation, post-intervention and at four weeks follow-up. Fifty-six participants participated (18 T-VCT, 19 O-VCT, 19 UC). Thirty-four completed treatment and follow-up assessments. Of the participants that completed, adherence was good with 16 treatments provided over (median of) 8.4, 7.5 and 9 weeks for T-VCT, O-VCT and UC respectively. No adverse events were reported. Post-treatment improvements in walking speed, symmetry, balance and functional mobility were seen in all treatment arms. Outpatient based treadmill and over-ground walking adaptability practice using visual cues are feasible and may improve mobility and balance. Future studies should continue a carefully phased approach using identified methods to improve retention. Clinicaltrials.gov NCT01600391.

Goal-oriented cognitive rehabilitation in early-stage dementia: study protocol for a multi-centre single-blind randomised controlled trial (GREAT)

PubMed Central

2013-01-01

Background Preliminary evidence suggests that goal-oriented cognitive rehabilitation (CR) may be a clinically effective intervention for people with early-stage Alzheimer’s disease, vascular or mixed dementia and their carers. This study aims to establish whether CR is a clinically effective and cost-effective intervention for people with early-stage dementia and their carers. Methods/design In this multi-centre, single-blind randomised controlled trial, 480 people with early-stage dementia, each with a carer, will be randomised to receive either treatment as usual or cognitive rehabilitation (10 therapy sessions over 3 months, followed by 4 maintenance sessions over 6 months). We will compare the effectiveness of cognitive rehabilitation with that of treatment as usual with regard to improving self-reported and carer-rated goal performance in areas identified as causing concern by people with early-stage dementia; improving quality of life, self-efficacy, mood and cognition of people with early-stage dementia; and reducing stress levels and ameliorating quality of life for carers of participants with early-stage dementia. The incremental cost-effectiveness of goal-oriented cognitive rehabilitation compared to treatment as usual will also be examined. Discussion If the study confirms the benefits and cost-effectiveness of cognitive rehabilitation, it will be important to examine how the goal-oriented cognitive rehabilitation approach can most effectively be integrated into routine health-care provision. Our aim is to provide training and develop materials to support the implementation of this approach following trial completion. Trial registration Current Controlled Trials ISRCTN21027481 PMID:23710796

Stapler versus scalpel resection followed by hand-sewn closure of the pancreatic remnant for distal pancreatectomy.

PubMed

Probst, Pascal; Hüttner, Felix J; Klaiber, Ulla; Knebel, Phillip; Ulrich, Alexis; Büchler, Markus W; Diener, Markus K

2015-11-06

Resections of the pancreatic body and tail reaching to the left of the superior mesenteric vein are defined as distal pancreatectomy. Most distal pancreatectomies are elective treatments for chronic pancreatitis, benign or malignant diseases, and they have high morbidity rates of up to 40%. Pancreatic fistula formation is the main source of postoperative morbidity, associated with numerous further complications. Researchers have proposed several surgical resection and closure techniques of the pancreatic remnant in an attempt to reduce these complications. The two most common techniques are scalpel resection followed by hand-sewn closure of the pancreatic remnant and stapler resection and closure. To compare the rates of pancreatic fistula in people undergoing distal pancreatectomy using scalpel resection followed by hand-sewn closure of the pancreatic remnant versus stapler resection and closure. We searched Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE, Biosis and Science Citation Index from database inception to October 2015. We included randomised controlled trials (RCTs) comparing stapler versus scalpel resection followed by hand-sewn closure of the pancreatic remnant for distal pancreatectomy (irrespective of language or publication status). Two authors independently assessed trials for inclusion and extracted the data. Taking into consideration the clinical heterogeneity between the trials (e.g. different endpoint definitions), we analysed data using a random-effects model with Review Manager (RevMan), calculating risk ratio (RR) or mean difference (MD) with 95% confidence intervals (CI). In two eligible trials, a total of 381 participants underwent distal pancreatic resection and were randomised to closure of the pancreatic remnant either with stapler (n = 191) or scalpel resection followed by hand-sewn closure (n = 190). One was a single centre pilot RCT and the other was a multicentre blinded RCT. The single centre pilot RCT evaluated 69 participants in five intervention arms (stapler, hand-sewn, fibrin glue, mesh and pancreaticojejunostomy), although we only assessed the stapler and hand-sewn closure groups (14 and 15 participants, respectively). The multicentre RCT had two interventional arms: stapler (n = 177) and hand-sewn closure (n = 175). The rate of postoperative pancreatic fistula was the main outcome, and it occurred in 79 of 190 participants in the hand-sewn group compared to 65 of 191 participants in the stapler group. Neither the individual trials nor the meta-analysis showed a significant difference between resection techniques (RR 0.90; 95% CI 0.55 to 1.45; P = 0.66). In the same way, postoperative mortality and operation time did not differ significantly. The single centre RCT had an unclear risk of bias in the randomisation, allocation and both blinding domains. However, the much larger multicentre RCT had a low risk of bias in all domains. Due to the small number of events and the wide confidence intervals that cannot exclude clinically important benefit or harm with stapler versus hand-sewn closure, there is a serious possibility of imprecision, making the overall quality of evidence moderate. The quality of evidence is moderate and mainly based on the high weight of the results of one multicentre RCT. Unfortunately, there are no other completed RCTs on this topic except for one relevant ongoing trial. Neither stapler nor scalpel resection followed by hand-sewn closure of the pancreatic remnant for distal pancreatectomy showed any benefit compared to the other method in terms of postoperative pancreatic fistula, overall postoperative mortality or operation time. Currently, the choice of closure is left up to the preference of the individual surgeon and the anatomical characteristics of the patient. Another (non-European) multicentre trial (e.g. with an equality or non-inferiority design) would help to corroborate the findings of this meta-analysis. Future trials assessing novel methods of stump closure should compare them either with stapler or hand-sewn closure as a control group to ensure comparability of results.

Intramedullary nailing for the treatment of aseptic femoral shaft non-unions after plating failure: effectiveness and timing.

PubMed

Megas, Panagiotis; Syggelos, Spyros A; Kontakis, Georgios; Giannakopoulos, Andreas; Skouteris, Georgios; Lambiris, Elias; Panagiotopoulos, Elias

2009-07-01

This retrospective, multicentre study aimed to evaluate reamed intramedullary nailing (IMN) for the treatment of 30 cases of aseptic femoral shaft non-union after plating failure. Following nailing, 29 non-unions had healed by a mean 7.93 months. In one case a hypertrophic non-union required renailing after 8 months, using a nail of greater diameter, and united within five further months. Healing times were not related to whether the fracture was open or closed, the type non-union or the type of fracture. The delay from the initial plating to intramedullary nailing had a statistically significant effect on healing time and final outcome. This treatment is cost effective and should be implemented as soon as the non-union is diagnosed.

Atrial antitachycardia pacing and managed ventricular pacing in bradycardia patients with paroxysmal or persistent atrial tachyarrhythmias: the MINERVA randomized multicentre international trial.

PubMed

Boriani, Giuseppe; Tukkie, Raymond; Manolis, Antonis S; Mont, Lluis; Pürerfellner, Helmut; Santini, Massimo; Inama, Giuseppe; Serra, Paolo; de Sousa, João; Botto, Giovanni Luca; Mangoni, Lorenza; Grammatico, Andrea; Padeletti, Luigi

2014-09-14

Atrial fibrillation (AF) is a common comorbidity in bradycardia patients. Advanced pacemakers feature atrial preventive pacing and atrial antitachycardia pacing (DDDRP) and managed ventricular pacing (MVP), which minimizes unnecessary right ventricular pacing. We evaluated whether DDDRP and MVP might reduce mortality, morbidity, or progression to permanent AF when compared with standard dual-chamber pacing (Control DDDR). In a randomized, parallel, single-blind, multi-centre trial we enrolled 1300 patients with bradycardia and previous atrial tachyarrhythmias, in whom a DDDRP pacemaker had recently been implanted. History of permanent AF and third-degree atrioventricular block were exclusion criteria. After a 1-month run-in period, 1166 eligible patients, aged 74 ± 9 years, 50% females, were randomized to Control DDDR, DDDRP + MVP, or MVP. Analysis was intention-to-treat. The primary outcome, i.e. the 2-year incidence of a combined endpoint composed of death, cardiovascular hospitalizations, or permanent AF, occurred in 102/385 (26.5%) Control DDDR patients, in 76/383 (19.8%) DDDRP + MVP patients [hazard ratio (HR) = 0.74, 95% confidence interval 0.55-0.99, P = 0.04 vs. Control DDDR] and in 85/398 (21.4%) MVP patients (HR = 0.89, 95% confidence interval 0.77-1.03, P = 0.125 vs. Control DDDR). When compared with Control DDDR, DDDRP + MVP reduced the risk for AF longer than 1 day (HR = 0.66, 95% CI 0.52-0.85, P < 0.001), AF longer than 7 days (HR = 0.52, 95% CI 0.36-0.73, P < 0.001), and permanent AF (HR = 0.39, 95% CI 0.21-0.75, P = 0.004). In patients with bradycardia and atrial tachyarrhythmias, DDDRP + MVP is superior to standard dual-chamber pacing. The primary endpoint was significantly lowered through the reduction of the progression of atrial tachyarrhythmias to permanent AF. NCT00262119. © The Author 2014. Published by Oxford University Press on behalf of the European Society of Cardiology.

Paroxetine and fluoxetine in pregnancy: a prospective, multicentre, controlled, observational study

PubMed Central

Diav-Citrin, Orna; Shechtman, Svetlana; Weinbaum, Dafna; Wajnberg, Rebecka; Avgil, Meytal; Di Gianantonio, Elena; Clementi, Maurizio; Weber-Schoendorfer, Corinna; Schaefer, Christof; Ornoy, Asher

2008-01-01

WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT In recent years there has been concern regarding the possibility that selective serotonin reuptake inhibitors (SSRIs) cause an increased rate of congenital cardiovascular anomalies. As of today, there is still debate in the literature as to the possible effects of paroxetine and fluoxetine on the embryonic cardiovascular system. WHAT THIS STUDY ADDS Based on prospective data from three Teratogen Information Services, we have demonstrated an increased rate of congenital cardiovascular anomalies among the offspring of fluoxetine- and paroxetine-treated mothers. AIMS Recent studies have suggested a possible association between maternal use of selective serotonin reuptake inhibitors (SSRIs) in early pregnancy and cardiovascular anomalies. The aim of the present study was to evaluate the teratogenic risk of paroxetine and fluoxetine. METHODS This multicentre, prospective, controlled study evaluated the rate of major congenital anomalies after first-trimester gestational exposure to paroxetine, fluoxetine or nonteratogens. RESULTS We followed up 410 paroxetine, 314 fluoxetine first-trimester exposed pregnancies and 1467 controls. After exclusion of genetic and cytogenetic anomalies, there was a higher rate of major anomalies in the SSRI groups compared with the controls [paroxetine 18/348 (5.2%), fluoxetine 12/253 (4.7%) and controls 34/1359 (2.5%)]. The main risk applied to cardiovascular anomalies [paroxetine 7/348 (2.0%), crude odds ratio (OR) 3.47, 95% confidence interval (CI) 1.13, 10.58; fluoxetine 7/253 (2.8%), crude OR, 4.81 95% CI 1.56, 14.71; and controls 8/1359 (0.6%)]. On logistic regression analysis only cigarette smoking of ≥10 cigarettes day−1 and fluoxetine exposure were significant variables for cardiovascular anomalies. The adjusted ORs for paroxetine and fluoxetine were 2.66 (95% CI 0.80, 8.90) and 4.47 (95% CI 1.31, 15.27), respectively. CONCLUSION This study suggests a possible association between cardiovascular anomalies and first-trimester exposure to fluoxetine. PMID:18754846

Study protocol of a multicentre randomised controlled trial of self-help cognitive behaviour therapy for working women with menopausal symptoms (MENOS@Work).

PubMed

Hunter, Myra S; Hardy, Claire; Norton, Sam; Griffiths, Amanda

2016-10-01

Hot flushes and night sweats (HFNS) - the main symptoms of the menopause transition - can reduce quality of life and are particularly difficult to manage at work. A cognitive behaviour therapy (CBT) intervention has been developed specifically for HFNS that is theoretically based and shown to reduce significantly the impact of HFNS in several randomised controlled trials (RCTs). Self-help CBT has been found to be as effective as group CBT for these symptoms, but these interventions are not widely available in the workplace. This paper describes the protocol of an RCT aiming to assess the efficacy of CBT for menopausal symptoms implemented in the workplace, with a nested qualitative study to examine acceptability and feasibility. One hundred menopausal working women, aged 45-60 years, experiencing bothersome HFNS for two months will be recruited from several (2-10) large organisations into a multicentre randomised controlled trial. Women will be randomly assigned to either treatment (a self-help CBT intervention lasting 4 weeks) or to a no treatment-wait control condition (NTWC), following a screening interview, consent, and completion of a baseline questionnaire. All participants will complete follow-up questionnaires at 6 weeks and 20 weeks post-randomisation. The primary outcome is the rating of HFNS; secondary measures include HFNS frequency, mood, quality of life, attitudes to menopause, HFNS beliefs and behaviours, work absence and presenteeism, job satisfaction, job stress, job performance, disclosure to managers and turnover intention. Adherence, acceptability and feasibility will be assessed at 20 weeks post-randomisation in questionnaires and qualitative interviews. Upon trial completion, the control group will also be offered the intervention. This is the first randomised controlled trial of a self-management intervention tailored for working women who have troublesome menopausal symptoms. Clin.Gov NCT02623374. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

A prospective international Aspergillus terreus survey: an EFISG, ISHAM and ECMM joint study.

PubMed

Risslegger, B; Zoran, T; Lackner, M; Aigner, M; Sánchez-Reus, F; Rezusta, A; Chowdhary, A; Taj-Aldeen, S J; Arendrup, M C; Oliveri, S; Kontoyiannis, D P; Alastruey-Izquierdo, A; Lagrou, K; Lo Cascio, G; Meis, J F; Buzina, W; Farina, C; Drogari-Apiranthitou, M; Grancini, A; Tortorano, A M; Willinger, B; Hamprecht, A; Johnson, E; Klingspor, L; Arsic-Arsenijevic, V; Cornely, O A; Meletiadis, J; Prammer, W; Tullio, V; Vehreschild, J-J; Trovato, L; Lewis, R E; Segal, E; Rath, P-M; Hamal, P; Rodriguez-Iglesias, M; Roilides, E; Arikan-Akdagli, S; Chakrabarti, A; Colombo, A L; Fernández, M S; Martin-Gomez, M T; Badali, H; Petrikkos, G; Klimko, N; Heimann, S M; Houbraken, J; Uzun, O; Edlinger, M; Fuente, S de la; Lass-Flörl, C

2017-10-01

A prospective international multicentre surveillance study was conducted to investigate the prevalence and amphotericin B susceptibility of Aspergillus terreus species complex infections. A total of 370 cases from 21 countries were evaluated. The overall prevalence of A. terreus species complex among the investigated patients with mould-positive cultures was 5.2% (370/7116). Amphotericin B MICs ranged from 0.125 to 32 mg/L, (median 8 mg/L). Aspergillus terreus species complex infections cause a wide spectrum of aspergillosis and the majority of cryptic species display high amphotericin B MICs. Copyright © 2017. Published by Elsevier Ltd.

Multicentre propensity score-matched analysis of conventional versus extended abdominoperineal excision for low rectal cancer.

PubMed

Ortiz, H; Ciga, M A; Armendariz, P; Kreisler, E; Codina-Cazador, A; Gomez-Barbadillo, J; Garcia-Granero, E; Roig, J V; Biondo, S

2014-06-01

Abdominal perineal excision (APE) was originally described with levator ani removal for rectal cancer. An even wider, more aggressive extralevator resection for APE has been proposed. Although some surgeons are performing a very wide 'extralevator APE (ELAPE)', there are few data to recommend it routinely. This multicentre study aimed to compare outcomes of APE and ELAPE. A multicentre propensity case-matched analysis comparing two surgical approaches (APE and ELAPE) was performed. All patients who underwent abdominoperineal resection of a rectal tumour were considered for the analysis. Tumour height was defined by magnetic resonance imaging measurement and patients with stage II-III tumours had neoadjuvant radiochemotherapy. Involvement of the circumferential resection margin (CRM) and intraoperative tumour perforation were the main outcome measures. A logistic regression model was used to study the relationship between the surgical approaches and outcomes. From January 2008 to March 2013 a total of 1909 consecutive patients underwent APE or ELAPE, of whom 914 matched patients (457 in each group) formed the cohort for analysis. Intraoperative tumour perforation occurred in 7.9 and 7.7 per cent of patients during APE and ELAPE respectively (P = 0.902), and there was CRM involvement in 13.1 and 13.6 per cent (P = 0.846). There were no differences between APE and ELAPE in terms of postoperative complication rates (52.3 versus 48.1 per cent; P = 0.209), need for reoperation (7.7 versus 7.0 per cent; P = 0.703), perineal wound problems (26.0 versus 21.9 per cent; P = 0.141), mortality rate (2.0 versus 2.0 per cent; P = 1.000) and local recurrence rate at 2 years (2.7 versus 5.6 per cent; P = 0.664). ELAPE does not improve rates of CRM involvement, intraoperative tumour perforation, local recurrence or mortality. © 2014 BJS Society Ltd. Published by John Wiley & Sons Ltd.

Computerized detection of breast lesions in multi-centre and multi-instrument DCE-MR data using 3D principal component maps and template matching

NASA Astrophysics Data System (ADS)

Ertas, Gokhan; Doran, Simon; Leach, Martin O.

2011-12-01

In this study, we introduce a novel, robust and accurate computerized algorithm based on volumetric principal component maps and template matching that facilitates lesion detection on dynamic contrast-enhanced MR. The study dataset comprises 24 204 contrast-enhanced breast MR images corresponding to 4034 axial slices from 47 women in the UK multi-centre study of MRI screening for breast cancer and categorized as high risk. The scans analysed here were performed on six different models of scanner from three commercial vendors, sited in 13 clinics around the UK. 1952 slices from this dataset, containing 15 benign and 13 malignant lesions, were used for training. The remaining 2082 slices, with 14 benign and 12 malignant lesions, were used for test purposes. To prevent false positives being detected from other tissues and regions of the body, breast volumes are segmented from pre-contrast images using a fast semi-automated algorithm. Principal component analysis is applied to the centred intensity vectors formed from the dynamic contrast-enhanced T1-weighted images of the segmented breasts, followed by automatic thresholding to eliminate fatty tissues and slowly enhancing normal parenchyma and a convolution and filtering process to minimize artefacts from moderately enhanced normal parenchyma and blood vessels. Finally, suspicious lesions are identified through a volumetric sixfold neighbourhood connectivity search and calculation of two morphological features: volume and volumetric eccentricity, to exclude highly enhanced blood vessels, nipples and normal parenchyma and to localize lesions. This provides satisfactory lesion localization. For a detection sensitivity of 100%, the overall false-positive detection rate of the system is 1.02/lesion, 1.17/case and 0.08/slice, comparing favourably with previous studies. This approach may facilitate detection of lesions in multi-centre and multi-instrument dynamic contrast-enhanced breast MR data.

Value of Additional Digital Breast Tomosynthesis for Preoperative Staging of Breast Cancer in Dense Breasts.

PubMed

Krammer, Julia; Stepniewski, Kathrin; Kaiser, Clemens G; Brade, Joachim; Riffel, Philipp; Schoenberg, Stefan O; Wasser, Klaus

2017-09-01

This retrospective study was initiated to determine the diagnostic value of additional preoperative breast tomosynthesis (DBT) for breast cancer staging in dense breasts. Sixty-six patients (69 breasts) with findings of American College of Radiology category 3 or 4 with Breast Imaging Reporting and Data System 5, 6 or 0 were included. All patients underwent digital mammography and additional DBT. A total of 40/69 (58%) cancers were detected on both mammography and DBT, 23 (33.3%) were only seen on DBT (p=0.0001); 6/69 (8.7%) carcinomas were not detected by either method, of which three were invasive lobular carcinomas. Sensitivity for multifocal/multicentric disease was significantly higher on DBT (12/19, 63.2%) compared to mammography (4/19, 21.1%) (p=0.02), specificity was comparable (96.0% vs. 90.0%). Multifocal/multicentric disease was not detected on mammography nor DBT in 7/19 (36.8%) patients, including three invasive lobular carcinomas. DBT may significantly improve preoperative breast cancer staging in patients with dense breasts compared to conventional mammography alone. Nevertheless, limitations have to be expected in the case of invasive lobular carcinoma. Copyright© 2017, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.

Zarzio®, biosimilar of filgrastim, in prophylaxis of chemotherapy-induced neutropenia in routine practice: a French prospective multicentric study.

PubMed

Nahon, Sophie; Rastkhah, Mansour; Ben Abdelghani, Meher; Soumoudronga, Ravaka-Fatoma; Gasnereau, Isabelle; Labourey, Jean-Luc

2016-05-01

Chemotherapy-induced neutropenia is a serious and potentially life-threatening consequence of cancer treatment. Prophylactic treatment with granulocyte-colony stimulating factor (G-CSF) decreases the incidence of febrile neutropenia, the rate of hospitalization, and the use of antibiotics in patients at risk. The aim of this study was to assess efficacy, safety, and use of Zarzio(®)-biosimilar of Neupogen(®) (G-CSF; filgrastim)-in prophylaxis of chemotherapy-induced neutropenia in current practice in cancer patients. We conducted an observational, prospective, longitudinal, and multicentric study in France. The incidence of neutropenia was evaluated at each cycle of chemotherapy. One hundred eighty-four patients (women, 64.7 %; mean age, 61.7 years) with solid tumor (89.7 %; breast cancer, 50.5 %) or non-Hodgkin lymphoma (10.3 %) were included. The risk of febrile neutropenia based on chemotherapy regimen was >20 % for 32.1 % of patients. No case of febrile neutropenia was reported. Neutropenia was the cause of hospitalization and/or antibiotic therapy in 10 patients. The most frequent adverse events related to Zarzio(®) were pain, in particular bone pain. No serious adverse event related to Zarzio(®) was reported. The results obtained in real-life conditions confirm that Zarzio(®) is efficient and well tolerated in cancer patients.

Ethical approval for research involving geographically dispersed subjects: unsuitability of the UK MREC/LREC system and relevance to uncommon genetic disorders

PubMed Central

Lewis, J C; Tomkins, S; Sampson, J R

2001-01-01

Objectives—To assess the process involved in obtaining ethical approval for a single-centre study involving geographically dispersed subjects with an uncommon genetic disorder. Design—Observational data of the application process to 53 local research ethics committees (LRECs) throughout Wales, England and Scotland. The Multicentre Research Ethics Committee (MREC) for Wales had already granted approval. Results—Application to the 53 LRECs required 24,552 sheets of paper and took two months of the researcher's time. The median time taken for approval was 39 days with only seven (13%) of committees responding within the recommended 21 days. In at least nineteen cases (36%) a subcommittee considered the application. Thirty-three committees (62%) accepted the proposal without amendments but, of the remainder, four (8%) requested changes outside of the remit of LRECs. Discussion—Difficulties still exist with the system for obtaining ethical approval for studies involving a single centre but with patients at multiple sites, as is often required for genetic observational research. As such studies differ from true multicentre studies, it may be advantageous to develop a separate and specific process of application to ensure that resources are not unnecessarily expended in the quest for ethical approval. Key Words: Research ethics • MREC • LREC PMID:11579194

Transanal haemorrhoidal artery echodoppler ligation and anopexy (THD) is effective for II and III degree haemorrhoids: a prospective multicentric study.

PubMed

Infantino, A; Bellomo, R; Dal Monte, P P; Salafia, C; Tagariello, C; Tonizzo, C A; Spazzafumo, L; Romano, G; Altomare, D F

2010-08-01

We report a multicentric prospective study which aimed to evaluate Doppler-assisted ligation of the terminal haemorrhoidal arteries (THD) for II and III degree haemorrhoids. A total of 112 patients from five colorectal units, including 81 men, mean age 48 +/- 13 years, with II degree (39) and III degree (73) haemorrhoids were treated by Doppler-guided transanal de-arterialization and anopexy using a new device (THD). The mean operative time was 33.9 +/- 8.8 minutes, and the mean number of ligatures applied was 7.2 +/- 1.5. Postoperatively, 72% of patients did not need analgesics and the other 28% used nonsteroidal antiinflammatory drugs 1-3 times/day for less than 2 days. All the patients were operated as a day case. Early postoperative complications included haemorrhoidal thrombosis (2 patients), bleeding (1) treated by haemostatic suture, dysuria (6) and acute urinary retention (1). After a mean follow-up of 15.6 +/- 6.5 months (range 6-32), 2/105 (20.9%) patients complained of minor bleeding, while mild pain was still present in 4/51 patients (7.8%). There were no statistically significant differences in the sample population regarding the gender or stage of the disease. Tenesmus was cured in 15/17 patients, dyschaezia in 20/22 patients and mucous soiling in 10/10 patients. No new cases of altered defaecation or faecal incontinence were recorded. Overall, 85.7% of patients were cured and 7.1% improved. Residual haemorrhoids were treated by elastic band ligation in nine (8%) patients and by surgical excision in further five patients (4.5%). Doppler-assisted ligation of the terminal branches of the haemorrhoidal arteries for II and III degree haemorrhoids is highly effective and painless. Complications are few and the technique can be performed as a day case.

Distinct features distinguishing IgG4-related disease from multicentric Castleman’s disease

PubMed Central

Sasaki, Takanori; Akiyama, Mitsuhiro; Kaneko, Yuko; Mori, Takehiko; Yasuoka, Hidekata; Suzuki, Katsuya; Yamaoka, Kunihiro; Okamoto, Shinichiro; Takeuchi, Tsutomu

2017-01-01

Objectives Differentiating IgG4-related disease (IgG4-RD) from multicentric Castleman’s disease (MCD) is challenging because both diseases present high serum IgG4. The objective of this study is to clarify the differences in characteristics and identify a clinically useful approach to differentiate these two diseases. Methods Forty-five consecutive patients with untreated active IgG4-RD and 33 patients with MCD were included in this study, who visited our institution from January 2000 to August 2016. The clinical and laboratory findings for the patients of the two diseases were compared. Various combinations of the distinctive findings were evaluated to identify the most efficient differentiating features between IgG4-RD and MCD. Results The levels of serum IgG4 were not different between the two diseases. Orbits, lacrimal glands, salivary glands or pancreas were involved in 88.9% of IgG4-RD cases and only in 3.0% of MCD cases. All MCD cases involved lymph nodes. Atopic history was characteristic for IgG4-RD. The levels of C reactive protein (CRP) with a cut-off of 0.80 mg/dL and IgA with a cut-off of 330 mg/dL were the most distinctive. The combination of ‘Orbits, lacrimal glands, salivary glands or pancreas involvement, atopic history, or non-involvement of lymph node’ and ‘CRP ≤ 0.8 mg/dL or IgA ≤ 330 mg/dL’ yielded the probability of 97.8% in IgG4-RD, while that of 3.0 % in patients with MCD. Conclusions Our study revealed distinct features between IgG4-RD and MCD. Differentiating between the diseases based on those distinct features, including distribution of organ involvement, atopic history, levels of IgA and CRP, was a useful approach. PMID:28959455

Cycle control and side effects of a new combiphasic oral contraceptive regimen.

PubMed

Dieben, T O; op ten Berg, M T; Coelingh Bennink, H J

1994-07-01

In a multicentre study 882 women were treated during a total of 12,850 cycles with a new combiphasic contraceptive: CTR 24. The study period was 18 cycles. The combiphasic preparation CTR 24 contains 25 micrograms desogestrel (CAS 54024-22-5) plus 40 micrograms ethinylestradiol (CAS 57-63-6) daily for the first 7 days followed by the combination of 125 micrograms desogestrel and 30 micrograms ethinyl-estradiol daily for the subsequent 15 days. The bleeding patterns were analysed over pill cycles and a comparison was made between starters and switchers. The cycle control of the combination was very good. The side effect profile was favourable.

Comparing meta-analysis and ecological-longitudinal analysis in time-series studies. A case study of the effects of air pollution on mortality in three Spanish cities

PubMed Central

Saez, M; Figueiras, A; Ballester, F; Perez-Hoyos, S; Ocana, R; Tobias, A

2001-01-01

STUDY OBJECTIVE—The objective of this paper is to introduce a different approach, called the ecological-longitudinal, to carrying out pooled analysis in time series ecological studies. Because it gives a larger number of data points and, hence, increases the statistical power of the analysis, this approach, unlike conventional ones, allows the complementation of aspects such as accommodation of random effect models, of lags, of interaction between pollutants and between pollutants and meteorological variables, that are hardly implemented in conventional approaches.
DESIGN—The approach is illustrated by providing quantitative estimates of the short-term effects of air pollution on mortality in three Spanish cities, Barcelona, Valencia and Vigo, for the period 1992-1994. Because the dependent variable was a count, a Poisson generalised linear model was first specified. Several modelling issues are worth mentioning. Firstly, because the relations between mortality and explanatory variables were non-linear, cubic splines were used for covariate control, leading to a generalised additive model, GAM. Secondly, the effects of the predictors on the response were allowed to occur with some lag. Thirdly, the residual autocorrelation, because of imperfect control, was controlled for by means of an autoregressive Poisson GAM. Finally, the longitudinal design demanded the consideration of the existence of individual heterogeneity, requiring the consideration of mixed models.
MAIN RESULTS—The estimates of the relative risks obtained from the individual analyses varied across cities, particularly those associated with sulphur dioxide. The highest relative risks corresponded to black smoke in Valencia. These estimates were higher than those obtained from the ecological-longitudinal analysis. Relative risks estimated from this latter analysis were practically identical across cities, 1.00638 (95% confidence intervals 1.0002, 1.0011) for a black smoke increase of 10 µg/m3 and 1.00415 (95% CI 1.0001, 1.0007) for a increase of 10 µg/m3 of sulphur dioxide. Because the statistical power is higher than in the individual analysis more interactions were statistically significant, especially those among air pollutants and meteorological variables.
CONCLUSIONS—Air pollutant levels were related to mortality in the three cities of the study, Barcelona, Valencia and Vigo. These results were consistent with similar studies in other cities, with other multicentric studies and coherent with both, previous individual, for each city, and multicentric studies for all three cities.


Keywords: air pollution; mortality; longitudinal studies PMID:11351001

The foundation of NCVD PCI Registry: the Malaysia's first multi-centre interventional cardiology project.

PubMed

Liew, H B; Rosli, M A; Wan Azman, W A; Robaayah, Z; Sim, K H

2008-09-01

The National Cardiovascular Database for Percutaneous Coronary Intervention (NCVD PCI) Registry is the first multicentre interventional cardiology project, involving the main cardiac centres in the country. The ultimate goal of NCVD PCI is to provide a contemporary appraisal of PCI in Malaysia. This article introduces the foundation, the aims, methodology, database collection and preliminary results of the first six-month database.

Malignant insulinoma with hepatic and pulmonary metastases associated with primary hyperparathyroidism. Case report and review of the literature

PubMed Central

A., Albu; A., Zirnea; O., Georgescu; D., Terzea; D., Jinga; S., Fica

2008-01-01

Malignant insulinomas are rare tumors (10% of insulinomas) that often present as multicentric macro nodules with multiple liver metastases before diagnosis. We report the case of a 55 year old female with a medical history of severe hypoglycemic attacks for two months. Blood tests showed a decreased value of glycemia (30mg/dl) associated with increased insulin level (16μU/ml) and an increased glycemia/insulinemia ratio of 1.87 supporting the diagnosis of insulinoma. Abdominal CT showed a 1.5 cm mass localized in the head of the pancreas with disseminated hepatic tumors, confirmed as neuroendocrine metastases by biopsy (which proved the presence of a malignant insulinoma). Primary hyperparathyroidism was diagnosed based on mild elevation of calcium (10.4 mg/dl) associated with a high level of PTH (71,2 pg/ml). The coexistence of the two endocrinopathies suggested the presence of type 1 multiple endocrine neoplasia (MEN 1). Because of multiple hepatic masses and liver function impairment, surgery and hepatic artery embolization were not performed. Somatostatin analog therapy was started with symptomatic control in the beginning, but rapid loss of beneficial effect. Finally, systemic chemotherapy with doxorubicin was administered, but the disease was progressive and after three months we decided to stop it. The patient died at home after one month, probably in hypoglycemic coma. PMID:20108468

Problems in developing an instrument for the rapid assessment of personality status.

PubMed

Van Horn, E; Manley, C; Leddy, D; Cicchetti, D; Tyrer, P

2000-06-01

To assess the validity of a quick assessment instrument (10 minutes) for assessing personality status, the Rapid Personality Assessment Schedule (PAS-R). The PAS-R was evaluated in psychotic patients recruited in one of the centres involved in a multicentre randomised controlled trial of intensive vs standard case management (the UK700 case management trial). Patients were assessed using both a full version of the PAS (PAS-I - ICD version) and the PAS-R. The weighted kappa statistic was used to gauge the (criterion-related) validity of the PAS-R using the PAS-I as the gold standard. Both measure code personality status using a four-point rating of severity in addition to recording individual categories of personality disorder. One hundred fifty-five (77%) of 201 patients recruited were assessed with both instruments. The weighted kappa statistic was 0.31, suggesting only moderate agreement between the PAS-I and PAS-R instruments under the four-point rating format, and 0.39 for the dichotomous personality disorder/no disorder separation. The sensitivity (64%) and specificity (82%) of the PAS-R in predicting PAS-I personality disorder were as satisfactory as for other screening instruments but still somewhat disappointing, and the PAS-R had an overall diagnostic accuracy of 78%. The PAS-R is a quick and rough method of detecting personality abnormality but is not a substitute for a fuller assessment.

Rationale of the BREAst cancer e-healTH [BREATH] multicentre randomised controlled trial: An Internet-based self-management intervention to foster adjustment after curative breast cancer by decreasing distress and increasing empowerment

PubMed Central

2012-01-01

Background After completion of curative breast cancer treatment, patients go through a transition from patient to survivor. During this re-entry phase, patients are faced with a broad range of re-entry topics, concerning physical and emotional recovery, returning to work and fear of recurrence. Standard and easy-accessible care to facilitate this transition is lacking. In order to facilitate adjustment for all breast cancer patients after primary treatment, the BREATH intervention is aimed at 1) decreasing psychological distress, and 2) increasing empowerment, defined as patients’ intra- and interpersonal strengths. Methods/design The non-guided Internet-based self-management intervention is based on cognitive behavioural therapy techniques and covers four phases of recovery after breast cancer (Looking back; Emotional processing; Strengthening; Looking ahead). Each phase of the fully automated intervention has a fixed structure that targets consecutively psychoeducation, problems in everyday life, social environment, and empowerment. Working ingredients include Information (25 scripts), Assignment (48 tasks), Assessment (10 tests) and Video (39 clips extracted from recorded interviews). A non-blinded, multicentre randomised controlled, parallel-group, superiority trial will be conducted to evaluate the effectiveness of the BREATH intervention. In six hospitals in the Netherlands, a consecutive sample of 170 will be recruited of women who completed primary curative treatment for breast cancer within 4 months. Participants will be randomly allocated to receive either usual care or usual care plus access to the online BREATH intervention (1:1). Changes in self-report questionnaires from baseline to 4 (post-intervention), 6 and 10 months will be measured. Discussion The BREATH intervention provides a psychological self-management approach to the disease management of breast cancer survivors. Innovative is the use of patients’ own strengths as an explicit intervention target, which is hypothesized to serve as a buffer to prevent psychological distress in long-term survivorship. In case of proven (cost) effectiveness, the BREATH intervention can serve as a low-cost and easy-accessible intervention to facilitate emotional, physical and social recovery of all breast cancer survivors. Trial registration This study is registered at the Netherlands Trial Register (NTR2935) PMID:22958799

Effectiveness of systemic family therapy versus treatment as usual for young people after self-harm: a pragmatic, phase 3, multicentre, randomised controlled trial.

PubMed

Cottrell, David J; Wright-Hughes, Alexandra; Collinson, Michelle; Boston, Paula; Eisler, Ivan; Fortune, Sarah; Graham, Elizabeth H; Green, Jonathon; House, Allan O; Kerfoot, Michael; Owens, David W; Saloniki, Eirini-Christina; Simic, Mima; Lambert, Fiona; Rothwell, Justine; Tubeuf, Sandy; Farrin, Amanda J

2018-03-01

Self-harm in adolescents is common and repetition occurs in a high proportion of these cases. Scarce evidence exists for effectiveness of interventions to reduce self-harm. This pragmatic, multicentre, randomised, controlled trial of family therapy versus treatment as usual was done at 40 UK Child and Adolescent Mental Health Services (CAMHS) centres. We recruited young people aged 11-17 years who had self-harmed at least twice and presented to CAMHS after self-harm. Participants were randomly assigned (1:1) to receive manualised family therapy delivered by trained and supervised family therapists or treatment as usual by local CAMHS. Participants and therapists were aware of treatment allocation; researchers were masked. The primary outcome was hospital attendance for repetition of self-harm in the 18 months after group assignment. Primary and safety analyses were done in the intention-to-treat population. The trial is registered at the ISRCTN registry, number ISRCTN59793150. Between Nov 23, 2009, and Dec 31, 2013, 3554 young people were screened and 832 eligible young people consented to participation and were randomly assigned to receive family therapy (n=415) or treatment as usual (n=417). Primary outcome data were available for 795 (96%) participants. Numbers of hospital attendances for repeat self-harm events were not significantly different between the groups (118 [28%] in the family therapy group vs 103 [25%] in the treatment as usual group; hazard ratio 1·14 [95% CI 0·87-1·49] p=0·33). Similar numbers of adverse events occurred in both groups (787 in the family therapy group vs 847 in the treatment as usual group). For adolescents referred to CAMHS after self-harm, having self-harmed at least once before, our family therapy intervention conferred no benefits over treatment as usual in reducing subsequent hospital attendance for self-harm. Clinicians are therefore still unable to recommend a clear, evidence-based intervention to reduce repeated self-harm in adolescents. National Institute for Health Research Health Technology Assessment programme. Copyright © 2018 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license. Published by Elsevier Ltd.. All rights reserved.

The MUK five protocol: a phase II randomised, controlled, parallel group, multi-centre trial of carfilzomib, cyclophosphamide and dexamethasone (CCD) vs. cyclophosphamide, bortezomib (Velcade) and dexamethasone (CVD) for first relapse and primary refractory multiple myeloma.

PubMed

Brown, Sarah; Hinsley, Samantha; Ballesteros, Mónica; Bourne, Sue; McGarry, Paul; Sherratt, Debbie; Flanagan, Louise; Gregory, Walter; Cavenagh, Jamie; Owen, Roger; Williams, Cathy; Kaiser, Martin; Low, Eric; Yong, Kwee

2016-01-01

Multiple myeloma is a plasma cell tumour with an annual incidence in the UK of approximately 40-50 per million i.e. about 4500 new cases per annum. The triple combination cyclophosphamide, bortezomib (Velcade®) and dexamethasone (CVD) is an effective regimen at relapse and has emerged in recent years as the standard therapy at first relapse in the UK. Carfilzomib has good activity as a single agent in the relapsed setting, and it is expected that efficacy will be improved when used in combination with dexamethasone and cyclophosphamide. MUK Five is a phase II open label, randomised, controlled, parallel group, multi-centre trial that will compare the activity of carfilzomib, cyclophosphamide and dexamethasone (CCD) with that of CVD, given over an equivalent treatment period (24 weeks), in participants with multiple myeloma at first relapse, or refractory to no more than 1 line of treatment. In addition, the study also aims to assess the utility of a maintenance schedule of carfilzomib in these participants. The primary objective of the trial is to assess whether CCD provides non-inferior activity in terms of ≥ VGPR rates at 24 weeks, and whether the addition of maintenance treatment with carfilzomib to CCD provides superior activity in terms of progression-free survival, as compared to CCD with no maintenance. Secondary objectives include comparing toxicity profiles, further summarizing and comparing the activity of the different treatment arms and analysis of the effect of each treatment arm on minimal residual disease status. The development of carfilzomib offers the opportunity to further explore the anti-tumour efficacy of proteasome inhibition and, based on the available evidence, it is important and timely to obtain data on the activity, toxicity and tolerability of this drug. In contrast to ongoing phase III trials, this phase II trial has a unique subset of participants diagnosed with multiple myeloma at first relapse or refractory to no more than 1 line of treatment and will also evaluate the utility of maintenance with carfilzomib for up to 18 months and investigate minimal residual disease status to provide information on depth of response and the prognostic impact thereof. The trial is registered under ISRCTN17354232, December 2012.

[Magnet ingestions in children: a French multicenter study].

PubMed

Talvard, M; Mouttalib, S; Flaum, V; Viala, J; Galinier, P; Olives, J-P; Mas, E

2015-01-01

Digestive complications related to the ingestion of magnetic foreign bodies in children are increasing, especially in Asia and North America. In France, several case reports have been reported since 2008. We conducted a retrospective multicentric study to evaluate the frequency of ingestion of magnet foreign bodies and to describe the complicated cases that have occurred in France over the last 5 years. We report 40 cases of which 60% were multiple magnet ingestions. Eighty-eight percent of the children of the group who had swallowed multiple magnets needed interventional management by endoscopy (33%) or surgery (58%). Only two children (12.5%) of the group who swallowed one magnet required removal. This problem is not uncommon in France (2% of the 1132 foreign bodies investigated in the Toulouse center over 5 years), which justifies clear information for healthcare professionals and caregivers in order to avoid potential intestinal complications. We suggest interventional management or very close monitoring in the cases of multiple magnet ingestion. Meanwhile, in the majority of confirmed cases of simple magnet ingestions, we propose home monitoring. Copyright © 2014 Elsevier Masson SAS. All rights reserved.

The safe and responsible disposal of unused controlled drugs.

PubMed

Ahmed, Iftikhar; Majeed, Amer

There are well-defined legal requirements for the safe storage, handling and disposal of controlled drugs (CDs): The Misuse of Drugs Act 1971, and Safer Management of Controlled Drugs (Department of Health, 2007). Clinical staff involved in the prescription and administration of CDs to patients are responsible and accountable for the appropriate disposal of these drugs because of the risk of substance abuse. A review of current practice, as followed by staff involved in the use and disposal of CDs, has been evaluated in a multi-centre audit. This audit showed that a wide variation in attitude towards disposal of CDs exists among medical and non-medical staff, and that the sample hospitals are falling short of meeting proposed standards.

Digital breast tomosynthesis for detecting multifocal and multicentric breast cancer: influence of acquisition geometry on model observer performance in breast phantom images

NASA Astrophysics Data System (ADS)

Wen, Gezheng; Park, Subok; Markey, Mia K.

2017-03-01

Multifocal and multicentric breast cancer (MFMC), i.e., the presence of two or more tumor foci within the same breast, has an immense clinical impact on treatment planning and survival outcomes. Detecting multiple breast tumors is challenging as MFMC breast cancer is relatively uncommon, and human observers do not know the number or locations of tumors a priori. Digital breast tomosynthesis (DBT), in which an x-ray beam sweeps over a limited angular range across the breast, has the potential to improve the detection of multiple tumors.1, 2 However, prior efforts to optimize DBT image quality only considered unifocal breast cancers (e.g.,3-9), so the recommended geometries may not necessarily yield images that are informative for the task of detecting MFMC. Hence, the goal of this study is to employ a 3D multi-lesion (ml) channelized-Hotelling observer (CHO) to identify optimal DBT acquisition geometries for MFMC. Digital breast phantoms and simulated DBT scanners of different geometries (e.g., wide or narrow arc scans, different number of projections in each scan) were used to generate image data for the simulation study. Multiple 3D synthetic lesions were inserted into different breast regions to simulate MF cases and MC cases. 3D partial least squares (PLS) channels, and 3D Laguerre-Gauss (LG) channels were estimated to capture discriminant information and correlations among signals in locally varying anatomical backgrounds, enabling the model observer to make both image-level and location-specific detection decisions. The 3D ml-CHO with PLS channels outperformed that with LG channels in this study. The simulated MC cases and MC cases were not equally difficult for the ml-CHO to detect across the different simulated DBT geometries considered in this analysis. Also, the results suggest that the optimal design of DBT may vary as the task of clinical interest changes, e.g., a geometry that is better for finding at least one lesion may be worse for counting the number of lesions.

[Post-stroke speech disorder treated with acupuncture and psychological intervention combined with rehabilitation training: a randomized controlled trial].

PubMed

Wang, Ling; Liu, Shao-ming; Liu, Min; Li, Bao-jun; Hui, Zhen-liang; Gao, Xiang

2011-06-01

To assess the clinical efficacy on post-stroke speech disorder treated with acupuncture and psychological intervention combined with rehabilitation training. The multi-central randomized controlled study was adopted. One hundred and twenty cases of brain stroke were divided into a speech rehabilitation group (control group), a speech rehabilitation plus acupuncture group (observation group 1) and a speech rehabilitation plus acupuncture combined with psychotherapy group (observation group 2), 40 cases in each one. The rehabilitation training was conducted by a professional speech trainer. In acupuncture treatment, speech function area in scalp acupuncture, Jinjin (EX-HN 12) and Yuye (EX-HN 13) in tongue acupuncture and Lianquan (CV 23) were the basic points. The supplementary points were selected according to syndrome differentiation. Bloodletting method was used in combination with acupuncture. Psychotherapy was applied by the physician in psychiatric department of the hospital. The corresponding programs were used in each group. Examination of Aphasia of Chinese of Beijing Hospital was adopted to observe the oral speech expression, listening comprehension and reading and writing ability. After 21-day treatment, the total effective rate was 92.5% (37/40) in observation group 1, 97.5% (39/40) in observation group 2 and 87.5% (35/40) in control group. The efficacies were similar in comparison among 3 groups. The remarkable effective rate was 15.0% (6/40) in observation group 1, 50.0% (20/40) in observation group 2 and 2.5% (1/40) in control group. The result in observation group 2 was superior to the other two groups (P<0.01, P<0.001). In comparison of the improvements of oral expression, listening comprehension, reading and writing ability, all of the 3 groups had achieved the improvements to different extents after treatment (P<0.01, P<0.001). The results in observation group 2 were better than those in observation group 1 and control group. Acupuncture and psychological intervention combined with rehabilitation training is obviously advantageous in the treatment of post-stroke speech disorder.

CHOP chemotherapy for the treatment of canine multicentric T-cell lymphoma.

PubMed

Rebhun, R B; Kent, M S; Borrofka, S A E B; Frazier, S; Skorupski, K; Rodriguez, C O

2011-03-01

Dogs with multicentric T-cell lymphoma are commonly treated with CHOP chemotherapy protocols that include cyclophosphamide, doxorubicin, vincristine and prednisone. The purpose of this study was to evaluate the use of CHOP chemotherapy for dogs with multicentric T-cell lymphoma. Identification of prognostic factors in this specific subset of dogs was of secondary interest. Twenty-three out of 24 dogs responded to CHOP chemotherapy and these dogs remained on the protocol for a median of 146 days. No variable was associated with progression free survival (PFS) including stage, substage, hypercalcemia or radiographic evidence of a cranial mediastinal mass. The median overall survival time (OST) for all dogs was 235 days. Dogs that were thrombocytopenic at presentation experienced a significantly longer OST (323 versus 212 days, P=0.01). © 2010 Blackwell Publishing Ltd.

Comparison of risk patterns in carcinoma and melanoma of the skin in men: a multi-centre case–case–control study

PubMed Central

Zanetti, R; Rosso, S; Martinez, C; Nieto, A; Miranda, A; Mercier, M; Loria, D I; Østerlind, A; Greinert, R; Navarro, C; Fabbrocini, G; Barbera, C; Sancho-Garnier, H; Gafà, L; Chiarugi, A; Mossotti, R

2006-01-01

We directly compared risk factors between 214 histologically confirmed melanomas (CMM), 215 basal-cell carcinomas (BCC) and 139 squamous-cell carcinomas (SCC) in a multiple case–case–control study with 349 controls from patients without dermatological disease admitted to the same hospitals. Subjects with fair hair had a significant risk increase for all types of tumours at a comparable level (ORadj for blonde hair: CMM 2.3; SCC 2.4; BCC 2.3). The effect of pale eyes was significant and similar for CMM and BCC (ORadj 2.6). Intermittent sun exposure measured in hours spent at beach during holidays was significant for both CMM (ORadj 2.6 for more than 7000 lifelong hours) and BCC (ORadj 2.1 for more than 7000 lifelong hours), while SCC exhibited a significant risk increase for chronic exposure to sunlight measured in hours of outdoor work (ORadj 2.2 for more than 6000 lifelong hours). In the case–case comparison using a multinomial logistic regression model, we found a statistically significant risk difference for pale eyes, and number of naevi in the CMM group, compared to other skin cancers. For intermittent sun exposure, there was a significant risk difference of BCC when compared to the risk of SCC. Factors influencing risk of SCC are different, with chronic exposure to sun playing a major role in causing this type of carcinoma. PMID:16495934

Microbiological profile and clinical characteristics of diabetic foot infection in northern China: a retrospective multicentre survey in the Beijing area.

PubMed

Li, Xiangyan; Qi, Xin; Yuan, Geheng; Ju, Shang; Yu, Zhengya; Deng, Wei; Liu, Yanjun; Li, Yufeng; Bu, Xiujun; Ding, Mingchao; Li, Quan; Guo, Xiaohui

2018-02-01

We aimed to define the microbiological characteristics of diabetic foot infection in patients in the Beijing area and to explore the demographic and clinical factors correlated with pathogen distribution. As part of a retrospective multicentre surveillance program conducted in eight hospitals in Beijing 2010-2014, we recruited all inpatients for whom bacterial culture had been performed. Demographic, clinical, laboratory and surgery data were obtained from medical records. Statistical analysis was performed to analyse data on microbiological and clinical characteristics.Results/Key findings. A total of 456 cases were included. The culture positivity was 95.4 %. Among all patients with positive cultures, 88 cases (20.2 %) had polymicrobial infections. Five hundred and fifty-one species were isolated from all specimens, including 39.6 % Gram-positive bacteria and 57.5 % Gram-negative bacteria. Enterobacteriaceae accounted for 41.0 % of all isolates. Staphylococcus aureus (17.1 %), Pseudomonas aeruginosa (13.1 %), Proteus spp. (9.8 %), Escherichia coli (9.3 %) and coagulase-negative Staphylococcus (8.3 %) were the most frequently isolated species. The rate of resistance to methicillin was 24.5 % for S. aureus. The susceptibility of P. aeruginosa to all antibiotics was over 60 %. The rate of extended-spectrum β-lactamase production among E. coli was 52.6 %. P. aeruginosa and Enterobacteriaceae show high sensitivity to piperacillin/tazobactam, carbapenems and amikacin. Multivariate analysis showed that patient age >60 years was independently associated with Gram-negative rods. Enterobacteriaceae were the most frequently isolated organisms in our area. Older patients were more likely to suffer from Gram-negative rod infections. Gram-negative rods show high sensitivity to piperacillin/tazobactam, carbapenems and amikacin.

Prospective, Multicentre, Nationwide Clinical Data from 600 Cases of Acute Pancreatitis

PubMed Central

Párniczky, Andrea; Kui, Balázs; Szentesi, Andrea; Balázs, Anita; Szűcs, Ákos; Mosztbacher, Dóra; Czimmer, József; Sarlós, Patrícia; Bajor, Judit; Gódi, Szilárd; Vincze, Áron; Illés, Anita; Szabó, Imre; Pár, Gabriella; Takács, Tamás; Czakó, László; Szepes, Zoltán; Rakonczay, Zoltán; Izbéki, Ferenc; Gervain, Judit; Halász, Adrienn; Novák, János; Crai, Stefan; Hritz, István; Góg, Csaba; Sümegi, János; Golovics, Petra; Varga, Márta; Bod, Barnabás; Hamvas, József; Varga-Müller, Mónika; Papp, Zsuzsanna; Sahin-Tóth, Miklós; Hegyi, Péter

2016-01-01

Objective The aim of this study was to analyse the clinical characteristics of acute pancreatitis (AP) in a prospectively collected, large, multicentre cohort and to validate the major recommendations in the IAP/APA evidence-based guidelines for the management of AP. Design Eighty-six different clinical parameters were collected using an electronic clinical research form designed by the Hungarian Pancreatic Study Group. Patients 600 adult patients diagnosed with AP were prospectively enrolled from 17 Hungarian centres over a two-year period from 1 January 2013. Main Results With respect to aetiology, biliary and alcoholic pancreatitis represented the two most common forms of AP. The prevalence of biliary AP was higher in women, whereas alcoholic AP was more common in men. Hyperlipidaemia was a risk factor for severity, lack of serum enzyme elevation posed a risk for severe AP, and lack of abdominal pain at admission demonstrated a risk for mortality. Abdominal tenderness developed in all the patients with severe AP, while lack of abdominal tenderness was a favourable sign for mortality. Importantly, lung injury at admission was associated with mortality. With regard to laboratory parameters, white blood cell count and CRP were the two most sensitive indicators for severe AP. The most common local complication was peripancreatic fluid, whereas the most common distant organ failure in severe AP was lung injury. Deviation from the recommendations in the IAP/APA evidence-based guidelines on fluid replacement, enteral nutrition and timing of interventions increased severity and mortality. Conclusions Analysis of a large, nationwide, prospective cohort of AP cases allowed for the identification of important determinants of severity and mortality. Evidence-based guidelines should be observed rigorously to improve outcomes in AP. PMID:27798670

Tumour stage and gender predict recurrence and second primary malignancies in head and neck cancer: a multicentre study within the INHANCE consortium.

PubMed

Leoncini, Emanuele; Vukovic, Vladimir; Cadoni, Gabriella; Giraldi, Luca; Pastorino, Roberta; Arzani, Dario; Petrelli, Livia; Wünsch-Filho, Victor; Toporcov, Tatiana Natasha; Moyses, Raquel Ayub; Matsuo, Keitaro; Bosetti, Cristina; La Vecchia, Carlo; Serraino, Diego; Simonato, Lorenzo; Merletti, Franco; Boffetta, Paolo; Hashibe, Mia; Lee, Yuan-Chin Amy; Boccia, Stefania

2018-05-19

Recurrence and second primary cancer (SPC) continue to represent major obstacles to long-term survival in head and neck cancer (HNC). Our aim was to evaluate whether established demographics, lifestyle-related risk factors for HNC and clinical data are associated with recurrence and SPC in HNC. We conducted a multicentre study by using data from five studies members of the International Head and Neck Cancer Epidemiology consortium-Milan, Rome, Western Europe, Sao Paulo, and Japan, totalling 4005 HNC cases with a median age of 59 (interquartile range 52-67). Multivariate hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated for recurrence and SPC. During follow-up, 1161 (29%) patients had recurrence and 343 (8.6%) developed SPC. Advanced tumour stage was associated with increased risk of recurrence in HNC overall (HR = 1.76, 95% CI 1.41-2.19). Women with laryngeal cancer had a reduced risk of recurrence compared to men (HR = 0.39, 95% CI: 0.24-0.74). Concerning predictors of SPC, advanced age (HR = 1.02; 95% CI: 1.00-1.04) and alcohol consumption (> 1 drink per day, HR = 2.11; 95% CI: 1.13-3.94) increased the risk of SPC among patients with laryngeal cancer. Additionally, women were at higher risk of SPC, in HNC overall group (HR = 1.68; 95% CI: 1.13-2.51) and oropharyngeal cancer group (HR = 1.74; 95% CI: 1.02-2.98). Tumour stage and male gender (larynx only) were positive predictors of cancer recurrence in HNC patients. Predictors of SPC were advanced age and alcohol use among laryngeal cancer cases, and female gender for oropharyngeal and HNC overall.

Dose specification for hippocampal sparing whole brain radiotherapy (HS WBRT): considerations from the UK HIPPO trial QA programme.

PubMed

Megias, Daniel; Phillips, Mark; Clifton-Hadley, Laura; Harron, Elizabeth; Eaton, David J; Sanghera, Paul; Whitfield, Gillian

2017-03-01

The HIPPO trial is a UK randomized Phase II trial of hippocampal sparing (HS) vs conventional whole-brain radiotherapy after surgical resection or radiosurgery in patients with favourable prognosis with 1-4 brain metastases. Each participating centre completed a planning benchmark case as part of the dedicated radiotherapy trials quality assurance programme (RTQA), promoting the safe and effective delivery of HS intensity-modulated radiotherapy (IMRT) in a multicentre trial setting. Submitted planning benchmark cases were reviewed using visualization for radiotherapy software (VODCA) evaluating plan quality and compliance in relation to the HIPPO radiotherapy planning and delivery guidelines. Comparison of the planning benchmark data highlighted a plan specified using dose to medium as an outlier by comparison with those specified using dose to water. Further evaluation identified that the reported plan statistics for dose to medium were lower as a result of the dose calculated at regions of PTV inclusive of bony cranium being lower relative to brain. Specification of dose to water or medium remains a source of potential ambiguity and it is essential that as part of a multicentre trial, consideration is given to reported differences, particularly in the presence of bone. Evaluation of planning benchmark data as part of an RTQA programme has highlighted an important feature of HS IMRT dosimetry dependent on dose being specified to water or medium, informing the development and undertaking of HS IMRT as part of the HIPPO trial. Advances in knowledge: The potential clinical impact of differences between dose to medium and dose to water are demonstrated for the first time, in the setting of HS whole-brain radiotherapy.

Diversity of Clostridium difficile PCR ribotypes in Europe: results from the European, multicentre, prospective, biannual, point-prevalence study of Clostridium difficile infection in hospitalised patients with diarrhoea (EUCLID), 2012 and 2013.

PubMed

Davies, Kerrie A; Ashwin, Helen; Longshaw, Christopher M; Burns, David A; Davis, Georgina L; Wilcox, Mark H

2016-07-21

Clostridium difficile infection (CDI) is the major cause of infective diarrhoea in healthcare environments. As part of the European, multicentre, prospective, biannual, point-prevalence study of Clostridium difficile infection in hospitalised patients with diarrhoea (EUCLID), the largest C. difficile epidemiological study of its type, PCR ribotype distribution of C. difficile isolates in Europe was investigated. PCR ribotyping was performed on 1,196 C. difficile isolates from diarrhoeal samples sent to the European coordinating laboratory in 2012-13 and 2013 (from two sampling days) by 482 participating hospitals from 19 European countries. A total of 125 ribotypes were identified, of which ribotypes 027 (19%, n =222), 001/072 (11%, n = 134) and 014/020 (10%, n = 119) were the most prevalent. Distinct regional patterns of ribotype distribution were noted. Of 596 isolates from patients with toxin-positive stools (CDI cases), ribotype 027 accounted for 22% (32/144) of infections in cases aged from 18 to less than 65 years, but the prevalence decreased in those aged ≥ 65 years (14% (59/412)) and further decreased in those aged ≥ 81 years (9% (18/195)). The prevalence of ribotype 027 and 176, but not other epidemic strains, was inversely proportional to overall ribotype diversity (R(2) = 0.717). This study highlights an increased diversity of C. difficile ribotypes across Europe compared with previous studies, with considerable intercountry variation in ribotype distribution. Continuous surveillance programmes are necessary to monitor the changing epidemiology of C. difficile. This article is copyright of The Authors, 2016.

Anti-interleukin 6 receptor tocilizumab in refractory uveitis associated with Behçet's disease: multicentre retrospective study.

PubMed

Atienza-Mateo, Belén; Calvo-Río, Vanesa; Beltrán, Emma; Martínez-Costa, Lucía; Valls-Pascual, Elia; Hernández-Garfella, Marisa; Atanes, Antonio; Cordero-Coma, Miguel; Miquel Nolla, Joan; Carrasco-Cubero, Carmen; Loricera, Javier; González-Vela, María C; Vegas-Revenga, Nuria; Fernández-Díaz, Carlos; Demetrio-Pablo, Rosalía; Domínguez-Casas, Lucía C; Luis Martín-Varillas, José; Palmou-Fontana, Natalia; Hernández, José L; González-Gay, Miguel Á; Blanco, Ricardo

2018-05-01

To assess the efficacy of tocilizumab (TCZ) in refractory uveitis of Behçet's disease (BD). Multicentre study of patients with BD-associated uveitis. Patients were refractory to conventional and biologic immunosuppressive drugs. The main outcome measures were intraocular inflammation, macular thickness, visual acuity and corticosteroid-sparing effects. We studied 11 patients (7 men) (20 affected eyes); median age 35 years. Uveitis was bilateral in nine patients. The patterns of ocular involvement were panuveitis (n = 8, with retinal vasculitis in 4), anterior uveitis (n = 2) and posterior uveitis (n = 1). Cystoid macular oedema was present in seven patients. The clinical course was recurrent (n = 7) or chronic (n = 4). Before TCZ, patients had received systemic corticosteroids, conventional immunosuppressants and the following biologic agents: adalimumab (n = 8), infliximab (n = 4), canakimumab (n = 1), golimumab (n = 3), etanercept (n = 1). TCZ was used as monotherapy or combined with conventional immunosuppressants at 8 mg/kg/i.v./4 weeks (n = 10) or 162 mg/s.c./week (n = 1). At TCZ onset the following extraocular manifestations were present: oral and/or genital ulcers (n = 7), arthritis (n = 4), folliculitis/pseudofolliculitis (n = 4), erythema nodosum (n = 2), livedo reticularis (n = 1) and neurological involvement (n = 2). TCZ yielded rapid and maintained improvement in all ocular parameters of the patients, with complete remission in eight of them. However, this was not the case for the extraocular manifestations, since TCZ was only effective in three of them. After a mean (s.d.) follow-up of 9.5 (8.05) months, TCZ was withdrawn in two cases, due to a severe infusion reaction and arthritis impairment, respectively. TCZ could be a therapeutic option in patients with BD and refractory uveitis.

Impact of the Tohoku earthquake and tsunami on pneumonia hospitalisations and mortality among adults in northern Miyagi, Japan: a multicentre observational study.

PubMed

Daito, Hisayoshi; Suzuki, Motoi; Shiihara, Jun; Kilgore, Paul E; Ohtomo, Hitoshi; Morimoto, Konosuke; Ishida, Masayuki; Kamigaki, Taro; Oshitani, Hitoshi; Hashizume, Masahiro; Endo, Wataru; Hagiwara, Koichi; Ariyoshi, Koya; Okinaga, Shoji

2013-06-01

On 11 March 2011, the Tohoku earthquake and tsunami struck off the coast of northeastern Japan. Within 3 weeks, an increased number of pneumonia admissions and deaths occurred in local hospitals. A multicentre survey was conducted at three hospitals in Kesennuma City (population 74 000), northern Miyagi Prefecture. All adults aged ≥18 years hospitalised between March 2010 and June 2011 with community-acquired pneumonia were identified using hospital databases and medical records. Segmented regression analyses were used to quantify changes in the incidence of pneumonia. A total of 550 pneumonia hospitalisations were identified, including 325 during the pre-disaster period and 225 cases during the post-disaster period. The majority (90%) of the post-disaster pneumonia patients were aged ≥65 years, and only eight cases (3.6%) were associated with near-drowning in the tsunami waters. The clinical pattern and causative pathogens were almost identical among the pre-disaster and post-disaster pneumonia patients. A marked increase in the incidence of pneumonia was observed during the 3-month period following the disaster; the weekly incidence rates of pneumonia hospitalisations and pneumonia-associated deaths increased by 5.7 times (95% CI 3.9 to 8.4) and 8.9 times (95% CI 4.4 to 17.8), respectively. The increases were largest among residents in nursing homes followed by those in evacuation shelters. A substantial increase in the pneumonia burden was observed among adults after the Tohoku earthquake and tsunami. Although the exact cause remains unresolved, multiple factors including population aging and stressful living conditions likely contributed to this pneumonia outbreak.

Impact of the Tohoku earthquake and tsunami on pneumonia hospitalisations and mortality among adults in northern Miyagi, Japan: a multicentre observational study

PubMed Central

Daito, Hisayoshi; Suzuki, Motoi; Shiihara, Jun; Kilgore, Paul E; Ohtomo, Hitoshi; Morimoto, Konosuke; Ishida, Masayuki; Kamigaki, Taro; Oshitani, Hitoshi; Hashizume, Masahiro; Endo, Wataru; Hagiwara, Koichi; Ariyoshi, Koya; Okinaga, Shoji

2013-01-01

Background On 11 March 2011, the Tohoku earthquake and tsunami struck off the coast of northeastern Japan. Within 3 weeks, an increased number of pneumonia admissions and deaths occurred in local hospitals. Methods A multicentre survey was conducted at three hospitals in Kesennuma City (population 74 000), northern Miyagi Prefecture. All adults aged ≥18 years hospitalised between March 2010 and June 2011 with community-acquired pneumonia were identified using hospital databases and medical records. Segmented regression analyses were used to quantify changes in the incidence of pneumonia. Results A total of 550 pneumonia hospitalisations were identified, including 325 during the pre-disaster period and 225 cases during the post-disaster period. The majority (90%) of the post-disaster pneumonia patients were aged ≥65 years, and only eight cases (3.6%) were associated with near-drowning in the tsunami waters. The clinical pattern and causative pathogens were almost identical among the pre-disaster and post-disaster pneumonia patients. A marked increase in the incidence of pneumonia was observed during the 3-month period following the disaster; the weekly incidence rates of pneumonia hospitalisations and pneumonia-associated deaths increased by 5.7 times (95% CI 3.9 to 8.4) and 8.9 times (95% CI 4.4 to 17.8), respectively. The increases were largest among residents in nursing homes followed by those in evacuation shelters. Conclusions A substantial increase in the pneumonia burden was observed among adults after the Tohoku earthquake and tsunami. Although the exact cause remains unresolved, multiple factors including population aging and stressful living conditions likely contributed to this pneumonia outbreak. PMID:23422213

Vulvar cancer in Tunisia: Epidemiological and clinicopathological features multicentric study.

PubMed

Kehila, Mehdi; Harabi, Souad; Mhiri, Raoudha; Touhami, Omar; Abouda, Hassine Saber; Khlifi, Abdeljalil; Hsairi, Mohamed; Chelli, Dalenda; Derbel, Mohamed; Kebaili, Sahbi; Boujelbane, Nadia; Chaabene, Kais; Chanoufi, Mohamed Badis

2017-06-01

To describe for the first time the epidemiologic and clinico-pathologic characteristics of vulvar cancer in Tunisia. Two parts are distinguished in this study: Part1: Multicentric retrospective study about the characteristics of all cancer cases diagnosed during a 17-years period (January 1998-December 2014) in three departments of Gynecology and Obstetrics: one in south Tunisia and two in the capital. Part 2: To determine the Incidence trend of invasive vulvar cancer in North Tunisia 1994-2009, on the basis of North Cancer Registry of Tunisia. A total of 76 cases of vulvar cancer were recorded. The median age at diagnosis was 65.4years and 86.9% of patients were more than 55years old. The symptomatology was dominated by vulvar pruritus in 48.7%. The average size of the tumor was 3.96cm. Stage III was the most frequent (53.7%) followed by stage II (28.3%). Only 10.4% of tumors were at stage I. The most common histologic type of vulvar malignancy was squamous cell carcinoma (SCC) (94.7%). Standardized incidence varied from 1.2/100 000 (1994) to 0.5/100 000 (2009). There was significant decrease of Standardized incidence (APC of -8.8% per year, 95% CI: -5.5%, -9.0%-p<0.001). Vulvar cancer in Tunisia is a rare disease, occurs mostly in elderly women, and is diagnosed at advanced stages. Our findings emphasize that a greater effort should be made to facilitate early diagnosis, as treatment in earlier stages is less extensive and potentially curative. Copyright © 2017 National Cancer Institute, Cairo University. Production and hosting by Elsevier B.V. All rights reserved.

Prevalence of obesity in paediatric psoriasis and its impact on disease severity and progression.

PubMed

Ergun, Tulin; Seckin Gencosmanoglu, Dilek; Karakoc-Aydiner, Elif; Salman, Andac; Tekin, Burak; Bulbul-Baskan, Emel; Alpsoy, Erkan; Cakıroglu, Aylin; Onsun, Nahide

2017-11-01

The current literature suggests there is a possible connection between paediatric psoriasis and obesity. However, there is a paucity of research on the influence of increased adiposity on the severity of paediatric psoriasis and disease progression. We aimed to compare the prevalence of being overweight or obese in paediatric psoriasis patients and controls and assess the potential impact of being overweight/obese on disease severity and progression of disease. This multicentre prospective case-control study included 289 psoriasis patients (aged < 18 years) treated and followed up by one of the four university hospitals in Turkey. The control group consisted of 151 consecutive age-matched and sex-matched children who lacked a personal or family history of psoriasis. The participants' characteristics, psoriasis-related parametres (e.g., initial subtype, psoriasis area and severity index, presence of psoriatic arthritis) and body mass index were determined. The difference between the prevalence of being overweight/obese among psoriatics (28%) and the control group (19%) was significant (P = 0.024). Being overweight/obese had no significant impact on disease severity and unresponsiveness to topical treatment. Within a median follow-up time of 12 months, 23% of our patients with localised disease at disease onset progressed to generalised disease. The impact of being overweight/obese on disease progression was found to be non-significant; however, disease duration was found to have a significant impact on disease progression (P = 0.026). Although it is not associated with disease severity and course, increased bodyweight may be a health problem for psoriatic children. © 2016 The Australasian College of Dermatologists.

The pre-mir-27a variant rs895819 may contribute to type 2 diabetes mellitus susceptibility in an Iranian cohort.

PubMed

Ghaedi, H; Tabasinezhad, M; Alipoor, B; Shokri, F; Movafagh, A; Mirfakhraie, R; Omrani, M D; Masotti, A

2016-10-01

The study was aimed at investigating the association between hsa-mir-27a polymorphism rs895819 (T/C) and type 2 diabetes mellitus (T2DM) susceptibility in a large Iranian cohort. In this case-control study, the investigated population consisted of T2DM patients (n = 204) and sex- and age-matched controls (n = 209). We used the polymerase chain reaction and restriction fragment length polymorphism (PCR-RFLP) for genotyping. We observed significant differences between T2DM patients and controls for weight (p = 0.002), BMI (p < 0.001), systolic blood pressure (p < 0.001), diastolic blood pressure (p < 0.001), fasting plasma glucose (p < 0.001), triglyceride (p = 0.004) and LDL cholesterol (p = 0.051). Moreover, we found that genotype distributions were significantly different between groups (p < 0.05) and that the rs895819-C allele is more frequent in controls (p = 0.030, OR = 0.72, 95 % CI 0.53-0.97). Our study shows that rs895819 in hsa-mir-27a is associated with T2DM susceptibility and that the C allele conveyed a protective role against T2DM. Larger multicentric and specific functional studies will be necessary to obtain a deeper comprehension of the role of rs895819 and hsa-mir-27a and how they are involved in the development of diabetes.

Does Quality of Radiotherapy Predict Outcomes of Multicentre Cooperative Group Trials? A Literature Review

PubMed Central

Fairchild, Alysa; Straube, William; Laurie, Fran; Followill, David

2013-01-01

Central review of radiotherapy (RT) delivery within multicentre clinical trials was initiated in the early 1970’s in the USA. Early quality assurance (QA) publications often focused on metrics related to process, logistics and timing. Our objective was to review the available evidence supporting correlation of RT quality with clinical outcomes within cooperative group trials. Medline search was performed to identify multicentre studies which described central subjective assessment of RT protocol compliance (quality). Data abstracted included method of central review, definition of deviations, and clinical outcomes. Seventeen multicentre studies (1980–2012) were identified, plus one Patterns of Care Study. Disease sites were hematologic, head and neck, lung, breast and pancreas. Between 0% and 97% of treatment plans received an overall grade of acceptable. In seven trials, failure rates were significantly higher after inadequate versus adequate RT. 5/9 and 2/5 trials reported significantly worse overall and progression-free survival after poor quality RT, respectively. One reported a significant correlation and two reported non-significant trends towards increased toxicity with non-compliant RT. Although more data are required, protocol-compliant RT may decrease failure rates and increase overall survival and likely contributes to the ability of collected data to answer the central trial question. PMID:23683829

Granulocyte-macrophage colony stimulating factor administered as prophylaxis for reduction of sepsis in extremely preterm, small for gestational age neonates (the PROGRAMS trial): a single-blind, multicentre, randomised controlled trial.

PubMed

Carr, Robert; Brocklehurst, Peter; Doré, Caroline J; Modi, Neena

2009-01-17

Systemic sepsis is a major cause of death in preterm neonates. There are compelling theoretical reasons why treatment with haemopoietic colony-stimulating factors might reduce sepsis and improve outcomes, and as a consequence these agents have entered into use in neonatal medicine without adequate evidence. We assessed whether granulocyte-macrophage colony stimulating factor (GM-CSF) administered as prophylaxis to preterm neonates at high risk of neutropenia would reduce sepsis, mortality, and morbidity. We undertook a single-blind, multicentre, randomised controlled trial in 26 centres between June, 2000, and June, 2006. 280 neonates of below or equal to 31 weeks' gestation and below the 10th centile for birthweight were randomised within 72 h of birth to receive GM-CSF 10 microg/kg per day subcutaneously for 5 days or standard management. From recruitment to day 28 a detailed daily clinical record form was completed by the treating clinicians. Primary outcome was sepsis-free survival to 14 days from trial entry. Analysis was by intention to treat. This study is registered as an International Standard Randomised Controlled Trial, number ISRCTN42553489. Neutrophil counts after trial entry rose significantly more rapidly in infants treated with GM-CSF than in control infants during the first 11 days (difference between neutrophil count slopes 0.34 x 10(9)/L/day; 95% CI 0.12-0.56). There was no significant difference in sepsis-free survival for all infants (93 of 139 treated infants, 105 of 141 control infants; difference -8%, 95% CI -18 to 3). A meta-analysis of this trial and previous published prophylactic trials showed no survival benefit. Early postnatal prophylactic GM-CSF corrects neutropenia but does not reduce sepsis or improve survival and short-term outcomes in extremely preterm neonates.

Patient-specific rehearsal prior to EVAR: a pilot study.

PubMed

Desender, L; Rancic, Z; Aggarwal, R; Duchateau, J; Glenck, M; Lachat, M; Vermassen, F; Van Herzeele, I

2013-06-01

This study aims to evaluate feasibility, face validity, influence on technical factors and subjective sense of utility of patient-specific rehearsal (PsR) prior to endovascular aortic aneurysm repair (EVAR). A prospective, multicentre pilot study. Patients suitable for EVAR were enrolled and a three-dimensional (3D) model of the patient's anatomy was generated. Less than 24 h prior to the real case, rehearsals were conducted in the laboratory or clinical angiosuite. Technical metrics were recorded during both procedures. A subjective questionnaire was used to evaluate realism, technical and human factor aspects (scale 1-5). Ten patients were enrolled. In one case, the treatment plan was altered based on PsR. In 7/9 patients, the rehearsal significantly altered the optimal C-arm position for the proximal landing zone and an identical fluoroscopy angle was chosen in the real procedure. All team members found the rehearsal useful for selecting the optimal fluoroscopy angle (median 4). The realism of the EVAR procedure simulation was rated highly (median 4). All team members found the PsR useful to prepare the individual team members and the entire team (median 4). PsR for EVAR permits creation of realistic case studies. Subjective evaluation indicates that it may influence optimal C-arm angles and be valuable to prepare the entire team. A randomised controlled trial (RCT) is planned to evaluate how this technology may influence technical and team performance, ultimately leading to improved patient safety. Copyright © 2013 European Society for Vascular Surgery. Published by Elsevier Ltd. All rights reserved.

Alarm Variables for Dengue Outbreaks: A Multi-Centre Study in Asia and Latin America

PubMed Central

Bowman, Leigh R.; Tejeda, Gustavo S.; Coelho, Giovanini E.; Sulaiman, Lokman H.; Gill, Balvinder S.; McCall, Philip J.; Olliaro, Piero L.; Ranzinger, Silvia R.; Quang, Luong C.; Ramm, Ronald S.; Kroeger, Axel; Petzold, Max G.

2016-01-01

Background Worldwide, dengue is an unrelenting economic and health burden. Dengue outbreaks have become increasingly common, which place great strain on health infrastructure and services. Early warning models could allow health systems and vector control programmes to respond more cost-effectively and efficiently. Methodology/Principal Findings The Shewhart method and Endemic Channel were used to identify alarm variables that may predict dengue outbreaks. Five country datasets were compiled by epidemiological week over the years 2007–2013. These data were split between the years 2007–2011 (historic period) and 2012–2013 (evaluation period). Associations between alarm/ outbreak variables were analysed using logistic regression during the historic period while alarm and outbreak signals were captured during the evaluation period. These signals were combined to form alarm/ outbreak periods, where 2 signals were equal to 1 period. Alarm periods were quantified and used to predict subsequent outbreak periods. Across Mexico and Dominican Republic, an increase in probable cases predicted outbreaks of hospitalised cases with sensitivities and positive predictive values (PPV) of 93%/ 83% and 97%/ 86% respectively, at a lag of 1–12 weeks. An increase in mean temperature ably predicted outbreaks of hospitalised cases in Mexico and Brazil, with sensitivities and PPVs of 79%/ 73% and 81%/ 46% respectively, also at a lag of 1–12 weeks. Mean age was predictive of hospitalised cases at sensitivities and PPVs of 72%/ 74% and 96%/ 45% in Mexico and Malaysia respectively, at a lag of 4–16 weeks. Conclusions/Significance An increase in probable cases was predictive of outbreaks, while meteorological variables, particularly mean temperature, demonstrated predictive potential in some countries, but not all. While it is difficult to define uniform variables applicable in every country context, the use of probable cases and meteorological variables in tailored early warning systems could be used to highlight the occurrence of dengue outbreaks or indicate increased risk of dengue transmission. PMID:27348752

Effect of endoscopic transpapillary biliary drainage with/without endoscopic sphincterotomy on post-endoscopic retrograde cholangiopancreatography pancreatitis in patients with biliary stricture (E-BEST): a protocol for a multicentre randomised controlled trial

PubMed Central

Kato, Shin; Kuwatani, Masaki; Sugiura, Ryo; Sano, Itsuki; Kawakubo, Kazumichi; Ono, Kota; Sakamoto, Naoya

2017-01-01

Introduction The effect of endoscopic sphincterotomy prior to endoscopic biliary stenting to prevent post-endoscopic retrograde cholangiopancreatography pancreatitis remains to be fully elucidated. The aim of this study is to prospectively evaluate the non-inferiority of non-endoscopic sphincterotomy prior to stenting for naïve major duodenal papilla compared with endoscopic sphincterotomy prior to stenting in patients with biliary stricture. Methods and analysis We designed a multicentre randomised controlled trial, for which we will recruit 370 patients with biliary stricture requiring endoscopic biliary stenting from 26 high-volume institutions in Japan. Patients will be randomly allocated to the endoscopic sphincterotomy group or the non-endoscopic sphincterotomy group. The main outcome measure is the incidence of pancreatitis within 2 days of initial transpapillary biliary drainage. Data will be analysed on completion of the study. We will calculate the 95% confidence intervals (CIs) of the incidence of pancreatitis in each group and analyse weather the difference in both groups with 95% CIs is within the non-inferiority margin (6%) using the Wald method. Ethics and dissemination This study has been approved by the institutional review board of Hokkaido University Hospital (IRB: 016–0181). Results will be submitted for presentation at an international medical conference and published in a peer-reviewed journal. Trial registration number The University Hospital Medical Information Network ID: UMIN000025727 Pre-results. PMID:28801436

A randomised trial of high and low pressure level settings on an adjustable ventriculoperitoneal shunt valve for idiopathic normal pressure hydrocephalus: results of the Dutch evaluation programme Strata shunt (DEPSS) trial.

PubMed

Delwel, Ernst J; de Jong, Dirk A; Dammers, Ruben; Kurt, Erkan; van den Brink, Wimar; Dirven, Clemens M F

2013-07-01

In treating idiopathic normal pressure hydrocephalus (INPH) with a shunt there is always a risk of underdrainage or overdrainage. The hypothesis is tested whether patients treated using an adjustable valve preset at the highest opening pressure leads to comparable good clinical results with less subdural effusions than in a control group with an opening pressure preset at a low pressure level. A multicentre prospective randomised trial was performed on a total of 58 patients suspected of INPH. Thirty patients were assigned to (control) group 1 and received a Strata shunt (Medtronic, Goleta, USA) with the valve preset at a performance level (PL) of 1.0, while 28 patients were assigned to group 2 and received a Strata shunt with the valve preset at PL 2.5. In this group the PL was allowed to be lowered until improvement or radiological signs of overdrainage were met. Significantly more subdural effusions were observed in the improved patients of group 1. There was no statistically significant difference in improvement between both groups overall. On the basis of this multicentre prospective randomised trial it is to be recommended to treat patients with INPH with a shunt with an adjustable valve, preset at the highest opening pressure and lowered until clinical improvement or radiological signs of overdrainage occur although slower improvement and more shunt adjustments might be the consequence.

Lack of efficacy of a reduced microparticle diet in a multi-centred trial of patients with active Crohn's disease.

PubMed

Lomer, Miranda C E; Grainger, Stephen L; Ede, Roland; Catterall, Adrian P; Greenfield, Simon M; Cowan, Russell E; Vicary, F Robin; Jenkins, Anthony P; Fidler, Helen; Harvey, Rory S; Ellis, Richard; McNair, Alistair; Ainley, Colin C; Thompson, Richard P H; Powell, Jonathan J

2005-03-01

Dietary microparticles, which are bacteria-sized and non-biological, found in the modern Western diet, have been implicated in both the aetiology and pathogenesis of Crohn's disease. Following on from the findings of a previous pilot study, we aimed to confirm whether a reduction in the amount of dietary microparticles facilitates induction of remission in patients with active Crohn's disease, in a single-blind, randomized, multi-centre, placebo controlled trial. Eighty-three patients with active Crohn's disease were randomly allocated in a 2 x 2 factorial design to a diet low or normal in microparticles and/or calcium for 16 weeks. All patients received a reducing dose of prednisolone for 6 weeks. Outcome measures were Crohn's disease activity index, Van Hees index, quality of life and a series of objective measures of inflammation including erythrocyte sedimentation rate, C-reactive protein, intestinal permeability and faecal calprotectin. After 16 weeks patients returned to their normal diet and were followed up for a further 36 weeks. Dietary manipulation provided no added effect to corticosteroid treatment on any of the outcome measures during the dietary trial (16 weeks) or follow-up (to 1 year); e.g., for logistic regression of Crohn's disease activity index based rates of remission (P=0.1) and clinical response (P=0.8), in normal versus low microparticle groups. Our adequately powered and carefully controlled dietary trial found no evidence that reducing microparticle intake aids remission in active Crohn's disease.

[The discharge form: advantages and limits legionellosis cases individuation].

PubMed

Trerotoli, P; Montagna, M T; Borella, P; Romano Spica, V; Stancanelli, G; Triassi, M; Serio, G; Napoli, C; Soldano, S; Tatò, D; Vercilli, F; Gentile, C; Quaranta, G; Volpe, M; Ambrosio, A; Santarpia, R; Montegrosso, S

2003-01-01

Despite legionellosis surveillance is active in Italy since many years, the disease notification appears still undervalued. A multicentric survey was carried out among 5 big Italian hospitals. It examined 11,435 discharge forms (1999-2001), reporting pneumonia diagnosis. Legionellosis (II class of notify system for infectious disease) was studied among pneumonia diagnosis by discharge forms. According to the ICD9-CM, there's no specific code for legionellosis (this disease is included among "others gram-negative pneumonia"). So the presumed pneumonia imputable to Legionella spp were the 2.7% of the whole number of analyzed discharge forms. Besides, the data regarding the other pneumonia showed that the etiological agent was specified only in the 11.2% of the case. This situation could be rectified both introducing adequate discharge forms codes and promoting the etiological diagnosis during the hospital stay.

[Estimation of the population attributable fraction due to obesity in hospital admissions for flu valued according to Body Mass Index (BMI) and CUN-BAE].

PubMed

Dávila-Batista, V; Carriedo, D; Díez, F; Pueyo Bastida, A; Martínez Durán, B; Martin, V

2018-03-01

The obesity pandemic together with the influenza pandemic could lead to a significant burden of disease. The body mass index (BMI) does not discriminate obesity appropriately. The CUN-BAE has recently been used as an estimate of body fatness for Caucasians, including BMI, gender, and age. The aim of this study is to assess the population attributable fraction of hospital admissions due to influenza, due to the body fatness measured with the BMI, and the CUN-BAE. A multicentre study was conducted using matched case-controls. Cases were hospital admissions with the influenza confirmed by the RT-PCR method between 2009 and 2011. The risk of hospital admission and the population attribuible fraction were calculated using the BMI or the CUN-BAE for each adiposity category in a conditional logical regression analysis adjusted for confounding variables. The analyzes were estimated in the total sample, in unvaccinated people, and those less than 65 years-old. A total of 472 hospitalised cases and 493 controls were included in the study. Compared to normal weight, the aOR of influenza hospital admissions increases with each level of BMI (aOR=1.26; 2.06 and 11.64) and CUN-BAE (aOR=2.78; 4.29; 5.43 and 15.18). The population attributable fraction of influenza admissions using CUN-BAE is 3 times higher than that estimated with BMI (0,72 vs. 0,27), with the differences found being similar the non-vaccinated and under 65 year-olds. The BMI could be underestimating the burden of disease attributable to obesity in individuals hospitalised with influenza. There needs to be an appropriate assessment of the impact of obesity and vaccine recommendation criteria. Copyright © 2017 Sociedad Española de Médicos de Atención Primaria (SEMERGEN). Publicado por Elsevier España, S.L.U. All rights reserved.

Factors associated with coronary artery disease and stroke in adults with congenital heart disease.

PubMed

Bokma, Jouke P; Zegstroo, Ineke; Kuijpers, Joey M; Konings, Thelma C; van Kimmenade, Roland R J; van Melle, Joost P; Kiès, Philippine; Mulder, Barbara J M; Bouma, Berto J

2018-04-01

To determine factors associated with coronary artery disease (CAD) and ischaemic stroke in ageing adult congenital heart disease (ACHD) patients. We performed a multicentre case-control study, using data from the national CONgenital CORvitia (CONCOR) registry to identify ACHD patients within five participating centres. Patients with CAD were matched (1:2 ratio) with ACHD patients without CAD on age, CHD defect group and gender. Patients with ischaemic stroke (or transient ischaemic attack) were matched similarly. Medical charts were reviewed and a standardised questionnaire was used to determine presence of risk factors. Of 6904 ACHD patients, a total of 55 cases with CAD (80% male, mean age 55.1±12.4 years) and 56 cases with stroke (46% male, mean age 46.9±15.2) were included and matched with control patients. In multivariable logistic regression analysis, traditional atherosclerotic risk factors (hypertension (OR 2.45; 95% CI 1.15 to 5.23), hypercholesterolaemia (OR 3.99; 95% CI 1.62 to 9.83) and smoking (OR 2.25; 95% CI 1.09 to 4.66)) were associated with CAD. In contrast, these risk factors were not associated with ischaemic stroke. In multivariable analysis, stroke was associated with previous shunt operations (OR 4.20; 95% CI 1.36 to 12.9), residual/unclosed septal defects (OR 2.38; 95% CI 1.03 to 5.51) and left-sided mechanical valves (OR 2.67; 95% CI 1.09 to 6.50). Traditional atherosclerotic risk factors were associated with CAD in ACHD patients. In contrast, ischaemic stroke was related to factors (previous shunts, septal defects, mechanical valves) suggesting a cardioembolic aetiology. These findings may inform surveillance and prevention strategies. © 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.

Routine versus on demand removal of the syndesmotic screw; a protocol for an international randomised controlled trial (RODEO-trial).

PubMed

Dingemans, S A; Birnie, M F N; Sanders, F R K; van den Bekerom, M P J; Backes, M; van Beeck, E; Bloemers, F W; van Dijkman, B; Flikweert, E; Haverkamp, D; Holtslag, H R; Hoogendoorn, J M; Joosse, P; Parkkinen, M; Roukema, G; Sosef, N; Twigt, B A; van Veen, R N; van der Veen, A H; Vermeulen, J; Winkelhagen, J; van der Zwaard, B C; van Dieren, S; Goslings, J C; Schepers, T

2018-01-31

Syndesmotic injuries are common and their incidence is rising. In case of surgical fixation of the syndesmosis a metal syndesmotic screw is used most often. It is however unclear whether this screw needs to be removed routinely after the syndesmosis has healed. Traditionally the screw is removed after six to 12 weeks as it is thought to hamper ankle functional and to be a source of pain. Some studies however suggest this is only the case in a minority of patients. We therefore aim to investigate the effect of retaining the syndesmotic screw on functional outcome. This is a pragmatic international multicentre randomised controlled trial in patients with an acute syndesmotic injury for which a metallic syndesmotic screw was placed. Patients will be randomised to either routine removal of the syndesmotic screw or removal on demand. Primary outcome is functional recovery at 12 months measured with the Olerud-Molander Score. Secondary outcomes are quality of life, pain and costs. In total 194 patients will be needed to demonstrate non-inferiority between the two interventions at 80% power and a significance level of 0.025 including 15% loss to follow-up. If removal on demand of the syndesmotic screw is non-inferior to routine removal in terms of functional outcome, this will offer a strong argument to adopt this as standard practice of care. This means that patients will not have to undergo a secondary procedure, leading to less complications and subsequent lower costs. This study was registered at the Netherlands Trial Register (NTR5965), Clinicaltrials.gov ( NCT02896998 ) on July 15th 2016.

Prevention of preterm delivery with vaginal progesterone in women with preterm labour (4P): randomised double-blind placebo-controlled trial.

PubMed

Martinez de Tejada, B; Karolinski, A; Ocampo, M C; Laterra, C; Hösli, I; Fernández, D; Surbek, D; Huespe, M; Drack, G; Bunader, A; Rouillier, S; López de Degani, G; Seidenstein, E; Prentl, E; Antón, J; Krähenmann, F; Nowacki, D; Poncelas, M; Nassif, J C; Papera, R; Tuma, C; Espoile, R; Tiberio, O; Breccia, G; Messina, A; Peker, B; Schinner, E; Mol, B W; Kanterewicz, L; Wainer, V; Boulvain, M; Othenin-Girard, V; Bertolino, M V; Irion, O

2015-01-01

To evaluate the effectiveness of 200 mg of daily vaginal natural progesterone to prevent preterm birth in women with preterm labour. Multicentre, randomised, double-blind, placebo-controlled trial. Twenty-nine centres in Switzerland and Argentina. A total of 385 women with preterm labour (24(0/7) to 33(6/7) weeks of gestation) treated with acute tocolysis. Participants were randomly allocated to either 200 mg daily of self-administered vaginal progesterone or placebo within 48 hours of starting acute tocolysis. Primary outcome was delivery before 37 weeks of gestation. Secondary outcomes were delivery before 32 and 34 weeks, adverse effects, duration of tocolysis, re-admissions for preterm labour, length of hospital stay, and neonatal morbidity and mortality. The study was ended prematurely based on results of the intermediate analysis. Preterm birth occurred in 42.5% of women in the progesterone group versus 35.5% in the placebo group (relative risk [RR] 1.2; 95% confidence interval [95% CI] 0.93-1.5). Delivery at <32 and <34 weeks did not differ between the two groups (12.9 versus 9.7%; [RR 1.3; 95% CI 0.7-2.5] and 19.7 versus 12.9% [RR 1.5; 95% CI 0.9-2.4], respectively). The duration of tocolysis, hospitalisation, and recurrence of preterm labour were comparable between groups. Neonatal morbidity occurred in 44 (22.8%) cases on progesterone versus 35 (18.8%) cases on placebo (RR: 1.2; 95% CI 0.82-1.8), whereas there were 4 (2%) neonatal deaths in each study group. There is no evidence that the daily administration of 200 mg vaginal progesterone decreases preterm birth or improves neonatal outcome in women with preterm labour. © 2014 Royal College of Obstetricians and Gynaecologists.

Genome-wide association study of sporadic brain arteriovenous malformations.

PubMed

Weinsheimer, Shantel; Bendjilali, Nasrine; Nelson, Jeffrey; Guo, Diana E; Zaroff, Jonathan G; Sidney, Stephen; McCulloch, Charles E; Al-Shahi Salman, Rustam; Berg, Jonathan N; Koeleman, Bobby P C; Simon, Matthias; Bostroem, Azize; Fontanella, Marco; Sturiale, Carmelo L; Pola, Roberto; Puca, Alfredo; Lawton, Michael T; Young, William L; Pawlikowska, Ludmila; Klijn, Catharina J M; Kim, Helen

2016-09-01

The pathogenesis of sporadic brain arteriovenous malformations (BAVMs) remains unknown, but studies suggest a genetic component. We estimated the heritability of sporadic BAVM and performed a genome-wide association study (GWAS) to investigate association of common single nucleotide polymorphisms (SNPs) with risk of sporadic BAVM in the international, multicentre Genetics of Arteriovenous Malformation (GEN-AVM) consortium. The Caucasian discovery cohort included 515 BAVM cases and 1191 controls genotyped using Affymetrix genome-wide SNP arrays. Genotype data were imputed to 1000 Genomes Project data, and well-imputed SNPs (>0.01 minor allele frequency) were analysed for association with BAVM. 57 top BAVM-associated SNPs (51 SNPs with p<10(-05) or p<10(-04) in candidate pathway genes, and 6 candidate BAVM SNPs) were tested in a replication cohort including 608 BAVM cases and 744 controls. The estimated heritability of BAVM was 17.6% (SE 8.9%, age and sex-adjusted p=0.015). None of the SNPs were significantly associated with BAVM in the replication cohort after correction for multiple testing. 6 SNPs had a nominal p<0.1 in the replication cohort and map to introns in EGFEM1P, SP4 and CDKAL1 or near JAG1 and BNC2. Of the 6 candidate SNPs, 2 in ACVRL1 and MMP3 had a nominal p<0.05 in the replication cohort. We performed the first GWAS of sporadic BAVM in the largest BAVM cohort assembled to date. No GWAS SNPs were replicated, suggesting that common SNPs do not contribute strongly to BAVM susceptibility. However, heritability estimates suggest a modest but significant genetic contribution. 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/

Endocarditis in patients with ascending aortic prosthetic graft: a case series from a national multicentre registry.

PubMed

Ramos, Antonio; García-Montero, Carlos; Moreno, Alfonso; Muñoz, Patricia; Ruiz-Morales, Josefa; Sánchez-Espín, Gemma; Porras, Carlos; Sousa, Dolores; Castelo, Laura; Del Carmen Fariñas, María; Gutiérrez, Francisco; Reguera, José María; Plata, Antonio; Bouza, Emilio; Antorrena, Isabel; de Alarcón, Arístides; Pericás, José Manuel; Gurguí, Mercedes; Rodríguez-Abella, Hugo; Ángel Goenaga, Miguel; Antonio Oteo, José; García-Pavía, Pablo

2016-12-01

Endocarditis in patients with ascending aortic prosthetic graft (AAPG) is a life-threatening complication. The purpose of this study was to examine the clinical presentation and prognosis of patients with AAPG endocarditis included in a large prospective infectious endocarditis multicentre study. From January 2008 to April 2015, 3200 consecutive patients with infectious endocarditis according to the modified Duke criteria, were prospectively included in the 'Spanish Collaboration on Endocarditis Registry (GAMES)' registry. Twenty-seven definite episodes of endocarditis (0.8%) occurred in patients with AAPG. During the study period, 27 cases of endocarditis were detected in patients with AAPG. The median age of patients was 61 years [interquartile range (IQR) 51-68 years] and 23 (85.2%) patients were male. The median time from AAPG surgery to the episode of AAPG infection was 24 months (IQR 6-108 months). The most frequently isolated micro-organisms were coagulase-negative staphylococci and S. aureus (11 patients, 40.7%). Four patients (14.8%) underwent medical treatment, whereas surgery was performed in 21 (77.7%). Two patients (7.4%) died before surgery could be performed. The median hospital stay prior to surgery was 7 days (IQR 4-21 days). Surgery consisted of replacing previous grafts with a composite aortic graft (10 cases) or aortic homograft (2 patients), and removal of a large vegetation attached to the valve of a composite tube (1 case). Nine patients had an infected aortic valve prosthesis without evidence of involvement of the AAPG. Isolated redo-aortic valve replacement was performed in 8 (88.9%) of these patients. Reinfection occurring during 1 year of follow-up was not detected in any patient. Two patients (7.4%) died while awaiting surgery and 6 did so after surgery (22.2%). A New York Heart Association (NYHA) Class IV was associated with mortality in patients undergoing surgery (P < 0.019). Most cases of endocarditis in patients with AAPG occur late after initial surgery. Mortality rate of patients with AAPG endocarditis who undergo surgery is acceptable. NYHA Class IV before surgery is associated with an increased postoperative mortality. © The Author 2016. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.

Study protocol. IDUS - Instrumental delivery & ultrasound: a multi-centre randomised controlled trial of ultrasound assessment of the fetal head position versus standard care as an approach to prevent morbidity at instrumental delivery.

PubMed

Murphy, Deirdre J; Burke, Gerard; Montgomery, Alan A; Ramphul, Meenakshi

2012-09-13

Instrumental deliveries are commonly performed in the United Kingdom and Ireland, with rates of 12 - 17% in most centres. Knowing the exact position of the fetal head is a pre-requisite for safe instrumental delivery. Traditionally, diagnosis of the fetal head position is made on transvaginal digital examination by delineating the suture lines of the fetal skull and the fontanelles. However, the accuracy of transvaginal digital examination can be unreliable and varies between 20% and 75%. Failure to identify the correct fetal head position increases the likelihood of failed instrumental delivery with the additional morbidity of sequential use of instruments or second stage caesarean section. The use of ultrasound in determining the position of the fetal head has been explored but is not part of routine clinical practice. A multi-centre randomised controlled trial is proposed. The study will take place in two large maternity units in Ireland with a combined annual birth rate of 13,500 deliveries. It will involve 450 nulliparous women undergoing instrumental delivery after 37 weeks gestation. The main outcome measure will be incorrect diagnosis of the fetal head position. A study involving 450 women will have 80% power to detect a 10% difference in the incidence of inaccurate diagnosis of the fetal head position with two-sided 5% alpha. It is both important and timely to evaluate the use of ultrasound to diagnose the fetal head position prior to instrumental delivery before routine use can be advocated. The overall aim is to reduce the incidence of incorrect diagnosis of the fetal head position prior to instrumental delivery and improve the safety of instrumental deliveries. Current Controlled Trials ISRCTN72230496.

General anaesthesia versus local anaesthesia for carotid surgery (GALA): a multicentre, randomised controlled trial.

PubMed

Lewis, S C; Warlow, C P; Bodenham, A R; Colam, B; Rothwell, P M; Torgerson, D; Dellagrammaticas, D; Horrocks, M; Liapis, C; Banning, A P; Gough, M; Gough, M J

2008-12-20

The effect of carotid endarterectomy in lowering the risk of stroke ipsilateral to severe atherosclerotic carotid-artery stenosis is offset by complications during or soon after surgery. We compared surgery under general anaesthesia with that under local anaesthesia because prediction and avoidance of perioperative strokes might be easier under local anaesthesia than under general anaesthesia. We undertook a parallel group, multicentre, randomised controlled trial of 3526 patients with symptomatic or asymptomatic carotid stenosis from 95 centres in 24 countries. Participants were randomly assigned to surgery under general (n=1753) or local (n=1773) anaesthesia between June, 1999 and October, 2007. The primary outcome was the proportion of patients with stroke (including retinal infarction), myocardial infarction, or death between randomisation and 30 days after surgery. Analysis was by intention to treat. The trial is registered with Current Control Trials number ISRCTN00525237. A primary outcome occurred in 84 (4.8%) patients assigned to surgery under general anaesthesia and 80 (4.5%) of those assigned to surgery under local anaesthesia; three events per 1000 treated were prevented with local anaesthesia (95% CI -11 to 17; risk ratio [RR] 0.94 [95% CI 0.70 to 1.27]). The two groups did not significantly differ for quality of life, length of hospital stay, or the primary outcome in the prespecified subgroups of age, contralateral carotid occlusion, and baseline surgical risk. We have not shown a definite difference in outcomes between general and local anaesthesia for carotid surgery. The anaesthetist and surgeon, in consultation with the patient, should decide which anaesthetic technique to use on an individual basis. The Health Foundation (UK) and European Society of Vascular Surgery.

A phase III, multi-centre, double-masked randomised controlled trial of adjunctive intraocular and peri-ocular steroid (triamcinolone acetonide) versus standard treatment in eyes undergoing vitreoretinal surgery for open globe trauma (ASCOT): statistical analysis plan.

PubMed

Lo, Jessica W; Bunce, Catey; Charteris, David; Banerjee, Philip; Phillips, Rachel; Cornelius, Victoria R

2016-08-02

Open globe ocular trauma complicated by intraocular scarring (proliferative vitreoretinopathy) is a relatively rare, blinding, but potentially treatable condition for which, at present, surgery is often unsatisfactory and visual results frequently poor. To date, no pharmacological adjuncts to surgery have been proven to be effective. The aim of the Adjunctive Steroid Combination in Ocular Trauma (ASCOT) randomised controlled trial is to determine whether adjunctive steroid (triamcinolone acetonide), given at the time of surgery, can improve the outcome of vitreoretinal surgery in patients with open globe ocular trauma. This article presents the statistical analysis plan for the main publication as approved and signed off by the Trial Steering Committee prior to the first data extraction for the Data Monitoring Committee meeting report. ASCOT is a pragmatic, multi-centre, parallel-group, double-masked randomised controlled trial. The aim of the study is to recruit from 20-25 centres in the United Kingdom and randomise 300 eyes (from 300 patients) into two treatment arms. Both groups will receive standard surgical treatment and care; the intervention arm will additionally receive a pre-operative steroid combination (triamcinolone acetonide) into the vitreous cavity consisting of 4 mg/0.1 ml and 40 mg/1 ml sub-Tenon's. Participants will be followed for 6 months post-surgery. The primary outcome is the proportion of patients achieving a clinically meaning improvement in visual acuity in the study eye at 6 months after initial surgery, defined as a 10 letter score improvement in the ETDRS (the standard scale to test visual acuity). ISRCTN30012492 . Registered on 5 September 2014. EudraCT2014-002193-37 . Registered on 5 September 2014.

A phase 2, open-label, multicenter study of the long-term safety of siltuximab (an anti-interleukin-6 monoclonal antibody) in patients with multicentric Castleman disease.

PubMed

van Rhee, Frits; Casper, Corey; Voorhees, Peter M; Fayad, Luis E; van de Velde, Helgi; Vermeulen, Jessica; Qin, Xiang; Qi, Ming; Tromp, Brenda; Kurzrock, Razelle

2015-10-06

Multicentric Castleman disease (MCD) is a rare, systemic lymphoproliferative disorder driven by interleukin (IL)-6 overproduction. Siltuximab, an anti-IL-6 monoclonal antibody, has demonstrated durable tumor and symptomatic responses in a multinational, randomized, placebo-controlled study of MCD. This preplanned safety analysis was conducted to evaluate the long-term safety of siltuximab treatment among 19 patients with MCD who had stable disease or better and were enrolled in a phase-1 study and subsequent ongoing, open-label, phase-2 extension study. Dosing was 11 mg/kg administered intravenously every 3 weeks, per protocol, or every 6 weeks at the investigator's discretion. Safety monitoring focused on potential risks associated with the anti-IL-6 mechanism of action. Investigator-assessed disease control status was also documented. Median treatment duration for the 19 patients was 5.1 (range 3.4, 7.2) years, with 14 (74%) patients treated for >4 years. Grade-≥ 3 adverse events (AEs) reported in >1 patient included hypertension (n = 3) and nausea, cellulitis, and fatigue (n = 2 each). Grade-≥ 3 AEs at least possibly attributed to siltuximab were leukopenia, lymphopenia, and a serious AE of polycythemia (n = 1 each). Hypertriglyceridemia and hypercholesterolemia (total cholesterol) were reported in 8 and 9 patients, respectively. No disease relapses were observed, and 8 of 19 patients were able to switch to an every-6-week dosing schedule. All MCD patients in this extension study have received siltuximab for a prolonged duration (up to 7 years) without evidence of cumulative toxicity or treatment discontinuations and with few serious infections. All patients are alive, demonstrate sustained disease control, and continue to receive siltuximab.

Guided Internet-based versus face-to-face clinical care in the management of tinnitus: study protocol for a multi-centre randomised controlled trial.

PubMed

Beukes, Eldré W; Baguley, David M; Allen, Peter M; Manchaiah, Vinaya; Andersson, Gerhard

2017-04-21

Innovative strategies are required to improve access to evidence-based tinnitus interventions. A guided Internet-based cognitive behavioural therapy (iCBT) intervention for tinnitus was therefore developed for a U.K. Initial clinical trials indicated efficacy of iCBT at reducing tinnitus severity and associated comorbidities such as insomnia and depression. The aim of this phase III randomised controlled trial is to compare this new iCBT intervention with an established intervention, namely face-to-face clinical care for tinnitus. This will be a multi-centre study undertaken across three hospitals in the East of England. The design is a randomised, two-arm, parallel-group, non-inferiority trial with a 2-month follow-up. The experimental group will receive the guided iCBT intervention, whereas the active control group will receive the usual face-to-face clinical care. An independent researcher will randomly assign participants, using a computer-generated randomisation schedule, after stratification for tinnitus severity. There will be 46 participants in each group. The primary assessment measure will be the Tinnitus Functional Index. Data analysis will establish whether non-inferiority is achieved using a pre-defined non-inferiority margin. This protocol outlines phase III of a clinical trial comparing a new iCBT with established face-to-face care for tinnitus. If guided iCBT for tinnitus proves to be as effective as the usual tinnitus care, it may be a viable additional management route for individuals with tinnitus. This could increase access to evidence-based effective tinnitus care and reduce the pressures on existing health care systems. ClinicalTrials.gov identifier: NCT02665975 . Registered on 22 January 2016.

The nutrition-based comprehensive intervention study on childhood obesity in China (NISCOC): a randomised cluster controlled trial.

PubMed

Li, Yanping; Hu, Xiaoqi; Zhang, Qian; Liu, Ailing; Fang, Hongyun; Hao, Linan; Duan, Yifan; Xu, Haiquan; Shang, Xianwen; Ma, Jun; Xu, Guifa; Du, Lin; Li, Ying; Guo, Hongwei; Li, Tingyu; Ma, Guansheng

2010-05-02

Childhood obesity and its related metabolic and psychological abnormalities are becoming serious health problems in China. Effective, feasible and practical interventions should be developed in order to prevent the childhood obesity and its related early onset of clinical cardiovascular diseases. The objective of this paper is to describe the design of a multi-centred random controlled school-based clinical intervention for childhood obesity in China. The secondary objective is to compare the cost-effectiveness of the comprehensive intervention strategy with two other interventions, one only focuses on nutrition education, the other only focuses on physical activity. The study is designed as a multi-centred randomised controlled trial, which included 6 centres located in Beijing, Shanghai, Chongqing, Shandong province, Heilongjiang province and Guangdong province. Both nutrition education (special developed carton style nutrition education handbook) and physical activity intervention (Happy 10 program) will be applied in all intervention schools of 5 cities except Beijing. In Beijing, nutrition education intervention will be applied in 3 schools and physical activity intervention among another 3 schools. A total of 9750 primary students (grade 1 to grade 5, aged 7-13 years) will participate in baseline and intervention measurements, including weight, height, waist circumference, body composition (bioelectrical impendence device), physical fitness, 3 days dietary record, physical activity questionnaire, blood pressure, plasma glucose and plasma lipid profiles. Data concerning investments will be collected in our study, including costs in staff training, intervention materials, teachers and school input and supervising related expenditure. Present study is the first and biggest multi-center comprehensive childhood obesity intervention study in China. Should the study produce comprehensive results, the intervention strategies would justify a national school-based program to prevent childhood obesity in China.

Evaluation of postoperative recovery in day surgery patients using a mobile phone application: a multicentre randomized trial.

PubMed

Jaensson, M; Dahlberg, K; Eriksson, M; Nilsson, U

2017-11-01

Many patients undergoing anaesthesia and surgery experience postoperative complications. Our aim was to investigate whether a systematic follow-up smartphone-based assessment, using recovery assessment by phone points (RAPP) compared with standard care, had a positive effect on day surgery patients' postoperative recovery. We also investigated whether there were differences in women and men's recovery and recovery scores. The study was a single-blind, multicentre randomized controlled trial. A total of 997 patients were randomly allocated to either RAPP or standard care. The Swedish web version of a quality of recovery (SwQoR) questionnaire was used to evaluate the patients' postoperative recovery, either on paper or using an application (RAPP) on postoperative days seven and 14. On postoperative day seven the RAPP group reported significantly better values in seven out of 24 items of the SwQoR: sleeping difficulties; not having a general feeling of wellbeing; having difficulty feeling relaxed/comfortable; and dizziness; headache; pain in the surgical wound; and a swollen surgical wound compared with the control group, implying a good postoperative recovery. Both men and women in the RAPP group reported significantly better values (and, hence good postoperative recovery) compared with the control group in the items sleeping difficulties; not having a general feeling of wellbeing and pain in the surgical wound. Measurement of patient-reported outcomes using a smartphone-based application was associated with decreased discomfort from several postoperative symptoms. Systematic e-assessment can thereby increase patients' quality of recovery and identify key areas for improvement in perioperative care. NCT02492191. © The Author 2017. Published by Oxford University Press on behalf of the British Journal of Anaesthesia.

A EUropean study on effectiveness and sustainability of current Cardiac Rehabilitation programmes in the Elderly: Design of the EU-CaRE randomised controlled trial.

PubMed

Prescott, Eva; Meindersma, Esther P; van der Velde, Astrid E; Gonzalez-Juanatey, Jose R; Iliou, Marie Christine; Ardissino, Diego; Zoccai, Giuseppe Biondi; Zeymer, Uwe; Prins, Leonie F; Van't Hof, Arnoud Wj; Wilhelm, Matthias; de Kluiver, Ed P

2016-10-01

Cardiac rehabilitation (CR) is an evidence-based intervention to increase survival and quality of life. Yet studies consistently show that elderly patients are less frequently referred to CR, show less uptake and more often drop out of CR programmes. The European study on effectiveness and sustainability of current cardiac rehabilitation programmes in the elderly (EU-CaRE) project consists of an observational study and an open prospective, investigator-initiated multicentre randomised controlled trial (RCT) involving mobile telemonitoring guided CR (mCR). The aim of EU-CaRE is to map the efficiency of current CR of the elderly in Europe, and to investigate whether mCR is an effective alternative in terms of efficacy, adherence and sustainability. The EU-CaRE study includes patients aged 65 years or older with ischaemic heart disease or who have undergone heart valve surgery. A total of 1760 patients participating in existing CR programmes in eight regions of Europe will be included. Of patients declining regular CR, 238 will be included in the RCT and randomised in two study arms. The experimental group (mCR) will receive a personalised home-based programme while the control group will receive no advice or coaching throughout the study period. Outcomes will be assessed after the end of CR and at 12 months follow-up. The primary outcome is VO 2peak and secondary outcomes include variables describing CR uptake, adherence, efficacy and sustainability. The study will provide important information to improve CR in the elderly. The EU-CaRE RCT is the first European multicentre study of mCR as an alternative for elderly patients not attending usual CR. © The European Society of Cardiology 2016.

Feasibility study from a randomized controlled trial of standard closure of a stoma site vs biological mesh reinforcement.

PubMed

2016-09-01

Hernia formation occurs at closed stoma sites in up to 30% of patients. The Reinforcement of Closure of Stoma Site (ROCSS) randomized controlled trial is evaluating whether placement of biological mesh during stoma closure safely reduces hernia rates compared with closure without mesh, without increasing surgical or wound complications. This paper aims to report recruitment, deliverability and safety from the internal feasibility study. A multicentre, patient and assessor blinded, randomized controlled trial, delivered through surgical trainee research networks. A 90-patient internal feasibility study assessed recruitment, randomization, deliverability and early (30 day) safety of the novel surgical technique (ClinicalTrials.gov registration number NCT02238964). The feasibility study recruited 90 patients from the 104 considered for entry (45 to mesh, 45 to no mesh). Seven of eight participating centres randomized patients within 30 days of opening. Overall, 41% of stomas were created for malignant disease and 73% were ileostomies. No mesh-specific complications occurred. Thirty-one postoperative adverse events were experienced by 31 patients, including surgical site infection (9%) and postoperative ileus (6%). One mesh was removed for re-access to the abdominal cavity, for reasons unrelated to the mesh. Independent review by the Data Monitoring and Ethics Committee of adverse event data by treatment allocation found no safety concerns. Multicentre randomization to this trial of biological mesh is feasible, with no early safety concerns. Progression to the full Phase III trial has continued. ROCSS shows that trainee research networks can efficiently develop and deliver complex interventional surgical trials. Colorectal Disease © 2016 The Association of Coloproctology of Great Britain and Ireland.

Patient satisfaction with switching to esomeprazole from existing proton pump inhibitor therapy for gastro-oesophageal reflux disease: an observational, multicentre study.

PubMed

Hoogendoorn, Robert J; Groeneveld, Lex; Kwee, J Andy

2009-01-01

To determine treatment satisfaction in patients with gastro-oesophageal reflux disease (GORD) when switched to esomeprazole. This observational, multicentre study conducted in the Netherlands included primary-care patients being treated with a proton pump inhibitor (PPI) [omeprazole, pantoprazole, rabeprazole or lansoprazole] for GORD who were switched to esomeprazole by their physician. After a median of 28 days' esomeprazole therapy, patients' satisfaction was assessed using a questionnaire. Patients self-rated whether they were 'more satisfied', felt there was 'no difference' or were 'less satisfied' with esomeprazole compared with previous PPI therapy. Symptom control, concomitant medication use and tolerability were also assessed. Overall, 4929 patients were included in this study; of these, only 21.9% were satisfied with PPI treatment at consultation (i.e. prior to switching to esomeprazole). Following switching to esomeprazole therapy, 88.0% of patients were satisfied with therapy and only 26.9% of patients were still experiencing symptoms (vs 84.0% at consultation); 71.3% were more satisfied with esomeprazole than with their previous PPI, most frequently because they had fewer or no symptoms. Among patients who had been using concomitant therapy to control GORD symptoms, 62.0% were no longer using any such medication. Of the 1069 patients who had been satisfied with their previous PPI therapy, 39.4% were even more satisfied with esomeprazole. Esomeprazole was well tolerated; the most commonly reported adverse events were nausea/vomiting and headache, and no treatment-related serious adverse events occurred. Among primary-care patients receiving PPI therapy for GORD, switching to esomeprazole therapy impacts positively on treatment satisfaction and symptom control.

Comparison of intravenous versus combined oral and intravenous antimicrobial prophylaxis (COMBINE) for the prevention of surgical site infection in elective colorectal surgery: study protocol for a multicentre, double-blind, randomised controlled clinical trial

PubMed Central

Vignaud, Marie; Paugam-Burtz, Catherine; Garot, Matthias; Jaber, Samir; Slim, Karem; Panis, Yves; Lucet, Jean-Christophe; Bourdier, Justine; Morand, Dominique; Pereira, Bruno; Futier, Emmanuel

2018-01-01

Introduction Surgical site infections (SSIs) account for 30% of all healthcare-associated infections, with reported rates ranging from 8% and 30% after colorectal surgery and are associated with increased morbidity and mortality rates, length of hospital stay and costs in healthcare. Administration of systemic antimicrobial prophylaxis before surgery is recommended to reduce the risk of SSI, but the optimal regimen remains unclear. We aim to evaluate whether a combined oral and intravenous antimicrobial prophylaxis could be more effective to reduce the incidence of SSI after colorectal surgery, as compared with the standard practice of intravenous antimicrobial prophylaxis alone. Methods and analysis Comparison of intravenous versus combined oral and intravenous antimicrobial prophylaxis (COMBINE) trial is a randomised, placebo-controlled, parallel, double-blind, multicentre study of 960 patients undergoing elective colorectal surgery. Patients will be randomly allocated in a 1:1 ratio to receive either combined oral and intravenous antimicrobial prophylaxis or intravenous antibiotic prophylaxis alone, stratified by centre, the surgical procedure (laparoscopic or open surgery) and according to the surgical skin antisepsis (chlorexidine–alcohol or povidione-iodine alcoholic solution). The primary endpoint is the rate of SSI by day 30 following surgery, with SSI defined by the criteria developed by the Centers for Disease Control and Prevention. Data will be analysed on the intention-to-treat principle and a per-protocol basis. Ethics and dissemination COMBINE trial has been approved by an independent ethics committee for all study centres. Participant recruitment began in May 2016. Results will be published in international peer-reviewed medical journals. Trial registration number EudraCT 2015-002559-84; NCT02618720. PMID:29654027

The impact of DECISION+2 on patient intention to engage in shared decision making: secondary analysis of a multicentre clustered randomized trial.

PubMed

Couët, Nicolas; Labrecque, Michel; Robitaille, Hubert; Turcotte, Stéphane; Légaré, France

2015-12-01

Training health professionals in shared decision making (SDM) may influence their patients' intention to engage in SDM. To assess the impact of DECISION+2, a SDM training programme for family physicians about the use of antibiotics to treat acute respiratory infections (ARIs), on their patients' intention to engage in SDM in future consultations. Secondary analysis of a multicentre clustered randomized trial. Three hundred and fifty-nine patients consulting family physicians about an ARI in nine family practice teaching units (FPTUs). DECISION+2 (two-hour online tutorial, two-hour workshop, and decision support tools) was offered in the experimental group (five FPTUs, 162 physicians, 181 patients). Usual care was provided in the control group (four FPTUs, 108 physicians, 178 patients). Change in patients' intention scores (range -3 to +3) between pre- and post-consultation. The mean ± SD [median] scores of intention to engage in SDM were high in both study groups before consultation (DECISION+2 group: 1.4 ± 1.0 [1.7]; control group: 1.5 ± 1.1 [1.7]) and increased in both groups after consultation (DECISION+2 group: 2.1 ± 1.1 [2.7]; control group: 1.9 ± 1.2 [2.3]). Change of intention, classified as either increased, stable or decreased, was not statistically associated with the exposure to the DECISION+2 programme after adjusting for the cluster design (proportional odds ratio = 1.5; 95% confidence interval = 0.8-3.0). DECISION+2 had no significant impact on patients' intention to engage in SDM for choosing to use antibiotics or not to treat an ARI in future consultations. Patient-targeted interventions may be necessary to achieve this purpose. © 2014 John Wiley & Sons Ltd.

Study design and methodology for a multicentre, randomised controlled trial of transcranial direct current stimulation as a treatment for unipolar and bipolar depression.

PubMed

Alonzo, Angelo; Aaronson, Scott; Bikson, Marom; Husain, Mustafa; Lisanby, Sarah; Martin, Donel; McClintock, Shawn M; McDonald, William M; O'Reardon, John; Esmailpoor, Zeinab; Loo, Colleen

2016-11-01

Transcranial Direct Current Stimulation (tDCS) is a new, non-invasive neuromodulation approach for treating depression that has shown promising efficacy. The aim of this trial was to conduct the first international, multicentre randomised controlled trial of tDCS as a treatment for unipolar and bipolar depression. The study recruited 120 participants across 6 sites in the USA and Australia. Participants received active or sham tDCS (2.5mA, 20 sessions of 30min duration over 4weeks), followed by a 4-week open label active treatment phase and a 4-week taper phase. Mood and neuropsychological outcomes were assessed with the primary antidepressant outcome measure being the Montgomery-Asberg Depression Rating Scale (MADRS). A neuropsychological battery was administered to assess safety and examine cognitive effects. The study also investigated the possible influence of genetic polymorphisms on outcomes. The trial was triple-blinded. Participants, tDCS treaters and study raters were blinded to each participant's tDCS group allocation in the sham-controlled phase. Specific aspects of tDCS administration, device operation and group allocation were designed to optimise the integrity of blinding. Outcome measures will be tested using a mixed effects repeated measures analysis with the primary factors being Time as a repeated measure, tDCS condition (sham or active) and Diagnosis (unipolar or bipolar). A restricted number of random and fixed factors will be included as required to account for extraneous differences. As a promising treatment, tDCS has excellent potential for translation into widespread clinical use, being cost effective, portable, easy to operate and well tolerated. Copyright © 2016 Elsevier Inc. All rights reserved.

Feasibility and Preliminary Efficacy of Visual Cue Training to Improve Adaptability of Walking after Stroke: Multi-Centre, Single-Blind Randomised Control Pilot Trial

PubMed Central

Hollands, Kristen L.; Pelton, Trudy A.; Wimperis, Andrew; Whitham, Diane; Tan, Wei; Jowett, Sue; Sackley, Catherine M.; Wing, Alan M.; Tyson, Sarah F.; Mathias, Jonathan; Hensman, Marianne; van Vliet, Paulette M.

2015-01-01

Objectives Given the importance of vision in the control of walking and evidence indicating varied practice of walking improves mobility outcomes, this study sought to examine the feasibility and preliminary efficacy of varied walking practice in response to visual cues, for the rehabilitation of walking following stroke. Design This 3 arm parallel, multi-centre, assessor blind, randomised control trial was conducted within outpatient neurorehabilitation services Participants Community dwelling stroke survivors with walking speed <0.8m/s, lower limb paresis and no severe visual impairments Intervention Over-ground visual cue training (O-VCT), Treadmill based visual cue training (T-VCT), and Usual care (UC) delivered by physiotherapists twice weekly for 8 weeks. Main outcome measures: Participants were randomised using computer generated random permutated balanced blocks of randomly varying size. Recruitment, retention, adherence, adverse events and mobility and balance were measured before randomisation, post-intervention and at four weeks follow-up. Results Fifty-six participants participated (18 T-VCT, 19 O-VCT, 19 UC). Thirty-four completed treatment and follow-up assessments. Of the participants that completed, adherence was good with 16 treatments provided over (median of) 8.4, 7.5 and 9 weeks for T-VCT, O-VCT and UC respectively. No adverse events were reported. Post-treatment improvements in walking speed, symmetry, balance and functional mobility were seen in all treatment arms. Conclusions Outpatient based treadmill and over-ground walking adaptability practice using visual cues are feasible and may improve mobility and balance. Future studies should continue a carefully phased approach using identified methods to improve retention. Trial Registration Clinicaltrials.gov NCT01600391 PMID:26445137

Safety and effectiveness of antiretroviral drugs during pregnancy, delivery and breastfeeding for prevention of mother-to-child transmission of HIV-1: the Kesho Bora Multicentre Collaborative Study rationale, design, and implementation challenges.

PubMed

2011-01-01

To evaluate strategies to reduce HIV-1 transmission through breastfeeding, a multicentre study including a nested randomized controlled trial was implemented in five research sites in West, East and South Africa (The Kesho Bora Study). The aim was to optimize the use of antiretroviral (ARV) drugs during pregnancy, delivery and breastfeeding to prevent mother-to-child transmission of HIV-1 (PMTCT) and to preserve the health of the HIV-1-infected mother. The study included long-term ARV treatment for women with advanced disease, and short-course ARV prophylaxis stopped at delivery for women with early disease. Women with intermediate disease participated in a randomized controlled trial to compare safety and efficacy of triple-ARV prophylaxis prolonged during breastfeeding with short-course ARV prophylaxis stopped at delivery. Between January 2005 and August 2008 a total of 1140 women were enrolled. This paper describes the study design, interventions and protocol amendments introduced to adapt to evolving scientific knowledge, international guidelines and availability of ARV treatment. The paper highlights the successes and challenges during the conduct of the trial. The Kesho Bora Study included one of the few randomized controlled trials to assess safety and efficacy of ARV prophylaxis continued during breastfeeding and the only randomized trial to assess maternal prophylaxis started during pregnancy. The findings have been important for informing international and national guidelines on MTCT prevention in developing countries where, due to poverty, lack of reliable and affordable supply of replacement feed and stigma associated with HIV/AIDS, HIV-infected women have little or no option other than to breastfeed their infants. (ISRCTN71468401). Copyright © 2010 Elsevier Inc. All rights reserved.

The PACT trial: PAtient Centered Telerehabilitation: effectiveness of software-supported and traditional mirror therapy in patients with phantom limb pain following lower limb amputation: protocol of a multicentre randomised controlled trial.

PubMed

Rothgangel, Andreas Stefan; Braun, Susy; Schulz, Ralf Joachim; Kraemer, Matthias; de Witte, Luc; Beurskens, Anna; Smeets, Rob Johannes

2015-01-01

Non-pharmacological interventions such as mirror therapy are gaining increased recognition in the treatment of phantom limb pain; however, the evidence in people with phantom limb pain is still weak. In addition, compliance to self-delivered exercises is generally low. The aim of this randomised controlled study is to investigate the effectiveness of mirror therapy supported by telerehabilitation on the intensity, duration and frequency of phantom limb pain and limitations in daily activities compared to traditional mirror therapy and care as usual in people following lower limb amputation. A three-arm multi-centre randomised controlled trial will be performed. Participants will be randomly assigned to care as usual, traditional mirror therapy or mirror therapy supported by telerehabilitation. During the first 4 weeks, at least 10 individual sessions will take place in every group. After the first 4 weeks, participants will be encouraged to perform self-delivered exercises over a period of 6 weeks. Outcomes will be assessed at 4 and 10 weeks after baseline and at 6 months follow-up. The primary outcome measure is the average intensity of phantom limb pain during the last week. Secondary outcome measures include the different dimensions of phantom limb pain, pain-related limitations in daily activities, global perceived effect, pain-specific self-efficacy, and quality of life. Several questions concerning the study design that emerged during the preparation of this trial will be discussed. This will include how these questions were addressed and arguments for the choices that were made. Copyright © 2014 Australian Physiotherapy Association. Published by Elsevier B.V. All rights reserved.

Effect of pain neurophysiology education on physiotherapy students' understanding of chronic pain, clinical recommendations and attitudes towards people with chronic pain: a randomised controlled trial.

PubMed

Colleary, G; O'Sullivan, K; Griffin, D; Ryan, C G; Martin, D J

2017-12-01

To investigate the effect of pain neurophysiology education (PNE) on student physiotherapists': (1) knowledge of chronic pain; (2) attitudes towards patients with chronic pain; and (3) clinical recommendations for patients with chronic pain. Multicentre single-blind randomised controlled trial. One UK and one Irish university. Seventy-two student physiotherapists. Participants received either PNE (intervention) or a control education. Both were delivered in a 70-minute group lecture. (1) The Revised Pain Neurophysiology Quiz to assess knowledge; (2) the Health Care Pain Attitudes and Impairment Relationship Scale (HC-PAIRS) to assess attitudes; and (3) a case vignette to assess the appropriateness of clinical recommendations. Post education, the PNE group had a greater increase in pain neurophysiology knowledge [mean difference 4.0 (95% confidence interval 3.2 to 4.7), P<0.01] and more improved attitudes [-17.5 (95% confidence interval -22.1 to -12.9), P<0.01] compared with the control group. Post education, students in the PNE group were more likely to make appropriate recommendations regarding work (94% vs 56%), exercise (92% vs 56%), activity (94% vs 67%) and bed rest (69% vs 33%) compared with those in the control group (P<0.05). The improvements in knowledge, attitudes and recommendations for pain management show that PNE is a potentially valuable part of the education of physiotherapy students, and could be used on a more widespread basis. There is a need to investigate whether these findings can be replicated in other healthcare professions, and how well these reported changes lead to changes in actual clinical behaviour and the clinical outcomes of patients. Copyright © 2017 Chartered Society of Physiotherapy. Published by Elsevier Ltd. All rights reserved.

The challenges of implementing a multi-centre audit of end-of-life care in care homes.

PubMed

Levy, Jean; Kinley, Julie; Conway, Frances

2016-11-02

This article aims to share the experience of a hospice in facilitating a multi-centre audit of end-of-life care in care homes, particularly noting the challenges and enablers of carrying out the audit. The audit was a retrospective multi-centre survey of bereaved relatives/next of kin of residents who died in the care home, using an anonymous, validated questionnaire: the Family Perception of Care Scale. Questionnaires were sent 3-months after bereavement. Returned questionnaires were analysed using SPSS and Excel. The care homes were in areas encompassing outer and inner city populations. The team identified eight challenges to the audit process, in particular, embedding procedures within the care homes, non-responses and developing action plans for improvement. Overall, the audit provided an indication of where improvements could be made and where care was already excellent, built confidence and increased expertise in the care-home staff.

Repeated seasonal influenza vaccination among elderly in Europe: Effects on laboratory confirmed hospitalised influenza.

PubMed

Rondy, Marc; Launay, Odile; Castilla, Jesus; Costanzo, Simona; Puig-Barberà, Joan; Gefenaite, Giedre; Larrauri, Amparo; Rizzo, Caterina; Pitigoi, Daniela; Syrjänen, Ritva K; Machado, Ausenda; Kurečić Filipović, Sanja; Krisztina Horváth, Judit; Paradowska-Stankiewicz, Iwona; Marbus, Sierk; Moren, Alain

2017-08-03

In Europe, annual influenza vaccination is recommended to elderly. From 2011 to 2014 and in 2015-16, we conducted a multicentre test negative case control study in hospitals of 11 European countries to measure influenza vaccine effectiveness (IVE) against laboratory confirmed hospitalised influenza among people aged ≥65years. We pooled four seasons data to measure IVE by past exposures to influenza vaccination. We swabbed patients admitted for clinical conditions related to influenza with onset of severe acute respiratory infection ≤7days before admission. Cases were patients RT-PCR positive for influenza virus and controls those negative for any influenza virus. We documented seasonal vaccination status for the current season and the two previous seasons. We recruited 5295 patients over the four seasons, including 465A(H1N1)pdm09, 642A(H3N2), 278 B case-patients and 3910 controls. Among patients unvaccinated in both previous two seasons, current seasonal IVE (pooled across seasons) was 30% (95%CI: -35 to 64), 8% (95%CI: -94 to 56) and 33% (95%CI: -43 to 68) against influenza A(H1N1)pdm09, A(H3N2) and B respectively. Among patients vaccinated in both previous seasons, current seasonal IVE (pooled across seasons) was -1% (95%CI: -80 to 43), 37% (95%CI: 7-57) and 43% (95%CI: 1-68) against influenza A(H1N1)pdm09, A(H3N2) and B respectively. Our results suggest that, regardless of patients' recent vaccination history, current seasonal vaccine conferred some protection to vaccinated patients against hospitalisation with influenza A(H3N2) and B. Vaccination of patients already vaccinated in both the past two seasons did not seem to be effective against A(H1N1)pdm09. To better understand the effect of repeated vaccination, engaging in large cohort studies documenting exposures to vaccine and natural infection is needed. Copyright © 2017 The Author(s). Published by Elsevier Ltd.. All rights reserved.

Adjuvant Intrahepatic Injection Iodine-131-Lipiodol Improves Prognosis of Patients with Hepatocellular Carcinoma After Resection: a Meta-Analysis.

PubMed

Hong, Ye; Wu, Lu-Peng; Ye, Feng; Zhou, Yan-Ming

2015-12-01

High incidence of intrahepatic recurrence is a major surgical limitation following hepatectomy of hepatocellular carcinoma (HCC). This study was intended to investigate the effects of adjuvant intrahepatic injection of iodine-131-lipiodol on disease recurrence and survival in patients with HCC who underwent resection. A computerized literature search was performed to identify relevant articles. Data synthesis was performed using Review Manager 5.0 software, and results are presented as odds ratio (OR) with 95 % confidence intervals. Two randomized controlled trials and three case-control studies with a total of 334 participants were analyzed. Iodine-131-lipiodol treatment achieved significantly lower rates of intrahepatic recurrence (OR = 0.48, 95 % confidence interval (95 % CI) = 0.30-0.74; P = 0.001) and early recurrence (<2 year) (OR = 0.45, 95 % CI = 0.23-0.89; P = 0.02). Likewise, iodine-131-lipiodol treatment improved both the 5-year disease-free survival and overall survival significantly (OR = 1.85, 95 % CI = 1.13-3.03; P = 0.01; OR = 2.00, 95 % CI = 0.99-4.04; P = 0.05, respectively). Adjuvant intrahepatic injection of iodine-131-lipiodol resulted in a preventive effect on recurrence and improved survival after resection of HCC. Further larger, multi-centred, randomized prospective trial is warranted.

Involvement of leucocyte/endothelial cell interactions in anorexia nervosa.

PubMed

Víctor, Víctor M; Rovira-Llopis, Susana; Saiz-Alarcón, Vanessa; Sangüesa, Maria C; Rojo-Bofill, Luis; Bañuls, Celia; de Pablo, Carmen; Álvarez, Ángeles; Rojo, Luis; Rocha, Milagros; Hernández-Mijares, Antonio

2015-07-01

Anorexia nervosa is a common psychiatric disorder in adolescence and is related to cardiovascular complications. Our aim was to study the effect of anorexia nervosa on metabolic parameters, leucocyte-endothelium interactions, adhesion molecules and proinflammatory cytokines. This multicentre, cross-sectional, case-control study employed a population of 24 anorexic female patients and 36 controls. We evaluated anthropometric and metabolic parameters, interactions between leucocytes polymorphonuclear neutrophils (PMN) and human umbilical vein endothelial cells (HUVEC), proinflammatory cytokines such as tumour necrosis factor alpha (TNF-α) and interleukin-6 (IL-6) and soluble cellular adhesion molecules (CAMs) including E-selectin, vascular cell adhesion molecule-1 (VCAM-1) and intercellular adhesion molecule-1 (ICAM-1). Anorexia nervosa was related to a decrease in weight, body mass index, waist circumference, systolic blood pressure, glucose, insulin and HOMA-IR, and an increase in HDL cholesterol. These effects disappeared after adjusting for BMI. Anorexia nervosa induced a decrease in PMN rolling velocity and an increase in PMN rolling flux and PMN adhesion. Increases in IL-6 and TNF-α and adhesion molecule VCAM-1 were also observed. This study supports the hypothesis of an association between anorexia nervosa, inflammation and the induction of leucocyte-endothelium interactions. These findings may explain, in part at least, the increased risk of vascular disease among patients with anorexia nervosa. © 2015 Stichting European Society for Clinical Investigation Journal Foundation.

The HubBLe Trial: haemorrhoidal artery ligation (HAL) versus rubber band ligation (RBL) for symptomatic second- and third-degree haemorrhoids: a multicentre randomised controlled trial and health-economic evaluation.

PubMed

Brown, Steven; Tiernan, Jim; Biggs, Katie; Hind, Daniel; Shephard, Neil; Bradburn, Mike; Wailoo, Allan; Alshreef, Abualbishr; Swaby, Lizzie; Watson, Angus; Radley, Simon; Jones, Oliver; Skaife, Paul; Agarwal, Anil; Giordano, Pasquale; Lamah, Marc; Cartmell, Mark; Davies, Justin; Faiz, Omar; Nugent, Karen; Clarke, Andrew; MacDonald, Angus; Conaghan, Phillip; Ziprin, Paul; Makhija, Rohit

2016-11-01

Optimal surgical intervention for low-grade haemorrhoids is unknown. Rubber band ligation (RBL) is probably the most common intervention. Haemorrhoidal artery ligation (HAL) is a novel alternative that may be more efficacious. The comparison of HAL with RBL for the treatment of grade II/III haemorrhoids. A multicentre, parallel-group randomised controlled trial. UK NHS and Personal Social Services. 17 NHS Trusts. Patients aged ≥ 18 years presenting with grade II/III (second- and third-degree) haemorrhoids, including those who have undergone previous RBL. HAL with Doppler probe compared with RBL. Primary outcome - recurrence at 1 year post procedure; secondary outcomes - recurrence at 6 weeks; haemorrhoid severity score; European Quality of Life-5 Dimensions, 5-level version (EQ-5D-5L); Vaizey incontinence score; pain assessment; complications; and cost-effectiveness. A total of 370 participants entered the trial. At 1 year post procedure, 30% of the HAL group had evidence of recurrence compared with 49% after RBL [adjusted odds ratio (OR) = 2.23, 95% confidence interval (CI) 1.42 to 3.51; p  = 0.0005]. The main reason for the difference was the number of extra procedures required to achieve improvement/cure. If a single HAL is compared with multiple RBLs then only 37.5% recurred in the RBL arm (adjusted OR 1.35, 95% CI 0.85 to 2.15; p  = 0.20). Persistence of significant symptoms at 6 weeks was lower in both arms than at 1 year (9% HAL and 29% RBL), suggesting significant deterioration in both groups over the year. Symptom score, EQ-5D-5L and Vaizey score improved in both groups compared with baseline, but there was no difference between interventions. Pain was less severe and of shorter duration in the RBL group; most of the HAL group who had pain had mild to moderate pain, resolving by 3 weeks. Complications were low frequency and not significantly different between groups. It appeared that HAL was not cost-effective compared with RBL. In the base-case analysis, the difference in mean total costs was £1027 higher for HAL. Quality-adjusted life-years (QALYs) were higher for HAL; however, the difference was very small (0.01) resulting in an incremental cost-effectiveness ratio of £104,427 per additional QALY. At 1 year, although HAL resulted in fewer recurrences, recurrence was similar to repeat RBL. Symptom scores, complications, EQ-5D-5L and continence score were no different, and patients had more pain in the early postoperative period after HAL. HAL is more expensive and unlikely to be cost-effective in terms of incremental cost per QALY. Blinding of participants and site staff was not possible. The incidence of recurrence may continue to increase with time. Further follow-up would add to the evidence regarding long-term clinical effectiveness and cost-effectiveness. The polysymptomatic nature of haemorrhoidal disease requires a validated scoring system, and the data from this trial will allow further assessment of validity of such a system. These data add to the literature regarding treatment of grade II/III haemorrhoids. The results dovetail with results from the eTHoS study [Watson AJM, Hudson J, Wood J, Kilonzo M, Brown SR, McDonald A, et al. Comparison of stapled haemorrhoidopexy with traditional excisional surgery for haemorrhoidal disease (eTHoS): a pragmatic, multicentre, randomised controlled trial. Lancet 2016, in press.] comparing stapled haemorrhoidectomy with excisional haemorrhoidectomy. Combined results will allow expansion of analysis, allowing surgeons to tailor their treatment options to individual patients. Current Controlled Trials ISRCTN41394716. This project was funded by the NIHR Health Technology Assessment programme and will be published in full in Health Technology Assessment ; Vol. 20, No. 88. See the NIHR Journals Library website for further project information.

The multicentre south European study 'Helios'. II: Different sun exposure patterns in the aetiology of basal cell and squamous cell carcinomas of the skin.

PubMed Central

Rosso, S.; Zanetti, R.; Martinez, C.; Tormo, M. J.; Schraub, S.; Sancho-Garnier, H.; Franceschi, S.; Gafà, L.; Perea, E.; Navarro, C.; Laurent, R.; Schrameck, C.; Talamini, R.; Tumino, R.; Wechsler, J.

1996-01-01

The role of sun exposure in development of basal cell and squamous cell carcinomas among different populations from south Europe was investigated. Between 1989 and 1993 we interviewed incident cases and a random population sample of controls from five centres where a cancer registry was operating, whereas we selected a sample of hospital-based cases and controls from the other three centres. We gathered information on life-long exposure to sunlight during different activities. Results are analysed for 1549 basal cell carcinoma (BCC) cases and 228 squamous cell carcinoma (SCC) cases compared with 1795 controls. We observed a statistically significant increase of risk of SCC with increasing sun exposure beyond a threshold of 70,000 cumulated hours of exposure in a lifetime. Sun exposures during work and holidays were, however, inversely correlated. Odds ratios (ORs) of SCC were up to eight or nine times the reference for the highest exposures (200,000 cumulated hours or more). BCC exhibited a 2-fold increase of risk for lower exposure (8000-10,000 cumulated hours in a lifetime) with a plateau and a slight decrease of risk for the highest exposures (100,000 cumulated hours or more). Outdoor work showed a significantly increased risk of SCC (OR 1.6 for more than 54,000 cumulated hours of exposure in a lifetime), whereas recreational activities such as sun exposure during holidays at the beach (OR 1.6 for more than 2600 cumulated hours of exposure in a lifetime) or during water sports (OR 1.6 for more than 2600 cumulated hours of exposure in a lifetime) were associated with an increased risk of BCC. Risk patterns were different in poor or good tanners with a significant risk trend for good tanners, whereas poor tanners were on a plateau of increased risk at any level of exposure. Solar radiation is associated with a risk of BCC even for relatively short periods of exposure such as during holidays and sports, whereas SCC develops later if exposure continues. The skin's ability to tan modulates the risk of BCC; subjects who tan poorly have a steady risk increase, whereas people who tan easily develop cancer only after prolonged exposures. PMID:8645596

Patch test reactions to mite antigens: a GERDA multicentre study. Groupe d'Etudes et de Recherches en Dermato-Allergie.

PubMed

Castelain, M; Birnbaum, J; Castelain, P Y; Ducombs, G; Grosshans, E; Jelen, G; Lacroix, M; Meynadier, J; Mougeolle, J M; Lachapelle, J M

1993-11-01

We performed patch tests with Dermatophagoides pteronyssinus (Dp) antigens from 2 different sources in 355 non-randomly selected patients with atopic dermatitis (AD) and 398 subjects of a control group. The study demonstrated that contact sensitization to mites occurred in an appreciable % of AD cases (20.8%), using commonly available assay products. The differences recorded between the 2 materials tested were related to the concentration of P1 antigen. Non-atopic patients rarely showed positive reactions to Dp (0.75%), when strict criteria for readings were applied and if 2 readings were performed. Patients with positive patch tests did not necessarily show positive immediate skin tests. It would be useful to carry out tests systematically in atopic patients, even if it is not yet known what modern treatment would be best for the patient. Laboratories still do not provide standardized house dust mite preparations--measuring and codifying their biological activity--for use in patch tests. It is to be hoped that the extension of this type of test will lead to the production of better test materials, in syringes with homogeneous dispersion and concentration.

Characterisation of the opposing effects of G6PD deficiency on cerebral malaria and severe malarial anaemia

PubMed Central

Clarke, Geraldine M; Rockett, Kirk; Kivinen, Katja; Hubbart, Christina; Jeffreys, Anna E; Rowlands, Kate; Jallow, Muminatou; Conway, David J; Bojang, Kalifa A; Pinder, Margaret; Usen, Stanley; Sisay-Joof, Fatoumatta; Sirugo, Giorgio; Toure, Ousmane; Thera, Mahamadou A; Konate, Salimata; Sissoko, Sibiry; Niangaly, Amadou; Poudiougou, Belco; Mangano, Valentina D; Bougouma, Edith C; Sirima, Sodiomon B; Modiano, David; Amenga-Etego, Lucas N; Ghansah, Anita; Koram, Kwadwo A; Wilson, Michael D; Enimil, Anthony; Evans, Jennifer; Amodu, Olukemi K; Olaniyan, Subulade; Apinjoh, Tobias; Mugri, Regina; Ndi, Andre; Ndila, Carolyne M; Uyoga, Sophie; Macharia, Alexander; Peshu, Norbert; Williams, Thomas N; Manjurano, Alphaxard; Sepúlveda, Nuno; Clark, Taane G; Riley, Eleanor; Drakeley, Chris; Reyburn, Hugh; Nyirongo, Vysaul; Kachala, David; Molyneux, Malcolm; Dunstan, Sarah J; Phu, Nguyen Hoan; Quyen, Nguyen Ngoc; Thai, Cao Quang; Hien, Tran Tinh; Manning, Laurens; Laman, Moses; Siba, Peter; Karunajeewa, Harin; Allen, Steve; Allen, Angela; Davis, Timothy ME; Michon, Pascal; Mueller, Ivo; Molloy, Síle F; Campino, Susana; Kerasidou, Angeliki; Cornelius, Victoria J; Hart, Lee; Shah, Shivang S; Band, Gavin; Spencer, Chris CA; Agbenyega, Tsiri; Achidi, Eric; Doumbo, Ogobara K; Farrar, Jeremy; Marsh, Kevin; Taylor, Terrie; Kwiatkowski, Dominic P

2017-01-01

Glucose-6-phosphate dehydrogenase (G6PD) deficiency is believed to confer protection against Plasmodium falciparum malaria, but the precise nature of the protective effect has proved difficult to define as G6PD deficiency has multiple allelic variants with different effects in males and females, and it has heterogeneous effects on the clinical outcome of P. falciparum infection. Here we report an analysis of multiple allelic forms of G6PD deficiency in a large multi-centre case-control study of severe malaria, using the WHO classification of G6PD mutations to estimate each individual’s level of enzyme activity from their genotype. Aggregated across all genotypes, we find that increasing levels of G6PD deficiency are associated with decreasing risk of cerebral malaria, but with increased risk of severe malarial anaemia. Models of balancing selection based on these findings indicate that an evolutionary trade-off between different clinical outcomes of P. falciparum infection could have been a major cause of the high levels of G6PD polymorphism seen in human populations. DOI: http://dx.doi.org/10.7554/eLife.15085.001 PMID:28067620

Hemicraniectomy after middle cerebral artery infarction with life-threatening Edema trial (HAMLET). Protocol for a randomised controlled trial of decompressive surgery in space-occupying hemispheric infarction.

PubMed

Hofmeijer, Jeannette; Amelink, G Johan; Algra, Ale; van Gijn, Jan; Macleod, Malcolm R; Kappelle, L Jaap; van der Worp, H Bart

2006-09-11

Patients with a hemispheric infarct and massive space-occupying brain oedema have a poor prognosis. Despite maximal conservative treatment, the case fatality rate may be as high as 80%, and most survivors are left severely disabled. Non-randomised studies suggest that decompressive surgery reduces mortality substantially and improves functional outcome of survivors. This study is designed to compare the efficacy of decompressive surgery to improve functional outcome with that of conservative treatment in patients with space-occupying supratentorial infarction The study design is that of a multi-centre, randomised clinical trial, which will include 112 patients aged between 18 and 60 years with a large hemispheric infarct with space-occupying oedema that leads to a decrease in consciousness. Patients will be randomised to receive either decompressive surgery in combination with medical treatment or best medical treatment alone. Randomisation will be stratified for the intended mode of conservative treatment (intensive care or stroke unit care). The primary outcome measure will be functional outcome, as determined by the score on the modified Rankin Scale, at one year.

Proximal femoral fractures: Principles of management and review of literature.

PubMed

Mittal, Ravi; Banerjee, Sumit

2012-06-01

The purpose of this study was to review the principles involved in the management of proximal femoral fractures as reported in the literature. A medical literature search in the MEDLINE (PubMed) and Cochrane database was undertaken to review strategies and principles in proximal femoral fracture treatment. Randomized control trials and meta analysis were given preference while case reports/small series were rejected. Early anatomical reduction and surgical fixation remains the best option to reduce the risk of complications like non-union and avascular necrosis in treating fracture neck femurs. Cancellous screws continue to be the preferred treatment for fixation of neck femur fractures in younger population until the benefit of using sliding hip screws is validated by large multicentric studies. In the geriatric age group, early prosthetic replacement brings down the mortality and morbidity associated with neck femur fractures. Sliding hip screw (DHS) is the best available option for stable inter trochanteric fractures. The use of intramedullary nails e.g. PFN is beneficial in treating inter trochanteric fractures with comminution and loss of lateral buttress. Intramedullary implants have been proven to have increased success rates in subtrochanteric fractures and should be preferred over extramedullary plate fixation systems.

Proximal femoral fractures: Principles of management and review of literature

PubMed Central

Mittal, Ravi; Banerjee, Sumit

2012-01-01

Purpose The purpose of this study was to review the principles involved in the management of proximal femoral fractures as reported in the literature. Methods: A medical literature search in the MEDLINE (PubMed) and Cochrane database was undertaken to review strategies and principles in proximal femoral fracture treatment. Randomized control trials and meta analysis were given preference while case reports/small series were rejected. Results and conclusions: Early anatomical reduction and surgical fixation remains the best option to reduce the risk of complications like non-union and avascular necrosis in treating fracture neck femurs. Cancellous screws continue to be the preferred treatment for fixation of neck femur fractures in younger population until the benefit of using sliding hip screws is validated by large multicentric studies. In the geriatric age group, early prosthetic replacement brings down the mortality and morbidity associated with neck femur fractures. Sliding hip screw (DHS) is the best available option for stable inter trochanteric fractures. The use of intramedullary nails e.g. PFN is beneficial in treating inter trochanteric fractures with comminution and loss of lateral buttress. Intramedullary implants have been proven to have increased success rates in subtrochanteric fractures and should be preferred over extramedullary plate fixation systems. PMID:25983451

Satisfaction level and asthma control among Malaysian asthma patients on Symbicort Maintenance and Reliever Therapy (SMART) in the primary care setting (SMARTEST study).

PubMed

Liam, Chong-Kin; Pang, Yong-Kek; Chua, Keong-Tiong

2014-06-01

To evaluate Malaysian patients' satisfaction levels and asthma control with Symbicort SMART® in the primary care setting. This is a cross-sectional, multicentre study involving adult patients with persistent asthma who were prescribed only Symbicort SMART in the preceding one month prior to recruitment. Patients' satisfaction with Symbicort SMART and asthma control were evaluated using the self-administered Satisfaction with Asthma Treatment Questionnaire (SATQ) and the Asthma Control Test (ACT). Asthma was controlled (ACT score >20) in 189 (83%) of 228 patients. The mean overall SATQ score for patients with controlled asthma was 5.65 indicating a high satisfaction level, which was positively correlated with high ACT scores. There were differences in asthma control based on ethnicity, number of unscheduled visits and treatment compliance. Symbicort SMART resulted in a high satisfaction level and asthma control among Malaysian patients treated in the primary care setting and it is an effective and appealing treatment for asthmatic patients.

Multicentric Evaluation of New Commercial Enzyme Immunoassays for the Detection of Immunoglobulin M and Total Antibodies against Hepatitis A Virus▿

PubMed Central

Arcangeletti, M. C.; Dussaix, E.; Ferraglia, F.; Roque-Afonso, A. M.; Graube, A.; Chezzi, C.

2011-01-01

A multicentric clinical study was conducted on representative sera from 1,738 European and U.S. subjects for the evaluation of new anti-hepatitis A virus enzyme immunoassays from Bio-Rad Laboratories. Comparison with reference DiaSorin S.p.A. tests confirmed the good performance of Bio-Rad assays (99.85% and 99.47% overall agreement in detecting total antibodies and IgM, respectively). PMID:21653739

[Evaluation of the Family-based Familien stärken-Program for Preventing Substance Abuse and Behavior Problems in Youth].

PubMed

Stappenbeck, J; Wendell, A; Thomasius, R

2015-09-01

The Strengthening Families Program was developed in the USA and is regarded as an effective family-based prevention programme for youth. The evaluation of an adapted German version was carried out as a randomised-controlled multicentre trial. 292 families were recruited, 150 followed the intervention, and 142 received a minimal intervention. Acceptance from families and programme facilitators was high. Results about the effectiveness will be reported as soon as follow-up assessments are completed. © Georg Thieme Verlag KG Stuttgart · New York.

Evaluation of web-based annotation of ophthalmic images for multicentric clinical trials.

PubMed

Chalam, K V; Jain, P; Shah, V A; Shah, Gaurav Y

2006-06-01

An Internet browser-based annotation system can be used to identify and describe features in digitalized retinal images, in multicentric clinical trials, in real time. In this web-based annotation system, the user employs a mouse to draw and create annotations on a transparent layer, that encapsulates the observations and interpretations of a specific image. Multiple annotation layers may be overlaid on a single image. These layers may correspond to annotations by different users on the same image or annotations of a temporal sequence of images of a disease process, over a period of time. In addition, geometrical properties of annotated figures may be computed and measured. The annotations are stored in a central repository database on a server, which can be retrieved by multiple users in real time. This system facilitates objective evaluation of digital images and comparison of double-blind readings of digital photographs, with an identifiable audit trail. Annotation of ophthalmic images allowed clinically feasible and useful interpretation to track properties of an area of fundus pathology. This provided an objective method to monitor properties of pathologies over time, an essential component of multicentric clinical trials. The annotation system also allowed users to view stereoscopic images that are stereo pairs. This web-based annotation system is useful and valuable in monitoring patient care, in multicentric clinical trials, telemedicine, teaching and routine clinical settings.

Are power calculations useful? A multicentre neuroimaging study

PubMed Central

Suckling, John; Henty, Julian; Ecker, Christine; Deoni, Sean C; Lombardo, Michael V; Baron-Cohen, Simon; Jezzard, Peter; Barnes, Anna; Chakrabarti, Bhismadev; Ooi, Cinly; Lai, Meng-Chuan; Williams, Steven C; Murphy, Declan GM; Bullmore, Edward

2014-01-01

There are now many reports of imaging experiments with small cohorts of typical participants that precede large-scale, often multicentre studies of psychiatric and neurological disorders. Data from these calibration experiments are sufficient to make estimates of statistical power and predictions of sample size and minimum observable effect sizes. In this technical note, we suggest how previously reported voxel-based power calculations can support decision making in the design, execution and analysis of cross-sectional multicentre imaging studies. The choice of MRI acquisition sequence, distribution of recruitment across acquisition centres, and changes to the registration method applied during data analysis are considered as examples. The consequences of modification are explored in quantitative terms by assessing the impact on sample size for a fixed effect size and detectable effect size for a fixed sample size. The calibration experiment dataset used for illustration was a precursor to the now complete Medical Research Council Autism Imaging Multicentre Study (MRC-AIMS). Validation of the voxel-based power calculations is made by comparing the predicted values from the calibration experiment with those observed in MRC-AIMS. The effect of non-linear mappings during image registration to a standard stereotactic space on the prediction is explored with reference to the amount of local deformation. In summary, power calculations offer a validated, quantitative means of making informed choices on important factors that influence the outcome of studies that consume significant resources. PMID:24644267

[Tumor markers for bladder cancer: up-to-date study by the Kiel Tumor Bank].

PubMed

Hautmann, S; Eggers, J; Meyhoff, H; Melchior, D; Munk, A; Hamann, M; Naumann, M; Braun, P M; Jünemann, K P

2007-11-01

The number of noninvasive diagnostic tests for bladder cancer has increased tremendously over the last years with a large number of experimental and commercial tests. Comparative analyses of tests for diagnosis, follow-up, and recurrence detection of bladder cancer were performed retrospectively as well as prospectively, unicentrically, and multicentrically. An analysis of multicentric studies with large patient numbers compared with our own Kiel Tumor Bank data is presented. The Kiel Tumor Bank data looked prospectively at 106 consecutive bladder tumor patients from the year 2006. Special focus was put on urine cytology as a reference test, as well as the commercial NMP 22 Bladder Chek. The analysis of the NMP 22 Bladder Chek showed an overall sensitivity of 69% for all tumor grades and stages, with a specificity of 76%. Comparison to multicentric data with an overall sensitivity of 75% for all tumor grades and stages, with a specificity of 73%, showed results similar to those in the literature. Urine cytology showed a comparable overall sensitivity of 73% for all tumor grades and stages, with a specificity of 80%. A large number of noninvasive tests for bladder cancer follow-up with reasonable sensitivity and specificity can currently be used. Because of limited numbers of prospective randomized multicentric studies, no single particular marker for bladder cancer screening can be recommended at this point in time.

Effects of unstratified and centre-stratified randomization in multi-centre clinical trials.

PubMed

Anisimov, Vladimir V

2011-01-01

This paper deals with the analysis of randomization effects in multi-centre clinical trials. The two randomization schemes most often used in clinical trials are considered: unstratified and centre-stratified block-permuted randomization. The prediction of the number of patients randomized to different treatment arms in different regions during the recruitment period accounting for the stochastic nature of the recruitment and effects of multiple centres is investigated. A new analytic approach using a Poisson-gamma patient recruitment model (patients arrive at different centres according to Poisson processes with rates sampled from a gamma distributed population) and its further extensions is proposed. Closed-form expressions for corresponding distributions of the predicted number of the patients randomized in different regions are derived. In the case of two treatments, the properties of the total imbalance in the number of patients on treatment arms caused by using centre-stratified randomization are investigated and for a large number of centres a normal approximation of imbalance is proved. The impact of imbalance on the power of the study is considered. It is shown that the loss of statistical power is practically negligible and can be compensated by a minor increase in sample size. The influence of patient dropout is also investigated. The impact of randomization on predicted drug supply overage is discussed. Copyright © 2010 John Wiley & Sons, Ltd.

Changing prevalence patterns in endoscopic and histological diagnosis of gastritis? Data from a cross-sectional Central European multicentre study.

PubMed

Wolf, Eva-Maria; Plieschnegger, Wolfgang; Geppert, Michael; Wigginghaus, Bernd; Höss, Gabriele M; Eherer, Andreas; Schneider, Nora I; Hauer, Almuthe; Rehak, Peter; Vieth, Michael; Langner, Cord

2014-05-01

Traditionally, Helicobacter infection is considered to be the most common cause of gastritis. In the cross-sectional Central European histoGERD trial, we assessed the prevalence of different types of gastritis, correlating histological and endoscopic diagnoses. A total of 1123 individuals participated in an observational multicentre study. Endoscopists classified individuals as positive or negative for gastritis and rendered the putative cause. Pathologists evaluated biopsy specimens based upon the Updated Sydney System. Histological diagnosis of gastritis was made in 639 (56.9%) participants. In all, 210 (18.7%) individuals were diagnosed with Helicobacter gastritis, 215 (19.1%) with post Helicobacter gastritis, 234 (20.8%) with reactive gastropathy, 26 (2.3%) with autoimmune gastritis, and 6 (0.5%) with focally enhanced gastritis related to Crohn's disease. In 46 out of 639 (7.2%) individuals diagnosed with gastritis, combinations of different histological subtypes were noted the most common being reactive gastropathy and post Helicobacter gastritis. Endoscopic diagnosis of gastritis was made in 534 (47.6%) individuals. Reactive gastropathy was more common than active Helicobacter gastritis, and the majority of cases attributable to Helicobacter infection were no longer ongoing, i.e. post Helicobacter gastritis. Agreement between histological and endoscopic diagnoses was better in reactive gastropathy than in Helicobacter gastritis. Copyright © 2014 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.

Real-world use of the second-generation cobalt-chromium sirolimus-eluting stents: 12-month results from the prospective multicentre FOCUS registry.

PubMed

Zhang, Feng; Ge, Junbo; Qian, Juying; Ge, Lei; Zhou, Jun

2012-12-20

The FOCUS registry is a prospective, multicentre, web-based programme designed to collect clinical outcome data from real-world patients receiving the second-generation cobalt-chromium sirolimus-eluting stent (CoCr-SES). From March 2009 to February 2010, a total of 5,084 patients from 83 centres who were eligible to receive CoCr-SES were enrolled in the FOCUS registry. The primary endpoint was 12-month major adverse cardiac events (MACE, defined as the composite of cardiac death, myocardial infarction [MI], and target vessel revascularisation [TVR]). One-year data were available for 5,013 (98.6%) of the 5,084 patients enrolled. The primary endpoint occurred in 174 (3.47%) of 5,013 patients, consisting of 43 (0.86%) cardiac deaths, 132 (2.63%) MI, and 46 (0.92%) TVR. According to the Academic Research Consortium definition, definite and probable stent thrombosis (ST) occurred in 0.52% (26/5,013) of patients, including 19 cases of early ST and 7 of late ST. The 12-month MACE rates were 3.73% and 2.60% for extended-use and standard-use patients, respectively (p=0.065). The second-generation CoCr-SES was associated with low rates of 12-month MACE and ST in a broad spectrum of patients, thereby confirming the clinical safety and efficacy of this stent in a real-world setting.

Paediatric and adolescent traumatic gastrointestinal injuries: results of a European multicentre analysis.

PubMed

Fischerauer, E E; Zötsch, S; Capito, C; Bonnard, A; Sárközy, S; Berndt, J; Hosie, S; Beltra Pico, R; Steinau, G; Wiejek, A; Czauderna, P; Çelik, A; Lain Fernandez, A; Ibanez, V M; Esposito, C; Saxena, A K

2013-10-01

Paediatric gastrointestinal injuries (GIIs) are rare, and the aim of this multicentre study was to evaluate their outcomes in a large cohort. Hospital databases of 10 European paediatric surgical centres were reviewed for paediatric traumatic GIIs managed between 2000-2010. Ninety-seven patients with a median age of 9 years (0-17 years) were identified, with 72 blunt and 25 penetrating GIIs. Initial diagnostics in 90 patients led to correct diagnosis in 71%. Diagnostics were delayed in 26 patients (median 24 h). Eighty-two patients required surgery (67 laparotomy, 12 laparoscopy and three other approaches). There was a 50% conversion in the laparoscopic group. Median hospital stay was 10 days (range 1-137 days), with longer duration influenced by associated injuries (n = 41). Diagnosis <24 h was associated with significantly shorter hospital stay compared to more than 24 h (p = 0.011). In one-third of patients, morbidities were not related to a diagnostic delay or type of injury. There were five lethal outcomes, four due to associated injuries. Initial diagnostics in traumatic paediatric GIIs provide false negatives in one-third of patients. Diagnostic delay <24 h is associated with a significantly shorter hospital stay. Although laparoscopy is associated with a conversion rate of 50%, it can be used for diagnosis in suspected cases to avoid nontherapeutic laparotomy. ©2013 Foundation Acta Paediatrica. Published by John Wiley & Sons Ltd.

Ethical dilemmas of a large national multi-centre study in Australia: time for some consistency.

PubMed

Driscoll, Andrea; Currey, Judy; Worrall-Carter, Linda; Stewart, Simon

2008-08-01

To examine the impact and obstacles that individual Institutional Research Ethics Committee (IRECs) had on a large-scale national multi-centre clinical audit called the National Benchmarks and Evidence-based National Clinical guidelines for Heart failure management programmes Study. Multi-centre research is commonplace in the health care system. However, IRECs continue to fail to differentiate between research and quality audit projects. The National Benchmarks and Evidence-based National Clinical guidelines for Heart failure management programmes study used an investigator-developed questionnaire concerning a clinical audit for heart failure programmes throughout Australia. Ethical guidelines developed by the National governing body of health and medical research in Australia classified the National Benchmarks and Evidence-based National Clinical guidelines for Heart failure management programmes Study as a low risk clinical audit not requiring ethical approval by IREC. Fifteen of 27 IRECs stipulated that the research proposal undergo full ethical review. None of the IRECs acknowledged: national quality assurance guidelines and recommendations nor ethics approval from other IRECs. Twelve of the 15 IRECs used different ethics application forms. Variability in the type of amendments was prolific. Lack of uniformity in ethical review processes resulted in a six- to eight-month delay in commencing the national study. Development of a national ethics application form with full ethical review by the first IREC and compulsory expedited review by subsequent IRECs would resolve issues raised in this paper. IRECs must change their ethics approval processes to one that enhances facilitation of multi-centre research which is now normative process for health services. The findings of this study highlight inconsistent ethical requirements between different IRECs. Also highlighted are the obstacles and delays that IRECs create when undertaking multi-centre clinical audits. However, in our clinical practice it is vital that clinical audits are undertaken for evaluation purposes. The findings of this study raise awareness of inconsistent ethical processes and highlight the need for expedient ethical review for clinical audits.

Efficacy and safety of saxagliptin in combination with metformin as initial therapy in Chinese patients with type 2 diabetes: Results from the START study, a multicentre, randomized, double-blind, active-controlled, phase 3 trial.

PubMed

Dou, Jingtao; Ma, Jianhua; Liu, Jun; Wang, Changjiang; Johnsson, Eva; Yao, Hui; Zhao, June; Pan, Changyu

2018-03-01

To assess the efficacy and safety of saxagliptin plus metformin over 24 weeks in pharmacotherapy-naïve Chinese patients with type 2 diabetes mellitus and inadequate glycaemic control (HbA1c, 8.0%-12.0%). In this multicentre, double-blind, active-controlled study (The START study: NCT02273050, clinicaltrials.gov), patients were randomized (1:1:1) to saxagliptin 5 mg plus metformin, saxagliptin 5 mg plus placebo or metformin plus placebo. Saxagliptin was taken once daily; metformin was taken once/twice daily and was titrated from 500 mg to a maximum of 2000 mg/d over 8 weeks. The primary end point was change in HbA1c from baseline to Week 24. Data from 630 patients (66.5% men; mean age, 50.1 years; mean body mass index, 26.6 kg/m 2 ; mean HbA1c, 9.4%; mean diabetes duration, 0.81 years) were analysed. Mean reduction in HbA1c was greater with saxagliptin plus metformin (-3.0%) than with saxagliptin plus placebo (-2.1%; P < .001) or metformin plus placebo (-2.8%; P = .034). Changes in mean fasting plasma glucose, 120-minute postprandial glucose, and 180-minute postprandial glucose area under the curve were greater, and more patients achieved a therapeutic glycaemic response, with saxagliptin plus metformin than with either monotherapy. Hypoglycaemic events were infrequent (<2%). Incidence of adverse events was similar among groups; upper respiratory tract infection and diarrhoea were most common. Saxagliptin 5 mg plus metformin significantly improved glycaemic control compared with either monotherapy in treatment-naïve Chinese patients with type 2 diabetes, and was well tolerated. © 2017 John Wiley & Sons Ltd.

A pragmatic multi-centre randomised controlled trial of fluid loading in high-risk surgical patients undergoing major elective surgery--the FOCCUS study.

PubMed

Cuthbertson, Brian H; Campbell, Marion K; Stott, Stephen A; Elders, Andrew; Hernández, Rodolfo; Boyers, Dwayne; Norrie, John; Kinsella, John; Brittenden, Julie; Cook, Jonathan; Rae, Daniela; Cotton, Seonaidh C; Alcorn, David; Addison, Jennifer; Grant, Adrian

2011-01-01

Fluid strategies may impact on patient outcomes in major elective surgery. We aimed to study the effectiveness and cost-effectiveness of pre-operative fluid loading in high-risk surgical patients undergoing major elective surgery. This was a pragmatic, non-blinded, multi-centre, randomised, controlled trial. We sought to recruit 128 consecutive high-risk surgical patients undergoing major abdominal surgery. The patients underwent pre-operative fluid loading with 25 ml/kg of Ringer's solution in the six hours before surgery. The control group had no pre-operative fluid loading. The primary outcome was the number of hospital days after surgery with cost-effectiveness as a secondary outcome. A total of 111 patients were recruited within the study time frame in agreement with the funder. The median pre-operative fluid loading volume was 1,875 ml (IQR 1,375 to 2,025) in the fluid group compared to 0 (IQR 0 to 0) in controls with days in hospital after surgery 12.2 (SD 11.5) days compared to 17.4 (SD 20.0) and an adjusted mean difference of 5.5 days (median 2.2 days; 95% CI -0.44 to 11.44; P = 0.07). There was a reduction in adverse events in the fluid intervention group (P = 0.048) and no increase in fluid based complications. The intervention was less costly and more effective (adjusted average cost saving: £2,047; adjusted average gain in benefit: 0.0431 quality adjusted life year (QALY)) and has a high probability of being cost-effective. Pre-operative intravenous fluid loading leads to a non-significant reduction in hospital length of stay after high-risk major surgery and is likely to be cost-effective. Confirmatory work is required to determine whether these effects are reproducible, and to confirm whether this simple intervention could allow more cost-effective delivery of care. Prospective Clinical Trials, ISRCTN32188676.

A multicentre phase III randomised controlled single-masked clinical trial evaluating the clinical efficacy and safety of light-masks at preventing dark-adaptation in the treatment of early diabetic macular oedema (CLEOPATRA): study protocol for a randomised controlled trial.

PubMed

Sivaprasad, Sobha; Arden, Geoffrey; Prevost, A Toby; Crosby-Nwaobi, Roxanne; Holmes, Helen; Kelly, Joanna; Murphy, Caroline; Rubin, Gary; Vasconcelos, Joanna; Hykin, Philip

2014-11-22

This study will evaluate hypoxia, as a novel concept in the pathogenesis of diabetic macular oedema (DMO). As the oxygen demand of the eye is maximum during dark-adaptation, we hypothesize that wearing light-masks during sleep will cause regression and prevent the development and progression of DMO. The study protocol comprises both an efficacy and mechanistic evaluation to test this hypothesis. This is a phase III randomised controlled single-masked multicentre clinical trial to test the clinical efficacy of light-masks at preventing dark-adaptation in the treatment of non-central DMO. Three hundred patients with non-centre-involving DMO in at least one eye will be randomised 1:1 to light-masks and control masks (with no light) to be used during sleep at night for a period of 24 months. The primary outcome is regression of non-central oedema by assessing change in the zone of maximal retinal thickness at baseline on optical coherence tomography (SD-OCT). Secondary outcomes will evaluate the prevention of development and progression of DMO by assessing changes in retinal thickness in different regions of the macula, macular volume, refracted visual acuity and level of retinopathy. Safety parameters will include sleep disturbance. Adverse events and measures of compliance will be assessed over 24 months. Participants recruited to the mechanistic sub-study will have additional retinal oximetry, multifocal electroretinography (ERG) and microperimetry to evaluate the role of hypoxia by assessing and comparing changes induced by supplemental oxygen and the light-masks at 12 months. The outcomes of this study will provide insight into the pathogenesis of DMO and provide evidence on whether a simple, non-invasive device in the form of a light-mask can help prevent the progression to centre-involving DMO and visual impairment in people with diabetes.

Multicentre Double-Blind Placebo-Controlled Food Challenge Study in Children Sensitised to Cashew Nut.

PubMed

van der Valk, Johanna P M; Gerth van Wijk, Roy; Dubois, Anthony E J; de Groot, Hans; Reitsma, Marit; Vlieg-Boerstra, Berber; Savelkoul, Huub F J; Wichers, Harry J; de Jong, Nicolette W

2016-01-01

Few studies with a limited number of patients have provided indications that cashew-allergic patients may experience severe allergic reactions to minimal amounts of cashew nut. The objectives of this multicentre study were to assess the clinical relevance of cashew nut sensitisation, to study the clinical reaction patterns in double-blind placebo-controlled food challenge tests and to establish the amount of cashew nuts that can elicit an allergic reaction. A total of 179 children were included (median age 9.0 years; range 2-17 years) with cashew nut sensitisation and a clinical history of reactions to cashew nuts or unknown exposure. Sensitised children who could tolerate cashew nuts were excluded. The study included three clinical visits and a telephone consultation. During the first visit, the medical history was evaluated, physical examinations were conducted, blood samples were drawn and skin prick tests were performed. The children underwent a double-blind placebo-controlled food challenge test with cashew nut during the second and third visits. The study showed that 137 (76.5%) of the sensitised children suspected of allergy to cashew nut had a positive double-blind placebo-controlled food challenge test, with 46% (63) manifesting subjective symptoms to the lowest dose of 1 mg cashew nut protein and 11% (15) developing objective symptoms to the lowest dose. Children most frequently had gastro-intestinal symptoms, followed by oral allergy and skin symptoms. A total of 36% (49/137) of the children experienced an anaphylactic reaction and 6% (8/137) of the children were treated with epinephrine. This prospective study demonstrated a strikingly high percentage of clinical reactions to cashew nut in this third line population. Severe allergic reactions, including anaphylaxis requiring epinephrine, were observed. These reactions were to minimal amounts of cashew nut, demonstrated the high potency of this allergens. www.ncbi.nlm.nih.gov/pubmed NTR3572.

Multicentre Double-Blind Placebo-Controlled Food Challenge Study in Children Sensitised to Cashew Nut

PubMed Central

van der Valk, Johanna P. M.; Gerth van Wijk, Roy; Dubois, Anthony E. J.; de Groot, Hans; Reitsma, Marit; Vlieg-Boerstra, Berber; Savelkoul, Huub F. J.; Wichers, Harry J.; de Jong, Nicolette W.

2016-01-01

Background Few studies with a limited number of patients have provided indications that cashew-allergic patients may experience severe allergic reactions to minimal amounts of cashew nut. The objectives of this multicentre study were to assess the clinical relevance of cashew nut sensitisation, to study the clinical reaction patterns in double-blind placebo-controlled food challenge tests and to establish the amount of cashew nuts that can elicit an allergic reaction. Methods and Findings A total of 179 children were included (median age 9.0 years; range 2–17 years) with cashew nut sensitisation and a clinical history of reactions to cashew nuts or unknown exposure. Sensitised children who could tolerate cashew nuts were excluded. The study included three clinical visits and a telephone consultation. During the first visit, the medical history was evaluated, physical examinations were conducted, blood samples were drawn and skin prick tests were performed. The children underwent a double-blind placebo-controlled food challenge test with cashew nut during the second and third visits. The study showed that 137 (76.5%) of the sensitised children suspected of allergy to cashew nut had a positive double-blind placebo-controlled food challenge test, with 46% (63) manifesting subjective symptoms to the lowest dose of 1 mg cashew nut protein and 11% (15) developing objective symptoms to the lowest dose. Children most frequently had gastro-intestinal symptoms, followed by oral allergy and skin symptoms. A total of 36% (49/137) of the children experienced an anaphylactic reaction and 6% (8/137) of the children were treated with epinephrine. Conclusion This prospective study demonstrated a strikingly high percentage of clinical reactions to cashew nut in this third line population. Severe allergic reactions, including anaphylaxis requiring epinephrine, were observed. These reactions were to minimal amounts of cashew nut, demonstrated the high potency of this allergens. Trial Registration www.ncbi.nlm.nih.gov/pubmed NTR3572 PMID:26967158

One-year follow-up results from AUGMENT-HF: a multicentre randomized controlled clinical trial of the efficacy of left ventricular augmentation with Algisyl in the treatment of heart failure.

PubMed

Mann, Douglas L; Lee, Randall J; Coats, Andrew J S; Neagoe, Gheorghe; Dragomir, Dinu; Pusineri, Enrico; Piredda, Massimo; Bettari, Luca; Kirwan, Bridget-Anne; Dowling, Robert; Volterrani, Maurizio; Solomon, Scott D; Sabbah, Hani N; Hinson, Andy; Anker, Stefan D

2016-03-01

AUGMENT-HF was an international, multicentre, prospective, open-label, randomized, controlled evaluation testing the hypothesis that Algisyl (injectable calcium alginate hydrogel) is superior to standard medical therapy (SMT) for improving functional capacity and clinical outcomes in patients with advanced heart failure (HF). We previously reported results following 6 months of follow-up. This report presents the results from 1 year of extended follow up for this clinical trial. We enrolled 78 patients with advanced HF, randomized (1:1), to Algisyl with SMT or SMT alone as previously reported. Patient inclusion criteria were LVEF ≤35%, peak VO2 of 9.0-14.5 mL/min/kg and LV end-diastolic diameter (LVEDD) index 30-40 mm/m(2) (LVEDD/body surface area). Patients must have been on stable, evidence-based therapy for HF. A total of 58 patients, mean age 62.3 ± 9.6 years, with ischaemic (57.7%) or non-ischaemic (42.3%) HF completed 12 months of follow-up. Treatment with Algisyl was associated with improved peak VO2 at 12 months; treatment effect vs. control of +2.10 mL/kg/min (95% confidence interval 0.96-3.24, P < 0.001). Statistically significant improvements were observed for VO2 at anaerobic threshold, 6-min walk test distance, and NYHA functional class (all P < 0.001). Through 12 months of follow-up there were 4 (10.5%) deaths in the control group and 9 (22.5%) deaths in the Algisyl group. Algisyl in addition to SMT was more effective than SMT alone for providing sustained 1-year benefits in exercise capacity, symptoms, and clinical status for patients with advanced HF. These data support larger clinical evaluations of this novel therapy. © 2015 The Authors European Journal of Heart Failure © 2015 European Society of Cardiology.

Design of a multicentre randomized controlled trial to assess the safety and efficacy of dose titration by specialized nurses in patients with heart failure. ETIFIC study protocol.

PubMed

Oyanguren, Juana; García-Garrido, LLuisa; Nebot Margalef, Magdalena; Lekuona, Iñaki; Comin-Colet, Josep; Manito, Nicolás; Roure, Julia; Ruiz Rodriguez, Pilar; Enjuanes, Cristina; Latorre, Pedro; Torcal Laguna, Jesús; García-Gutiérrez, Susana

2017-11-01

Heart failure (HF) is associated with many hospital admissions and relatively high mortality, rates decreasing with administration of beta-blockers (BBs), angiotensin-converting-enzyme inhibitors, angiotensin II receptor blockers, and mineralocorticoid receptor antagonists. The effect is dose dependent, suboptimal doses being common in clinical practice. The 2012 European guidelines recommend close monitoring and dose titration by HF nurses. Our main aim is to compare BB doses achieved by patients after 4 months in intervention (HF nurse-managed) and control (cardiologist-managed) groups. Secondary aims include comparing doses of the other aforementioned drugs achieved after 4 months, adverse events, and outcomes at 6 months in the two groups. We have designed a multicentre (20 hospitals) non-inferiority randomized controlled trial, including patients with new-onset HF, left ventricular ejection fraction ≤40%, and New York Heart Association class II-III, with no contraindications to BBs. We will also conduct qualitative analysis to explore potential barriers to and facilitators of dose titration by HF nurses. In the intervention group, HF nurses will implement titration as prescribed by cardiologists, following a protocol. In controls, cardiologists will both prescribe and titrate doses. The study variables are doses of each of the drugs after 4 months relative to the target dose (%), New York Heart Association class, left ventricular ejection fraction, N-terminal pro B-type natriuretic peptide levels, 6 min walk distance, comorbidities, renal function, readmissions, mortality, quality of life, and psychosocial characteristics. The trial seeks to assess whether titration by HF nurses of drugs recommended in practice guidelines is safe and not inferior to direct management by cardiologists. The results could have an impact on clinical practice. © 2017 The Authors. ESC Heart Failure published by John Wiley & Sons Ltd on behalf of the European Society of Cardiology.

A pragmatic multi-centre randomised controlled trial of fluid loading in high-risk surgical patients undergoing major elective surgery - the FOCCUS study

PubMed Central

2011-01-01

Introduction Fluid strategies may impact on patient outcomes in major elective surgery. We aimed to study the effectiveness and cost-effectiveness of pre-operative fluid loading in high-risk surgical patients undergoing major elective surgery. Methods This was a pragmatic, non-blinded, multi-centre, randomised, controlled trial. We sought to recruit 128 consecutive high-risk surgical patients undergoing major abdominal surgery. The patients underwent pre-operative fluid loading with 25 ml/kg of Ringer's solution in the six hours before surgery. The control group had no pre-operative fluid loading. The primary outcome was the number of hospital days after surgery with cost-effectiveness as a secondary outcome. Results A total of 111 patients were recruited within the study time frame in agreement with the funder. The median pre-operative fluid loading volume was 1,875 ml (IQR 1,375 to 2,025) in the fluid group compared to 0 (IQR 0 to 0) in controls with days in hospital after surgery 12.2 (SD 11.5) days compared to 17.4 (SD 20.0) and an adjusted mean difference of 5.5 days (median 2.2 days; 95% CI -0.44 to 11.44; P = 0.07). There was a reduction in adverse events in the fluid intervention group (P = 0.048) and no increase in fluid based complications. The intervention was less costly and more effective (adjusted average cost saving: £2,047; adjusted average gain in benefit: 0.0431 quality adjusted life year (QALY)) and has a high probability of being cost-effective. Conclusions Pre-operative intravenous fluid loading leads to a non-significant reduction in hospital length of stay after high-risk major surgery and is likely to be cost-effective. Confirmatory work is required to determine whether these effects are reproducible, and to confirm whether this simple intervention could allow more cost-effective delivery of care. Trial registration Prospective Clinical Trials, ISRCTN32188676 PMID:22177541

Multicentre randomized controlled trial comparing ferric(III)carboxymaltose infusion with oral iron supplementation in the treatment of preoperative anaemia in colorectal cancer patients.

PubMed

Borstlap, W A A; Buskens, C J; Tytgat, K M A J; Tuynman, J B; Consten, E C J; Tolboom, R C; Heuff, G; van Geloven, N; van Wagensveld, B A; C A Wientjes, C A; Gerhards, M F; de Castro, S M M; Jansen, J; van der Ven, A W H; van der Zaag, E; Omloo, J M; van Westreenen, H L; Winter, D C; Kennelly, R P; Dijkgraaf, M G W; Tanis, P J; Bemelman, W A

2015-06-28

At least a third of patients with a colorectal carcinoma who are candidate for surgery, are anaemic preoperatively. Preoperative anaemia is associated with increased morbidity and mortality. In general practice, little attention is paid to these anaemic patients. Some will have oral iron prescribed others not. The waiting period prior to elective colorectal surgery could be used to optimize a patients' physiological status. The aim of this study is to determine the efficacy of preoperative intravenous iron supplementation in comparison with the standard preoperative oral supplementation in anaemic patients with colorectal cancer. In this multicentre randomized controlled trial, patients with an M0-staged colorectal carcinoma who are scheduled for curative resection and with a proven iron deficiency anaemia are eligible for inclusion. Main exclusion criteria are palliative surgery, metastatic disease, neoadjuvant chemoradiotherapy (5 × 5 Gy = no exclusion) and the use of Recombinant Human Erythropoietin within three months before inclusion or a blood transfusion within a month before inclusion. Primary endpoint is the percentage of patients that achieve normalisation of the haemoglobin level between the start of the treatment and the day of admission for surgery. This study is a superiority trial, hypothesizing a greater proportion of patients achieving the primary endpoint in favour of iron infusion compared to oral supplementation. A total of 198 patients will be randomized to either ferric(III)carboxymaltose infusion in the intervention arm or ferrofumarate in the control arm. This study will be performed in ten centres nationwide and one centre in Ireland. This is the first randomized controlled trial to determine the efficacy of preoperative iron supplementation in exclusively anaemic patients with a colorectal carcinoma. Our trial hypotheses a more profound haemoglobin increase with intravenous iron which may contribute to a superior optimisation of the patient's condition and possibly a decrease in postoperative morbidity. ClincalTrials.gov: NCT02243735 .

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.

A cognitive behavioral based group intervention for children with a chronic illness and their parents: a multicentre randomized controlled trial.

PubMed

Scholten, Linde; Willemen, Agnes M; Grootenhuis, Martha A; Maurice-Stam, Heleen; Schuengel, Carlo; Last, Bob F

2011-07-14

Coping with a chronic illness (CI) challenges children's psychosocial functioning and wellbeing. Cognitive-behavioral intervention programs that focus on teaching the active use of coping strategies may prevent children with CI from developing psychosocial problems. Involvement of parents in the intervention program may enhance the use of learned coping strategies in daily life, especially on the long-term. The primary aim of the present study is to examine the effectiveness of a cognitive behavioral based group intervention (called 'Op Koers') 1 for children with CI and of a parallel intervention for their parents. A secondary objective is to investigate why and for whom this intervention works, in order to understand the underlying mechanisms of the intervention effect. This study is a multicentre randomized controlled trial. Participants are children (8 to 18 years of age) with a chronic illness, and their parents, recruited from seven participating hospitals in the Netherlands. Participants are randomly allocated to two intervention groups (the child intervention group and the child intervention combined with a parent program) and a wait-list control group. Primary outcomes are child psychosocial functioning, wellbeing and child disease related coping skills. Secondary outcomes are child quality of life, child general coping skills, child self-perception, parental stress, quality of parent-child interaction, and parental perceived vulnerability. Outcomes are evaluated at baseline, after 6 weeks of treatment, and at a 6 and 12-month follow-up period. The analyses will be performed on the basis of an intention-to-treat population. This study evaluates the effectiveness of a group intervention improving psychosocial functioning in children with CI and their parents. If proven effective, the intervention will be implemented in clinical practice. Strengths and limitations of the study design are discussed. Current Controlled Trials ISRCTN60919570.

Long-term integrated telerehabilitation of COPD Patients: a multicentre randomised controlled trial (iTrain).

PubMed

Zanaboni, Paolo; Dinesen, Birthe; Hjalmarsen, Audhild; Hoaas, Hanne; Holland, Anne E; Oliveira, Cristino Carneiro; Wootton, Richard

2016-08-22

Pulmonary rehabilitation (PR) is an effective intervention for the management of people with chronic obstructive pulmonary disease (COPD). However, available resources are often limited, and many patients bear with poor availability of programmes. Sustaining PR benefits and regular exercise over the long term is difficult without any exercise maintenance strategy. In contrast to traditional centre-based PR programmes, telerehabilitation may promote more effective integration of exercise routines into daily life over the longer term and broaden its applicability and availability. A few studies showed promising results for telerehabilitation, but mostly with short-term interventions. The aim of this study is to compare long-term telerehabilitation with unsupervised exercise training at home and with standard care. An international multicentre randomised controlled trial conducted across sites in three countries will recruit 120 patients with COPD. Participants will be randomly assigned to telerehabilitation, treadmill and control, and followed up for 2 years. The telerehabilitation intervention consists of individualised exercise training at home on a treadmill, telemonitoring by a physiotherapist via videoconferencing using a tablet computer, and self-management via a customised website. Patients in the treadmill arm are provided with a treadmill only to perform unsupervised exercise training at home. Patients in the control arm are offered standard care. The primary outcome is the combined number of hospitalisations and emergency department presentations. Secondary outcomes include changes in health status, quality of life, anxiety and depression, self-efficacy, subjective impression of change, physical performance, level of physical activity, and personal experiences in telerehabilitation. This trial will provide evidence on whether long-term telerehabilitation represents a cost-effective strategy for the follow-up of patients with COPD. The delivery of telerehabilitation services will also broaden the availability of PR and maintenance strategies, especially to those living in remote areas and with no access to centre-based exercise programmes. ClinicalTrials.gov: NCT02258646 .

Impairment-oriented training or Bobath therapy for severe arm paresis after stroke: a single-blind, multicentre randomized controlled trial.

PubMed

Platz, T; Eickhof, C; van Kaick, S; Engel, U; Pinkowski, C; Kalok, S; Pause, M

2005-10-01

To study the effects of augmented exercise therapy time for arm rehabilitation as either Bobath therapy or the impairment-oriented training (Arm BASIS training) in stroke patients with arm severe paresis. Single blind, multicentre randomized control trial. Three inpatient neurorehabilitation centres. Sixty-two anterior circulation ischaemic stroke patients. Random assignment to three group: (A) no augmented exercise therapy time, (B) augmented exercise therapy time as Bobath therapy and (C) augmented exercise therapy time as Arm BASIS training. Fugl-Meyer arm motor score. Secondary measure: Action Research Arm Test (ARA). Ancillary measures: Fugl-Meyer arm sensation and joint motion/pain scores and the Ashworth Scale (elbow flexors). An overall effect of augmented exercise therapy time on Fugl-Meyer scores after four weeks was not corroborated (mean and 95% confidence interval (CI) of change scores: no augmented exercise therapy time (n=20) 8.8, 5.2-12.3; augmented exercise therapy time (n=40) 9.9, 6.8-13.9; p = 0.2657). The group who received the augmented exercise therapy time as Arm BASIS training (n=20) had, however, higher gains than the group receiving the augmented exercise therapy time as Bobath therapy (n=20) (mean and 95% CI of change scores: Bobath 7.2, 2.6-11.8; BASIS 12.6, 8.4-16.8; p = 0.0432). Passive joint motion/pain deteriorated less in the group who received BASIS training (mean and 95% CI of change scores: Bobath -3.2, -5.2 to -1.1; BASIS 0.1, -1.8-2.0; p = 0.0090). ARA, Fugl-Meyer arm sensation, and Ashworth Scale scores were not differentially affected. The augmented exercise therapy time as Arm BASIS training enhanced selective motor control. Type of training was more relevant for recovery of motor control than therapeutic time spent.

Epidemiological risk factors for adult dengue in Singapore: an 8-year nested test negative case control study.

PubMed

Yung, Chee Fu; Chan, Siew Pang; Thein, Tun Linn; Chai, Siaw Ching; Leo, Yee Sin

2016-07-08

Understanding changes in the ecology and epidemiology of dengue is important to ensure resource intensive control programmes are targeted effectively as well as to inform future dengue vaccination strategies. We analyzed data from a multicentre longitudinal prospective study of fever in adults using a nested test negative case control approach to identify epidemiological risk factors for dengue disease in Singapore. From April 2005 to February 2013, adult patients presenting with fever within 72 h at selected public primary healthcare clinics and a tertiary hospital in Singapore were recruited. Acute and convalescent blood samples were collected and used to diagnose dengue using both PCR and serology methods. A dengue case was defined as having a positive RT-PCR result for DENV OR evidence of serological conversion between acute and convalescent blood samples. Similarly, controls were chosen from patients in the cohort who tested negative for dengue using the same laboratory methods. The host epidemiological factors which increased the likelihood of dengue disease amongst adults in Singapore were those aged between 21 and 40 years old (2 fold increase) while in contrast, Malay ethnicity was protective (OR 0.57, 95%CI 0.35 to 0.91) against dengue disease. Spatial factors which increased the odds of acquiring dengue was residing at a foreign workers dormitory or hostel (OR 3.25, 95 % CI 1.84 to 5.73) while individuals living in the North-West region of the country were less likely to get dengue (OR 0.50, 95%CI 0.29 to 0.86). Other factors such as gender, whether one primarily works indoors or outdoors, general dwelling type or floor, the type of transportation one uses to work, travel history, as well as self-reported history of mosquito bite or household dengue/fever were not useful in helping to inform a diagnosis of dengue. We have demonstrated a test negative study design to better understand the epidemiological risk factors of adult dengue over multiple seasons. We were able to discount other previously speculated factors such as gender, whether one primarily works indoors or outdoors, dwelling floor in a building and the use of public transportation as having no effect on one's risk of getting dengue.

Effectiveness and tolerability of fixed-dose combination enalapril plus nitrendipine in hypertensive patients: results of the 3-month observational, post-marketing, multicentre, prospective CENIT study.

PubMed

Sierra, Alejandro de la; Roca-Cusachs, Alejandro; Redón, Josep; Marín, Rafael; Luque, Manuel; Figuera, Mariano de la; Garcia-Garcia, Margarida; Falkon, Liliana

2009-01-01

Monotherapy with any class of antihypertensive drug effectively controls blood pressure (BP) in only about 50% of patients. Consequently, the majority of patients with hypertension require combined therapy with two or more medications. This study aimed to evaluate the effectiveness (systolic BP [SBP]/diastolic BP [DBP] control) and tolerability of the fixed-dose combination enalapril/nitrendipine 10 mg/20 mg administered as a single daily dose in hypertensive patients. This was a post-authorization, multicentre, prospective, observational study conducted in primary care with a 3-month follow-up. Patients throughout Spain with uncontrolled hypertension (> or =140/90 mmHg for patients without diabetes mellitus, or > or =130/85 mmHg for patients with diabetes) on monotherapy or with any combination other than enalapril + nitrendipine, or who were unable to tolerate their previous antihypertensive therapy, were recruited. Change from previous to study treatment was according to usual clinical practice. BP was measured once after 5 minutes of rest in the sitting position. Therapeutic response was defined as follows: 'controlled' meant controlled BP (<140/90 mmHg for nondiabetic patients, or <130/85 mmHg for diabetic patients); 'response' meant controlled BP, or a decrease in SBP of > or =20 mmHg and in DBP of > or =10 mmHg. The main laboratory test parameters were documented at baseline and after 3 months. Patients aged >65 years, with diabetes, with isolated systolic hypertension (ISH; SBP > or =140 mmHg for patients without diabetes, SBP > or =130 mmHg for patients with diabetes) and who were obese (body mass index [BMI] > or =30 kg/m2) were analysed separately. Of 6537 patients included, 5010 and 6354 patients were assessed in effectiveness and tolerability analyses, respectively. In the tolerability analysis population, there were 3023 men (47.6%) and 3321 women (52.4%). The mean (+/- SD) age of the tolerability analysis group was 62.8 (+/- 10.7) years. A total of 71.1% of the patients presented at least one clinical cardiovascular risk factor other than hypertension, with the most frequent being dyslipidaemia (42.3%), obesity (29.2%) and diabetes (23.9%). After 3 months of treatment, SBP and DBP showed mean (+/- SD) decreases of 26.5 (+/- 14.4) mmHg and 14.9 (+/- 9.0) mmHg, respectively, and 73.0% of patients responded to treatment while 40.9% achieved BP control (70.8%/36.1% in 2658 patients aged >65 years; 61.7%/46.8% in 1521 patients with diabetes; 55.3%/44.2% in 731 patients with ISH; 72.0%/36.4% in 1762 obese patients). Adverse events were reported in 10.8% of patients (n = 689). During the follow-up period, ten patients died and seven patients had serious adverse events; in no case was a causal relationship attributed to the study product. The rate of SBP/DBP control achieved demonstrates the effectiveness of the fixed-dose enalapril/nitrendipine 10 mg/20 mg combination administered as a single daily dose in patients with essential hypertension not adequately controlled with monotherapy or with any combination other than enalapril + nitrendipine. The proportion and type of adverse events reported were as expected and have already been described for both components of the enalapril/nitrendipine 10 mg/20 mg combination. These results confirm the effectiveness of a strategy based on a fixed-dose enalapril/nitrendipine 10 mg/20 mg combination in reducing BP and achieving BP control goals.

[Serodiagnosis of toxoplasmosis: a comparative multicenter study of a standard scale through various actual tests and expression of the results in international units. Groupe de travail toxoplasmose du Contrôle national de qualité en parasotologie. Syndicat des fabricants de réactifs de laboratoire. Groupe de travail standardisation des tests sérologiques du Réseau européen de lutte contre la toxoplasmose congénitale].

PubMed

Petithory, J C; Ambroise-Thomas, P; De Loye, J; Pelloux, H; Goullier-Fleuret, A; Milgram, M; Buffard, C; Garin, J P

1996-01-01

Reported are the results of a multicentre study involving 40 laboratories that was carried out in France to assess all the currently available methods used for the serodiagnosis of toxoplasmosis. For this purpose 10 batches of control sera were prepared with titres in the range 0-260 IU per ml. These sera were tested in nine laboratories using immunofluorescence methods; in three laboratories using dye tests; in forty laboratories using enzyme-linked immunosorbent assay; in four laboratories using direct agglutination and haemagglutination; in seven laboratories using the high-sensitivity IgG agglutination test; and in three laboratories using the latex agglutination test. In this way, 70 series of titrations were carried out using seven procedures and the results were compared with those obtained using the WHO reference serum in 15 cases, with the French national E6 serum in 16 other cases, and in 39 cases using 15 reference sera supplied by the reagent manufacturers. Rigorous comparison of the tests was not possible in all cases because one aim of the study was to ensure that the tests were carried out under the usual working conditions that prevailed in the participating laboratories. The results obtained indicate that the serological tests currently available for toxoplasmosis are acceptable for its serodiagnosis. Presentation of the titres in IU has advantages; however, caution is required since the definition of IU varies according to the test and reagents used. It is therefore essential that the conditions and limits for a positive reaction be carefully defined in each case, especially for commercially available kits.

Multi-vendor, multicentre comparison of contrast-enhanced SSFP and T2-STIR CMR for determining myocardium at risk in ST-elevation myocardial infarction

PubMed Central

Nordlund, David; Klug, Gert; Heiberg, Einar; Koul, Sasha; Larsen, Terje H.; Hoffmann, Pavel; Metzler, Bernhard; Erlinge, David; Atar, Dan; Aletras, Anthony H.; Carlsson, Marcus; Engblom, Henrik; Arheden, Håkan

2016-01-01

Aims Myocardial salvage, determined by cardiac magnetic resonance imaging (CMR), is used as end point in cardioprotection trials. To calculate myocardial salvage, infarct size is related to myocardium at risk (MaR), which can be assessed by T2-short tau inversion recovery (T2-STIR) and contrast-enhanced steady-state free precession magnetic resonance imaging (CE-SSFP). We aimed to determine how T2-STIR and CE-SSFP perform in determining MaR when applied in multicentre, multi-vendor settings. Methods and results A total of 215 patients from 17 centres were included after percutaneous coronary intervention (PCI) for ST-elevation myocardial infarction. CMR was performed within 1–8 days. These patients participated in the MITOCARE or CHILL-MI cardioprotection trials. Additionally, 8 patients from a previous study, imaged 1 day post-CMR, were included. Late gadolinium enhancement, T2-STIR, and CE-SSFP images were acquired on 1.5T MR scanners (Philips, Siemens, or GE). In 65% of the patients, T2-STIR was of diagnostic quality compared with 97% for CE-SSFP. In diagnostic quality images, there was no difference in MaR by T2-STIR and CE-SSFP (bias: 0.02 ± 6%, P = 0.96, r2 = 0.71, P < 0.001), or between treatment and control arms. No change in size or quality of MaR nor ability to identify culprit artery was seen over the first week after the acute event (P = 0.44). Conclusion In diagnostic quality images, T2-STIR and CE-SSFP provide similar estimates of MaR, were constant over the first week, and were not affected by treatment. CE-SSFP had a higher degree of diagnostic quality images compared with T2 imaging for sequences from two out of three vendors. Therefore, CE-SSFP is currently more suitable for implementation in multicentre, multi-vendor clinical trials. PMID:27002140

Oxygen titration after resuscitation from out-of-hospital cardiac arrest: A multi-centre, randomised controlled pilot study (the EXACT pilot trial).

PubMed

Bray, Janet E; Hein, Cindy; Smith, Karen; Stephenson, Michael; Grantham, Hugh; Finn, Judith; Stub, Dion; Cameron, Peter; Bernard, Stephen

2018-04-21

Recent studies suggest the administration of 100% oxygen to hyperoxic levels following return-of-spontaneous-circulation (ROSC) post-cardiac arrest may be harmful. However, the feasibility and safety of oxygen titration in the prehospital setting is unknown. We conducted a multi-centre, phase-2 study testing whether prehospital titration of oxygen results in an equivalent number of patients arriving at hospital with oxygen saturations SpO2 ≥ 94%. We enrolled unconscious adults with: sustained ROSC; initial shockable rhythm; an advanced airway; and an SpO2 ≥ 95%. Initially (Sept 2015-March 2016) patients were randomised 1:1 to either 2 L/minute (L/min) oxygen (titrated) or >10 L/min oxygen (control) via a bag-valve reservoir. However, one site experienced a high number of desaturations (SpO2 < 94%) in the titrated arm and this arm was changed (April 2016) to an initial reduction of oxygen to 4 L/min then, if tolerated, to 2 L/min, and the desaturation limit was decreased to <90%. We randomised 61 patients to titrated (n = 37: 2L/min = 20 and 2-4 L/min = 17) oxygen or control (n = 24). Patients allocated to titrated oxygen were more likely to desaturate compared to controls ((SpO2 < 94%: 43% vs. 4%, p = 0.001; SpO2 < 90%: 19% vs. 4%, p = 0.09). The majority of desaturations (81%) occurred at 2L/min. On arrival at hospital the majority of patients had a SpO2 ≥ 94% (titrated: 90% vs. control: 100%) and all patients had a SpO2 ≥ 90%. One patient (control) re-arrested. Survival to hospital discharge was similar. Oxygen titration post-ROSC is feasible in the prehospital environment, but incremental titration commencing at 4L/min oxygen flow may be needed to maintain an oxygen saturation >90% (NCT02499042). Copyright © 2018 Elsevier B.V. All rights reserved.

Six-month exercise training program to treat post-thrombotic syndrome: a randomized controlled two-centre trial

PubMed Central

Kahn, Susan R.; Shrier, Ian; Shapiro, Stan; Houweling, Adrielle H.; Hirsch, Andrew M.; Reid, Robert D.; Kearon, Clive; Rabhi, Khalil; Rodger, Marc A.; Kovacs, Michael J.; Anderson, David R.; Wells, Philip S.

2011-01-01

Background Exercise training may have the potential to improve post-thrombotic syndrome, a frequent, chronic complication of deep venous thrombosis. We conducted a randomized controlled two-centre pilot trial to assess the feasibility of a multicentre-based evaluation of a six-month exercise training program to treat post-thrombotic syndrome and to obtain preliminary data on the effectiveness of such a program. Methods Patients were randomized to receive exercise training (a six-month trainer-supervised program) or control treatment (an education session with monthly phone follow-ups). Levels of eligibility, consent, adherence and retention were used as indicators of study feasibility. Primary outcomes were change from baseline to six months in venous disease-specific quality of life (as measured using the Venous Insufficiency Epidemiological and Economic Study Quality of Life [VEINES-QOL] questionnaire) and severity of post-thrombotic syndrome (as measured by scores on the Villalta scale) in the exercise training group versus the control group, assessed by t tests. Secondary outcomes were change in generic quality of life (as measured using the Short-Form Health Survey-36 [SF-36] questionnaire), category of severity of post-thrombotic syndrome, leg strength, leg flexibility and time on treadmill. Results Of 95 patients with post-thrombotic syndrome, 69 were eligible, 43 consented and were randomized, and 39 completed the study. Exercise training was associated with improvement in VEINES-QOL scores (exercise training mean change 6.0, standard deviation [SD] 5.1 v. control mean change 1.4, SD 7.2; difference 4.6, 95% CI 0.54 to 8.7; p = 0.027) and improvement in scores on the Villalta scale (exercise training mean change −3.6, SD 3.7 v. control mean change −1.6, SD 4.3; difference −2.0, 95% CI −4.6 to 0.6; p = 0.14). Most secondary outcomes also showed greater improvement in the exercise training group. Interpretation Exercise training may improve post-thrombotic syndrome. It would be feasible to definitively evaluate exercise training as a treatment for post-thrombotic syndrome in a large multicentre trial. PMID:21098066