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

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.

Internet-based transfer of cardiac ultrasound images

NASA Technical Reports Server (NTRS)

Firstenberg, M. S.; Greenberg, N. L.; Garcia, M. J.; Morehead, A. J.; Cardon, L. A.; Klein, A. L.; Thomas, J. D.

2000-01-01

A drawback to large-scale multicentre studies is the time required for the centralized evaluation of diagnostic images. We evaluated the feasibility of digital transfer of echocardiographic images to a central laboratory for rapid and accurate interpretation. Ten patients undergoing trans-oesophageal echocardiographic scanning at three sites had representative single images and multiframe loops stored digitally. The images were analysed in the ordinary way. All images were then transferred via the Internet to a central laboratory and reanalysed by a different observer. The file sizes were 1.5-72 MByte and the transfer rates achieved were 0.6-4.8 Mbit/min. Quantitative measurements were similar between most on-site and central laboratory measurements (all P > 0.25), although measurements differed for left atrial width and pulmonary venous systolic velocities (both P < 0.05). Digital transfer of echocardiographic images and data to a central laboratory may be useful for multicentre trials.

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.

[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.

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.

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

WebBioBank: a new platform for integrating clinical forms and shared neurosignal analyses to support multi-centre studies in Parkinson's Disease.

PubMed

Rossi, Elena; Rosa, Manuela; Rossi, Lorenzo; Priori, Alberto; Marceglia, Sara

2014-12-01

The web-based systems available for multi-centre clinical trials do not combine clinical data collection (Electronic Health Records, EHRs) with signal processing storage and analysis tools. However, in pathophysiological research, the correlation between clinical data and signals is crucial for uncovering the underlying neurophysiological mechanisms. A specific example is the investigation of the mechanisms of action for Deep Brain Stimulation (DBS) used for Parkinson's Disease (PD); the neurosignals recorded from the DBS target structure and clinical data must be investigated. The aim of this study is the development and testing of a new system dedicated to a multi-centre study of Parkinson's Disease that integrates biosignal analysis tools and data collection in a shared and secure environment. We designed a web-based platform (WebBioBank) for managing the clinical data and biosignals of PD patients treated with DBS in different clinical research centres. Homogeneous data collection was ensured in the different centres (Operative Units, OUs). The anonymity of the data was preserved using unique identifiers associated with patients (ID BAC). The patients' personal details and their equivalent ID BACs were archived inside the corresponding OU and were not uploaded on the web-based platform; data sharing occurred using the ID BACs. The system allowed researchers to upload different signal processing functions (in a .dll extension) onto the web-based platform and to combine them to define dedicated algorithms. Four clinical research centres used WebBioBank for 1year. The clinical data from 58 patients treated using DBS were managed, and 186 biosignals were uploaded and classified into 4 categories based on the treatment (pharmacological and/or electrical). The user's satisfaction mean score exceeded the satisfaction threshold. WebBioBank enabled anonymous data sharing for a clinical study conducted at multiple centres and demonstrated the capabilities of the signal processing chain configuration as well as its effectiveness and efficiency for integrating the neurophysiological results with clinical data in multi-centre studies, which will allow the future collection of homogeneous data in large cohorts of patients. Copyright © 2014 Elsevier Inc. All rights reserved.

Developing a social media platform for nurses.

PubMed

Jackson, Jennifer; Kennedy, Maggie

2015-11-18

Social media tools provide opportunities for nurses to connect with colleagues and patients and to advance personally and professionally. This article describes the process of developing an innovative social media platform at a large, multi-centre teaching hospital, The Ottawa Hospital, Canada, and its benefits for nurses. The platform, TOH Nurses, was developed using a nursing process approach, involving assessment, planning, implementation and evaluation. The aim of this initiative was to address the barriers to communication inherent in the large number of nurses employed by the organisation, the physical size of the multi-centre hospital and the shift-work nature of nursing. The platform was used to provide educational materials for clinical nurses, and to share information about professional practice. The implications of using a social media platform in a healthcare setting were considered carefully during its development and implementation, including concerns regarding privacy and confidentiality.

Safeguarding the Future of Urological Research and Delivery of Clinical Excellence by Harnessing the Power of Youth to Spearhead Urological Research.

PubMed

Kasivisvanathan, Veeru; Kutikov, Alexander; Manning, Todd G; McGrath, John; Resnick, Matthew J; Sedelaar, J P Michiel; Silay, Mesrur S

2018-05-01

Trainee-led collaboratives offer exciting new perspectives and approaches to urological research. They provide a central network of expertise in methodology, mentoring, and knowledge of research processes that allows the conduct of large multicentre studies that can recruit quickly. This provides the consultant workforce of tomorrow with the skills required to deliver practice-changing clinical studies in urology. Copyright © 2017 European Association of Urology. Published by Elsevier B.V. All rights reserved.

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.

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.

ESPGHAN 2012 Guidelines for Coeliac Disease Diagnosis: Validation Through a Retrospective Spanish Multicentric Study.

PubMed

Donat, Ester; Ramos, Jose M; Sánchez-Valverde, Félix; Moreno, Ana; Martinez, Maria-Jose; Leis, Rosaura; Peña-Quintana, Luis; Castillejo, Gemma; Fernández, Sonia; Garcia, Zuriñe; Ortigosa, Luis; Balmaseda, Elena; Marugán, José-Manuel; Eizaguirre, Francisco-Javier; Lorenzo, Helena; Barrio, Josefa; Ribes-Koninckx, Carmen

2016-02-01

A large retrospective multicentre study was conducted in Spain to evaluate the efficiency of the new European Society for Pediatric Gastroenterology, Hepatology, and Nutrition (ESPGHAN) criteria for the diagnosis of coeliac disease (CD). The study protocol was approved by the ethics committee of Hospital Universitari i Politècnic La Fe (Valencia, Spain). The present study included 2177 children (ages 0.6-15.9 years) with small bowel biopsy (SBB) performed for diagnostic purposes (from 2000 to 2009) and with a minimum 2-year follow-up after biopsy. CD was diagnosed in 2126 patients (97.5%) and excluded in 51 (2.5%). Tissue transglutaminase antibodies (TG2A), anti-endomysial antibodies (EMA), and human leukocyte antigen (HLA) were reported in 751 patients, 640 symptomatic and 111 asymptomatic. TG2A levels >10 times the upper limit of normal, plus positive EMA and HLA DQ2 and/or DQ8 haplotypes, were found in 336 symptomatic patients, all of them with final diagnosis of CD. In 65 of 69 asymptomatic patients, 65 had confirmed CD and 4 did not have CD. According to the 2012 ESPGHAN guidelines, SBB may have been omitted in 52% of the symptomatic patients with CD with serologic and HLA available data. Gluten challenge was performed in 158 children, 75 of them <2 years at first biopsy. Only 1 patient in whom according to the new proposed diagnostic criteria gluten challenge would not have been mandatory did not relapse. Our results support the new ESPGHAN 2012 guidelines for diagnosis of CD can be safely used without the risk of overdiagnosis. A prospective multicentre study is needed to confirm our results.

DALI: Defining Antibiotic Levels in Intensive care unit patients: a multi-centre point of prevalence study to determine whether contemporary antibiotic dosing for critically ill patients is therapeutic.

PubMed

Roberts, Jason A; De Waele, Jan J; Dimopoulos, George; Koulenti, Despoina; Martin, Claude; Montravers, Philippe; Rello, Jordi; Rhodes, Andrew; Starr, Therese; Wallis, Steven C; Lipman, Jeffrey

2012-07-06

The clinical effects of varying pharmacokinetic exposures of antibiotics (antibacterials and antifungals) on outcome in infected critically ill patients are poorly described. A large-scale multi-centre study (DALI Study) is currently underway describing the clinical outcomes of patients achieving pre-defined antibiotic exposures. This report describes the protocol. DALI will recruit over 500 patients administered a wide range of either beta-lactam or glycopeptide antibiotics or triazole or echinocandin antifungals in a pharmacokinetic point-prevalence study. It is anticipated that over 60 European intensive care units (ICUs) will participate. The primary aim will be to determine whether contemporary antibiotic dosing for critically ill patients achieves plasma concentrations associated with maximal activity. Secondary aims will compare antibiotic pharmacokinetic exposures with patient outcome and will describe the population pharmacokinetics of the antibiotics included. Various subgroup analyses will be conducted to determine patient groups that may be at risk of very low or very high concentrations of antibiotics. The DALI study should inform clinicians of the potential clinical advantages of achieving certain antibiotic pharmacokinetic exposures in infected critically ill patients.

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.

The impact of study design and diagnostic approach in a large multi-centre ADHD study. Part 1: ADHD symptom patterns

PubMed Central

2011-01-01

Background The International Multi-centre ADHD Genetics (IMAGE) project with 11 participating centres from 7 European countries and Israel has collected a large behavioural and genetic database for present and future research. Behavioural data were collected from 1068 probands with the combined type of attention deficit/hyperactivity disorder (ADHD-CT) and 1446 'unselected' siblings. The aim was to analyse the IMAGE sample with respect to demographic features (gender, age, family status, and recruiting centres) and psychopathological characteristics (diagnostic subtype, symptom frequencies, age at symptom detection, and comorbidities). A particular focus was on the effects of the study design and the diagnostic procedure on the homogeneity of the sample in terms of symptom-based behavioural data, and potential consequences for further analyses based on these data. Methods Diagnosis was based on the Parental Account of Childhood Symptoms (PACS) interview and the DSM-IV items of the Conners' teacher questionnaire. Demographics of the full sample and the homogeneity of a subsample (all probands) were analysed by using robust statistical procedures which were adjusted for unequal sample sizes and skewed distributions. These procedures included multi-way analyses based on trimmed means and winsorised variances as well as bootstrapping. Results Age and proband/sibling ratios differed between participating centres. There was no significant difference in the distribution of gender between centres. There was a significant interaction between age and centre for number of inattentive, but not number of hyperactive symptoms. Higher ADHD symptom frequencies were reported by parents than teachers. The diagnostic symptoms differed from each other in their frequencies. The face-to-face interview was more sensitive than the questionnaire. The differentiation between ADHD-CT probands and unaffected siblings was mainly due to differences in hyperactive/impulsive symptoms. Conclusions Despite a symptom-based standardized inclusion procedure according to DSM-IV criteria with defined symptom thresholds, centres may differ markedly in probands' ADHD symptom frequencies. Both the diagnostic procedure and the multi-centre design influence the behavioural characteristics of a sample and, thus, may bias statistical analyses, particularly in genetic or neurobehavioral studies. PMID:21473745

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.

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

Publication and non-publication of clinical trials: longitudinal study of applications submitted to a research ethics committee.

PubMed

von Elm, Erik; Röllin, Alexandra; Blümle, Anette; Huwiler, Karin; Witschi, Mark; Egger, Matthias

2008-04-05

Not all clinical trials are published, which may distort the evidence that is available in the literature. We studied the publication rate of a cohort of clinical trials and identified factors associated with publication and nonpublication of results. We analysed the protocols of randomized clinical trials of drug interventions submitted to the research ethics committee of University Hospital (Inselspital) Bern, Switzerland from 1988 to 1998. We identified full articles published up to 2006 by searching the Cochrane CENTRAL database (issue 02/2006) and by contacting investigators. We analyzed factors associated with the publication of trials using descriptive statistics and logistic regression models. 451 study protocols and 375 corresponding articles were analyzed. 233 protocols resulted in at least one publication, a publication rate of 52%. A total of 366 (81%) trials were commercially funded, 47 (10%) had non-commercial funding. 346 trials (77%) were multi-centre studies and 272 of these (79%) were international collaborations. In the adjusted logistic regression model non-commercial funding (Odds Ratio [OR] 2.42, 95% CI 1.14-5.17), multi-centre status (OR 2.09, 95% CI 1.03-4.24), international collaboration (OR 1.87, 95% CI 0.99-3.55) and a sample size above the median of 236 participants (OR 2.04, 95% CI 1.23-3.39) were associated with full publication. In this cohort of applications to an ethics committee in Switzerland, only about half of clinical drug trials were published. Large multi-centre trials with non-commercial funding were more likely to be published than other trials, but most trials were funded by industry.

Cognition and bimanual performance in children with unilateral cerebral palsy: protocol for a multicentre, cross-sectional study.

PubMed

Hoare, Brian; Ditchfield, Michael; Thorley, Megan; Wallen, Margaret; Bracken, Jenny; Harvey, Adrienne; Elliott, Catherine; Novak, Iona; Crichton, Ali

2018-05-08

Motor outcomes of children with unilateral cerebral palsy are clearly documented and well understood, yet few studies describe the cognitive functioning in this population, and the associations between the two is poorly understood. Using two hands together in daily life involves complex motor and cognitive processes. Impairment in either domain may contribute to difficulties with bimanual performance. Research is yet to derive whether, and how, cognition affects a child's ability to use their two hands to perform bimanual tasks. This study will use a prospective, cross-sectional multi-centre observational design. Children (aged 6-12 years) with unilateral cerebral palsy will be recruited from one of five Australian treatment centres. We will examine associations between cognition, bimanual performance and brain neuropathology (lesion type and severity) in a sample of 131 children. The primary outcomes are: Motor - the Assisting Hand Assessment; Cognitive - Executive Function; and Brain - lesion location on structural MRI. Secondary data collected will include: Motor - Box and Blocks, ABILHAND- Kids, Sword Test; Cognitive - standard neuropsychological measures of intelligence. We will use generalized linear modelling and structural equation modelling techniques to investigate relationships between bimanual performance, executive function and brain lesion location. This large multi-centre study will examine how cognition affects bimanual performance in children with unilateral cerebral palsy. First, it is anticipated that distinct relationships between bimanual performance and cognition (executive function) will be identified. Second, it is anticipated that interrelationships between bimanual performance and cognition will be associated with common underlying neuropathology. Findings have the potential to improve the specificity of existing upper limb interventions by providing more targeted treatments and influence the development of novel methods to improve both cognitive and motor outcomes in children with unilateral cerebral palsy. ACTRN12614000631606 ; Date of retrospective registration 29/05/2014.

The frequency of occurrence and nature of recombinant feline leukemia viruses in the induction of multicentric lymphoma by infection of the domestic cat with FeLV-945.

PubMed

Ahmad, Shamim; Levy, Laura S

2010-08-01

During feline leukemia virus (FeLV) infection in the domestic cat, viruses with a novel envelope gene arise by recombination between endogenous FeLV-related elements and the exogenous infecting species. These recombinant viruses (FeLV-B) are of uncertain disease association, but have been linked to the induction of thymic lymphoma. To assess the role of FeLV-B in the induction of multicentric lymphoma and other non-T-cell disease, the frequency of occurrence and nature of FeLV-B were examined in diseased tissues from a large collection of FeLV-infected animals. Diseased tissues were examined by Southern blot and PCR amplification to detect the presence of FeLV-B. Further analysis was performed to establish the recombination junctions and infectivity of FeLV-B in diseased tissues. The results confirmed the frequent association of FeLV-B with thymic lymphoma but showed infrequent generation, low levels and lack of infectivity of FeLV-B in non-T-cell diseases including multicentric lymphoma.

Multi-centric universal pseudonymisation for secondary use of the EHR.

PubMed

Lo Iacono, Luigi

2007-01-01

This paper discusses the importance of protecting the privacy of patient data kept in an Electronic Health Record (EHR) in the case, where it leaves the control- and protection-sphere of the health care realm for secondary uses such as clinical or epidemiological research projects, health care research, assessment of treatment quality or economic assessments. The paper focuses on multi-centric studies, where various data sources are linked together using Grid technologies. It introduces a pseudonymisation system which enables a multi-centric universal pseudonymisation, meaning that a patient's identity will result in the same pseudonym, regardless of which participating study center the patient data is collected.

Vestibular migraine: who is the patient?

PubMed

Colombo, Bruno; Teggi, Roberto

2017-05-01

Vestibular migraine has been classified as a specific entity in which vestibular symptomatology is defined as part of the migrainous disorder. New and appropriate diagnostic criteria have been proposed by the Barany and International Headache Societies. The diagnosis of vestibular migraine mainly depends on the patient history. The NIVE project is a prospectic multicentric study on vestibular migraine. The aim of this project is to evaluate demographics, epidemiology, clinical manifestations of migraine and vertigo in a large cohort of Caucasian patients affected by vestibular migraine.

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.

[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.

Effects of combined exercise training and electromyostimulation treatments in chronic heart failure: A prospective multicentre study.

PubMed

Iliou, Marie C; Vergès-Patois, Bénédicte; Pavy, Bruno; Charles-Nelson, Anais; Monpère, Catherine; Richard, Rudy; Verdier, Jean C

2017-08-01

Background Exercise training as part of a comprehensive cardiac rehabilitation is recommended for patients with cardiac heart failure. It is a valuable method for the improvement of exercise tolerance. Some studies reported a similar improvement with quadricipital electrical myostimulation, but the effect of combined exercise training and electrical myostimulation in cardiac heart failure has not been yet evaluated in a large prospective multicentre study. Purpose The aim of this study was to determine whether the addition of low frequency electrical myostimulation to exercise training may improve exercise capacity and/or muscular strength in cardiac heart failure patients. Methods Ninety-one patients were included (mean age: 58 ± 9 years; New York Heart Association II/III: 52/48%, left ventricular ejection fraction: 30 ± 7%) in a prospective French study. The patients were randomised into two groups: 41 patients in exercise training and 50 in exercise training + electrical myostimulation. All patients underwent 20 exercise training sessions. In addition, in the exercise training + electrical myostimulation group, patients underwent 20 low frequency (10 Hz) quadricipital electrical myostimulation sessions. Each patient underwent a cardiopulmonary exercise test, a six-minute walk test, a muscular function evaluation and a quality of life questionnaire, before and at the end of the study. Results A significant improvement of exercise capacity (Δ peak oxygen uptake+15% in exercise training group and +14% in exercise training + electrical myostimulation group) and of quality of life was observed in both groups without statistically significant differences between the two groups. Mean creatine kinase level increased in the exercise training group whereas it remained stable in the combined group. Conclusions This prospective multicentre study shows that electrical myostimulation on top of exercise training does not demonstrate any significant additional improvement in exercise capacity in cardiac heart failure patients.

Calculating the risk of a pancreatic fistula after a pancreaticoduodenectomy: a systematic review

PubMed Central

Vallance, Abigail E; Young, Alastair L; Macutkiewicz, Christian; Roberts, Keith J; Smith, Andrew M

2015-01-01

Background A post-operative pancreatic fistula (POPF) is a major cause of morbidity and mortality after a pancreaticoduodenectomy (PD). This systematic review aimed to identify all scoring systems to predict POPF after a PD, consider their clinical applicability and assess the study quality. Method An electronic search was performed of Medline (1946–2014) and EMBASE (1996–2014) databases. Results were screened according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, and quality assessed according to the QUIPS (quality in prognostic studies) tool. Results Six eligible scoring systems were identified. Five studies used the International Study Group on Pancreatic Fistula (ISGPF) definition. The proposed scores feature between two and five variables and of the 16 total variables, the majority (12) featured in only one score. Three scores could be fully completed pre-operatively whereas 1 score included intra-operative and two studies post-operative variables. Four scores were internally validated and of these, two scores have been subject to subsequent multicentre review. The median QUIPS score was 38 out of 50 (range 16–50). Conclusion These scores show potential in calculating the individualized patient risk of POPF. There is, however, much variation in current scoring systems and further validation in large multicentre cohorts is now needed. PMID:26456948

Videoconferencing for site initiations in clinical studies: Mixed methods evaluation of usability, acceptability, and impact on recruitment.

PubMed

Randell, Rebecca; Backhouse, Michael R; Nelson, E Andrea

2016-12-01

A critical issue for multicentre clinical studies is conducting site initiations, ensuring sites are trained in study procedures and comply with relevant governance requirements before they begin recruiting patients. How technology can support site initiations has not previously been explored. This study sought to evaluate use of off-the-shelf web-based videoconferencing to deliver site initiations for a large national multicentre study. Participants in the initiations, including podiatrists, diabetologists, trial coordinators, and research nurses, completed an online questionnaire based on the System Usability Scale (SUS) (N = 15). This was followed by semi-structured interviews, with a consultant diabetologist, a trial coordinator, and three research nurses, exploring perceived benefits and limitations of videoconferencing. The mean SUS score for the videoconferencing platform was 87.2 (SD = 13.7), suggesting a good level of usability. Interview participants perceived initiations delivered by videoconferencing as being more interactive and easier to follow than those delivered by teleconference. In comparison to face-to-face initiations, videoconferencing takes less time, easily fitting in with the work of staff at the local sites. Perceptions of impact on communication varied according to the hardware used. Off-the-shelf videoconferencing is a viable alternative to face-to-face site initiations and confers advantages over teleconferencing.

Acceptability of the female condom in different groups of women in South Africa--a multicentred study to inform the national female condom introductory strategy.

PubMed

Beksinska, M E; Rees, V H; McIntyre, J A; Wilkinson, D

2001-08-01

To assess the acceptability of the female condom to different groups of women and their partners in South Africa. Descriptive, cross-sectional study. Multicentre study conducted in five sites. The study recruited 678 women from five centres to an acceptability trial of the female condom. Acceptability and successful use varied between the centres. Factors affecting successful use and willingness and intention to use the method again. In total, 209 women used the condom at least once. Discontinuation rates were high, with partner reluctance to try the method as the main reason given for discontinuation at all sites. Women who had previous experience with the male condom or who received a more intensive training session generally found the device easier to use. The main issues concerning women were over-lubrication (27%) and concern that the device was too large (28%). The majority of women said that they would be interested in using the method again (86%) and would recommend it to friends (95%). Overcoming partner opposition is an important issue to address when introducing the method. The study was used to address the national introductory strategy of the female condom, which began in 1998.

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.

Do occupational exposures to vinyl chloride cause hepatocellular carcinoma and cirrhosis?

PubMed

Lotti, Marcello

2017-05-01

Controversy exists about the association between occupational exposures to vinyl chloride and hepatocellular carcinoma and cirrhosis. Two large multicentre mortality cohort studies, one American and another European, reported higher mortality for primary cancer of liver and biliary tract. However, the American study was not able to rule out misclassification, because based on death certificates and under the heading primary liver cancers, some angiosarcomas, the typical neoplasia associated with vinyl chloride, may have been included. The American study does not report on cirrhosis mortality. The European study also reports higher mortality of primary liver cancer, but contrary to the American study in a further analysis based on 10 verified cases of hepatocellular carcinoma, an exposure-response trend with duration of employment and with cumulative exposure to vinyl chloride was detected. A smaller cohort belonging to this multicentre cohort confirmed these results. Meta-analyses based on the two large cohorts concluded for a small excess of primary liver cancer, although misclassification could not be ruled out. Excess risk of cirrhosis was reported in the European cohort, in a subcohort and in a cross-sectional study. However, a meta-analysis did not confirm this excess. Several critical appraisals of the literature reached antithetical conclusions about hepatocellular carcinoma, cirrhosis and occupational exposures to vinyl chloride. For both hepatocellular carcinoma and cirrhosis, a study suggests an additive and multiplicative effect of vinyl chloride exposure with viral hepatitis and alcohol consumption respectively. Pathology reports seem to indicate a possible development of hepatocellular carcinoma but not of cirrhosis after high exposures to vinyl chloride. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Impact of the recent recession on self-harm: Longitudinal ecological and patient-level investigation from the Multicentre Study of Self-harm in England.

PubMed

Hawton, Keith; Bergen, Helen; Geulayov, Galit; Waters, Keith; Ness, Jennifer; Cooper, Jayne; Kapur, Navneet

2016-02-01

Economic recessions are associated with increases in suicide rates but there is little information for non-fatal self-harm. To investigate the impact of the recent recession on rates of self-harm in England and problems faced by patients who self-harm. Analysis of data from the Multicentre Study of Self-harm in England for 2001-2010 and local employment statistics for Oxford, Manchester and Derby, including interrupted time series analyses to estimate the effect of the recession on rates of self-harm. Rates of self-harm increased in both genders in Derby and in males in Manchester in 2008-2010, but not in either gender in Oxford, results which largely followed changes in general population unemployment. More patients who self-harm were unemployed in 2008-10 compared to before the recession. The proportion in receipt of sickness or disability allowances decreased. More patients of both genders had employment and financial problems in 2008-2010 and more females also had housing problems, changes which were also largely found in employed patients. We have assumed that the recession began in 2008 and information on problems was only available for patients having a psychosocial assessment. Increased rates of self-harm were found in areas where there were greater rises in rates of unemployment. Work, financial and housing problems increased in people who self-harmed. Changes in welfare benefits may have contributed. None. Copyright © 2015 Elsevier B.V. All rights reserved.

The clinical and genetic spectrum of catecholaminergic polymorphic ventricular tachycardia: findings from an international multicentre registry.

PubMed

Roston, Thomas M; Yuchi, Zhiguang; Kannankeril, Prince J; Hathaway, Julie; Vinocur, Jeffrey M; Etheridge, Susan P; Potts, James E; Maginot, Kathleen R; Salerno, Jack C; Cohen, Mitchell I; Hamilton, Robert M; Pflaumer, Andreas; Mohammed, Saira; Kimlicka, Lynn; Kanter, Ronald J; LaPage, Martin J; Collins, Kathryn K; Gebauer, Roman A; Temple, Joel D; Batra, Anjan S; Erickson, Christopher; Miszczak-Knecht, Maria; Kubuš, Peter; Bar-Cohen, Yaniv; Kantoch, Michal; Thomas, Vincent C; Hessling, Gabriele; Anderson, Chris; Young, Ming-Lon; Choi, Sally H J; Cabrera Ortega, Michel; Lau, Yung R; Johnsrude, Christopher L; Fournier, Anne; Van Petegem, Filip; Sanatani, Shubhayan

2018-03-01

Catecholaminergic polymorphic ventricular tachycardia (CPVT) is an ion channelopathy characterized by ventricular arrhythmia during exertion or stress. Mutations in RYR2-coded Ryanodine Receptor-2 (RyR2) and CASQ2-coded Calsequestrin-2 (CASQ2) genes underlie CPVT1 and CPVT2, respectively. However, prognostic markers are scarce. We sought to better characterize the phenotypic and genotypic spectrum of CPVT, and utilize molecular modelling to help account for clinical phenotypes. This is a Pediatric and Congenital Electrophysiology Society multicentre, retrospective cohort study of CPVT patients diagnosed at <19 years of age and their first-degree relatives. Genetic testing was undertaken in 194 of 236 subjects (82%) during 3.5 (1.4-5.3) years of follow-up. The majority (60%) had RyR2-associated CPVT1. Variant locations were predicted based on a 3D structural model of RyR2. Specific residues appear to have key structural importance, supported by an association between cardiac arrest and mutations in the intersubunit interface of the N-terminus, and the S4-S5 linker and helices S5 and S6 of the RyR2 C-terminus. In approximately one quarter of symptomatic patients, cardiac events were precipitated by only normal wakeful activities. This large, multicentre study identifies contemporary challenges related to the diagnosis and prognostication of CPVT patients. Structural modelling of RyR2 can improve our understanding severe CPVT phenotypes. Wakeful rest, rather than exertion, often precipitated life-threatening cardiac events. Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2017. For Permissions, please email: journals.permissions@oup.com.

The feasibility and cost of a large multicentre audit of process and outcome of prostatectomy.

PubMed Central

Emberton, M; Neal, D E; Black, N; Harrison, M; Fordham, M; McBrien, M P; Williams, R E; McPherson, K; Develin, H B

1995-01-01

Objective--To determine the feasibility of performing multicentre process and outcome audits of common interventions taking prostatic procedures as an example. Design--Prospective, cohort study. Setting--All National Health Service and independent hospitals in Northern, Wessex, Mersey, and South West Thames health regions. Patients--5361 men undergoing prostatectomy identified by 103 of the 107 urologists and general surgeons performing prostatectomy in the study regions. Main measures-- Rates of participation by surgeons and patients; completeness of clinical data provided by surgeons; patient response rate and completeness of patient derived data; and cost. Results--Most surgeons (103,96%) agreed to participate. Overall, the proportion of eligible patients invited to take part was high (89%), although this was only measured in South West Thames, where dedicated data collectors were employed. Few men (80, 1.5%) declined to participate. Of those surviving for three months after surgery, 82.4% (4226) completed and returned the postal questionnaire. The response rate was higher in South West Thames (86.7%) than in the other regions (80.6%-80.8%). The audit was well received: 91% of patients found the questionnaire easy to complete and only 2.3% of them disapproved. Completeness of data was high with both the hospital and patient questionnaires. Missing data occurred in less than 5% of responses to most questions. The attributable cost was 34.50 pounds per patient identified or 44 pounds for patients in whom either the treatment outcome or vital status was known three months after their prostatectomy. Conclusions--This multicentre audit of process and outcome of prostatectomy proved feasible in terms of surgeon participation, patient identification, and the quantity and quality of data collection. Whether the cost was warranted will depend on how surgeons use the audit data to modify their practice. PMID:10156395

Genomic analysis of the origins and evolution of multicentric diffuse lower-grade gliomas.

PubMed

Hayes, Josie; Yu, Yao; Jalbert, Llewellyn E; Mazor, Tali; Jones, Lindsey E; Wood, Matthew D; Walsh, Kyle M; Bengtsson, Henrik; Hong, Chibo; Oberndorfer, Stefan; Roetzer, Thomas; Smirnov, Ivan V; Clarke, Jennifer L; Aghi, Manish K; Chang, Susan M; Nelson, Sarah J; Woehrer, Adelheid; Phillips, Joanna J; Solomon, David A; Costello, Joseph F

2018-04-09

Rare multicentric lower-grade gliomas (LGGs) represent a unique opportunity to study the heterogeneity among distinct tumor foci in a single patient and to infer their origins and parallel patterns of evolution. In this study, we integrate clinical features, histology, and immunohistochemistry for 4 patients with multicentric LGG, arising both synchronously and metachronously. For 3 patients we analyze the phylogeny of the lesions using exome sequencing, including one case with a total of 8 samples from the 2 lesions. One patient was diagnosed with multicentric isocitrate dehydrogenase 1 (IDH1) mutated diffuse astrocytomas harboring distinct IDH1 mutations, R132H and R132C; the latter mutation has been associated with Li-Fraumeni syndrome, which was subsequently confirmed in the patient's germline DNA and shown in additional cases with The Cancer Genome Atlas data. In another patient, phylogenetic analysis of synchronously arising grade II and grade III diffuse astrocytomas demonstrated a single shared mutation, IDH1 R132H, and revealed convergent evolution via non-overlapping mutations in ATRX and TP53. In 2 cases, there was divergent evolution of IDH1-mutated and 1p/19q-codeleted oligodendroglioma and IDH1-mutated and 1p/19q-intact diffuse astrocytoma, occurring synchronously in one case and metachronously in a second. Each tumor in multicentric LGG cases may arise independently or may diverge very early in their development, presenting as genetically and histologically distinct tumors. Comprehensive sampling of these lesions can therefore significantly alter diagnosis and management. Additionally, somatic IDH1 R132C mutation in either multicentric or solitary LGG identifies unsuspected germline TP53 mutation, validating the limited number of published cases.

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.

Rapid update on childhood immune thrombocytopenic purpure.

PubMed

Cole, Catherine H

2012-05-01

Most childhood immune thrombocytopenic purpure is benign, self-limiting and requires no therapy. However, questions remain: (i) to treat or not; (ii) bone marrow examination or not; and (iii) admit to hospital or not. These questions have dominated the literature and we still need a prospective large multi-centre study of these issues to determine a useful bleeding score, quality of life measure and a measure of parental anxiety. © 2011 The Author. Journal of Paediatrics and Child Health © 2011 Paediatrics and Child Health Division (Royal Australasian College of Physicians).

Management of large bowel obstruction with self-expanding metal stents. A multicentre retrospective study of factors determining outcome.

PubMed

Geraghty, J; Sarkar, S; Cox, T; Lal, S; Willert, R; Ramesh, J; Bodger, K; Carlson, G L

2014-06-01

UK cancer guidelines recommend patients with colonic obstruction due to suspected malignancy be considered for stenting with a self-expanding metal stent (SEMS). Considerable variation in practice exists due to a lack of expertise, technical difficulties and other, as yet ill-defined features. This retrospective multi-centre study aims to determine the outcome following colonic stenting for large bowel obstruction and identify factors associated with successful intervention. A regional programme of colonic stenting for large bowel obstruction, in five UK centres from 2005 to 2010 was evaluated for outcome including technical and clinical success, survival, complications and reoperation. A SEMS was inserted in 334 patients, including 264 (79.0%) for palliation and 52 (15.6%) as a bridge to surgery. Technical success was achieved in 292 (87.4%) patients, with 46 (13.8%) experiencing a complication or technical failure. Reoperation was required in 39 (14.8%) patients stented for palliation of colorectal cancer of whom 16 (6.1%) subsequently required a colostomy. A one-stage primary anastomosis was achieved in 35 (67.3%) of the 52 patients undergoing stenting as a bridge to resection. Technical success did not vary by indication or site of obstruction (P = 0.60) but was higher for operators who had performed more than 10 procedures (OR 3.34, P = 0.001). ASA grade ≥3 predicted a worse clinical outcome (OR 0.43, P = 0.04). The through-the-scope (TTS) endoscopy technique was more successful than radiological placement alone (90.3% vs 74.8%, P < 0.001). Experienced operators using a TTS technique achieved a better outcome for the emergency management of large bowel obstruction. Older, sicker patients and those with extracolonic and benign strictures fared less well. Colorectal Disease © 2014 The Association of Coloproctology of Great Britain and Ireland.

Clinical aspects of ECL-cell abnormalities.

PubMed Central

Hirschowitz, B. I.

1998-01-01

ECL cell hyperplasia results from hypergastrinemia, and in man this occurs due to achlorhydria in atrophic gastritis (pernicious anemia [PA]) and gastrinoma (Zollinger-Ellison syndrome [ZES]). Progression to neoplasia, i.e., ECL cell carcinoids (usually small, multicentric and non-functional), occurs in some five to 10 percent of patients with PA where they remain gastrin-dependent and reversible by normalization of serum gastrin by antrectomy. Even if untreated, the carcinoids are almost invariably benign and do not cause death. In ZES, ECL cell hyperplasia is progressive due to hypergastrinemia. However, carcinoids develop only in the MEN-I subtype but pose no additional threat of malignancy. A conservative approach is recommended for small multicentric carcinoids, and the tumors do not need removal. By contrast, single, large, non-gastrin-dependent carcinoids represent a different biological and clinical problem and are frequently malignant. PMID:10461361

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

The effect of a perioperative ketamine infusion on the incidence of chronic postsurgical pain-a pilot study.

PubMed

Peyton, P J; Wu, C; Jacobson, T; Hogg, M; Zia, F; Leslie, K

2017-07-01

Chronic postsurgical pain (CPSP) is a common and debilitating complication of major surgery. We undertook a pilot study at three hospitals to assess the feasibility of a proposed large multicentre placebo-controlled randomised trial of intravenous perioperative ketamine to reduce the incidence of CPSP. Ketamine, 0.5 mg/kg pre-incision, 0.25 mg/kg/hour intraoperatively and 0.1 mg/kg/hour for 24 hours, or placebo, was administered to 80 patients, recruited over a 15-month period, undergoing abdominal or thoracic surgery under general anaesthesia. The primary endpoint was CPSP in the area of the surgery reported at six-month telephone follow-up using a structured questionnaire. Fourteen patients (17.5%) reported CPSP (relative risk [95% confidence interval] if received ketamine 1.18 [0.70 to 1.98], P =0.56). Four patients in the treatment group and three in the control group reported ongoing analgesic use to treat CPSP and two patients in each group reported their worst pain in the previous 24 hours at ≥3/10 at six months. There were no significant differences in adverse event rates, quality of recovery scores, or cumulative morphine equivalents consumption in the first 72 hours. Numeric Rating Scale pain scores (median [interquartile range, IQR]) for average pain in the previous 24 hours among those patients reporting CPSP were 17.5 [0 to 40] /100 with no difference between treatment groups. A large (n=4,000 to 5,000) adequately powered multicentre trial is feasible using this population and methodology.

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.

[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.

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.

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.

Development of a new multimedia instrument to measure cancer-specific quality of life in Portuguese-speaking patients with varying literacy skills.

PubMed

Paiva, Carlos Eduardo; Siquelli, Felipe Augusto Ferreira; Zaia, Gabriela Rossi; de Andrade, Diocésio Alves Pinto; Borges, Marcos Aristoteles; Jácome, Alexandre A; Giroldo, Gisele Augusta Sousa Nascimento; Santos, Henrique Amorim; Hahn, Elizabeth A; Uemura, Gilberto; Paiva, Bianca Sakamoto Ribeiro

2016-01-01

To develop and validate a new multimedia instrument to measure health-related quality of life (HRQOL) in Portuguese-speaking patients with cancer. A mixed-methods study conducted in a large Brazilian Cancer Hospital. The instrument was developed along the following sequential phases: identification of HRQOL issues through qualitative content analysis of individual interviews, evaluation of the most important items according to the patients, review of the literature, evaluation by an expert committee, and pretesting. In sequence, an exploratory factor analysis was conducted (pilot testing, n = 149) to reduce the number of items and to define domains and scores. The psychometric properties of the IQualiV-OG-21 were measured in a large multicentre Brazilian study (n = 323). A software containing multimedia resources were developed to facilitate self-administration of IQualiV-OG-21; its feasibility and patients' preferences ("paper and pencil" vs. software) were further tested (n = 54). An exploratory factor analysis reduced the 30-item instrument to 21 items. The IQualiV-OG-21 was divided into 6 domains: emotional, physical, existential, interpersonal relationships, functional and financial. The multicentre study confirmed that it was valid and reliable. The electronic multimedia instrument was easy to complete and acceptable to patients. Regarding preferences, 61.1 % of them preferred the electronic format in comparison with the paper and pencil format. The IQualiV-OG-21 is a new valid and reliable multimedia HRQOL instrument that is well-understood, even by patients with low literacy skills, and can be answered quickly. It is a useful new tool that can be translated and tested in other cultures and languages.

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.

Recommendations of the VAC2VAC workshop on the design of multi-centre validation studies.

PubMed

Halder, Marlies; Depraetere, Hilde; Delannois, Frédérique; Akkermans, Arnoud; Behr-Gross, Marie-Emmanuelle; Bruysters, Martijn; Dierick, Jean-François; Jungbäck, Carmen; Kross, Imke; Metz, Bernard; Pennings, Jeroen; Rigsby, Peter; Riou, Patrice; Balks, Elisabeth; Dobly, Alexandre; Leroy, Odile; Stirling, Catrina

2018-03-01

Within the Innovative Medicines Initiative 2 (IMI 2) project VAC2VAC (Vaccine batch to vaccine batch comparison by consistency testing), a workshop has been organised to discuss ways of improving the design of multi-centre validation studies and use the data generated for product-specific validation purposes. Moreover, aspects of validation within the consistency approach context were addressed. This report summarises the discussions and outlines the conclusions and recommendations agreed on by the workshop participants. Copyright © 2018.

Do all the European surgeons perform the same D2? The need of D2 audit in Europe.

PubMed

Bencivenga, Maria; Verlato, Giuseppe; Mengardo, Valentina; Weindelmayer, Jacopo; Allum, William H

2018-06-04

Although D2 lymphadenectomy is the standard of care for radical intent surgical treatment of gastric cancer, the real compliance with D2 dissection in Europe is still unknown. The aim of the present study is to analyze the variation in lymph-node harvesting reported after D2 dissection in European series and to present a European project aiming at evaluating the real compliance with D2 lymphadenectomy. A PubMed search for papers using the key words "D2 lymphadenectomy" and "gastric cancer" from 2008 to 2017 was undertaken. Only studies by European authors in English language reporting the number of retrieved lymph nodes after D2 lymphadenectomy were included. The results of literature review were descriptively reported. The literature survey yielded 16 studies: 2 RCTs, 3 observational multicentre studies, and 11 observational monocentric studies. A large variability was found in the number of retrieved nodes, which, overall, was the lowest in the surgical series from Eastern Europe (16.6 and 19.9 in the Lithuanian and Hungarian series, respectively) and the highest in an Italian RCT. The within-study variability was also quite high, especially in multicentre RCTs and observational studies. Sample size tended to have a larger effect on the variability of lymph nodes retrieved than on its actual value. However, in both cases, the relation was not significant, due to the low number of studies considered. There is a large variability in the number of retrieved nodes after D2 dissection in European series. This reflects, at least partly, different approaches to D2 lymphadenectomy by European surgeons and may be responsible of the different outcomes observed in patients with gastric cancer across Europe. Therefore, there is the need to standardize the practice of D2 gastrectomy in Europe and to define possible variations of D2 procedures according to tumour's characteristics.

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.

Cross-centre replication of suppressed burrowing behaviour as an ethologically relevant pain outcome measure in the rat: a prospective multicentre study.

PubMed

Wodarski, Rachel; Delaney, Ada; Ultenius, Camilla; Morland, Rosie; Andrews, Nick; Baastrup, Catherine; Bryden, Luke A; Caspani, Ombretta; Christoph, Thomas; Gardiner, Natalie J; Huang, Wenlong; Kennedy, Jeffrey D; Koyama, Suguru; Li, Dominic; Ligocki, Marcin; Lindsten, Annika; Machin, Ian; Pekcec, Anton; Robens, Angela; Rotariu, Sanziana M; VoB, Sabrina; Segerdahl, Marta; Stenfors, Carina; Svensson, Camilla I; Treede, Rolf-Detlef; Uto, Katsuhiro; Yamamoto, Kazumi; Rutten, Kris; Rice, Andrew S C

2016-10-01

Burrowing, an ethologically relevant rodent behaviour, has been proposed as a novel outcome measure to assess the global impact of pain in rats. In a prospective multicentre study using male rats (Wistar, Sprague-Dawley), replication of suppressed burrowing behaviour in the complete Freund adjuvant (CFA)-induced model of inflammatory pain (unilateral, 1 mg/mL in 100 µL) was evaluated in 11 studies across 8 centres. Following a standard protocol, data from participating centres were collected centrally and analysed with a restricted maximum likelihood-based mixed model for repeated measures. The total population (TP-all animals allocated to treatment; n = 249) and a selected population (SP-TP animals burrowing over 500 g at baseline; n = 200) were analysed separately, assessing the effect of excluding "poor" burrowers. Mean baseline burrowing across studies was 1113 g (95% confidence interval: 1041-1185 g) for TP and 1329 g (1271-1387 g) for SP. Burrowing was significantly suppressed in the majority of studies 24 hours (7 studies/population) and 48 hours (7 TP, 6 SP) after CFA injections. Across all centres, significantly suppressed burrowing peaked 24 hours after CFA injections, with a burrowing deficit of -374 g (-479 to -269 g) for TP and -498 g (-609 to -386 g) for SP. This unique multicentre approach first provided high-quality evidence evaluating suppressed burrowing as robust and reproducible, supporting its use as tool to infer the global effect of pain on rodents. Second, our approach provided important informative value for the use of multicentre studies in the future.

Open-label, multicentre safety study of vemurafenib in 3219 patients with BRAFV600 mutation-positive metastatic melanoma: 2-year follow-up data and long-term responders' analysis.

PubMed

Blank, Christian U; Larkin, James; Arance, Ana M; Hauschild, Axel; Queirolo, Paola; Del Vecchio, Michele; Ascierto, Paolo A; Krajsova, Ivana; Schachter, Jacob; Neyns, Bart; Garbe, Claus; Chiarion Sileni, Vanna; Mandalà, Mario; Gogas, Helen; Espinosa, Enrique; Hospers, Geke A P; Miller, Wilson H; Robson, Susan; Makrutzki, Martina; Antic, Vladan; Brown, Michael P

2017-07-01

The orally available BRAF kinase inhibitor vemurafenib is an effective and tolerable treatment option for patients with metastatic melanoma harbouring BRAF V600 mutations. We assessed the safety of vemurafenib in a large population of patients with few alternative treatment options; we report updated 2-year safety. This was an open-label, multicentre study of vemurafenib (960 mg bid) in patients with previously treated or untreated BRAF mutation-positive metastatic melanoma (cobas ® 4800 BRAF V600 Mutation Test). The primary end-point was safety; efficacy end-points were secondary. An exploratory analysis was performed to assess safety outcomes in patients with long duration of response (DOR) (≥12 or ≥24 months). After a median follow-up of 32.2 months (95% CI, 31.1-33.2 months), 3079/3219 patients (96%) had discontinued treatment. Adverse events (AEs) were largely consistent with previous reports; the most common all-grade treatment-related AEs were arthralgia (37%), alopecia (25%) and hyperkeratosis (23%); the most common grade 3/4 treatment-related AEs were squamous cell carcinoma of the skin (8%) and keratoacanthoma (8%). In the exploratory analysis, patients with DOR ≥12 months (n = 287) or ≥24 months (n = 133) were more likely to experience grade 3/4 AEs than the overall population. No new specific safety signals were observed with longer vemurafenib exposure. After 2 years' follow-up, safety was maintained in this large group of patients with BRAF V600 mutation-positive metastatic melanoma who are more representative of routine clinical practice than typical clinical trial populations. These data suggest that long-term vemurafenib treatment is effective and tolerable without the development of new safety signals. Copyright © 2017 Elsevier Ltd. 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.

'Away Days' in multi-centre randomised controlled trials: a questionnaire survey of their use and a case study on the effect of one Away Day on patient recruitment.

PubMed

Jefferson, Laura; Cook, Liz; Keding, Ada; Brealey, Stephen; Handoll, Helen; Rangan, Amar

2015-11-06

'Away Days' (trial promotion and training events for trial site personnel) are a well-established method used by trialists to encourage engagement of research sites in the recruitment of patients to multi-centre randomised controlled trials (RCTs). We explored the use of Away Days in multi-centre RCTs and analysed the effect on patient recruitment in a case study. Members of the United Kingdom Trial Managers' Network were surveyed in June 2013 to investigate their experiences in the design and conduct of Away Days in RCTs. We used data from a multi-centre pragmatic surgical trial to explore the effects of an Away Day on the screening and recruitment of patients. A total of 94 people responded to the survey. The majority (78%), who confirmed had organised an Away Day previously, found them to be useful. This is despite their costs.. There was no evidence, however, from the analysis of data from a surgical trial that attendance at an Away Day increased the number of patients screened or recruited at participating sites. Although those responsible for managing RCTs in the UK tend to believe that trial Away Days are beneficial, evidence from a multi-centre surgical trial shows no improvement on a key indicator of trial success. This points to the need to carefully consider the aims, design and conduct of Away Days. Further more rigorous research nested within RCTs would be valuable to evaluate the design and conduct of Away Days. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

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

Species distribution and susceptibility profile to fluconazole, voriconazole and MXP-4509 of 551 clinical yeast isolates from a Romanian multi-centre study.

PubMed

Minea, B; Nastasa, V; Moraru, R F; Kolecka, A; Flonta, M M; Marincu, I; Man, A; Toma, F; Lupse, M; Doroftei, B; Marangoci, N; Pinteala, M; Boekhout, T; Mares, M

2015-02-01

This is the first multi-centre study regarding yeast infections in Romania. The aim was to determine the aetiological spectrum and susceptibility pattern to fluconazole, voriconazole and the novel compound MXP-4509. The 551 isolates were identified using routine laboratory methods, matrix-assisted laser desorption ionisation time-of-flight mass spectrometry (MALDI-TOF MS) and DNA sequence analysis. Susceptibility testing was performed using the European Committee for Antimicrobial Susceptibility Testing (EUCAST) method and breakpoints. The yeasts originated from superficial infections (SUP, 51.5 %), bloodstream infections (BSI, 31.6 %) and deep-seated infections (DEEP, 16.9 %), from patients of all ages. Nine genera and 30 species were identified. The 20 Candida species accounted for 94.6 % of all isolates. C. albicans was the overall leading pathogen (50.5 %). Lodderomyces elongisporus is reported for the first time as a fungaemia cause in Europe. C. glabrata and Saccharomyces cerevisiae, as well as the non-Candida spp. and non-albicans Candida spp. groups, showed decreased fluconazole susceptibility (<75 %). The overall fluconazole resistance was 10.2 %. C. krusei accounted for 27 of the 56 fluconazole-resistant isolates. The overall voriconazole resistance was 2.5 % and was due mainly to C. glabrata and C. tropicalis isolates. Fluconazole resistance rates for the three categories of infection were similar to the overall value; voriconazole resistance rates differed: 4 % for BSI, 3.2 % for DEEP and 1.4 % for SUP. The antifungal activity of MXP-4509 was superior to voriconazole against C. glabrata and many fluconazole-resistant isolates. There was a large percentage of non-albicans Candida isolates. A large part of the high fluconazole resistance was not acquired but intrinsic, resulting from the high percentage of C. krusei.

Accelerated Titration of Oxytocin in Nulliparous Women with Labour Dystocia: Results of the ACTION Pilot Randomized Controlled Trial.

PubMed

Dy, Jessica; Rainey, Jenna; Walker, Mark C; Fraser, William; Smith, Graeme N; White, Ruth Rennicks; Waddell, Patti; Janoudi, Ghayath; Corsi, Daniel J; Wei, Shu Qin

2018-06-01

The primary objective was to determine the feasibility of a large RCT assessing the effectiveness of an accelerated oxytocin titration (AOT) protocol compared with a standard gradual oxytocin titration (GOT) in reducing the risk of CS in nulliparous women diagnosed with dystocia in the first stage of labour. The secondary objective was to obtain preliminary data on the safety and efficacy of the foregoing AOT protocol. This was a multicentre, double-masked, parallel-group pilot RCT. This study was conducted in three Canadian birthing centres. A total of 79 term nulliparous women carrying a singleton pregnancy in spontaneous labour, with a diagnosis of labour dystocia, were randomized to receive either GOT (initial dose 2 mU/min with increments of 2 mU/min) or AOT (initial dose 4 mU/min with increments of 4 mU/min), in a 1:1 ratio. An intention-to-treat analysis was applied. A total of 252 women were screened and approached, 137 (54.4%) consented, and 79 (31.3%) were randomized. Overall protocol adherence was 76 of 79 (96.2%). Of the women randomized, 10 (25.6%) allocated to GOT had a CS compared with six (15.0%) allocated to AOT (Fisher exact test P = 0.27). This pilot study demonstrated that a large, multicentre RCT is not only feasible, but also necessary to assess the effectiveness and safety of an AOT protocol for labour augmentation with regard to CS rate and indicators of maternal and perinatal morbidities. Copyright © 2018 Society of Obstetricians and Gynaecologists of Canada. Published by Elsevier Inc. All rights reserved.

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.

Using DTI to assess white matter microstructure in cerebral small vessel disease (SVD) in multicentre studies

PubMed Central

Croall, Iain D.; Lohner, Valerie; Moynihan, Barry; Khan, Usman; Hassan, Ahamad; O’Brien, John T.; Morris, Robin G.; Tozer, Daniel J.; Cambridge, Victoria C.; Harkness, Kirsty; Werring, David J.; Blamire, Andrew M.; Ford, Gary A.; Barrick, Thomas R.

2017-01-01

Diffusion tensor imaging (DTI) metrics such as fractional anisotropy (FA) and mean diffusivity (MD) have been proposed as clinical trial markers of cerebral small vessel disease (SVD) due to their associations with outcomes such as cognition. However, studies investigating this have been predominantly single-centre. As clinical trials are likely to be multisite, further studies are required to determine whether associations with cognition of similar strengths can be detected in a multicentre setting. One hundred and nine patients (mean age =68 years) with symptomatic lacunar infarction and confluent white matter hyperintensities (WMH) on MRI was recruited across six sites as part of the PRESERVE DTI substudy. After handling missing data, 3T-MRI scanning was available from five sites on five scanner models (Siemens and Philips), alongside neuropsychological and quality of life (QoL) assessments. FA median and MD peak height were extracted from DTI histogram analysis. Multiple linear regressions were performed, including normalized brain volume, WMH lesion load, and n° lacunes as covariates, to investigate the association of FA and MD with cognition and QoL. DTI metrics from all white matter were significantly associated with global cognition (standardized β =0.268), mental flexibility (β =0.306), verbal fluency (β =0.376), and Montreal Cognitive Assessment (MoCA) (β =0.273). The magnitudes of these associations were comparable with those previously reported from single-centre studies found in a systematic literature review. In this multicentre study, we confirmed associations between DTI parameters and cognition, which were similar in strength to those found in previous single-centre studies. The present study supports the use of DTI metrics as biomarkers of disease progression in multicentre studies. PMID:28487471

Rates of self-harm presenting to general hospitals: a comparison of data from the Multicentre Study of Self-Harm in England and Hospital Episode Statistics

PubMed Central

Turnbull, Pauline; Hawton, Keith; Geulayov, Galit; Waters, Keith; Ness, Jennifer; Townsend, Ellen; Khundakar, Kazem; Kapur, Nav

2016-01-01

Objective Rates of hospital presentation for self-harm in England were compared using different national and local data sources. Design The study was descriptive and compared bespoke data collection methods for recording self-harm presentations to hospital with routinely collected hospital data. Setting Local area data on self-harm from the 3 centres of the Multicentre Study of Self-harm in England (Oxford, Manchester and Derby) were used along with national and local routinely collected data on self-harm admissions and emergency department attendances from Hospital Episode Statistics (HES). Primary outcome Rate ratios were calculated to compare rates of self-harm generated using different data sources nationally and locally (between 2010 and 2012) and rates of hospital presentations for self-harm were plotted over time (between 2003 and 2012), based on different data sources. Results The total number of self-harm episodes between 2010 and 2012 was 13 547 based on Multicentre Study data, 9600 based on HES emergency department data and 8096 based on HES admission data. Nationally, routine HES data underestimated overall rates of self-harm by approximately 60% compared with rates based on Multicentre Study data (rate ratio for HES emergency department data, 0.41 (95% CI 0.35 to 0.49); rate ratio for HES admission data, 0.42 (95% CI 0.36 to 0.49)). Direct local area comparisons confirmed an overall underascertainment in the HES data, although the difference varied between centres. There was a general increase in self-harm over time according to HES data which contrasted with a fall and then a rise in the Multicentre Study data. Conclusions There was a consistent underestimation of presentations for self-harm recorded by HES emergency department data, and fluctuations in year-on-year figures. HES admission data appeared more reliable but missed non-admitted episodes. Routinely collected data may miss important trends in self-harm and cannot be used in isolation as the basis for a robust national indicator of self-harm. PMID:26883238

Generalisation and extension of a web-based data collection system for clinical studies using Java and CORBA.

PubMed

Eich, H P; Ohmann, C

1999-01-01

Inadequate informatical support of multi-centre clinical trials lead to pure quality. In order to support a multi-centre clinical trial a data collection via WWW and Internet based on Java has been developed. In this study a generalization and extension of this prototype has been performed. The prototype has been applied to another clinical trial and a knowledge server based on C+t has been integrated via CORBA. The investigation and implementation of security aspects of web-based data collection is now under evaluation.

The self-assessed psychological comorbidities of prurigo in European patients: A multi-centre study in 13 countries.

PubMed

Brenaut, Emilie; Halvorsen, Jon Anders; Dalgard, Florence J; Lien, Lars; Balieva, Flora; Sampogna, Francesca; Linder, Dennis; Evers, Andrea W M; Jemec, Gregor B E; Gieler, Uwe; Szepietowski, Jacek; Poot, Françoise; Altunay, Ilknur K; Finlay, Andrew Y; Salek, Sam S; Szabo, Csanad; Lvov, Andrey; Marron, Servando E; Tomas-Aragones, Lucia; Kupfer, Jörg; Misery, Laurent

2018-06-19

Prurigo is defined by the presence of chronic pruritus and multiple localized or generalized pruriginous lesions. The aim of this study was to assess the psychological burden of prurigo in patients of European countries. In this multicentre European study, 3635 general dermatology outpatients and 1359 controls were included. Socio-demographic data and answers to questionnaires (regarding quality of life, general health, anxiety and depression and suicidal ideation) were collected. There were 27 patients with prurigo; of these, 63% were men, and the mean age was 58.6 years. Among patients with prurigo, 10/27 (37%) suffered from anxiety and 8/27 (29%) from depression. Suicidal ideation was reported by 5/27 (19%) of patients, and for 4 out of these 5 patients, suicidal ideation was related to their skin disease. These frequencies were higher than in the 10 commonest dermatological diseases (including psoriasis, atopic dermatitis and leg ulcers for example). The impact on quality of life was severe, with a mean DLQI of 12.4, with an extreme impact on quality of life for 23% of patients and a very large impact for 27% of patients. The psychological comorbidities of prurigo are common, greater than those of other skin diseases, and their impact on quality of life is significant. Thus, it is important to study this condition and to find new treatments. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

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.

Cross-centre replication of suppressed burrowing behaviour as an ethologically relevant pain outcome measure in the rat: a prospective multicentre study

PubMed Central

Wodarski, Rachel; Delaney, Ada; Ultenius, Camilla; Morland, Rosie; Andrews, Nick; Baastrup, Catherine; Bryden, Luke A.; Caspani, Ombretta; Christoph, Thomas; Gardiner, Natalie J.; Huang, Wenlong; Kennedy, Jeffrey D.; Koyama, Suguru; Li, Dominic; Ligocki, Marcin; Lindsten, Annika; Machin, Ian; Pekcec, Anton; Robens, Angela; Rotariu, Sanziana M.; Voß, Sabrina; Segerdahl, Marta; Stenfors, Carina; Svensson, Camilla I.; Treede, Rolf-Detlef; Uto, Katsuhiro; Yamamoto, Kazumi; Rutten, Kris; Rice, Andrew S.C.

2016-01-01

Abstract Burrowing, an ethologically relevant rodent behaviour, has been proposed as a novel outcome measure to assess the global impact of pain in rats. In a prospective multicentre study using male rats (Wistar, Sprague-Dawley), replication of suppressed burrowing behaviour in the complete Freund adjuvant (CFA)-induced model of inflammatory pain (unilateral, 1 mg/mL in 100 µL) was evaluated in 11 studies across 8 centres. Following a standard protocol, data from participating centres were collected centrally and analysed with a restricted maximum likelihood-based mixed model for repeated measures. The total population (TP—all animals allocated to treatment; n = 249) and a selected population (SP—TP animals burrowing over 500 g at baseline; n = 200) were analysed separately, assessing the effect of excluding “poor” burrowers. Mean baseline burrowing across studies was 1113 g (95% confidence interval: 1041-1185 g) for TP and 1329 g (1271-1387 g) for SP. Burrowing was significantly suppressed in the majority of studies 24 hours (7 studies/population) and 48 hours (7 TP, 6 SP) after CFA injections. Across all centres, significantly suppressed burrowing peaked 24 hours after CFA injections, with a burrowing deficit of −374 g (−479 to −269 g) for TP and −498 g (−609 to −386 g) for SP. This unique multicentre approach first provided high-quality evidence evaluating suppressed burrowing as robust and reproducible, supporting its use as tool to infer the global effect of pain on rodents. Second, our approach provided important informative value for the use of multicentre studies in the future. PMID:27643836

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

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.

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

Phenotypic Description of the Spanish Multicentre Genetic Glaucoma Group Cohort

PubMed Central

Gamundi, Maria José; Duch, Susana; Rios, Jose; Carballo, Miguel; Study Group, EMEIGG

2017-01-01

Introduction The aim of the study was to make a phenotypic description of the Spanish multicentre glaucoma group cohort of patients. Design Retrospective, observational, multicentre, cohort study. Material and Methods The clinical charts of 152 patients with hereditary glaucoma from18 Spanish eye centres were reviewed in order to make an epidemiologic description of the type of glaucoma and associated factors. True hereditary cases were compared with familiar cases according to the Gong et al. criteria. Results 61% were true hereditary cases and 39% familiar cases. Ocular comorbidity, optic disc damage, and visual field mean defect were significantly more severe in hereditary patients, who required significantly more first-line hypotensive drugs and surgical interventions to control intraocular pressure than familiar patients. Conclusions The strength of the hereditary component of glaucoma seems to worsen the clinical course, causing more structural and functional damage and requiring more intense glaucoma treatment. The family history of glaucoma should be carefully investigated and taken into consideration when making treatment decisions or intensifying previous treatment. PMID:29082038

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

Differential Item Functioning in the SF-36 Physical Functioning and Mental Health Sub-Scales: A Population-Based Investigation in the Canadian Multicentre Osteoporosis Study.

PubMed

Lix, Lisa M; Wu, Xiuyun; Hopman, Wilma; Mayo, Nancy; Sajobi, Tolulope T; Liu, Juxin; Prior, Jerilynn C; Papaioannou, Alexandra; Josse, Robert G; Towheed, Tanveer E; Davison, K Shawn; Sawatzky, Richard

2016-01-01

Self-reported health status measures, like the Short Form 36-item Health Survey (SF-36), can provide rich information about the overall health of a population and its components, such as physical, mental, and social health. However, differential item functioning (DIF), which arises when population sub-groups with the same underlying (i.e., latent) level of health have different measured item response probabilities, may compromise the comparability of these measures. The purpose of this study was to test for DIF on the SF-36 physical functioning (PF) and mental health (MH) sub-scale items in a Canadian population-based sample. Study data were from the prospective Canadian Multicentre Osteoporosis Study (CaMos), which collected baseline data in 1996-1997. DIF was tested using a multiple indicators multiple causes (MIMIC) method. Confirmatory factor analysis defined the latent variable measurement model for the item responses and latent variable regression with demographic and health status covariates (i.e., sex, age group, body weight, self-perceived general health) produced estimates of the magnitude of DIF effects. The CaMos cohort consisted of 9423 respondents; 69.4% were female and 51.7% were less than 65 years. Eight of 10 items on the PF sub-scale and four of five items on the MH sub-scale exhibited DIF. Large DIF effects were observed on PF sub-scale items about vigorous and moderate activities, lifting and carrying groceries, walking one block, and bathing or dressing. On the MH sub-scale items, all DIF effects were small or moderate in size. SF-36 PF and MH sub-scale scores were not comparable across population sub-groups defined by demographic and health status variables due to the effects of DIF, although the magnitude of this bias was not large for most items. We recommend testing and adjusting for DIF to ensure comparability of the SF-36 in population-based investigations.

Prevalence, risk factors and associated adverse pregnancy outcomes of anaemia in Chinese pregnant women: a multicentre retrospective study.

PubMed

Lin, Li; Wei, Yumei; Zhu, Weiwei; Wang, Chen; Su, Rina; Feng, Hui; Yang, Huixia

2018-04-23

Anaemia in pregnant women is a public health problem, especially in developing countries. The aim of this study was to assess the prevalence and related risk factors of anaemia during pregnancy in a large multicentre retrospective study (n = 44,002) and to determine the adverse pregnancy outcomes in women with or without anaemia. The study is a secondary data analysis of a retrospective study named "Gestational diabetes mellitus Prevalence Survey (GPS) study in China". Structured questionnaires were used to collect socio-demographic characteristics, haemoglobin levels and pregnancy outcomes from all the participants. Anaemia in pregnancy is defined as haemoglobin < 110 g/L. We used SPSS software to assess the predictors of anaemia and associated adverse pregnancy outcomes. The overall prevalence of anaemia was 23.5%. Maternal anaemia was significantly associated with maternal age ≥ 35 years (AOR = 1.386), family per capita monthly income< 1000 CNY (AOR = 1.671), rural residence (AOR = 1.308) and pre-pregnancy BMI < 18.5 kg/m 2 (AOR = 1.237). Adverse pregnancy outcomes, including GDM, polyhydramnios, preterm birth, low birth weight (< 2500 g), neonatal complications and NICU admission, increased significantly (P < 0.001) in those with anaemia than those without. The results indicated that anaemia continues to be a severe health problem among pregnant women in China. Anaemia is associated with adverse pregnancy outcomes. Pregnant women should receive routine antenatal care and be given selective iron supplementation when appropriate.

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

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.

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.

Epidemiological and clinical characteristics and behaviours of individuals with newly diagnosed HIV infection: a multicentre study in north Italy.

PubMed

Casari, S; Suligoi, B; Camoni, L; Pavan, A; Macchi, L; Capelli, M; Paraninfo, G; Compostella, S; Castelli, F; Carosi, G; Donato, F

2012-12-01

We aimed to investigate socio-demographic, clinical and epidemiological characteristics and behaviours of subjects with new HIV diagnosis. We carried out a multi-centre cross-sectional study comprising 17 infectious diseases units in the Lombardy Region, North Italy. All subjects with a first positive test for HIV infection examined in 2008-09 were interviewed using a structured questionnaire. 472 patients were enrolled (mean age 39.8 years, standard deviation [SD] 11.5), mostly males (78%), and born in Italy (77%). The most common routes of HIV transmission were heterosexual intercourse (49%) and sex among men who have sex with men (MSM) (40%). Never/sometimes use of a condom with occasional partners was associated with male gender, heterosexual transmission route, and with >10 sexual partners in their lifetime. 47% had previous HIV negative tests. Having had more than 2 previous HIV negative tests was associated with younger age, MSM transmission route, CD4+ lymphocyte count >350/microl and self-perception of risk. This study shows that there is a large portion of the adult population, especially heterosexual men aged 45 years and over, who are at high risk of acquiring and transmitting HIV infection and undergoing the HIV diagnostic test late, due to risk behaviours combined with a low perception of being at risk. Compared to people infected by heterosexual contacts, MSM show a greater awareness of being at risk of infection, but this knowledge has a low impact in reducing at-risk behaviours.

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.

Anterior transversalis fascia approach versus preperitoneal space approach for inguinal hernia repair in residents in northern China: study protocol for a prospective, multicentre, randomised, controlled trial

PubMed Central

Fan, Qing; Zhang, De-wei; Yang, Da-ye; Li, Hong-wu; Wei, Shi-bo; Yang, Liang; Yang, Fu-quan; Zhang, Shao-jun; Wu, Yao-qiang; An, Wei-de; Dai, Zhong-shu; Jiang, Hui-yong; Wang, Fu-rong; Qiao, Shi-feng; Li, Hang-yu

2017-01-01

Introduction Many surgical techniques have been used to repair abdominal wall defects in the inguinal region based on the anatomic characteristics of this region and can be categorised as ‘tension’ repair or ‘tension-free’ repair. Tension-free repair is the preferred technique for inguinal hernia repair. Tension-free repair of inguinal hernia can be performed through either the anterior transversalis fascia approach or the preperitoneal space approach. There are few large sample, randomised controlled trials investigating the curative effects of the anterior transversalis fascia approach versus the preperitoneal space approach for inguinal hernia repair in patients in northern China. Methods and analysis This will be a prospective, large sample, multicentre, randomised, controlled trial. Registration date is 1 December 2016. Actual study start date is 6 February 2017. Estimated study completion date is June 2020. A cohort of over 720 patients with inguinal hernias will be recruited from nine institutions in Liaoning Province, China. Patient randomisation will be stratified by centre to undergo inguinal hernia repair via the anterior transversalis fascia approach or the preperitoneal approach. Primary and secondary outcome assessments will be performed at baseline (prior to surgery), predischarge and at postoperative 1 week, 1 month, 3 months, 1 year and 2 years. The primary outcome is the incidence of postoperative chronic inguinal pain. The secondary outcome is postoperative complications (including rates of wound infection, haematoma, seroma and hernia recurrence). Ethics and dissemination This trial will be conducted in accordance with the Declaration of Helsinki and supervised by the institutional review board of the Fourth Affiliated Hospital of China Medical University (approval number 2015–027). All patients will receive information about the trial in verbal and written forms and will give informed consent before enrolment. The results will be published in peer-reviewed journals or disseminated through conference presentations. Trial registration number NCT02984917; preresults. PMID:28860228

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.

European multicentre validation study of the accuracy of E/e' ratio in estimating invasive left ventricular filling pressure: EURO-FILLING study.

PubMed

Galderisi, Maurizio; Lancellotti, Patrizio; Donal, Erwan; Cardim, Nuno; Edvardsen, Thor; Habib, Gilbert; Magne, Julien; Maurer, Gerald; Popescu, Bogdan A

2014-07-01

The non-invasive estimation of left ventricular filling pressures (LVFPs) represents a main goal in the clinical setting. Current recommendations encourage the use of pulsed-wave Tissue Doppler for calculating the ratio between the preload-dependent transmitral E velocity and the average of septal and lateral early diastolic velocities (e') of the mitral annulus. Despite its wide use, real utility of the E/e' ratio has been recently challenged in patients with either very advanced heart failure or preserved left ventricular (LV) ejection fraction. However, only few studies performed the invasive and non-invasive estimation of LVFP simultaneously. The EURO-FILLING Study will validate the E/e' ratio (and additional non-invasive estimates) against simultaneously measured LVFP obtained by left heart catheterization in a multicentre study involving reference European echo laboratories collecting a wide population sample size of cardiac patients with and without heart failure. The EURO-FILLING study is a large, prospective observational study in which simultaneous assessment of invasive and non-invasive measurements of LVFP will be acquired in eight reference European centres. Centralized reading of the collected parameters will be performed in a core laboratory. Not only standardized echo Doppler measurements but also novel echo parameters such as LV global longitudinal strain and global atrial strain (obtainable by two-dimensional speckle tracking echocardiography) will be tested for predicting invasive measurements of LVFP. The EURO-FILLING study is expected to provide important information on non-invasive assessment of LVFP and to contribute to the standardization of this assessment in clinical practice. Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2014. For permissions please email: journals.permissions@oup.com.

Obstetric risk indicators for labour dystocia in nulliparous women: A multi-centre cohort study

PubMed Central

Kjærgaard, Hanne; Olsen, Jørn; Ottesen, Bent; Nyberg, Per; Dykes, Anna-Karin

2008-01-01

Background In nulliparous women dystocia is the most common obstetric problem and its etiology is largely unknown. The frequency of augmentation and cesarean delivery related to dystocia is high although it is not clear if a slow progress justifies the interventions. Studies of risk factors for dystocia often do not provide diagnostic criteria for the diagnosis. The aim of the present study was to identify obstetric and clinical risk indicators of dystocia defined by strict and explicit criteria. Methods A multi-centre population based cohort study with prospectively collected data from 2810 nulliparous women in term spontaneous labour with a singleton infant in cephalic presentation. Data were collected by self-administered questionnaires and clinical data-records. Logistic regression analyses were used to estimate adjusted Odds Ratios (OR) and 95% confidence intervals (CI) are given. Results The following characteristics, present at admission to hospital, were associated with dystocia during labour (OR, 95% CI): dilatation of cervix < 4 cm (1.63, 1.38–1.92), tense cervix (1.31, 1.04–1.65), thick lower segment (1.32, 1.09–1.61), fetal head above the inter-spinal diameter (2.29, 1.80–2.92) and poor fetal head-to-cervix contact (1.83, 1.31–2.56). The use of epidural analgesia (5.65, 4.33–7.38) was also associated with dystocia. Conclusion Vaginal examinations at admission provide useful information on risk indicators for dystocia. The strongest risk indicator was use of epidural analgesia and if part of that is causal, it is of concern. PMID:18837972

European Network of Bipolar Research Expert Centre (ENBREC): a network to foster research and promote innovative care.

PubMed

Henry, Chantal; Andreassen, Ole A; Barbato, Angelo; Demotes-Mainard, Jacques; Goodwin, Guy; Leboyer, Marion; Vieta, Eduard; Nolen, Willem A; Kessing, Lars Vedel; Scott, Jan; Bauer, Michael

2013-01-01

Bipolar disorders rank as one of the most disabling illnesses in working age adults worldwide. Despite this, the quality of care offered to patients with this disorder is suboptimal, largely due to limitations in our understanding of the pathology. Improving this scenario requires the development of a critical mass of expertise and multicentre collaborative projects. Within the framework of the European FP7 programme, we developed a European Network of Bipolar Research Expert Centres (ENBREC) designed specifically to facilitate EU-wide studies. ENBREC provides an integrated support structure facilitating research on disease mechanisms and clinical outcomes across six European countries (France, Germany, Italy, Norway, Spain and the UK). The centres are adopting a standardised clinical assessment that explores multiple aspects of bipolar disorder through a structured evaluation designed to inform clinical decision-making as well as being applicable to research. Reliable, established measures have been prioritised, and instruments have been translated and validated when necessary. An electronic healthcare record and monitoring system (e-ENBREC©) has been developed to collate the data. Protocols to conduct multicentre clinical observational studies and joint studies on cognitive function, biomarkers, genetics, and neuroimaging are in progress; a pilot study has been completed on strategies for routine implementation of psycho-education. The network demonstrates 'proof of principle' that expert centres across Europe can collaborate on a wide range of basic science and clinical programmes using shared protocols. This paper is to describe the network and how it aims to improve the quality and effectiveness of research in a neglected priority area.

A teaching intervention in a contouring dummy run improved target volume delineation in locally advanced non-small cell lung cancer: Reducing the interobserver variability in multicentre clinical studies.

PubMed

Schimek-Jasch, Tanja; Troost, Esther G C; Rücker, Gerta; Prokic, Vesna; Avlar, Melanie; Duncker-Rohr, Viola; Mix, Michael; Doll, Christian; Grosu, Anca-Ligia; Nestle, Ursula

2015-06-01

Interobserver variability in the definition of target volumes (TVs) is a well-known confounding factor in (multicentre) clinical studies employing radiotherapy. Therefore, detailed contouring guidelines are provided in the prospective randomised multicentre PET-Plan (NCT00697333) clinical trial protocol. This trial compares strictly FDG-PET-based TV delineation with conventional TV delineation in patients with locally advanced non-small cell lung cancer (NSCLC). Despite detailed contouring guidelines, their interpretation by different radiation oncologists can vary considerably, leading to undesirable discrepancies in TV delineation. Considering this, as part of the PET-Plan study quality assurance (QA), a contouring dummy run (DR) consisting of two phases was performed to analyse the interobserver variability before and after teaching. In the first phase of the DR (DR1), radiation oncologists from 14 study centres were asked to delineate TVs as defined by the study protocol (gross TV, GTV; and two clinical TVs, CTV-A and CTV-B) in a test patient. A teaching session was held at a study group meeting, including a discussion of the results focussing on discordances in comparison to the per-protocol solution. Subsequently, the second phase of the DR (DR2) was performed in order to evaluate the impact of teaching. Teaching after DR1 resulted in a reduction of absolute TVs in DR2, as well as in better concordance of TVs. The Overall Kappa(κ) indices increased from 0.63 to 0.71 (GTV), 0.60 to 0.65 (CTV-A) and from 0.59 to 0.63 (CTV-B), demonstrating improvements in overall interobserver agreement. Contouring DRs and study group meetings as part of QA in multicentre clinical trials help to identify misinterpretations of per-protocol TV delineation. Teaching the correct interpretation of protocol contouring guidelines leads to a reduction in interobserver variability and to more consistent contouring, which should consequently improve the validity of the overall study results.

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.

Acute Lameness in a Roller Pigeon ( Columba livia ) with Multicentric Lymphosarcoma.

PubMed

Williams, Susan M; Williams, Robert J; Gogal, Robert M

2017-06-01

A 3-yr-old adult female roller pigeon ( Columba livia ) used as part of a breeding pair for an ongoing research study presented with acute left limb lameness. Palpation of the left leg and region revealed a large lump near the coxofemoral joint. The bird was able to ambulate in the cage, but would not brood her hatchling. The bird was humanely euthanized and necropsy was performed. Grossly, multiple large white to pale tan nodules were noted in the pancreas, lung, rib cage, intestines, and unilaterally in the left kidney. Microscopic examination of the various organs revealed neoplastic proliferation of round cells consistent with lymphoblasts. Immunohistochemistry was performed with the use of antibodies to CD3, CD79a, CD20, and CD21 to phenotype the cells. The results indicated that the neoplastic infiltrating cells were predominantly of T-cell origin.

A double blind multicentre study of OM-8980 and auranofin in rheumatoid arthritis.

PubMed Central

Vischer, T L

1988-01-01

The therapeutic efficacy of the immunomodulator OM-8980 in rheumatoid arthritis was compared with that of auranofin, an oral gold salt, in a double blind, randomised multicentre study lasting six months. Seventy patients were treated with auranofin and 75 with OM-8980. The patients of both groups improved significantly at three and six months for all the clinical parameters observed: Ritchie index, number of swollen joints, morning stiffness, pain, grip strength, intake of non-steroidal anti-inflammatory drugs, and erythrocyte sedimentation rate. No serious side effects were observed in either group. The patients receiving auranofin had more adverse reactions, mainly affecting the gastrointestinal system. PMID:3041924

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

Evaluation of Glaucoma Progression in Large-Scale Clinical Data: The Japanese Archive of Multicentral Databases in Glaucoma (JAMDIG).

PubMed

Fujino, Yuri; Asaoka, Ryo; Murata, Hiroshi; Miki, Atsuya; Tanito, Masaki; Mizoue, Shiro; Mori, Kazuhiko; Suzuki, Katsuyoshi; Yamashita, Takehiro; Kashiwagi, Kenji; Shoji, Nobuyuki

2016-04-01

To develop a large-scale real clinical database of glaucoma (Japanese Archive of Multicentral Databases in Glaucoma: JAMDIG) and to investigate the effect of treatment. The study included a total of 1348 eyes of 805 primary open-angle glaucoma patients with 10 visual fields (VFs) measured with 24-2 or 30-2 Humphrey Field Analyzer (HFA) and intraocular pressure (IOP) records in 10 institutes in Japan. Those with 10 reliable VFs were further identified (638 eyes of 417 patients). Mean total deviation (mTD) of the 52 test points in the 24-2 HFA VF was calculated, and the relationship between mTD progression rate and seven variables (age, mTD of baseline VF, average IOP, standard deviation (SD) of IOP, previous argon/selective laser trabeculoplasties (ALT/SLT), previous trabeculectomy, and previous trabeculotomy) was analyzed. The mTD in the initial VF was -6.9 ± 6.2 dB and the mTD progression rate was -0.26 ± 0.46 dB/year. Mean IOP during the follow-up period was 13.5 ± 2.2 mm Hg. Age and SD of IOP were related to mTD progression rate. However, in eyes with average IOP below 15 and also 13 mm Hg, only age and baseline VF mTD were related to mTD progression rate. Age and the degree of VF damage were related to future progression. Average IOP was not related to the progression rate; however, fluctuation of IOP was associated with faster progression, although this was not the case when average IOP was below 15 mm Hg.

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.

Unique blood culture for diagnosis of bloodstream infections in emergency departments: a prospective multicentre study.

PubMed

Dargère, S; Parienti, J-J; Roupie, E; Gancel, P-E; Wiel, E; Smaiti, N; Loiez, C; Joly, L-M; Lemée, L; Pestel-Caron, M; du Cheyron, D; Verdon, R; Leclercq, R; Cattoir, V

2014-11-01

Detection of microorganisms by blood cultures (BCs) is essential in managing patients with bacteraemia. Rather than the number of punctures, the volume of blood drawn is considered paramount in efficient and reliable detection of microorganisms. We performed a 1-year prospective multicentre study in adult emergency departments of three French university hospitals comparing two methods for BCs: a unique blood culture (UBC) collecting a large volume of blood (40 mL) and the standard method of multiple blood cultures (MBC). The performances of both methods for bacterial contamination and efficient microbial detection were compared, each patient serving as his own control. Amongst the 2314 patients included, three hundred were positive for pathogens (n=245) or contaminants (n=55). Out of the 245 patients, 11 were positive for pathogens by UBC but negative by MBC and seven negative by UBC but positive by MBC (p 0.480). In the subgroup of 137 patients with only two BCs, UBC was superior to MBC (p 0.044). Seven and 17 patients had contaminated BCs by UBC and MBC only, respectively (p 0.062). Considering the sums of pathogens missed and contaminants, UBC significantly outperformed MBC (p 0.045). Considering the complete picture of cost savings, efficient detection of microorganisms and decrease in contaminations, UBC offers an interesting alternative to MBC. © 2014 The Authors Clinical Microbiology and Infection © 2014 European Society of Clinical Microbiology and Infectious Diseases.

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.

Use of anteromedial thigh perforator flap and immunological implications of Gorlin-Goltz syndrome: a case study.

PubMed

Scalise, A; Calamita, R; Tartaglione, C; Bolletta, E; Di Benedetto, G; Pierangeli, M

2016-12-02

Gorlin-Goltz syndrome is mainly characterised by the development of numerous multicentric and relapsing cutaneous basal cell carcinomas (BCCs). A major problem for patients with Gorlin-Goltz syndrome is the large amount of BCCs that can invade the deep underlying structures, especially the face. Here, we describe the case of a 23-year-old male affected by Gorlin-Goltz syndrome. He had recurrent BCCs on a hairless scalp and dorsum since he was 17 years old and underwent four surgical procedures to excise BCCs, including a reconstruction with anteromedial thigh perforator flap. For each of the surgical procedures, a phenotypic study on peripheral blood mononuclear cells using flow cytometry was performed on the same day of surgery, and on days 7, 14 and 21 after surgery. The role of the tumour-specific cytolytic immune response as a potential future treatment of syndromic BCCs and its trend in relation to surgical ablation of large portions of tumour tissue was examined, and the cosmetic and therapeutic results are shown.

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

Proteomic prediction and Renin angiotensin aldosterone system Inhibition prevention Of early diabetic nephRopathy in TYpe 2 diabetic patients with normoalbuminuria (PRIORITY): essential study design and rationale of a randomised clinical multicentre trial.

PubMed

Lindhardt, Morten; Persson, Frederik; Currie, Gemma; Pontillo, Claudia; Beige, Joachim; Delles, Christian; von der Leyen, Heiko; Mischak, Harald; Navis, Gerjan; Noutsou, Marina; Ortiz, Alberto; Ruggenenti, Piero Luigi; Rychlik, Ivan; Spasovski, Goce; Rossing, Peter

2016-03-02

Diabetes mellitus affects 9% of the European population and accounts for 15% of healthcare expenditure, in particular, due to excess costs related to complications. Clinical trials aiming for earlier prevention of diabetic nephropathy by renin angiotensin system blocking treatment in normoalbumuric patients have given mixed results. This might reflect that the large fraction of normoalbuminuric patients are not at risk of progression, thereby reducing power in previous studies. A specific risk classifier based on urinary proteomics (chronic kidney disease (CKD)273) has been shown to identify normoalbuminuric diabetic patients who later progressed to overt kidney disease, and may hold the potential for selection of high-risk patients for early intervention. Combining the ability of CKD273 to identify patients at highest risk of progression with prescription of preventive aldosterone blockade only to this high-risk population will increase power. We aim to confirm performance of CKD273 in a prospective multicentre clinical trial and test the ability of spironolactone to delay progression of early diabetic nephropathy. Investigator-initiated, prospective multicentre clinical trial, with randomised double-masked placebo-controlled intervention and a prospective observational study. We aim to include 3280 type 2 diabetic participants with normoalbuminuria. The CKD273 classifier will be assessed in all participants. Participants with high-risk pattern are randomised to treatment with spironolactone 25 mg once daily, or placebo, whereas, those with low-risk pattern will be observed without intervention other than standard of care. Treatment or observational period is 3 years.The primary endpoint is development of confirmed microalbuminuria in 2 of 3 first morning voids urine samples. The study will be conducted under International Conference on Harmonisation - Good clinical practice (ICH-GCP) requirements, ethical principles of Declaration of Helsinki and national laws. This first new biomarker-directed intervention trial aiming at primary prevention of diabetic nephropathy may pave the way for personalised medicine approaches in treatment of diabetes complications. NCT02040441; Pre-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/

Ethical issues: the multi-centre low-risk ethics/governance review process and AMOSS.

PubMed

Vaughan, Geraldine; Pollock, Wendy; Peek, Michael J; Knight, Marian; Ellwood, David; Homer, Caroline S; Pulver, Lisa Jackson; McLintock, Claire; Ho, Maria T; Sullivan, Elizabeth A

2012-04-01

The Australasian Maternity Outcomes Surveillance System (AMOSS) conducts surveillance and research of rare and serious conditions in pregnancy. This multi-centre population health study is considered low risk with minimal ethical impact. To describe the ethics/governance review pathway undertaken by AMOSS. Prospective, descriptive study during 2009-2011 of the governance/ethical review processes required to gain approval for Australian and New Zealand (ANZ) maternity units with more than 50 births per year (n = 303) to participate in AMOSS. Review processes ranged from a single application for 24 NZ sites, a single application for eligible hospitals in two Australian states, full Health Research Ethics Committee (HREC) applications for individual hospitals, through simple letters of support. As of September 2011, 46 full/expedited ethics applications, 131 site governance applications and 136 letters of support requests were made over 33 months, involving an estimated 3261 hours by AMOSS staff/investigators, and an associated resource burden by participating sites, to obtain approval to receive nonidentifiable data from 291 hospitals. The AMOSS research system provides an important resource to enhance knowledge of conditions that cause rare and serious maternal morbidity. Yet the highly variable ethical approval processes required to implement this study have been excessively repetitive and burdensome. This process jeopardises timely, efficient research project implementation, without corresponding benefits to research participants. The resource burden to establish research governance for AMOSS confirms the urgent need for the Harmonisation of Multi-centre Ethical Review (HoMER) to further streamline ethics/governance review processes for multi-centre research. © 2011 The Authors. Australian and New Zealand Journal of Obstetrics and Gynaecology © 2011 The Royal Australian and New Zealand College of Obstetricians and Gynaecologists.

The 'aerobic/resistance/inspiratory muscle training hypothesis in heart failure'.

PubMed

Laoutaris, Ioannis D

2018-01-01

Evidence from large multicentre exercise intervention trials in heart failure patients, investigating both moderate continuous aerobic training and high intensity interval training, indicates that the 'crème de la crème' exercise programme for this population remains to be found. The 'aerobic/resistance/inspiratory (ARIS) muscle training hypothesis in heart failure' is introduced, suggesting that combined ARIS muscle training may result in maximal exercise pathophysiological and functional benefits in heart failure patients. The hypothesis is based on the decoding of the 'skeletal muscle hypothesis in heart failure' and on revision of experimental evidence to date showing that exercise and functional intolerance in heart failure patients are associated not only with reduced muscle endurance, indication for aerobic training (AT), but also with reduced muscle strength and decreased inspiratory muscle function contributing to weakness, dyspnoea, fatigue and low aerobic capacity, forming the grounds for the addition of both resistance training (RT) and inspiratory muscle training (IMT) to AT. The hypothesis will be tested by comparing all potential exercise combinations, ARIS, AT/RT, AT/IMT, AT, evaluating both functional and cardiac indices in a large sample of heart failure patients of New York Heart Association class II-III and left ventricular ejection fraction ≤35% ad hoc by the multicentre randomized clinical trial, Aerobic Resistance, InSpiratory Training OutcomeS in Heart Failure (ARISTOS-HF trial).

Lifelong vegetarianism and breast cancer risk: a large multicentre case control study in India.

PubMed

Gathani, Toral; Barnes, Isobel; Ali, Raghib; Arumugham, Rajkumar; Chacko, Raju; Digumarti, Raghunadharao; Jivarajani, Parimal; Kannan, Ravi; Loknatha, Dasappa; Malhotra, Hemant; Mathew, Beela S

2017-01-18

The lower incidence of breast cancer in Asian populations where the intake of animal products is lower than that of Western populations has led some to suggest that a vegetarian diet might reduce breast cancer risk. Between 2011 and 2014 we conducted a multicentre hospital based case-control study in eight cancer centres in India. Eligible cases were women aged 30-70 years, with newly diagnosed invasive breast cancer (ICD10 C50). Controls were frequency matched to the cases by age and region of residence and chosen from the accompanying attendants of the patients with cancer or those patients in the general hospital without cancer. Information about dietary, lifestyle, reproductive and socio-demographic factors were collected using an interviewer administered structured questionnaire. Multivariate logistic regression models were used to estimate the odds ratio (OR) and 95% confidence intervals for the risk of breast cancer in relation to lifelong vegetarianism, adjusting for known risk factors for the disease. The study included 2101 cases and 2255 controls. The mean age at recruitment was similar in cases (49.7 years (SE 9.7)) and controls (49.8 years (SE 9.1)). About a quarter of the population were lifelong vegetarians and the rates varied significantly by region. On multivariate analysis, with adjustment for known risk factors for the disease, the risk of breast cancer was not decreased in lifelong vegetarians (OR 1.09 (95% CI 0.93-1.29)). Lifelong exposure to a vegetarian diet appears to have little, if any effect on the risk of breast cancer.

Multicentric Comparative Analytical Performance Study for Molecular Detection of Low Amounts of Toxoplasma gondii from Simulated Specimens▿ †

PubMed Central

Sterkers, Yvon; Varlet-Marie, Emmanuelle; Cassaing, Sophie; Brenier-Pinchart, Marie-Pierre; Brun, Sophie; Dalle, Frédéric; Delhaes, Laurence; Filisetti, Denis; Pelloux, Hervé; Yera, Hélène; Bastien, Patrick

2010-01-01

Although screening for maternal toxoplasmic seroconversion during pregnancy is based on immunodiagnostic assays, the diagnosis of clinically relevant toxoplasmosis greatly relies upon molecular methods. A problem is that this molecular diagnosis is subject to variation of performances, mainly due to a large diversity of PCR methods and primers and the lack of standardization. The present multicentric prospective study, involving eight laboratories proficient in the molecular prenatal diagnosis of toxoplasmosis, was a first step toward the harmonization of this diagnosis among university hospitals in France. Its aim was to compare the analytical performances of different PCR protocols used for Toxoplasma detection. Each center extracted the same concentrated Toxoplasma gondii suspension and tested serial dilutions of the DNA using its own assays. Differences in analytical sensitivities were observed between assays, particularly at low parasite concentrations (≤2 T. gondii genomes per reaction tube), with “performance scores” differing by a 20-fold factor among laboratories. Our data stress the fact that differences do exist in the performances of molecular assays in spite of expertise in the matter; we propose that laboratories work toward a detection threshold defined for a best sensitivity of this diagnosis. Moreover, on the one hand, intralaboratory comparisons confirmed previous studies showing that rep529 is a more adequate DNA target for this diagnosis than the widely used B1 gene. But, on the other hand, interlaboratory comparisons showed differences that appear independent of the target, primers, or technology and that hence rely essentially on proficiency and care in the optimization of PCR conditions. PMID:20610670

Paediatric in-patient prescribing errors in Malaysia: a cross-sectional multicentre study.

PubMed

Khoo, Teik Beng; Tan, Jing Wen; Ng, Hoong Phak; Choo, Chong Ming; Bt Abdul Shukor, Intan Nor Chahaya; Teh, Siao Hean

2017-06-01

Background There is a lack of large comprehensive studies in developing countries on paediatric in-patient prescribing errors in different settings. Objectives To determine the characteristics of in-patient prescribing errors among paediatric patients. Setting General paediatric wards, neonatal intensive care units and paediatric intensive care units in government hospitals in Malaysia. Methods This is a cross-sectional multicentre study involving 17 participating hospitals. Drug charts were reviewed in each ward to identify the prescribing errors. All prescribing errors identified were further assessed for their potential clinical consequences, likely causes and contributing factors. Main outcome measures Incidence, types, potential clinical consequences, causes and contributing factors of the prescribing errors. Results The overall prescribing error rate was 9.2% out of 17,889 prescribed medications. There was no significant difference in the prescribing error rates between different types of hospitals or wards. The use of electronic prescribing had a higher prescribing error rate than manual prescribing (16.9 vs 8.2%, p < 0.05). Twenty eight (1.7%) prescribing errors were deemed to have serious potential clinical consequences and 2 (0.1%) were judged to be potentially fatal. Most of the errors were attributed to human factors, i.e. performance or knowledge deficit. The most common contributing factors were due to lack of supervision or of knowledge. Conclusions Although electronic prescribing may potentially improve safety, it may conversely cause prescribing errors due to suboptimal interfaces and cumbersome work processes. Junior doctors need specific training in paediatric prescribing and close supervision to reduce prescribing errors in paediatric in-patients.

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.

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.

Anthropometric protocols for the construction of new international fetal and newborn growth standards: the INTERGROWTH-21st Project.

PubMed

Cheikh Ismail, L; Knight, H E; Bhutta, Z; Chumlea, W C

2013-09-01

The primary aim of the INTERGROWTH-21(st) Project is to construct new, prescriptive standards describing optimal fetal and preterm postnatal growth. The anthropometric measurements include the head circumference, recumbent length and weight of the infants, and the stature and weight of the parents. In such a large, international, multicentre project, it is critical that all study sites follow standardised protocols to ensure maximal validity of the growth and nutrition indicators used. This paper describes, in detail, the selection of anthropometric personnel, equipment, and measurement and calibration protocols used to construct the new standards. Implementing these protocols at each study site ensures that the anthropometric data are of the highest quality to construct the international standards. © 2013 Royal College of Obstetricians and Gynaecologists.

High interpatient variability of treosulfan exposure is associated with early toxicity in paediatric HSCT: a prospective multicentre study.

PubMed

van der Stoep, M Y Eileen C; Bertaina, Alice; Ten Brink, Marloes H; Bredius, Robbert G; Smiers, Frans J; Wanders, Dominique C M; Moes, Dirk Jan A R; Locatelli, Franco; Guchelaar, Henk-Jan; Zwaveling, Juliëtte; Lankester, Arjan C

2017-12-01

Treosulfan-based conditioning is increasingly employed in paediatric haematopoietic stem cell transplantation (HSCT). Data on treosulfan pharmacokinetics in children are scarce, and the relationship between treosulfan exposure, toxicity and clinical outcome is unresolved. In this multicentre prospective observational study, we studied treosulfan pharmacokinetics and the drug's relationship with regimen-related toxicity and early clinical outcome in 77 paediatric patients. Treosulfan dose was 30 g/m 2 , administered over 3 consecutive days in infants <1 year old (n = 12) and 42 g/m 2 in children ≥1 year old (n = 65). Mean day 1 treosulfan exposure was 1744 ± 795 mg*h/l (10 g/m 2 ) and 1561 ± 511 mg*h/l (14 g/m 2 ), with an inter-individual variability of 56 and 33% in the respective groups. High treosulfan exposure (>1650 mg*h/l) was associated with an increased risk of mucosal [Odds ratio (OR) 4·40; 95% confidence interval (CI) 1·19-16·28, P = 0·026] and skin toxicity (OR 4·51; 95% CI 1·07-18·93, P = 0·040). No correlation was found between treosulfan exposure and the early clinical outcome parameters: engraftment, acute graft-versus-host disease and donor chimerism. Our study provides the first evidence in a large cohort of paediatric patients of high variability in treosulfan pharmacokinetics and an association between treosulfan exposure and early toxicity. Ongoing studies will reveal whether treosulfan exposure is related to long-term disease-specific outcome and late treatment-related toxicity. © 2017 John Wiley & Sons Ltd.

Treatment influencing down-staging in EORTC Melanoma Group sentinel node histological protocol compared with complete step-sectioning: a national multicentre study.

PubMed

Riber-Hansen, Rikke; Hastrup, Nina; Clemmensen, Ole; Behrendt, Nille; Klausen, Siri; Ramsing, Mette; Spaun, Eva; Hamilton-Dutoit, Stephen Jacques; Steiniche, Torben

2012-02-01

Metastasis size in melanoma sentinel lymph nodes (SLNs) is an emerging prognostic factor. Two European melanoma treatment trials include SLN metastasis diameters as inclusion criteria. Whilst diameter estimates are sensitive to the number of sections examined, the level of this bias is largely unknown. We performed a prospective multicentre study to compare the European Organisation for Research and Treatment of Cancer (EORTC) recommended protocol with a protocol of complete step-sectioning. One hundred and thirty-three consecutive SLNs from seven SLN centres were analysed by five central sections 50μm apart (EORTC Protocol) followed by complete 250μm step-sectioning. Overall, 29 patients (21.8%) were SLN-positive. The EORTC Protocol missed eight of these metastases (28%), one metastasis measuring less than 0.1mm in diameter, seven measuring between 0.1 and 1mm. Complete step-sectioning at 250μm intervals (Extensive Protocol) missed one metastasis (3%) that measured less than 0.1mm. Thirteen treatment courses (34%) performed if inclusion was based on the Combined Protocol would not be performed if assessed by the EORTC Protocol. Thus, 10 patients would be without completion lymph node dissection (EORTC MINITUB study), whilst three patients would not be eligible for anti-CTLA4 trial (EORTC protocol 18071). The corresponding number with the Extensive Protocol would be three; one patient for the MINITUB registration study and two patients for the anti-CTLA4 study. Examining SLNs by close central sectioning alone (EORTC Protocol) misses a substantial number of metastases and underestimates the maximum metastasis diameter, leading to important changes in patient eligibility for various treatment protocols. Copyright © 2011 Elsevier Ltd. All rights reserved.

Design of the FemCure study: prospective multicentre study on the transmission of genital and extra-genital Chlamydia trachomatis infections in women receiving routine care.

PubMed

Dukers-Muijrers, Nicole H T M; Wolffs, Petra F G; Eppings, Lisanne; Götz, Hannelore M; Bruisten, Sylvia M; Schim van der Loeff, Maarten F; Janssen, Kevin; Lucchesi, Mayk; Heijman, Titia; van Benthem, Birgit H; van Bergen, Jan E; Morre, Servaas A; Herbergs, Jos; Kok, Gerjo; Steenbakkers, Mieke; Hogewoning, Arjan A; de Vries, Henry J; Hoebe, Christian J P A

2016-08-08

In women, anorectal infections with Chlamydia trachomatis (CT) are about as common as genital CT, yet the anorectal site remains largely untested in routine care. Anorectal CT frequently co-occurs with genital CT and may thus often be treated co-incidentally. Nevertheless, post-treatment detection of CT at both anatomic sites has been demonstrated. It is unknown whether anorectal CT may play a role in post-treatment transmission. This study, called FemCure, in women who receive routine treatment (either azithromycin or doxycycline) aims to understand the post-treatment transmission of anorectal CT infections, i.e., from their male sexual partner(s) and from and to the genital region of the same woman. The secondary objective is to evaluate other reasons for CT detection by nucleic acid amplification techniques (NAAT) such as treatment failure, in order to inform guidelines to optimize CT control. A multicentre prospective cohort study (FemCure) is set up in which genital and/or anorectal CT positive women (n = 400) will be recruited at three large Dutch STI clinics located in South Limburg, Amsterdam and Rotterdam. The women self-collect anorectal and vaginal swabs before treatment, and at the end of weeks 1, 2, 4, 6, 8, 10, and 12. Samples are tested for presence of CT-DNA (by NAAT), load (by quantitative polymerase chain reaction -PCR), viability (by culture and viability PCR) and CT type (by multilocus sequence typing). Sexual exposure is assessed by online self-administered questionnaires and by testing samples for Y chromosomal DNA. Using logistic regression models, the impact of two key factors (i.e., sexual exposure and alternate anatomic site of infection) on detection of anorectal and genital CT will be assessed. The FemCure study will provide insight in the role of anorectal chlamydia infection in maintaining the CT burden in the context of treatment, and it will provide practical recommendations to reduce avoidable transmission. Implications will improve care strategies that take account of anorectal CT. ClinicalTrials.gov Identifier: NCT02694497 .

Diagnostic Evaluation of Des-Gamma-Carboxy Prothrombin versus α-Fetoprotein for Hepatitis B Virus-Related Hepatocellular Carcinoma in China: A Large-Scale, Multicentre Study

PubMed Central

Zheng, Lei; Yin, Yuepeng; Zou, Zhenzhen; Zhou, Feiguo; Zhou, Weiping; Shen, Feng; Gao, Chunfang

2016-01-01

An efficient serum marker for hepatocellular carcinoma (HCC) is currently lacking and requires intensive exploration. We aimed to evaluate the performance of des-gamma-carboxy prothrombin (DCP) for identifying hepatitis B virus-related HCC in a large, multicentre study in China. A total of 1034 subjects in three cohorts (A, B, and C) including HCC and various non-HCC controls were enrolled from 4 academic medical centers in China from January 2011 to February 2014. Blind parallel detections were conducted for DCP and AFP. The area under the receiver operating characteristic curve (AUC) was used to evaluate the diagnostic efficacies. In cohort A, which comprised 521 subjects, including patients with HCC, liver metastasis, liver cirrhosis (LC), and liver hemangiomas as well as healthy controls (HCs), the accuracy of DCP for distinguishing HCC from various controls was 6.2–9.7% higher than that of AFP. In cohort B, which comprised 447 subjects, including patients with HCC, LC, and chronic hepatitis B as well as HC, the accuracy of DCP was further elevated (12.3–20.67% higher than that of AFP). The superiority of DCP to AFP was more profound in the surveillance of early HCC [AUC 0.837 (95% CI: 0.771–0.903) vs. 0.650 (0.555–0.745)] and AFP-negative HCC [AUC: 0.856 (0.798–0.914)] and in discriminating HCC from LC (accuracy: 92.9% vs.64.71%). Higher DCP levels were associated with worse clinical behaviors and shorter disease-free survival. DCP not only is complementary to AFP in identifying AFP-negative HCC and in excluding AFP-positive non-HCC (liver cirrhosis), but also demonstrates improved performance in HCC surveillance, early diagnosis, treatment response and recurrence monitoring in the HBV-related population. PMID:27070780

Multicentre evaluation of a novel vaginal dose reporting method in 153 cervical cancer patients.

PubMed

Westerveld, Henrike; de Leeuw, Astrid; Kirchheiner, Kathrin; Dankulchai, Pittaya; Oosterveld, Bernard; Oinam, Arun; Hudej, Robert; Swamidas, Jamema; Lindegaard, Jacob; Tanderup, Kari; Pötter, Richard; Kirisits, Christian

2016-09-01

Recently, a vaginal dose reporting method for combined EBRT and BT in cervical cancer patients was proposed. The current study was to evaluate vaginal doses with this method in a multicentre setting, wherein different applicators, dose rates and protocols were used. In a subset of patients from the EMBRACE study, vaginal doses were evaluated. Doses at the applicator surface left/right and anterior/posterior and at 5mm depth were measured. In addition, the dose at the Posterior-Inferior Border of Symphysis (PIBS) vaginal dose point and PIBS±2cm, corresponding to the mid and lower vagina, was measured. 153 patients from seven institutions were included. Large dose variations expressed in EQD2 with α/β=3Gy were seen between patients, in particular at the top left and right vaginal wall (median 195 (range 61-947)Gy/178 (61-980)Gy, respectively). At 5mm depth, doses were 98 (55-212)Gy/91 (54-227)Gy left/right, and 71 (51-145)Gy/67 (49-189)Gy anterior/posterior, respectively. The dose at PIBS and PIBS±2cm was 41 (3-81)Gy, 54 (32-109)Gy and 5 (1-51)Gy, respectively. At PIBS+2cm (mid vagina) dose variation was coming from BT. The variation at PIBS-2cm (lower vagina) was mainly dependent on EBRT field border location. This novel method for reporting vaginal doses coming from EBRT and BT through well-defined dose points gives a robust representation of the dose along the vaginal axis. In addition, it allows comparison of vaginal dose between patients from different centres. The doses at the PIBS points represent the doses at the mid and lower parts of the vagina. Large variations in dose throughout the vagina were observed between patients and centres. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Psoriatic arthritis treatment regimens, therapy duration and reasons for cessation in the biologics era: a multi-centre Australian study.

PubMed

Tymms, Kathleen; Kelly, Ayano; Bird, Paul; Griffiths, Hedley; de Jager, Julien; Littlejohn, Geoff; Louw, Sandra; Roberts, Lynden; Youssef, Peter; Zochling, Jane; Nichols, Dave

2018-02-01

To describe the treatment regimens, duration of therapy and reasons for disease-modifying antirheumatic drug (DMARD) cessation in a large psoriatic arthritis (PsA) cohort. A retrospective non-interventional multi-centre study using Audit4 electronic medical records, with de-identified, routinely collected clinical data from rheumatology practices in the OPAL consortium (Optimising Patient outcomes in Australian rheumatoLogy) during November 2015. Baseline characteristics, type and duration of conventional and biologic DMARDs (cDMARD and bDMARD, respectively), disease activity (Disease Activity Score of 28 joints C-reactive protein [DAS28-CRP]), and reasons for treatment cessation were recorded. A total of 3422 rheumatologist-diagnosed PsA patients were included: 60% female, mean age 54 years and disease duration 10 years. Of patients with treatment recorded (n = 2948), 46% were on cDMARD monotherapy, 19% bDMARD monotherapy, 13% combination bDMARD and cDMARDs, 11% combination cDMARDs and 10% no DMARDs. Of those with DAS28-CRP results (n = 494), the highest mean DAS28-CRP was 3.32 on combination cDMARDs, and the lowest was 2.19 on bDMARD monotherapy. Median duration on cDMARD monotherapy was 33.5 months (n = 2232), on bDMARD monotherapy 110.1 months (n = 751), on combination bDMARD and cDMARDs 68.5 months (n = 559). The most common reasons for cessation of cDMARD monotherapy was adverse reactions (41%), for bDMARD monotherapy lack of efficacy (26%), and for combination bDMARD and cDMARDs treatment completed or no longer required (37%). Most PsA patients were prescribed DMARD therapies with a large proportion receiving cDMARDs. Patients on combination cDMARD therapies had the highest DAS28-CRP results. Adverse reactions were the most common reason for cessation of cDMARD monotherapy, whereas for bDMARD monotherapy it was lack of efficacy. © 2017 Asia Pacific League of Associations for Rheumatology and John Wiley & Sons Australia, Ltd.

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.

An integrated Diet Monitoring Solution for nutrigenomic research.

PubMed

Conti, Costanza; Rossi, Elena; Marceglia, Sara; Tauro, Vittorio; Rizzi, Federica; Lazzaroni, Monica; Barlassina, Cristina; Soldati, Laura; Cusi, Daniele

2015-01-01

The emergence of evidence pointing at diet as key risk factor for chronic diseases and at gene-diet interactions as key elements in the interplay between an individual genetic background and his/her lifestyle, pave the way for studies in nutrigenomics. Such studies need an integrated solution to collect, monitor and analyse a large set of data. In the frame of ATHENA, a European Commission FP7 project, we developed an integrated platform, called Dietary Monitoring Solution enabling the collection of phenotypic, genetic and lifestyle information, linked to a mHealth application tool. The data collection solution allows maintaining anonymized information and supports a number of features making it particularly suited for multicentre studies. The mHealth application was designed to translate the knowledge generated from research into a personalised prevention programme and to support the patient adherence to the programme.

Multicentric epitheliotropic T-cell lymphoma in an African hedgehog (Atelerix albiventris).

PubMed

Chung, Tae-Ho; Kim, Hyo-Jin; Choi, Ul-Soo

2014-12-01

A 2-year-old female African hedgehog was presented with a 5-month history of pruritus, and diffuse spine and hair loss. A dermatologic examination revealed erythema, excoriation, scales, and crusting affecting the face, flanks, forelimbs, hindlimbs, and dorsal and ventral abdomen. Fine-needle aspiration was performed and skin biopsies were taken from several lesions for cytologic and histologic evaluation. The aspirates yielded smears characterized by a monomorphic population of medium-sized to large lymphocytes with scant to moderate amounts of clear to moderately basophilic cytoplasm and distinct nucleoli along with a low number of cytoplasmic fragments. On histopathologic examination, there were dense dermal lymphoid infiltrates invading the dermis and a monomorphic population of round cells that had infiltrated the overlying epidermis. Epitheliotropic cutaneous lymphoma was diagnosed based on morphologic features. Additional immunochemical analysis using anti-CD3 and anti-CD79a antibodies revealed strong CD3 expression by the tumor cells, which confirmed epitheliotropic cutaneous T-cell lymphoma. This is the first description of a multicentric pattern of epitheliotropic cutaneous T-cell lymphoma in an African hedgehog. © 2014 American Society for Veterinary Clinical Pathology.

A personal history of the MASTER Trial and its link to the clinical trials network of the Australian and New Zealand College of Anaesthetists.

PubMed

Rigg, J R A

2016-07-01

The aim of this paper is to link the history of the Multicentre Australian Study of Epidural Anaesthesia in high risk surgery, the MASTER Trial, the first National Health and Medical Research Council (NHMRC) funded multicentre randomised clinical trial in Australia led by anaesthetist researchers, and the decision of The Australian and New Zealand College of Anaesthetists (ANZCA) to establish a clinical trials network, in 2003, to the success of contemporary researchers in Australia and New Zealand in anaesthesia and perioperative medicine.

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.

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

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

The importance of dietary change for men diagnosed with and at risk of prostate cancer: a multi-centre interview study with men, their partners and health professionals.

PubMed

Avery, Kerry N L; Donovan, Jenny L; Horwood, Jeremy; Neal, David E; Hamdy, Freddie C; Parker, Chris; Wade, Julia; Lane, Athene

2014-05-03

The diagnosis of prostate cancer (PC) can provide a trigger for dietary change, and there is evidence that healthier diets may improve quality of life and clinical outcomes. However, men's views about dietary change in PC survivorship are largely unknown. This multi-centre qualitative interview study explored men's views about dietary change in PC survivorship, to better understand motivations for, and barriers to, achieving desired changes. The role of radical and active surveillance treatments on dietary change and the influence of men's partners were examined. Focus groups also evaluated stakeholder opinion, including healthcare professionals, about the provision of dietary advice to PC patients. A multi-centre interview study explored views about diet and motivations for, and barriers to, dietary change in men at elevated risk or diagnosed with PC following prostate specific antigen (PSA) testing. 58 men and 11 partners were interviewed. Interviews and focus groups were undertaken with 11 healthcare professionals, 5 patients and 4 partners to evaluate stakeholders' opinions about the feasibility and acceptability of providing dietary advice to PC patients. Data were analysed using methods of constant comparison and thematic analysis. Over half of diagnosed men reported making dietary changes, primarily to promote general or prostate health or facilitate coping, despite their uncertainty about diet-PC links. Interest in dietary advice was high. Information needs varied depending on treatment received, with men on active surveillance more frequently modifying their diet and regarding this as an adjunct therapy. Men considered their partners integral to implementing changes. Provision of dietary advice to men diagnosed with PC was considered by healthcare professionals and men to be feasible and appropriate in the context of a holistic 'care package'. Many men make positive dietary changes after PC diagnosis, which are perceived by men and their partners to bring psychological and general health benefits and could help future dietary intervention trials. Men and their partners desire more and better dietary information that may support PC survivorship, particularly among those embarking on active surveillance/monitoring programmes. There are opportunities for healthcare professionals to support PC patients both clinically and psychologically by the routine integration of healthy eating advice into survivorship care plans.

Evolution of ischemic damage and behavioural deficit over 6 months after MCAo in the rat: Selecting the optimal outcomes and statistical power for multi-centre preclinical trials

PubMed Central

Churilov, Leonid; Sidon, T. Kate; Aleksoska, Elena; Cox, Susan F.; Macleod, Malcolm R.; Howells, David W.

2017-01-01

Key disparities between the timing and methods of assessment in animal stroke studies and clinical trial may be part of the reason for the failure to translate promising findings. This study investigates the development of ischemic damage after thread occlusion MCAo in the rat, using histological and behavioural outcomes. Using the adhesive removal test we investigate the longevity of behavioural deficit after ischemic stroke in rats, and examine the practicality of using such measures as the primary outcome for future studies. Ischemic stroke was induced in 132 Spontaneously Hypertensive Rats which were assessed for behavioural and histological deficits at 1, 3, 7, 14, 21, 28 days, 12 and 24 weeks (n>11 per timepoint). The basic behavioural score confirmed induction of stroke, with deficits specific to stroke animals. Within 7 days, these deficits resolved in 50% of animals. The adhesive removal test revealed contralateral neglect for up to 6 months following stroke. Sample size calculations to facilitate the use of this test as the primary experimental outcome resulted in cohort sizes much larger than are the norm for experimental studies. Histological damage progressed from a necrotic infarct to a hypercellular area that cleared to leave a fluid filled cavity. Whilst absolute volume of damage changed over time, when corrected for changes in hemispheric volume, an equivalent area of damage was lost at all timepoints. Using behavioural measures at chronic timepoints presents significant challenges to the basic science community in terms of the large number of animals required and the practicalities associated with this. Multicentre preclinical randomised controlled trials as advocated by the MultiPART consortium may be the only practical way to deal with this issue. PMID:28182727

Design and baseline characteristics of the Food4Me study: a web-based randomised controlled trial of personalised nutrition in seven European countries.

PubMed

Celis-Morales, Carlos; Livingstone, Katherine M; Marsaux, Cyril F M; Forster, Hannah; O'Donovan, Clare B; Woolhead, Clara; Macready, Anna L; Fallaize, Rosalind; Navas-Carretero, Santiago; San-Cristobal, Rodrigo; Kolossa, Silvia; Hartwig, Kai; Tsirigoti, Lydia; Lambrinou, Christina P; Moschonis, George; Godlewska, Magdalena; Surwiłło, Agnieszka; Grimaldi, Keith; Bouwman, Jildau; Daly, E J; Akujobi, Victor; O'Riordan, Rick; Hoonhout, Jettie; Claassen, Arjan; Hoeller, Ulrich; Gundersen, Thomas E; Kaland, Siv E; Matthews, John N S; Manios, Yannis; Traczyk, Iwona; Drevon, Christian A; Gibney, Eileen R; Brennan, Lorraine; Walsh, Marianne C; Lovegrove, Julie A; Alfredo Martinez, J; Saris, Wim H M; Daniel, Hannelore; Gibney, Mike; Mathers, John C

2015-01-01

Improving lifestyle behaviours has considerable potential for reducing the global burden of non-communicable diseases, promoting better health across the life-course and increasing well-being. However, realising this potential will require the development, testing and implementation of much more effective behaviour change interventions than are used conventionally. Therefore, the aim of this study was to conduct a multi-centre, web-based, proof-of-principle study of personalised nutrition (PN) to determine whether providing more personalised dietary advice leads to greater improvements in eating patterns and health outcomes compared to conventional population-based advice. A total of 5,562 volunteers were screened across seven European countries; the first 1,607 participants who fulfilled the inclusion criteria were recruited into the trial. Participants were randomly assigned to one of the following intervention groups for a 6-month period: Level 0-control group-receiving conventional, non-PN advice; Level 1-receiving PN advice based on dietary intake data alone; Level 2-receiving PN advice based on dietary intake and phenotypic data; and Level 3-receiving PN advice based on dietary intake, phenotypic and genotypic data. A total of 1,607 participants had a mean age of 39.8 years (ranging from 18 to 79 years). Of these participants, 60.9 % were women and 96.7 % were from white-European background. The mean BMI for all randomised participants was 25.5 kg m(-2), and 44.8 % of the participants had a BMI ≥ 25.0 kg m(-2). Food4Me is the first large multi-centre RCT of web-based PN. The main outcomes from the Food4Me study will be submitted for publication during 2015.

Surfactant Need by Gestation for Very Preterm Babies Initiated on Early Nasal CPAP: A Danish Observational Multicentre Study of 6,628 Infants Born 2000-2013.

PubMed

Wiingreen, Rikke; Greisen, Gorm; Ebbesen, Finn; Petersen, Jesper Padkær; Zachariassen, Gitte; Henriksen, Tine Brink; Mølholm Hansen, Bo

2017-01-01

In recent years, early nasal continuous positive airway pressure (nCPAP) as respiratory support for preterm infants is being advocated as an alternative to prophylactic surfactant and treatment with mechanical ventilation. A number of infants treated with early nCPAP do not need treatment with surfactant, but few studies provide data on this. Since the 1990s, the first approach to respiratory support to preterm infants in Denmark has been early nCPAP combined with surfactant administration by the INSURE method by which the infant is intubated and surfactant administration is followed by rapid extubation to nCPAP if possible. To investigate how often surfactant was administered in preterm infants with a gestational age below 34 weeks treated with early nCPAP as a first approach to respiratory support. An observational multicentre study including all inborn infants with a gestational age below 34 weeks admitted to 1 of the 4 level 3 neonatal intensive care units in Denmark in the period from 2000 to 2013. A total of 6,628 infants were included in this study. We found that surfactant was administered in 1,056 of 1,799 (59%; 95% CI: 57-61%), in 821 of 2,864 (29%; 95% CI: 27-31%), and in 132 of 1,796 (7%; 95% CI: 6-8%) of the infants with a gestational age from 24 to 27, 28 to 31, and 32 to 33 weeks and 6 days, respectively. A large proportion of preterm infants treated with early nCPAP as the first approach to respiratory support was never treated with surfactant. © 2017 S. Karger AG, Basel.

A multicentre study of meticillin-resistant Staphylococcus aureus in acute bacterial skin and skin-structure infections in China: susceptibility to ceftaroline and molecular epidemiology.

PubMed

Zhang, Hui; Xiao, Meng; Kong, Fanrong; O'Sullivan, Matthew V N; Mao, Lei-Li; Zhao, Hao-Ran; Zhao, Ying; Wang, He; Xu, Ying-Chun

2015-04-01

Ceftaroline is a novel cephalosporin with activity against Gram-positive organisms, including meticillin-resistant Staphylococcus aureus (MRSA). The objective of this study was to investigate the susceptibility to ceftaroline of hospital-associated MRSA (HA-MRSA) isolates causing acute bacterial skin and skin-structure infections (ABSSSIs) in China and to examine their relationship by genotyping. A total of 251 HA-MRSA isolates causing ABSSSIs were collected from a multicentre study involving 56 hospitals in 38 large cities across 26 provinces in mainland China. All isolates were characterised by multilocus sequence typing (MLST), staphylococcal cassette chromosome mec (SCCmec) typing, spa typing and detection of the Panton-Valentine leukocidin locus (lukS-PV and lukF-PV). Minimum inhibitory concentrations (MICs) of 14 antimicrobial agents, including ceftaroline, were determined by broth microdilution and were interpreted using Clinical and Laboratory Standards Institute breakpoints. The ceftaroline MIC50 and MIC90 values (MICs that inhibit 50% and 90% of the isolates, respectively) were 1 μg/mL and 2 μg/mL, respectively; 33.5% (n=84) of the isolates studied were ceftaroline-non-susceptible, with MICs of 2 μg/mL, but no isolate exhibited ceftaroline resistance (MIC>2 μg/mL). All of the ceftaroline-non-susceptible isolates belonged to the predominant HA-MRSA clones: 95.2% (n=80) from MLST clonal complex 8 (CC8), with the remaining 4.8% (n=4) from CC5. The high rate of non-susceptibility to ceftaroline amongst HA-MRSA causing ABSSSIs in China is concerning. Copyright © 2015 Elsevier B.V. and the International Society of Chemotherapy. All rights reserved.

All for one and one for all: The value of grassroots collaboration in clinical research.

PubMed

Al Wattar, Bassel H; Tamblyn, Jennifer

2017-08-01

Collaboration in health research is common in current practice. Engaging grassroots clinicians in the evidence synthesis and research process can deliver impactful results and reduce research wastage. The UKARCOG is a group of specialty trainees in obstetrics and gynaecology in the UK aiming to promote women's health research by delivering high-quality impactful research and national audit projects. The collaborative enables trainees to develop essential academic skills and roll out multicentre research projects at high cost-effectiveness. Collective research work can face a number of challenges such as establishing a joint authorship style, gaining institutional support and acquiring funds to boost networking and deliver large scales studies. Copyright © 2017 Elsevier B.V. All rights reserved.

Montelukast (Singulair) and Pregnancy

MedlinePlus

... 2009. Montelukast use during pregnancy: a multicentre, prospective, comparative study of infant outcomes Eur J Clin Pharmacol. ... Conditions of Use Site By: Marketing and Advertising Design Group

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.

Ethics review as a component of institutional approval for a multicentre continuous quality improvement project: the investigator's perspective.

PubMed

Ezzat, Hanna; Ross, Sue; von Dadelszen, Peter; Morris, Tara; Liston, Robert; Magee, Laura A

2010-07-30

For ethical approval of a multicentre study in Canada, investigators must apply separately to individual Research Ethics Boards (REBs). In principle, the protection of human research subjects is of utmost importance. However, in practice, the process of multicentre ethics review can be time consuming and costly, requiring duplication of effort for researchers and REBs. We used our experience with ethical review of The Canadian Perinatal Network (CPN), to gain insight into the Canadian system. The applications forms of 16 different REBs were abstracted for a list of standardized items. The application process across sites was compared. Correspondence between the REB and the investigators was documented in order to construct a timeline to approval, identify the specific issues raised by each board, and describe how they were resolved. Each REB had a different application form. Most (n = 9) had a two or three step application process. Overall, it took a median of 31 days (range 2-174 days) to receive an initial response from the REB. Approval took a median of 42 days (range 4-443 days). Privacy and consent were the two major issues raised. Several additional minor or administrative issues were raised which delayed approval. For CPN, the Canadian REB process of ethical review proved challenging. REBs acted independently and without unified application forms or submission procedures. We call for a critical examination of the ethical, privacy and institutional review processes in Canada, to determine the best way to undertake multicentre review.

Cerebral sinus venous thromboses in children with acute lymphoblastic leukaemia - a multicentre study from the Nordic Society of Paediatric Haematology and Oncology.

PubMed

Ranta, Susanna; Tuckuviene, Ruta; Mäkipernaa, Anne; Albertsen, Birgitte K; Frisk, Tony; Tedgård, Ulf; Jónsson, Ólafur G; Pruunsild, Kaie; Gretenkort Andersson, Nadine; Winther Gunnes, Maria; Saulyte Trakymiene, Sonata; Frandsen, Thomas; Heyman, Mats; Ruud, Ellen; Helgestad, Jon

2015-02-01

We present a prospective multicentre cohort of 20 children with acute lymphoblastic leukaemia (ALL) and cerebral sinus venous thrombosis (CSVT). The study covers a period of 5 years and comprises 1038 children treated according to the Nordic Society of Paediatric Haematology and Oncology (NOPHO) ALL 2008 protocol. The cumulative incidence of CSVT was 2%. Sixteen of the thromboses were related to asparaginase and 16 to steroids. Most CSVTs occurred in the consolidation phase. Nearly all were treated with low molecular weight heparin without bleeding complications. Mortality related to CSVT directly or indirectly was 10%, emphasizing the importance of this complication. © 2014 John Wiley & Sons Ltd.

Early 2016/17 vaccine effectiveness estimates against influenza A(H3N2): I-MOVE multicentre case control studies at primary care and hospital levels in Europe

PubMed Central

Kissling, Esther; Rondy, Marc

2017-01-01

We measured early 2016/17 season influenza vaccine effectiveness (IVE) against influenza A(H3N2) in Europe using multicentre case control studies at primary care and hospital levels. IVE at primary care level was 44.1%, 46.9% and 23.4% among 0–14, 15–64 and ≥ 65 year-olds, and 25.7% in the influenza vaccination target group. At hospital level, IVE was 2.5%, 7.9% and 2.4% among ≥ 65, 65–79 and ≥ 80 year-olds. As in previous seasons, we observed suboptimal IVE against influenza A(H3N2). PMID:28230524

Implantable hemodynamic monitoring (the Chronicle IHM system): remote telemonitoring for patients with heart failure.

PubMed

Ho, C

2008-01-01

(1) Remote monitoring for ambulatory heart failure patients uses an implantable device to record hemodynamic data and transmit it to a central server for continuous assessment. (2) Preliminary evidence from observational studies suggests a potential for reducing hospitalizations with the use of right ventricle implantable hemodynamic monitoring (IHM). However, although a multicentre, randomized controlled trial (COMPASS-HF) showed a reduction in hospitalizations in the IHM group the results were not statistically significant and the US Food and Drug Administration panel concluded the trial failed to meet its primary efficacy endpoint. (3) In the COMPASS-HF study the most common device-related complication was lead dislodgement. (4) Large randomized controlled trials are needed to demonstrate the clinical utility of IHM, particularly in terms of its impact on reducing hospitalization and improving patient outcomes.

The economic burden of incisional ventral hernia repair: a multicentric cost analysis.

PubMed

Gillion, J-F; Sanders, D; Miserez, M; Muysoms, F

2016-12-01

A systematic review of literature led us to take note that little was known about the costs of incisional ventral hernia repair (IVHR). Therefore we wanted to assess the actual costs of IVHR. The total costs are the sum of direct (hospital costs) and indirect (sick leave) costs. The direct costs were retrieved from a multi-centric cost analysis done among a large panel of 51 French public hospitals, involving 3239 IVHR. One hundred and thirty-two unitary expenditure items were thoroughly evaluated by the accountants of a specialized public agency (ATIH) dedicated to investigate the costs of the French Health Care system. The indirect costs (costs of the post-operative inability to work and loss of profit due to the disruption in the ongoing work) were estimated from the data the Hernia Club registry, involving 790 patients, and over a large panel of different Collective Agreements. The mean total cost for an IVHR in France in 2011 was estimated to be 6451€, ranging from 4731€ for unemployed patients to 10,107€ for employed patients whose indirect costs (5376€) were slightly higher than the direct costs. Reducing the incidence of incisional hernia after abdominal surgery with 5 % for instance by implementation of the European Hernia Society Guidelines on closure of abdominal wall incisions, or maybe even by use of prophylactic mesh augmentation in high risk patients could result in a national cost savings of 4 million Euros.

Efficient, quality-assured data capture in operational research through innovative use of open-access technology

PubMed Central

Naik, B.; Guddemane, D. K.; Bhat, P.; Wilson, N.; Sreenivas, A. N.; Lauritsen, J. M.; Rieder, H. L.

2013-01-01

Ensuring quality of data during electronic data capture has been one of the most neglected components of operational research. Multicentre studies are also challenged with issues about logistics of travel, training, supervision, monitoring and troubleshooting support. Allocating resources to these issues can pose a significant bottleneck for operational research in resource-limited settings. In this article, we describe an innovative and efficient way of coordinating data capture in multicentre operational research using a combination of three open access technologies—EpiData for data capture, Dropbox for sharing files and TeamViewer for providing remote support. PMID:26392997

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.

Protocol for a multicentre, multistage, prospective study in China using system-based approaches for consistent improvement in surgical safety.

PubMed

Yu, Xiaochu; Jiang, Jingmei; Liu, Changwei; Shen, Keng; Wang, Zixing; Han, Wei; Liu, Xingrong; Lin, Guole; Zhang, Ye; Zhang, Ying; Ma, Yufen; Bo, Haixin; Zhao, Yupei

2017-06-15

Surgical safety has emerged as a crucial global health issue in the past two decades. Although several safety-enhancing tools are available, the pace of large-scale improvement remains slow, especially in developing countries such as China. The present project (Modern Surgery and Anesthesia Safety Management System Construction and Promotion) aims to develop and validate system-based integrated approaches for reducing perioperative deaths and complications using a multicentre, multistage design. The project involves collection of clinical and outcome information for 1 20 000 surgical inpatients at four regionally representative academic/teaching general hospitals in China during three sequential stages: preparation and development, effectiveness validation and improvement of implementation for promotion. These big data will provide the evidence base for the formulation, validation and improvement processes of a system-based stratified safety intervention package covering the entire surgical pathway. Attention will be directed to managing inherent patient risks and regulating medical safety behaviour. Information technology will facilitate data collection and intervention implementation, provide supervision mechanisms and guarantee transfer of key patient safety messages between departments and personnel. Changes in rates of deaths, surgical complications during hospitalisation, length of stay, system adoption and implementation rates will be analysed to evaluate effectiveness and efficiency. This study was approved by the institutional review boards of Peking Union Medical College Hospital, First Hospital of China Medical University, Qinghai Provincial People's Hospital, Xiangya Hospital Central South University and the Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences. Study findings will be disseminated via peer-reviewed journals, conference presentations and patent papers. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

The 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.

Protocol for a multicentre, multistage, prospective study in China using system-based approaches for consistent improvement in surgical safety

PubMed Central

Yu, Xiaochu; Jiang, Jingmei; Liu, Changwei; Shen, Keng; Wang, Zixing; Han, Wei; Liu, Xingrong; Lin, Guole; Zhang, Ye; Zhang, Ying; Ma, Yufen; Bo, Haixin; Zhao, Yupei

2017-01-01

Introduction Surgical safety has emerged as a crucial global health issue in the past two decades. Although several safety-enhancing tools are available, the pace of large-scale improvement remains slow, especially in developing countries such as China. The present project (Modern Surgery and Anesthesia Safety Management System Construction and Promotion) aims to develop and validate system-based integrated approaches for reducing perioperative deaths and complications using a multicentre, multistage design. Methods and analysis The project involves collection of clinical and outcome information for 1 20 000 surgical inpatients at four regionally representative academic/teaching general hospitals in China during three sequential stages: preparation and development, effectiveness validation and improvement of implementation for promotion. These big data will provide the evidence base for the formulation, validation and improvement processes of a system-based stratified safety intervention package covering the entire surgical pathway. Attention will be directed to managing inherent patient risks and regulating medical safety behaviour. Information technology will facilitate data collection and intervention implementation, provide supervision mechanisms and guarantee transfer of key patient safety messages between departments and personnel. Changes in rates of deaths, surgical complications during hospitalisation, length of stay, system adoption and implementation rates will be analysed to evaluate effectiveness and efficiency. Ethics and dissemination This study was approved by the institutional review boards of Peking Union Medical College Hospital, First Hospital of China Medical University, Qinghai Provincial People’s Hospital, Xiangya Hospital Central South University and the Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences. Study findings will be disseminated via peer-reviewed journals, conference presentations and patent papers. PMID:28619774

Diagnosis, symptoms, frequency and mortality of 260 patients with urea cycle disorders from a 21-year, multicentre study of acute hyperammonaemic episodes.

PubMed

Summar, Marshall L; Dobbelaere, Dries; Brusilow, Saul; Lee, Brendan

2008-10-01

A large longitudinal interventional study of patients with a urea cycle disorder (UCD) in hyperammonaemic crisis was undertaken to amass a significant body of data on their presenting symptoms and survival. Between 1982 and 2003, as part of the FDA approval process, data were collected on patients receiving an intravenous combination of nitrogen scavenging drugs (Ammonul sodium phenylacetate and sodium benzoate (10%, 10%)) for the treatment of hyperammonaemic crises caused by urea cycle disorders. A final diagnosis of a UCD was made for 260 patients, representing 975 episodes of hospitalization. Only 34% of these patients presented within the first 30 days of life and had a mortality rate of 32%. The most common presenting symptoms were neurological (80%), or gastrointestinal (33%). This cohort is the largest collection of patients reported for these diseases and the first large cohort in the United States. Surprisingly, the majority (66%) of patients with heritable causes of hyperammonaemia present beyond the neonatal period (>30 days). Patients with late-onset presenting disorders exhibited prolonged survival compared to the neonatal-presenting group.

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

Salmeterol versus slow-release theophylline combined with ketotifen in nocturnal asthma: a multicentre trial. French Multicentre Study Group.

PubMed

Muir, J F; Bertin, L; Georges, D

1992-11-01

We wished to assess the efficacy of inhaled salmeterol (SML; 50 micrograms b.i.d.) compared to a combination of slow-release theophylline and ketotifen p.o. (TK; T 300 mg+K 1 mg b.i.d.) for the treatment of nocturnal asthma. Ninety six patients with nocturnal asthma, (forced expiratory volume in one second (FEV1) 60-90% of predicted value, reversibility > or = 15%, at least two nocturnal awakenings per week) were eligible for a multicentre, double-blind, double-dummy cross-over study (14-day run-in, two successive 28-day treatment periods). Efficacy was assessed as success/failure, success being defined as the complete disappearance of nocturnal symptoms/awakening during the last week of each treatment period. There was a statistically significant difference between SML and TK for this criterion: 46% and 39% success with SML during periods I (first 28-day period) and II (following the cross-over), compared to only 15% and 26% with TK, respectively (p < 0.01). SML was also significantly better for the other criteria (lung function, rescue salbutamol intake during day and night). Side-effects were five times less frequent in SML-treated patients (p < 0.004). Efficacy and tolerance of SML were obviously far better than those of TK in patients with nocturnal asthma.

[Role of Institutional Review Boards for multi-centre studies in national health services research - a cross-sectional study of the effort to obtain secondary ethical approvals for the DACAPO study].

PubMed

Blecha, Sebastian; Thomann-Hackner, Kathrin; Brandstetter, Susanne; Dodoo-Schittko, Frank; Seboek, Philipp; Apfelbacher, Christian; Graf, Bernhard M; Bein, Thomas

2015-09-01

Health services research (HSR) is of fundamental importance for the continuous improvement of preventive, diagnostic or therapeutic measures. The conduct of multi-centre HSR studies requires that ethical approval by Institutional review boards (IRB's) is obtained. We documented the effort, the complexity and the man power necessary to obtain secondary ethical approval for a national HSR in Germany ("Surviving the Acute Respiratory Distress Syndrome" [DACAPO-study]). Having obtained a primary ethical approval by the IRB of Regensburg University, the time, correspondence, necessity for amendments, corrections, or additional costs by 34 IRB's for 64 participating study centers was documented. The complete obtainment was found to be time consuming and associated with a high workload and man power. A time span of seven month was needed to receive votes from all IRB's. The median time span was 25,5 days (25 %/75 % percentile 13 and 42 days, respectively). Requirements in terms of corrections or amendments were inhomogeneous and frequent changes were necessary. There were additional fees for secondary votes of 4328,40 €. Total costs for the study center Regensburg were 21.193,40 € (2,6 % of the grant volume). Obtaining all ethical approvals for a multi-centre observational HSR study in Germany is complex and time consuming. Various and inhomogeneous formalities may delay the plan and realization of HSR. A Homogenization and simplification of the procedure of ethics votes should be discussed. © Georg Thieme Verlag KG Stuttgart · New York.

Improving site selection in clinical studies: a standardised, objective, multistep method and first experience results.

PubMed

Hurtado-Chong, Anahí; Joeris, Alexander; Hess, Denise; Blauth, Michael

2017-07-12

A considerable number of clinical studies experience delays, which result in increased duration and costs. In multicentre studies, patient recruitment is among the leading causes of delays. Poor site selection can result in low recruitment and bad data quality. Site selection is therefore crucial for study quality and completion, but currently no specific guidelines are available. Selection of sites adequate to participate in a prospective multicentre cohort study was performed through an open call using a newly developed objective multistep approach. The method is based on use of a network, definition of objective criteria and a systematic screening process. Out of 266 interested sites, 24 were shortlisted and finally 12 sites were selected to participate in the study. The steps in the process included an open call through a network, use of selection questionnaires tailored to the study, evaluation of responses using objective criteria and scripted telephone interviews. At each step, the number of candidate sites was quickly reduced leaving only the most promising candidates. Recruitment and quality of data went according to expectations in spite of the contracting problems faced with some sites. The results of our first experience with a standardised and objective method of site selection are encouraging. The site selection method described here can serve as a guideline for other researchers performing multicentre studies. ClinicalTrials.gov: NCT02297581. © 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.

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.

Perspectives of gene expression profiling for diagnosis and therapy in haematological malignancies.

PubMed

Bacher, Ulrike; Kohlmann, Alexander; Haferlach, Torsten

2009-05-01

Considering the heterogeneity of leukaemias and the widening spectrum of therapeutic strategies, novel diagnostic methods are urgently needed for haematological malignancies. For a decade, gene expression profiling (GEP) has been applied in leukaemia research. Thus, various studies demonstrated worldwide that the majority of genetically defined leukaemia subtypes are accurately predictable by GEP, for example, with respect to reciprocal rearrangements in acute myeloid leukaemia (AML). Moreover, novel prognostically relevant gene classifiers were developed as, for example, in normal karyotype AML. Considering the lymphatic malignancies, GEP studies defined novel clinically relevant subtypes in diffuse large B cell lymphoma (DLBCL), and improved the discrimination of Burkitt lymphoma and DLBCL cases, overcoming considerable overlaps of these entities that exist from morphological and genetic perspectives. Treatment-specific sensitivity assays are being developed for targeted drugs such as farnesyl transferase inhibitors in AML or imatinib in BCR-ABL1 positive acute lymphoblastic leukaemia (ALL). Irrespectively of these proceedings, an introduction of the microarray technology in haematological practice requires diagnostic algorithms and strategies for interaction with currently established diagnostic techniques. Large multicentre studies such as the MILE Study (Microarray Innovations in LEukemia) aim at translating this methodology into clinical routine workflows and to catalyze this process.

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.

Four years of experience with the Australian kidney paired donation programme.

PubMed

Cantwell, Linda; Woodroffe, Claudia; Holdsworth, Rhonda; Ferrari, Paolo

2015-03-01

New approaches to increase kidney transplantation rates through expansion of live donor kidney transplantation have become necessary due to ongoing shortage of deceased donor organs. These strategies include desensitization in antibody-incompatible transplants to overcome the barrier of blood group incompatibility or human leucocyte antigen antibodies between recipient and donor and kidney paired donation (KPD) programmes. In KPD, a kidney transplant candidate with an incompatible live donor joins a registry of other incompatible pairs in order to find potentially compatible transplant solutions. To match the largest possible number of donor-recipient pairs while minimizing immunologic risk, KPD programmes use sophisticated algorithms to identify suitable matches with simultaneous two-way or more complex multi-way exchanges as well as including non-directed anonymous donors to start a chain of compatible transplantations. Because of the significant immunologic barriers when fewer donor options are available, the optimal solution for difficult-to-match, highly sensitized patients is access to more potential donors using large multi-centre or national KPD registries. This review focuses on the first 4 years of experience with the Australian multi-centre KPD programme that was established in October 2010. © 2014 Asian Pacific Society of Nephrology.

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.

Multicentre dose audit for clinical trials of radiation therapy in Asia

PubMed Central

Fukuda, Shigekazu; Fukumura, Akifumi; Nakamura, Yuzuru-Kutsutani; Jianping, Cao; Cho, Chul-Koo; Supriana, Nana; Dung, To Anh; Calaguas, Miriam Joy; Devi, C.R. Beena; Chansilpa, Yaowalak; Banu, Parvin Akhter; Riaz, Masooma; Esentayeva, Surya; Kato, Shingo; Karasawa, Kumiko; Tsujii, Hirohiko

2017-01-01

Abstract A dose audit of 16 facilities in 11 countries has been performed within the framework of the Forum for Nuclear Cooperation in Asia (FNCA) quality assurance program. The quality of radiation dosimetry varies because of the large variation in radiation therapy among the participating countries. One of the most important aspects of international multicentre clinical trials is uniformity of absolute dose between centres. The National Institute of Radiological Sciences (NIRS) in Japan has conducted a dose audit of participating countries since 2006 by using radiophotoluminescent glass dosimeters (RGDs). RGDs have been successfully applied to a domestic postal dose audit in Japan. The authors used the same audit system to perform a dose audit of the FNCA countries. The average and standard deviation of the relative deviation between the measured and intended dose among 46 beams was 0.4% and 1.5% (k = 1), respectively. This is an excellent level of uniformity for the multicountry data. However, of the 46 beams measured, a single beam exceeded the permitted tolerance level of ±5%. We investigated the cause for this and solved the problem. This event highlights the importance of external audits in radiation therapy. PMID:27864507

International Collaboration Enhances Cancer Screening Efforts

Cancer.gov

CGH is working with the International Agency for Research on CancerExit Disclaimer (IARC) and the Pan American Health Organization (PAHO) on the ESTAMPA Study, a multi-centric study of cervical cancer screening and triage with HPV testing.

Ethics review as a component of institutional approval for a multicentre continuous quality improvement project: the investigator's perspective

PubMed Central

2010-01-01

Background For ethical approval of a multicentre study in Canada, investigators must apply separately to individual Research Ethics Boards (REBs). In principle, the protection of human research subjects is of utmost importance. However, in practice, the process of multicentre ethics review can be time consuming and costly, requiring duplication of effort for researchers and REBs. We used our experience with ethical review of The Canadian Perinatal Network (CPN), to gain insight into the Canadian system. Methods The applications forms of 16 different REBs were abstracted for a list of standardized items. The application process across sites was compared. Correspondence between the REB and the investigators was documented in order to construct a timeline to approval, identify the specific issues raised by each board, and describe how they were resolved. Results Each REB had a different application form. Most (n = 9) had a two or three step application process. Overall, it took a median of 31 days (range 2-174 days) to receive an initial response from the REB. Approval took a median of 42 days (range 4-443 days). Privacy and consent were the two major issues raised. Several additional minor or administrative issues were raised which delayed approval. Conclusions For CPN, the Canadian REB process of ethical review proved challenging. REBs acted independently and without unified application forms or submission procedures. We call for a critical examination of the ethical, privacy and institutional review processes in Canada, to determine the best way to undertake multicentre review. PMID:20673343

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.

Gender and regional differences in perceived job stress across Europe.

PubMed

de Smet, P; Sans, S; Dramaix, M; Boulenguez, C; de Backer, G; Ferrario, M; Cesana, G; Houtman, I; Isacsson, S O; Kittel, F; Ostergren, P O; Peres, I; Pelfrene, E; Romon, M; Rosengren, A; Wilhelmsen, L; Kornitzer, M

2005-10-01

Over the last 20 years stress at work has been found to be predictive of several conditions such as coronary heart disease, high blood pressure and non-specific sick leave. The Karasek demand/control/strain concept has been the most widely used in prospective epidemiological studies. To describe distribution in Karasek's demand/control (DC) dimensions as well as prevalence of strain in samples from different parts of Europe grouped into three regions (South, Middle, Sweden), adjusting for occupation. To describe gender differences in Karasek's DC dimensions along with strain prevalence and assess the regional stability of those differences in different occupational groups. The Job stress, Absenteeism and Coronary heart disease in Europe (JACE) study, a Concerted Action (Biomed I) of the European Union, is a multicentre prospective cohort epidemiological study: 38,019 subjects at work aged 35-59 years were surveyed at baseline. Standardised techniques were used for occupation coding (International Standardised Classification of Occupations) and for the DC model (Karasek scale): five items for the psychological demand and nine items for the control or decision latitude dimensions, respectively. A total of 34,972 subjects had a complete data set. There were important regional differences in the Karasek scales and in prevalence of strain even after adjustment for occupational class. Mean demand and control were higher in the Swedish centres when compared to two centres in Milano and Barcelona (Southern region) and values observed in four centres (Ghent, Brussels, Lille and Hoofddorp) in Middle Europe were closer to those observed in the Southern cities than to those obtained in the Swedish cities. Clerks (ISCO 4) and, more specifically, office clerks (ISCO 41) exhibited the smallest regional variation. In a multivariate model, the factor 'region' explained a small fraction of total variance. In the two Southern centres as well as in the four Middle European centres, men perceived marginally less job-demand as compared to women whereas the reverse was observed in the two Swedish centres. Differences were larger for control: men appeared to perceive more control at work than did women. In a multivariate model, gender explained a small fraction whereas occupational level explained a large fraction of the variance. In this standardised multicentre European study Karasek's DC model showed large gender and occupational differences whereas geographic region explained a small fraction of the total DC variance, notwithstanding large differences in labour market and working conditions as pointed out by the European Commission as recently as 2000.

CTRI – Clicking to greater transparency and accountability

PubMed Central

George, Bobby

2012-01-01

A clinical trial registry (CTR) is an official platform for registering a clinical trial (CT) with an objective of providing increased transparency and access to CTs to the public at large. Clinical Trials Registry - India (CTRI) is a free online public record system for registration of CTs being conducted in India. The vision of the CTRI is to ensure that every CT conducted in the region is prospectively registered with full disclosure of the trial data set items. With more number of CTs being conducted in the country, with a large number being global multicentre trials, it is binding on the industry/investigators/sponsor to comply with the requirements laid down. While there are pros and cons, there is enough scope for improvement of CTRI. PMID:23293758

[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.

Intensive care unit patients with lower respiratory tract nosocomial infections: the ENIRRIs project.

PubMed

De Pascale, Gennaro; Ranzani, Otavio T; Nseir, Saad; Chastre, Jean; Welte, Tobias; Antonelli, Massimo; Navalesi, Paolo; Garofalo, Eugenio; Bruni, Andrea; Coelho, Luis Miguel; Skoczynski, Szymon; Longhini, Federico; Taccone, Fabio Silvio; Grimaldi, David; Salzer, Helmut J F; Lange, Christoph; Froes, Filipe; Artigas, Antoni; Díaz, Emili; Vallés, Jordi; Rodríguez, Alejandro; Panigada, Mauro; Comellini, Vittoria; Fasano, Luca; Soave, Paolo M; Spinazzola, Giorgia; Luyt, Charles-Edouard; Alvarez-Lerma, Francisco; Marin, Judith; Masclans, Joan Ramon; Chiumello, Davide; Pezzi, Angelo; Schultz, Marcus; Mohamed, Hafiz; Van Der Eerden, Menno; Hoek, Roger A S; Gommers, D A M P J; Pasquale, Marta Di; Civljak, Rok; Kutleša, Marko; Bassetti, Matteo; Dimopoulos, George; Nava, Stefano; Rios, Fernando; Zampieri, Fernando G; Povoa, Pedro; Bos, Lieuwe D; Aliberti, Stefano; Torres, Antoni; Martín-Loeches, Ignacio

2017-10-01

The clinical course of intensive care unit (ICU) patients may be complicated by a large spectrum of lower respiratory tract infections (LRTI), defined by specific epidemiological, clinical and microbiological aspects. A European network for ICU-related respiratory infections (ENIRRIs), supported by the European Respiratory Society, has been recently established, with the aim at studying all respiratory tract infective episodes except community-acquired ones. A multicentre, observational study is in progress, enrolling more than 1000 patients fulfilling the clinical, biochemical and radiological findings consistent with a LRTI. This article describes the methodology of this study. A specific interest is the clinical impact of non-ICU-acquired nosocomial pneumonia requiring ICU admission, non-ventilator-associated LRTIs occurring in the ICU, and ventilator-associated tracheobronchitis. The clinical meaning of microbiologically negative infectious episodes and specific details on antibiotic administration modalities, dosages and duration are also highlighted. Recently released guidelines address many unresolved questions which might be answered by such large-scale observational investigations. In light of the paucity of data regarding such topics, new interesting information is expected to be obtained from our network research activities, contributing to optimisation of care for critically ill patients in the ICU.

High-Volume Repeaters of Self-Harm.

PubMed

Ness, Jennifer; Hawton, Keith; Bergen, Helen; Waters, Keith; Kapur, Navneet; Cooper, Jayne; Steeg, Sarah; Clarke, Martin

2016-11-01

Repetition of self-harm is common and is strongly associated with suicide. Despite this, there is limited research on high-volume repetition. To investigate individuals with high-volume repeat self-harm attendances to the emergency department (ED), including their patterns of attendance and mortality. Data from the Multicentre Study of Self-Harm in England were used. High-volume repetition was defined as ⩾15 attendances within 4 years. An attendance timeline was constructed for each high-volume repeater (HVR) and the different patterns of attendance were explored using an executive sorting task and hierarchical cluster analysis. A small proportion of self-harm patients are HVRs (0.6%) but they account for a large percentage of self-harm attendances (10%). In this study, the new methodological approach resulted in three types of attendance patterns. All of the HVRs had clusters of attendance and a greater proportion died from external causes compared with non-HVRs. The approach used in this study offers a new method for investigating this problem that could have both clinical and research benefits. The need for early intervention is highlighted by the large number of self-harm episodes per patient, the clustered nature of attendances, and the higher prevalence of death from external causes.

Glutamine: an obligatory parenteral nutrition substrate in critical care therapy.

PubMed

Stehle, Peter; Kuhn, Katharina S

2015-01-01

Critical illness is characterized by glutamine depletion owing to increased metabolic demand. Glutamine is essential to maintain intestinal integrity and function, sustain immunologic response, and maintain antioxidative balance. Insufficient endogenous availability of glutamine may impair outcome in critically ill patients. Consequently, glutamine has been considered to be a conditionally essential amino acid and a necessary component to complete any parenteral nutrition regimen. Recently, this scientifically sound recommendation has been questioned, primarily based on controversial findings from a large multicentre study published in 2013 that evoked considerable uncertainty among clinicians. The present review was conceived to clarify the most important questions surrounding glutamine supplementation in critical care. This was achieved by addressing the role of glutamine in the pathophysiology of critical illness, summarizing recent clinical studies in patients receiving parenteral nutrition with intravenous glutamine, and describing practical concepts for providing parenteral glutamine in critical care.

Glutamine: An Obligatory Parenteral Nutrition Substrate in Critical Care Therapy

PubMed Central

Stehle, Peter; Kuhn, Katharina S.

2015-01-01

Critical illness is characterized by glutamine depletion owing to increased metabolic demand. Glutamine is essential to maintain intestinal integrity and function, sustain immunologic response, and maintain antioxidative balance. Insufficient endogenous availability of glutamine may impair outcome in critically ill patients. Consequently, glutamine has been considered to be a conditionally essential amino acid and a necessary component to complete any parenteral nutrition regimen. Recently, this scientifically sound recommendation has been questioned, primarily based on controversial findings from a large multicentre study published in 2013 that evoked considerable uncertainty among clinicians. The present review was conceived to clarify the most important questions surrounding glutamine supplementation in critical care. This was achieved by addressing the role of glutamine in the pathophysiology of critical illness, summarizing recent clinical studies in patients receiving parenteral nutrition with intravenous glutamine, and describing practical concepts for providing parenteral glutamine in critical care. PMID:26495301

Fixation using alternative implants for the treatment of hip fractures (FAITH): design and rationale for a multi-centre randomized trial comparing sliding hip screws and cancellous screws on revision surgery rates and quality of life in the treatment of femoral neck fractures.

PubMed

2014-06-26

Hip fractures are a common type of fragility fracture that afflict 293,000 Americans (over 5,000 per week) and 35,000 Canadians (over 670 per week) annually. Despite the large population impact the optimal fixation technique for low energy femoral neck fractures remains controversial. The primary objective of the FAITH study is to assess the impact of cancellous screw fixation versus sliding hip screws on rates of revision surgery at 24 months in individuals with femoral neck fractures. The secondary objective is to determine the impact on health-related quality of life, functional outcomes, health state utilities, fracture healing, mortality and fracture-related adverse events. FAITH is a multi-centre, multi-national randomized controlled trial utilizing minimization to determine patient allocation. Surgeons in North America, Europe, Australia, and Asia will recruit a total of at least 1,000 patients with low-energy femoral neck fractures. Using central randomization, patients will be allocated to receive surgical treatment with cancellous screws or a sliding hip screw. Patient outcomes will be assessed at one week (baseline), 10 weeks, 6, 12, 18, and 24 months post initial fixation. We will independently adjudicate revision surgery and complications within 24 months of the initial fixation. Outcome analysis will be performed using a Cox proportional hazards model and likelihood ratio test. This study represents major international efforts to definitively resolve the treatment of low-energy femoral neck fractures. This trial will not only change current Orthopaedic practice, but will also set a benchmark for the conduct of future Orthopaedic trials. The FAITH trial is registered at ClinicalTrials.gov (Identifier NCT00761813).

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.

Multicentre analysis of long-term outcome after surgical resection for gastric cancer liver metastases.

PubMed

Kinoshita, T; Kinoshita, T; Saiura, A; Esaki, M; Sakamoto, H; Yamanaka, T

2015-01-01

The efficacy of surgical resection for gastric cancer liver metastases (GCLMs) is currently debated. Hitherto, no large-scale clinical studies have been conducted. This retrospective multicentre study analysed a database of consecutive patients with either synchronous or metachronous metastases who underwent surgical R0 resection for GCLM between 1990 and 2010. Clinical data were collected from five cancer centres in Japan. Survival curves were assessed, and clinical parameters were evaluated to identify predictors of prognosis. A total of 256 patients were enrolled. The mean(s.d.) number of hepatic tumours resected was 2.0(2.4). The surgical mortality rate was 1.6 per cent. Median follow-up was 65 (range 1-261) months. Recurrences were detected in 192 patients (75.0 per cent). The median interval from hepatic resection to recurrence was 7 (range 1-72) months, and the dominant site of recurrence was the liver (72.4 per cent). Actuarial 1-, 3- and 5-year overall and recurrence-free survival rates were 77.3, 41.9 and 31.1 per cent, and 43.6, 32.4 and 30.1 per cent, respectively. Median overall and recurrence-free survival times were 31.1 and 9.4 months respectively. Multivariable analysis identified serosal invasion of the primary gastric cancer (hazard ratio (HR) 1.50; P = 0.012), three or more liver metastases (HR 2.33; P < 0.001) and liver tumour diameter at least 5 cm (HR 1.62; P = 0.005) as independent predictors of poor survival. Clinically resectable GCLM is rare, but strict and careful patient selection can lead to long-term survival following R0 surgical resection. © 2014 BJS Society Ltd. Published by John Wiley & Sons Ltd.

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

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.

Online versus Live Delivery of Education to Pharmacists in a Large Multicentre Health Region: A Non-inferiority Assessment of Learning Outcomes.

PubMed

Taylor, Robert; Jung, Joanne; Loewen, Peter; Spencer, Carrie; Dossa, Anar; de Lemos, Jane

2013-07-01

The prevalence of online modules for continuing education in the health professions has been increasing in recent years. However, the effectiveness of online modules for pharmacist learning has not been thoroughly studied. The primary aim of this study was to determine if providing education to pharmacists through a self-paced enhanced online module was non-inferior to a face-to-face learning module with respect to knowledge application on the topic of postoperative insulin dosing. Secondary aims were to determine pharmacists' knowledge gain and retention, as well as their satisfaction with the modules. The participants in this prospective, randomized, parallel-group non-inferiority trial were pharmacists in a large multicentre health region. Outcomes were measured by comparing scores obtained on pre- and post-module knowledge-assessment questionnaires. A between-group difference in change on knowledge application scores of less than 25 percentage points was the predetermined non-inferiority margin. A total of 74 pharmacists consented to participate, 38 randomly assigned to use the enhanced online module and 36 to attend the face-to-face learning session. For questions examining knowledge application, the mean improvement achieved by the online learning group was 26 percentage points greater than that achieved by the face-to-face learning group (95% confidence interval [CI] 25 to 27; p < 0.001). For questions testing knowledge gain, the improvement achieved by the online learning group was 7 percentage points less than that achieved by the face-to-face learning group (95% CI 2 to 12; p = 0.008). Therefore, the enhanced online module was deemed to be non-inferior to the face-to-face learning session in terms of knowledge application and knowledge gain. Insufficient data were available to analyze the secondary outcome of knowledge retention over time. Participant satisfaction was similar for the 2 groups (p = 0.62). The self-paced enhanced online module was non-inferior to facilitated face-to-face learning in terms of improving application and knowledge of insulin dosing. Pharmacists had similar levels of satisfaction with the 2 modes of learning.

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

Acute kidney injury in critically ill patients with haematological malignancies: results of a multicentre cohort study from the Groupe de Recherche en Réanimation Respiratoire en Onco-Hématologie.

PubMed

Darmon, Michael; Vincent, François; Canet, Emmanuel; Mokart, Djamel; Pène, Frédéric; Kouatchet, Achille; Mayaux, Julien; Nyunga, Martine; Bruneel, Fabrice; Rabbat, Antoine; Lebert, Christine; Perez, Pierre; Renault, Anne; Meert, Anne-Pascale; Benoit, Dominique; Hamidfar, Rebecca; Jourdain, Mercé; Schlemmer, Benoit; Chevret, Sylvie; Lemiale, Virginie; Azoulay, Elie

2015-12-01

Cancer patients are at high risk for acute kidney injury (AKI), which is associated with high morbidity and mortality. We sought to appraise the incidence, risk factors, and outcome of AKI in a large multicentre cohort study of critically ill patients with haematological malignancies. We used a retrospective analysis of a prospectively collected database. The study was carried out in 17 university or university-affiliated centres in France and Belgium between 2010 and 2012. AKI was defined according to the Acute Kidney Injury Network (AKIN) definition. Of the 1011 patients admitted into the intensive care unit (ICU) during the study period, 1009 were included in this study. According to the AKIN definition, 671 patients (66.5%) developed an AKI during their ICU stay, of which 258 patients (38.4%) were AKI stage 1, 75 patients (11.2%) AKI stage 2 and 338 patients (50.4%) AKI stage 3. After adjustment for confounders, main adverse risk factors of AKI were older age, severity [non-renal Sequential Organ Failure Assessment (SOFA)], history of hypertension, tumour lysis syndrome, exposure to nephrotoxic agents and myeloma. Hospital mortality was 44.3% in patients with AKI and 25.4% in patients without AKI (P < 0.0001). After adjustment for confounders, AKI was independently associated with hospital mortality [OR 1.65 (95% CI 1.19-2.29)]. Overall, 271 patients required renal replacement therapy (RRT), of whom 57.2% died during their hospital stay as compared with 31.2% (P < 0.0001) in those not requiring RRT. Two-thirds of critically ill patients with haematological malignancies developed AKI. Hospital mortality in this population of patients developing AKI or requiring RRT is close to that in general ICU population. © The Author 2015. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved.

A new responder criterion (relative effect per patient (REPP) > 0.2) externally validated in a large total hip replacement multicenter cohort (EUROHIP).

PubMed

Huber, J; Hüsler, J; Dieppe, P; Günther, K P; Dreinhöfer, K; Judge, A

2016-03-01

To validate a new method to identify responders (relative effect per patient (REPP) >0.2) using the OMERACT-OARSI criteria as gold standard in a large multicentre sample. The REPP ([score before - after treatment]/score before treatment) was calculated for 845 patients of a large multicenter European cohort study for THR. The patients with a REPP >0.2 were defined as responders. The responder rate was compared to the gold standard (OMERACT-OARSI criteria) using receiver operator characteristic (ROC) curve analysis for sensitivity, specificity and percentage of appropriately classified patients. With the criterion REPP>0.2 85.4% of the patients were classified as responders, applying the OARSI-OMERACT criteria 85.7%. The new method had 98.8% sensitivity, 94.2% specificity and 98.1% of the patients were correctly classified compared to the gold standard. The external validation showed a high sensitivity and also specificity of a new criterion to identify a responder compared to the gold standard method. It is simple and has no uncertainties due to a single classification criterion. Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.

Multicentre standardisation of chest MRI as radiation-free outcome measure of lung disease in young children with cystic fibrosis.

PubMed

Wielpütz, Mark O; von Stackelberg, Oyunbileg; Stahl, Mirjam; Jobst, Bertram J; Eichinger, Monika; Puderbach, Michael U; Nährlich, Lutz; Barth, Sandra; Schneider, Christian; Kopp, Matthias V; Ricklefs, Isabell; Buchholz, Michael; Tümmler, Burkhard; Dopfer, Christian; Vogel-Claussen, Jens; Kauczor, Hans-Ulrich; Mall, Marcus A

2018-05-24

A recent single-centre study demonstrated that MRI is sensitive to detect early abnormalities in the lung and response to therapy in infants and preschool children with cystic fibrosis (CF) supporting MRI as an outcome measure of early CF lung disease. However, the feasibility of multicentre standardisation remains unknown. To determine the feasibility of multicentre standardisation of chest MRI in infants and preschool children with CF. A standardised chest 1.5 T MRI protocol was implemented across four specialised CF centres. Following training and initiation visits, 42 infants and preschool children (mean age 3.2 ± 1.5 years, range 0-6 years) with clinically stable CF underwent MRI and chest X-ray (CXR). Image quality and lung abnormalities were assessed using a standardised questionnaire and an established CF MRI and CXR score. MRI was successfully performed with diagnostic quality in all patients (100%). Incomplete lung coverage was observed in 6% and artefacts also in 6% of sequence acquisitions, but these were compensated by remaining sequences in all patients. The range of the MRI score in CF patients was similar across centres with a mean global MRI score of 13.3 ± 5.8. Cross-validation of the MRI against the CXR score revealed a moderate correlation (r = 0.43-0.50, p < 0.01). Our results demonstrate that multicentre standardisation of chest MRI is feasible and support its use as radiation-free outcome measure of lung disease in infants and preschool children with CF. Copyright © 2018 European Cystic Fibrosis Society. Published by Elsevier B.V. All rights reserved.

Current status of gene expression profiling in the diagnosis and management of acute leukaemia.

PubMed

Bacher, Ulrike; Kohlmann, Alexander; Haferlach, Torsten

2009-06-01

Gene expression profiling (GEP) enables the simultaneous investigation of the expression of tens of thousands of genes and was successfully introduced in leukaemia research a decade ago. Aiming to better understand the diversity of genetic aberrations in acute myeloid leukaemia (AML) and acute lymphoblastic leukaemia (ALL), pioneer studies investigated and confirmed the predictability of many cytogenetic and molecular subclasses in AML and ALL. In addition, GEP can define new prognostic subclasses within distinct leukaemia subgroups, as illustrated in AML with normal karyotype. Another approach is the development of treatment-specific sensitivity assays, which might contribute to targeted therapy studies. Finally, GEP might enable the detection of new molecular targets for therapy in patients with acute leukaemia. Meanwhile, large multicentre studies, e.g. the Microarray Innovations in LEukaemia (MILE) study, prepare for a standardised introduction of GEP in leukaemia diagnostic algorithms, aiming to translate this novel methodology into clinical routine for the benefit of patients with the complex disorders of AML and ALL.

Reference values for voluntary and stimulated single-fibre EMG using concentric needle electrodes: a multicentre prospective study.

PubMed

Kokubun, Norito; Sonoo, Masahiro; Imai, Tomihiro; Arimura, Yumiko; Kuwabara, Satoshi; Komori, Tetsuo; Kobayashi, Masahito; Nagashima, Takahide; Hatanaka, Yuki; Tsuda, Emiko; Misawa, Sonoko; Abe, Tatsuya; Arimura, Kimiyoshi

2012-03-01

The aim of this study is to establish reference values for single-fibre electromyography (SFEMG) using concentric needles in a prospective, multicentre study. Voluntary or stimulated SFEMG at the extensor digitorum communis (EDC) or frontalis (FRO) muscles was conducted in 56-63 of a total of 69 normal subjects below the age of 60years at six Japanese institutes. The cut-off values for mean consecutive difference (MCD) of individual potentials were calculated using +2.5 SD or 95% prediction limit (one-tail) of the upper 10th percentile MCD value for individual subjects. The cut-off values for individual MCD (+2.5 SD) were 56.8μs for EDC-V (voluntary SFEMG for EDC), 58.8μs for EDC-S (stimulated SFEMG for EDC), 56.8μs for FRO-V (voluntary SFEMG for FRO) and 51.0μs for FRO-S (stimulated SFEMG for FRO). The false positive rates using these cut-off values were around 2%. The +2.5 SD and 95% prediction limit might be two optimal cut-off values, depending on the clinical question. The obtained reference values were larger than those reported previously using concentric needles, but might better coincide with conventional values. This is the first multicentre study reporting reference values for SFEMG using concentric needles. The way to determine cut-off values and the statistically correct definition of the percentile were discussed. Copyright © 2011 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved.

Persistent occiput posterior: OUTcomes following digital rotation: a pilot randomised controlled trial.

PubMed

Graham, Kathryn; Phipps, Hala; Hyett, Jon A; Ludlow, Joanne P; Mackie, Adam; Marren, Anthony; De Vries, Bradley

2014-06-01

To determine the feasibility of a multicentre randomised controlled trial (RCT) to investigate whether digital rotation of the fetal head from occiput posterior (OP) position in the second stage of labour reduces the risk of operative delivery (defined as caesarean section (CS) or instrumental delivery). We conducted the study between December 2010 and December 2011 in a tertiary referral hospital in Australia. A transabdominal ultrasound was performed early in the second stage of labour on women with cephalic, singleton pregnancies to determine the fetal position. Those women with a fetus in the OP position were randomised to either a digital rotation or a sham procedure. In all other ways, participants received their usual intrapartum care. Data regarding demographics, mode of delivery, labour, post natal period and neonatal outcomes were collected. One thousand and four women were consented, 834 achieved full dilatation, and 30 were randomised. An additional portable ultrasound scan and a blinded 'sham' digital rotation were acceptable to women and staff. Operative delivery rates were 13/15 in the digital rotation (four CS and nine instrumental) and 12/15 in the sham (three CS and nine instrumental) groups, respectively. A large double-blinded multicentre RCT would be feasible and acceptable to women and staff. Strategies to improve recruitment such as consenting women with an effective epidural in active labour should be considered. This would be the first RCT to answer a clinically important question which could significantly affect the operative delivery rate in Australia and internationally. © 2014 The Royal Australian and New Zealand College of Obstetricians and Gynaecologists.

A Multi-centre Study to Assess the Long-term Performance of the Summit™ Hip in Primary Total Hip Replacement

ClinicalTrials.gov

2016-08-03

Rheumatoid Arthritis; Osteoarthritis; Post-traumatic Arthritis; Collagen Disorders; Avascular Necrosis; Traumatic Femoral Fractures; Nonunion of Femoral Fractures; Congenital Hip Dysplasia; Slipped Capital Femoral Epiphysis

Feasibility of implementing a practice guideline for fall prevention on geriatric wards: a multicentre study.

PubMed

Milisen, Koen; Coussement, Joke; Arnout, Hanne; Vanlerberghe, Virginie; De Paepe, Leen; Schoevaerdts, Didier; Lambert, Margareta; Van Den Noortgate, Nele; Delbaere, Kim; Boonen, Steven; Dejaeger, Eddy

2013-04-01

About 40% of all adverse events in hospital are falls, but only about one in three Belgian hospitals have a fall prevention policy in place. The implementation of a national practice guideline is urgently needed. This multicentre study aimed to determine the feasibility of a previously developed guideline. SETTING, PARTICIPANTS AND METHOD: Seventeen geriatric wards, selected at random out of 40 Belgian hospitals who agreed to take part in the study, evaluated the fall prevention guideline. After the one-month test period, 49 healthcare workers completed a questionnaire on the feasibility of the guideline. At the end of the study, 512 geriatric patients had been assessed using the practice guideline. The average time spent per patient on case finding, multifactorial assessment and initiating a treatment plan was 5.1, 76.1 and 30.6 min, respectively. For most risk assessments and risk modifications, several disciplines considered themselves as being responsible and capable. The majority (more than 69%) of the respondents judged the practice guideline as useful, but only a small majority (62.3%) believed that the guideline could be successfully integrated into their daily practice over a longer period of time. Barriers for implementation included a large time investment (81.1%), lack of communication between the different disciplines (35.8%), lack of motivation of the patient (34.0%), lack of multidisciplinary teamwork (28.3%), and lack of interest from the hospital management (15.4%). Overall, the guideline was found useful, and for each risk factor (except for visual impairment), at least one discipline felt responsible and capable. Towards future implementation of the guideline, following steps should be considered: division of the risk-factor assessment duties and interventions among different healthcare workers; patient education; appointment of a fall prevention coordinator; development of a fall prevention policy with support from the management of the hospital. Copyright © 2012 Elsevier Ltd. All rights reserved.

External validation of prognostic models to predict risk of gestational diabetes mellitus in one Dutch cohort: prospective multicentre cohort study.

PubMed

Lamain-de Ruiter, Marije; Kwee, Anneke; Naaktgeboren, Christiana A; de Groot, Inge; Evers, Inge M; Groenendaal, Floris; Hering, Yolanda R; Huisjes, Anjoke J M; Kirpestein, Cornel; Monincx, Wilma M; Siljee, Jacqueline E; Van 't Zelfde, Annewil; van Oirschot, Charlotte M; Vankan-Buitelaar, Simone A; Vonk, Mariska A A W; Wiegers, Therese A; Zwart, Joost J; Franx, Arie; Moons, Karel G M; Koster, Maria P H

2016-08-30

 To perform an external validation and direct comparison of published prognostic models for early prediction of the risk of gestational diabetes mellitus, including predictors applicable in the first trimester of pregnancy.  External validation of all published prognostic models in large scale, prospective, multicentre cohort study.  31 independent midwifery practices and six hospitals in the Netherlands.  Women recruited in their first trimester (<14 weeks) of pregnancy between December 2012 and January 2014, at their initial prenatal visit. Women with pre-existing diabetes mellitus of any type were excluded.  Discrimination of the prognostic models was assessed by the C statistic, and calibration assessed by calibration plots.  3723 women were included for analysis, of whom 181 (4.9%) developed gestational diabetes mellitus in pregnancy. 12 prognostic models for the disorder could be validated in the cohort. C statistics ranged from 0.67 to 0.78. Calibration plots showed that eight of the 12 models were well calibrated. The four models with the highest C statistics included almost all of the following predictors: maternal age, maternal body mass index, history of gestational diabetes mellitus, ethnicity, and family history of diabetes. Prognostic models had a similar performance in a subgroup of nulliparous women only. Decision curve analysis showed that the use of these four models always had a positive net benefit.  In this external validation study, most of the published prognostic models for gestational diabetes mellitus show acceptable discrimination and calibration. The four models with the highest discriminative abilities in this study cohort, which also perform well in a subgroup of nulliparous women, are easy models to apply in clinical practice and therefore deserve further evaluation regarding their clinical impact. 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.

Pathogenesis-based treatments in primary Sjogren's syndrome using artificial intelligence and advanced machine learning techniques: a systematic literature review.

PubMed

Foulquier, Nathan; Redou, Pascal; Le Gal, Christophe; Rouvière, Bénédicte; Pers, Jacques-Olivier; Saraux, Alain

2018-05-17

Big data analysis has become a common way to extract information from complex and large datasets among most scientific domains. This approach is now used to study large cohorts of patients in medicine. This work is a review of publications that have used artificial intelligence and advanced machine learning techniques to study physio pathogenesis-based treatments in pSS. A systematic literature review retrieved all articles reporting on the use of advanced statistical analysis applied to the study of systemic autoimmune diseases (SADs) over the last decade. An automatic bibliography screening method has been developed to perform this task. The program called BIBOT was designed to fetch and analyze articles from the pubmed database using a list of keywords and Natural Language Processing approaches. The evolution of trends in statistical approaches, sizes of cohorts and number of publications over this period were also computed in the process. In all, 44077 abstracts were screened and 1017 publications were analyzed. The mean number of selected articles was 101.0 (S.D. 19.16) by year, but increased significantly over the time (from 74 articles in 2008 to 138 in 2017). Among them only 12 focused on pSS but none of them emphasized on the aspect of pathogenesis-based treatments. To conclude, medicine progressively enters the era of big data analysis and artificial intelligence, but these approaches are not yet used to describe pSS-specific pathogenesis-based treatment. Nevertheless, large multicentre studies are investigating this aspect with advanced algorithmic tools on large cohorts of SADs patients.

Comparison of laparoscopic stone surgery and percutaneous nephrolithotomy in the management of large upper urinary stones: a meta-analysis.

PubMed

Zhao, Chenming; Yang, Huan; Tang, Kun; Xia, Ding; Xu, Hua; Chen, Zhiqiang; Ye, Zhangqun

2016-11-01

For the treatment of large upper urinary stones percutaneous nephrolithotomy (PCNL) is generally considered the first choice, and Laparoscopic Stone Surgery (LSS) is an alternative. We aim to compare the efficiency and safety of PCNL with LSS, as far as the management of large upper urinary stones is concerned. A systematic search from Pubmed, Web of Science, Wiley Online Library and Elsevier was performed up to August 1, 2015 for the relevant published studies. After data extraction and quality assessment, meta-analysis was performed using the RevMan 5.3 software. 15 eligible trials evaluating LSS vs. PCNL were identified including 6 prospective and 9 retrospective studies with 473 patients undergoing LSS and 523 patients undergoing PCNL. Although LSS led to longer operative time (p = 0.01) and higher open conversion rate (p = 0.02), patients might benefit from significantly fewer overall complications (p = 0.03), especially lower bleeding rate (p = 0.02), smaller drop in hemoglobin level (p < 0.001), less need of blood transfusion (p = 0.01). The stone free rate was also higher for LSS compared with PCNL (p < 0.001) with less secondary/complementary procedure (p = 0.006). There was no significant difference in other demographic parameters between the two groups. Our data suggests that LSS turns out to be a safe and feasible alternative to PCNL for large upper urinary stones with less bleeding and higher stone free rate. Because of the inherent limitations of the included studies, further large sample prospective, multi-centric studies and randomized control trials should be undertaken to confirm our findings.

Feasibility of surveillance of changes in human fertility and semen quality.

PubMed

Stewart, T M; Brown, E H; Venn, A; Mbizvo, M T; Farley, T M; Garrett, C; Baker, H W

2001-01-01

There is concern that male fertility is declining, but this is difficult to study because few men volunteer for studies of semen quality, and recruitment bias may over-represent the subfertile. The Human Reproduction Programme of the World Health Organization developed a protocol for multicentre studies of fertility involving a questionnaire for pregnant women to obtain time to pregnancy (TTP): the number of menstrual cycles taken to conceive. Male characteristics and semen quality will be determined in a subset of the partners. Our aim was to validate the TTP questionnaire, and to examine potential recruitment bias and feasibility of conducting large-scale surveillance of fertility. The questionnaire was administered to 120 pregnant women (16-32 weeks). Validation included internal reliability by consistency of responses, test-re-test reliability by repeat administration (20 women) and accuracy by comparison of gestational age from first antenatal ultrasound and menstrual dates. Internal reliability was high. Agreement between categorical responses on re-testing was very good (k > 0.8). In both the re-test and gestational age analysis, differences in TTP of 1 cycle were found (standard deviation <0.25 cycles). In this small pilot study there was no evidence of recruitment bias. Response rates indicate the feasibility of surveillance of fertility in large maternity centres.

The EMBARC European Bronchiectasis Registry: protocol for an international observational study

PubMed Central

Aliberti, Stefano; Polverino, Eva; Vendrell, Montserrat; Crichton, Megan; Loebinger, Michael; Dimakou, Katerina; Clifton, Ian; van der Eerden, Menno; Rohde, Gernot; Murris-Espin, Marlene; Masefield, Sarah; Gerada, Eleanor; Shteinberg, Michal; Ringshausen, Felix; Haworth, Charles; Boersma, Wim; Rademacher, Jessica; Hill, Adam T.; Aksamit, Timothy; O'Donnell, Anne; Morgan, Lucy; Milenkovic, Branislava; Tramma, Leandro; Neves, Joao; Menendez, Rosario; Paggiaro, Perluigi; Botnaru, Victor; Skrgat, Sabina; Wilson, Robert; Goeminne, Pieter; De Soyza, Anthony; Welte, Tobias; Torres, Antoni; Elborn, J. Stuart; Blasi, Francesco

2016-01-01

Bronchiectasis is one of the most neglected diseases in respiratory medicine. There are no approved therapies and few large-scale, representative epidemiological studies. The EMBARC (European Multicentre Bronchiectasis Audit and Research Collaboration) registry is a prospective, pan-European observational study of patients with bronchiectasis. The inclusion criterion is a primary clinical diagnosis of bronchiectasis consisting of: 1) a clinical history consistent with bronchiectasis; and 2) computed tomography demonstrating bronchiectasis. Core exclusion criteria are: 1) bronchiectasis due to known cystic fibrosis; 2) age <18 years; and 3) patients who are unable or unwilling to provide informed consent. The study aims to enrol 1000 patients by April 2016 across at least 20 European countries, and 10 000 patients by March 2020. Patients will undergo a comprehensive baseline assessment and will be followed up annually for up to 5 years with the goal of providing high-quality longitudinal data on outcomes, treatment patterns and quality of life. Data from the registry will be available in the form of annual reports. and will be disseminated in conference presentations and peer-reviewed publications. The European Bronchiectasis Registry aims to make a major contribution to understanding the natural history of the disease, as well as guiding evidence-based decision making and facilitating large randomised controlled trials. PMID:27730179

Diagnosis, Symptoms, Frequency and Mortality of 260 Patients with Urea Cycle Disorders from a 21-Year, Multicentre Study of Acute Hyperammonaemic Episodes

PubMed Central

Summar, Marshall L.; Dobbelaere, Dries; Brusilow, Saul; Lee, Brendan

2009-01-01

Aim A large longitudinal interventional study of patients with a urea cycle disorder (UCD) in hyperammonaemic crisis was undertaken to amass a significant body of data on their presenting symptoms and survival. Methods Between 1982 and 2003, as part of the FDA approval process, data were collected on patients receiving an intravenous combination of nitrogen scavenging drugs (Ammonul® sodium phenylacetate and sodium benzoate, 10%, 10%) for the treatment of hyperammonaemic crises caused by urea cycle disorders. Results A final diagnosis of a UCD was made for 260 patients, representing 975 episodes of hospitalisation. Only 34% of these patients presented within the first 30 days of life and had a mortality rate of 32%. The most common presenting symptoms were neurological (80%) or gastrointestinal (33%). This cohort is the largest collection of patients reported for these diseases and the first large cohort in the USA. Conclusion Surprisingly, the majority (66%) of patients with heritable causes of hyperammonaemia present beyond the neonatal period (>30 days). Patients with late-onset presenting disorders exhibited prolonged survival compared to the neonatal-presenting group. PMID:18647279

Multiple intraosseous hemangiomas-investigation and role of N-butylcyanoacrylate in management.

PubMed

Syal, Rajan; Tyagi, Isha; Goyal, Amit; Barai, Sukanto; Parihar, Anit

2007-05-01

Primary intraosseous hemangiomas are rare (0.7% of all osseous neoplasms), benign, slow-growing neoplasms. These lesions are usually solitary. We are reporting a case of multicentric intraosseous hemangiomas. Investigation, treatment options, and role of N-butylcyanoacrylate (NBCA) in management will be discussed. A 20-year-old man had multicentric intraosseous hemangiomas involving the skull bones, mandible, vertebra, pelvic bone, and tibial tuberosity. N-butylcyanoacrylate was used by direct puncture technique using a transosseous transcutaneous route to control profuse bleeding from the retromolar region. To the best of our knowledge, this is the first reported case with such extensive multicentric intraosseous hemangiomas. N-butylcyanoacrylate by direct puncture technique can be an effective method to devascularize and stabilize low-flow intraosseous vascular tumors. (c) 2007 Wiley Periodicals, Inc.

Multicentre dose audit for clinical trials of radiation therapy in Asia.

PubMed

Mizuno, Hideyuki; Fukuda, Shigekazu; Fukumura, Akifumi; Nakamura, Yuzuru-Kutsutani; Jianping, Cao; Cho, Chul-Koo; Supriana, Nana; Dung, To Anh; Calaguas, Miriam Joy; Devi, C R Beena; Chansilpa, Yaowalak; Banu, Parvin Akhter; Riaz, Masooma; Esentayeva, Surya; Kato, Shingo; Karasawa, Kumiko; Tsujii, Hirohiko

2017-05-01

A dose audit of 16 facilities in 11 countries has been performed within the framework of the Forum for Nuclear Cooperation in Asia (FNCA) quality assurance program. The quality of radiation dosimetry varies because of the large variation in radiation therapy among the participating countries. One of the most important aspects of international multicentre clinical trials is uniformity of absolute dose between centres. The National Institute of Radiological Sciences (NIRS) in Japan has conducted a dose audit of participating countries since 2006 by using radiophotoluminescent glass dosimeters (RGDs). RGDs have been successfully applied to a domestic postal dose audit in Japan. The authors used the same audit system to perform a dose audit of the FNCA countries. The average and standard deviation of the relative deviation between the measured and intended dose among 46 beams was 0.4% and 1.5% (k = 1), respectively. This is an excellent level of uniformity for the multicountry data. However, of the 46 beams measured, a single beam exceeded the permitted tolerance level of ±5%. We investigated the cause for this and solved the problem. This event highlights the importance of external audits in radiation therapy. © The Author 2016. Published by Oxford University Press on behalf of The Japan Radiation Research Society and Japanese Society for Radiation Oncology.

PANSAID-PAracetamol and NSAID in combination: detailed statistical analysis plan for a randomised, blinded, parallel, four-group multicentre clinical trial.

PubMed

Thybo, Kasper Højgaard; Jakobsen, Janus Christian; Hägi-Pedersen, Daniel; Pedersen, Niels Anker; Dahl, Jørgen Berg; Schrøder, Henrik Morville; Bülow, Hans Henrik; Bjørck, Jan Gottfrid; Overgaard, Søren; Mathiesen, Ole; Wetterslev, Jørn

2017-10-10

Effective postoperative pain management is essential for the rehabilitation of the surgical patient. The PANSAID trial evaluates the analgesic effects and safety of the combination of paracetamol and ibuprofen. This paper describes in detail the statistical analysis plan for the primary publication to prevent outcome reporting bias and data-driven analysis results. The PANSAID trial is a multicentre, randomised, controlled, parallel, four-group clinical trial comparing the beneficial and harmful effects of different doses and combinations of paracetamol and ibuprofen in patients having total hip arthroplastic surgery. Patients, caregivers, physicians, investigators, and statisticians are blinded to the intervention. The two co-primary outcomes are 24-h consumption of morphine and proportion of patients with one or more serious adverse events within 90 days after surgery. Secondary outcomes are pain scores during mobilisation and at rest at 6 and 24 h postoperatively, and the proportion of patients with one or more adverse events within 24 h postoperatively. PANSAID will provide a large trial with low risk of bias regarding benefits and harms of the combination of paracetamol and ibuprofen used in a perioperative setting. ClinicalTrials.org identifier: NCT02571361 . Registered on 7 October 2015.

Compliance with clothing regulations and traffic flow in the operating room: a multi-centre study of staff discipline during surgical procedures.

PubMed

Loison, G; Troughton, R; Raymond, F; Lepelletier, D; Lucet, J-C; Avril, C; Birgand, G

2017-07-01

This multi-centre study assessed operating room (OR) staff compliance with clothing regulations and traffic flow during surgical procedures. Of 1615 surgical attires audited, 56% respected the eight clothing measures. Lack of compliance was mainly due to inappropriate wearing of jewellery (26%) and head coverage (25%). In 212 procedures observed, a median of five people [interquartile range (IQR) 4-6] were present at the time of incision. The median frequency of entries to/exits from the OR was 10.6/h (IQR 6-29) (range 0-93). Reasons for entries to/exits from the OR were mainly to obtain materials required in the OR (N=364, 44.5%). ORs with low compliance with clothing regulations tended to have higher traffic flows, although the difference was not significant (P=0.12). Copyright © 2017 The Healthcare Infection Society. Published by Elsevier Ltd. All rights reserved.

[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.

Mode of delivery and risk of intracranial haemorrhage in newborns with severe haemophilia A: a multicentre study in Gulf region.

PubMed

Nazir, H F; Al Lawati, T; Beshlawi, I; AlSharidah, S; Elshinawy, M; Alkasim, F; Khanani, M F; Tarawa, A; Al Subhi, T; Alrawas, A; Al Riyami, W; Al Kindi, S; Al Saadi, K; Al-Lamki, S; Wali, Y

2016-05-01

The optimum mode of delivery in a known carrier of a haemophilia A is still an issue of debate. This study was conducted to report a multicentre experience in Gulf Cooperation Council (GCC) on the incidence of intracranial haemorrhage (ICH) in newborns with severe haemophilia A delivered by different modalities. We have conducted a retrospective/prospective multicentre cohort study including a total of seven hospitals distributed in four GCC countries between 1998 and Jan 2015. A total of 163 patient with severe haemophilia A (factor VIII <1%) were enrolled in this study, age ranged between 2 weeks to 18 years. Most of the patients were born by spontaneous vaginal delivery (SVD) (131, 80.4%), whereas 26 patients (16%) were born by CS and only six patients were born by instrumental delivery (3.7%), five of them by vacuum and one was delivered using forceps. Five out of 163 patients developed ICH during the first 2 weeks of life (3.1%). Two of them were born by SVD (2/131; 1.5%) and two were born by instrumental delivery (2/6; 33.3%). Only one patient among those who were born by caesarean section developed ICH (1/26; 3.8%). Assisted vaginal delivery was associated with a significant risk of ICH, in comparison to SVD and CS (P = 0.0093). Normal vaginal delivery is still considered a safe journey through the birth canal for haemophilic newborns particularly in this area of the world. Larger prospective studies might be needed to define an evidence-based optimal mode of delivery for the haemophilia carrier expecting an affected child. © 2015 John Wiley & Sons Ltd.

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.

N-acetylcysteine – passe-partout or much ado about nothing?

PubMed Central

Aitio, Mirja-Liisa

2006-01-01

In experimental studies, the old mucolytic agent N-acetylcysteine (NAC) has had beneficial effects in disorders supposedly linked to oxidative stress. Numerous, mainly small clinical trials with variable doses have yielded inconsistent results in a wide variety of diseases. NAC added to the conventional therapy of human immunodeficiency virus infection might be of benefit; in respect of chronic obstructive pulmonary disease, systematic reviews and meta-analyses suggested that prolonged treatment with NAC is efficacious, but a recent multicentre study has questioned this. In a large intervention trial on cancer recurrence, NAC was ineffective. NAC infusions have been widely used in acute hepatic failure but convincing evidence of its benefits is lacking. A preliminary study reported that NAC is effective in preventing radiocontrast-induced nephropathy but thereafter highly mixed results have been published, and even meta-analyses disagree on its efficacy. In intensive care NAC has mostly been a disappointment but recently it has ‘given promises’ in surgery with cardiopulmonary bypass. NAC therapy is routine only in paracetamol intoxication. PMID:16390346

[Multi-central controlled study on three-part massage therapy for treatment of insomnia of deficiency of both the heart and spleen].

PubMed

Zhou, Yun-feng; Wei, Yu-long; Zhang, Pu-lin; Gao, Shan; Ning, Guo-li; Zhang, Zhen-qiang; Hu, Bin; Wang, Dan-yi; Yan, Mei-rong; Liu, Wen-jun

2006-06-01

To make multi-central clinical evaluation for three-part massage therapy for treatment of insomnia of deficiency of both the heart and spleen. One hundred and sixty-six cases were randomly divided into a test group (n = 84) and a control group (n = 82). Multi-central, randomized and controlled methods were adopted. The test group were treated by the three-part massage therapy, i. e. acupoints at the head, abdomen and back were massaged, once each day; and the control group by oral administration of Guipi Pills [symbol: see text], 8 pills each time, thrice daily. The treatment was given for 15 consecutive days and then the therapeutic effects were observed. Sixty-seven cases were cured, 11 markedly effective, 3 effective, and 3 ineffective in the test group, and the corresponding figures were 10, 21, 29 and 22 in the control group with a very significant difference between the two groups (P< 0.001). The test group was superior to the control group in improvement for Pittsburgh Sleep Quality Index (PSQI), Sleepless Anxiety Scale (SAS) and Sleepless Depression Scale (SDS) (P < 0.001). The three-part massage therapy has definite therapeutic effect on insomnia of deficiency of both the heart and spleen with safety.

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.

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.

Immune tolerance: critical issues of factor dose, purity and treatment complications.

PubMed

DiMichele, D M

2006-12-01

The current practice of immune tolerance induction (ITI) therapy has been largely influenced by the results of small institutional studies and three large registries. However, many questions remain. Successful outcome predictors for ITI in haemophilia A have been suggested by the analyses of two of these registries. Among these predictors, factor VIII (FVIII) dose/dosing regimen remains a controversial outcome parameter, demonstrating a strong direct relationship to ITI success in the international registry and a weaker inverse relationship in the North American registry. There is an international multicentre prospective randomized trial underway to further study the role of FVIII dose in successful ITI induction in a good risk haemophilia A inhibitor patient cohort. FVIII purity also remains an unproved ITI outcome predictor. Institutional experience with von-Willebrand-factor-containing products has suggested its therapeutic advantage in both inhibitor development and eradication. The International ITI Study, although not designed to answer this particular question, may be able to determine an impact on outcome depending on the final distribution of investigator choice of product among the study subjects. Much less is known about the influence of factor IX (FIX) dose and purity on ITI success in haemophilia B. Importantly, nephrotic syndrome has been a major determinant of ITI failure in FIX inhibitor patients, particularly those with the allergic phenotype. Unfortunately, large prospective randomized trials in this group will not be feasible. Rather, we will have to rely on prospectively collected registry data to build our knowledge base of inhibitors and ITI in haemophilia B.

Phenotyping of subjects for large scale studies on patients with IBS.

PubMed

Boeckxstaens, G E; Drug, V; Dumitrascu, D; Farmer, A D; Hammer, J; Hausken, T; Niesler, B; Pohl, D; Pojskic, L; Polster, A; Simren, M; Goebel-Stengel, M; Van Oudenhove, L; Vassallo, M; Wensaas, K-A; Aziz, Q; Houghton, L A

2016-08-01

Irritable bowel syndrome (IBS) is a complex condition with multiple factors contributing to its aetiology and pathophysiology. Aetiologically these include genetics, life-time events and environment, and physiologically, changes in motility, central processing, visceral sensitivity, immunity, epithelial permeability and gastrointestinal microflora. Such complexity means there is currently no specific reliable biomarker for IBS, and thus IBS continues to be diagnosed and classified according to symptom based criteria, the Rome Criteria. Carefully phenotyping and characterisation of a 'large' pool of IBS patients across Europe and even the world however, might help identify sub-populations with accuracy and consistency. This will not only aid future research but improve tailoring of treatment and health care of IBS patients. The aim of this position paper is to discuss the requirements necessary to standardize the process of selecting and phenotyping IBS patients and how to organise the collection and storage of patient information/samples in such a large multi-centre pan European/global study. We include information on general demographics, gastrointestinal symptom assessment, psychological factors, quality of life, physiological evaluation, genetic/epigenetic and microbiota analysis, biopsy/blood sampling, together with discussion on the organisational, ethical and language issues associated with implementing such a study. The proposed approach and documents selected to be used in such a study was the result of a thoughtful and thorough four-year dialogue amongst experts associated with the European COST action BM1106 GENIEUR (www.GENIEUR.eu). © 2016 John Wiley & Sons Ltd.

Influence of magnetic field strength and image registration strategy on voxel-based morphometry in a study of Alzheimer's disease.

PubMed

Marchewka, Artur; Kherif, Ferath; Krueger, Gunnar; Grabowska, Anna; Frackowiak, Richard; Draganski, Bogdan

2014-05-01

Multi-centre data repositories like the Alzheimer's Disease Neuroimaging Initiative (ADNI) offer a unique research platform, but pose questions concerning comparability of results when using a range of imaging protocols and data processing algorithms. The variability is mainly due to the non-quantitative character of the widely used structural T1-weighted magnetic resonance (MR) images. Although the stability of the main effect of Alzheimer's disease (AD) on brain structure across platforms and field strength has been addressed in previous studies using multi-site MR images, there are only sparse empirically-based recommendations for processing and analysis of pooled multi-centre structural MR data acquired at different magnetic field strengths (MFS). Aiming to minimise potential systematic bias when using ADNI data we investigate the specific contributions of spatial registration strategies and the impact of MFS on voxel-based morphometry in AD. We perform a whole-brain analysis within the framework of Statistical Parametric Mapping, testing for main effects of various diffeomorphic spatial registration strategies, of MFS and their interaction with disease status. Beyond the confirmation of medial temporal lobe volume loss in AD, we detect a significant impact of spatial registration strategy on estimation of AD related atrophy. Additionally, we report a significant effect of MFS on the assessment of brain anatomy (i) in the cerebellum, (ii) the precentral gyrus and (iii) the thalamus bilaterally, showing no interaction with the disease status. We provide empirical evidence in support of pooling data in multi-centre VBM studies irrespective of disease status or MFS. Copyright © 2013 Wiley Periodicals, Inc.

The need for obtaining accurate nationwide estimates of diabetes prevalence in India - Rationale for a national study on diabetes

PubMed Central

Anjana, R.M.; Ali, M.K.; Pradeepa, R.; Deepa, M.; Datta, M.; Unnikrishnan, R.; Rema, M.; Mohan, V.

2011-01-01

According to the World Diabetes Atlas, India is projected to have around 51 million people with diabetes. However, these data are based on small sporadic studies done in some parts of the country. Even a few multi-centre studies that have been done, have several limitations. Also, marked heterogeneity between States limits the generalizability of results. Other studies done at various time periods also lack uniform methodology, do not take into consideration ethnic differences and have inadequate coverage. Thus, till date there has been no national study on the prevalence of diabetes which are truly representative of India as a whole. Moreover, the data on diabetes complications is even more scarce. Therefore, there is an urgent need for a large well-planned national study, which could provide reliable nationwide data, not only on prevalence of diabetes, but also on pre-diabetes, and the complications of diabetes in India. A study of this nature will have enormous public health impact and help policy makers to take action against diabetes in India. PMID:21537089

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.

Spa therapy in the treatment of knee osteoarthritis: a large randomised multicentre trial

PubMed Central

Forestier, R; Desfour, H; Tessier, J-M; Françon, A; Foote, A M; Genty, C; Rolland, C; Roques, C-F; Bosson, J-L

2010-01-01

Objective To determine whether spa therapy, plus home exercises and usual medical treatment provides any benefit over exercises and usual treatment, in the management of knee osteoarthritis. Methods Large multicentre randomised prospective clinical trial of patients with knee osteoarthritis according to the American College of Rheumatology criteria, attending French spa resorts as outpatients between June 2006 and April 2007. Zelen randomisation was used so patients were ignorant of the other group and spa personnel were not told which patients were participating. The main endpoint criteria were patient self-assessed. All patients continued usual treatments and performed daily standardised home exercises. The spa therapy group also received 18 days of spa therapy (massages, showers, mud and pool sessions). Main Endpoint The number of patients achieving minimal clinically important improvement (MCII) at 6 months, defined as ≥19.9 mm on the visual analogue pain scale and/or ≥9.1 points in a normalised Western Ontario and McMaster Universities osteoarthritis index function score and no knee surgery. Results The intention to treat analysis included 187 controls and 195 spa therapy patients. At 6 months, 99/195 (50.8%) spa group patients had MCII and 68/187 (36.4%) controls (χ2=8.05; df=1; p=0.005). However, no improvement in quality of life (Short Form 36) or patient acceptable symptom state was observed at 6 months. Conclusion For patients with knee osteoarthritis a 3-week course of spa therapy together with home exercises and usual pharmacological treatments offers benefit after 6 months compared with exercises and usual treatment alone, and is well tolerated. Trial registration number NCT00348777. PMID:19734131

Development of a Multi-Centre Clinical Trial Data Archiving and Analysis Platform for Functional Imaging

NASA Astrophysics Data System (ADS)

Driscoll, Brandon; Jaffray, David; Coolens, Catherine

2014-03-01

Purpose: To provide clinicians & researchers participating in multi-centre clinical trials with a central repository for large volume dynamic imaging data as well as a set of tools for providing end-to-end testing and image analysis standards of practice. Methods: There are three main pieces to the data archiving and analysis system; the PACS server, the data analysis computer(s) and the high-speed networks that connect them. Each clinical trial is anonymized using a customizable anonymizer and is stored on a PACS only accessible by AE title access control. The remote analysis station consists of a single virtual machine per trial running on a powerful PC supporting multiple simultaneous instances. Imaging data management and analysis is performed within ClearCanvas Workstation® using custom designed plug-ins for kinetic modelling (The DCE-Tool®), quality assurance (The DCE-QA Tool) and RECIST. Results: A framework has been set up currently serving seven clinical trials spanning five hospitals with three more trials to be added over the next six months. After initial rapid image transfer (+ 2 MB/s), all data analysis is done server side making it robust and rapid. This has provided the ability to perform computationally expensive operations such as voxel-wise kinetic modelling on very large data archives (+20 GB/50k images/patient) remotely with minimal end-user hardware. Conclusions: This system is currently in its proof of concept stage but has been used successfully to send and analyze data from remote hospitals. Next steps will involve scaling up the system with a more powerful PACS and multiple high powered analysis machines as well as adding real-time review capabilities.

Intra-patient variability of thromboelastographic parameters following in vivo and ex vivo administration of recombinant activated factor VII in haemophilia patients. A multi-centre, randomised trial.

PubMed

Kenet, G; Stenmo, C B; Blemings, A; Wegert, W; Goudemand, J; Krause, M; Schramm, W; Kirchmaier, C; Martinowitz, U

2010-02-01

Thromboelastography methods have been used to predict or monitor treatment of haemophilia patients with recombinant activated factor VII (rFVIIa). However, neither of the two thromboelastographic methods (ROTEM and TEG) has as yet been validated. This multi-centre, randomised trial compared both methods in terms of intra- and inter- patient variability following in vivo and ex vivo rFVIIa administration to haemophilia A and B patients with and without inhibitors. Patients ((3)16 years old) received the same intravenous rFVIIa dose (45, 90 or 180 microg/kg) twice, 1-12 weeks apart. Blood samples were collected pre-dose and 15, 60, 120 and 240 minutes post-dose for ROTEM and TEG analysis. Pre-dose samples were also spiked ex vivo with rFVIIa (0.6, 1.2 or 2.4 microg/ml), to correspond to the three in vivo doses. Twenty-six haemophilia A and four haemophilia B patients were enrolled. A significant treatment effect was observed with in vivo rFVIIa (p<0.05) with more pronounced effects in inhibitor (n=14) versus non-inhibitor (n=16) patients. There was a strong positive correlation between ROTEM and TEG parameters. Intra- and inter-patient variation was large for all thromboelastography parameters at all time points and rFVIIa doses. Intra-patient variation was generally lower for non-inhibitor than inhibitor patients, and lower following ex vivo spiking versus in vivo rFVIIa administration. In conclusion, there was a clear effect of rFVIIa on all thromboelastography parameters, but the large intra- and inter-patient variability following in vivo rFVIIa administration renders the use of our method unsuitable for dose-response prediction for haemophilia patients in the clinical setting.

Prosthetic valve endocarditis: who needs surgery? A multicentre study of 104 cases

PubMed Central

Habib, G; Tribouilloy, C; Thuny, F; Giorgi, R; Brahim, A; Amazouz, M; Remadi, J-P; Nadji, G; Casalta, J-P; Coviaux, F; Avierinos, J-F; Lescure, X; Riberi, A; Weiller, P-J; Metras, D; Raoult, D

2005-01-01

Objectives: To identify the prognostic markers of a bad outcome in a large population of 104 patients with prosthetic valve endocarditis (PVE), and to study the influence of medical versus surgical strategy on outcome in PVE and thus to identify patients for whom surgery may be beneficial. Design: Multicentre study. Methods and results: Among 104 patients, 22 (21%) died in hospital. Factors associated with in-hospital death were severe co-morbidity (6% of survivors v 41% of those who died, p  =  0.05), renal failure (28% v 45%, p  =  0.05), moderate to severe regurgitation (22% v 54%, p  =  0.006), staphylococcal infection (16% v 54%, p  =  0.001), severe heart failure (22% v 64%, p  =  0.001), and occurrence of any complication (60% v 90%, p  =  0.05). By multivariate analysis, severe heart failure (odds ratio 5.5) and Staphylococcus aureus infection (odds ratio 6.1) were the only independent predictors of in-hospital death. Among 82 in-hospital survivors, 21 (26%) died during a 32 month follow up. A Cox proportional hazards model identified early PVE, co-morbidity, severe heart failure, staphylococcus infection, and new prosthetic dehiscence as independent predictors of long term mortality. Mortality was not significantly different between surgical and non-surgical patients (17% v 25%, respectively, not significant). However, both in-hospital and long term mortality were reduced by a surgical approach in high risk subgroups of patients with staphylococcal PVE and complicated PVE. Conclusions: Firstly, PVE not only carries a high in-hospital mortality risk but also is associated with high long term mortality and needs close follow up after the initial episode. Secondly, congestive heart failure, early PVE, staphylococcal infection, and complicated PVE are associated with a bad outcome. Thirdly, subgroups of patients could be identified for whom surgery is associated with a better outcome: patients with staphylococcal and complicated PVE. Early surgery is strongly recommended for these patients. PMID:15958370

Gram-negative prosthetic joint infection: outcome of a debridement, antibiotics and implant retention approach. A large multicentre study.

PubMed

Rodríguez-Pardo, D; Pigrau, C; Lora-Tamayo, J; Soriano, A; del Toro, M D; Cobo, J; Palomino, J; Euba, G; Riera, M; Sánchez-Somolinos, M; Benito, N; Fernández-Sampedro, M; Sorli, L; Guio, L; Iribarren, J A; Baraia-Etxaburu, J M; Ramos, A; Bahamonde, A; Flores-Sánchez, X; Corona, P S; Ariza, J

2014-11-01

We aim to evaluate the epidemiology and outcome of gram-negative prosthetic joint infection (GN-PJI) treated with debridement, antibiotics and implant retention (DAIR), identify factors predictive of failure, and determine the impact of ciprofloxacin use on prognosis. We performed a retrospective, multicentre, observational study of GN-PJI diagnosed from 2003 through to 2010 in 16 Spanish hospitals. We define failure as persistence or reappearance of the inflammatory joint signs during follow-up, leading to unplanned surgery or repeat debridement>30 days from the index surgery related death, or suppressive antimicrobial therapy. Parameters predicting failure were analysed with a Cox regression model. A total of 242 patients (33% men; median age 76 years, interquartile range (IQR) 68-81) with 242 episodes of GN-PJI were studied. The implants included 150 (62%) hip, 85 (35%) knee, five (2%) shoulder and two (1%) elbow prostheses. There were 189 (78%) acute infections. Causative microorganisms were Enterobacteriaceae in 78%, Pseudomonas spp. in 20%, and other gram-negative bacilli in 2%. Overall, 19% of isolates were ciprofloxacin resistant. DAIR was used in 174 (72%) cases, with an overall success rate of 68%, which increased to 79% after a median of 25 months' follow-up in ciprofloxacin-susceptible GN-PJIs treated with ciprofloxacin. Ciprofloxacin treatment exhibited an independent protective effect (adjusted hazard ratio (aHR) 0.23; 95% CI, 0.13-0.40; p<0.001), whereas chronic renal impairment predicted failure (aHR, 2.56; 95% CI, 1.14-5.77; p 0.0232). Our results confirm a 79% success rate in ciprofloxacin-susceptible GN-PJI treated with debridement, ciprofloxacin and implant retention. New therapeutic strategies are needed for ciprofloxacin-resistant PJI. © 2014 The Authors Clinical Microbiology and Infection © 2014 European Society of Clinical Microbiology and Infectious 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.

Prevalence and characterization of azole-resistant Aspergillus fumigatus in patients with cystic fibrosis: a prospective multicentre study in Germany.

PubMed

Seufert, R; Sedlacek, L; Kahl, B; Hogardt, M; Hamprecht, A; Haase, G; Gunzer, F; Haas, A; Grauling-Halama, S; MacKenzie, C R; Essig, A; Stehling, F; Sutharsan, S; Dittmer, S; Killengray, D; Schmidt, D; Eskandarian, N; Steinmann, E; Buer, J; Hagen, F; Meis, J F; Rath, P-M; Steinmann, J

2018-04-19

Aspergillus fumigatus is the most prevalent filamentous fungus in the respiratory tract of patients with cystic fibrosis (CF). The aim of this prospective multicentre study was to investigate the prevalence of azole-resistant A. fumigatus (ARAF) in respiratory secretions from CF patients across Germany and to characterize ARAF isolates by phenotypic and molecular methods. Twelve tertiary care centres from Germany participated in the study. In total, 2888 A. fumigatus isolates from 961 CF patients were screened for ARAF by using azole-containing agar plates. Antifungal susceptibility testing of isolates was performed by broth microdilution according to EUCAST guidelines. Analysis of mutations mediating resistance was performed using PCR and sequencing of the cyp51A gene. Furthermore, genotyping by microsatellite PCR was performed. Of a total of 2888 A. fumigatus isolates, 101 isolates from 51 CF patients were found to be azole resistant (prevalence per patient 5.3%). The Essen centre had the highest prevalence (9.1%) followed by Munich (7.8%), Münster (6.0%) and Hannover (5.2%). Most ARAF isolates (n = 89) carried the TR34/L98H mutation followed by eight G54E/R, one TR46/Y121F/T289A and one F219S mutation. In two isolates no mutation was found. Genotyping results showed no major clustering. Forty-five percent of CF patients with ARAF had previously received azole therapy. This is the first multicentre study analysing the prevalence of ARAF isolates in German CF patients. Because of a resistance rate of up to 9%, susceptibility testing of A. fumigatus isolates from CF patients receiving antifungal treatment should be part of standard diagnostic work-up.

Barriers and facilitators experienced in collaborative prospective research in orthopaedic oncology: A qualitative study.

PubMed

Rendon, J S; Swinton, M; Bernthal, N; Boffano, M; Damron, T; Evaniew, N; Ferguson, P; Galli Serra, M; Hettwer, W; McKay, P; Miller, B; Nystrom, L; Parizzia, W; Schneider, P; Spiguel, A; Vélez, R; Weiss, K; Zumárraga, J P; Ghert, M

2017-05-01

As tumours of bone and soft tissue are rare, multicentre prospective collaboration is essential for meaningful research and evidence-based advances in patient care. The aim of this study was to identify barriers and facilitators encountered in large-scale collaborative research by orthopaedic oncological surgeons involved or interested in prospective multicentre collaboration. All surgeons who were involved, or had expressed an interest, in the ongoing Prophylactic Antibiotic Regimens in Tumour Surgery (PARITY) trial were invited to participate in a focus group to discuss their experiences with collaborative research in this area. The discussion was digitally recorded, transcribed and anonymised. The transcript was analysed qualitatively, using an analytic approach which aims to organise the data in the language of the participants with little theoretical interpretation. The 13 surgeons who participated in the discussion represented orthopaedic oncology practices from seven countries (Argentina, Brazil, Italy, Spain, Denmark, United States and Canada). Four categories and associated themes emerged from the discussion: the need for collaboration in the field of orthopaedic oncology due to the rarity of the tumours and the need for high level evidence to guide treatment; motivational factors for participating in collaborative research including establishing proof of principle, learning opportunity, answering a relevant research question and being part of a collaborative research community; barriers to participation including funding, personal barriers, institutional barriers, trial barriers, and administrative barriers and facilitators for participation including institutional facilitators, leadership, authorship, trial set-up, and the support of centralised study coordination. Orthopaedic surgeons involved in an ongoing international randomised controlled trial (RCT) were motivated by many factors to participate. There were a number of barriers to and facilitators for their participation. There was a collective sense of fatigue experienced in overcoming these barriers, which was mirrored by a strong collective sense of the importance of, and need for, collaborative research in this field. The experiences were described as essential educational first steps to advance collaborative studies in this area. Knowledge gained from this study will inform the development of future large-scale collaborative research projects in orthopaedic oncology. Cite this article: J. S. Rendon, M. Swinton, N. Bernthal, M. Boffano, T. Damron, N. Evaniew, P. Ferguson, M. Galli Serra, W. Hettwer, P. McKay, B. Miller, L. Nystrom, W. Parizzia, P. Schneider, A. Spiguel, R. Vélez, K. Weiss, J. P. Zumárraga, M. Ghert. Barriers and facilitators experienced in collaborative prospective research in orthopaedic oncology: A qualitative study. Bone Joint Res 2017;6:-314. DOI: 10.1302/2046-3758.65.BJR-2016-0192.R1. © 2017 Ghert et al.

Clavicle fractures: epidemiology, classification and treatment of 2 422 fractures in the Swedish Fracture Register; an observational study.

PubMed

Kihlström, Caroline; Möller, Michael; Lönn, Katarina; Wolf, Olof

2017-02-15

Large multi-centre studies of clavicle fractures have so far been missing. The aim of this observational study was to describe the epidemiology, classification and treatment of clavicle fractures in the The Swedish Fracture Register (SFR) that collects national prospective data from large fracture populations. Data were retrieved from the SFR on all clavicle fractures sustained by patients ≥ 15 years of age in 2013-2014 (n = 2 422) with regards to date of injury, cause of injury, fracture classification and treatment. Sixty-eight per cent of the clavicle fractures occurred in males. The largest subgroup was males aged 15-24 years, representing 21% of clavicle fractures. At the ages of 65 years and above, females sustained more clavicle fractures than males. Same-level falls and bicycle accidents were the most common injury mechanisms. Displaced midshaft fractures constituted 43% of all fractures and were the most frequently operated fractures. Seventeen per cent of the patients underwent operative treatment within 30 days of the injury, where plate fixation was the choice of treatment in 94% of fractures. The largest patient group was young males. Displaced midshaft fractures were the most common type of clavicle fracture as well as the most frequently operated type of fracture.

An exploratory, large-scale study of pain and quality of life outcomes in cancer patients with moderate or severe pain, and variables predicting improvement.

PubMed

Maximiano, Constanza; López, Iker; Martín, Cristina; Zugazabeitia, Luis; Martí-Ciriquián, Juan L; Núñez, Miguel A; Contreras, Jorge; Herdman, Michael; Traseira, Susana; Provencio, Mariano

2018-01-01

There have been few large-scale, real world studies in Spain to assess change in pain and quality of life (QOL) outcomes in cancer patients with moderate to severe pain. This study aimed to assess changes on both outcomes after 3 months of usual care and to investigate factors associated with change in QoL. Large, multi-centre, observational study in patients with lung, head and neck, colorectal or breast cancer experiencing a first episode of moderate to severe pain while attending one of the participating centres. QoL was assessed using the EuroQol-5D questionnaire and pain using the Brief Pain Inventory (BPI). Instruments were administered at baseline and after 3 months of follow up. Multivariate analyses were used to assess the impact of treatment factors, demographic and clinical variables, pain and other symptoms on QoL scores. 1711 patients were included for analysis. After 3 months of usual care, a significant improvement was observed in pain and QoL in all four cancer groups (p<0.001). Effect sizes were medium to large on the BPI and EQ-5D Index and Visual Analogue Scale (VAS). Improvements were seen on the majority of EQ-5D dimensions in all patient groups, though breast cancer patients showed the largest gains. Poorer baseline performance status (ECOG) and the presence of anxiety/depression were associated with significantly poorer QOL outcomes. Improvements in BPI pain scores were associated with improved QoL. In the four cancer types studied, pain and QoL outcomes improved considerably after 3 months of usual care. Improvements in pain made a substantial contribution to QoL gains whilst the presence of anxiety and depression and poor baseline performance status significantly constrained improvement.

A Randomised Multi-centre Study to Compare the Long-term Performance of the Future Hip to 3 Other Implants in Primary Total Hip Replacement

ClinicalTrials.gov

2016-10-06

Osteoarthritis; Post-traumatic Arthritis; Collagen Disorders; Avascular Necrosis; Traumatic Femoral Fractures; Nonunion of Femoral Fractures; Congenital Hip Dysplasia; Slipped Capital Femoral Epiphysis; Perthes Disease

A Multi-centre Study to Assess the Long-term Performance of the Pinnacle™ Cup With a Polyethylene-on-metal Bearing in Primary Total Hip Replacement

ClinicalTrials.gov

2017-06-27

Rheumatoid Arthritis; Osteoarthritis; Post-traumatic Arthritis; Collagen Disorders; Avascular Necrosis; Traumatic Femoral Fractures; Nonunion of Femoral Fractures; Congenital Hip Dysplasia; Slipped Capital Femoral Epiphysis

The Omega-3 fatty acids (Fish Oils) and Aspirin in Vascular access OUtcomes in REnal Disease (FAVOURED) study: the updated final trial protocol and rationale of post-initiation trial modifications.

PubMed

Viecelli, Andrea K; Pascoe, Elaine; Polkinghorne, Kevan R; Hawley, Carmel; Paul-Brent, Peta-Anne; Badve, Sunil V; Cass, Alan; Heritier, Stephane; Kerr, Peter G; Mori, Trevor A; Robertson, Amanda; Seong, Hooi L; Irish, Ashley B

2015-06-27

The FAVOURED study is an international multicentre, double-blind, placebo-controlled trial which commenced recruitment in 2008 and examines whether omega-3 polyunsaturated fatty acids (omega-3 PUFAs) either alone or in combination with aspirin will effectively reduce primary access failure of de novo arteriovenous fistulae (AVF) in patients with stage 4 and 5 chronic kidney disease. Publication of new evidence derived from additional studies of clopidogrel and a high screen failure rate due to prevalent aspirin usage prompted an updated trial design. The original trial protocol published in 2009 has undergone two major amendments, which were implemented in 2011. Firstly, the primary outcome 'early thrombosis' at 3 months following AVF creation was broadened to a more clinically relevant outcome of 'AVF access failure'; a composite of thrombosis, AVF abandonment and cannulation failure at 12 months. Secondly, participants unable to cease using aspirin were allowed to be enrolled and randomised to omega-3 PUFAs or placebo. The revised primary aim of the FAVOURED study is to test the hypothesis that omega-3 PUFAs will reduce rates of AVF access failure within 12 months following AVF surgery. The secondary aims are to examine the effect of omega-3 PUFAs and aspirin on the individual components of the primary end-point, to examine the safety of study interventions and assess central venous catheter requirement as a result of access failure. This multicentre international clinical trial was amended to address the clinically relevant question of whether the usability of de novo AVF at 12 months can be improved by the early use of omega-3 PUFAs and to a lesser extent aspirin. This study protocol amendment was made in response to a large trial demonstrating that clopidogrel is effective in safely preventing primary AVF thrombosis, but ineffective at increasing functional patency. Secondly, including patients taking aspirin will enroll a more representative cohort of haemodialysis patients, who are significantly older with a higher prevalence of cardiovascular disease and diabetes which may increase event rates and the power of the study. Australia & New Zealand Clinical Trial Register (ACTRN12607000569404).

Computers and the orthopaedic office.

PubMed

Berumen, Edmundo; Barllow, Fidel Dobarganes; Fong, Fransisco Javier; Lopez, Jorge Arturo

2002-01-01

The advance of today's medicine could be linked very closely to the history of computers through the last twenty years. In the beginning the first attempt to build a computer was trying to help us with mathematical calculations. This has changed recently and computers are now linked to x-ray machines, CT scanners, and MRIs. Being able to share information is one of the goals of the future. Today's computer technology has helped a great deal to allow orthopaedic surgeons from around the world to consult on a difficult case or to become a part of a large database. Obtaining the results from a method of treatment using a multicentric information study can be done on a regular basis. In the future, computers will help us to retrieve information from patients' clinical history directly from a hospital database or by portable memory cards that will carry every radiograph or video from previous surgeries.

Intrahepatic Cholangiocarcinoma: expert consensus statement

PubMed Central

Weber, Sharon M; Ribero, Dario; O=Reilly, Eileen M; Kokudo, Norihiro; Miyazaki, Masaru; Pawlik, Timothy M

2015-01-01

An American Hepato-Pancreato-Biliary Association (AHPBA)-sponsored consensus meeting of expert panellists met on 15 January 2014 to review current evidence on the management of intrahepatic cholangiocarcinoma (ICC) in order to establish practice guidelines and to agree on consensus statements. The treatment of ICC requires a coordinated, multidisciplinary approach to optimize survival. Biopsy is not necessary if the surgeon suspects ICC and is planning curative resection, although biopsy should be obtained before systemic or locoregional therapies are initiated. Assessment of resectability is best accomplished using cross-sectional imaging [computed tomography (CT) or magnetic resonance imaging (MRI)], but the role of positron emission tomography (PET) is unclear. Resectability in ICC is defined by the ability to completely remove the disease while leaving an adequate liver remnant. Extrahepatic disease, multiple bilobar or multicentric tumours, and lymph node metastases beyond the primary echelon are contraindications to resection. Regional lymphadenectomy should be considered a standard part of surgical therapy. In patients with high-risk features, the routine use of diagnostic laparoscopy is recommended. The preoperative diagnosis of combined hepatocellular carcinoma and cholangiocarcinoma (cHCC–CC) by imaging studies is extremely difficult. Surgical resection remains the mainstay of treatment, but survival is worse than in HCC alone. There are no adequately powered, randomized Phase III trials that can provide definitive recommendations for adjuvant therapy for ICC. Patients with high-risk features (lymphovascular invasion, multicentricity or satellitosis, large tumours) should be encouraged to enrol in clinical trials and to consider adjuvant therapy. Cisplatin plus gemcitabine represents the standard-of-care, front-line systemic therapy for metastatic ICC. Genomic analyses of biliary cancers support the development of targeted therapeutic interventions. PMID:26172134

Characterization and Multicentric Validation of a Common Standard for Toxoplasma gondii Detection Using Nucleic Acid Amplification Assays

PubMed Central

Varlet-Marie, Emmanuelle; Sterkers, Yvon; Brenier-Pinchart, Marie-Pierre; Cassaing, Sophie; Dalle, Frédéric; Delhaes, Laurence; Filisetti, Denis; Pelloux, Hervé; Touafek, Fériel; Yera, Hélène

2014-01-01

The molecular diagnosis of toxoplasmosis essentially relies upon laboratory-developed methods and suffers from lack of standardization, hence the large diversity of performances between laboratories. Moreover, quantifications of parasitic loads differ among centers, a fact which prevents the possible prediction of the severity of this disease as a function of parasitic loads. The objectives of this multicentric study performed in eight proficient laboratories of the Molecular Biology Pole of the French National Reference Center for Toxoplasmosis (NRC-T) were (i) to assess the suitability of a lyophilized preparation of Toxoplasma gondii as a common standard for use in this PCR-based molecular diagnosis and (ii) to make this standard available to the community. High-quality written procedures were used for the production and qualification of this standard. Three independent batches of this standard, containing concentrations ranging from 104 to 0.01 T. gondii genome equivalents per PCR, were first assessed: the linear dynamic range was ≥6 log, the intra-assay coefficients of variation (CV) from a sample containing 10 T. gondii organisms per PCR were 0.3% to 0.42%, and the interassay CV over a 2-week period was 0.76% to 1.47%. A further assessment in eight diagnostic centers showed that the standard is stable, robust, and reliable. These lyophilized standards can easily be produced at a larger scale when needed and can be made widely available at the national level. To our knowledge, this is the first quality control assessment of a common standard which is usable both for self-evaluation in laboratories and for accurate quantification of parasitic loads in T. gondii prenatal infections. PMID:25187637

Characterization and multicentric validation of a common standard for Toxoplasma gondii detection using nucleic acid amplification assays.

PubMed

Varlet-Marie, Emmanuelle; Sterkers, Yvon; Brenier-Pinchart, Marie-Pierre; Cassaing, Sophie; Dalle, Frédéric; Delhaes, Laurence; Filisetti, Denis; Pelloux, Hervé; Touafek, Fériel; Yera, Hélène; Bastien, Patrick

2014-11-01

The molecular diagnosis of toxoplasmosis essentially relies upon laboratory-developed methods and suffers from lack of standardization, hence the large diversity of performances between laboratories. Moreover, quantifications of parasitic loads differ among centers, a fact which prevents the possible prediction of the severity of this disease as a function of parasitic loads. The objectives of this multicentric study performed in eight proficient laboratories of the Molecular Biology Pole of the French National Reference Center for Toxoplasmosis (NRC-T) were (i) to assess the suitability of a lyophilized preparation of Toxoplasma gondii as a common standard for use in this PCR-based molecular diagnosis and (ii) to make this standard available to the community. High-quality written procedures were used for the production and qualification of this standard. Three independent batches of this standard, containing concentrations ranging from 10(4) to 0.01 T. gondii genome equivalents per PCR, were first assessed: the linear dynamic range was ≥ 6 log, the intra-assay coefficients of variation (CV) from a sample containing 10 T. gondii organisms per PCR were 0.3% to 0.42%, and the interassay CV over a 2-week period was 0.76% to 1.47%. A further assessment in eight diagnostic centers showed that the standard is stable, robust, and reliable. These lyophilized standards can easily be produced at a larger scale when needed and can be made widely available at the national level. To our knowledge, this is the first quality control assessment of a common standard which is usable both for self-evaluation in laboratories and for accurate quantification of parasitic loads in T. gondii prenatal infections. Copyright © 2014, American Society for Microbiology. All Rights Reserved.

Detection of drug resistance mutations at low plasma HIV-1 RNA load in a European multicentre cohort study.

PubMed

Prosperi, Mattia C F; Mackie, Nicola; Di Giambenedetto, Simona; Zazzi, Maurizio; Camacho, Ricardo; Fanti, Iuri; Torti, Carlo; Sönnerborg, Anders; Kaiser, Rolf; Codoñer, Francisco M; Van Laethem, Kristel; Bansi, Loveleen; van de Vijver, David A M C; Geretti, Anna Maria; De Luca, Andrea

2011-08-01

Guidelines indicate a plasma HIV-1 RNA load of 500-1000 copies/mL as the minimal threshold for antiretroviral drug resistance testing. Resistance testing at lower viral load levels may be useful to guide timely treatment switches, although data on the clinical utility of this remain limited. We report here the influence of viral load levels on the probability of detecting drug resistance mutations (DRMs) and other mutations by routine genotypic testing in a large multicentre European cohort, with a focus on tests performed at a viral load <1000 copies/mL. A total of 16 511 HIV-1 reverse transcriptase and protease sequences from 11 492 treatment-experienced patients were identified, and linked to clinical data on viral load, CD4 T cell counts and antiretroviral treatment history. Test results from 3162 treatment-naive patients served as controls. Multivariable analysis was employed to identify predictors of reverse transcriptase and protease DRMs. Overall, 2500/16 511 (15.14%) test results were obtained at a viral load <1000 copies/mL. Individuals with viral load levels of 1000-10000 copies/mL showed the highest probability of drug resistance to any drug class. Independently from other measurable confounders, treatment-experienced patients showed a trend for DRMs and other mutations to decrease at viral load levels <500 copies/mL. Genotypic testing at low viral load may identify emerging antiretroviral drug resistance at an early stage, and thus might be successfully employed in guiding prompt management strategies that may reduce the accumulation of resistance and cross-resistance, viral adaptive changes, and larger viral load increases.

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

Chronic Peripheral Inflammation is Associated With Cognitive Impairment in Schizophrenia: Results From the Multicentric FACE-SZ Dataset

PubMed Central

Bulzacka, Ewa; Boyer, Laurent; Schürhoff, Franck; Godin, Ophélia; Berna, Fabrice; Brunel, Lore; Andrianarisoa, Méja; Aouizerate, Bruno; Capdevielle, Delphine; Chéreau-Boudet, Isabelle; Chesnoy-Servanin, Gabrielle; Danion, Jean-Marie; Dubertret, Caroline; Dubreucq, Julien; Faget, Catherine; Gabayet, Franck; Le Gloahec, Tifenn; Llorca, Pierre-Michel; Mallet, Jasmina; Misdrahi, David; Rey, Romain; Richieri, Raphaëlle; Passerieux, Christine; Roux, Paul; Yazbek, Hanan; Leboyer, Marion; Fond, Guillaume

2016-01-01

Objectives: Inflammation, measured by abnormal blood C-reactive protein (CRP) level, has been described in schizophrenia (SZ), being inconsistently related to impaired cognitive functions. The aim of the present study is to investigate cognitive impairment associated with abnormal CRP levels in a large multi-centric sample of community-dwelling SZ patients, using a comprehensive neuropsychological battery. Method: Three hundred sixty-nine community-dwelling stable SZ subjects (76.2% men, mean age 32.7 y) were included and tested with a comprehensive battery of neuropsychological tests. Abnormal CRP level was defined as >3mg/L. Results: Multiple factor analysis revealed that abnormal CRP levels, found in 104 patients (28.2%), were associated with impaired General Intellectual Ability and Abstract Reasoning (aOR = 0.56, 95% CI 0.35–0.90, P = .014), independently of age, sex, education level, psychotic symptomatology, treatments, and addiction comorbidities. Abnormal CRP levels were also associated with the decline of all components of working memory (respectively effect size [ES] = 0.25, P = .033; ES = 0.27, P = .04; ES = 0.33, P = .006; and ES = 0.38, P = .004) and a wide range of other impaired cognitive functions, including memory (ES = 0.26, P = .026), learning abilities (ES = 0.28, P = .035), semantic memory (ES = 0.26, P = .026), mental flexibility (ES = 0.26, P = .044), visual attention (ES = 0.23, P = .004) and speed of processing (ES = 0.23, P = .043). Conclusion: Our results suggest that abnormal CRP level is associated with cognitive impairment in SZ. Evaluating the effectiveness of neuroprotective anti-inflammatory strategies is needed in order to prevent cognitive impairment in SZ. PMID:27143795

Dasatinib first-line: Multicentric Italian experience outside clinical trials.

PubMed

Breccia, Massimo; Stagno, Fabio; Luciano, Luigiana; Abruzzese, Elisabetta; Annunziata, Mario; D'Adda, Mariella; Maggi, Alessandro; Sgherza, Nicola; Russo-Rossi, Antonella; Pregno, Patrizia; Castagnetti, Fausto; Iurlo, Alessandra; Latagliata, Roberto; Cedrone, Michele; Di Renzo, Nicola; Sorà, Federica; Rege-Cambrin, Giovanna; La Nasa, Giorgio; Scortechini, Anna Rita; Greco, Giovanna; Franceschini, Luca; Sica, Simona; Bocchia, Monica; Crugnola, Monica; Orlandi, Esther; Guarini, Attilio; Specchia, Giorgina; Rosti, Gianantonio; Saglio, Giuseppe; Alimena, Giuliana

2016-01-01

Dasatinib was approved for the treatment of chronic phase (CP) chronic myeloid leukemia (CML) patients in first line therapy based on the demonstration of efficacy and safety reported in patients enrolled in clinical trials. We describe a multicentric Italian "real-life" experience of dasatinib used as frontline treatment outside clinical trials. One hundred and nine patients (median age 54 years) were treated from January 2012 to December 2013. Increased incidence of high risk patients were detected according to stratification (26% according to Sokal score, 19% according to Euro score and 16% according to EUTOS) when compared to company sponsored studies. Median time from diagnosis to start of dasatinib was 18 days. Ten patients received unscheduled starting dose (6 patients 50mg and 4 patients 80 mg QD), whereas 99 patients started with 100mg QD. At 3 months, 92% of patients achieved a BCR-ABL ratio less than 10%. At 6 months, the rate of CCyR was 91% and the rate of MR3 was 40%, with 8% of the patients reaching MR4.5. Ninety-three patients were evaluable at 12 months: the rate of MR3 was 62%, with MR4.5 being achieved by 19% of the patients. At a median follow-up of 12 months, 27 patients (24.7%) were receiving the drug at reduced dose. Two patients (1.8%) experienced a lymphoid blast crisis and the overall incidence of resistance was 8%. As regards safety, the major side effects recorded were thrombocytopenia, neutropenia and pleural effusions, which occurred in 22%, 10% and 8% of patients, respectively. Present results, achieved in a large cohort of patients treated outside clinical trials, further confirm the efficacy and safety of dasatinib as firstline treatment in CML. Copyright © 2015 Elsevier Ltd. All rights reserved.

Biopsy and selective recall compared with immediate large loop excision in management of women with low grade abnormal cervical cytology referred for colposcopy: multicentre randomised controlled trial.

PubMed

2009-07-28

To compare the effectiveness of punch biopsy and selective recall for treatment versus a policy of immediate treatment by large loop excision in the management of women with low grade abnormal cervical cytology referred for colposcopy. Multicentre individually randomised controlled trial, nested within the NHS cervical screening programmes. Grampian, Tayside, and Nottingham. 1983 women, aged 20-59, with cytology showing borderline nuclear abnormalities or mild dyskaryosis, October 1999-October 2002. Immediate large loop excision or up to four targeted punch biopsies taken immediately with recall for treatment (by large loop excision) if these showed cervical intraepithelial neoplasia grade II or III or worse. Participants were followed for three years, concluding with an exit colposcopy. Clinical end points: cumulative incidence of cervical intraepithelial neoplasia grade II or worse and grade III or worse at three years. Clinically significant anxiety and depression and self reported after effects assessed six weeks after colposcopy, biopsies, or large loop excision. 879 women (44%) had a normal transformation zone at colposcopy and had no further procedures at that time. Colposcopists were less likely to classify the transformation zone as abnormal when the allocation was large loop excision (603 (60%) in the biopsy and selective recall group; 501 (51%) in the immediate large loop excision group). Of women randomised to biopsy and recall, 157 (16%) required a second clinic visit for treatment. Specimens from almost 60% (n=296) of women who underwent immediate large loop excision showed no cervical intraepithelial neoplasia (31%; n=156) or showed cervical intraepithelial neoplasia grade I (28%; n=140). The percentages of women diagnosed with grade II or worse up to and including the exit examination were 22% (n=216) in the biopsy and recall arm and 23% (n=228) in the immediate large loop excision arm. There was no significant difference between the arms in cumulative incidence of cervical intraepithelial neoplasia grade II or worse (adjusted relative for risk large loop excision v biopsy 1.04, 95% confidence interval 0.86 to 1.25) or grade III or worse (1.03, 0.79 to 1.34). A greater proportion of disease was detected at initial investigation and less during follow-up and at exit in the immediate large loop excision arm, but time of detection did not differ significantly between arms. Levels of anxiety and depression and reported pain did not differ between arms. Higher proportions of women randomised to large loop excision reported moderate or more severe bleeding and discharge. A policy of targeted punch biopsies with subsequent treatment for cervical intraepithelial neoplasia grade II or III and cytological surveillance for grade I or less provides the best balance between benefits and harms for the management of women with low grade abnormal cytology referred for colposcopy. Immediate large loop excision results in overtreatment and more after effects and should not be recommended. ISRCTN 34841617.

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.

[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.

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.

Outcomes of cup revision for ilio-psoas impingement after total hip arthroplasty: Retrospective study of 46 patients.

PubMed

Batailler, C; Bonin, N; M Wettstein; Nogier, A; Martres, S; Ollier, E; May, O; Lustig, S

2017-12-01

Impingement of the ilio-psoas tendon on the acetabular component is a cause of pain after total hip arthroplasty (THA). Studies of cup revision for ilio-psoas impingement (IPI) are scarce and limited in size. We therefore conducted a large multicentre retrospective study with the following objectives: to assess the effectiveness of cup replacement in resolving the impingement syndrome, to determine the frequency and nature of complications after cup revision for IPI, and to identify pre-operative factors associated with good outcomes of cup revision for IPI. Cup revision is effective in resolving the pain due to IPI in selected patients. This retrospective multicentre study included 46 patients who underwent cup revision because of IPI. Before the revision, 38 (83%) patients had prominence of the anterior cup rim (mean, 9.9±4.5mm (range, 2-22mm) by radiography and 35 (76%) had cup malposition (anteversion<10° and/or inclination>50°). Mean follow-up was 21months (range, 6months to 6 years) and no patient was lost to follow-up. Outcomes at last follow-up were assessed based on the Oxford Hip Score (OHS), patient satisfaction index, complications, and revisions. At last follow-up, 39 (85%) patients were satisfied with the revision procedure, a significant improvement versus baseline was noted in the OHS (mean, 43±6; range, 25-48; P<0.001), and 41 patients were free of pain during hip flexion (P<0.001 versus baseline). Complications occurred in 3 (6.5%) patients, but only one complication was severe (deep infection). Recurrent groin pain was reported by 4 (8.7%) patients at last follow-up. None of the factors studied predicted the outcome of revision surgery. Cup revision for IPI after THA is effective in relieving the groin pain in 80% of patients with anterior cup rim prominence and/or cup malposition. However, complications can occur. Tenotomy may be preferable when the diagnosis is in doubt and/or cup position is acceptable. IV, retrospective observational study. Published by Elsevier Masson SAS.

The PneuCarriage Project: A Multi-Centre Comparative Study to Identify the Best Serotyping Methods for Examining Pneumococcal Carriage in Vaccine Evaluation Studies.

PubMed

Satzke, Catherine; Dunne, Eileen M; Porter, Barbara D; Klugman, Keith P; Mulholland, E Kim

2015-11-01

The pneumococcus is a diverse pathogen whose primary niche is the nasopharynx. Over 90 different serotypes exist, and nasopharyngeal carriage of multiple serotypes is common. Understanding pneumococcal carriage is essential for evaluating the impact of pneumococcal vaccines. Traditional serotyping methods are cumbersome and insufficient for detecting multiple serotype carriage, and there are few data comparing the new methods that have been developed over the past decade. We established the PneuCarriage project, a large, international multi-centre study dedicated to the identification of the best pneumococcal serotyping methods for carriage studies. Reference sample sets were distributed to 15 research groups for blinded testing. Twenty pneumococcal serotyping methods were used to test 81 laboratory-prepared (spiked) samples. The five top-performing methods were used to test 260 nasopharyngeal (field) samples collected from children in six high-burden countries. Sensitivity and positive predictive value (PPV) were determined for the test methods and the reference method (traditional serotyping of >100 colonies from each sample). For the alternate serotyping methods, the overall sensitivity ranged from 1% to 99% (reference method 98%), and PPV from 8% to 100% (reference method 100%), when testing the spiked samples. Fifteen methods had ≥70% sensitivity to detect the dominant (major) serotype, whilst only eight methods had ≥70% sensitivity to detect minor serotypes. For the field samples, the overall sensitivity ranged from 74.2% to 95.8% (reference method 93.8%), and PPV from 82.2% to 96.4% (reference method 99.6%). The microarray had the highest sensitivity (95.8%) and high PPV (93.7%). The major limitation of this study is that not all of the available alternative serotyping methods were included. Most methods were able to detect the dominant serotype in a sample, but many performed poorly in detecting the minor serotype populations. Microarray with a culture amplification step was the top-performing method. Results from this comprehensive evaluation will inform future vaccine evaluation and impact studies, particularly in low-income settings, where pneumococcal disease burden remains high.

Maternal side-effects after multiple courses of antenatal corticosteroids (MACS): the three-month follow-up of women in the randomized controlled trial of MACS for preterm birth study.

PubMed

Murphy, Kellie E; Hannah, Mary E; Willan, Andrew R; Ohlsson, Arne; Kelly, Edmond N; Matthews, Stephen G; Saigal, Saroj; Asztalos, Elizabeth; Ross, Sue; Delisle, Marie-France; Tomat, Laura; Amankwah, Kofi; Guselle, Patricia; Gafni, Amiram; Lee, Shoo K; Armson, B Anthony

2011-09-01

A single course of antenatal corticosteroids (ACS) is associated with a reduction in respiratory distress syndrome and neonatal death. Multiple Courses of Antenatal Corticosteroids Study (MACS), a study involving 1858 women, was a multicentre randomized placebo-controlled trial of multiple courses of ACS, given every 14 days until 33+6 weeks or birth, whichever came first. The primary outcome of the study, a composite of neonatal mortality and morbidity, was similar for the multiple ACS and placebo groups (12.9% vs. 12.5%), but infants exposed to multiple courses of ACS weighed less, were shorter, and had smaller head circumferences. Thus for women who remain at increased risk of preterm birth, multiple courses of ACS (every 14 days) are not recommended. Chronic use of corticosteroids is associated with numerous side effects including weight gain and depression. The aim of this postpartum assessment was to ascertain if multiple courses of ACS were associated with maternal side effects. Three months postpartum, women who participated in MACS were asked to complete a structured questionnaire that asked about maternal side effects of corticosteroid use during MACS and included the Edinburgh Postnatal Depression Scale. Women were also asked to evaluate their study participation. Of the 1858 women randomized, 1712 (92.1%) completed the postpartum questionnaire. There were no significant differences in the risk of maternal side effects between the two groups. Large numbers of women met the criteria for postpartum depression (14.1% in the ACS vs. 16.0% in the placebo group). Most women (94.1%) responded that they would participate in the trial again. In pregnancy, corticosteroids are given to women for fetal lung maturation and for the treatment of various maternal diseases. In this international multicentre randomized controlled trial, multiple courses of ACS (every 14 days) were not associated with maternal side effects, and the majority of women responded that they would participate in such a study again.

The PneuCarriage Project: A Multi-Centre Comparative Study to Identify the Best Serotyping Methods for Examining Pneumococcal Carriage in Vaccine Evaluation Studies

PubMed Central

Satzke, Catherine; Dunne, Eileen M.; Porter, Barbara D.; Klugman, Keith P.; Mulholland, E. Kim

2015-01-01

Background The pneumococcus is a diverse pathogen whose primary niche is the nasopharynx. Over 90 different serotypes exist, and nasopharyngeal carriage of multiple serotypes is common. Understanding pneumococcal carriage is essential for evaluating the impact of pneumococcal vaccines. Traditional serotyping methods are cumbersome and insufficient for detecting multiple serotype carriage, and there are few data comparing the new methods that have been developed over the past decade. We established the PneuCarriage project, a large, international multi-centre study dedicated to the identification of the best pneumococcal serotyping methods for carriage studies. Methods and Findings Reference sample sets were distributed to 15 research groups for blinded testing. Twenty pneumococcal serotyping methods were used to test 81 laboratory-prepared (spiked) samples. The five top-performing methods were used to test 260 nasopharyngeal (field) samples collected from children in six high-burden countries. Sensitivity and positive predictive value (PPV) were determined for the test methods and the reference method (traditional serotyping of >100 colonies from each sample). For the alternate serotyping methods, the overall sensitivity ranged from 1% to 99% (reference method 98%), and PPV from 8% to 100% (reference method 100%), when testing the spiked samples. Fifteen methods had ≥70% sensitivity to detect the dominant (major) serotype, whilst only eight methods had ≥70% sensitivity to detect minor serotypes. For the field samples, the overall sensitivity ranged from 74.2% to 95.8% (reference method 93.8%), and PPV from 82.2% to 96.4% (reference method 99.6%). The microarray had the highest sensitivity (95.8%) and high PPV (93.7%). The major limitation of this study is that not all of the available alternative serotyping methods were included. Conclusions Most methods were able to detect the dominant serotype in a sample, but many performed poorly in detecting the minor serotype populations. Microarray with a culture amplification step was the top-performing method. Results from this comprehensive evaluation will inform future vaccine evaluation and impact studies, particularly in low-income settings, where pneumococcal disease burden remains high. PMID:26575033

Emergence agitation during recovery from intracranial surgery under general anaesthesia: a protocol and statistical analysis plan for a prospective multicentre cohort study.

PubMed

Yan, Li-Mei; Chen, Han; Yu, Rong-Guo; Wang, Zhu-Heng; Zhou, Guan-Hua; Wang, Yong-Jin; Zhang, Xia; Xu, Ming; Chen, Lu; Zhou, Jian-Xin

2015-04-21

Emergence agitation after intracranial surgery is an important clinical issue during anaesthesia recovery. The aim of this multicentre cohort study is to investigate the incidence of emergence agitation, identify the risk factors and determine clinical outcomes in adult patients after intracranial surgery under general anaesthesia. Additionally, we will deliberately clarify the relationship between postoperative pneumocephalus and agitation. The present study is a prospective multicentre cohort study. Five intensive care units (ICUs) in China will participate in the study. Consecutive adult patients admitted to the ICUs after intracranial surgery will be enrolled. Sedation-Agitation Scale (SAS) or Richmond Agitation-Sedation Scale (RASS) will be used to evaluate the patients 12 h after the enrolment. Agitation is defined as an SAS score of 5-7, or an RASS score of +2 to +4. According to the maximal SAS and RASS score, patients will be divided into two cohorts: the agitation group and the non-agitation group. Factors potentially related to emergence agitation will be collected at study entry, during anaesthesia and operation, during postoperative care. Univariate analyses between the agitation and the non-agitation groups will be performed. The stepwise backward logistic regression will be carried out to identify the independent predictors of agitation. Patients will be followed up for 72 h after the operation. Accidental self-extubation of the endotracheal tube and removal of other catheters will be documented. The use of sedatives and analgesics will be collected. Ethics approval has been obtained from each of five participating hospitals. Study findings will be disseminated through peer-reviewed publications and conference presentations. NCT02318199. 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.

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

Influence of quality of care and individual patient characteristics on quality of life and return to work in survivors of the acute respiratory distress syndrome: protocol for a prospective, observational, multi-centre patient cohort study (DACAPO).

PubMed

Brandstetter, Susanne; Dodoo-Schittko, Frank; Blecha, Sebastian; Sebök, Philipp; Thomann-Hackner, Kathrin; Quintel, Michael; Weber-Carstens, Steffen; Bein, Thomas; Apfelbacher, Christian

2015-12-17

Health-related quality of life (HRQoL) and return to work are important outcomes in critical care medicine, reaching beyond mortality. Little is known on factors predictive of HRQoL and return to work in critical illness, including the acute respiratory distress syndrome (ARDS), and no evidence exists on the role of quality of care (QoC) for outcomes in survivors of ARDS. It is the aim of the DACAPO study ("Surviving ARDS: the influence of QoC and individual patient characteristics on quality of life") to investigate the role of QoC and individual patient characteristics on quality of life and return to work. A prospective, observational, multi-centre patient cohort study will be performed in Germany, using hospitals from the "ARDS Network Germany" as the main recruiting centres. It is envisaged to recruit 2400 patients into the DACAPO study and to analyse a study population of 1500 survivors. They will be followed up until 12 months after discharge from hospital. QoC will be assessed as process quality, structural quality and volume at the institutional level. The main outcomes (HRQoL and return to work) will be assessed by self-report questionnaires. Further data collection includes general medical and ARDS-related characteristics of patients as well as sociodemographic and psycho-social parameters. Multilevel hierarchical modelling will be performed to analyse the effects of QoC and individual patient characteristics on outcomes, taking the cluster structure of the data into account. By obtaining comprehensive data at patient and hospital level using a prospective multi-centre design, the DACAPO-study is the first study investigating the influence of QoC on individual outcomes of ARDS survivors.

Assessment of temporal association of relapse of canine multicentric lymphoma with components of the CHOP protocol: Is cyclophosphamide the weakest link?

PubMed

Wang, Shang-Lin; Lee, Jih-Jong; Liao, Albert Taiching

2016-07-01

Combination chemotherapy, using cyclophosphamide, hydroxydaunorubicin, vincristine and prednisolone (CHOP), is the most commonly used treatment for canine lymphoma. Most affected dogs respond during the initial stages of chemotherapy, but many relapse. The aim of this study was to evaluate the relationship between the use of specific chemotherapy drugs and clinical relapse, using the modified Madison-Wisconsin, 25 week chemotherapy protocol. Forty-one of 68 dogs affected with multicentric lymphoma relapsed during the treatment period. Relapse occurred more frequently after the administration of cyclophosphamide (n = 24; P < 0.01), compared with vincristine (n = 9) or doxorubicin (n = 5). Therefore, the therapeutic outcome of traditional CHOP-based chemotherapy might be improved by replacing cyclophosphamide with other cytotoxic drugs. Copyright © 2016 Elsevier Ltd. All rights reserved.

Cognitive Modifiability of Children with Developmental Disabilities: A Multicentre Study Using Feuerstein's Instrumental Enrichment-Basic Program

ERIC Educational Resources Information Center

Kozulin, A.; Lebeer, J.; Madella-Noja, A.; Gonzalez, F.; Jeffrey, I.; Rosenthal, N.; Koslowsky, M.

2010-01-01

The study aimed at exploring the effectiveness of cognitive intervention with the new "Instrumental Enrichment Basic" program (IE-basic), based on Feuerstein's theory of structural cognitive modifiability that contends that a child's cognitive functioning can be significantly modified through mediated learning intervention. The IE-basic…

[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.

Colorectal cancer and its association with the metabolic syndrome: a Malaysian multi-centric case-control study.

PubMed

Ulaganathan, V; Kandiah, M; Zalilah, M S; Faizal, J A; Fijeraid, H; Normayah, K; Gooi, B H; Othman, R

2012-01-01

Colorectal cancer (CRC) and the metabolic syndrome (MetS) are both on the rise in Malaysia. A multi-centric case-control study was conducted from December 2009 to January 2011 to determine any relationship between the two. Patients with confirmed CRC based on colonoscopy findings and cancer free controls from five local hospitals were assessed for MetS according to the International Diabetes Federation (IDF) definition. Each index case was matched for age, gender and ethnicity with two controls (140: 280). MetS among cases was highly prevalent (70.7%), especially among women (68.7%). MetS as an entity increased CRC risk by almost three fold independently (OR=2.61, 95%CI=1.53-4.47). In men MetS increased the risk of CRC by two fold (OR=2.01, 95%CI, 1.43-4.56), demonstrating an increasing trend in risk with the number of Mets components observed. This study provides evidence for a positive association between the metabolic syndrome and colorectal cancer. A prospective study on the Malaysian population is a high priority to confirm these findings.

Development and validation of a paediatric long-bone fracture classification. A prospective multicentre study in 13 European paediatric trauma centres

PubMed Central

2011-01-01

Background The aim of this study was to develop a child-specific classification system for long bone fractures and to examine its reliability and validity on the basis of a prospective multicentre study. Methods Using the sequentially developed classification system, three samples of between 30 and 185 paediatric limb fractures from a pool of 2308 fractures documented in two multicenter studies were analysed in a blinded fashion by eight orthopaedic surgeons, on a total of 5 occasions. Intra- and interobserver reliability and accuracy were calculated. Results The reliability improved with successive simplification of the classification. The final version resulted in an overall interobserver agreement of κ = 0.71 with no significant difference between experienced and less experienced raters. Conclusions In conclusion, the evaluation of the newly proposed classification system resulted in a reliable and routinely applicable system, for which training in its proper use may further improve the reliability. It can be recommended as a useful tool for clinical practice and offers the option for developing treatment recommendations and outcome predictions in the future. PMID:21548939

Endoscopic tri-modal imaging for detection of early neoplasia in Barrett's oesophagus: a multi-centre feasibility study using high-resolution endoscopy, autofluorescence imaging and narrow band imaging incorporated in one endoscopy system.

PubMed

Curvers, W L; Singh, R; Song, L-M Wong-Kee; Wolfsen, H C; Ragunath, K; Wang, K; Wallace, M B; Fockens, P; Bergman, J J G H M

2008-02-01

To investigate the diagnostic potential of endoscopic tri-modal imaging and the relative contribution of each imaging modality (i.e. high-resolution endoscopy (HRE), autofluorescence imaging (AFI) and narrow-band imaging (NBI)) for the detection of early neoplasia in Barrett's oesophagus. Prospective multi-centre study. Tertiary referral centres. 84 Patients with Barrett's oesophagus. The Barrett's oesophagus was inspected with HRE followed by AFI. All lesions detected with HRE and/or AFI were subsequently inspected in detail by NBI for the presence of abnormal mucosal and/or microvascular patterns. Biopsies were obtained from all suspicious lesions for blinded histopathological assessment followed by random biopsies. (1) Number of patients with early neoplasia diagnosed by HRE and AFI; (2) number of lesions with early neoplasia detected with HRE and AFI; and (3) reduction of false positive AFI findings after NBI. Per patient analysis: AFI identified all 16 patients with early neoplasia identified with HRE and detected an additional 11 patients with early neoplasia that were not identified with HRE. In three patients no abnormalities were seen but random biopsies revealed HGIN. After HRE inspection, AFI detected an additional 102 lesions; 19 contained HGIN/EC (false positive rate of AFI after HRE: 81%). Detailed inspection with NBI reduced this false positive rate to 26%. In this international multi-centre study, the addition of AFI to HRE increased the detection of both the number of patients and the number of lesions with early neoplasia in patients with Barrett's oesophagus. The false positive rate of AFI was reduced after detailed inspection with NBI.

One-year multicentre outcomes of transapical aortic valve implantation using the SAPIEN XT™ valve: the PREVAIL transapical study.

PubMed

Walther, Thomas; Thielmann, Matthias; Kempfert, Joerg; Schroefel, Holger; Wimmer-Greinecker, Gerhard; Treede, Hendrik; Wahlers, Thorsten; Wendler, Olaf

2013-05-01

The study aimed to evaluate 1-year outcomes of the multicentre PREVAIL transapical (TA) study of TA-aortic valve implantation (AVI) in high-risk patients. From September 2009 to August 2010, a total of 150 patients, aged 81.6 ± 5.8 years, 40.7% female, were included at 12 European TA-AVI experienced sites. Patients received 23 (n = 36), 26 (n = 57) and 29 mm (n = 57) second-generation SAPIEN XT™ (Edwards Lifesciences, Irvine, CA, USA) valves. The mean logistic EuroSCORE was 24.3 ± 7.0, and mean Society Thoracic Surgeons score was 7.5 ± 4.4%. Survival was 91.3% at 30 days and 77.9% at 1 year. Subgroup analysis revealed survivals of 91.7/88.9, 86.0/70.2, 96.55/91.2% for patients receiving 23-, 26- and 29-mm valves at 30 days and at 1 year, respectively. Transthoracic echocardiography revealed preserved left ventricular ejection fraction and low gradients. Aortic incompetence was none in 41/48, trace 30/36, mild 22/12 and moderate in 7/4% at discharge and 1 year. Walking distance increased from 221 (postimplant) to 284 m (at 1 year, P = 0.0004). Three patients required reoperation due to increasing aortic incompetence during follow-up. Causes of mortality at 1 year were cardiac (n = 7), stroke (n = 1) and others (n = 5). The European PREVAIL multicentre trial demonstrates good functionality and good outcomes for TA-AVI using the second-generation SAPIEN XT prosthesis and the ASCENDRA-II delivery system. The 29-mm SAPIEN XT valve was successfully introduced and showed excellent results.

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.

Dose escalation study to evaluate safety, tolerability and efficacy of intravenous etoposide phosphate administration in 27 dogs with multicentric lymphoma

PubMed Central

Hordeaux, Juliette; Bouchaert, Emmanuel; Gomes, Bruno

2017-01-01

Comparative oncology has shown that naturally occurring canine cancers are of valuable and translatable interest for the understanding of human cancer biology and the characterization of new therapies. This work was part of a comparative oncology project assessing a new, clinical-stage topoisomerase II inhibitor and comparing it with etoposide in dogs with spontaneous lymphoma with the objective to translate findings from dogs to humans. Etoposide is a topoisomerase II inhibitor widely used in various humans’ solid and hematopoietic cancer, but little data is available concerning its potential antitumor efficacy in dogs. Etoposide phosphate is a water-soluble prodrug of etoposide which is expected to be better tolerated in dogs. The objectives of this study were to assess the safety, the tolerability and the efficacy of intravenous etoposide phosphate in dogs with multicentric lymphoma. Seven dose levels were evaluated in a traditional 3+3 phase I design. Twenty-seven owned-dogs with high-grade multicentric lymphoma were enrolled and treated with three cycles of etoposide phosphate IV injections every 2 weeks. Adverse effects were graded according to the Veterinary Cooperative Oncology Group criteria. A complete end-staging was realized 45 days after inclusion. The maximal tolerated dose was 300 mg/m2. At this dose level, the overall response rate was 83.3% (n = 6, 3 PR and 2 CR). Only a moderate reversible gastrointestinal toxicity, no severe myelotoxicity and no hypersensitivity reaction were reported at this dose level. Beyond the characterization of etoposide clinical efficacy in dogs, this study underlined the clinical and therapeutic homologies between dog and human lymphomas. PMID:28505195

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

Nine-Months Clinical Outcome of Biodegradable Polymer Coated Sirolimus-eluting Stent System: A Multi-Centre "Real-World" Experience.

PubMed

Sarma, Raghava; Prajapati, Jayesh; Raheem, Asif; Thakkar, Kamlesh; Kothari, Shivani; Thakkar, Ashok

2015-08-01

The main culprit in first-generation drug eluting stents is 'durable' polymer, whose continuous presence may impair arterial healing and ultimately have a negative impact on late outcomes. The main enigma behind the biodegradable polymer usage is its degradation after elution of drug. This reduces adverse events in unselected patients with complex coronary artery lesions treated with biodegradable polymer coated sirolimus-eluting stents. The aim of the INDOLIMUS-G Registry was to evaluate safety and efficacy of the Indolimus (Sahajanand Medical Technologies Pvt. Ltd., Surat, India) sirolimus-eluting stents in large cohorts of unselected patients with complex coronary artery lesions. It is a multi-centre, non-randomized retrospective registry with a clear aim of evaluating safety and efficacy of the Indolimus sirolimus-eluting stents in consecutive patients enrolled between April 2012 and May 2014. The primary end-point of the study was major adverse cardiac events (MACE), which is a composite of cardiac death, myocardial infarction (MI), target lesion revascularization (TLR), target vessel revascularization (TVR) and stent thrombosis (ST) at the end of follow-up. Clinical follow-up were scheduled at the end of 30-days, 6-months, and 9-months period. The mean age of enrolled patients was 52.6 ± 11.0 years. A total of 1137 lesions were intervened successfully with 1242 stents (1.09 ± 0.30 stent per lesion). The average stent length and diameter was 27.42 ± 9.01 mm and 3.12 ± 0.36 mm respectively. There were 740 (73.40%) male patients, indicating their high prevalence. Diabetes, hypertension and totally occluded lesions were found in 372 (36.90%), 408 (40.47%) and 170 (16.86%) patients, respectively. This showed that study also included high risk complex lesions and not ideal recruited lesions. The incidence of MACE at 30-days, 6-months and 9-months were 3 (0.30%), 18 (1.80%) and 22 (2.20%) respectively. At 9-months, TLR was found in 6 (0.50%) patients. There were 2 (0.20%) cases of ST, 10 (1.0%) cases of MI and 4 (0.40%) cases of cardiac death at 9-month follow-up. The lower incidence of MACE, TLR and ST at 9-month follow-up clearly delineates safety and efficacy of Indolimus SES in large cohorts of unselected patients with complex coronary lesions.

Oral ondansetron versus domperidone for symptomatic treatment of vomiting during acute gastroenteritis in children: multicentre randomized controlled trial.

PubMed

Marchetti, Federico; Maestro, Alessandra; Rovere, Francesca; Zanon, Davide; Arrighini, Alberto; Bertolani, Paolo; Biban, Paolo; Da Dalt, Liviana; Di Pietro, Pasquale; Renna, Salvatore; Guala, Andrea; Mannelli, Francesco; Pazzaglia, Anna; Messi, Gianni; Perri, Francesco; Reale, Antonino; Urbino, Antonio Francesco; Valletta, Enrico; Vitale, Antonio; Zangardi, Tiziana; Tondelli, Maria Teresa; Clavenna, Antonio; Bonati, Maurizio; Ronfani, Luca

2011-02-10

Vomiting in children with acute gastroenteritis (AG) is not only a direct cause of fluid loss but it is also a major factor of failure of oral rehydration therapy (ORT). Physicians who provide care to paediatric patients in the emergency department (ED) usually prescribe intravenous fluid therapy (IVT) for mild or moderate dehydration when vomiting is the major symptom. Thus, effective symptomatic treatment of vomiting would lead to an important reduction in the use of IVT and, consequently, of the duration of hospital stay and of frequency of hospital admission. Available evidence on symptomatic treatment of vomiting shows the efficacy of the most recently registered molecule (ondansetron) but a proper evaluation of antiemetics drugs largely used in clinical practice, such as domperidone, is lacking. To compare the efficacy of ondansetron and domperidone for the symptomatic treatment of vomiting in children with AG who have failed ORT. Multicentre, double-blind randomized controlled trial conducted in paediatric EDs. Children aged from 1 to 6 years who vomiting, with a presumptive clinical diagnosis of AG, and without severe dehydration will be included. After the failure of a initial ORS administration in ED, eligible children will be randomized to receive: 1) ondansetron syrup (0,15 mg/Kg of body weight); 2) domperidone syrup (0,5 mg/Kg of body weight); 3) placebo. The main study outcome will be the percentage of patients needing nasogastric or IVT after symptomatic oral treatment failure, defined as vomiting or fluid refusal after a second attempt of ORT. Data relative to study outcomes will be collected at 30 minute intervals for a minimum of 6 hours. A telephone follow up call will be made 48 hours after discharge. A total number of 540 children (i.e. 180 patients in each arm) will be enrolled. The trial results would provide evidence on the efficacy of domperidone, which is largely used in clinical practice despite the lack of proper evaluation and a controversial safety profile, as compared to ondansetron, which is not yet authorized in Italy despite evidence supporting its efficacy in treating vomiting. The trial results would contribute to a reduction in the use of IVT and, consequently, in hospital admissions in children with AG. The design of this RCT, which closely reflect current clinical practice in EDs, will allow immediate transferability of results. ClinicalTrials.gov: NCT01257672.

Standardisation of neonatal clinical practice.

PubMed

Bhutta, Z A; Giuliani, F; Haroon, A; Knight, H E; Albernaz, E; Batra, M; Bhat, B; Bertino, E; McCormick, K; Ochieng, R; Rajan, V; Ruyan, P; Cheikh Ismail, L; Paul, V

2013-09-01

The International Fetal and Newborn Growth Consortium for the 21(st) Century (INTERGROWTH-21(st) ) is a large-scale, population-based, multicentre project involving health institutions from eight geographically diverse countries, which aims to assess fetal, newborn and preterm growth under optimal conditions. Given the multicentre nature of the project and the expected number of preterm births, it is vital that all centres follow the same standardised clinical care protocols to assess and manage preterm infants, so as to ensure maximum validity of the resulting standards as indicators of growth and nutrition with minimal confounding. Moreover, it is well known that evidence-based clinical practice guidelines can reduce the delivery of inappropriate care and support the introduction of new knowledge into clinical practice. The INTERGROWTH-21(st) Neonatal Group produced an operations manual, which reflects the consensus reached by members of the group regarding standardised definitions of neonatal morbidities and the minimum standards of care to be provided by all centres taking part in the project. The operational definitions and summary management protocols were developed by consensus through a Delphi process based on systematic reviews of relevant guidelines and management protocols by authoritative bodies. This paper describes the process of developing the Basic Neonatal Care Manual, as well as the morbidity definitions and standardised neonatal care protocols applied across all the INTERGROWTH-21(st) participating centres. Finally, thoughts about implementation strategies are presented. © 2013 Royal College of Obstetricians and Gynaecologists.

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.

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.

Evaluation of a 15-week CHOP protocol for the treatment of canine multicentric lymphoma.

PubMed

Burton, J H; Garrett-Mayer, E; Thamm, D H

2013-12-01

Dose intense CHOP protocols have been shown to improve outcome for people with non-Hodgkin's lymphoma, but evaluation of dose intense CHOP protocols for canine lymphoma is currently limited. The hypothesis of this retrospective study was that a 15-week dose intense CHOP protocol would have shorter treatment duration with similar efficacy to other doxorubicin-based multidrug protocols. Thirty-one client owned dogs with multicentric lymphoma were treated with a 15-week CHOP chemotherapy protocol with an overall response rate of 100% and a median progression-free interval (PFI) of 140 days [95% confidence interval (CI) 91-335 days]. Dogs that had two or more treatment delays had significantly prolonged PFI and overall survival in multivariate analysis. Dose intensity did not correlate with patient outcome. Dogs experiencing multiple treatment delays secondary to adverse events may receive their individual maximally tolerated dose while dogs with no adverse events may be underdosed. Future studies should focus on individual patient dose optimization. © 2012 Blackwell Publishing Ltd.

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.

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.

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.

The effectiveness of 2-implant overdentures - a pragmatic international multicentre study.

PubMed

Rashid, F; Awad, M A; Thomason, J M; Piovano, A; Spielberg, G P; Scilingo, E; Mojon, P; Müller, F; Spielberg, M; Heydecke, G; Stoker, G; Wismeijer, D; Allen, F; Feine, J S

2011-03-01

The purpose of this multicentre observational study was to determine patient satisfaction with either conventional dentures or mandibular 2-implant overdentures in a 'real world' setting. Two hundred and three edentulous patients (mean age 68·8 ± 10·4 years) were recruited at eight centres located in North America, South America and Europe. The patients were provided with new mandibular conventional dentures or implant overdentures supported by two implants and ball attachments. At baseline and at 6 months post-treatment, they rated their satisfaction with their mandibular prostheses on 100-mm visual analogue scale questionnaires. One hundred and two (50·2%) participants had valid baseline and 6-month satisfaction data. Although both groups reported improvements, the implant overdenture group reported significantly higher ratings of overall satisfaction, comfort, stability, ability to speak and ability to chew. These results suggest that edentulous patients who choose mandibular implant overdentures have significantly greater improvements in satisfaction, despite their relatively higher cost, than those who choose new conventional dentures. © 2010 Blackwell Publishing Ltd.

Clinical Trials in Dentistry: A Cross-sectional Analysis of World Health Organization-International Clinical Trial Registry Platform.

PubMed

Sivaramakrishnan, Gowri; Sridharan, Kannan

2016-06-01

Clinical trials are the back bone for evidence-based practice (EBP) and recently EBP has been considered the best source of treatment strategies available. Clinical trial registries serve as databases of clinical trials. As regards to dentistry in specific data on the number of clinical trials and their quality is lacking. Hence, the present study was envisaged. Clinical trials registered in WHO-ICTRP (http://apps.who.int/trialsearch/AdvSearch.aspx) in dental specialties were considered. The details assessed from the collected trials include: Type of sponsors; Health condition; Recruitment status; Study design; randomization, method of randomization and allocation concealment; Single or multi-centric; Retrospective or prospective registration; and Publication status in case of completed studies. A total of 197 trials were identified. Maximum trials were from United States (n = 30) and United Kingdom (n = 38). Seventy six trials were registered in Clinical Trials.gov, 54 from International Standards of Reporting Clinical Trials, 13 each from Australia and New Zealand Trial Register and Iranian Registry of Clinical Trials, 10 from German Clinical Trial Registry, eight each from Brazilian Clinical Trial Registry and Nederland's Trial Register, seven from Japan Clinical Trial Registry, six from Clinical Trial Registry of India and two from Hong Kong Clinical Trial Registry. A total of 78.7% studies were investigator-initiated and 64% were completed while 3% were terminated. Nearly four-fifths of the registered trials (81.7%) were interventional studies of which randomized were the large majority (94.4%) with 63.2% being open label, 20.4% using single blinding technique and 16.4% were doubled blinded. The number, methodology and the characteristics of clinical trials in dentistry have been noted to be poor especially in terms of being conducted multi-centrically, employing blinding and the method for randomization and allocation concealment. More emphasis has to be laid down on the quality of trials being conducted in order to provide justice in the name of EBP. Copyright © 2016 Elsevier Inc. All rights reserved.

Optimization of brain PET imaging for a multicentre trial: the French CATI experience.

PubMed

Habert, Marie-Odile; Marie, Sullivan; Bertin, Hugo; Reynal, Moana; Martini, Jean-Baptiste; Diallo, Mamadou; Kas, Aurélie; Trébossen, Régine

2016-12-01

CATI is a French initiative launched in 2010 to handle the neuroimaging of a large cohort of subjects recruited for an Alzheimer's research program called MEMENTO. This paper presents our test protocol and results obtained for the 22 PET centres (overall 13 different scanners) involved in the MEMENTO cohort. We determined acquisition parameters using phantom experiments prior to patient studies, with the aim of optimizing PET quantitative values to the highest possible per site, while reducing, if possible, variability across centres. Jaszczak's and 3D-Hoffman's phantom measurements were used to assess image spatial resolution (ISR), recovery coefficients (RC) in hot and cold spheres, and signal-to-noise ratio (SNR). For each centre, the optimal reconstruction parameters were chosen as those maximizing ISR and RC without a noticeable decrease in SNR. Point-spread-function (PSF) modelling reconstructions were discarded. The three figures of merit extracted from the images reconstructed with optimized parameters and routine schemes were compared, as were volumes of interest ratios extracted from Hoffman acquisitions. The net effect of the 3D-OSEM reconstruction parameter optimization was investigated on a subset of 18 scanners without PSF modelling reconstruction. Compared to the routine parameters of the 22 PET centres, average RC in the two smallest hot and cold spheres and average ISR remained stable or were improved with the optimized reconstruction, at the expense of slight SNR degradation, while the dispersion of values was reduced. For the subset of scanners without PSF modelling, the mean RC of the smallest hot sphere obtained with the optimized reconstruction was significantly higher than with routine reconstruction. The putamen and caudate-to-white matter ratios measured on 3D-Hoffman acquisitions of all centres were also significantly improved by the optimization, while the variance was reduced. This study provides guidelines for optimizing quantitative results for multicentric PET neuroimaging trials.

Epidemiological, virological and clinical characteristics of HBV infection in 223 HIV co-infected patients: a French multi-centre collaborative study.

PubMed

Thibault, Vincent; Gaudy-Graffin, Catherine; Colson, Philippe; Gozlan, Joël; Schnepf, Nathalie; Trimoulet, Pascale; Pallier, Coralie; Saune, Karine; Branger, Michel; Coste, Marianne; Thoraval, Francoise Roudot

2013-03-15

Chronic hepatitis B (CHB) is a clinical concern in human immunodeficiency virus (HIV)-infected individuals due to substantial prevalence, difficulties to treat, and severe liver disease outcome. A large nationwide cross-sectional multicentre analysis of HIV-HBV co-infected patients was designed to describe and identify parameters associated with virological and clinical outcome of CHB in HIV-infected individuals with detectable HBV viremia. A multicenter collaborative cross-sectional study was launched in 19 French University hospitals distributed through the country. From January to December 2007, HBV load, genotype, clinical and epidemiological characteristics of 223 HBV-HIV co-infected patients with an HBV replication over 1000 IU/mL were investigated. Patients were mostly male (82%, mean age 42 years). Genotype distribution (A 52%; E 23.3%; D 16.1%) was linked to risk factors, geographic origin, and co-infection with other hepatitis viruses. This genotypic pattern highlights divergent contamination event timelines by HIV and HBV viruses. Most patients (74.7%) under antiretroviral treatment were receiving a drug with anti-HBV activity, including 47% receiving TDF. Genotypic lamivudine-resistance detected in 26% of the patients was linked to duration of lamivudine exposure, age, CD4 count and HIV load. Resistance to adefovir (rtA181T/V) was detected in 2.7% of patients. Advanced liver lesions were observed in 54% of cases and were associated with an older age and lower CD4 counts but not with viral load or genotype. Immune escape HBsAg variants were seldom detected. Despite the detection of advanced liver lesions in most patients, few were not receiving anti-HBV drugs and for those treated with the most potent anti-HBV drugs, persistent replication suggested non-optimal adherence. Heterogeneity in HBV strains reflects epidemiological differences that may impact liver disease progression. These findings are strong arguments to further optimize clinical management and to promote vaccination in HIV-infected patients.

Predictors of increasing BMI during the course of diabetes in children and adolescents with type 1 diabetes: data from the German/Austrian DPV multicentre survey.

PubMed

Fröhlich-Reiterer, Elke E; Rosenbauer, Joachim; Bechtold-Dalla Pozza, Susanne; Hofer, Sabine E; Schober, Edith; Holl, Reinhard W

2014-08-01

Increased weight gain has been reported prior to disease onset (accelerator hypothesis) and as a side effect of intensified insulin therapy in type 1 diabetes (T1D). Paediatric studies are complicated by the age-dependency and gender-dependency of BMI, and also by a trend towards obesity in the general population. The aim of this study was to evaluate factors related to the increase in BMI during the course of diabetes in children and adolescents with T1D in a large multicentre survey. Within the DPV database (Diabetespatienten Verlaufsdokumentation) a standardised, prospective, computer-based documentation programme, data of 53,108 patients with T1D, aged <20 years, were recorded in 248 centres. 12,774 patients (53% male, mean age 13.4±3.9, mean diabetes duration 4.7±3.0 years and mean age at diabetes onset 8.7±4.0 years) were included in this analysis. Population-based German reference data were used to calculate BMI-SDS and define overweight and obesity. 12.5% of T1D patients were overweight and 2.8% were obese. Multiple longitudinal regression analysis revealed that female gender, low BMI at diabetes onset, intensified insulin therapy and higher insulin dose, as well as pubertal diabetes onset, long diabetes duration and onset in earlier calendar years among girls, were related to higher BMI-SDS increase during the course of diabetes (p<0.01; all). Intensified insulin regimen is associated with weight gain during T1D treatment, in addition to demographic variables. Optimisation of diabetes management, especially in females, might limit weight gain in order to reduce overweight and obesity together with comorbidities among paediatric T1D patients. 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.

Fixation using alternative implants for the treatment of hip fractures (FAITH): design and rationale for a multi-centre randomized trial comparing sliding hip screws and cancellous screws on revision surgery rates and quality of life in the treatment of femoral neck fractures

PubMed Central

2014-01-01

Background Hip fractures are a common type of fragility fracture that afflict 293,000 Americans (over 5,000 per week) and 35,000 Canadians (over 670 per week) annually. Despite the large population impact the optimal fixation technique for low energy femoral neck fractures remains controversial. The primary objective of the FAITH study is to assess the impact of cancellous screw fixation versus sliding hip screws on rates of revision surgery at 24 months in individuals with femoral neck fractures. The secondary objective is to determine the impact on health-related quality of life, functional outcomes, health state utilities, fracture healing, mortality and fracture-related adverse events. Methods/Design FAITH is a multi-centre, multi-national randomized controlled trial utilizing minimization to determine patient allocation. Surgeons in North America, Europe, Australia, and Asia will recruit a total of at least 1,000 patients with low-energy femoral neck fractures. Using central randomization, patients will be allocated to receive surgical treatment with cancellous screws or a sliding hip screw. Patient outcomes will be assessed at one week (baseline), 10 weeks, 6, 12, 18, and 24 months post initial fixation. We will independently adjudicate revision surgery and complications within 24 months of the initial fixation. Outcome analysis will be performed using a Cox proportional hazards model and likelihood ratio test. Discussion This study represents major international efforts to definitively resolve the treatment of low-energy femoral neck fractures. This trial will not only change current Orthopaedic practice, but will also set a benchmark for the conduct of future Orthopaedic trials. Trial registration The FAITH trial is registered at ClinicalTrials.gov (Identifier NCT00761813). PMID:24965132

Integrative medicine for subacute stroke rehabilitation: a study protocol for a multicentre, randomised, controlled trial.

PubMed

Fang, Jianqiao; Chen, Lifang; Chen, Luni; Wang, Chao; Keeler, Crystal Lynn; Ma, Ruijie; Xu, Shouyu; Shen, Laihua; Bao, Yehua; Ji, Conghua

2014-12-04

Many patients with stroke receive integrative medicine in China, which includes the basic treatment of Western medicine and routine rehabilitation, in conjunction with acupuncture and Chinese medicine. The question of whether integrative medicine is efficacious for stroke rehabilitation is still controversial and very little research currently exists on the integrated approach for this condition. Consequently, we will conduct a multicentre, randomised, controlled, assessor-blinded clinical trial to assess the effectiveness of integrative medicine on stroke rehabilitation. 360 participants recruited from three large Chinese medical hospitals in Zhejiang Province will be randomly divided into the integrative medicine rehabilitation (IMR) group and the conventional rehabilitation (CR) group in a 1:1 ratio. Participants in the IMR group will receive acupuncture and Chinese herbs in addition to basic Western medicine and rehabilitation treatment. The CR group will not receive acupuncture and Chinese herbal medicine. The assessment data will be collected at baseline, 4 and 8 weeks postrandomisation, and then at 12 weeks' follow-up. The primary outcome is measured by the Modified Barthel Index. The secondary outcomes are the National Institutes of Health Stroke Scale (NIHSS), Fugl-Meyer Assessment, the mini-mental state examination and Montreal Cognitive, Hamilton's Depression Scale and Self-Rating Depression Scale, and the incidence of adverse events. Ethical approval was obtained from ethics committees of three hospitals. The results will be disseminated in a peer-reviewed journal and presented at international congresses. The results will also be disseminated to patients by telephone, during follow-up calls inquiring on patient's post-study health status. Chinese Clinical Trial Register: ChiCTR-TRC-12001972, http://www.chictr.org/en/proj/show.aspx?proj=2561. 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.

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.

Phlebitis risk varies by peripheral venous catheter site and increases after 96 hours: a large multi-centre prospective study.

PubMed

Cicolini, Giancarlo; Manzoli, Lamberto; Simonetti, Valentina; Flacco, Maria Elena; Comparcini, Dania; Capasso, Lorenzo; Di Baldassarre, Angela; Eltaji Elfarouki, Ghaleb

2014-11-01

This multi-centre prospective field study evaluated whether peripheral venous catheter site of insertion influences the risk of catheter-related phlebitis. Potential predictors of phlebitis were also investigated. Millions of patients worldwide use peripheral venous catheters, which frequently cause local complications including phlebitis, infection and obstruction. Although phlebitis predictors have been broadly investigated, uncertainties remain on the potential effect of cannulation anatomical site, duration and the appropriate time for catheter removal. A prospective cohort design was carried out from January-June 2012. The clinical course of each patient who received a new peripheral venous catheter for any cause in five Italian hospitals was followed by trained nurses until catheter removal. The presence of phlebitis was assessed every 24 hours using the Visual Infusion Phlebitis score. Analyses were based upon multilevel mixed-effects regression. The final sample consisted of 1498 patients. The average time for catheters in situ was 65·6 hours and 23·6% of the catheters were in place beyond 96 hours. Overall phlebitis incidence was 15·4%, 94·4% of which were grade 1. The likelihood of phlebitis independently increased with increasing catheter duration, being highest after 96 hours. Compared with patients with catheter placed in the dorsum of the hand (22·8% of the sample), those with the catheter located in the antecubital fossa (34·1%) or forearm were less likely to have a phlebitis of any grade. Antecubital fossa and forearm veins may be preferential sites for peripheral venous cannulation. Our results support Centers for Disease Control and Prevention recommendations to replace catheters in adults no later than 96 hours. A relevant proportion of healthcare personnel did not adhere to such guidelines - more attention to this issue is required. © 2014 John Wiley & Sons Ltd.

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.

Utility of prior cultures in predicting antibiotic resistance of bloodstream infections due to Gram-negative pathogens: a multicentre observational cohort study.

PubMed

MacFadden, D R; Coburn, B; Shah, N; Robicsek, A; Savage, R; Elligsen, M; Daneman, N

2018-05-01

Appropriate empiric antibiotic therapy in patients with bloodstream infections due to Gram-negative pathogens can improve outcomes. We evaluated the utility of prior microbiologic results for guiding empiric treatment in Gram-negative bloodstream infections. We conducted a multicentre observational cohort study in two large health systems in Canada and the United States, including 1832 hospitalized patients with Gram-negative bloodstream infection (community, hospital and intensive care unit acquired) from April 2010 to March 2015. Among 1832 patients with Gram-negative bloodstream infection, 28% (n = 504) of patients had a documented prior Gram-negative organism from a nonscreening culture within the previous 12 months. A most recent prior Gram-negative organism resistant to a given antibiotic was strongly predictive of the current organism's resistance to the same antibiotic. The overall specificity was 0.92 (95% confidence interval (CI) 0.91-0.93), and positive predictive value was 0.66 (95% CI 0.61-0.70) for predicting antibiotic resistance. Specificities and positive predictive values ranged from 0.77 to 0.98 and 0.43 to 0.78, respectively, across different antibiotics, organisms and patient subgroups. Increasing time between cultures was associated with a decrease in positive predictive value but not specificity. An heuristic based on a prior resistant Gram-negative pathogen could have been applied to one in four patients and in these patients would have changed therapy in one in five. In patients with a bloodstream infection with a Gram-negative organism, identification of a most recent prior Gram-negative organism resistant to a drug of interest (within the last 12 months) is highly specific for resistance and should preclude use of that antibiotic. Copyright © 2017 European Society of Clinical Microbiology and Infectious Diseases. Published by Elsevier Ltd. All rights reserved.

Comparative evaluation of saliva collection methods for proteome analysis.

PubMed

Golatowski, Claas; Salazar, Manuela Gesell; Dhople, Vishnu Mukund; Hammer, Elke; Kocher, Thomas; Jehmlich, Nico; Völker, Uwe

2013-04-18

Saliva collection devices are widely used for large-scale screening approaches. This study was designed to compare the suitability of three different whole-saliva collection approaches for subsequent proteome analyses. From 9 young healthy volunteers (4 women and 5 men) saliva samples were collected either unstimulated by passive drooling or stimulated using a paraffin gum or Salivette® (cotton swab). Saliva volume, protein concentration and salivary protein patterns were analyzed comparatively. Samples collected using paraffin gum showed the highest saliva volume (4.1±1.5 ml) followed by Salivette® collection (1.8±0.4 ml) and drooling (1.0±0.4 ml). Saliva protein concentrations (average 1145 μg/ml) showed no significant differences between the three sampling schemes. Each collection approach facilitated the identification of about 160 proteins (≥2 distinct peptides) per subject, but collection-method dependent variations in protein composition were observed. Passive drooling, paraffin gum and Salivette® each allows similar coverage of the whole saliva proteome, but the specific proteins observed depended on the collection approach. Thus, only one type of collection device should be used for quantitative proteome analysis in one experiment, especially when performing large-scale cross-sectional or multi-centric studies. Copyright © 2013 Elsevier B.V. All rights reserved.

Data warehousing methods and processing infrastructure for brain recovery research.

PubMed

Gee, T; Kenny, S; Price, C J; Seghier, M L; Small, S L; Leff, A P; Pacurar, A; Strother, S C

2010-09-01

In order to accelerate translational neuroscience with the goal of improving clinical care it has become important to support rapid accumulation and analysis of large, heterogeneous neuroimaging samples and their metadata from both normal control and patient groups. We propose a multi-centre, multinational approach to accelerate the data mining of large samples and facilitate data-led clinical translation of neuroimaging results in stroke. Such data-driven approaches are likely to have an early impact on clinically relevant brain recovery while we simultaneously pursue the much more challenging model-based approaches that depend on a deep understanding of the complex neural circuitry and physiological processes that support brain function and recovery. We present a brief overview of three (potentially converging) approaches to neuroimaging data warehousing and processing that aim to support these diverse methods for facilitating prediction of cognitive and behavioral recovery after stroke, or other types of brain injury or disease.

Antibiotic resistance and population structure of cystic fibrosis Pseudomonas aeruginosa isolates from a Spanish multi-centre study.

PubMed

López-Causapé, Carla; de Dios-Caballero, Juan; Cobo, Marta; Escribano, Amparo; Asensio, Óscar; Oliver, Antonio; Del Campo, Rosa; Cantón, Rafael; Solé, Amparó; Cortell, Isidoro; Asensio, Oscar; García, Gloria; Martínez, María Teresa; Cols, María; Salcedo, Antonio; Vázquez, Carlos; Baranda, Félix; Girón, Rosa; Quintana, Esther; Delgado, Isabel; de Miguel, María Ángeles; García, Marta; Oliva, Concepción; Prados, María Concepción; Barrio, María Isabel; Pastor, María Dolores; Olveira, Casilda; de Gracia, Javier; Álvarez, Antonio; Escribano, Amparo; Castillo, Silvia; Figuerola, Joan; Togores, Bernat; Oliver, Antonio; López, Carla; de Dios Caballero, Juan; Tato, Marta; Máiz, Luis; Suárez, Lucrecia; Cantón, Rafael

2017-09-01

The first Spanish multi-centre study on the microbiology of cystic fibrosis (CF) was conducted from 2013 to 2014. The study involved 24 CF units from 17 hospitals, and recruited 341 patients. The aim of this study was to characterise Pseudomonas aeruginosa isolates, 79 of which were recovered from 75 (22%) patients. The study determined the population structure, antibiotic susceptibility profile and genetic background of the strains. Fifty-five percent of the isolates were multi-drug-resistant, and 16% were extensively-drug-resistant. Defective mutS and mutL genes were observed in mutator isolates (15.2%). Considerable genetic diversity was observed by pulsed-field gel electrophoresis (70 patterns) and multi-locus sequence typing (72 sequence types). International epidemic clones were not detected. Fifty-one new and 14 previously described array tube (AT) genotypes were detected by AT technology. This study found a genetically unrelated and highly diverse CF P. aeruginosa population in Spain, not represented by the epidemic clones widely distributed across Europe, with multiple combinations of virulence factors and high antimicrobial resistance rates (except for colistin). Copyright © 2017 Elsevier B.V. and International Society of Chemotherapy. All rights reserved.

Ultrasound in polycystic ovary syndrome--the measuring of ovarian stroma and relationship with circulating androgens: results of a multicentric study.

PubMed

Fulghesu, A M; Angioni, S; Frau, E; Belosi, C; Apa, R; Mioni, R; Xamin, N; Capobianco, G P; Dessole, S; Fruzzetti, F; Lazzarini, V; Minerba, L; Melis, G B; Lanzone, A

2007-09-01

The introduction of transvaginal approach in ultrasound (US) has enabled the accurate evaluation of the structure of the ovary and stroma. Stroma represents an acknowledged US marker for polycystic ovary syndrome (PCOS). The proportion revealed between the stroma and the ovary surface in the median section (S/A ratio) had been indicated as a reliable marker for hyperandrogenism. In order to verify the feasibility of this determination in routine use and to confirm the efficacy of S/A ratio in predicting hyperandrogenism in PCOS, a multicentric study was performed in association with five Italian research groups. A total of 418 subjects of fertile age presenting oligomenorrhoea or secondary amenorrhoea, enlarged ovaries measuring >10 cm(3) and/or >12 follicles measuring 2-9 mm in diameter took part in the study. Clinical, US and hormonal evaluations were performed in the early follicular phase or on random days in amenorrhoeic subjects. US assessment included ovarian volume, follicle number, ovarian and stroma area in median section. The hormonal study included a baseline plasma determination of LH, FSH, estradiol (E(2)), androstenedione (A), testosterone (T), dehydroepiandrosteronesulphate, 17-hydroxy-progesterone, sex hormone-binding globulin and prolactin. Correlations and receiver operator curves were used in statistical analysis of data. S/A was found to be the best significant predictor of elevated A and T levels. In order to ascertain significant cut-off values in relation to A and T levels Youden indexes were calculated and indicated 0.32 as the best cut-off for the S/A ratio. This work underlines the importance of stroma measure in improving US diagnosis of PCOS and suggest that this parameter may be used in routine clinical practice. In fact, multicentre study demonstrated the easy feasibility of such procedure without need of sophisticated machines or intensive training for operators.

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's disease associated with inherited epidermolysis bullosa.

PubMed

Kawakami, Yoshio; Nishibu, Akiko; Kikuchi, Satoshi; Ohtsuka, Mikio; Nakamura, Koichiro; Nozawa, Yoshihiro; Abe, Masafumi; Iwatsuki, Keiji; Kaneko, Fumio

2003-09-01

Multicentric Castleman's disease (MCD) is a rare disorder characterized by fever, polyclonal hypergammaglobulinemia, and generalized lymphadenopathy. It has three histological characteristics: a recognizable architecture, germinal center abnormalities, and plasmacytosis. Inherited epidermolysis bullosa (EB) is also a rare disorder caused by a genetic defect. We report a 43-year-old patient with dystrophic EB, non-Hallopeau-Siemens recessive type or dominant type, displaying clinicopathologic features of MCD. In addition, his serum interleukin-6, which is thought to be responsible for the clinical symptoms in MCD, was elevated.

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.

Phantom for assessment of fat suppression in large field-of-view diffusion-weighted magnetic resonance imaging

NASA Astrophysics Data System (ADS)

Winfield, J. M.; Douglas, N. H. M.; deSouza, N. M.; Collins, D. J.

2014-05-01

We present the development and application of a phantom for assessment and optimization of fat suppression over a large field-of-view in diffusion-weighted magnetic resonance imaging at 1.5 T and 3 T. A Perspex cylinder (inner diameter 185 mm, height 300 mm) which contains a second cylinder (inner diameter 140 mm) was constructed. The inner cylinder was filled with water doped with copper sulphate and sodium chloride and the annulus was filled with corn oil, which closely matches the spectrum and longitudinal relaxation times of subcutaneous abdominal fat. Placement of the phantom on the couch at 45° to the z-axis presented an elliptical cross-section, which was of a similar size and shape to axial abdominal images. The use of a phantom for optimization of fat suppression allowed quantitative comparison between studies without the differences introduced by variability between human subjects. We have demonstrated that the phantom is suitable for selection of inversion delay times, spectral adiabatic inversion recovery delays and assessment of combinatorial methods of fat suppression. The phantom is valuable in protocol development and the assessment of new techniques, particularly in multi-centre trials.

An evaluation of the feasibility, cost and value of information of a multicentre randomised controlled trial of intravenous immunoglobulin for sepsis (severe sepsis and septic shock): incorporating a systematic review, meta-analysis and value of information analysis.

PubMed

Soares, M O; Welton, N J; Harrison, D A; Peura, P; Shankar- Hari, M; Harvey, S E; Madan, J J; Ades, A E; Palmer, S J; Rowan, K M

2012-01-01

Sepsis is a syndrome characterised by a systemic inflammatory response to infection that leads to rapid acute organ failure and potentially rapid decline to death. Intravenous immunoglobulin (IVIG), a blood product derived from human donor blood, has been proposed as an adjuvant therapy for sepsis. To describe current practice in the management of adult patients severely ill with sepsis (severe sepsis or septic shock) in the UK; to assess the clinical effectiveness of IVIG for severe sepsis and septic shock and to obtain the appropriate inputs for the relative efficacy parameters, and the key uncertainties associated with these parameters, required to populate the decision model; to develop a decision-analytic model structure and identify key parameter inputs consistent with the decision problem and relevant to an NHS setting; and to populate the decision model and determine the cost-effectiveness of IVIG and to estimate the value of additional primary research. Existing literature on IVIG and severe sepsis. Existing case-mix and outcome data on critical care admissions. Survey data on management of admissions with severe sepsis. Databases searched for clinical effectiveness were Cochrane Infectious Diseases Group Specialized Trials Register, the Cochrane Trials Register, MEDLINE and EMBASE. Dates searched were 1 January 2002 to 2 October 2009 to update previous Cochrane review. Databases searched for cost-effectiveness were NHS Economic Evaluation Database (NHS EED) to 2 October 2009, MEDLINE, MEDLINE In-Process & Other Non-Indexed Citations and EMBASE to 20 October 2009. Systematic literature searching with data extraction, descriptive analysis and clinical effectiveness and cost-effectiveness modelling of IVIG in severe sepsis. Additional primary data analysis. Expected value of information (EVI) analysis. Our meta-analysis, the first to simultaneously allow for type of IVIG (IVIG or immunoglobulin M-enriched polyclonal IVIG), choice of control (no treatment or albumin), study quality/publication bias and other potential covariates, indicated that the treatment effect of IVIG on mortality for patients with severe sepsis is borderline significant with a large degree of heterogeneity in treatment effect between individual studies. Modelling indicated that there were issues with bias associated with trial methodology, publication and small-study effects with the current evidence. The large degree of heterogeneity in treatment effects between studies, however, could be explained (best-fitting model) by a measure of study quality (i.e. use of albumin as control - as an indicator of proper blinding to treatment as a proxy for study quality - associated with decreased effect) and duration of IVIG therapy (longer duration associated with increased effect). In-depth discussion within the Expert Group on duration of IVIG therapy, with daily dose and total dose also clearly inter-related, indicated no clear clinical rationale for this association and exposed a lack of evidence on the understanding of the mechanism of action of IVIG in severe sepsis. Although the EVI analyses suggested substantial expected net benefit from a large, multicentre randomised controlled trial (RCT) evaluating the clinical effectiveness of IVIG, the remaining uncertainties around the design of such a study mean that we are unable to recommend it at this time. As has been identified in previous meta-analyses, there are issues with the methodological quality of the available evidence. Although the results highlight the value for money obtained in conducting further primary research in this area, the biggest limitation for such research regards the uncertainties over the mechanism of action of IVIG and the heterogeneous nature of severe sepsis. Resolving these would allow for better definition of the plausibility of the effectiveness scenarios presented and, consequently, a better understanding of the cost-effectiveness of this treatment. This information would also inform the design of future, primary evaluative research. Our recommendations for future research focus on filling the knowledge gaps to inform a future multicentre RCT prior to recommending its immediate design and conduct. The National Institute for Health Research Health Technology Assessment programme.

Aneurysmal SubArachnoid Hemorrhage—Red Blood Cell Transfusion And Outcome (SAHaRA): a pilot randomised controlled trial protocol

PubMed Central

English, Shane W; Fergusson, D; Chassé, M; Lauzier, F; Griesdale, D; Algird, A; Kramer, A; Tinmouth, A; Lum, C; Sinclair, J; Marshall, S; Dowlatshahi, D; Boutin, A; Pagliarello, G; McIntyre, L A

2016-01-01

Introduction Anaemia is common in aneurysmal subarachnoid haemorrhage (aSAH) and is a potential critical modifiable factor affecting secondary injury. Despite physiological evidence and management guidelines that support maintaining a higher haemoglobin level in patients with aSAH, current practice is one of a more restrictive approach to transfusion. The goal of this multicentre pilot trial is to determine the feasibility of successfully conducting a red blood cell (RBC) transfusion trial in adult patients with acute aSAH and anaemia (Hb ≤100 g/L), comparing a liberal transfusion strategy (Hb ≤100 g/L) with a restrictive strategy (Hb ≤80 g/L) on the combined rate of death and severe disability at 12 months. Methods Design This is a multicentre open-label randomised controlled pilot trial at 5 academic tertiary care centres. Population We are targeting adult aSAH patients within 14 days of their initial bleed and with anaemia (Hb ≤110 g/L). Randomisation Central computer-generated randomisation, stratified by centre, will be undertaken from the host centre. Randomisation into 1 of the 2 treatment arms will occur when the haemoglobin levels of eligible patients fall to ≤100 g/L. Intervention Patients will be randomly assigned to either a liberal (threshold: Hb ≤100 g/L) or a restrictive transfusion strategy (threshold: Hb ≤80 g/L). Outcome Primary: Centre randomisation rate over the study period. Secondary: (1) transfusion threshold adherence; (2) study RBC transfusion protocol adherence; and (3) outcome assessment including vital status at hospital discharge, modified Rankin Score at 6 and 12 months and Functional Independence Measure and EuroQOL Quality of Life Scale scores at 12 months. Outcome measures will be reported in aggregate. Ethics and dissemination The study protocol has been approved by the host centre (OHSN-REB 20150433-01H). This study will determine the feasibility of conducting the large pragmatic RCT comparing 2 RBC transfusion strategies examining the effect of a liberal strategy on 12-month outcome following aSAH. Trial registration number NCT02483351; Pre-results. PMID:27927658

Prevalence of adherence to treatment in homebound elderly people in primary health care: a descriptive, cross-sectional, multicentre study.

PubMed

Cárdenas-Valladolid, Juan; Martín-Madrazo, Carmen; Salinero-Fort, Miguel A; Carrillo de-Santa Pau, Enrique; Abánades-Herranz, Juan C; de Burgos-Lunar, Carmen

2010-08-01

Adherence to the therapeutic plan is one of the most important health issues in terms of treatment efficacy, healthcare costs and patient safety. Unfortunately, homebound elderly patients are especially vulnerable to nonadherence because they have higher morbidity rates combined with cognitive and social problems that hinder their correct use of drugs. The level of therapeutic adherence in homebound elderly people has not been adequately studied. To estimate the prevalence of therapeutic adherence, using the Morisky-Green test, in homebound elderly patients taking polypharmacy (defined as use of four or more drugs), and to study the factors associated with adherence. This was a descriptive, cross-sectional, multicentre study. A total of 327 patients were selected by random start systematic sampling from the total number of homebound patients taking four or more drugs in Healthcare Area 4 of the Madrid Autonomous Region, Spain. Through an in-home survey of patients and their caregivers, information was gathered on sociodemographic data, co-morbidities, number of hospital admissions, responsibility for purchasing and preparation of the medication, level of cognitive impairment (Pfeiffer questionnaire), functional dependence in activities of daily living (Katz Index), knowledge of the disease (Batalla test), adherence to treatment (Morisky-Green test), visual and auditory perception, and caregiver burden (Zarit interview). Of the homebound patients, 65.7% (95% CI 60.6, 70.9) had good adherence to treatment. The variables most negatively associated with therapeutic adherence, after adjustment for age, sex, number of drugs, knowledge of the disease, and cognitive function, were a large caregiver burden (odds ratio [OR] 3.09; 95% CI 1.75, 5.48) and impaired hearing (OR 2.00; 95% CI 1.17, 3.40). There was also a trend toward a positive association between nonadherence and patients aged <85 years (OR 1.57; 95% CI 0.93, 2.65) and patients who had nine or more drug prescriptions (OR 1.59; 95% CI 0.96, 2.65). Poor therapeutic adherence in homebound elderly patients receiving polypharmacy is a serious problem affecting one of every three individuals concerned, and is directly related to caregiver burden, regardless of age, sex, cognitive status or number of drugs administered.

A new MRI rating scale for progressive supranuclear palsy and multiple system atrophy: validity and reliability

PubMed Central

Rolland, Yan; Vérin, Marc; Payan, Christine A; Duchesne, Simon; Kraft, Eduard; Hauser, Till K; Jarosz, Josef; Deasy, Neil; Defevbre, Luc; Delmaire, Christine; Dormont, Didier; Ludolph, Albert C; Bensimon, Gilbert

2011-01-01

Aim To evaluate a standardised MRI acquisition protocol and a new image rating scale for disease severity in patients with progressive supranuclear palsy (PSP) and multiple systems atrophy (MSA) in a large multicentre study. Methods The MRI protocol consisted of two-dimensional sagittal and axial T1, axial PD, and axial and coronal T2 weighted acquisitions. The 32 item ordinal scale evaluated abnormalities within the basal ganglia and posterior fossa, blind to diagnosis. Among 760 patients in the study population (PSP=362, MSA=398), 627 had per protocol images (PSP=297, MSA=330). Intra-rater (n=60) and inter-rater (n=555) reliability were assessed through Cohen's statistic, and scale structure through principal component analysis (PCA) (n=441). Internal consistency and reliability were checked. Discriminant and predictive validity of extracted factors and total scores were tested for disease severity as per clinical diagnosis. Results Intra-rater and inter-rater reliability were acceptable for 25 (78%) of the items scored (≥0.41). PCA revealed four meaningful clusters of covarying parameters (factor (F) F1: brainstem and cerebellum; F2: midbrain; F3: putamen; F4: other basal ganglia) with good to excellent internal consistency (Cronbach α 0.75–0.93) and moderate to excellent reliability (intraclass coefficient: F1: 0.92; F2: 0.79; F3: 0.71; F4: 0.49). The total score significantly discriminated for disease severity or diagnosis; factorial scores differentially discriminated for disease severity according to diagnosis (PSP: F1–F2; MSA: F2–F3). The total score was significantly related to survival in PSP (p<0.0007) or MSA (p<0.0005), indicating good predictive validity. Conclusions The scale is suitable for use in the context of multicentre studies and can reliably and consistently measure MRI abnormalities in PSP and MSA. Clinical Trial Registration Number The study protocol was filed in the open clinical trial registry (http://www.clinicaltrials.gov) with ID No NCT00211224. PMID:21386111

The surface glycoprotein of a natural feline leukemia virus subgroup A variant, FeLV-945, as a determinant of disease outcome.

PubMed

Bolin, Lisa L; Ahmad, Shamim; Levy, Laura S

2011-10-15

Feline leukemia virus (FeLV) is a natural retrovirus of domestic cats associated with degenerative, proliferative and malignant diseases. Studies of FeLV infection in a cohort of naturally infected cats were undertaken to examine FeLV variation, the selective pressures operative in FeLV infection that lead to predominance of natural variants, and the consequences for infection and disease progression. A unique variant, designated FeLV-945, was identified as the predominant isolate in the cohort and was associated with non-T-cell diseases including multicentric lymphoma. FeLV-945 was assigned to the FeLV-A subgroup based on sequence analysis and receptor utilization, but was shown to differ in sequence from a prototype member of FeLV-A, designated FeLV-A/61E, in the long terminal repeat (LTR) and the surface glycoprotein gene (SU). A unique sequence motif in the FeLV-945 LTR was shown to function as a transcriptional enhancer and to confer a replicative advantage. The FeLV-945 SU protein was observed to differ in sequence as compared to FeLV-A/61E within functional domains known to determine receptor selection and binding. Experimental infection of newborn cats was performed using wild type FeLV-A/61E or recombinant FeLV-A/61E in which the LTR (61E/945L) or LTR and SU (61E/945SL) were exchanged for that of FeLV-945. Infection with either FeLV-A/61E or 61E/945L resulted in T-cell lymphoma of the thymus, although 61E/945L caused disease significantly more rapidly. In contrast, infection with 61E/945SL resulted in the rapid induction of a multicentric lymphoma of B-cell origin, thus recapitulating the outcome of natural infection and implicating FeLV-945 SU as a determinant of disease outcome. Recombinant FeLV-B was detected infrequently and at low levels in multicentric lymphomas, and was thereby not implicated in disease induction. Preliminary studies of receptor interaction indicated that virus particles bearing FeLV-945 SU bind to the FeLV-A receptor more efficiently than do particles bearing FeLV-A/61E SU, and that soluble SU proteins expressed from the viruses demonstrate the same differential binding phenotype. Preliminary mutational analysis of FeLV-945 was performed by exchanging regions containing either the primary receptor binding determinant, VRA, the secondary determinant, VRB, or a proline-rich region, PRR, with that of FeLV-A/61E. Results implicated a region containing VRA as a minor contributor, while a region containing VRB largely conferred increased binding efficiency. Copyright © 2011 Elsevier B.V. All rights reserved.

Retrospective analysis for treatment of naïve canine multicentric lymphoma with a 15-week, maintenance-free CHOP protocol.

PubMed

Curran, K; Thamm, D H

2016-08-01

Standard of care treatment of dogs with multicentric lymphoma includes combination chemotherapy with cyclophosphamide, doxorubicin, vincristine and prednisone (CHOP); however, owners may be hesitant to commit the resources necessary to complete a lengthy, multi-drug protocol. One hundred thirty-four client-owned dogs with multicentric lymphoma were treated with a 15-week CHOP chemotherapy protocol. The overall response rate was 98% with 104 dogs experiencing a complete response (CR). The median progression-free survival (PFS) time for all dogs was 176 days, and the median disease-specific overall survival time was 311 days. Prognostic factors identified on multivariate analysis as significant for PFS included substage, immunophenotype, hospitalization for adverse events, need for dose reduction, presence of neutrophilia at diagnosis, presence of anemia and experiencing a CR as best response to therapy. In conclusion, this protocol may be a viable alternative to CHOP protocols using a larger number of treatments. © 2015 John Wiley & Sons Ltd.

Should Aggressive Surgical Local Control Be Attempted in All Patients with Metastatic or Pelvic Ewing's Sarcoma?

PubMed Central

Thorpe, Steven W.; Weiss, Kurt R.; Goodman, Mark A.; Heyl, Alma E.; McGough, Richard L.

2012-01-01

In previous reports, patients with Ewing's sarcoma received radiation therapy (XRT) for definitive local control because metastatic disease and pelvic location were thought to preclude aggressive local treatment. We sought to determine if single-site metastatic disease should be treated differently from multicentric-metastatic disease. We also wanted to reinvestigate the impact of XRT, pelvic location, and local recurrence on outcomes. Our results demonstrated a significant difference in overall survival (OS) between patients with either localized disease or a single-metastatic site and patients with multicentric-metastatic disease (P = 0.004). Local control was also found to be an independent predictor of outcomes as demonstrated by a significant difference in OS between those with and without local recurrence (P = 0.001). Axial and pelvic location did not predict a decreased OS. Based on these results, we concluded that pelvic location and the diagnosis of metastatic disease at diagnosis should not preclude aggressive local control, except in cases of multicentric-metastatic disease. PMID:22550427

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.

Decision aid on breast cancer screening reduces attendance rate: results of a large-scale, randomized, controlled study by the DECIDEO group

PubMed Central

Bourmaud, Aurelie; Soler-Michel, Patricia; Oriol, Mathieu; Regnier, Véronique; Tinquaut, Fabien; Nourissat, Alice; Bremond, Alain; Moumjid, Nora; Chauvin, Franck

2016-01-01

Controversies regarding the benefits of breast cancer screening programs have led to the promotion of new strategies taking into account individual preferences, such as decision aid. The aim of this study was to assess the impact of a decision aid leaflet on the participation of women invited to participate in a national breast cancer screening program. This Randomized, multicentre, controlled trial. Women aged 50 to 74 years, were randomly assigned to receive either a decision aid or the usual invitation letter. Primary outcome was the participation rate 12 months after the invitation. 16 000 women were randomized and 15 844 included in the modified intention-to-treat analysis. The participation rate in the intervention group was 40.25% (3174/7885 women) compared with 42.13% (3353/7959) in the control group (p = 0.02). Previous attendance for screening (RR = 6.24; [95%IC: 5.75-6.77]; p < 0.0001) and medium household income (RR = 1.05; [95%IC: 1.01-1.09]; p = 0.0074) were independently associated with attendance for screening. This large-scale study demonstrates that the decision aid reduced the participation rate. The decision aid activate the decision making process of women toward non-attendance to screening. These results show the importance of promoting informed patient choices, especially when those choices cannot be anticipated. PMID:26883201

Indicators of quality of antenatal care: a pilot study.

PubMed

Vause, S; Maresh, M

1999-03-01

To pilot a list of indicators of quality of antenatal care across a range of maternity care settings. For each indicator to determine what is achieved in current clinical practice, to facilitate the setting of audit standards and calculation of appropriate sample sizes for audit. A multicentre retrospective observational study. Nine maternity units in the United Kingdom. 20,771 women with a singleton pregnancy, who were delivered between 1 August 1994 and 31 July 1995. Nine of the eleven suggested indicators were successfully piloted. Two indicators require further development. In seven of the nine hospitals external cephalic version was not commonly performed. There were wide variations in the proportions of women screened for asymptomatic bacteriuria. Screening of women from ethnic minorities for haemoglobinopathy was more likely in hospitals with a large proportion of non-caucasian women. A large number of Rhesus negative women did not have a Rhesus antibody check performed after 28 weeks of gestation and did not receive anti-D immunoglobulin after a potentially sensitising event during pregnancy. As a result of the study appropriate sample sizes for future audit could be calculated. Measuring the extent to which evidence-based interventions are used in routine clinical practice provides a more detailed picture of the strengths and weaknesses in an antenatal service than traditional outcomes such as perinatal mortality rates. Awareness of an appropriate sample size should prevent waste of time and resources on inconclusive audits.

Understanding Resident Ratings of Teaching in the Workplace: A Multi-Centre Study

ERIC Educational Resources Information Center

Fluit, Cornelia R. M. G.; Feskens, Remco; Bolhuis, Sanneke; Grol, Richard; Wensing, Michel; Laan, Roland

2015-01-01

Providing clinical teachers with feedback about their teaching skills is a powerful tool to improve teaching. Evaluations are mostly based on questionnaires completed by residents. We investigated to what extent characteristics of residents, clinical teachers, and the clinical environment influenced these evaluations, and the relation between…

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.

The utility of e-Learning to support training for a multicentre bladder online adaptive radiotherapy trial (TROG 10.01-BOLART).

PubMed

Foroudi, Farshad; Pham, Daniel; Bressel, Mathias; Tongs, David; Rolfo, Aldo; Styles, Colin; Gill, Suki; Kron, Tomas

2013-10-01

An e-Learning programme appeared useful for providing training and information regarding a multi-centre image guided radiotherapy trial. The aim of this study is to demonstrate the utility of this e-Learning programme. Modules were created on relevant pelvic anatomy, Cone Beam CT soft tissue recognition and trial details. Radiation therapist participants' knowledge and confidence were evaluated before, at the end of, and after at least 6 weeks of e-Learning (long term). One hundred and eighty-five participants were recruited from 12 centres, with 118 in the first, and 67 in the second cohort. One hundred and forty-six participants had two tests (pre and post e-Learning) and 39 of these had three tests (pre, post, and long term). There was an increase confidence after completion of modules (p<0.001). The first cohort pre scores increased from 67 ± 11 to 79 ± 8 (p<0.001) post. The long term same question score was 73 ± 14 (p=0.025, comparing to pre-test), and different questions' score was 77 ± 13 (p=0.014). In the second cohort, pre-test scores were 64 ± 10, post-test same question score 78 ± 9 (p<0.001) and different questions' score 81 ± 11 (p<0.001). e-Learning for a multi-centre clinical trial was feasible and improved confidence and knowledge. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

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.

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

The value of magnetic resonance imaging as a biomarker for amyotrophic lateral sclerosis: a systematic review.

PubMed

Grolez, G; Moreau, C; Danel-Brunaud, V; Delmaire, C; Lopes, R; Pradat, P F; El Mendili, M M; Defebvre, L; Devos, D

2016-08-27

Amyotrophic lateral sclerosis (ALS) is a fatal, rapidly progressive neurodegenerative disease that mainly affects the motor system. A number of potentially neuroprotective and neurorestorative disease-modifying drugs are currently in clinical development. At present, the evaluation of a drug's clinical efficacy in ALS is based on the ALS Functional Rating Scale Revised, motor tests and survival. However, these endpoints are general, variable and late-stage measures of the ALS disease process and thus require the long-term assessment of large cohorts. Hence, there is a need for more sensitive radiological biomarkers. Various sequences for magnetic resonance imaging (MRI) of the brain and spinal cord have may have value as surrogate biomarkers for use in future clinical trials. Here, we review the MRI findings in ALS, their clinical correlations, and their limitations and potential role as biomarkers. The PubMed database was screened to identify studies using MRI in ALS. We included general MRI studies with a control group and an ALS group and longitudinal studies even if a control group was lacking. A total of 116 studies were analysed with MRI data and clinical correlations. The most disease-sensitive MRI patterns are in motor regions but the brain is more broadly affected. Despite the existing MRI biomarkers, there is a need for large cohorts with long term MRI and clinical follow-up. MRI assessment could be improved by standardized MRI protocols with multicentre studies.

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.

Folliculitis decalvans: a multicentre review of 82 patients.

PubMed

Vañó-Galván, S; Molina-Ruiz, A M; Fernández-Crehuet, P; Rodrigues-Barata, A R; Arias-Santiago, S; Serrano-Falcón, C; Martorell-Calatayud, A; Barco, D; Pérez, B; Serrano, S; Requena, L; Grimalt, R; Paoli, J; Jaén, P; Camacho, F M

2015-09-01

Folliculitis decalvans (FD) is a rare neutrophilic scarring alopecia that represents a therapeutic challenge for dermatologists. To describe the epidemiology, comorbidities, clinical presentation, diagnostic findings and therapeutic options in a large series of patients with FD. This retrospective multicentre review includes patients diagnosed with FD based on clinical and histopathologic findings. The clinical severity was determined by the maximum diameter of the largest alopecic patch (slight: <2 cm, moderate: 2-4.99 cm, severe: 5 cm or more). Response to therapy was assessed as improvement, worsening or stabilization depending on the clinical symptoms (pruritus and trichodynia), inflammatory signs (erythema, pustules and crusts) and the extension of the alopecic patch. Overall, 82 patients (52 males and 30 females) with a mean age of 35 years were included. No significant comorbidities were present. A family history was present in three males. Severe FD was observed in 17 patients (21%). The independent factors associated with severe FD after multivariate analysis were: onset of FD before 25 years of age and presence of pustules. Oral antibiotics (tetracyclines and the combination of clindamycin and rifampicin) improved 90% and 100% of the patients, with a mean duration of response of 4.6 and 7.2 months respectively. The onset of FD before 25 years of age and the presence of pustules within the alopecic patch were associated with severe FD. Tetracyclines and the combination of clindamycin and rifampicin were the most useful treatments. © 2015 European Academy of Dermatology and Venereology.

Multi-centre evaluation of the Determine HIV Combo assay when used for point of care testing in a high risk clinic-based population.

PubMed

Conway, Damian P; Holt, Martin; McNulty, Anna; Couldwell, Deborah L; Smith, Don E; Davies, Stephen C; Cunningham, Philip; Keen, Phillip; Guy, Rebecca

2014-01-01

Determine HIV Combo (DHC) is the first point of care assay designed to increase sensitivity in early infection by detecting both HIV antibody and antigen. We conducted a large multi-centre evaluation of DHC performance in Sydney sexual health clinics. We compared DHC performance (overall, by test component and in early infection) with conventional laboratory HIV serology (fourth generation screening immunoassay, supplementary HIV antibody, p24 antigen and Western blot tests) when testing gay and bisexual men attending four clinic sites. Early infection was defined as either acute or recent HIV infection acquired within the last six months. Of 3,190 evaluation specimens, 39 were confirmed as HIV-positive (12 with early infection) and 3,133 were HIV-negative by reference testing. DHC sensitivity was 87.2% overall and 94.4% and 0% for the antibody and antigen components, respectively. Sensitivity in early infection was 66.7% (all DHC antibody reactive) and the DHC antigen component detected none of nine HIV p24 antigen positive specimens. Median HIV RNA was higher in false negative than true positive cases (238,025 vs. 37,591 copies/ml; p = 0.022). Specificity overall was 99.4% with the antigen component contributing to 33% of false positives. The DHC antibody component detected two thirds of those with early infection, while the DHC antigen component did not enhance performance during point of care HIV testing in a high risk clinic-based population.

INTER-ACT: prevention of pregnancy complications through an e-health driven interpregnancy lifestyle intervention - study protocol of a multicentre randomised controlled trial.

PubMed

Bogaerts, Annick; Ameye, Lieveke; Bijlholt, Margriet; Amuli, Kelly; Heynickx, Dorine; Devlieger, Roland

2017-05-26

Excessive maternal pre-pregnancy and gestational weight gain are related to pregnancy- and birth outcomes. The interpregnancy time window offers a unique opportunity to intervene in order to acquire a healthy lifestyle before the start of a new pregnancy. INTER-ACT is an e-health driven multicentre randomised controlled intervention trial targeting women at high risk of pregnancy- and birth related complications. Eligible women are recruited for the study at day 2 or 3 postpartum. At week 6 postpartum, participants are randomised into the intervention or control arm of the study. The intervention focuses on weight, diet, physical activity and mental well-being, and comprises face-to-face coaching, in which behavioural change techniques are central, and use of a mobile application, which is Bluetooth-connected to a weighing scale and activity tracker. The intervention is rolled out postpartum (4 coaching sessions between week 6 and month 6) and in a new pregnancy (3 coaching sessions, one in each trimester of pregnancy); the mobile app is used throughout the two intervention phases. Data collection includes data from the medical record of the participants (pregnancy outcomes and medical history), anthropometric data (height, weight, waist- and hip circumferences, skinfold thickness and body composition by bio-electrical impedance analysis), data from the mobile app (physical activity and weight; intervention group only) and questionnaires (socio-demographics, breastfeeding, food intake, physical activity, lifestyle, psychosocial factors and process evaluation). Medical record data are collected at inclusion and at delivery of the subsequent pregnancy. All other data are collected at week 6 and month 6 postpartum and every subsequent 6 months until a new pregnancy, and in every trimester in the new pregnancy. Primary outcome is the composite endpoint score of pregnancy-induced hypertension, gestational diabetes mellitus, caesarean section, and large-for-gestational-age infant in the subsequent pregnancy. INTER-ACT is a unique randomised controlled lifestyle intervention trial in its implementation between pregnancies and during the subsequent pregnancy, with an e-health driven approach. ClinicalTrials.gov Identifier: NCT02989142 . Registered August 2016.

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

Effect of personalised citizen assistance for social participation (APIC) on older adults’ health and social participation: study protocol for a pragmatic multicentre randomised controlled trial (RCT)

PubMed Central

Levasseur, Mélanie; Dubois, Marie-France; Filliatrault, Johanne; Vasiliadis, Helen-Maria; Lacasse-Bédard, Joanie; Tourigny, André; Levert, Marie-Josée; Gabaude, Catherine; Lefebvre, Hélène; Berger, Valérie; Eymard, Chantal

2018-01-01

Introduction The challenges of global ageing and the growing burden of chronic diseases require innovative interventions acting on health determinants like social participation. Many older adults do not have equitable opportunities to achieve full social participation, and interventions might underempower their personal and environmental resources and only reach a minority. To optimise current practices, the Accompagnement-citoyen Personnalisé d’Intégration Communautaire (APIC), an intervention demonstrated as being feasible and having positive impacts, needs further evaluation. Methods and analysis A pragmatic multicentre, prospective, two-armed, randomised controlled trial will evaluate: (1) the short-term and long-term effects of the APIC on older adults’ health, social participation, life satisfaction and healthcare services utilisation and (2) its cost-effectiveness. A total of 376 participants restricted in at least one instrumental activity of daily living and living in three large cities in the province of Quebec, Canada, will be randomly assigned to the experimental or control group using a centralised computer-generated random number sequence procedure. The experimental group will receive weekly 3-hour personalised stimulation sessions given by a trained volunteer over the first 12 months. Sessions will encourage empowerment, gradual mobilisation of personal and environmental resources and community integration. The control group will receive the publicly funded universal healthcare services available to all Quebecers. Over 2 years (baseline and 12, 18 and 24 months later), self-administered questionnaires will assess physical and mental health (primary outcome; version 2 of the 36-item Short-Form Health Survey, converted to SF-6D utility scores for quality-adjusted life years), social participation (Social Participation Scale) and life satisfaction (Life Satisfaction Index-Z). Healthcare services utilisation will be recorded and costs of each intervention calculated. Ethics and dissemination The Research Ethics Committee of the CIUSSS Estrie – CHUS has approved the study (MP-31-2018-2424). An informed consent form will be read and signed by all study participants. Findings will be published and presented at conferences. Trial registration number NCT03161860; Pre-results. PMID:29605819

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

Protocol of a multi-centre randomised controlled trial of a web-based information intervention with nurse-delivered telephone support for haematological cancer patients and their support persons.

PubMed

Bryant, Jamie; Sanson-Fisher, Rob; Stevenson, William; Smits, Rochelle; Henskens, Frans; Wei, Andrew; Tzelepis, Flora; D'Este, Catherine; Paul, Christine; Carey, Mariko

2015-04-17

High rates of anxiety, depression and unmet needs are evident amongst haematological cancer patients undergoing treatment and their Support Persons. Psychosocial distress may be minimised by ensuring that patients are sufficiently involved in decision making, provided with tailored information and adequate preparation for potentially threatening procedures. To date, there are no published studies evaluating interventions designed to reduce psychosocial distress and unmet needs specifically in patients with haematological cancers and their Support Persons. This study will examine whether access to a web-based information tool and nurse-delivered telephone support reduces depression, anxiety and unmet information needs for haematological cancer patients and their Support Persons. A non-blinded, parallel-group, multi-centre randomised controlled trial will be conducted to compare the effectiveness of a web-based information tool and nurse-delivered telephone support with usual care. Participants will be recruited from the haematology inpatient wards of five hospitals in New South Wales, Australia. Patients diagnosed with acute myeloid leukaemia, acute lymphoblastic leukaemia, Burkitt's lymphoma, Lymphoblastic lymphoma (B or T cell), or Diffuse Large B-Cell lymphoma and their Support Persons will be eligible to participate. Patients and their Support Persons will be randomised as dyads. Participants allocated to the intervention will receive access to a tailored web-based tool that provides accurate, up-to-date and personalised information about: cancer and its causes; treatment options including treatment procedures information; complementary and alternative medicine; and available support. Patients and Support Persons will complete self-report measures of anxiety, depression and unmet needs at 2, 4, 8 and 12 weeks post-recruitment. Patient and Support Person outcomes will be assessed independently. This study will assess whether providing information and support using web-based and telephone support address the major psychosocial challenges faced by haematological patients and their Support Persons. The approach, if found to be effective, has potential to improve psychosocial outcomes for haematological and other cancer patients, reduce the complexity and burden of meeting patients' psychosocial needs for health care providers with high potential for translation into clinical practice. ACTRN12612000720819.

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/

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/.

Correction to: Incidence of severe sepsis and septic shock in German intensive care units: the prospective, multicentre INSEP study.

PubMed

Marx, Gernot

2018-01-01

The members of the SepNet Critical Care Trials Group were provided in such a way that they could not be indexed as collaborators on PubMed. The publisher apologizes for this error and is pleased to list the members of the group here.

Activity and participation, quality of life and user satisfaction outcomes of environmental control systems and smart home technology: a systematic review.

PubMed

Brandt, Ase; Samuelsson, Kersti; Töytäri, Outi; Salminen, Anna-Liisa

2011-01-01

To examine activity and participation, quality of life, and user satisfaction outcomes of environmental control systems (ECSs) and smart home technology (SHT) interventions for persons with impairments. A systematic review. Seventeen databases, three conference proceedings, and two journals were searched without language or study design restrictions covering the period January 1993 - June 2009. Reviewers selected studies, extracted data, and assessed the methodological quality independently. Of 1739 studies identified, five effect studies and six descriptive studies were included. One study was on SHT and the remainder on ECS; functionalities were overlapping. The studies varied in most aspects, and no synthesis could be drawn. However, ECS/SHT tended to increase study participants' independence, instrumental activities of daily living, socialising, and quality of life. Two studies showed high user satisfaction. The level of evidence was regarded as low, mainly due to small study sizes, lacking confounder control, and a majority of descriptive studies. Due to few and small studies and study diversity, it was not possible to determine whether ECS/SHT have positive outcomes for persons with impairment, even though the technologies seem to be promising. High quality outcomes studies such as randomised controlled trials, when feasible, and large longitudinal multi-centre studies are required.

[Low-dose omega-3 fatty acids as lipid lowering agents in the practice. A field study of ambulatory patients in general practice].

PubMed

Zakaria, B; Bertsch, S

1992-04-10

BASICS: Clinical trials have shown that omega-3 fatty acids are also effective at smaller doses than those so far recommended for lowering lipid concentrations. Testing this finding in a large number of unselected outpatients. Open multicentric trial involving 197 patients with dyslipoproteinemia. Treatment comprised omega-3 fatty acids, 1.1 to 1.4 g per day administered for a period of 12 weeks. After 12 weeks of treatment, serum triglycerides decreased on average by about 23%, total cholesterol by about 10%, and LDL cholesterol by about 5%. HDL cholesterol rose by an average of 16%. The fish oil preparation (Eicosapen, Nycomed, Munich) was well tolerated; a fishy taste and mild gastrointestinal complaints led to discontinuation of treatment in only four cases. It was also found that the effect of omega-3 fatty acids was appreciably greater in hypertensives than in patients with normal blood pressure--not only on systolic and diastolic blood pressure, but also on serum triglycerides and HDL.

Blood Biomarkers in Idiopathic Pulmonary Fibrosis.

PubMed

Guiot, Julien; Moermans, Catherine; Henket, Monique; Corhay, Jean-Louis; Louis, Renaud

2017-06-01

Idiopathic pulmonary fibrosis (IPF) is a progressive and lethal lung disease of unknown origin whose incidence has been increasing over the latest decade partly as a consequence of population ageing. New anti-fibrotic therapy including pirfenidone and nintedanib have now proven efficacy in slowing down the disease. Nevertheless, diagnosis and follow-up of IPF remain challenging. This review examines the recent literature on potentially useful blood molecular and cellular biomarkers in IPF. Most of the proposed biomarkers belong to chemokines (IL-8, CCL18), proteases (MMP-1 and MMP-7), and growth factors (IGBPs) families. Circulating T cells and fibrocytes have also gained recent interest in that respect. Up to now, though several interesting candidates are profiling there has not been a single biomarker, which proved to be specific of the disease and predictive of the evolution (decline of pulmonary function test values, risk of acute exacerbation or mortality). Large scale multicentric studies are eagerly needed to confirm the utility of these biomarkers.

Mitochondrial imaging in live or fixed tissues using a luminescent iridium complex.

PubMed

Sorvina, Alexandra; Bader, Christie A; Darby, Jack R T; Lock, Mitchell C; Soo, Jia Yin; Johnson, Ian R D; Caporale, Chiara; Voelcker, Nicolas H; Stagni, Stefano; Massi, Massimiliano; Morrison, Janna L; Plush, Sally E; Brooks, Douglas A

2018-05-29

Mitochondrial morphology is important for the function of this critical organelle and, accordingly, altered mitochondrial structure is exhibited in many pathologies. Imaging of mitochondria can therefore provide important information about disease presence and progression. However, mitochondrial imaging is currently limited by the availability of agents that have the capacity to image mitochondrial morphology in both live and fixed samples. This can be particularly problematic in clinical studies or large, multi-centre cohort studies, where tissue archiving by fixation is often more practical. We previously reported the synthesis of an iridium coordination complex [Ir(ppy) 2 (MeTzPyPhCN)] + ; where ppy is a cyclometalated 2-phenylpyridine and TzPyPhCN is the 5-(5-(4-cyanophen-1-yl)pyrid-2-yl)tetrazolate ligand; and showed that this complex (herein referred to as IraZolve-Mito) has a high specificity for mitochondria in live cells. Here we demonstrate that IraZolve-Mito can also effectively stain mitochondria in both live and fixed tissue samples. The staining protocol proposed is versatile, providing a universal procedure for cell biologists and pathologists to visualise mitochondria.

[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.

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.

Lymphoscintigraphy and SPECT/CT in multicentric and multifocal breast cancer: does each tumour have a separate drainage pattern? Results of a Dutch multicentre study (MULTISENT).

PubMed

Brouwer, O R; Vermeeren, L; van der Ploeg, I M C; Valdés Olmos, R A; Loo, C E; Pereira-Bouda, L M; Smit, F; Neijenhuis, P; Vrouenraets, B C; Sivro-Prndelj, F; Jap-a-Joe, S M; Borgstein, P J; Rutgers, E J Th; Oldenburg, H S A

2012-07-01

To investigate whether lymphoscintigraphy and SPECT/CT after intralesional injection of radiopharmaceutical into each tumour separately in patients with multiple malignancies in one breast yields additional sentinel nodes compared to intralesional injection of the largest tumour only. Patients were included prospectively at four centres in The Netherlands. Lymphatic flow was studied using planar lymphoscintigraphy and SPECT/CT until 4 h after administration of (99m)Tc-nanocolloid in the largest tumour. Subsequently, the smaller tumour(s) was injected intratumorally followed by the same imaging sequence. Sentinel nodes were intraoperatively localized using a gamma ray detection probe and vital blue dye. Included in the study were 50 patients. Additional lymphatic drainage was depicted after the second and/or third injection in 32 patients (64%). Comparison of planar images and SPECT/CT images after consecutive injections enabled visualization of the number and location of additional sentinel nodes (32 axillary, 11 internal mammary chain, 2 intramammary, and 1 interpectoral. A sentinel node contained metastases in 17 patients (34%). In five patients with a tumour-positive node in the axilla that was visualized after the first injection, an additional involved axillary node was found after the second injection. In two patients, isolated tumour cells were found in sentinel nodes that were only visualized after the second injection, whilst the sentinel nodes identified after the first injection were tumour-negative. Lymphoscintigraphy and SPECT/CT after consecutive intratumoral injections of tracer enable lymphatic mapping of each tumour separately in patients with multiple malignancies within one breast. The high incidence of additional sentinel nodes draining from tumours other than the largest one suggests that separate tumour-related tracer injections may be a more accurate approach to mapping and sampling of sentinel nodes in patients with multicentric or multifocal breast cancer.

Trauma airway management in emergency departments: a multicentre, prospective, observational study in Japan.

PubMed

Nakao, Shunichiro; Kimura, Akio; Hagiwara, Yusuke; Hasegawa, Kohei

2015-02-04

Although successful airway management is essential for emergency trauma care, comprehensive studies are limited. We sought to characterise current trauma care practice of airway management in the emergency departments (EDs) in Japan. Analysis of data from a prospective, observational, multicentre registry-the Japanese Emergency Airway Network (JEAN) registry. 13 academic and community EDs from different geographic regions across Japan. 723 trauma patients who underwent emergency intubation from March 2010 through August 2012. ED characteristics, patient and operator demographics, methods of airway management, intubation success or failure at each attempt and adverse events. A total of 723 trauma patients who underwent emergency intubation were eligible for the analysis. Traumatic cardiac arrest comprised 32.6% (95% CI 29.3% to 36.1%) of patients. Rapid sequence intubation (RSI) was the initial method chosen in 23.9% (95% CI 21.0% to 27.2%) of all trauma patients and in 35.5% (95% CI 31.4% to 39.9%) of patients without cardiac arrest. Overall, intubation was successful in ≤3 attempts in 96% of patients (95% CI 94.3% to 97.2%). There was a wide variation in the initial methods of intubation; RSI as the initial method was performed in 0-50.9% of all trauma patients among 12 EDs. Similarly, there was a wide variation in success rates and adverse event rates across the EDs. Success rates varied between 35.5% and 90.5% at the first attempt, and 85.1% and 100% within three attempts across the 12 EDs. In this multicentre prospective study in Japan, we observed a high overall success rate in airway management during trauma care. However, the methods of intubation and success rates were highly variable among hospitals. 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.

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

Magnetic resonance mammography in comparison with mammography in the discovery of multifocal, multicentric and bilateral lesions of breast cancer.

PubMed

Bakhtavar, Khadijeh; Saran, Maryam; Behzadifar, Masoud; Farsi, Maryam

2017-08-01

Breast cancer is one of the health system problems and important diseases that is rising in developing and advanced countries. This study aimed to determine the difference of Magnetic Resonance Mammography (MRM) findings versus mammography in detecting multifocal, multi-centric and malignant bilateral lesions in patients with known breast cancer in Tehran. This cross-sectional study was conducted in Iran and Tehran among breast cancer patients between January 2015 and February 2016. Patients were included in the study prior to surgery, at the request of a surgeon with the aim of detecting multifocal, multi-centric and bilateral lesions. Demographic information was also collected from patients. The results for quantitative variables were expressed as mean and standard deviations, and for qualitative variables, were expressed as relative and absolute frequency. Chi-square test was used to compare the two methods. SPSS Ver.24 (IBM) software was used to analyze the data. Thirty-nine patients were enrolled in the study. The mean age of patients in this study was 48.46±6.836. In mammography, 13 (33.3%) had Composition C and 26 (66.7%) had Composition D according to the type of Composition. In total, 25 patients (89.3%) had one lesion and 3 patients (10.7%) had more than two lesions. In MRM, all lesions observed were mass (54 masses). The number of lesions found in MRM was 27 patients with one lesion (58.9%), 6 patients with two lesions (20.5%) and 5 patients with three lesions (20.6%). MRM detected more lesions compared to mammography (p<0.0001). The value of Chi-square test with a degree of freedom and error level of 0.05 was 3.71 and p<0.0001 that showed a significant relationship between the number of MRM findings in comparison with mammography. The results of our study showed that two or more lesions and bilateral lesions in MRM were more than mammography in women with B Breast Composition C, D; the findings showed that MRM has a better ability to detect breast masses, and can affect the patient's surgical procedure.

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

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.

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.

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.

Nonepithelial tumors of the nasal cavity, paranasal sinuses, and nasopharynx. A clinicopathologic study. VI. Fibrous tissue tumors (fibroma, fibromatosis, fibrosarcoma).

PubMed

Fu, Y S; Perzin, K H

1976-06-01

In a study of 256 nonepithelial neoplasms involving the nasal cavity, paranasal sinuses, and nasopharynx, 23 lesions were classified as fibrous tissue tumors, including four cases of "fibroma", six of fibromatosis, and thirteen of fibrosarcoma. The clinical findings associated with these lesions are described, their histologic features illustrated, results of therapy presented and clinicopathologic correlations made. The "fibromas" presented a small localized nodules. None recurred after local excision. Fibromatosis, a locally aggressive tumor, does not metastasize, but may cause considerable morbidity or even death due to local infiltration which may be difficult to control surgically. Fibrosarcoma may cause death either by local infiltration or by metastasis, but has a better prognosis than most other sarcomas of this region. We recommend that a large en block resection be performed initially for fibromatosis and fibrosarcoma growing in this area, after the diagnosis has been made by biopsy. In this series, including patients who had more than one operation, recurrent tumor was seen following 10 of 12 limited local excisions performed for fibromatosis and fibrosarcoma, but in only one of 13 patients after a large bloc resection. The problems involved in histologically differentiating fibrous tissue tumors from other lesions are discussed. A patient with the rare syndrome of multicentric fibromatosis with spontaneous regression of lesions is presented.

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.

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 .

Haemodialysis-membrane biocompatibility and mortality of patients with dialysis-dependent acute renal failure: a prospective randomised multicentre trial. International Multicentre Study Group.

PubMed

Jörres, A; Gahl, G M; Dobis, C; Polenakovic, M H; Cakalaroski, K; Rutkowski, B; Kisielnicka, E; Krieter, D H; Rumpf, K W; Guenther, C; Gaus, W; Hoegel, J

1999-10-16

There is controversy as to whether haemodialysis-membrane biocompatibility (ie, the potential to activate complement and neutrophils) influences mortality of patients with acute renal failure. We did a prospective randomised multicentre trial in patients with dialysis-dependent acute renal failure treated with two different types of low-flux membrane. 180 patients with acute renal failure were randomly assigned bioincompatible Cuprophan (n=90) or polymethyl-methacrylate (n=90) membranes. The main outcome was survival 14 days after the end of therapy (treatment success). Odds ratios for survival were calculated and the two groups were compared by Fisher's exact test. Analyses were based on patients treated according to protocol (76 Cuprophan, 84 polymethyl methacrylate). At the start of dialysis, the groups did not differ significantly in age, sex, severity of illness (as calculated by APACHE II scores), prevalence of oliguria, or biochemical measures of acute renal failure. 44 patients (58% [95% CI 46-69]) assigned Cuprophan membranes and 50 patients (60% [48-70]) assigned polymethyl-methacrylate membranes survived. The odds ratio for treatment failure on Cuprophan compared with polymethyl-methacrylate membranes was 1.07 (0.54-2.11; p=0.87). No difference between Cuprophan and polymethyl-methacrylate membranes was detected when the analysis was adjusted for age and APACHE II score. 18 patients in the Cuprophan group and 20 in the polymethyl-methacrylate group had clinical complications of therapy (mainly hypotension). There were no differences in outcome for patients with dialysis-dependent acute renal failure between those treated with Cuprophan membranes and those treated with polymethyl-methacrylate membranes.

The European Multicentre Bronchiectasis Audit and Research Collaboration (EMBARC): experiences from a successful ERS Clinical Research Collaboration.

PubMed

Chalmers, James D; Crichton, Megan; Goeminne, Pieter C; Loebinger, Michael R; Haworth, Charles; Almagro, Marta; Vendrell, Montse; De Soyza, Anthony; Dhar, Raja; Morgan, Lucy; Blasi, Francesco; Aliberti, Stefano; Boyd, Jeanette; Polverino, Eva

2017-09-01

In contrast to airway diseases like chronic obstructive pulmonary disease or asthma, and rare diseases such as cystic fibrosis, there has been little research and few clinical trials in bronchiectasis. Guidelines are primarily based on expert opinion and treatment is challenging because of the heterogeneous nature of the disease. In an effort to address decades of underinvestment in bronchiectasis research, education and clinical care, the European Multicentre Bronchiectasis Audit and Research Collaboration (EMBARC) was established in 2012 as a collaborative pan-European network to bring together bronchiectasis researchers. The European Respiratory Society officially funded EMBARC in 2013 as a Clinical Research Collaboration, providing support and infrastructure to allow the project to grow. EMBARC has now established an international bronchiectasis registry that is active in more than 30 countries both within and outside Europe. Beyond the registry, the network participates in designing and facilitating clinical trials, has set international research priorities, promotes education and has participated in producing the first international bronchiectasis guidelines. This manuscript article the development, structure and achievements of EMBARC from 2012 to 2017. To understand the role of Clinical Research Collaborations as the major way in which the European Respiratory Society can stimulate clinical research in different disease areasTo understand some of the key features of successful disease registriesTo review key epidemiological, clinical and translational studies of bronchiectasis contributed by the European Multicentre Bronchiectasis Audit and Research Collaboration (EMBARC) project in the past 5 yearsTo understand the key research priorities identified by EMBARC for the next 5 years.

The European Multicentre Bronchiectasis Audit and Research Collaboration (EMBARC): experiences from a successful ERS Clinical Research Collaboration

PubMed Central

Crichton, Megan; Goeminne, Pieter C.; Loebinger, Michael R.; Haworth, Charles; Almagro, Marta; Vendrell, Montse; De Soyza, Anthony; Dhar, Raja ; Morgan, Lucy; Blasi, Francesco; Aliberti, Stefano; Boyd, Jeanette; Polverino, Eva

2017-01-01

In contrast to airway diseases like chronic obstructive pulmonary disease or asthma, and rare diseases such as cystic fibrosis, there has been little research and few clinical trials in bronchiectasis. Guidelines are primarily based on expert opinion and treatment is challenging because of the heterogeneous nature of the disease. In an effort to address decades of underinvestment in bronchiectasis research, education and clinical care, the European Multicentre Bronchiectasis Audit and Research Collaboration (EMBARC) was established in 2012 as a collaborative pan-European network to bring together bronchiectasis researchers. The European Respiratory Society officially funded EMBARC in 2013 as a Clinical Research Collaboration, providing support and infrastructure to allow the project to grow. EMBARC has now established an international bronchiectasis registry that is active in more than 30 countries both within and outside Europe. Beyond the registry, the network participates in designing and facilitating clinical trials, has set international research priorities, promotes education and has participated in producing the first international bronchiectasis guidelines. This manuscript article the development, structure and achievements of EMBARC from 2012 to 2017. Educational aims To understand the role of Clinical Research Collaborations as the major way in which the European Respiratory Society can stimulate clinical research in different disease areas To understand some of the key features of successful disease registries To review key epidemiological, clinical and translational studies of bronchiectasis contributed by the European Multicentre Bronchiectasis Audit and Research Collaboration (EMBARC) project in the past 5 years To understand the key research priorities identified by EMBARC for the next 5 years PMID:28894479

Recent advances in the understanding of severe cutaneous adverse reactions.

PubMed

Adler, N R; Aung, A K; Ergen, E N; Trubiano, J; Goh, M S Y; Phillips, E J

2017-11-01

Severe cutaneous adverse reactions (SCARs) encompass a heterogeneous group of delayed hypersensitivity reactions, which are most frequently caused by drugs. Our understanding of several aspects of SCAR syndromes has evolved considerably over the last decade. This review explores evolving knowledge of the immunopathogenic mechanisms, pharmacogenomic associations, in vivo and ex vivo diagnostics for causality assessment, and medication cross-reactivity data related to SCAR syndromes. Given the rarity and severity of these diseases, multidisciplinary collaboration through large international, national and/or multicentre networks to collect prospective data on patients with SCAR syndromes should be prioritized. This will further enhance a systematized framework for translating epidemiological, clinical and immunopathogenetic advances into preventive efforts and improved outcomes for patients. © 2017 British Association of Dermatologists.

Meeting the privacy requirements for the development of a multi-centre patient registry in Canada: the Rick Hansen Spinal Cord Injury Registry.

PubMed

Noonan, Vanessa K; Thorogood, Nancy P; Joshi, Phalgun B; Fehlings, Michael G; Craven, B Catharine; Linassi, Gary; Fourney, Daryl R; Kwon, Brian K; Bailey, Christopher S; Tsai, Eve C; Drew, Brian M; Ahn, Henry; Tsui, Deborah; Dvorak, Marcel F

2013-05-01

Privacy legislation addresses concerns regarding the privacy of personal information; however, its interpretation by research ethics boards has resulted in significant challenges to the collection, management, use and disclosure of personal health information for multi-centre research studies. This paper describes the strategy used to develop the national Rick Hansen Spinal Cord Injury Registry (RHSCIR) in accordance with privacy statutes and benchmarked against best practices. An analysis of the regional and national privacy legislation was conducted to determine the requirements for each of the 31 local RHSCIR sites and the national RHSCIR office. A national privacy and security framework was created for RHSCIR that includes a governance structure, standard operating procedures, training processes, physical and technical security and privacy impact assessments. The framework meets a high-water mark in ensuring privacy and security of personal health information nationally and may assist in the development of other national or international research initiatives. Copyright © 2013 Longwoods Publishing.

Meeting the Privacy Requirements for the Development of a Multi-Centre Patient Registry in Canada: The Rick Hansen Spinal Cord Injury Registry

PubMed Central

Noonan, Vanessa K.; Thorogood, Nancy P.; Joshi, Phalgun B.; Fehlings, Michael G.; Craven, B. Catharine; Linassi, Gary; Fourney, Daryl R.; Kwon, Brian K.; Bailey, Christopher S.; Tsai, Eve C.; Drew, Brian M.; Ahn, Henry; Tsui, Deborah; Dvorak, Marcel F.

2013-01-01

Privacy legislation addresses concerns regarding the privacy of personal information; however, its interpretation by research ethics boards has resulted in significant challenges to the collection, management, use and disclosure of personal health information for multi-centre research studies. This paper describes the strategy used to develop the national Rick Hansen Spinal Cord Injury Registry (RHSCIR) in accordance with privacy statutes and benchmarked against best practices. An analysis of the regional and national privacy legislation was conducted to determine the requirements for each of the 31 local RHSCIR sites and the national RHSCIR office. A national privacy and security framework was created for RHSCIR that includes a governance structure, standard operating procedures, training processes, physical and technical security and privacy impact assessments. The framework meets a high-water mark in ensuring privacy and security of personal health information nationally and may assist in the development of other national or international research initiatives. PMID:23968640

FIRST-line support for Assistance in Breathing in Children (FIRST-ABC): a multicentre pilot randomised controlled trial of high-flow nasal cannula therapy versus continuous positive airway pressure in paediatric critical care.

PubMed

Ramnarayan, Padmanabhan; Lister, Paula; Dominguez, Troy; Habibi, Parviz; Edmonds, Naomi; Canter, Ruth R; Wulff, Jerome; Harrison, David A; Mouncey, Paul M; Peters, Mark J

2018-06-04

Although high-flow nasal cannula therapy (HFNC) has become a popular mode of non-invasive respiratory support (NRS) in critically ill children, there are no randomised controlled trials (RCTs) comparing it with continuous positive airway pressure (CPAP). We performed a pilot RCT to explore the feasibility, and inform the design and conduct, of a future large pragmatic RCT comparing HFNC and CPAP in paediatric critical care. In this multi-centre pilot RCT, eligible patients were recruited to either Group A (step-up NRS) or Group B (step-down NRS). Participants were randomised (1:1) using sealed opaque envelopes to either CPAP or HFNC as their first-line mode of NRS. Consent was sought after randomisation in emergency situations. The primary study outcomes were related to feasibility (number of eligible patients in each group, proportion of eligible patients randomised, consent rate, and measures of adherence to study algorithms). Data were collected on safety and a range of patient outcomes in order to inform the choice of a primary outcome measure for the future RCT. Overall, 121/254 eligible patients (47.6%) were randomised (Group A 60%, Group B 44.2%) over a 10-month period (recruitment rate for Group A, 1 patient/site/month; Group B, 2.8 patients/site/month). In Group A, consent was obtained in 29/33 parents/guardians approached (87.9%), while in Group B 84/118 consented (71.2%). Intention-to-treat analysis included 113 patients (HFNC 59, CPAP 54). Most reported adverse events were mild/moderate (HFNC 8/59, CPAP 9/54). More patients switched treatment from HFNC to CPAP (Group A: 7/16, 44%; Group B: 9/43, 21%) than from CPAP to HFNC (Group A: 3/13, 23%; Group B: 5/41, 12%). Intubation occurred within 72 h in 15/59 (25.4%) of HFNC patients and 10/54 (18.5%) of CPAP patients (p = 0.38). HFNC patients experienced fewer ventilator-free days at day 28 (Group A: 19.6 vs. 23.5; Group B: 21.8 vs. 22.2). Our pilot trial confirms that, following minor changes to consent procedures and treatment algorithms, it is feasible to conduct a large national RCT of non-invasive respiratory support in the paediatric critical care setting in both step-up and step-down NRS patients. clinicaltrials.gov, NCT02612415 . Registered on 23 November 2015.

Oral ondansetron versus domperidone for symptomatic treatment of vomiting during acute gastroenteritis in children: multicentre randomized controlled trial

PubMed Central

2011-01-01

Background Vomiting in children with acute gastroenteritis (AG) is not only a direct cause of fluid loss but it is also a major factor of failure of oral rehydration therapy (ORT). Physicians who provide care to paediatric patients in the emergency department (ED) usually prescribe intravenous fluid therapy (IVT) for mild or moderate dehydration when vomiting is the major symptom. Thus, effective symptomatic treatment of vomiting would lead to an important reduction in the use of IVT and, consequently, of the duration of hospital stay and of frequency of hospital admission. Available evidence on symptomatic treatment of vomiting shows the efficacy of the most recently registered molecule (ondansetron) but a proper evaluation of antiemetics drugs largely used in clinical practice, such as domperidone, is lacking. Objectives To compare the efficacy of ondansetron and domperidone for the symptomatic treatment of vomiting in children with AG who have failed ORT. Methods/Design Multicentre, double-blind randomized controlled trial conducted in paediatric EDs. Children aged from 1 to 6 years who vomiting, with a presumptive clinical diagnosis of AG, and without severe dehydration will be included. After the failure of a initial ORS administration in ED, eligible children will be randomized to receive: 1) ondansetron syrup (0,15 mg/Kg of body weight); 2) domperidone syrup (0,5 mg/Kg of body weight); 3) placebo. The main study outcome will be the percentage of patients needing nasogastric or IVT after symptomatic oral treatment failure, defined as vomiting or fluid refusal after a second attempt of ORT. Data relative to study outcomes will be collected at 30 minute intervals for a minimum of 6 hours. A telephone follow up call will be made 48 hours after discharge. A total number of 540 children (i.e. 180 patients in each arm) will be enrolled. Discussion The trial results would provide evidence on the efficacy of domperidone, which is largely used in clinical practice despite the lack of proper evaluation and a controversial safety profile, as compared to ondansetron, which is not yet authorized in Italy despite evidence supporting its efficacy in treating vomiting. The trial results would contribute to a reduction in the use of IVT and, consequently, in hospital admissions in children with AG. The design of this RCT, which closely reflect current clinical practice in EDs, will allow immediate transferability of results. Trial Registration ClinicalTrials.gov: NCT01257672 PMID:21310051

Critically Ill Patients and End-of-Life Decision-Making: The Senior Medical Resident Experience

ERIC Educational Resources Information Center

Ahern, Stephane P.; Doyle, Tina K.; Marquis, Francois; Lesk, Corey; Skrobik, Yoanna

2012-01-01

In order to improve the understanding of educational needs among residents caring for the critically ill, narrative accounts of 19 senior physician trainees participating in level of care decision-making were analyzed. In this multicentre qualitative study involving 9 university centers in Canada, in-depth interviews were conducted in either…

Psychological Problems in Children with Cerebral Palsy: A Cross-Sectional European Study

ERIC Educational Resources Information Center

Parkes, Jackie; White-Koning, Melanie; Dickinson, Heather O.; Thyen, Ute; Arnaud, Catherine; Beckung, Eva; Fauconnier, Jerome; Marcelli, Marco; McManus, Vicki; Michelsen, Susan I.; Parkinson, Kathryn; Colver, Allan

2008-01-01

Objectives: To describe psychological symptoms in 8-12-year-old children with cerebral palsy; to investigate predictors of these symptoms and their impact on the child and family. Design: A cross-sectional multi-centre survey. Participants: Eight hundred and eighteen children with cerebral palsy, aged 8-12 years, identified from population-based…

Foetal Antiepileptic Drug Exposure and Verbal versus Non-Verbal Abilities at Three Years of Age

ERIC Educational Resources Information Center

Meador, Kimford J.; Baker, Gus A.; Browning, Nancy; Cohen, Morris J.; Clayton-Smith, Jill; Kalayjian, Laura A.; Kanner, Andres; Liporace, Joyce D.; Pennell, Page B.; Privitera, Michael; Loring, David W.

2011-01-01

We previously reported that foetal valproate exposure impairs intelligence quotient. In this follow-up investigation, we examined dose-related effects of foetal antiepileptic drug exposure on verbal and non-verbal cognitive measures. This investigation is an ongoing prospective observational multi-centre study in the USA and UK, which has enrolled…

Rationale and design of a multicentre, randomized, placebo-controlled trial of mirabegron, a Beta3-adrenergic receptor agonist on left ventricular mass and diastolic function in patients with structural heart disease Beta3-left ventricular hypertrophy (Beta3-LVH).

PubMed

Pouleur, Anne-Catherine; Anker, Stefan; Brito, Dulce; Brosteanu, Oana; Hasenclever, Dirk; Casadei, Barbara; Edelmann, Frank; Filippatos, Gerasimos; Gruson, Damien; Ikonomidis, Ignatios; Lhommel, Renaud; Mahmod, Masliza; Neubauer, Stefan; Persu, Alexandre; Gerber, Bernhard L; Piechnik, Stefan; Pieske, Burkert; Pieske-Kraigher, Elisabeth; Pinto, Fausto; Ponikowski, Piotr; Senni, Michele; Trochu, Jean-Noël; Van Overstraeten, Nancy; Wachter, Rolf; Balligand, Jean-Luc

2018-06-22

Progressive left ventricular (LV) remodelling with cardiac myocyte hypertrophy, myocardial fibrosis, and endothelial dysfunction plays a key role in the onset and progression of heart failure with preserved ejection fraction. The Beta3-LVH trial will test the hypothesis that the β 3 adrenergic receptor agonist mirabegron will improve LV hypertrophy and diastolic function in patients with hypertensive structural heart disease at high risk for developing heart failure with preserved ejection fraction. Beta3-LVH is a randomized, placebo-controlled, double-blind, two-armed, multicentre, European, parallel group study. A total of 296 patients will be randomly assigned to receive either mirabegron 50 mg daily or placebo over 12 months. The main inclusion criterion is the presence of LV hypertrophy, that is, increased LV mass index (LVMi) or increased wall thickening by echocardiography. The co-primary endpoints are a change in LVMi by cardiac magnetic resonance imaging and a change in LV diastolic function (assessed by the E/e' ratio). Secondary endpoints include mirabegron's effects on cardiac fibrosis, left atrial volume index, maximal exercise capacity, and laboratory markers. Two substudies will evaluate mirabegron's effect on endothelial function by pulse amplitude tonometry and brown fat activity by positron emission tomography using 17F-fluorodeoxyglucose. Morbidity and mortality as well as safety aspects will also be assessed. Beta3-LVH is the first large-scale clinical trial to evaluate the effects of mirabegron on LVMi and diastolic function in patients with LVH. Beta3-LVH will provide important information about the clinical course of this condition and may have significant impact on treatment strategies and future trials in these patients. © 2018 The Authors. ESC Heart Failure published by John Wiley & Sons Ltd on behalf of the European Society of Cardiology.

Large multi-centre pilot randomized controlled trial testing a low-cost, tailored, self-help smoking cessation text message intervention for pregnant smokers (MiQuit).

PubMed

Naughton, Felix; Cooper, Sue; Foster, Katharine; Emery, Joanne; Leonardi-Bee, Jo; Sutton, Stephen; Jones, Matthew; Ussher, Michael; Whitemore, Rachel; Leighton, Matthew; Montgomery, Alan; Parrott, Steve; Coleman, Tim

2017-07-01

To estimate the effectiveness of pregnancy smoking cessation support delivered by short message service (SMS) text message and key parameters needed to plan a definitive trial. Multi-centre, parallel-group, single-blinded, individual randomized controlled trial. Sixteen antenatal clinics in England. Four hundred and seven participants were randomized to the intervention (n = 203) or usual care (n = 204). Eligible women were < 25 weeks gestation, smoked at least one daily cigarette (> 5 pre-pregnancy), were able to receive and understand English SMS texts and were not already using text-based cessation support. All participants received a smoking cessation leaflet; intervention participants also received a 12-week programme of individually tailored, automated, interactive, self-help smoking cessation text messages (MiQuit). Seven smoking outcomes, including validated continuous abstinence from 4 weeks post-randomization until 36 weeks gestation, design parameters for a future trial and cost-per-quitter. Using the validated, continuous abstinence outcome, 5.4% (11 of 203) of MiQuit participants were abstinent versus 2.0% (four of 204) of usual care participants [odds ratio (OR) = 2.7, 95% confidence interval (CI) = 0.93-9.35]. The Bayes factor for this outcome was 2.23. Completeness of follow-up at 36 weeks gestation was similar in both groups; provision of self-report smoking data was 64% (MiQuit) and 65% (usual care) and abstinence validation rates were 56% (MiQuit) and 61% (usual care). The incremental cost-per-quitter was £133.53 (95% CI = -£395.78 to 843.62). There was some evidence, although not conclusive, that a text-messaging programme may increase cessation rates in pregnant smokers when provided alongside routine NHS cessation care. © 2017 The Authors. Addiction published by John Wiley & Sons Ltd on behalf of Society for the Study of Addiction.

The European post-marketing observational sertindole study: an investigation of the safety of antipsychotic drug treatment.

PubMed

Kasper, Siegfried; Möller, Hans-Jürgen; Hale, Anthony

2010-02-01

The objective of the European Post-marketing Observational Serdolect((R)) (EPOS) Study was to compare the safety of treatment with Serdolect (sertindole) with that of usual treatment in patients with schizophrenia, in normal European clinical practice. The EPOS was a multicentre, multinational, referenced, cohort study. Patients were enrolled at 226 centres in ten European countries. The study was prematurely terminated in 1998 as a result of the temporary market suspension of sertindole. Termination of the study reduced the number of patients recruited from the planned 12,000 to 2,321. While the power of the study was weakened, it did provide useful mortality information, which may be useful for future long-term studies. Crude mortality in the sertindole and non-sertindole groups was 1.45 (95% confidence interval, CI 0.53-3.16) and 1.50 (CI 0.72-2.76) deaths/100 patient-years exposed, respectively. There were no more cardiac deaths in the sertindole group than in the non-sertindole group. QT interval prolongation did not translate into an increased risk of death. Sertindole was well tolerated and caused few extrapyramidal symptoms. Although CIs remained large, this post-marketing study does not provide any evidence against the use of sertindole under normal conditions. Sertindole was well tolerated and posed no significant safety problems.

The feasibility of using 'bring your own device' (BYOD) technology for electronic data capture in multicentre medical audit and research.

PubMed

Faulds, M C; Bauchmuller, K; Miller, D; Rosser, J H; Shuker, K; Wrench, I; Wilson, P; Mills, G H

2016-01-01

Large-scale audit and research projects demand robust, efficient systems for accurate data collection, handling and analysis. We utilised a multiplatform 'bring your own device' (BYOD) electronic data collection app to capture observational audit data on theatre efficiency across seven hospital Trusts in South Yorkshire in June-August 2013. None of the participating hospitals had a dedicated information governance policy for bring your own device. Data were collected by 17 investigators for 392 individual theatre lists, capturing 14,148 individual data points, 12, 852 (91%) of which were transmitted to a central database on the day of collection without any loss of data. BYOD technology enabled accurate collection of a large volume of secure data across multiple NHS organisations over a short period of time. Bring your own device technology provides a method for collecting real-time audit, research and quality improvement data within healthcare systems without compromising patient data protection. © 2015 The Association of Anaesthetists of Great Britain and Ireland.

Long term outcome and prognostic factors for large hepatocellular carcinoma (10 cm or more) after surgical resection.

PubMed

Pandey, Durgatosh; Lee, Kang-Hoe; Wai, Chun-Tao; Wagholikar, Gajanan; Tan, Kai-Chah

2007-10-01

Surgical resection is the standard treatment for hepatocellular carcinoma (HCC). However, the role of surgery in treatment of large tumors (10 cm or more) is controversial. We have analyzed, in a single centre, the long-term outcome associated with surgical resection in patients with such large tumors. We retrospectively investigated 166 patients who had undergone surgical resection between July 1995 and December 2006 because of large (10 cm or more) HCC. Survival analysis was done using the Kaplan-Meier method. Prognostic factors were evaluated using univariate and multivariate analyses. Of the 166 patients evaluated, 80% were associated with viral hepatitis and 48.2% had cirrhosis. The majority of patients underwent a major hepatectomy (48.2% had four or more segments resected and 9% had additional organ resection). The postoperative mortality was 3%. The median survival in our study was 20 months, with an actuarial 5-year and 10-year overall survival of 28.6% and 25.6%, respectively. Of these patients, 60% had additional treatment in the form of transarterial chemoembolization, radiofrequency ablation or both. On multivariate analysis, vascular invasion (P < 0.001), cirrhosis (P = 0.028), and satellite lesions/multicentricity (P = 0.006) were significant prognostic factors influencing survival. The patients who had none of these three risk factors had 5-year and 10-year overall survivals of 57.7% each, compared with 22.5% and 19.3%, respectively, for those with at least one risk factor (P < 0.001). Surgical resection for those with large HCC can be safely performed with a reasonable long-term survival. For tumors with poor prognostic factors, there is a pressing need for effective adjuvant therapy.

Cut-off of anthropometry measurement and nutritional status among elderly outpatient in Indonesia: multi-centre study.

PubMed

Setiati, Siti; Istanti, Rahmi; Andayani, Rejeki; Kuswardhani, R A Tuty; Aryana, I G P Suka; Putu, I Dewa; Apandi, M; Ichwani, Jusri; Soewoto, Sumarmi; Dinda, Rose; Mustika, Syifa

2010-10-01

To obtain the cut-off value of anthropometric measurements and nutritional status of elderly in Indonesia. A multicentre-cross sectional study was performed at 9 hospitals in Indonesia. The data collected comprises of samples characteristics, anthropometric measurements (weight, height, trisep, bisep, subscapular, suprailiac, and circumference of the hip, waist, arm, calf, and thigh), albumin value, MNA score and ADL Index of Barthel. A total of 702 subjects were collected. The average value of serum albumin is 4.28 g/dl, with 98% subjects had normal serum albumin (> 3.5 g/dl). The mean MNA score and BMI was 23.07 and 22.54 respectively. Most of subjects (56.70%) had risk of malnutrition based on MNA score, and 45.01% had normal nutritional status based on body mass index. Average value of several anthropometric measures (weight, stature, and body mass index; sub-scapular and supra-iliac skinfolds; thigh, calf, mid-arm, and waist circumferences) in various age groups in both groups of women and men were obtained. Cut-off values of various anthropometric indicators were also analyzed in this study with MNA as a gold standard. This study showed age related anthropometric measurement differences in both men and women aged 60 years and older.

Does item overlap render measured relationships between pain and challenging behaviour trivial? Results from a multicentre cross-sectional study in 13 German nursing homes.

PubMed

Kutschar, Patrick; Bauer, Zsuzsa; Gnass, Irmela; Osterbrink, Jürgen

2017-07-01

Several studies suggest that pain is a trigger for challenging behaviour in older adults with cognitive impairment. However, such measured relationships might be confounded due to item overlap as instruments share similar or identical items. The purpose of this study was to examine whether the frequently observed association between pain and challenging behaviour might be traced back to item overlap. This multicentre cross-sectional study was conducted in 13 nursing homes and examined pain (measure: Pain Assessment in Advanced Dementia Scale) and challenging behaviour (measure: Cohen-Mansfield Agitation Inventory) in 150 residents with severe cognitive impairment. The extent of item overlap was determined by juxtaposition of both measures' original items. As expected, comparison between these instruments revealed an extensive item overlap. The statistical relationship between the two phenomena can be traced back mainly to the contribution of the overlapping items, which renders the frequently stated relationship between pain and challenging behaviour trivial. The status quo of measuring such associations must be contested: constructs' discrimination and instruments' discrimination have to be discussed critically as item overlap may lead to biased conclusions and assumptions in research as well as to inadequate care measures in nursing practice. © 2017 John Wiley & Sons Ltd.

The effectiveness of influenza vaccination in preventing hospitalisations of elderly individuals in two influenza seasons: a multicentre case-control study, Spain, 2013/14 and 2014/15.

PubMed

Domínguez, Angela; Soldevila, Núria; Toledo, Diana; Godoy, Pere; Espejo, Elena; Fernandez, Maria Amelia; Mayoral, José María; Castilla, Jesús; Egurrola, Mikel; Tamames, Sonia; Astray, Jenaro; Morales-Suárez-Varela, María

2017-08-24

Influenza vaccination may limit the impact of influenza in the community. The aim of this study was to assess the effectiveness of influenza vaccination in preventing hospitalisation in individuals aged ≥ 65 years in Spain. A multicentre case-control study was conducted in 20 Spanish hospitals during 2013/14 and 2014/15. Patients aged ≥ 65 years who were hospitalised with laboratory-confirmed influenza were matched with controls according to sex, age and date of hospitalisation. Adjusted vaccine effectiveness (VE) was calculated by multivariate conditional logistic regression. A total of 728 cases and 1,826 matched controls were included in the study. Overall VE was 36% (95% confidence interval (CI): 22-47). VE was 51% (95% CI: 15-71) in patients without high-risk medical conditions and 30% (95% CI: 14-44) in patients with them. VE was 39% (95% CI: 20-53) in patients aged 65-79 years and 34% (95% CI: 11-51) in patients aged ≥ 80 years, and was greater against the influenza A(H1N1)pdm09 subtype than the A(H3N2) subtype. Influenza vaccination was effective in preventing hospitalisations of elderly individuals. This article is copyright of The Authors, 2017.

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

[Management of atherosclerotic renal-artery stenosis in 2016].

PubMed

Fournier, Thomas; Sens, Florence; Rouvière, Olivier; Millon, Antoine; Juillard, Laurent

2017-02-01

Endovascular revascularization as treatment of atherosclerotic renal-artery stenosis (aRAS) is controversial since 3 large and multicentric randomised trials (CORAL, ASTRAL, STAR) failed to prove the superiority of percutaneous transluminal renal-artery stenting (PTRAS) over medical treatment only (MT). However, considering the multiple bias of these trials, among which questionable inclusion criterias, these results must be extrapolated in clinical practice with caution. New pathophysiological data have been helping to understand why restoring blood flow does not necessarily lead to kidney function improvement. Today, the diagnostic approach must in one hand confirm the artery stenosis and on the other hand assess its severity and impact on the kidney. Therapeutic options still lie on the American guidelines published in 2006, since no study data can be reasonably used in everyday practice. However, particular sub-groups of patients who could benefit from revascularisation have been identified through recent cohort studies. Further prospective studies are needed in order to confirm the superiority of PTRAS in these populations. Meanwhile, multidisciplinary approach should be promoted, in order to provide the best treatment for each patient. Copyright © 2016 Association Société de néphrologie. Published by Elsevier SAS. All rights reserved.

Gone fishing in a fluid trial.

PubMed

Hjortrup, Peter B; Haase, Nicolai; Wetterslev, Jørn; Perner, Anders

2016-03-01

To maximise the yield of existing data by assessing the effect on mortality of being born under the zodiac sign Pisces in a trial of intravenous (IV) fluids. A retrospective observational study, with no predefined hypothesis or statistical analysis plan, of 26 Scandinavian intensive care units between 2009 and 2011. Patients aged 18 years or older with severe sepsis and in need of fluid resuscitation, randomised in the Scandinavian Starch for Severe Sepsis/ Septic Shock (6S) trial. Ninety-day mortality. We included all 798 randomised patients in our study; 70 (9%) were born under the sign of Pisces. The primary outcome (death within 90 days after randomisation) occurred in 25 patients (35.7%) in the Pisces group, compared with 348 patients (48%) in the non-Pisces group (relative risk, 0.75; 95% CI, 0.54-1.03; one-sided P = 0.03). In a multicentre randomised clinical trial of IV fluids, being born under the sign of Pisces was associated with a decreased risk of death. Our study shows that with convenient use of statistics and an enticing explanatory hypothesis, it is possible to achieve significant findings in post-hoc analyses of data from large trials.

Pattern of childhood leukaemia in University College Hospital, Ibadan.

PubMed

Babatunde, T O; Ogun, G O; Brown, B J; Akang, E E; Aken'Ova, Y A

2014-06-01

Leukaemias are haematological malignancies characterized by unregulated clonal proliferation of haematopoietic cells. To determine the pattern of childhood leukaemia in Ibadan. This was a retrospective study of leukaemia cases diagnosed at the University College Hospital (UCH), Ibadan between January 1991 and December 2010 in children less than 15 years of age. Data obtained was subjected to statistical analysis using the Statistical Package for Social Sciences version 20. There were 64 cases of childhood leukaemia, accounting for 10.2% of childhood cancers seen during this study period. The male to female ratio was 2:1 and modal age group was between 10 and 14 years. Thirty (46.9%) cases were acute lymphoblastic leukaemia (ALL), 22 (34.4%) were acute myelogenous leukaemia (AML) and 12 (18.8%) were unspecified acute leukaemias. There was no case of chronic myeloid or lymphocytic leukaemia. There has been a relative increase in the frequency of leukaemia cases at UCH, Ibadan, which may be largely explained by increased awareness and referrals. There is a need for further collaborative multicentre studies of childhood leukaemias in Nigeria and other developing countries and focused research on childhood leukaemias in order to unravel the aetiology.

Anthropometric standardisation and quality control protocols for the construction of new, international, fetal and newborn growth standards: the INTERGROWTH-21st Project.

PubMed

Cheikh Ismail, L; Knight, H E; Ohuma, E O; Hoch, L; Chumlea, W C

2013-09-01

The primary aim of the INTERGROWTH-21(st) Project is to construct new, prescriptive standards describing optimal fetal and preterm postnatal growth. The anthropometric measurements include the head circumference, recumbent length and weight of the infants, and the stature and weight of the parents. In such a large, international, multicentre project, it is critical that all study sites follow standardised protocols to ensure maximal validity of the growth and nutrition indicators used. This paper describes in detail the anthropometric training, standardisation and quality control procedures used to collect data for these new standards. The initial standardisation session was in Nairobi, Kenya, using newborns, which was followed by similar sessions in the eight participating study sites in Brazil, China, India, Italy, Kenya, Oman, UK and USA. The intraobserver and inter-observer technical error of measurement values for head circumference range from 0.3 to 0.4 cm, and for recumbent length from 0.3 to 0.5 cm. These standardisation protocols implemented at each study site worldwide ensure that the anthropometric data collected are of the highest quality to construct international growth standards. © 2013 Royal College of Obstetricians and Gynaecologists.

[Controversies in the conduction and evaluation of clinical trials results for the treatment in vasovagal syncope].

PubMed

Gajek, Jacek; Zyśko, Dorota; Halawa, Bogumił

2003-05-01

The vasovagal syncope is a reflex reaction to various stimuli leading to the marked hypotension with or without bradycardia with loss of consciousness and fall of postural muscle tone. The vast majority of the patients recover spontaneously but if the syncope occurs frequently and causes injury of the patients body it worsens the quality of life and needs appropriate treatment. The injuries requiring hospitalization occur approximately in 10% of the patients with vasovagal syncope. The aim of the therapy of affected patients is to diminish the syncope prevalence, to brake the neurocardiogenic reaction on an early stage or to prolong the duration of the presyncope phase to enable the patient prevention of the injury. The lack of clear diagnostic criteria and difficulties with estimation the efficacy of any particular therapeutic intervention in many clinical studies of different authors, inclusion to the studies patients with different clinical presentation stages of the disease contribute to different conclusions, which automatic use in the clinical practice is inappropriate. There is an urgent need to clear the methodological discrepancies and to conduct good planed, large, randomized, multicentre studies to assess the efficacy of different therapeutic methods in the treatment of vasovagal syncope.

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.

Review of Van earthquakes form an orthopaedic perspective: a multicentre retrospective study.

PubMed

Guner, Savas; Guner, Sukriye Ilkay; Isik, Yasemin; Gormeli, Gokay; Kalender, Ali Murat; Turktas, Ugur; Gokalp, Mehmet Ata; Gozen, Abdurrahim; Isik, Mustafa; Ozkan, Sezai; Turkozu, Tulin; Karadas, Sevdegul; Ceylan, Mehmet Fethi; Ediz, Levent; Bulut, Mehmet; Gunes, Yusuf; Gormeli, Ayse; Erturk, Cemil; Eseoglu, Metehan; Dursun, Recep

2013-01-01

This is a descriptive analysis, of victims of Turkey's October 23, 2011 and November 21, 2011 Van earthquakes. The goal of this study is investigated the injury profile of the both earthquakes in relation to musculoskeletal trauma. We retrospectively reviewed medical records of 3,965 patients admitted to in seven hospitals. A large share of these injuries were soft tissue injuries, followed by fractures, crush injuries, crush syndromes, nerve injuries, vascular injuries, compartment syndrome and joint dislocations. A total of 73 crush injuries were diagnosed and 31 of them were developed compartment syndrome. The patients with closed undisplaced fractures were treated with casting braces. For closed unstable fractures with good skin and soft-tissue conditions, open reduction and internal fixation was performed. All patients with open fracture had an external fixator applied after adequate debridement. Thirty one of 40 patients with compartment syndrome were treated by fasciotomy. For twelve of them, amputation was necessary. The most common procedure performed was debridement, followed by open reduction and internal fixation and closed reduction-casting, respectively. The results of this study may provide the basis for future development of strategy to optimise attempts at rescue and plan treatment of survivors with musculoskeletal injuries after earthquakes.

[Sonographically detectable splenic disorders in dogs with malignant lymphoma].

PubMed

Eberhardt, F; Köhler, C; Krastel, D; Winter, K; Alef, M; Kiefer, I

2015-01-01

To evaluate the frequency of different sonographic splenic disorders in dogs with different anatomic forms of malignant lymphoma. Additionally, the occurrence of the moth-eaten pattern in the parenchyma of the spleen in patients with diseases other than lymphoma should be investigated. Retrospective analysis of patient data collected from dogs histologically or cytologically diagnosed with malignant lymphoma and for which ultrasonographic images were available before the initiation of therapy. Patient data from dogs with a moth-eaten pattern within the splenic parenchyma were evaluated separately. Exclusion criterion was the administration of cytostatic agents prior to diagnosis. In 84% of 164 dogs with malignant lymphoma, an altered pattern of the spleen was diagnosed ultrasonographically. Ninety-four of these 137 patients had a moth-eaten pattern of the splenic parenchyma and 43 dogs displayed abnormalities in the form of splenomegaly, coarse echotexture or other changes of the parenchyma. When a moth-eaten pattern was diagnosed, the affected dogs suffered significantly more often from a multicentric lymphoma (95%) than from any other anatomical lymphoma form. Only one dog displayed a moth-eaten pattern of the splenic parenchyma without diagnosis of a malignant lymphoma. The positive predictive value of the moth-eaten pattern for malignant lymphoma was 99% and, in particular, for the multicentric lymphoma this was 95%. In total, 84% of the 164 dogs displayed a multicentric lymphoma, 5% a mediastinal or a cutaneous lymphoma, respectively, 4% a gastrointestinal lymphoma, and one animal had an ocular or renal lymphoma, respectively. Sonographic changes of the spleen are often diagnosed in dogs with malignant lymphoma, independent of the anatomical lymphoma form. When the moth-eaten pattern is observed, it is very likely that the affected dog suffers from a malignant lymphoma, most probably a multicentric lymphoma.

What is the degree of innovation routinely implemented in Dutch radiotherapy centres? A multicentre cross-sectional study.

PubMed

Jacobs, Maria; Boersma, Liesbeth; Dekker, Andre; Bosmans, Geert; van Merode, Frits; Verhaegen, Frank; de Ruysscher, Dirk; Swart, Rachelle; Kengen, Cindy; Lambin, Philippe

2016-11-01

To study the implementation of innovation activities in Dutch radiotherapy (RT) centres in a broad sense (product, technological, market and organizational innovations). A descriptive cross-sectional study was conducted in 15 Dutch RT centres. A list of innovations implemented from 2011 to 2013 was drawn up for each centre using semi-structured interviews. These innovations were classified into innovation categories according to previously defined innovation indicators. Where applicable, each innovation was rated by each centre on the effort required to implement it and on its expected effects, to get an impression of how far reaching and radical the innovations were and to be able to compare the number of innovations between centres. The participating RT centres in the Netherlands implemented 12 innovations per year on average (range 5-25); this number was not significantly different for academic (n = 13) or non-academic centres (n = 10). Several centres were dealing with the same innovations at the same time. The average required effort and expected output did not differ significantly between product, technological and organizational innovation or between academic and non-academic centres. The number of innovations observed per centre varied across a large range, with a large overlap in terms of the type of innovations that were implemented. Registering innovations using the innovation indicators applied in our study would make it possible to improve collaboration between centres, e.g. with common training modules, to avoid duplication of work. Advances in knowledge: This study is the first of its kind investigating innovation implementation in RT in a broad sense.

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.

Multicentric evaluation of the impact of central tumour location when comparing rates of N1 upstaging in patients undergoing video-assisted and open surgery for clinical Stage I non-small-cell lung cancer.

PubMed

Decaluwé, Herbert; Petersen, René Horsleben; Brunelli, Alex; Pompili, Cecilia; Seguin-Givelet, Agathe; Gust, Lucile; Aigner, Clemens; Falcoz, Pierre-Emmanuel; Rinieri, Philippe; Augustin, Florian; Sokolow, Youri; Verhagen, Ad; Depypere, Lieven; Papagiannopoulos, Kostas; Gossot, Dominique; D'Journo, Xavier Benoit; Guerrera, Francesco; Baste, Jean-Marc; Schmid, Thomas; Stanzi, Alessia; Van Raemdonck, Dirk; Bardet, Jeremy; Thomas, Pascal-Alexandre; Massard, Gilbert; Fieuws, Steffen; Moons, Johnny; Dooms, Christophe; De Leyn, Paul; Hansen, Henrik Jessen

2017-09-27

Large retrospective series have indicated lower rates of cN0 to pN1 nodal upstaging after video-assisted thoracic surgery (VATS) compared with open resections for Stage I non-small-cell lung cancer (NSCLC). The objective of our multicentre study was to investigate whether the presumed lower rate of N1 upstaging after VATS disappears after correction for central tumour location in a multivariable analysis. Consecutive patients operated for PET-CT based clinical Stage I NSCLC were selected from prospectively managed surgical databases in 11 European centres. Central tumour location was defined as contact with bronchovascular structures on computer tomography and/or visibility on standard bronchoscopy. Eight hundred and ninety-five patients underwent pulmonary resection by VATS (n = 699, 9% conversions) or an open technique (n = 196) in 2014. Incidence of nodal pN1 and pN2 upstaging was 8% and 7% after VATS and 15% and 6% after open surgery, respectively. pN1 was found in 27% of patients with central tumours. Less central tumours were operated on by VATS compared with the open technique (12% vs 28%, P < 0.001). Logistic regression analysis showed that only tumour location had a significant impact on N1 upstaging (OR 6.2, confidence interval 3.6-10.8; P < 0.001) and that the effect of surgical technique (VATS versus open surgery) was no longer significant when accounting for tumour location. A quarter of patients with central clinical Stage I NSCLC was upstaged to pN1 at resection. Central tumour location was the only independent factor associated with N1 upstaging, undermining the evidence for lower N1 upstaging after VATS resections. Studies investigating N1 upstaging after VATS compared with open surgery should be interpreted with caution due to possible selection bias, i.e. relatively more central tumours in the open group with a higher chance of N1 upstaging. © The Author 2017. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.

DNA cards: determinants of DNA yield and quality in collecting genetic samples for pharmacogenetic studies.

PubMed

Mas, Sergi; Crescenti, Anna; Gassó, Patricia; Vidal-Taboada, Jose M; Lafuente, Amalia

2007-08-01

As pharmacogenetic studies frequently require establishment of DNA banks containing large cohorts with multi-centric designs, inexpensive methods for collecting and storing high-quality DNA are needed. The aims of this study were two-fold: to compare the amount and quality of DNA obtained from two different DNA cards (IsoCode Cards or FTA Classic Cards, Whatman plc, Brentford, Middlesex, UK); and to evaluate the effects of time and storage temperature, as well as the influence of anticoagulant ethylenediaminetetraacetic acid on the DNA elution procedure. The samples were genotyped by several methods typically used in pharmacogenetic studies: multiplex PCR, PCR-restriction fragment length polymorphism, single nucleotide primer extension, and allelic discrimination assay. In addition, they were amplified by whole genome amplification to increase genomic DNA mass. Time, storage temperature and ethylenediaminetetraacetic acid had no significant effects on either DNA card. This study reveals the importance of drying blood spots prior to isolation to avoid haemoglobin interference. Moreover, our results demonstrate that re-isolation protocols could be applied to increase the amount of DNA recovered. The samples analysed were accurately genotyped with all the methods examined herein. In conclusion, our study shows that both DNA cards, IsoCode Cards and FTA Classic Cards, facilitate genetic and pharmacogenetic testing for routine clinical practice.

Nocturnal emergency department visits, duration of symptoms and risk of hospitalisation among adults with asthma exacerbations: a multicentre observational study.

PubMed

Yasuda, Hideto; Hagiwara, Yusuke; Watase, Hiroko; Hasegawa, Kohei

2016-08-12

We sought to compare the characteristics of patients with asthma presenting to the emergency department (ED) during the night-time with those of patients presenting at other times of the day, and to determine whether the time of ED presentation is associated with the risk of hospitalisation. A multicentre chart review study of 23 EDs across Japan. Patients aged 18-54 years with a history of physician-diagnosed asthma, presented to the ED between January 2009 and December 2011 OUTCOME MEASURES: The outcome of interest was hospitalisation, including admissions to an observation unit, inpatient unit and intensive care unit. Among the 1354 patients (30.1% in the night-time group vs 69.9% in the other time group) included in this study, the median age was 34 years and ∼40% were male. Overall 145 patients (10.7%) were hospitalised. Patients in the night-time group were more likely to have a shorter duration of symptoms (≤3 hours) before ED presentation than those in the other time group (25.9% in night-time vs 13.4% in other times; p<0.001). In contrast, there were no significant differences in respiratory rate, initial peak expiratory flow or ED asthma treatment between the two groups (p>0.05). Similarly, the risk of hospitalisation did not differ between the two groups (11.3% in night-time vs 10.5% in other times; p=0.65). In a multivariable model adjusting for potential confounders, the risk of hospitalisation in the night-time group was not statistically different from the other time group (OR, 1.10; 95% CI 0.74 to 1.61; p=0.63). This multicentre study in Japan demonstrated no significant difference in the risk of hospitalisations according to the time of ED presentation. 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 Multidisciplinary Evaluation of a Web-based eLearning Training Programme for SAFRON II (TROG 13.01): a Multicentre Randomised Study of Stereotactic Radiotherapy for Lung Metastases.

PubMed

Pham, D; Hardcastle, N; Foroudi, F; Kron, T; Bressel, M; Hilder, B; Chesson, B; Oates, R; Montgomery, R; Ball, D; Siva, S

2016-09-01

In technically advanced multicentre clinical trials, participating centres can benefit from a credentialing programme before participating in the trial. Education of staff in participating centres is an important aspect of a successful clinical trial. In the multicentre study of fractionated versus single fraction stereotactic ablative body radiotherapy in lung oligometastases (TROG 13.01), knowledge transfer of stereotactic ablative body radiotherapy techniques to the local multidisciplinary team is intended as part of the credentialing process. In this study, a web-based learning platform was developed to provide education and training for the multidisciplinary trial teams at geographically distinct sites. A web-based platform using eLearning software consisting of seven training modules was developed. These modules were based on extracranial stereotactic theory covering the following discrete modules: Clinical background; Planning technique and evaluation; Planning optimisation; Four-dimensional computed tomography simulation; Patient-specific quality assurance; Cone beam computed tomography and image guidance; Contouring organs at risk. Radiation oncologists, medical physicists and radiation therapists from hospitals in Australia and New Zealand were invited to participate in this study. Each discipline was enrolled into a subset of modules (core modules) and was evaluated before and after completing each module. The effectiveness of the eLearning training will be evaluated based on (i) knowledge retention after participation in the web-based training and (ii) confidence evaluation after participation in the training. Evaluation consisted of a knowledge test and confidence evaluation using a Likert scale. In total, 130 participants were enrolled into the eLearning programme: 81 radiation therapists (62.3%), 27 medical physicists (20.8%) and 22 radiation oncologists (16.9%). There was an average absolute improvement of 14% in test score (P < 0.001) after learning. This score improvement compared with initial testing was also observed in the long-term testing (>4 weeks) after completing the modules (P < 0.001). For most there was significant increase in confidence (P < 0.001) after completing all the modules. Copyright © 2016 The Royal College of Radiologists. Published by Elsevier Ltd. All rights reserved.

KSHV-associated multicentric Castleman disease: A tangle of different entities requiring multitarget treatment strategies.

PubMed

Carbone, Antonino; De Paoli, Paolo; Gloghini, Annunziata; Vaccher, Emanuela

2015-07-15

Multicentric Castleman Disease (MCD) is a lymphoproliferative disorder presenting with heterogeneous pathological and clinical features. It comprises disease entities with a complex aetiology and overlapping pathogenesis. MCD can be found in association with HIV infection, plasma-cell dyscrasias, Kaposi sarcoma (KS), B-cell lymphomas including primary effusion lymphoma (PEL) and its solid variant, and Hodgkin lymphoma. In KSHV-associated MCD cases, a common association is KS and a specific variant of lymphoma referred to as "plasmablastic lymphoma," also called "large B-cell lymphoma arising in KSHV-associated MCD" lacking EBV infection. MCD is often referred to as human interleukin-6 (hIL-6) syndrome, since an overproduction of IL-6 occurs in MCD-associated diseases as well as in MCD itself. hIL-6 and a viral IL-6 (vIL-6) homolog encoded by KSHV can independently or together lead to flares of KSHV-associated MCD. Recently, a new clinical entity was proposed to describe a severe systemic infection/reactivation of KSHV: KSHV inflammatory syndrome (KICS). KICS may contribute in inducing the inflammatory symptoms seen in some patients with severe KS or PEL. The precise relationship of KICS to KSHV-associated MCD is unclear and it is possible that KICS may be prodromal symptoms to frank KSHV-associated MCD. Options for treatment of KSHV-associated MCD and related diseases include monoclonal antibodies, chemotherapy, immune modulators, virus-activated cytotoxic therapy and antiviral therapies. A comprehensive understanding of the intricacies of the HIV-KSHV coinfection will probably lead to additional advances in therapy and managements for these disorders. © 2014 UICC.

Systemic review: Radiation therapy alone in medical non-operable endometrial carcinoma.

PubMed

van der Steen-Banasik, E; Christiaens, M; Shash, E; Coens, C; Casado, A; Herrera, F G; Ottevanger, P B

2016-09-01

Radiotherapy is a good option for inoperable and frail patients diagnosed with endometrial cancer. Because of the lack of large multicentre trials, a systematic review was performed in an attempt to get an overview on the feasibility and efficacy of this specific approach. We performed a bibliographic search for articles in English or French which were published in PubMed from the start of this database in January 1969 to identify publications on radiation therapy (RT) as single treatment for localised non-operable carcinoma of the endometrium. The review was completed following the preferred reporting items for systematic reviews and meta-analyses (PRISMA) guidelines. Twenty-five reports containing 2694 patients treated with RT as single treatment were identified that fulfilled the selection criteria. Disease-specific survival (DSS) at 5 years was reported for a cohort of 1322 (49.1%) patients. The combined DSS for this group of patients was 78.5% (range: 68.4-92%; 95% confidence interval: 74.5-82.5). External beam radiation therapy (EBRT) combined with brachytherapy (BT) was used in 1278 patients (47.4%), BT alone in 1383 patients (51.3%), and EBRT alone in 33 patients (1.2%). The average occurrence of grade III or worse late toxicity was 3.7% for EBRT + BT, 2.8% for BT alone, and 1.2% for EBRT alone. RT is in terms of disease control and toxicity, an acceptable option for non-surgical candidate patients. Prospective multicentre randomised or observational trials are needed to validate these results. Copyright © 2016 Elsevier Ltd. All rights reserved.

Role of Obesity Variables in Detecting Hypertension in an Iranian Population.

PubMed

Khashayar, Patricia; Aghaei Meybodi, Hamidreza; Rezaei Hemami, Mohsen; Larijani, Bagher

2017-09-01

As the high incidence of hypertension has been in conjunction with dramatic increase in the prevalence of obesity, many studies have suggested obesity as its underlying cause in diverse race and ethnic groups. The present study was designed to quantify the relationship between obesity variables and hypertension in Iranian population. A ROC curve analysis was also used to determine an optimal BMI cutoff for obesity with the aim of representing elevated incidence of hypertension in this population. The study population comprised of apparently healthy men and women who participated in the Iranian Multi-centric Osteoporosis Studies (IMOS), a multi-centric cross-sectional study carried out in urban areas of five great cities (Tehran, Tabriz, Mashhad, Shiraz and Bushehr). The anthropometric (weight, height, waist and hip circumferences) and blood pressure measures were reported in some 5724 subjects. The influence of these factors on systolic and diastolic blood pressure was assessed based on a list-wise method. There was a significant difference in the studied subjects anthropometric (weight classes (BMI), WC and HC, and WHR) and blood pressure variables; age, gender and weight, however, were the only factors significantly influencing SBP and DBP. Furthermore, BMI showed a significant impact on the overall risk of developing hypertension. General obesity rather than abdominal obesity is directly linked with higher blood pressure levels in Iranian population.

Czech multicenter research database of severe COPD

PubMed Central

Novotna, Barbora; Koblizek, Vladimir; Zatloukal, Jaromir; Plutinsky, Marek; Hejduk, Karel; Zbozinkova, Zuzana; Jarkovsky, Jiri; Sobotik, Ondrej; Dvorak, Tomas; Safranek, Petr

2014-01-01

Purpose Chronic obstructive pulmonary disease (COPD) has been recognized as a heterogeneous, multiple organ system-affecting disorder. The Global Initiative for Chronic Obstructive Lung Disease (GOLD) places emphasis on symptom and exacerbation management. The aim of this study is examine the course of COPD and its impact on morbidity and all-cause mortality of patients, with respect to individual phenotypes and GOLD categories. This study will also evaluate COPD real-life patient care in the Czech Republic. Patients and methods The Czech Multicentre Research Database of COPD is projected to last for 5 years, with the aim of enrolling 1,000 patients. This is a multicenter, observational, and prospective study of patients with severe COPD (post-bronchodilator forced expiratory volume in 1 second ≤60%). Every consecutive patient, who fulfils the inclusion criteria, is asked to participate in the study. Patient recruitment is done on the basis of signed informed consent. The study was approved by the Multicentre Ethical Committee in Brno, Czech Republic. Results The objective of this paper was to outline the methodology of this study. Conclusion The establishment of the database is a useful step in improving care for COPD subjects. Additionally, it will serve as a source of data elucidating the natural course of COPD, comorbidities, and overall impact on the patients. Moreover, it will provide information on the diverse course of the COPD syndrome in the Czech Republic. PMID:25419124

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

Corruption and research.

PubMed

Luna, Florencia

1999-07-01

Last year there was a heated debate regarding clinical trials with AZT carried out in developing countries. AIDS vaccine trials also posed various dilemmas and ethical problems. In this paper I will consider the possibility of corruption in bioethics, and international multi-centre research will be taken as an example. International clinical trials will be seen from another perspective. I will try to show that the possibility of systemic corruption should be considered when designing an international multi-centre research trial which may involve countries in very different situations regarding corruption. I will analyze three different approaches to this problem and suggest some strategies regarding their capacity to exclude the possibility of corruption.

Motives and Suicide Intent Underlying Hospital Treated Deliberate Self-Harm and Their Association with Repetition

ERIC Educational Resources Information Center

McAuliffe, Carmel; Arensman, Ella; Keeley, Helen S.; Corcoran, Paul; Fitzgerald, Anthony P.

2007-01-01

The association between motives for deliberate self-harm (DSH), level of suicide intent, and history of DSH is poorly understood. As part of the WHO/EURO Multicentre Study on Suicidal Behavior, the Suicide Intent Scale, and the Motives for Parasuicide Questionnaire were administered to 146 patients presenting with DSH in the Cork region in…

The clinical and cost-benefits of investing in neurobehavioural rehabilitation: a multi-centre study.

PubMed

Oddy, Michael; da Silva Ramos, Sara

2013-01-01

The aim of this study was to investigate the cost-benefits of a residential post-acute neurobehavioural rehabilitation programme and its effects on care needs and social participation of adults with acquired brain injury. Retrospective multi-centre design. Data on occupation, adaptability and level of support required were collected at admission, discharge and 6-months follow-up. Cost analysis was performed on cost estimates based on level of support. Significant gains were observed in all areas of functioning, with individuals progressing towards higher levels of independence and more participation in society upon discharge. Cost-benefits of up to £1.13 million were demonstrated for individuals admitted to rehabilitation within a year of sustaining a brain injury and of up to £0.86 million for those admitted more than 1 year after injury. Functional gains and reductions in levels of care required upon discharge were maintained 6 months later. These results demonstrate that post-acute neurobehavioural rehabilitation can have a positive impact on the lives of individuals with brain injury and that the associated costs are off-set by significant savings in the longer-term.

Efficacy and safety of a phytoestrogen preparation derived from Glycine max (L.) Merr in climacteric symptomatology: a multicentric, open, prospective and non-randomized trial.

PubMed

Albert, A; Altabre, C; Baró, F; Buendía, E; Cabero, A; Cancelo, M J; Castelo-Branco, C; Chantre, P; Duran, M; Haya, J; Imbert, P; Julía, D; Lanchares, J L; Llaneza, P; Manubens, M; Miñano, A; Quereda, F; Ribes, C; Vázquez, F

2002-03-01

A multicentric, open, prospective, observational and no-randomized clinical trial was carried out in Spain with 190 postmenopausal women receiving a soy preparation rich in isoflavones (PHYTO SOYA, capsules containing 17.5 mg isoflavones). The main object of the present study was to investigate its efficacy in alleviating the symptomatology derived from the lack of estrogen, mainly hot flushes, but also other symptoms such as sleep disorder, anxiety, depression, vaginal dryness, loss of libido and bone pain. Each patient received 35 mg isoflavones per day in two doses. During the four months' treatment, a statistically significant decrease in the number of hot flushes with PHYTO SOYA was experienced by 80.82% women; only 5,48% patients did not improve with the treatment. The average reduction was 47.8%, which is equivalent to 4 hot flushes. All the other studied parameters also showed a statistically significant decrease. No severe side-effects were reported and tolerance was excellent. Treatment with PHYTO SOYA resulted in a significant improvement of the symptomatology that accompanies the lack of estrogen during menopause.

Efficacy and safety of fluconazole in the treatment of systemic fungal infections in pediatric patients. Multicentre Study Group.

PubMed

Presterl, E; Graninger, W

1994-04-01

In a non-comparative multicentre trial 51 patients aged 24 days to 17 years received treatment with intravenous or oral fluconazole for suspected systemic fungal infections. Twenty-seven patients had confirmed infections, 26 being confirmed mycologically and 1 histologically. All isolates were Candida species. Of the 43 clinically assessed patients, 30 were considered cured, 7 improved and 6 experienced failure of therapy. Of 27 patients with confirmed fungal infections, 25 were assessed mycologically and all but one were considered cured. Of the six patients experiencing clinical failure, two had a confirmed infection and only one of these experienced mycological failure. This patient had a primary diagnosis of candidemia with persistence of Candida albicans and Candida parapsilosis. All 51 patients were evaluable for safety. No treatment-related adverse events required termination of treatment. Treatment-related side effects (diarrhea, vomiting, deafness) were reported by three of 51 patients, three patients had laboratory test abnormalities possibly related to fluconazole treatment, including elevation of liver enzyme levels and of the eosinophil count. Results of this study confirm the efficacy and safety of fluconazole in the treatment of pediatric patients with severe fungal infection.

Outcome of Heart Failure with Preserved Ejection Fraction: A Multicentre Spanish Registry

PubMed Central

Castillo, Juan C; Anguita1, Manuel P; Jiménez, Manuel

2009-01-01

Background: Studies on clinical features, treatment and prognosis of patients with congestive heart failure (CHF) and preserved left ventricular ejection fraction (LVEF) are few and their results frequently conflicting. Aims: To investigate the characteristics and long term prognosis of patients with CHF and preserved (≥ 45%) LVEF. Methods and Results: We conducted a prospective multicentre study with 4720 patients attended in 62 heart failure clinics from 1999 to 2003 in Spain (BADAPIC registry). LVEF was preserved in 30% patients. Age, female gender, prevalence of atrial fibrillation, hypertension and non-ischaemic cardiopathy were all significantly greater in patients with preserved LVEF. Mean follow-up was 40±12 months. Mortality and other cardiovascular complication rates during follow up were similar in both groups. On multivariate analysis ejection fraction was not an independent predictor for mortality. Survival at one and five years was similar in both groups (79% and 59% for patients with preserved LVEF and 78% and 57% for those with reduced LVEF, respectively). Conclusions: In the BADAPIC registry, a high percentage of heart failure patients had preserved LVEF. Although clinical differences were seen between groups, morbidity and mortality were similar in both groups. PMID:21037850

The clinical and cost-benefits of investing in neurobehavioural rehabilitation: A multi-centre study

PubMed Central

Oddy, Michael

2013-01-01

Primary objective The aim of this study was to investigate the cost-benefits of a residential post-acute neurobehavioural rehabilitation programme and its effects on care needs and social participation of adults with acquired brain injury. Research design Retrospective multi-centre design. Methods and procedures Data on occupation, adaptability and level of support required were collected at admission, discharge and 6-months follow-up. Cost analysis was performed on cost estimates based on level of support. Main outcomes and results Significant gains were observed in all areas of functioning, with individuals progressing towards higher levels of independence and more participation in society upon discharge. Conclusions Cost-benefits of up to £1.13 million were demonstrated for individuals admitted to rehabilitation within a year of sustaining a brain injury and of up to £0.86 million for those admitted more than 1 year after injury. Functional gains and reductions in levels of care required upon discharge were maintained 6 months later. These results demonstrate that post-acute neurobehavioural rehabilitation can have a positive impact on the lives of individuals with brain injury and that the associated costs are off-set by significant savings in the longer-term. PMID:24087973

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.

The organisation of physiotherapy for people with multiple sclerosis across Europe: a multicentre questionnaire survey.

PubMed

Rasova, Kamila; Freeman, Jenny; Martinkova, Patricia; Pavlikova, Marketa; Cattaneo, Davide; Jonsdottir, Johanna; Henze, Thomas; Baert, Ilse; Van Asch, Paul; Santoyo, Carme; Smedal, Tori; Beiske, Antonie Giæver; Stachowiak, Małgorzata; Kovalewski, Mariusz; Nedeljkovic, Una; Bakalidou, Daphne; Guerreiro, José Manuel Alves; Nilsagård, Ylva; Dimitrova, Erieta Nikolikj; Habek, Mario; Armutlu, Kadriye; Donzé, Cécile; Ross, Elaine; Ilie, Ana Maria; Martić, Andrej; Romberg, Anders; Feys, Peter

2016-10-06

Understanding the organisational set-up of physiotherapy services across different countries is increasingly important as clinicians around the world use evidence to improve their practice. This also has to be taken into consideration when multi-centre international clinical trials are conducted. This survey aimed to systematically describe organisational aspects of physiotherapy services for people with multiple sclerosis (MS) across Europe. Representatives from 72 rehabilitation facilities within 23 European countries completed an online web-based questionnaire survey between 2013 and 2014. Countries were categorised according to four European regions (defined by United Nations Statistics). Similarities and differences between regions were examined. Most participating centres specialized in rehabilitation (82 %) and neurology (60 %), with only 38 % specialising in MS. Of these, the Western based Specialist MS centres were predominately based on outpatient services (median MS inpatient ratio 0.14), whilst the Eastern based European services were mostly inpatient in nature (median MS inpatient ratio 0.5). In almost all participating countries, medical doctors - specialists in neurology (60 %) and in rehabilitation (64 %) - were responsible for referral to/prescription of physiotherapy. The most frequent reason for referral to/prescription of physiotherapy was the worsening of symptoms (78 % of centres). Physiotherapists were the most common members of the rehabilitation team; comprising 49 % of the team in Eastern countries compared to approximately 30 % in the rest of Europe. Teamwork was commonly adopted; 86 % of centres based in Western countries utilised the interdisciplinary model, whilst the multidisciplinary model was utilised in Eastern based countries (p = 0.046). This survey is the first to provide data about organisational aspects of physiotherapy for people with MS across Europe. Overall, care in key organisational aspects of service provision is broadly similar across regions, although some variations, for example the models of teamwork utilised, are apparent. Organisational framework specifics should be considered anytime a multi-centre study is conducted and results from such studies are applied.

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

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.

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

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

Multicentre prospective validation of a urinary peptidome-based classifier for the diagnosis of type 2 diabetic nephropathy

PubMed Central

Siwy, Justyna; Schanstra, Joost P.; Argiles, Angel; Bakker, Stephan J.L.; Beige, Joachim; Boucek, Petr; Brand, Korbinian; Delles, Christian; Duranton, Flore; Fernandez-Fernandez, Beatriz; Jankowski, Marie-Luise; Al Khatib, Mohammad; Kunt, Thomas; Lajer, Maria; Lichtinghagen, Ralf; Lindhardt, Morten; Maahs, David M; Mischak, Harald; Mullen, William; Navis, Gerjan; Noutsou, Marina; Ortiz, Alberto; Persson, Frederik; Petrie, John R.; Roob, Johannes M.; Rossing, Peter; Ruggenenti, Piero; Rychlik, Ivan; Serra, Andreas L.; Snell-Bergeon, Janet; Spasovski, Goce; Stojceva-Taneva, Olivera; Trillini, Matias; von der Leyen, Heiko; Winklhofer-Roob, Brigitte M.; Zürbig, Petra; Jankowski, Joachim

2014-01-01

Background Diabetic nephropathy (DN) is one of the major late complications of diabetes. Treatment aimed at slowing down the progression of DN is available but methods for early and definitive detection of DN progression are currently lacking. The ‘Proteomic prediction and Renin angiotensin aldosterone system Inhibition prevention Of early diabetic nephRopathy In TYpe 2 diabetic patients with normoalbuminuria trial’ (PRIORITY) aims to evaluate the early detection of DN in patients with type 2 diabetes (T2D) using a urinary proteome-based classifier (CKD273). Methods In this ancillary study of the recently initiated PRIORITY trial we aimed to validate for the first time the CKD273 classifier in a multicentre (9 different institutions providing samples from 165 T2D patients) prospective setting. In addition we also investigated the influence of sample containers, age and gender on the CKD273 classifier. Results We observed a high consistency of the CKD273 classification scores across the different centres with areas under the curves ranging from 0.95 to 1.00. The classifier was independent of age (range tested 16–89 years) and gender. Furthermore, the use of different urine storage containers did not affect the classification scores. Analysis of the distribution of the individual peptides of the classifier over the nine different centres showed that fragments of blood-derived and extracellular matrix proteins were the most consistently found. Conclusion We provide for the first time validation of this urinary proteome-based classifier in a multicentre prospective setting and show the suitability of the CKD273 classifier to be used in the PRIORITY trial. PMID:24589724

A tutorial on pilot studies: the what, why and how

PubMed Central

2010-01-01

Pilot studies for phase III trials - which are comparative randomized trials designed to provide preliminary evidence on the clinical efficacy of a drug or intervention - are routinely performed in many clinical areas. Also commonly know as "feasibility" or "vanguard" studies, they are designed to assess the safety of treatment or interventions; to assess recruitment potential; to assess the feasibility of international collaboration or coordination for multicentre trials; to increase clinical experience with the study medication or intervention for the phase III trials. They are the best way to assess feasibility of a large, expensive full-scale study, and in fact are an almost essential pre-requisite. Conducting a pilot prior to the main study can enhance the likelihood of success of the main study and potentially help to avoid doomed main studies. The objective of this paper is to provide a detailed examination of the key aspects of pilot studies for phase III trials including: 1) the general reasons for conducting a pilot study; 2) the relationships between pilot studies, proof-of-concept studies, and adaptive designs; 3) the challenges of and misconceptions about pilot studies; 4) the criteria for evaluating the success of a pilot study; 5) frequently asked questions about pilot studies; 7) some ethical aspects related to pilot studies; and 8) some suggestions on how to report the results of pilot investigations using the CONSORT format. PMID:20053272

Intestinal Parasitic Infections among Pregnant Women in Venezuela

PubMed Central

Rodríguez-Morales, Alfonso J.; Barbella, Rosa A.; Case, Cynthia; Arria, Melissa; Ravelo, Marisela; Perez, Henry; Urdaneta, Oscar; Gervasio, Gloria; Rubio, Nestor; Maldonado, Andrea; Aguilera, Ymora; Viloria, Anna; Blanco, Juan J.; Colina, Magdary; Hernández, Elizabeth; Araujo, Elianet; Cabaniel, Gilberto; Benitez, Jesús; Rifakis, Pedro

2006-01-01

Introduction. Intestinal parasitic infections, especially due to helminths, increase anemia in pregnant women. The results of this are low pregnancy weight gain and IUGR, followed by LBW, with its associated greater risks of infection and higher perinatal mortality rates. For these reasons, in the setting of no large previous studies in Venezuela about this problem, a national multicentric study was conducted. Methods. Pregnant women from nine states were studied, a prenatal evaluation with a coproparasitological study. Univariated and multivariated analyses were made to determine risk factors for intestinal parasitosis and related anemia. Results. During 19 months, 1038 pregnant women were included and evaluated. Intestinal parasitosis was evidenced in 73.9%: A lumbricoides 57.0%, T trichiura 36.0%, G lamblia 14.1%, E hystolitica 12.0%, N americanus 8.1%, E vermicularis 6.3%, S stercoralis 3.3%. Relative risk for anemia in those women with intestinal parasitosis was 2.56 (P < .01). Discussion. Intestinal parasitoses could be associated with conditions for development of anemia at pregnancy. These features reflect the need of routine coproparasitological study among pregnant women in rural and endemic zones for intestinal parasites. Further therapeutic and prophylactic protocols are needed. Additional research on pregnant intestinal parasitic infection impact on newborn health is also considered. PMID:17093349

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

Li Xiao; Zhou Xiangping, E-mail: xiangpingzhou46@163.com; Guan Yongsong

Experimental research involving animal models plays a critical role in the development and improvement of minimally invasive therapies for hepatocellular carcinoma (HCC). As a large animal, the pig is commonly used for surgery and interventional radiology research. In this study, liver multicentric HCC with cirrhosis was induced in six China Taihu pigs by intraperitoneal injection of 10 mg/kg of N-nitrosodiethylamine once a week for 3 months, followed by a period of 10-12 months without N-nitrosodiethylamine treatment. All pigs were in generally good health until the end of the study. The tumor nodules appeared hyperattenuating in the arterial phase of amore » dynamic computed tomography (CT) scan. Digital subtraction angiography (DSA) and CT angiography demonstrated that the tumors derived their blood supply mainly from the hepatic artery system. Lipiodol-CT showed Lipiodol retention in tumor areas. The histology and electron microscopic ultrastructure of the chemically induced liver HCC in this study resembled human HCC with a cirrhosis background. An immunohistochemistry study confirmed that the tumors were of hepatocyte origin. All highly, moderately, and poorly differentiated HCC tumors were identified in this study. Cholangiocarcinoma was not seen in any of the animals. Due to its comparable size to human anatomy, the pig liver HCC model would give a better scope for interventional and surgical manipulations than small animal models.« less

Anthropometrics and prognosis in diffuse large B-cell lymphoma: a multicentre study of 653 patients.

PubMed

Bendtsen, Mette Dahl; Munksgaard, Peter Svenssen; Severinsen, Marianne Tang; Bekric, Eric; Brieghel, Christian; Nielsen, Kristina Buchardi; Brown, Peter de Nully; Dybkaer, Karen; Johnsen, Hans Erik; Bøgsted, Martin; El-Galaly, Tarec Christoffer

2017-04-01

The impact of body mass index (BMI) and body surface area (BSA) on survival in diffuse large B-cell lymphoma (DLBCL) is controversial. Recent studies show superior outcomes for overweight and obese patients. A total of 653 R-CHOP(-like)-treated DLBCL patients were included in this retrospective cohort study. Patients, baseline clinicopathologic characteristics and treatment information were retrieved from the Danish Lymphoma Registry. Anthropometric measures were obtained from chemotherapy prescription charts. Underweight (BMI <18.5 kg/m 2 ) was associated with significantly worse progression-free survival (PFS) for male patients only in sex-stratified analyses (HR 3.92, 95% CI: 1.57-9.75, P = 0.003, for males; HR 1.65, 95% CI: 0.90-3.02, P = 0.107, for females). In multivariate analyses, underweight was associated with worse PFS for both sexes (HR 5.34, 95% CI: 2.07-13.79, P = 0.001, for males; HR 2.14, 95% CI: 1.12-4.08, P = 0.021, for females). Similar results were obtained in analyses of overall survival. In crude analyses, BSA <1.8 m 2 was associated with worse PFS for men and women (HR 1.65, 95% CI: 1.03-2.65, P = 0.039, for men; HR 1.62, 95% CI: 1.03-2.56, P = 0.037, for women). In multivariate analyses, however, these associations diminished. Our study demonstrates that underweight DLBCL patients have worse outcomes following R-CHOP as compared to normal as well as overweight patients. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Effectiveness and safety of bedaquiline-containing regimens in the treatment of MDR- and XDR-TB: a multicentre study.

PubMed

Borisov, Sergey E; Dheda, Keertan; Enwerem, Martin; Romero Leyet, Rodolfo; D'Ambrosio, Lia; Centis, Rosella; Sotgiu, Giovanni; Tiberi, Simon; Alffenaar, Jan-Willem; Maryandyshev, Andrey; Belilovski, Evgeny; Ganatra, Shashank; Skrahina, Alena; Akkerman, Onno; Aleksa, Alena; Amale, Rohit; Artsukevich, Janina; Bruchfeld, Judith; Caminero, Jose A; Carpena Martinez, Isabel; Codecasa, Luigi; Dalcolmo, Margareth; Denholm, Justin; Douglas, Paul; Duarte, Raquel; Esmail, Aliasgar; Fadul, Mohammed; Filippov, Alexey; Davies Forsman, Lina; Gaga, Mina; Garcia-Fuertes, Julia-Amaranta; García-García, José-María; Gualano, Gina; Jonsson, Jerker; Kunst, Heinke; Lau, Jillian S; Lazaro Mastrapa, Barbara; Teran Troya, Jorge Lazaro; Manga, Selene; Manika, Katerina; González Montaner, Pablo; Mullerpattan, Jai; Oelofse, Suzette; Ortelli, Martina; Palmero, Domingo Juan; Palmieri, Fabrizio; Papalia, Antonella; Papavasileiou, Apostolos; Payen, Marie-Christine; Pontali, Emanuele; Robalo Cordeiro, Carlos; Saderi, Laura; Sadutshang, Tsetan Dorji; Sanukevich, Tatsiana; Solodovnikova, Varvara; Spanevello, Antonio; Topgyal, Sonam; Toscanini, Federica; Tramontana, Adrian R; Udwadia, Zarir Farokh; Viggiani, Pietro; White, Veronica; Zumla, Alimuddin; Migliori, Giovanni Battista

2017-05-01

Large studies on bedaquiline used to treat multidrug-resistant (MDR-) and extensively drug-resistant tuberculosis (XDR-TB) are lacking. This study aimed to evaluate the safety and effectiveness of bedaquiline-containing regimens in a large, retrospective, observational study conducted in 25 centres and 15 countries in five continents.428 culture-confirmed MDR-TB cases were analysed (61.5% male; 22.1% HIV-positive, 45.6% XDR-TB). MDR-TB cases were admitted to hospital for a median (interquartile range (IQR)) 179 (92-280) days and exposed to bedaquiline for 168 (86-180) days. Treatment regimens included, among others, linezolid, moxifloxacin, clofazimine and carbapenems (82.0%, 58.4%, 52.6% and 15.3% of cases, respectively).Sputum smear and culture conversion rates in MDR-TB cases were 63.6% and 30.1%, respectively at 30 days, 81.1% and 56.7%, respectively at 60 days; 85.5% and 80.5%, respectively at 90 days and 88.7% and 91.2%, respectively at the end of treatment. The median (IQR) time to smear and culture conversion was 34 (30-60) days and 60 (33-90) days. Out of 247 culture-confirmed MDR-TB cases completing treatment, 71.3% achieved success (62.4% cured; 8.9% completed treatment), 13.4% died, 7.3% defaulted and 7.7% failed. Bedaquiline was interrupted due to adverse events in 5.8% of cases. A single case died, having electrocardiographic abnormalities that were probably non-bedaquiline related.Bedaquiline-containing regimens achieved high conversion and success rates under different nonexperimental conditions. Copyright ©ERS 2017.

Pressure ulcer knowledge of registered nurses, assistant nurses and student nurses: a descriptive, comparative multicentre study in Sweden.

PubMed

Gunningberg, Lena; Mårtensson, Gunilla; Mamhidir, Anna-Greta; Florin, Jan; Muntlin Athlin, Åsa; Bååth, Carina

2015-08-01

The aim of this study was to describe and compare the knowledge of registered nurses (RNs), assistant nurses (ANs) and student nurses (SNs) about preventing pressure ulcers (PUs). PU prevention behaviours in the clinical practice of RNs and ANs were also explored. A descriptive, comparative multicentre study was performed. Hospital wards and universities from four Swedish county councils participated. In total, 415 participants (RN, AN and SN) completed the Pressure Ulcer Knowledge Assessment Tool. The mean knowledge score for the sample was 58·9%. The highest scores were found in the themes 'nutrition' (83·1%) and 'risk assessment' (75·7%). The lowest scores were found in the themes 'reduction in the amount of pressure and shear' (47·5%) and 'classification and observation' (55·5%). RNs and SNs had higher scores than ANs on 'aetiology and causes'. SNs had higher scores than RNs and ANs on 'nutrition'. It has been concluded that there is a knowledge deficit in PU prevention among nursing staff in Sweden. A major educational campaign needs to be undertaken both in hospital settings and in nursing education. © 2013 The Authors. International Wound Journal © 2013 Medicalhelplines.com Inc and John Wiley & Sons Ltd.

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.

Clinical outcome after the use of a new craniocaudal expandable implant for vertebral compression fracture treatment: one year results from a prospective multicentric study.

PubMed

Noriega, David; Krüger, Antonio; Ardura, Francisco; Hansen-Algenstaedt, Nils; Hassel, Frank; Barreau, Xavier; Beyerlein, Jörg

2015-01-01

The purpose of this prospective multicentric observational study was to confirm the safety and clinical performance of a craniocaudal expandable implant used in combination with high viscosity PMMA bone cement for the treatment of vertebral compression fractures. Thirty-nine VCFs in 32 patients were treated using the SpineJack minimally invasive surgery protocol. Outcome was determined by using the Visual Analogue Scale for measuring pain, the Oswestry Disability Index for scoring functional capacity, and the self-reporting European Quality of Life scores for the quality of life. Safety was evaluated by reporting all adverse events. The occurrence of cement leakages was assessed by either radiographs or CT scan or both. Statistically significant improvements were found regarding pain, function, and quality of life. The global pain score reduction at 1 year was 80.9% compared to the preoperative situation and the result of the Oswestry Disability Index showed a decrease from 65.0% at baseline to 10.5% at 12 months postoperatively. The cement leakage rate was 30.8%. No device- or surgery-related complications were found. This observational study demonstrates promising and persistent results consisting of immediate and sustained pain relief and durable clinical improvement after the procedure and throughout the 1-year follow-up period.

MRI of the wrist in juvenile idiopathic arthritis: proposal of a paediatric synovitis score by a consensus of an international working group. Results of a multicentre reliability study.

PubMed

Damasio, Maria Beatrice; Malattia, Clara; Tanturri de Horatio, Laura; Mattiuz, Chiara; Pistorio, Angela; Bracaglia, Claudia; Barbuti, Domenico; Boavida, Peter; Juhan, Karen Lambot; Ording, Lil Sophie Mueller; Rosendahl, Karen; Martini, Alberto; Magnano, GianMichele; Tomà, Paolo

2012-09-01

MRI is a sensitive tool for the evaluation of synovitis in juvenile idiopathic arthritis (JIA). The purpose of this study was to introduce a novel MRI-based score for synovitis in children and to examine its inter- and intraobserver variability in a multi-centre study. Wrist MRI was performed in 76 children with JIA. On postcontrast 3-D spoiled gradient-echo and fat-suppressed T2-weighted spin-echo images, joint recesses were scored for the degree of synovial enhancement, effusion and overall inflammation independently by two paediatric radiologists. Total-enhancement and inflammation-synovitis scores were calculated. Interobserver agreement was poor to moderate for enhancement and inflammation in all recesses, except in the radioulnar and radiocarpal joints. Intraobserver agreement was good to excellent. For enhancement and inflammation scores, mean differences (95 % CI) between observers were -1.18 (-4.79 to 2.42) and -2.11 (-6.06 to 1.83). Intraobserver variability (reader 1) was 0 (-1.65 to 1.65) and 0.02 (-1.39 to 1.44). Intraobserver agreement was good. Except for the radioulnar and radiocarpal joints, interobserver agreement was not acceptable. Therefore, the proposed scoring system requires further refinement.

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.

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.

Receptor for advanced glycation end-products and ARDS prediction: a multicentre observational study.

PubMed

Jabaudon, Matthieu; Berthelin, Pauline; Pranal, Thibaut; Roszyk, Laurence; Godet, Thomas; Faure, Jean-Sébastien; Chabanne, Russell; Eisenmann, Nathanael; Lautrette, Alexandre; Belville, Corinne; Blondonnet, Raiko; Cayot, Sophie; Gillart, Thierry; Pascal, Julien; Skrzypczak, Yvan; Souweine, Bertrand; Blanchon, Loic; Sapin, Vincent; Pereira, Bruno; Constantin, Jean-Michel

2018-02-08

Acute respiratory distress syndrome (ARDS) prediction remains challenging despite available clinical scores. To assess soluble receptor for advanced glycation end-products (sRAGE), a marker of lung epithelial injury, as a predictor of ARDS in a high-risk population, adult patients with at least one ARDS risk factor upon admission to participating intensive care units (ICUs) were enrolled in a multicentre, prospective study between June 2014 and January 2015. Plasma sRAGE and endogenous secretory RAGE (esRAGE) were measured at baseline (ICU admission) and 24 hours later (day one). Four AGER candidate single nucleotide polymorphisms (SNPs) were also assayed because of previous reports of functionality (rs1800625, rs1800624, rs3134940, and rs2070600). The primary outcome was ARDS development within seven days. Of 500 patients enrolled, 464 patients were analysed, and 59 developed ARDS by day seven. Higher baseline and day one plasma sRAGE, but not esRAGE, were independently associated with increased ARDS risk. AGER SNP rs2070600 (Ser/Ser) was associated with increased ARDS risk and higher plasma sRAGE in this cohort, although confirmatory studies are needed to assess the role of AGER SNPs in ARDS prediction. These findings suggest that among at-risk ICU patients, higher plasma sRAGE may identify those who are more likely to develop ARDS.

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.

Is balance performance reduced after mild traumatic brain injury?: Interim analysis from chronic effects of neurotrauma consortium (CENC) multi-centre study.

PubMed

Walker, William C; Nowak, Kayla J; Kenney, Kimbra; Franke, Laura Manning; Eapen, Blessen C; Skop, Karen; Levin, Harvey; Agyemang, Amma A; Tate, David F; Wilde, Elisabeth A; Hinds, Sidney; Nolen, Tracy L

2018-06-12

Determine if mild traumatic brain injury (mTBI) history is associated with balance disturbances. Chronic Effects of Neurotrauma Consortium (CENC) centres. The CENC multi-centre study enrols post-9/11 era Service Members and Veterans with combat exposure. This sample (n = 322) consisted of enrolees completing initial evaluation by September 2016 at the three sites conducting computerized dynamic post-urography (CDP) testing. Observational study with cross-sectional analyses using structural equation modelling. Comprehensive structured interviews were used to diagnose all lifetime mild traumatic brain injuries (mTBIs). The outcome, Sensory Organization Test (SOT), was measured on CDP dual-plate force platform. Other studied variables were measured by structured interviews, record review and questionnaires. The overall positive/negative mTBI classification did not have a significant effect on the composite equilibrium score. However, the repetitive mTBI classification showed lower scores for participants with ≥ 3 mTBI versus 1-2 lifetime mTBIs. For repetitive mTBI, pain interference acted as a mediator for the indirect effect, and a direct effect was evident on some sensory condition equilibrium scores. These findings show that repeated mTBI, partially mediated by pain, may lead to later balance disturbances among military combatants. Further study of CDP outcomes within this accruing cohort is warranted.

Ibrutinib in Treating Relapsed or Refractory B-Cell Non-Hodgkin Lymphoma in Patients With HIV Infection

ClinicalTrials.gov

2015-08-18

Adult B Acute Lymphoblastic Leukemia; Chronic Lymphocytic Leukemia; Cutaneous B-Cell Non-Hodgkin Lymphoma; Extranodal Marginal Zone Lymphoma of Mucosa-Associated Lymphoid Tissue; HIV Infection; Intraocular Lymphoma; Multicentric Angiofollicular Lymphoid Hyperplasia; Nodal Marginal Zone Lymphoma; Recurrent Adult Acute Lymphoblastic Leukemia; Recurrent Adult Burkitt Lymphoma; Recurrent Adult Diffuse Large Cell Lymphoma; Recurrent Adult Diffuse Mixed Cell Lymphoma; Recurrent Adult Diffuse Small Cleaved Cell Lymphoma; Recurrent Adult Grade III Lymphomatoid Granulomatosis; Recurrent Adult Immunoblastic Lymphoma; Recurrent Adult Lymphoblastic Lymphoma; Recurrent Grade 1 Follicular Lymphoma; Recurrent Grade 2 Follicular Lymphoma; Recurrent Grade 3 Follicular Lymphoma; Recurrent Mantle Cell Lymphoma; Recurrent Marginal Zone Lymphoma; Recurrent Small Lymphocytic Lymphoma; Refractory Chronic Lymphocytic Leukemia; Refractory Hairy Cell Leukemia; Refractory Plasma Cell Myeloma; Small Intestinal Lymphoma; Splenic Marginal Zone Lymphoma; Testicular Lymphoma; Waldenstrom Macroglobulinemia

Radiomics: Extracting more information from medical images using advanced feature analysis

PubMed Central

Lambin, Philippe; Rios-Velazquez, Emmanuel; Leijenaar, Ralph; Carvalho, Sara; van Stiphout, Ruud G.P.M.; Granton, Patrick; Zegers, Catharina M.L.; Gillies, Robert; Boellard, Ronald; Dekker, André; Aerts, Hugo J.W.L.

2015-01-01

Solid cancers are spatially and temporally heterogeneous. This limits the use of invasive biopsy based molecular assays but gives huge potential for medical imaging, which has the ability to capture intra-tumoural heterogeneity in a non-invasive way. During the past decades, medical imaging innovations with new hardware, new imaging agents and standardised protocols, allows the field to move towards quantitative imaging. Therefore, also the development of automated and reproducible analysis methodologies to extract more information from image-based features is a requirement. Radiomics – the high-throughput extraction of large amounts of image features from radiographic images – addresses this problem and is one of the approaches that hold great promises but need further validation in multi-centric settings and in the laboratory. PMID:22257792

Acupuncture in urological practice--a survey of urologists in England.

PubMed

Tempest, Heidi; Reynard, John; Bryant, Richard J; Hamdy, Freddie C; Larré, Stéphane

2011-02-01

To determine the feasibility of obtaining cooperation from urologists in carrying out large-scale studies on the efficacy of acupuncture for the treatment of urological conditions, based on urologists' general views and knowledge of acupuncture. A questionnaire was distributed to 145 urologists within three training deaneries within England. A response rate of 70% (n=102) was achieved. The majority of urologists rated their knowledge of acupuncture as low (46%, n=46) and their general attitude towards acupuncture was neutral (54%, n=55). The majority of responding urologists (95%) thought that acupuncture may be of value in urological conditions, and acupuncture was suggested to patients by 30 urologists (29%). The urologists most likely to suggest acupuncture to their patients were typically over 40 years of age, more experienced, not in a training post, and since starting their urological career had changed their attitude towards acupuncture. In a multivariate analysis, a change of view regarding the efficacy of acupuncture was found to be the only variable significantly associated with a recommendation of acupuncture to patients. Although overall knowledge about acupuncture was poor, most responding urologists thought acupuncture may be useful for urological conditions. Those who had changed their views were most likely to suggest acupuncture to their patients. Acupuncture for urological conditions warrants further investigation and, as this study has shown high interest within the urological community large clinical trials involving multicentres may be feasible. Copyright © 2010 Elsevier Ltd. All rights reserved.

Thymoma: first large Indian experience.

PubMed

Rathod, S; Munshi, A; Paul, S; Ganesh, B; Prabhash, K; Agarwal, J P

2014-01-01

Thymoma is the most common tumor of the anterior mediastinum. Surgery is mainstay of treatment, with adjuvant radiation recommended for invasive thymoma. Because of rarity, prospective randomized trials may not be feasible even in multicentric settings hence the best possible evidence can be large series. Till date Thymoma has not been studied in Indian settings. All patients presenting to Thoracic disease management group at our Centre during 2006-2011 were screened. Sixty two patients' with histo-pathological confirmation of thymoma medical records could be retrieved and are presented in this study. Mosaoka staging and WHO classification was used. The clinical, therapeutic factors and follow up parameters were recorded and survival was calculated. Effects of prognostic factors were compared. Sixty two patients were identified (36M, 26F; age 22-84, median 51.5 years) and majorities (57%) of thymoma were stage I-II. WHO pathological subtype B was most common 30 (49%). Mean tumor size was smaller in patients with myasthenia (5.3cm) than the entire group (7.6cm). Neoadjuvant therapy was offered to five unresectable stages III or IV a patient's with 40% resectability rates. Median overall survival was 60 months (Inter quartile-range 3-44 months) with overall survival rate (OS) at three year being 90%. Resectable tumors had better outcomes (94%) than non resectable (81%) at three years. Mosaoka Stage was the only significant (P = 0.03) prognostic factor on multivariate analysis. This is first thymoma series from India with large number of patients where staging is an important prognostic factor and surgery is the mainstay of therapy. In Indian context aggressive multimodality treatment should be offered to advanced stage patients and which yields good survival rates and comparable.

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.

Metabolomic profiling in perinatal asphyxia: a promising new field.

PubMed

Denihan, Niamh M; Boylan, Geraldine B; Murray, Deirdre M

2015-01-01

Metabolomics, the latest "omic" technology, is defined as the comprehensive study of all low molecular weight biochemicals, "metabolites" present in an organism. As a systems biology approach, metabolomics has huge potential to progress our understanding of perinatal asphyxia and neonatal hypoxic-ischaemic encephalopathy, by uniquely detecting rapid biochemical pathway alterations in response to the hypoxic environment. The study of metabolomic biomarkers in the immediate neonatal period is not a trivial task and requires a number of specific considerations, unique to this disease and population. Recruiting a clearly defined cohort requires standardised multicentre recruitment with broad inclusion criteria and the participation of a range of multidisciplinary staff. Minimally invasive biospecimen collection is a priority for biomarker discovery. Umbilical cord blood presents an ideal medium as large volumes can be easily extracted and stored and the sample is not confounded by postnatal disease progression. Pristine biobanking and phenotyping are essential to ensure the validity of metabolomic findings. This paper provides an overview of the current state of the art in the field of metabolomics in perinatal asphyxia and neonatal hypoxic-ischaemic encephalopathy. We detail the considerations required to ensure high quality sampling and analysis, to support scientific progression in this important field.

Metabolomic Profiling in Perinatal Asphyxia: A Promising New Field

PubMed Central

Denihan, Niamh M.; Boylan, Geraldine B.; Murray, Deirdre M.

2015-01-01

Metabolomics, the latest “omic” technology, is defined as the comprehensive study of all low molecular weight biochemicals, “metabolites” present in an organism. As a systems biology approach, metabolomics has huge potential to progress our understanding of perinatal asphyxia and neonatal hypoxic-ischaemic encephalopathy, by uniquely detecting rapid biochemical pathway alterations in response to the hypoxic environment. The study of metabolomic biomarkers in the immediate neonatal period is not a trivial task and requires a number of specific considerations, unique to this disease and population. Recruiting a clearly defined cohort requires standardised multicentre recruitment with broad inclusion criteria and the participation of a range of multidisciplinary staff. Minimally invasive biospecimen collection is a priority for biomarker discovery. Umbilical cord blood presents an ideal medium as large volumes can be easily extracted and stored and the sample is not confounded by postnatal disease progression. Pristine biobanking and phenotyping are essential to ensure the validity of metabolomic findings. This paper provides an overview of the current state of the art in the field of metabolomics in perinatal asphyxia and neonatal hypoxic-ischaemic encephalopathy. We detail the considerations required to ensure high quality sampling and analysis, to support scientific progression in this important field. PMID:25802843

Automated astatination of biomolecules – a stepping stone towards multicenter clinical trials

PubMed Central

Aneheim, Emma; Albertsson, Per; Bäck, Tom; Jensen, Holger; Palm, Stig; Lindegren, Sture

2015-01-01

To facilitate multicentre clinical studies on targeted alpha therapy, it is necessary to develop an automated, on-site procedure for conjugating rare, short-lived, alpha-emitting radionuclides to biomolecules. Astatine-211 is one of the few alpha-emitting nuclides with appropriate chemical and physical properties for use in targeted therapies for cancer. Due to the very short range of the emitted α-particles, this therapy is particularly suited to treating occult, disseminated cancers. Astatine is not intrinsically tumour-specific; therefore, it requires an appropriate tumour-specific targeting vector, which can guide the radiation to the cancer cells. Consequently, an appropriate method is required for coupling the nuclide to the vector. To increase the availability of astatine-211 radiopharmaceuticals for targeted alpha therapy, their production should be automated. Here, we present a method that combines dry distillation of astatine-211 and a synthesis module for producing radiopharmaceuticals into a process platform. This platform will standardize production of astatinated radiopharmaceuticals, and hence, it will facilitate large clinical studies focused on this promising, but chemically challenging, alpha-emitting radionuclide. In this work, we describe the process platform, and we demonstrate the production of both astaine-211, for preclinical use, and astatine-211 labelled antibodies. PMID:26169786

Obstructive sleep apnea syndrome and hypothyroidism - merely concurrence or causal association?

PubMed

Kuczyński, Wojciech; Gabryelska, Agata; Mokros, Łukasz; Białasiewicz, Piotr

2016-01-01

The prevalence of obstructive sleep apnea-hypopnea syndrome (OSAHS) ranges from 4 to 7% in men and from 2 to 5% in women. Its deleterious consequences such as traffic accidents, cardiovascular complications increasing morbidity and mortality, make it a major health problem. Apart from obesity (a major risk factor for OSAHS), hypothyroid patients are prone to reveal this phenotype. Although hypothyroidism seems an acknowledged risk factor for OSAHS, some authors report the lack of clinically relevant association. The argument partly depends on the increased prevalence of hypothyroidism in OSAHS patients, but the epidemiological data is limited and somehow inconsistent; even less is known about sub-clinical hypothyroidism in OSAHS patients. Even if frequency of overt and sub-clinical hypothyroidism in OSAHS patients is comparable to the general population, screening for it seems beneficial, as hormone replacement therapy may improve sleep disordered breathing. Unfortunately, this favorable outcome was found only in a few studies with limited number of patients with hypothyroidism. Yet, despite the lack of international guidelines and no large multicentre studies on the topic available, we think that TSH screening might prove beneficial in vast majority of OSAHS patients.

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

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.

Determinants of total and specific IgE in infants with atopic dermatitis. ETAC Study Group. Early Treatment of the Atopic Child.

PubMed

1997-11-01

ETAC (Early Treatment of the Atopic Child), a multi-centre predominantly European study to investigate the potential for cetirizine to prevent the development of asthma in infants with atopic dermatitis has completed enrollment: 817 children have been randomised to 18 months' treatment with either active or placebo and a subsequent 18 months of post-treatment follow-up. Results of the therapeutic effects will not be available for some time, but the study has provided an opportunity to investigate influences on sensitization to allergens in a large cohort of 1-2 years olds with already established atopic dermatitis, resident in different countries and in different environments. The study shows that in infants with atopic dermatitis, raised serum total IgE has significantly different determinants from that a specific allergen sensitization. In infancy, increased total IgE is more affected by factors increasing risk of intercurrent infection and non-specific airway inflammation, such as environmental tobacco smoke exposure (p < 0.001) and the use of gas cookers (p = 0.02). Specific allergen sensitization as represented by detectable IgE antibodies is influenced primarily by allergen exposure. In Sweden, low level exposure to allergens is associated with reduced specific allergen sensitization rates even though the infants already have atopic dermatitis.

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

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.

Effects of metabolic syndrome on arterial function in different age groups: the Advanced Approach to Arterial Stiffness study.

PubMed

Topouchian, Jirar; Labat, Carlos; Gautier, Sylvie; Bäck, Magnus; Achimastos, Apostolos; Blacher, Jacques; Cwynar, Marcin; de la Sierra, Alejandro; Pall, Denes; Fantin, Francesco; Farkas, Katalin; Garcia-Ortiz, Luis; Hakobyan, Zoya; Jankowski, Piotr; Jelakovic, Ana; Kobalava, Zhanna; Konradi, Alexandra; Kotovskaya, Yulia; Kotsani, Marina; Lazareva, Irina; Litvin, Alexander; Milyagin, Viktor; Mintale, Iveta; Persson, Oscar; Ramos, Rafael; Rogoza, Anatoly; Ryliskyte, Ligita; Scuteri, Angelo; Sirenko, Yuriy; Soulis, Georges; Tasic, Nebojsa; Udovychenko, Maryna; Urazalina, Saule; Wohlfahrt, Peter; Zelveian, Parounak; Benetos, Athanase; Asmar, Roland

2018-04-01

The aim of the Advanced Approach to Arterial Stiffness study was to compare arterial stiffness measured simultaneously with two different methods in different age groups of middle-aged and older adults with or without metabolic syndrome (MetS). The specific effects of the different MetS components on arterial stiffness were also studied. This prospective, multicentre, international study included 2224 patients aged 40 years and older, 1664 with and 560 without MetS. Patients were enrolled in 32 centres from 18 European countries affiliated to the International Society of Vascular Health & Aging. Arterial stiffness was evaluated using the cardio-ankle vascular index (CAVI) and the carotid-femoral pulse wave velocity (CF-PWV) in four prespecified age groups: 40-49, 50-59, 60-74, 75-90 years. In this report, we present the baseline data of this study. Both CF-PWV and CAVI increased with age, with a higher correlation coefficient for CAVI (comparison of coefficients P < 0.001). Age-adjusted and sex-adjusted values of CF-PWV and CAVI were weakly intercorrelated (r = 0.06, P < 0.001). Age-adjusted and sex-adjusted values for CF-PWV but not CAVI were higher in presence of MetS (CF-PWV: 9.57 ± 0.06 vs. 8.65 ± 0.10, P < 0.001; CAVI: 8.34 ± 0.03 vs. 8.29 ± 0.04, P = 0.40; mean ± SEM; MetS vs. no MetS). The absence of an overall effect of MetS on CAVI was related to the heterogeneous effects of the components of MetS on this parameter: CAVI was positively associated with the high glycaemia and high blood pressure components, whereas lacked significant associations with the HDL and triglycerides components while exhibiting a negative association with the overweight component. In contrast, all five MetS components showed positive associations with CF-PWV. This large European multicentre study reveals a differential impact of MetS and age on CAVI and CF-PWV and suggests that age may have a more pronounced effect on CAVI, whereas MetS increases CF-PWV but not CAVI. This important finding may be due to heterogeneous effects of MetS components on CAVI. The clinical significance of these original results will be assessed during the longitudinal phase of the study.

The role of dosimetry audit in lung SBRT multi-centre clinical trials.

PubMed

Clark, Catharine H; Hurkmans, Coen W; Kry, Stephen F

2017-12-01

Stereotactic Body Radiotherapy (SBRT) in the lung is a challenging technique which requires high quality clinical trials to answer the un-resolved clinical questions. Quality assurance of these clinical trials not only ensures the safety of the treatment of the participating patients but also minimises the variation in treatment, thus allowing the lowest number of patient treatments to answer the trial question. This review addresses the role of dosimetry audits in the quality assurance process and considers what can be done to ensure the highest accuracy of dose calculation and delivery and it's assessment in multi-centre trials. Copyright © 2017 Associazione Italiana di Fisica Medica. Published by Elsevier Ltd. All rights reserved.

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.

Prevention of hospital infections by intervention and training (PROHIBIT): results of a pan-European cluster-randomized multicentre study to reduce central venous catheter-related bloodstream infections.

PubMed

van der Kooi, Tjallie; Sax, Hugo; Pittet, Didier; van Dissel, Jaap; van Benthem, Birgit; Walder, Bernhard; Cartier, Vanessa; Clack, Lauren; de Greeff, Sabine; Wolkewitz, Martin; Hieke, Stefanie; Boshuizen, Hendriek; van de Kassteele, Jan; Van den Abeele, Annemie; Boo, Teck Wee; Diab-Elschahawi, Magda; Dumpis, Uga; Ghita, Camelia; FitzGerald, Susan; Lejko, Tatjana; Leleu, Kris; Martinez, Mercedes Palomar; Paniara, Olga; Patyi, Márta; Schab, Paweł; Raglio, Annibale; Szilágyi, Emese; Ziętkiewicz, Mirosław; Wu, Albert W; Grundmann, Hajo; Zingg, Walter

2018-01-01

To test the effectiveness of a central venous catheter (CVC) insertion strategy and a hand hygiene (HH) improvement strategy to prevent central venous catheter-related bloodstream infections (CRBSI) in European intensive care units (ICUs), measuring both process and outcome indicators. Adult ICUs from 14 hospitals in 11 European countries participated in this stepped-wedge cluster randomised controlled multicentre intervention study. After a 6 month baseline, three hospitals were randomised to one of three interventions every quarter: (1) CVC insertion strategy (CVCi); (2) HH promotion strategy (HHi); and (3) both interventions combined (COMBi). Primary outcome was prospective CRBSI incidence density. Secondary outcomes were a CVC insertion score and HH compliance. Overall 25,348 patients with 35,831 CVCs were included. CRBSI incidence density decreased from 2.4/1000 CVC-days at baseline to 0.9/1000 (p < 0.0001). When adjusted for patient and CVC characteristics all three interventions significantly reduced CRBSI incidence density. When additionally adjusted for the baseline decreasing trend, the HHi and COMBi arms were still effective. CVC insertion scores and HH compliance increased significantly with all three interventions. This study demonstrates that multimodal prevention strategies aiming at improving CVC insertion practice and HH reduce CRBSI in diverse European ICUs. Compliance explained CRBSI reduction and future quality improvement studies should encourage measuring process indicators.

Crisaborole Ointment 2%: A Review in Mild to Moderate Atopic Dermatitis.

PubMed

Hoy, Sheridan M

2017-12-01

Crisaborole ointment 2% (Eucrisa™) is a novel, anti-inflammatory inhibitor of phosphodiesterase 4 (PDE4) that is available in the USA for the topical treatment of mild to moderate atopic dermatitis in patients aged ≥ 2 years. In two short-term (28 days), identically designed, multicentre, phase III studies in this patient population, topical therapy with crisaborole ointment 2% reduced disease severity and pruritus severity compared with vehicle, with the effect established early and sustained over the course of treatment. Improvements in the other signs of atopic dermatitis (erythema, exudation, excoriation, induration/papulation, and lichenification) were also seen. Crisaborole ointment 2% was generally well tolerated in the short-term studies, with its favorable safety profile maintained over the longer term (up to 52 weeks) in a multicentre, extension study. Most treatment-emergent adverse events (TEAEs) were of mild to moderate severity and considered unrelated to the study medication. Moreover, the incidence of application-site pain following short- and longer-term topical therapy with crisaborole ointment 2% was low. In conclusion, crisaborole ointment 2% is an effective and generally well tolerated new topical option for the management of mild to moderate atopic dermatitis in patients aged ≥ 2 years, with the potential to effectively treat this patient population over the longer term without the safety concerns associated with other current topical anti-inflammatory agents.

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.

Coping strategies for postpartum depression: a multi-centric study of 1626 women.

PubMed

Gutiérrez-Zotes, Alfonso; Labad, Javier; Martín-Santos, Rocío; García-Esteve, Luisa; Gelabert, Estel; Jover, Manuel; Guillamat, Roser; Mayoral, Fermín; Gornemann, Isolde; Canellas, Francesca; Gratacós, Mónica; Guitart, Montserrat; Roca, Miguel; Costas, Javier; Ivorra, Jose Luis; Navinés, Ricard; de Diego-Otero, Yolanda; Vilella, Elisabet; Sanjuan, Julio

2016-06-01

The transition to motherhood is stressful as it requires several important changes in family dynamics, finances, and working life, along with physical and psychological adjustments. This study aimed at determining whether some forms of coping might predict postpartum depressive symptomatology. A total of 1626 pregnant women participated in a multi-centric longitudinal study. Different evaluations were performed 8 and 32 weeks after delivery. Depression was assessed using the Edinburgh Postnatal Depression Scale (EPDS) and the structured Diagnostic Interview for Genetic Studies (DIGS). The brief Coping Orientation for Problem Experiences (COPE) scale was used to measure coping strategies 2-3 days postpartum. Some coping strategies differentiate between women with and without postpartum depression. A logistic regression analysis was used to explore the relationships between the predictors of coping strategies and major depression (according to DSM-IV criteria). In this model, the predictor variables during the first 32 weeks were self-distraction (OR 1.18, 95 % CI 1.04-1.33), substance use (OR 0.58, 95 % CI 0.35-0.97), and self-blame (OR 1.18, 95 % CI 1.04-1.34). In healthy women with no psychiatric history, some passive coping strategies, both cognitive and behavioral, are predictors of depressive symptoms and postpartum depression and help differentiate between patients with and without depression.

Multicentre study of fragrance allergy in Hungary. Immediate and late type reactions.

PubMed

Temesvári, Erzsébet; Németh, Ilona; Baló-Banga, Mátyás J; Husz, Sándor; Kohánka, Valéria; Somos, Zsuzsa; Judák, Rita; Remenyik, E V A; Szegedi, Andrea; Nebenführer, László; Mészáros, Csilla; Horváth, Attila

2002-06-01

The authors followed the frequency of fragrance contact sensitization in Hungary in a multicentre study in the years 1998 and 1999. A total of 3,604 patients were tested with fragrance mix (FM), and positive reactions were observed in 294 (8.2%). In 160 FM hypersensitive patients, the study was continued with patch testing of the mix constituents (cinnamic alcohol, cinnamic aldehyde, eugenol, amyl cinnamic aldehyde, hydroxycitronellal, geraniol, isoeugenol, oak moss absolute). Of the patients tested, 70.6% produced positive reactions to the constituents. FM contact sensitization was mainly observed in female patients (74.4%). The incidence of contact urticaria in FM hypersensitive patients was 6.1%. Simultaneous patch test trials of other environmental contact allergens, in both early and late evaluations, mainly confirmed hypersensitivity reactions to balsams. Female dominance of hypersensitivity reactions observed during testing the individual components of the mix was striking (82.4%). In positive skin reactions, cinnamic alcohol, isoeugenol and oak moss provoked skin symptoms most frequently. We also tested the 104 patients who produced negative reactions to FM with the constituent individual allergens, with 11.9% positive incidence. The clinical symptoms of the patients were above all manifest in the form of contact eczema, located on the hands, face, eyelids and axillae. With this study, the authors, members of the Hungarian Contact Dermatitis Research Group, call attention to one of the most frequent allergens in the environment.

A metadata-aware application for remote scoring and exchange of tissue microarray images

PubMed Central

2013-01-01

Background The use of tissue microarrays (TMA) and advances in digital scanning microscopy has enabled the collection of thousands of tissue images. There is a need for software tools to annotate, query and share this data amongst researchers in different physical locations. Results We have developed an open source web-based application for remote scoring of TMA images, which exploits the value of Microsoft Silverlight Deep Zoom to provide a intuitive interface for zooming and panning around digital images. We use and extend existing XML-based standards to ensure that the data collected can be archived and that our system is interoperable with other standards-compliant systems. Conclusion The application has been used for multi-centre scoring of TMA slides composed of tissues from several Phase III breast cancer trials and ten different studies participating in the International Breast Cancer Association Consortium (BCAC). The system has enabled researchers to simultaneously score large collections of TMA and export the standardised data to integrate with pathological and clinical outcome data, thereby facilitating biomarker discovery. PMID:23635078

Antimicrobial activity of a multispecies probiotic (Ecologic 641) against pathogens isolated from infected pancreatic necrosis.

PubMed

Ridwan, B U; Koning, C J M; Besselink, M G H; Timmerman, H M; Brouwer, E C; Verhoef, J; Gooszen, H G; Akkermans, L M A

2008-01-01

Although probiotic prophylaxis has been suggested to prevent small bowel bacterial overgrowth, bacterial translocation and infection of pancreatic necrosis in severe acute pancreatitis, limited data are available on their antimicrobial activity. Using the well-diffusion method, we studied the antimicrobial properties of a multispecies probiotic product (Ecologic 641) against a collection of pathogens cultured from infected pancreatic necrosis. All individual probiotic strains included in the multispecies preparation were able to inhibit the growth of the pathogens to some extent. However, the combination of the individual strains (i.e. the multispecies preparation) was able to inhibit all pathogenic isolates. Probiotic-free supernatants adjusted to pH 7 were not able to inhibit pathogen growth. Ecologic 641 is capable of inhibiting growth of a wide variety of pathogens isolated from infected pancreatic necrosis. The antimicrobial properties are to a large extent explained by the production of organic acids. Ecologic 641 is currently being used in a Dutch nationwide double-blind, placebo-controlled, randomized multicentre trial in patients with predicted severe acute pancreatitis.

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.

[Determinants of the choice of part time employment and nurses' satisfaction: a multicentre descriptive study].

PubMed

Ferrazzo, Martino; Filippi, Mauro; Meneghetti, Giulia; Palese, Alvisa

2012-01-01

To describe the main determinants for the choice of part time employment in Italian nurses and its' impact on work satisfaction. The main factors were identified with a focus-group. A questionnaire with 26 items for the choice of part time and 24 for work satisfaction was then devised and administered to part time nurses (503) of 5 North Italian hospitals. Two-hundred fifty-five nurses/471 answered the questionnaire. The choice of part time was voluntary for the large majority of nurses (251, 98.4%) except for 4 (1.6%) that asked for it for health problems (personal or of the spouse). Part time nurses are more satisfied for the relationships with colleagues (average 3; SD 0.6), the opportunity to deal with responsibilities (2.9; SD 0.6) and to have free time (2.9; SD 0.6). CONCLUSIONS; Part time is a need for mothers. Part time nurses complain for lack of access to information on patients and lack of involvement in ward projects and planned changes, possibly to be considered signals of isolation.

Effect of personalised citizen assistance for social participation (APIC) on older adults' health and social participation: study protocol for a pragmatic multicentre randomised controlled trial (RCT).

PubMed

Levasseur, Mélanie; Dubois, Marie-France; Filliatrault, Johanne; Vasiliadis, Helen-Maria; Lacasse-Bédard, Joanie; Tourigny, André; Levert, Marie-Josée; Gabaude, Catherine; Lefebvre, Hélène; Berger, Valérie; Eymard, Chantal

2018-03-31

The challenges of global ageing and the growing burden of chronic diseases require innovative interventions acting on health determinants like social participation. Many older adults do not have equitable opportunities to achieve full social participation, and interventions might underempower their personal and environmental resources and only reach a minority. To optimise current practices, the Accompagnement-citoyen Personnalisé d'Intégration Communautaire (APIC), an intervention demonstrated as being feasible and having positive impacts, needs further evaluation. A pragmatic multicentre, prospective, two-armed, randomised controlled trial will evaluate: (1) the short-term and long-term effects of the APIC on older adults' health, social participation, life satisfaction and healthcare services utilisation and (2) its cost-effectiveness. A total of 376 participants restricted in at least one instrumental activity of daily living and living in three large cities in the province of Quebec, Canada, will be randomly assigned to the experimental or control group using a centralised computer-generated random number sequence procedure. The experimental group will receive weekly 3-hour personalised stimulation sessions given by a trained volunteer over the first 12 months. Sessions will encourage empowerment, gradual mobilisation of personal and environmental resources and community integration. The control group will receive the publicly funded universal healthcare services available to all Quebecers. Over 2 years (baseline and 12, 18 and 24 months later), self-administered questionnaires will assess physical and mental health (primary outcome; version 2 of the 36-item Short-Form Health Survey, converted to SF-6D utility scores for quality-adjusted life years), social participation (Social Participation Scale) and life satisfaction (Life Satisfaction Index-Z). Healthcare services utilisation will be recorded and costs of each intervention calculated. The Research Ethics Committee of the CIUSSS Estrie - CHUS has approved the study (MP-31-2018-2424). An informed consent form will be read and signed by all study participants. Findings will be published and presented at conferences. NCT03161860; 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.

Bias towards dementia: are hip fracture trials excluding too many patients? A systematic review.

PubMed

Hebert-Davies, Jonah; Laflamme, G-Yves; Rouleau, Dominique

2012-12-01

Patients with hip fractures are older and often present many co-morbidities, including dementia. These patients cannot answer quality of life questionnaires and are generally excluded from trials. We hypothesized that a significant number of patients are being excluded from these studies and this may impact outcomes. This was a two part study; the first analyzing databases of two ongoing large-scale multi-centred hip fracture trials and the second being a systematic review. The FAITH and HEALTH studies were analyzed for exclusion incidence directly related to dementia. The second part consisted of a systematic search of all relevant studies within the last 20 years. In the FAITH study, a total of 1690 subjects were excluded, 375 (22.2%) of which were due to dementia or cognitive impairment. In the HEALTH study, 575 were excluded with dementia/cognitive impairment representing 207 patients (36%). Following the systematic review, 251 articles were identified 17 of which were retained. The overall prevalence of dementia was 27.9% (range 2-51%). Only two studies compared demented and non-demented groups. In these studies significant increases in both mortality and complications were found. In summary, when investigating hip fractures, choosing appropriate objective endpoints is essential to ensure results are also applicable to patients with dementia. Copyright © 2012 Elsevier Ltd. All rights reserved.

A multicentre 'end to end' dosimetry audit for cervix HDR brachytherapy treatment.

PubMed

Palmer, Antony L; Diez, Patricia; Gandon, Laura; Wynn-Jones, Andrea; Bownes, Peter; Lee, Chris; Aird, Edwin; Bidmead, Margaret; Lowe, Gerry; Bradley, David; Nisbet, Andrew

2015-02-01

To undertake the first multicentre fully 'end to end' dosimetry audit for HDR cervix brachytherapy, comparing planned and delivered dose distributions around clinical treatment applicators, with review of local procedures. A film-dosimetry audit was performed at 46 centres, including imaging, applicator reconstruction, treatment planning and delivery. Film dose maps were calculated using triple-channel dosimetry and compared to RTDose data from treatment planning systems. Deviations between plan and measurement were quantified at prescription Point A and using gamma analysis. Local procedures were also discussed. The mean difference between planned and measured dose at Point A was -0.6% for plastic applicators and -3.0% for metal applicators, at standard uncertainty 3.0% (k=1). Isodose distributions agreed within 1mm over a dose range 2-16Gy. Mean gamma passing rates exceeded 97% for plastic and metal applicators at 3% (local) 2mm criteria. Two errors were found: one dose normalisation error and one applicator library misaligned with the imaged applicator. Suggestions for quality improvement were also made. The concept of 'end to end' dosimetry audit for HDR brachytherapy has been successfully implemented in a multicentre environment, providing evidence that a high level of accuracy in brachytherapy dosimetry can be achieved. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Pharmaceutical trials in general practice: the first 100 protocols. An audit by the clinical research ethics committee of the Royal College of General Practitioners.

PubMed Central

Wise, P.; Drury, M.

1996-01-01

OBJECTIVE: To assess the outcome of 100 general practice based, multicentre research projects submitted to the ethics committee of the Royal College of General Practitioners by pharmaceutical companies or their agents between 1984 and 1989. DESIGN: Analysis of consecutive submitted protocols for stated objectives, study design, and outcomes; detailed review of committee minutes and correspondence in relation to amendment and approval; assessment of final reports submitted at conclusion of studies. SUBJECTS: 82 finally approved protocols, embracing 34,523 proposed trial subjects and 1195 proposed general practice investigators. MAIN OUTCOME MEASURES: Success at enrolling subjects and investigators; commencement and completion data; validity of final report's assessment of efficacy, safety, tolerability, and acceptability; and method of use and dissemination of findings. RESULTS: 18 studies were not approved and 45 had to be amended. Randomised controlled trials comprised 46 of the original submissions. Remuneration considerations, inadequate information or consent sheets, pregnancy safety, the need to discontinue existing therapy, and suboptimal scientific content were major reasons for rejecting studies or asking for amendments. Of the 82 approved studies 8 were not started. Shortfalls of investigators (of 39%) and trial subjects (of 37%) and an overall 23% withdrawal rate were responsible for a significant incidence of inconclusive results. Within the six year follow up interval, only 19 of the studies had been formally published. CONCLUSIONS: This audit identified substantial ethical concerns in the process of approving multicentre general practice pharmaceutical research. PMID:8939118

What is the degree of innovation routinely implemented in Dutch radiotherapy centres? A multicentre cross-sectional study

PubMed Central

Boersma, Liesbeth; Dekker, Andre; Bosmans, Geert; van Merode, Frits; Verhaegen, Frank; de Ruysscher, Dirk; Swart, Rachelle; Kengen, Cindy; Lambin, Philippe

2016-01-01

Objective: To study the implementation of innovation activities in Dutch radiotherapy (RT) centres in a broad sense (product, technological, market and organizational innovations). Methods: A descriptive cross-sectional study was conducted in 15 Dutch RT centres. A list of innovations implemented from 2011 to 2013 was drawn up for each centre using semi-structured interviews. These innovations were classified into innovation categories according to previously defined innovation indicators. Where applicable, each innovation was rated by each centre on the effort required to implement it and on its expected effects, to get an impression of how far reaching and radical the innovations were and to be able to compare the number of innovations between centres. Results: The participating RT centres in the Netherlands implemented 12 innovations per year on average (range 5–25); this number was not significantly different for academic (n = 13) or non-academic centres (n = 10). Several centres were dealing with the same innovations at the same time. The average required effort and expected output did not differ significantly between product, technological and organizational innovation or between academic and non-academic centres. Conclusion: The number of innovations observed per centre varied across a large range, with a large overlap in terms of the type of innovations that were implemented. Registering innovations using the innovation indicators applied in our study would make it possible to improve collaboration between centres, e.g. with common training modules, to avoid duplication of work. Advances in knowledge: This study is the first of its kind investigating innovation implementation in RT in a broad sense. PMID:27660890

Video-game based exercises for older people with chronic low back pain: a protocol for a feasibility randomised controlled trial (the GAMEBACK trial).

PubMed

Zadro, Joshua Robert; Shirley, Debra; Simic, Milena; Mousavi, Seyed Javad; Ceprnja, Dragana; Maka, Katherine; Ferreira, Paulo

2017-06-01

To investigate the feasibility of implementing a video-game exercise programme for older people with chronic low back pain (LBP). Single-centred single-blinded randomised controlled trial (RCT). Physiotherapy outpatient department in a public hospital in Western Sydney, Australia. We will recruit 60 participants over 55 years old with chronic LBP from the waiting list. Participants will be randomised to receive video-game exercise (n=30) or to remain on the waiting list (n=30) for 8 weeks, with follow up at 3 and 6 months. Participants engaging in video-game exercises will be unsupervised and will complete video-game exercise for 60minutes, 3 times per week. Participants allocated to remain on the waiting list will be encouraged to maintain their usual levels of physical activity. The primary outcomes for this feasibility study will be study processes (recruitment and response rates, adherence to and experience with the intervention, and incidence of adverse events) relevant to the future design of a large RCT. Estimates of treatment efficacy (point estimates and 95% confidence intervals) on pain self-efficacy, care seeking, physical activity, fear of movement/re-injury, pain, physical function, disability, falls-efficacy, strength, and walking speed, will be our secondary outcome measures. Recruitment for this trial began in November 2015. This study describes the rationale and processes of a feasibility study investigating a video-game exercise programme for older people with chronic LBP. Results from the feasibility study will inform on the design and sample required for a large multicentre RCT. Australian New Zealand Clinical Trials Registry: ACTRN12615000703505. Copyright © 2016 Chartered Society of Physiotherapy. Published by Elsevier Ltd. All rights reserved.

Prospective, Multi-Centre, Single-Arm Study of Mechanical Thrombectomy using Solitaire FR in Acute Ischemic Stroke-STAR

PubMed Central

Pereira, Vitor M; Gralla, Jan; Davalos, Antoni; Bonafé, Alain; Castaño, Carlos; Chapot, Rene; Liebeskind, David S; Nogueira, Raul G; Arnold, Marcel; Sztajzel, Roman; Liebig, Thomas; Goyal, Mayank; Besselmann, Michael; Moreno, Alfredo; Schroth, Gerhard

2013-01-01

Background and Purpose Mechanical thrombectomy using stent retriever devices have been advocated to increase revascularization in intracranial vessel occlusion. We present the results of a large prospective study on the use of the Solitaire FR in patients with acute ischemic stroke. Methods STAR was an international, multicenter, prospective, single-arm study of Solitaire FR thrombectomy in patients with large vessel anterior circulation strokes treated within 8 hours of symptom onset. Strict criteria for site selection were applied. The primary endpoint was the revascularization rate (3TICI 2b) of the occluded vessel as determined by an independent core lab. The secondary endpoint was the rate of good functional outcome (defined as 90-day modified Rankin scale (mRS) 0–2). Results A total of 202 patients were enrolled across 14 comprehensive stroke centers in Europe, Canada and Australia. The median age was 72 years, 60% were female patients. The median National Institute of Health Stroke Scale (NIHSS) was 17. Most proximal intracranial occlusion was the internal carotid artery in 18%, the middle cerebral artery in 82%. Successful revascularization was achieved in 79.2% of patients. Device and/or procedure related severe adverse events were found in 7.4%. Favorable neurological outcome was found in 57.9%. The mortality rate was 6.9%. Any intracranial hemorrhagic transformation was found in 18.8% of patients, 1.5% were symptomatic. Conclusions In this single arm study, treatment with the Solitaire™ FR device in intracranial anterior circulation occlusions results in high rates of revascularization, low risk of clinically relevant procedural complications, and good clinical outcomes in combination with low mortality at 90 days. Clinical Trial Registration This study is registered with ClinicalTrials.gov, number NCT01327989. PMID:23908066

Selecting for a sustainable workforce to meet the future healthcare needs of rural communities in Australia.

PubMed

Hay, M; Mercer, A M; Lichtwark, I; Tran, S; Hodgson, W C; Aretz, H T; Armstrong, E G; Gorman, D

2017-05-01

An undersupply of generalists doctors in rural communities globally led to widening participation (WP) initiatives to increase the proportion of rural origin medical students. In 2002 the Australian Government mandated that 25% of commencing Australian medical students be of rural origin. Meeting this target has largely been achieved through reduced standards of entry for rural relative to urban applicants. This initiative is based on the assumption that rural origin students will succeed during training, and return to practice in rural locations. One aim of this study was to determine the relationships between student geographical origin (rural or urban), selection scores, and future practice intentions of medical students at course entry and course exit. Two multicentre databases containing selection and future practice preferences (location and specialisation) were combined (5862), representing 54% of undergraduate medical students commencing from 2006 to 2013 across nine Australian medical schools. A second aim was to determine course performance of rural origin students selected on lower scores than their urban peers. Selection and course performance data for rural (461) and urban (1431) origin students commencing 2006-2014 from one medical school was used. For Aim 1, a third (33.7%) of rural origin students indicated a preference for future rural practice at course exit, and even fewer (6.7%) urban origin students made this preference. Results from logistic regression analyses showed significant independent predictors were rural origin (OR 4.0), lower Australian Tertiary Admissions Rank (ATAR) (OR 2.1), or lower Undergraduate Medical and Health Sciences Admissions Test Section 3 (non-verbal reasoning) (OR 1.3). Less than a fifth (17.6%) of rural origin students indicated a preference for future generalist practice at course exit. Significant predictors were female gender (OR 1.7) or lower ATAR (OR 1.2), but not rural origin. Fewer (10.5%) urban origin students indicated a preference for generalist practice at course exit. For Aim 2, results of Mann-Whitney U tests confirmed that slightly reducing selection scores does not result in increased failure, or meaningfully impaired performance during training relative to urban origin students. Our multicentre analysis supports success of the rural origin WP pathway to increase rural student participation in medical training. However, our findings confirm that current selection initiatives are insufficient to address the continuing problem of doctor maldistribution in Australia. We argue for further reform to current medical student selection, which remains largely determined by academic meritocracy. Our findings have relevance to the selection of students into health professions globally.

A new standardized data collection system for interdisciplinary thyroid cancer management: Thyroid COBRA.

PubMed

Tagliaferri, Luca; Gobitti, Carlo; Colloca, Giuseppe Ferdinando; Boldrini, Luca; Farina, Eleonora; Furlan, Carlo; Paiar, Fabiola; Vianello, Federica; Basso, Michela; Cerizza, Lorenzo; Monari, Fabio; Simontacchi, Gabriele; Gambacorta, Maria Antonietta; Lenkowicz, Jacopo; Dinapoli, Nicola; Lanzotti, Vito; Mazzarotto, Renzo; Russi, Elvio; Mangoni, Monica

2018-07-01

The big data approach offers a powerful alternative to Evidence-based medicine. This approach could guide cancer management thanks to machine learning application to large-scale data. Aim of the Thyroid CoBRA (Consortium for Brachytherapy Data Analysis) project is to develop a standardized web data collection system, focused on thyroid cancer. The Metabolic Radiotherapy Working Group of Italian Association of Radiation Oncology (AIRO) endorsed the implementation of a consortium directed to thyroid cancer management and data collection. The agreement conditions, the ontology of the collected data and the related software services were defined by a multicentre ad hoc working-group (WG). Six Italian cancer centres were firstly started the project, defined and signed the Thyroid COBRA consortium agreement. Three data set tiers were identified: Registry, Procedures and Research. The COBRA-Storage System (C-SS) appeared to be not time-consuming and to be privacy respecting, as data can be extracted directly from the single centre's storage platforms through a secured connection that ensures reliable encryption of sensible data. Automatic data archiving could be directly performed from Image Hospital Storage System or the Radiotherapy Treatment Planning Systems. The C-SS architecture will allow "Cloud storage way" or "distributed learning" approaches for predictive model definition and further clinical decision support tools development. The development of the Thyroid COBRA data Storage System C-SS through a multicentre consortium approach appeared to be a feasible tool in the setup of complex and privacy saving data sharing system oriented to the management of thyroid cancer and in the near future every cancer type. Copyright © 2018 European Federation of Internal Medicine. Published by Elsevier B.V. All rights reserved.

Prevalence of anterior pituitary dysfunction in patients following traumatic brain injury in a German multi-centre screening program.

PubMed

Berg, C; Oeffner, A; Schumm-Draeger, P-M; Badorrek, F; Brabant, G; Gerbert, B; Bornstein, S; Zimmermann, A; Weber, M; Broecker-Preuss, M; Mann, K; Herrmann, B L

2010-02-01

We determined the prevalence of anterior pituitary dysfunction in a multi-centre screening program across five German endocrine centres in patients rehabilitating from TBI (GCS<13). 246 patients (39+/-14 yrs; 133 males, 12+/-8 months after TBI) underwent a series of baseline endocrine tests with central assessment of TSH, free T4, prolactin, LH, FSH, testosterone (m), estradiol (f), cortisol, GH, and IGF-I. If IGF-I was <-2 SDS dynamic testing was performed. GHD was defined according to BMI-dependent cut-off values for GH response to GHRH+arginine of <4.2, <8.0 and <11.5 ng/ml in obese, overweight and lean subjects, respectively, or <3 micro g/l in ITT. Hypocortisolism was suggested when basal cortisol was <200 nmol/l and confirmed by ITT (peak<500 nmol/l). In TBI patients some degree of impaired pituitary function was shown in 21% (n=52/246). Total, multiple and isolated deficits were present in 1%, 2% and 18%, respectively. 19% had an IGF-I of <-1 SDS, 9% of <-2 SDS. In 5% GHD was confirmed. 9% had hypogonadism. 4% had hypocortisolism and 1% of patients had confirmed ACTH-deficiency. 12% had TSH-deficiency. In summary, in this large series carried out on an unselected group of TBI survivors we have found hypopituitarism in every fifth patient with predominantly secondary hypogonadism and hypothyreosis. Regarding somatotrope insufficiency IGF-I is decreased in 50% of GHD patients. These findings strongly suggest that patients who suffer head trauma should routinely undergo endocrine evaluation. J. A. Barth Verlag in Georg Thieme Verlag KG Stuttgart. New York.

Interobserver Agreement on Endoscopic Classification of Oesophageal Varices in Children.

PubMed

D'Antiga, Lorenzo; Betalli, Pietro; De Angelis, Paola; Davenport, Mark; Di Giorgio, Angelo; McKiernan, Patrick J; McLin, Valerie; Ravelli, Paolo; Durmaz, Ozlem; Talbotec, Cecile; Sturm, Ekkehard; Woynarowski, Marek; Burroughs, Andrew K

2015-08-01

Data regarding agreement on endoscopic features of oesophageal varices in children with portal hypertension (PH) are scant. The aim of this study was to evaluate endoscopic visualisation and classification of oesophageal varices in children by several European clinicians, to build a rational basis for future multicentre trials. Endoscopic pictures of the distal oesophagus of 100 children with a clinical diagnosis of PH were distributed to 10 endoscopists. Observers were requested to classify variceal size according to a 3-degree scale (small, medium, and large, class A), a 2-degree scale (small and large, class B), and to recognise red wales (presence or absence, class Red). Overall agreement was considered fair if Fleiss and Cohen κ test was ≥0.30, good if ≥0.40, excellent if ≥0.60, and perfect if ≥0.80. Agreement between observers was fair with class A (κ = 0.34) and class B (κ = 0.38), and good with class Red (κ = 0.49). The agreement was good on presence versus absence of varices (class A = 0.53, class B = 0.48). The agreement among the observers was good in class A when endoscopic features of severe PH (medium and large sizes, red marks) were grouped and compared with mild features (absent and small varices) (κ = 0.58). Experts working in different centres show a fairly good agreement on endoscopic features of PH in children, although a better training of paediatric endoscopists may improve the agreement in grading severity of varices in this setting.

Serological markers of hepatitis B in patients with alcoholic liver disease: a multi-centre survey

PubMed Central

Hislop, WS; Follett, EAC; Bouchier, IAD; MacSween, RNM

1981-01-01

In a study of 195 patients derived from five centres in northern Britain and with histologically confirmed alcoholic liver disease we have found an increased prevalence of serological markers of hepatitis B. This increased prevalence was found in each of the five centres; the overall frequency ranged from 11% sero-positivity in fatty liver, 12% in alcoholic hepatitis and 27% in cirrhosis. PMID:7276216

A scoring system to predict breast cancer mortality at 5 and 10 years.

PubMed

Paredes-Aracil, Esther; Palazón-Bru, Antonio; Folgado-de la Rosa, David Manuel; Ots-Gutiérrez, José Ramón; Compañ-Rosique, Antonio Fernando; Gil-Guillén, Vicente Francisco

2017-03-24

Although predictive models exist for mortality in breast cancer (BC) (generally all cause-mortality), they are not applicable to all patients and their statistical methodology is not the most powerful to develop a predictive model. Consequently, we developed a predictive model specific for BC mortality at 5 and 10 years resolving the above issues. This cohort study included 287 patients diagnosed with BC in a Spanish region in 2003-2016. time-to-BC death. Secondary variables: age, personal history of breast surgery, personal history of any cancer/BC, premenopause, postmenopause, grade, estrogen receptor, progesterone receptor, c-erbB2, TNM stage, multicentricity/multifocality, diagnosis and treatment. A points system was constructed to predict BC mortality at 5 and 10 years. The model was internally validated by bootstrapping. The points system was integrated into a mobile application for Android. Mean follow-up was 8.6 ± 3.5 years and 55 patients died of BC. The points system included age, personal history of BC, grade, TNM stage and multicentricity. Validation was satisfactory, in both discrimination and calibration. In conclusion, we constructed and internally validated a scoring system for predicting BC mortality at 5 and 10 years. External validation studies are needed for its use in other geographical areas.

Direct identification of microorganisms from positive blood cultures using the lysis-filtration technique and matrix assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF MS): a multicentre study.

PubMed

Farina, Claudio; Arena, Fabio; Casprini, Patrizia; Cichero, Paola; Clementi, Massimo; Cosentino, Marina; Degl'Innocenti, Roberto; Giani, Tommaso; Luzzaro, Francesco; Mattei, Romano; Mauri, Carola; Nardone, Maria; Rossolini, Gian Maria; Serna Ortega, Paula Andrea; Vailati, Francesca

2015-04-01

Microbial identification from blood cultures is essential to institute optimal antibiotic therapy and improve survival possibilities. Matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF MS) has been successfully applied to identify bacteria and yeasts from positive blood cultures broths. The aim of this multicentre study was to evaluate the reliability of the lysis-filtration technique associated with MALDI-TOF MS to directly identify microorganisms from 765 positive blood cultures collected in six Italian hospitals. Overall, 675/765 (78.1%) blood isolates were correctly identified at the species level, with significant differences between Gram-negative and Gram-positive bacteria (92.6%, and 69.8%, respectively). Some difficulties arise in identifying Streptococcus pneumoniae, Staphylococcus aureus, yeasts and anaerobes. The lysis-filtration protocol is a suitable procedure in terms of performance in identifying microorganisms, but it is quite expensive and technically time-consuming since the time of filtration is not regular for all the samples. The application of the MALDI-TOF MS technique to the direct microbial identification from positive blood cultures is a very promising approach, even if more experience must be gained to minimize errors and costs.

Efficacy and safety of pioglitazone added to alogliptin in Japanese patients with type 2 diabetes mellitus: a multicentre, randomized, double-blind, parallel-group, comparative study.

PubMed

Kaku, K; Katou, M; Igeta, M; Ohira, T; Sano, H

2015-12-01

A phase IV, multicentre, randomized, double-blind, parallel-group, comparative study was conducted in Japanese subjects with type 2 diabetes mellitus (T2DM) who had inadequate glycaemic control, despite treatment with alogliptin in addition to diet and/or exercise therapy. Subjects with glycated haemoglobin (HbA1c) concentrations of 6.9-10.5% were randomized to receive 16 weeks' double-blind treatment with pioglitazone 15 mg, 30 mg once daily or placebo added to alogliptin 25 mg once daily. The primary endpoint was the change in HbA1c from baseline at the end of treatment period (week 16). Both pioglitazone 15 and 30 mg combination therapy resulted in a significantly greater reduction in HbA1c than alogliptin monotherapy [-0.80 and -0.90% vs 0.00% (the least squares mean using analysis of covariance model); p < 0.0001, respectively]. The overall incidence rates of treatment-emergent adverse events were similar among the treatment groups. Pioglitazone/alogliptin combination therapy was effective and generally well tolerated in Japanese subjects with T2DM and is considered to be useful in clinical settings. © 2015 John Wiley & Sons Ltd.

Decompressive craniectomy and CSF disorders in children.

PubMed

Manfiotto, Marie; Mottolese, Carmine; Szathmari, Alexandru; Beuriat, Pierre-Aurelien; Klein, Olivier; Vinchon, Matthieu; Gimbert, Edouard; Roujeau, Thomas; Scavarda, Didier; Zerah, Michel; Di Rocco, Federico

2017-10-01

Decompressive craniectomy (DC) is a lifesaving procedure but is associated to several post-operative complications, namely cerebrospinal fluid (CSF) dynamics impairment. The aim of this multicentric study was to evaluate the incidence of such CSF alterations after DC and review their impact on the overall outcome. We performed a retrospective multicentric study to analyze the CSF disorders occurring in children aged from 0 to 17 years who had undergone a DC for traumatic brain injury (TBI) in the major Departments of Pediatric Neurosurgery of France between January 2006 and August 2016. Out of 150 children, ranging in age between 7 months and 17 years, mean 10.75 years, who underwent a DC for TBI in 10 French pediatric neurosurgical centers. Sixteen (6 males, 10 females) (10.67%) developed CSF disorders following the surgical procedure and required an extrathecal CSF shunting. External ventricular drainage increased the risk of further complications, especially cranioplasty infection (p = 0.008). CSF disorders affect a minority of children after DC for TBI. They may develop early after the DC but they may develop several months after the cranioplasty (8 months), consequently indicating the necessity of clinical and radiological close follow-up after discharge from the neurosurgical unit. External ventricular drainage and permanent CSF shunt placement increase significantly the risk of cranioplasty infection.

HPV and cofactors for invasive cervical cancer in Morocco: a multicentre case-control study.

PubMed

Berraho, Mohamed; Amarti-Riffi, Afaf; El-Mzibri, Mohammed; Bezad, Rachid; Benjaafar, Noureddine; Benideer, Abdelatif; Matar, Noureddine; Qmichou, Zinab; Abda, Naima; Attaleb, Mohammed; Znati, Kaoutar; El Fatemi, Hind; Bendahhou, Karima; Obtel, Majdouline; Filali Adib, Abdelhai; Mathoulin-Pelissier, Simone; Nejjari, Chakib

2017-06-20

Limited national information is available in Morocco on the prevalence and distribution of HPV-sub-types of cervical cancer and the role of other risk factors. The aim was to determine the frequency of HPV-sub-types of cervical cancer in Morocco and investigate risk factors for this disease. Between November 2009 and April 2012 a multicentre case-control study was carried out. A total of 144 cases of cervical cancer and 288 age-matched controls were included. Odds-ratios and corresponding confidence-intervals were computed by conditional logistic regression models. Current HPV infection was detected in 92.5% of cases and 13.9% of controls. HPV16 was the most common type for both cases and controls. Very strong associations between HPV-sub-types and cervical cancer were observed: total-HPV (OR = 39), HPV16 (OR = 49), HPV18 (OR = 31), and multiple infections (OR = 13). Education, high parity, sexual intercourse during menstruation, history of sexually transmitted infections, and husband's multiple sexual partners were also significantly associated with cervical cancer in the multivariate analysis. Our results could be used to establish a primary prevention program and to prioritize limited screening to women who have specific characteristics that may put them at an increased risk of cervical cancer.

Is breast conservative surgery a reasonable option in multifocal or multicentric tumors?

PubMed Central

Houvenaeghel, Gilles; Tallet, Agnès; Jalaguier-Coudray, Aurélie; Cohen, Monique; Bannier, Marie; Jauffret-Fara, Camille; Lambaudie, Eric

2016-01-01

The incidence of multifocal (MF) and multicentric (MC) carcinomas varies widely among clinical studies, depending on definitions and methods for pathological sampling. Magnetic resonance imaging is increasingly used because it can help identify additional and conventionally occult tumors with high sensitivity. However, false positive lesions might incorrectly influence treatment decisions. Therefore, preoperative biopsies must be performed to avoid unnecessary surgery. Most studies have shown higher lymph node involvement rates in MF/MC tumors than in unifocal tumors. However, the rate of local recurrences is usually low after breast conservative treatment (BCT) of MC/MF tumors. It has been suggested that BCT is a reasonable option for MC/MF tumors in women aged 50-69 years, with small tumors and absence of extensive ductal carcinoma in situ. A meta-analysis showed an apparent decreased overall survival in MC/MF tumors but data are controversial. Surgery should achieve both acceptable cosmetic results and negative margins, which requires thorough preoperative radiological workup and localization of lesions. Boost radiotherapy techniques must be evaluated since double boosts might result in increased toxicity, namely fibrosis. In conclusion, BCT is feasible in selected patients with MC/MF but the choice of surgery must be discussed in a multidisciplinary team comprising at least radiologists, surgeons and radiotherapists. PMID:27081646

DISCRIMINATION OF EMOTIONAL STATES AMONGST THE TAMILS

PubMed Central

Somasundaram, O.

1992-01-01

Leff has concluded from his analysis of the JPSS Study that the emotions of anxiety, depression and irritability are poorly discriminated amongst the population using non-Indo-European languages. The present author after analyzing similar data from the ICMR Multicentred Collaborative Study of Factors Associated with the Course and outcome of Schizophrenia that the Tamil population using Tamil, a non-Indo-European language is able to discriminate these emotions as well as the brethren speaking Hindi of lndo-European origin. PMID:21776093

A Realistic Seizure Prediction Study Based on Multiclass SVM.

PubMed

Direito, Bruno; Teixeira, César A; Sales, Francisco; Castelo-Branco, Miguel; Dourado, António

2017-05-01

A patient-specific algorithm, for epileptic seizure prediction, based on multiclass support-vector machines (SVM) and using multi-channel high-dimensional feature sets, is presented. The feature sets, combined with multiclass classification and post-processing schemes aim at the generation of alarms and reduced influence of false positives. This study considers 216 patients from the European Epilepsy Database, and includes 185 patients with scalp EEG recordings and 31 with intracranial data. The strategy was tested over a total of 16,729.80[Formula: see text]h of inter-ictal data, including 1206 seizures. We found an overall sensitivity of 38.47% and a false positive rate per hour of 0.20. The performance of the method achieved statistical significance in 24 patients (11% of the patients). Despite the encouraging results previously reported in specific datasets, the prospective demonstration on long-term EEG recording has been limited. Our study presents a prospective analysis of a large heterogeneous, multicentric dataset. The statistical framework based on conservative assumptions, reflects a realistic approach compared to constrained datasets, and/or in-sample evaluations. The improvement of these results, with the definition of an appropriate set of features able to improve the distinction between the pre-ictal and nonpre-ictal states, hence minimizing the effect of confounding variables, remains a key aspect.

Outcome of intrahepatic portosystemic shunt diagnosed prenatally.

PubMed

Francois, Bérengère; Gottrand, Fréderic; Lachaux, Alain; Boyer, Corinne; Benoit, Bernard; De Smet, Stéphanie

2017-12-01

We analyzed the characteristics of the population with congenital portosystemic shunt diagnosed during the antenatal period and the organization of their perinatal care. This multicentric retrospective study included all the patients with a prenatal diagnosis of congenital portosystemic shunt. Between 1999 and 2015, 12 patients were included. Prenatal diagnosis was done at a median 26.5 weeks of gestation (21-34). All the patients presented intrahepatic CPSS, three of them had associated congenital cardiopathy, and one a Bannayan-Zonana syndrome. Ten patients had simple outcome on conservative treatment, eight of them having a spontaneous closure of their portosystemic shunt within the first 2 years of life. One patient had surgical treatment which failed and he developed a focal nodular hyperplasia. Another patient had radiological interventional closure of his shunt which was complicated by a venal portal thrombosis. Outcome of intrahepatic portosystemic shunt diagnosed prenatally is good in the majority of cases. What is known: • Multiples studies exist on congenital porto systemic shunt but when the diagnosis is done after birth. • The evolution, management, and complication are well known. What is new: • There is very few studies with only patients diagnosed in antenatal and it is a large series of cases. • Outcome of intrahepatic portosystemic shunt diagnosed prenatally is good in the majority of cases.

Targeting Stable Rotors to Treat Atrial Fibrillation.

PubMed

Narayan, Sanjiv M; Krummen, David E

2012-09-01

Therapy for atrial fibrillation (AF) remains suboptimal, in large part because its mechanisms are unclear. While pulmonary vein ectopy may trigger AF, it remains uncertain how AF, once triggered, is actually sustained. Recent discoveries show that human AF is maintained by a small number of rotors or focal sources. AF sources are widely distributed in patient-specific locations, often remote from pulmonary veins and in the right atrium and stable for prolonged periods of time. In a multicentre experience, brief targeted ablation at sources (focal impulse and rotor modulation [FIRM]) terminated AF predominantly to sinus rhythm prior to pulmonary vein isolation and eliminated AF on rigorous followup. This review summarises the evidence for stable rotors and focal sources of human AF and their clinical role as ablation targets to eliminate paroxysmal, persistent and long-standing persistent AF.

Cohort Selection and Management Application Leveraging Standards-based Semantic Interoperability and a Groovy DSL

PubMed Central

Bucur, Anca; van Leeuwen, Jasper; Chen, Njin-Zu; Claerhout, Brecht; de Schepper, Kristof; Perez-Rey, David; Paraiso-Medina, Sergio; Alonso-Calvo, Raul; Mehta, Keyur; Krykwinski, Cyril

2016-01-01

This paper describes a new Cohort Selection application implemented to support streamlining the definition phase of multi-centric clinical research in oncology. Our approach aims at both ease of use and precision in defining the selection filters expressing the characteristics of the desired population. The application leverages our standards-based Semantic Interoperability Solution and a Groovy DSL to provide high expressiveness in the definition of filters and flexibility in their composition into complex selection graphs including splits and merges. Widely-adopted ontologies such as SNOMED-CT are used to represent the semantics of the data and to express concepts in the application filters, facilitating data sharing and collaboration on joint research questions in large communities of clinical users. The application supports patient data exploration and efficient collaboration in multi-site, heterogeneous and distributed data environments. PMID:27570644

The European Respiratory Society study on chronic obstructive pulmonary disease (EUROSCOP): recruitment methods and strategies.

PubMed

Löfdahl, C G; Postma, D S; Laitinen, L A; Ohlsson, S V; Pauwels, R A; Pride, N B

1998-03-01

The European Respiratory Society's study on chronic obstructive pulmonary disease (EUROSCOP) is a multicentre study performed initially in 12 countries to assess the effect of 3 years' treatment with inhaled corticosteroids on lung function decline in smokers with chronic obstructive pulmonary disease (COPD). It aimed at recruiting 50 subjects in 50 European centres. This study discusses the most successful, countrywise, recruitment strategies, an important issue since many multicentre European studies may follow in the future. The total number of recruited subjects was 2147 in 39 participating centres. In total, at least 25,000 screening spirometries were performed, and about 80,000 hospital records were checked. The most effective way of recruiting subjects was to screen subjects by spirometry after mass media campaigns (eight out of nine countries). Others used workplace screenings and different types of population survey, and only a few centres successfully recruited participants by hospital records. Inclusion criteria were slightly changed upon low initial accrual rate. Initial surveys in one country, where 2405 subjects were screened by spirometry, gave an important indication for the change of the inclusion criteria. Extension of the upper age limit from 60 to 65 yr considerably improved recruitment, as did a change of the upper limit of FEV1 from below 80% predicted normal to below 100% predicted normal, while maintaining the FEV1/VC ratio below 70%. A tremendous effort is needed to recruit individuals with preclinical COPD, but this is certainly feasible with adequate strategies adjusted to each country.

BreathDx - molecular analysis of exhaled breath as a diagnostic test for ventilator-associated pneumonia: protocol for a European multicentre observational study.

PubMed

van Oort, Pouline M P; Nijsen, Tamara; Weda, Hans; Knobel, Hugo; Dark, Paul; Felton, Timothy; Rattray, Nicholas J W; Lawal, Oluwasola; Ahmed, Waqar; Portsmouth, Craig; Sterk, Peter J; Schultz, Marcus J; Zakharkina, Tetyana; Artigas, Antonio; Povoa, Pedro; Martin-Loeches, Ignacio; Fowler, Stephen J; Bos, Lieuwe D J

2017-01-03

The diagnosis of ventilator-associated pneumonia (VAP) remains time-consuming and costly, the clinical tools lack specificity and a bedside test to exclude infection in suspected patients is unavailable. Breath contains hundreds to thousands of volatile organic compounds (VOCs) that result from host and microbial metabolism as well as the environment. The present study aims to use breath VOC analysis to develop a model that can discriminate between patients who have positive cultures and who have negative cultures with a high sensitivity. The Molecular Analysis of Exhaled Breath as Diagnostic Test for Ventilator-Associated Pneumonia (BreathDx) study is a multicentre observational study. Breath and bronchial lavage samples will be collected from 100 and 53 intubated and ventilated patients suspected of VAP. Breath will be analysed using Thermal Desorption - Gas Chromatography - Mass Spectrometry (TD-GC-MS). The primary endpoint is the accuracy of cross-validated prediction for positive respiratory cultures in patients that are suspected of VAP, with a sensitivity of at least 99% (high negative predictive value). To our knowledge, BreathDx is the first study powered to investigate whether molecular analysis of breath can be used to classify suspected VAP patients with and without positive microbiological cultures with 99% sensitivity. UKCRN ID number 19086, registered May 2015; as well as registration at www.trialregister.nl under the acronym 'BreathDx' with trial ID number NTR 6114 (retrospectively registered on 28 October 2016).

The MOAHLFA index of irritant sodium lauryl sulfate reactions: first results of a multicentre study on routine sodium lauryl sulfate patch testing.

PubMed

Uter, Wolfgang; Geier, Johannes; Becker, Detlef; Brasch, Jochen; Löffler, Harald

2004-01-01

In a multicentre study of the German Contact Dermatitis Research Group, sodium lauryl sulfate (SLS) 0.25% and 0.5% aq. has been added to routine allergen patch tests to assess its properties as a convenient diagnostic indicator of individual susceptibility to irritation at the time of patch testing. Previous studies indicated that irritant SLS reactivity may be related to individual factors such as age and sex. As these factors are, in turn, among the important predictors of contact allergy to many allergens, e.g. summarized in the 'MOAHLFA index', the impact of the MOAHLFA factors on irritant SLS patch test reactivity, and thus a potential for confounding, was assessed in the 5971 participating patients. As a result of 2 logistic regression analyses with an irritant reaction to 0.25% and 0.5% SLS, respectively, as outcome, male sex was identified as a relatively weak but significant risk factor (OR 1.38), while age 40 years or older was an even weaker risk factor (OR 1.22 and 1.15, respectively). Upon detailed analysis, no clear age gradient could, however, be identified. 1-day exposure time almost halved the odds of an irritant SLS reaction. In conclusion, this type of SLS patch test can be regarded as robust, indicating individual irritability relatively independent from the individual factors analysed here.

Developmental dysplasia of the hip: addressing evidence gaps with a multicentre prospective international study.

PubMed

Schaeffer, Emily K; Study Group, Ihdi; Mulpuri, Kishore

2018-05-07

There is a lack of high quality evidence available to guide clinical practice in the treatment and management of developmental dysplasia of the hip (DDH). Evidence has been limited by persistent confusion on diagnostic and classification terminology, variability in surgeon decision making and a reliance on single centre, retrospective studies with small patient numbers. To address gaps in knowledge regarding screening, diagnosis and management of DDH, the International Hip Dysplasia Institute began a multicentre, international prospective study on infants with hips dislocated at rest. This review discusses the current state of screening, diagnostic and management practices in DDH and addresses important unanswered questions that will be critical in identifying best practices and optimising patient outcomes. There is insufficient evidence to support universal ultrasound screening; instead, selective screening should be performed by 6-8 weeks of age on infants with risk factors of breech presentation, family history, or history of clinical hip instability. Follow-up of infants with risk factors and normal initial screening should be considered to at least 6 months of age. Brace treatment is a sensible first-line treatment for management of dislocated hips at rest in infants < 6 months of age. Early operative reduction may be considered as there is insufficient evidence to support a protective role for the ossific nucleus in the development of avascular necrosis.

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.

Clinical and diagnosis characteristics of breast cancers in women with a history of radiotherapy in the first 30years of life: A French multicentre cohort study.

PubMed

Demoor-Goldschmidt, C; Supiot, S; Oberlin, O; Helfre, S; Vigneron, C; Brillaud-Meflah, V; Bernier, V; Laprie, A; Ducassou, A; Claude, L; Mahé, M A; de Vathaire, F

2017-08-01

Irradiation (>3Gy) to the breast or axillae before 30years of age increases the risk of secondary breast cancer (SBC). The purpose of this article is to describe the clinical characteristics of SBC and the way of diagnosis in young women (before the age of national screening) in France who had received previous radiotherapy for a childhood or a young adulthood cancer. This retrospective, multicentre study reviewed the medical records of women with SBC before the age of the national screening who had received irradiation (≥3Gy) on part or all of the breast before 30years of age, for any type of tumour except BC. A total of 121 SBC were detected in 104 women with previous radiotherapy. Twenty percent of SBC were detected during regular breast screening and 16% of the women had a regular radiological follow-up. Our results points out that the main proportion of childhood cancer survivors did not benefit from the recommended breast cancer screening. This result is comparable to other previously published studies in other countries. A national screening programme is necessary and should take into account the patient's age, family history, personal medical history and previous radiotherapy to reduce the number of SBC diagnosed at an advanced stage. Copyright © 2017. Published by Elsevier B.V.

Treatment of anthracycline extravasation with Savene (dexrazoxane): results from two prospective clinical multicentre studies.

PubMed

Mouridsen, H T; Langer, S W; Buter, J; Eidtmann, H; Rosti, G; de Wit, M; Knoblauch, P; Rasmussen, A; Dahlstrøm, K; Jensen, P B; Giaccone, G

2007-03-01

The purpose of this study was to assess the efficacy and tolerability of i.v. dexrazoxane [Savene (EU), Totect (US)] as acute antidote in biopsy-verified anthracycline extravasation. Two prospective, open-label, single-arm, multicentre studies in patients with anthracycline extravasation were carried out. Patients with fluorescence-positive tissue biopsies were treated with a 3-day schedule of i.v. dexrazoxane (1000, 1000, and 500 mg/m(2)) starting no later than 6 h after the incident. Patients were assessed for efficacy (the possible need for surgical resection) and toxicity during the treatment period and regularly for the next 3 months. In 53 of 54 (98.2%) patients assessable for efficacy, the treatment prevented surgery-requiring necrosis. One patient (1.8%) required surgical debridement. Thirty-eight patients (71%) were able to continue their scheduled chemotherapy without postponement. Twenty-two patients (41%) experienced hospitalisation due to the extravasation. Mild pain (10 patients; 19%) and mild sensory disturbances (nine patients; 17%) were the most frequent sequelae. Haematologic toxicity was common as expected from the fact that the extravasation occurred during a chemotherapy course. Other toxic effects were transient elevation of alanine aminotransferases, nausea, and local pain at the dexrazoxane injection site. Dexrazoxane proved to be an effective and well-tolerated acute treatment with only one out of 54 assessable patients requiring surgical resection (1.8%).

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

[Prevalence of X-ray signs of femoroacetabular impingement in Mexican population].

PubMed

Gutiérrez-Ramos, R; Ávalos-Calderón, S A; Bahena-Peniche, L A

2017-01-01

Femoroacetabular impingement (FAI) is a suggested diagnosis for pain in the hip in the absence of other apparent causes. It is thought to be a cause of progressive arthrosis of the hip. Our objective was to determine the prevalence of radiographic data of FAI in the adult population without hip pathology over a period of six months. Analytical, observational, multicentric, ambispective and transverse study based on digital X-rays analysis. Measurements of the lateral center-edge angle of Wiberg, acetabular inclination, Tönnis angle and the neck shaft angle of the proximal femur were made; a pistol grip deformity of the femoral head, the triangular index and the shape of the coxofemoral joint were also evaluated. From a total of 212 hips evaluated, 104 were in males and 108 in females, with an average age of 42.81 years; 21 had a pistol grip deformity and a positive triangular index for cam type. The pincer type was found in 12 hips. In this multicentric study, the FAI cam type predominated in men on the right side; the pincer type predominated in women on the left side; this is similar to what has been reported in other populations. This study is limited by the wide variation in the femoral rotation; as an advantage, it was randomly carried out and provides some data on the prevalence of deformities of the hip, not previously registered.

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.

Standing up in multiple sclerosis (SUMS): protocol for a multi-centre randomised controlled trial evaluating the clinical and cost effectiveness of a home-based self-management standing frame programme in people with progressive multiple sclerosis.

PubMed

Freeman, J A; Hendrie, W; Creanor, S; Jarrett, L; Barton, A; Green, C; Marsden, J; Rogers, E; Zajicek, J

2016-05-05

Multiple sclerosis (MS) is an incurable, unpredictable but typically progressive neurological condition. It is the most common cause of neurological disability in young adults. Within 15 years of diagnosis, approximately 50 % of affected people are unable to walk unaided, and over time an estimated 25 % depend on a wheelchair. Typically, people with such limited mobility are excluded from clinical trials. Severely impaired people with MS spend much of their day sitting, often with limited ability to change position. In response, secondary complications can occur including: muscle wasting, pain, reduced skin integrity, spasms, limb stiffness, constipation, and associated psychosocial problems such as depression and lowered self-esteem. Effective self-management strategies, which can be implemented relatively easily and cheaply within people's homes, are needed to improve or maintain mobility and reduce sedentary behaviour. However this is challenging, particularly in the latter stages of disease. Regular supported standing using standing frames is one potential option. SUMS is a pragmatic multi-centre randomised controlled trial evaluating use of Oswestry standing frames with blinded outcome assessment and full economic evaluation. Participants will be randomly allocated (1:1) to either a home-based, self-management standing programme (with advice and support) along with their usual care or to usual care alone. Those in the intervention group will be asked to stand for a minimum of 30 min three times weekly over 20 weeks. Each participant will be followed-up at 20 and 36 weeks post baseline. The primary clinical outcome is motor function, assessed using the Amended Motor Club Assessment. The primary economic endpoint is quality-adjusted life years. The secondary outcomes include measures of explanatory physical impairments, key clinical outcomes, and health-related quality of life. An embedded qualitative component will explore participant's and carer's experiences of the standing programme. This is the first large scale multi-centre trial to assess the clinical and cost effectiveness of a home based standing frame programme for people who are severely impaired by MS. If demonstrated to be effective and cost-effective, we will use this evidence to develop recommendations for a health service delivery model which could be implemented across the United Kingdom. ISRCTN69614598 DATE OF REGISTRATION: 3.2.16 (retrospectively registered).

Exercise genomics--a paradigm shift is needed: a commentary.

PubMed

Bouchard, Claude

2015-12-01

The overarching goal of exercise genomics is to illuminate exercise biology and behaviour in order to better understand the preventive and therapeutic values of exercise. An ancillary aim is to understand the role of genomic variation in human physical attributes and sports performance. The aim of this report is to briefly comment on the current status of exercise genetics and genomics and to suggest potential improvements to the research agenda and translational activities. First, the genomic features of interest to the biology of exercise are defined. Then, the limit of the current focus on common variants and their implications for exercise genomics is highlighted. The need for a major paradigm shift in exercise genomics research is discussed with an emphasis on study designs and appropriately powered studies as well as on more mechanistic and functional research. Finally, a summary of current practices in translational activities compared with what best practice demands is introduced. One suggestion is that the research portfolio of exercise genomics be composed of a larger fraction of experimental and mechanistic investigations and a smaller fraction of observational studies. It is also recommended that research should shift to unbiased exploration of the genome using all the power of genomics, epigenomics and transcriptomics in combination with large observational but preferably experimental study designs, including Mendelian randomisation. In all cases, emphasis on replications is of paramount importance. This represents an extraordinary challenge that can only be met with large-scale collaborative and multicentre research programmes. 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/

Intelligence in DSM-IV combined type attention-deficit/hyperactivity disorder is not predicted by either dopamine receptor/transporter genes or other previously identified risk alleles for attention-deficit/hyperactivity disorder.

PubMed

Sonuga-Barke, Edmund J S; Brookes, Keeley-Joanne; Buitelaar, Jan; Anney, Richard; Bitsakou, Paraskevi; Baeyens, Dieter; Buschgens, Cathelijne; Chen, Wai; Christiansen, Hanna; Eisenberg, Jacques; Kuntsi, Jonna; Manor, Iris; Meliá, Amanda; Mulligan, Aisling; Rommelse, Nanda; Müller, Ueli C; Uebel, Henrik; Banaschewski, Tobias; Ebstein, Richard; Franke, Barbara; Gill, Michael; Miranda, Ana; Oades, Robert D; Roeyers, Herbert; Rothenberger, Aribert; Sergeant, Joseph; Steinhausen, Hans Christoph; Thompson, Margaret; Taylor, Eric; Asherson, Philip; Faraone, Stephen V

2008-04-05

A major goal of genetic studies of attention deficit hyperactivity disorder (ADHD) is to identify individual characteristics that might help segregate the disorder's inherent heterogeneity. [Mill et al. (2006); Arch Ger Psychiatry 63:462-469] recently reported a potentially important association between two dopamine-related risk polymorphisms (DRD4 variable number tandem repeat (VNTR) in exon 3 and DAT1 VNTR in the 3' UTR) and lowered IQ in ADHD. The objective of the current study was to replicate the [Mill et al. (2006); Arch Ger Psychiatry 63:462-469] findings in a clinical sample and to extend the analysis to a large range of alternative SNP markers of putative ADHD risk alleles identified in a recent study [Brookes et al. (2006); Mol Genet 11:934-953]. Participants were 1081 children and adolescents with a research-confirmed combined type ADHD diagnosis and 1300 unaffected siblings who took part in the International Multi-centre ADHD Genetics (IMAGE) project. They were recruited from multiple settings from across Europe: Belgium, Britain, Germany, Ireland, Israel, Netherlands, Spain and Switzerland. The results were that ADHD was associated with reduced IQ. However, there was no association between the two dopamine-related risk polymorphisms and IQ in either the probands or their siblings. Furthermore, other selected genetic markers previously demonstrated to be associated with ADHD in this sample were not associated with IQ. This large scale study with a clinically ascertained and regorously diagnosed sample failed to replicate the association between genetic polymorphisms in the dopamine system and IQ in ADHD. We also observed no association of other SNPs with IQ in ADHD. Copyright 2007 Wiley-Liss, Inc.

Tracking Parkinson's: Study Design and Baseline Patient Data.

PubMed

Malek, Naveed; Swallow, Diane M A; Grosset, Katherine A; Lawton, Michael A; Marrinan, Sarah L; Lehn, Alexander C; Bresner, Catherine; Bajaj, Nin; Barker, Roger A; Ben-Shlomo, Yoav; Burn, David J; Foltynie, Thomas; Hardy, John; Morris, Huw R; Williams, Nigel M; Wood, Nicholas; Grosset, Donald G

2015-01-01

There is wide variation in the phenotypic expression of Parkinson's disease (PD), which is driven by both genetic and epidemiological influences. To define and explain variation in the clinical phenotype of PD, in relation to genotypic variation. Tracking Parkinson's is a multicentre prospective longitudinal epidemiologic and biomarker study of PD. Patients attending specialist clinics in the United Kingdom with recent onset (<3.5 years) and young onset (diagnosed <50 years of age) PD were enrolled. Motor, non-motor and quality of life assessments were performed using validated scales. Cases are followed up 6 monthly up to 4.5 years for recent onset PD, and up to 1 year for young onset PD. We present here baseline clinical data from this large and demographically representative cohort. 2247 PD cases were recruited (1987 recent onset, 260 young onset). Recent onset cases had a mean (standard deviation, SD) age of 67.6 years (9.3) at study entry, 65.7% males, with disease duration 1.3 years (0.9), MDS-UPDRS 3 scores 22.9 (12.3), LEDD 295 mg/day (211) and PDQ-8 score 5.9 (4.8). Young onset cases were 53.5 years old (7.8) at study entry, 66.9% male, with disease duration 10.2 years (6.7), MDS-UPDRS 3 scores 27.4 (15.3), LEDD 926 mg/day (567) and PDQ-8 score 11.6 (6.1). We have established a large clinical PD cohort, consisting of young onset and recent onset cases, which is designed to evaluate variation in clinical expression, in relation to genetic influences, and which offers a platform for future imaging and biomarker research.

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.

Confirmation of TNIP1 but not RHOB and PSORS1C1 as systemic sclerosis risk factors in a large independent replication study

PubMed Central

Bossini-Castillo, Lara; Martin, Jose Ezequiel; Broen, Jasper; Simeon, Carmen P; Beretta, Lorenzo; Gorlova, Olga Y; Vonk, Madelon C; Ortego-Centeno, Norberto; Espinosa, Gerard; Carreira, Patricia; García de la Peña, Paloma; Oreiro, Natividad; Román-Ivorra, José Andrés; Castillo, María Jesús; González-Gay, Miguel A; Sáez-Comet, Luis; Castellví, Ivan; Schuerwegh, Annemie J; Voskuyl, Alexandre E; Hoffmann-Vold, Anna-Maria; Hesselstrand, Roger; Nordin, Annika; Lunardi, Claudio; Scorza, Raffaella; van Laar, Jacob M; Shiels, Paul G; Herrick, Ariane; Worthington, Jane; Fonseca, Carmen; Denton, Christopher; Tan, Filemon K; Arnett, Frank C; Assassi, Shervin; Koeleman, Bobby P; Mayes, Maureen D; Radstake, Timothy R D J; Martin, Javier

2013-01-01

Introduction A recent genome-wide association study in European systemic sclerosis (SSc) patients identified three loci (PSORS1C1, TNIP1 and RHOB) as novel genetic risk factors for the disease. The aim of this study was to replicate the previously mentioned findings in a large multicentre independent SSc cohort of Caucasian ancestry. Methods 4389 SSc patients and 7611 healthy controls from different European countries and the USA were included in the study. Six single nucleotide polymorphisms (SNP): rs342070, rs13021401 (RHOB), rs2233287, rs4958881, rs3792783 (TNIP1) and rs3130573 (PSORS1C1) were analysed. Overall significance was calculated by pooled analysis of all the cohorts. Haplotype analyses and conditional logistic regression analyses were carried out to explore further the genetic structure of the tested loci. Results Pooled analyses of all the analysed SNPs in TNIP1 revealed significant association with the whole disease (rs2233287 pMH=1.94×10−4, OR 1.19; rs4958881 pMH=3.26×10−5, OR 1.19; rs3792783 pMH=2.16×10−4, OR 1.19). These associations were maintained in all the subgroups considered. PSORS1C1 comparison showed association with the complete set of patients and all the subsets except for the anti-centromere-positive patients. However, the association was dependent on different HLA class II alleles. The variants in the RHOB gene were not associated with SSc or any of its subsets. Conclusions These data confirmed the influence of TNIP1 on an increased susceptibility to SSc and reinforced this locus as a common autoimmunity risk factor. PMID:22896740

Protocol for a multicentre, parallel-arm, 12-month, randomised, controlled trial of arthroscopic surgery versus conservative care for femoroacetabular impingement syndrome (FASHIoN).

PubMed

Griffin, D R; Dickenson, E J; Wall, P D H; Donovan, J L; Foster, N E; Hutchinson, C E; Parsons, N; Petrou, S; Realpe, A; Achten, J; Achana, F; Adams, A; Costa, M L; Griffin, J; Hobson, R; Smith, J

2016-08-31

Femoroacetabular impingement (FAI) syndrome is a recognised cause of young adult hip pain. There has been a large increase in the number of patients undergoing arthroscopic surgery for FAI; however, a recent Cochrane review highlighted that there are no randomised controlled trials (RCTs) evaluating treatment effectiveness. We aim to compare the clinical and cost-effectiveness of arthroscopic surgery versus best conservative care for patients with FAI syndrome. We will conduct a multicentre, pragmatic, assessor-blinded, two parallel arm, RCT comparing arthroscopic surgery to physiotherapy-led best conservative care. 24 hospitals treating NHS patients will recruit 344 patients over a 26-month recruitment period. Symptomatic adults with radiographic signs of FAI morphology who are considered suitable for arthroscopic surgery by their surgeon will be eligible. Patients will be excluded if they have radiographic evidence of osteoarthritis, previous significant hip pathology or previous shape changing surgery. Participants will be allocated in a ratio of 1:1 to receive arthroscopic surgery or conservative care. Recruitment will be monitored and supported by qualitative intervention to optimise informed consent and recruitment. The primary outcome will be pain and function assessed by the international hip outcome tool 33 (iHOT-33) measured 1-year following randomisation. Secondary outcomes include general health (short form 12), quality of life (EQ5D-5L) and patient satisfaction. The primary analysis will compare change in pain and function (iHOT-33) at 12 months between the treatment groups, on an intention-to-treat basis, presented as the mean difference between the trial groups with 95% CIs. The study is funded by the Health Technology Assessment Programme (13/103/02). Ethical approval is granted by the Edgbaston Research Ethics committee (14/WM/0124). The results will be disseminated through open access peer-reviewed publications, including Health Technology Assessment, and presented at relevant conferences. ISRCTN64081839; Pre-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/

Conservative management of CIN2: National Audit of British Society for Colposcopy and Cervical Pathology members' opinion.

PubMed

Macdonald, Madeleine; Smith, John H F; Tidy, John A; Palmer, Julia E

2018-04-01

There is no doubt that organised cervical screening programmes have significantly reduced the rates of cervical cancer by detection and treatment of high-grade cervical intraepithelial neoplasia (CIN2, CIN3). National UK guidelines do not differentiate between CIN2 and CIN3 as separate entities and recommend treatment for both, although a degree of uncertainty exists regarding the natural history of CIN2. This national survey of British Society for Colposcopy and Cervical Pathology members aimed to assess attitudes towards conservative management (CM) of CIN2 in the UK and identify potential selection criteria. In total, 511 members responded (response rate 32%); 55.6% offered CM for selective cases; 12.4% for all cases; 16.4% had formal guidelines. Most agreed age group was >40yrs (83%), HPV 16/18 positive (51.4%), smoking (60%), immuno-compromise (74.2%), and large lesion size (80.8%) were relative contraindications for CM. 75.9% favoured six-monthly monitoring, with 80.2% preferring excisional treatment for persistent high-grade disease. Many UK colposcopists manage CIN2 conservatively without formal guidelines. Potential selection criteria should be investigated by a multicentre study. Impact statement Although anecdotally some colposcopists manage many women with CIN2 conservatively, this National Audit of British Society for Colposcopy and Cytopathology members, we believe, is the first time this has been formally recorded. The survey assesses current attitudes towards conservative management (CM) of CIN2 and seeks to identify potential selection criteria that could be used to identify suitable women. It received over 500 responses and significantly, identified many colposcopists recommending CM of CIN2 for patients despite the lack of any formal guidance regarding this approach. The greater majority of respondents were keen to consider participating in a multicentre trial on CM of CIN2 targeting the UK screening population (25-64 years). The paper has international relevance as ACOG and ASCCP have recently changed their guidance for the management of CIN2 in younger women and now recommend CM with monitoring rather than first line ablative or excisional treatment due to concerns regarding overtreatment, especially in women who have not yet completed their family.

[How xenon works: neuro and cardioprotection mechanisms].

PubMed

Morais, Ricardo; Andrade, Luísa; Lourenço, André; Tavares, Jorge

2014-01-01

The Xenon, a noble gas, has anesthetics properties, associated with remarkable hemodynamic stability as well as cardioprotective, neuroprotective proprieties. Its physicochemical characteristics give him a quick induction and emergence of anesthesia, being free of deleterious effects in all organs and showing no teratogenicity. Such properties have led to a growing interest in improving the knowledge about this noble gas, in order to assess the mechanisms of neuro and cardioprotection induced and to assess the clinical indications for its use. Qualitative review of clinical trials on anesthesia with xenon. Studies were identified from MEDLINE and by hand-searching, using the following keywords: xenon, xenon anestesia, xenon neuroprotection, xenon cradioprotection. After several studies, including two randomized multicenter controlled trials, the use of xenon as an anesthetic in patients ASA I-II was approved in March 2007. However his use in clinical practice has been strongly limited by it's high price. It seems unlikely that the advantages it offers in relation to other anesthetics justify it's use in patients ASA I-II. Although, xenon may be a valuable asset in the reduction of co-morbilities and mortality in anesthesia of patients ASA III-IV, unfortunately, there are no large randomized control studies to prove it. Unfortunately, there are still no randomized or multicentric studies showing a favourable cost-benefit profile of xenon in ASA III-IV patients vs. other anaesthetics. The usefulness of xenon in Anesthesiology requires more studies to be defined.

Assessment of the Safety and Efficacy of a Raft-Forming Alginate Reflux Suppressant (Liquid Gaviscon) for the Treatment of Heartburn during Pregnancy

PubMed Central

Strugala, Vicki; Bassin, Julian; Swales, Valerie S.; Lindow, Stephen W.; Dettmar, Peter W.; Thomas, Edward C. M.

2012-01-01

Gastro-oesophageal reflux (GER) and the symptoms of heartburn and regurgitation are common in pregnancy. These symptoms are transient and mostly resolve postpartum but have a negative impact on quality of life. Here, we present a prospective clinical evaluation of the safety and efficacy of an alginate raft-forming oral suspension that is licensed for use in pregnancy. The study was a multicentre, prospective, open-label, and baseline-controlled study of Liquid Gaviscon (LG) in the treatment of heartburn in pregnant women with current symptoms of heartburn and/or reflux requiring treatment (recruited 144). The efficacy of the study medication was rated by the investigator (primary endpoint) and patient. Treatment was deemed to be a success in 91% of patients as judged by the investigator (95% CI 85.0–95.3) and 90% (95% CI 84.1–94.8) when assessed by the patient themselves. Very few adverse events or serious adverse events were reported that were considered to be related to the study medication, and these were consistent with the normal population incidences. Serum sodium levels remained unchanged. This prospective open-label study in a large number of pregnant women has shown that LG is both safe and highly efficacious in the treatment of heartburn and GER symptoms in pregnancy. PMID:23209926

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.

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.

Feasibility of a prospective, randomised, open-label, international multicentre, phase III, non-inferiority trial to assess the safety of active surveillance for low risk ductal carcinoma in situ - The LORD study.

PubMed

Elshof, Lotte E; Tryfonidis, Konstantinos; Slaets, Leen; van Leeuwen-Stok, A Elise; Skinner, Victoria P; Dif, Nicolas; Pijnappel, Ruud M; Bijker, Nina; Rutgers, Emiel J Th; Wesseling, Jelle

2015-08-01

The current debate on overdiagnosis and overtreatment of screen-detected ductal carcinoma in situ (DCIS) urges the need for prospective studies to address this issue. A substantial number of DCIS lesions will never form a health hazard, particularly if it concerns non- to slow-growing low-grade DCIS. The LORD study aims to evaluate the safety of active surveillance in women with low-risk DCIS. This is a randomised, international multicentre, open-label, phase III non-inferiority trial, led by the Dutch Breast Cancer Research Group (BOOG 2014-04) and the European Organization for Research and Treatment of Cancer (EORTC-BCG 1401). Standard treatment will be compared to active surveillance in 1240 women aged ⩾ 45 years with asymptomatic, screen-detected, pure low-grade DCIS based on vacuum-assisted biopsies of microcalcifications only. Both study arms will be monitored with annual digital mammography for a period of 10 years. The primary end-point is 10-year ipsilateral invasive breast cancer free percentage. Secondary end-points include patient reported outcomes, diagnostic biopsy rate during follow-up, ipsilateral mastectomy rate and translational research. To explore interest in and feasibility of the LORD study we conducted a survey among EORTC and BOOG centres. A vast majority of EORTC and BOOG responding centres expressed interest in participation in the LORD study. The proposed study design is endorsed by nearly all centres. Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.

The ‘Hothaps’ programme for assessing climate change impacts on occupational health and productivity: an invitation to carry out field studies

PubMed Central

Kjellstrom, Tord; Gabrysch, Sabine; Lemke, Bruno; Dear, Keith

2009-01-01

The ‘high occupational temperature health and productivity suppression’ programme (Hothaps) is a multi-centre health research and prevention programme aimed at quantifying the extent to which working people are affected by, or adapt to, heat exposure while working, and how global heating during climate change may increase such effects. The programme will produce essential new evidence for local, national and global assessment of negative impacts of climate change that have largely been overlooked. It will also identify and evaluate preventive interventions in different social and economic settings. Hothaps includes studies in any part of the world where hourly heat exposure exceeds physiological stress limits that may affect workers. This usually happens at temperatures above 25°C, depending on humidity, wind movement and heat radiation. Working people in low and middle-income tropical countries are particularly vulnerable, because many of them are involved in heavy physical work, either outdoors in strong sunlight or indoors without effective cooling. If high work intensity is maintained in workplaces with high heat exposure, serious health effects can occur, including heat stroke and death. Depending on the type of occupation, the required work intensity, and the level of heat stress, working people have to slow down their work in order to reduce internal body heat production and the risk of heat stroke. Thus, unless preventive interventions are used to reduce the heat stress on workers, their individual health and productivity will be affected and economic output per work hour will be reduced. Heat also influences other daily physical activities, unrelated to work, in all age groups. Poorer people without access to household or workplace cooling devices are most likely to be affected. The Hothaps programme includes a pilot study, heat monitoring of selected workplaces, qualitative studies of perceived heat impacts and preventative interventions, quantitative studies of impacts on health and productivity, and assessments of local impacts of climate change taking into account different applications of preventative interventions. Fundraising for the global programme is in progress and has enabled local field studies to start in 2009. Local funding support is also of great value and is being sought by several interested scientific partners. The Hothaps team welcomes independent use of the study protocols, but would be grateful for information about any planned, ongoing or completed studies of this type. Coordinated implementation of the protocols in multi-centre studies is also welcome. Eventually, the results of the Hothaps field studies will be used in global assessments of climate change-induced heat exposure increase in workplaces and its impacts on occupational health and productivity. These results will also be of value for the next assessment by the Intergovernmental Panel on Climate Change (IPCC) in 2013. PMID:20052425

The 'Hothaps' programme for assessing climate change impacts on occupational health and productivity: an invitation to carry out field studies.

PubMed

Kjellstrom, Tord; Gabrysch, Sabine; Lemke, Bruno; Dear, Keith

2009-11-11

The 'high occupational temperature health and productivity suppression' programme (Hothaps) is a multi-centre health research and prevention programme aimed at quantifying the extent to which working people are affected by, or adapt to, heat exposure while working, and how global heating during climate change may increase such effects. The programme will produce essential new evidence for local, national and global assessment of negative impacts of climate change that have largely been overlooked. It will also identify and evaluate preventive interventions in different social and economic settings.Hothaps includes studies in any part of the world where hourly heat exposure exceeds physiological stress limits that may affect workers. This usually happens at temperatures above 25 degrees C, depending on humidity, wind movement and heat radiation. Working people in low and middle-income tropical countries are particularly vulnerable, because many of them are involved in heavy physical work, either outdoors in strong sunlight or indoors without effective cooling. If high work intensity is maintained in workplaces with high heat exposure, serious health effects can occur, including heat stroke and death.Depending on the type of occupation, the required work intensity, and the level of heat stress, working people have to slow down their work in order to reduce internal body heat production and the risk of heat stroke. Thus, unless preventive interventions are used to reduce the heat stress on workers, their individual health and productivity will be affected and economic output per work hour will be reduced. Heat also influences other daily physical activities, unrelated to work, in all age groups. Poorer people without access to household or workplace cooling devices are most likely to be affected.The Hothaps programme includes a pilot study, heat monitoring of selected workplaces, qualitative studies of perceived heat impacts and preventative interventions, quantitative studies of impacts on health and productivity, and assessments of local impacts of climate change taking into account different applications of preventative interventions.Fundraising for the global programme is in progress and has enabled local field studies to start in 2009. Local funding support is also of great value and is being sought by several interested scientific partners. The Hothaps team welcomes independent use of the study protocols, but would be grateful for information about any planned, ongoing or completed studies of this type. Coordinated implementation of the protocols in multi-centre studies is also welcome. Eventually, the results of the Hothaps field studies will be used in global assessments of climate change-induced heat exposure increase in workplaces and its impacts on occupational health and productivity. These results will also be of value for the next assessment by the Intergovernmental Panel on Climate Change (IPCC) in 2013.

Performance of EuroSCORE II in a large US database: implications for transcatheter aortic valve implantation.

PubMed

Osnabrugge, Ruben L; Speir, Alan M; Head, Stuart J; Fonner, Clifford E; Fonner, Edwin; Kappetein, A Pieter; Rich, Jeffrey B

2014-09-01

Validation studies of European system for cardiac operative risk evaluation II (EuroSCORE II) have been limited to European datasets. Therefore, the aims of this study were to assess the performance of EuroSCORE II in a large multicentre US database, and compare it with the Society of Thoracic Surgeons Predicted Risk of Mortality (STS-PROM). In addition, implications for patient selection for transcatheter aortic valve implantation (TAVI) were explored. EuroSCORE II and the STS-PROM were calculated for 50 588 patients from a multi-institutional statewide database of all cardiac surgeries performed since 2003. Model performance was assessed using the area under the receiver operator curve (AUC), observed vs expected (O:E) ratios and calibration plots. Analyses were performed for isolated coronary artery bypass grafting (CABG) (n = 40 871), aortic valve replacement (AVR) (n = 4107), AVR + CABG (n = 3480), mitral valve (MV) replacement (n = 1071) and MV repair (n = 1059). The overall in-hospital mortality rate was 2.1%. EuroSCORE II was outperformed by the STS-PROM in the overall cohort with regard to discrimination (AUC = 0.77 vs 0.81, respectively; P < 0.001) and calibration (O:E = 0.68 vs 0.80, respectively). Discrimination for CABG was worse with EuroSCORE II (AUC = 0.77 vs STS-PROM: 0.81, P < 0.001). For other procedures discrimination was similar: AVR (AUC = 0.71 vs STS-PROM: 0.74, P = 0.40), AVR + CABG (AUC = 0.72 vs STS-PROM: 0.74, P = 0.47), MV repair (AUC = 0.82 vs STS-PROM: 0.86, P = 0.55) and MV replacement (AUC = 0.78 vs STS-PROM: 0.79, P = 0.69). Calibration of EuroSCORE II was worse for CABG (O:E = 0.68 vs STS-PROM: 0.80), similar in AVR + CABG (O:E = 0.76 vs STS-PROM: 0.70) and MV repair (O:E = 0.64 vs STS-PROM: 0.67), while EuroSCORE II may be more accurate in AVR (O:E = 0.96 vs STS-PROM: 0.76). Performance of both models improved when only recent cases (after 1 January 2008) were used. Ongoing TAVI trials aimed at patients with an estimated 4-10% risk of mortality are enrolling patients with mean estimated risks of 6.2% (EuroSCORE II) or 6.0% (STS-PROM), and an actual mortality rate of 4.6% (EuroSCORE II) or 4.8% (STS-PROM). In a large US multicentre database, the STS-PROM performs better than EuroSCORE II for CABG. However, EuroSCORE II is a reasonable alternative in low-risk CABG patients and in those undergoing other cardiac surgical procedures. Clinical trials and physicians that use these scores recruit and treat patients who are at a lower risk than anticipated. This potentially leads to overtreatment with an investigational device. Decision-making should not solely be based on risk scores, but should comprise multidisciplinary heart team discussions. © The Author 2014. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.

Intrathecal baclofen therapy in paediatrics: a study protocol for an Australian multicentre, 10-year prospective audit

PubMed Central

Stewart, Kirsty; Hutana, Gavin; Kentish, Megan

2017-01-01

Introduction Increasing clinical use of Intrathecal baclofen (ITB) in Australian tertiary paediatric hospitals, along with the need for standardised assessment and reporting of adverse events, saw the formation of the Australian Paediatric ITB Research Group (APIRG). APIRG developed a National ITB Audit tool designed to capture clinical outcomes and adverse events data for all Australian children and adolescents receiving ITB therapy. Methods and analysis The Australian ITB Audit is a 10 year, longitudinal, prospective, clinical audit collecting all adverse events and assessment data across body functions and structure, participation and activity level domains of the ICF. Data will be collected at baseline, 6 and 12 months with ongoing capture of all adverse event data. This is the first Australian study that aims to capture clinical and adverse event data from a complete population of children with neurological impairment receiving a specific intervention between 2011 and 2021. This multi-centre study will inform ITB clinical practice in children and adolescents, direct patient selection, record and aid decision making regarding adverse events and investigate the impact of ITB therapy on family and patient quality of life. Ethics and dissemination This project was approved by the individual Human Research Ethics committees at the six Australian tertiary hospitals involved in the study. Results will be published in various peer reviewed journals and presented at national and international conferences. Trial registration number ACTRN 12610000323022; Pre-results. PMID:28637739

Prospective evaluation of the International Neuroblastoma Staging System (INSS) and the International Neuroblastoma Response Criteria (INRC) in a multicentre setting.

PubMed

Castel, V; García-Miguel, P; Cañete, A; Melero, C; Navajas, A; Ruíz-Jiménez, J I; Navarro, S; Badal, M D

1999-04-01

The aim of this study was to classify prospectively a series of neuroblastoma tumours according to the International Neuroblastoma Staging System (INSS) and the International Neuroblastoma Response Criteria (INRC) and to evaluate the difficulties and pitfalls involved in a multicentre setting. Each hospital provided their data for central review. The surgical procedures and their complications were reported. Kaplan-Meier estimates of survival and event-free survival were calculated according to stage and response to therapy. From June 1992 to December 1996, 194 patients were included in the study, with a mean age of 2 years. Initial studies were performed according to INSS recommendations without major problems. INSS stage was correctly applied to all patients except for 9 (95%). Post-operative complications were observed in 15 patients (8.3%). Response to therapy (INRC) was studied in 63 stage 4 patients, 11 of whom were not classified correctly (17%). Differences in survival according to stage (INSS) and group of response to therapy (INRC) were statistically significant (P < 0.001). In conclusion the INSS was easy to use and separated different prognostic groups. Surgical complications and mortality did not increase in this series because of using the INSS. The feasibility of INRC was evaluated in a small series of stage 4 patients and the designation of response was problematic in a relatively high proportion of cases. The prognostic value of the different responses was highly significant, but less informative than had been hoped for.

[Cinacalcet in the management of normocalcaemic secondary hyperparathyroidism after kidney transplantation: one-year follow-up multicentre study].

PubMed

Torregrosa, Josep V; Morales, Enrique; Díaz, Juan M; Crespo, Josep; Bravo, Juan; Gómez, Gonzalo; Gentil, Miguel A; Rodríguez-Benot, Alberto; Rodríguez-García, Minerva; López-Jiménez, Verónica; Gutiérrez-Dalmau, Álex; Jimeno, Luisa; Pérez-Sáez, M José; Romero, Rafael; Gómez-Alamillo, Carlos

2014-01-01

The effect of cinacalcet in patients with persistent secondary hyperparathyroidism (SHPT) after kidney transplantation (RT) has mainly been reported in patients with secondary hypercalcaemia. Our objective was to assess the long-term effect of cinacalcet on patients with a RT and normocalcaemic SHPT. A one-year multicentre, observational, retrospective study that included kidney recipients with SHPT (intact parathyroid hormone [iPTH] >120 pg/ml) and calcium levels within the normal range (8.4-10.2 mg/dl). Patients began treatment with cinacalcet in clinical practice. 32 patients with a mean age (standard deviation [SD]) of 54 (11) years, 56% male, were included in the study. Treatment with cinacalcet began a median of 16 months after RT (median dose of 30 mg/day). Levels of iPTH decreased from a median (P25, P75) of 364 (220, 531) pg/ml at the start of the study to 187 (98, 320) after 6 months (48.6% reduction, P=.001) and to 145 (91, 195) after 12 months (60.2% reduction, P=.001), without there being changes in calcium and phosphorus levels (P=.214 and P=.216, respectively). No changes were observed in kidney function or anti-calcineuric drug levels. 3.1% of patients discontinued cinacalcet due to intolerance and 6.2% due to a lack of efficacy. In patients with normocalcaemic SHPT after RT, cinacalcet improves the control of serum PTH values without causing changes to calcaemia, phosphataemia or kidney function. Cinacalcet showed good tolerability.

International Rare Histiocytic Disorders Registry (IRHDR)

ClinicalTrials.gov

2018-04-18

Rare Histiocytic Disorders (RHDs); Juvenile Xanthogranuloma (JXG); Reticulohistiocytoma (Epithelioid Histiocytoma); Xanthoma Disseminatum (XD); Multicentric Reticulohistiocytosis (MRH); Systemic Juvenile Xanthogranuloma; Erdheim-Chester Disease (ECD); Multi-system Rosai-Dorfman Disease (RDD)

A multi-centre, parallel group superiority trial of silk therapeutic clothing compared to standard care for the management of eczema in children (CLOTHES Trial): study protocol for a randomised controlled trial.

PubMed

Harrison, Eleanor F; Haines, Rachel H; Cowdell, Fiona; Sach, Tracey H; Dean, Taraneh; Pollock, Ian; Burrows, Nigel P; Buckley, Hannah; Batchelor, Jonathan; Williams, Hywel C; Lawton, Sandra; Brown, Sara J; Bradshaw, Lucy E; Ahmed, Amina; Montgomery, Alan A; Mitchell, Eleanor J; Thomas, Kim S

2015-09-02

Eczema is a chronic, itchy skin condition that can have a large impact on the quality of life of patients and their families. People with eczema are often keen to try out non-pharmacological therapies like silk therapeutic garments that could reduce itching or the damage caused by scratching. However, the effectiveness and cost-effectiveness of these garments in the management of eczema has yet to be proven. The CLOTHES Trial will test the hypothesis that 'silk therapeutic garments plus standard eczema care' is superior to 'standard care alone' for children with moderate to severe eczema. Parallel group, observer-blind, pragmatic, multi-centre randomised controlled trial of 6 months' duration. Three hundred children aged 1 to 15 years with moderate to severe eczema will be randomised (1:1) to receive silk therapeutic garments plus standard eczema care, or standard eczema care alone. Primary outcome is eczema severity, as assessed by trained and blinded investigators at 2, 4 and 6 months (using the Eczema Area and Severity Index (EASI)). Secondary outcomes include: patient-reported eczema symptoms (collected weekly for 6 months to capture long-term control); global assessment of severity; quality of life of the child, family and main carer; use of standard eczema treatments (emollients, corticosteroids applied topically, calcineurin inhibitors applied topically and wet wraps); frequency of infections; and cost-effectiveness. The acceptability and durability of the clothing will also be assessed, as will adherence to wearing the garments. A nested qualitative study will assess the views of a subset of children wearing the garments and their parents, and those of healthcare providers and commissioners. Randomisation uses a computer-generated sequence of permuted blocks of randomly varying size, stratified by recruiting hospital and child's age (< 2 years; 2 to 5 years; > 5 years), and concealed using a secure web-based system. The sequence of treatment allocations will remain concealed until randomisation and data collection are complete. Recruitment is taking place from November 2013 to May 2015, and the trial will be completed in 2016. Full details of results will be published in the National Institute for Health Research Journal series. Current Controlled Trials ISRCTN77261365 (registered 11 November 2013).

Nifedipine versus atosiban for threatened preterm birth (APOSTEL III): a multicentre, randomised controlled trial.

PubMed

van Vliet, Elvira O G; Nijman, Tobias A J; Schuit, Ewoud; Heida, Karst Y; Opmeer, Brent C; Kok, Marjolein; Gyselaers, Wilfried; Porath, Martina M; Woiski, Mallory; Bax, Caroline J; Bloemenkamp, Kitty W M; Scheepers, Hubertina C J; Jacquemyn, Yves; Beek, Erik van; Duvekot, Johannes J; Franssen, Maureen T M; Papatsonis, Dimitri N; Kok, Joke H; van der Post, Joris A M; Franx, Arie; Mol, Ben W; Oudijk, Martijn A

2016-05-21

In women with threatened preterm birth, delay of delivery by 48 h allows antenatal corticosteroids to improve neonatal outcomes. For this reason, tocolytics are often administered for 48 h; however, there is no consensus about which drug results in the best maternal and neonatal outcomes. In the APOSTEL III trial we aimed to compare the effectiveness and safety of the calcium-channel blocker nifedipine and the oxytocin inhibitor atosiban in women with threatened preterm birth. We did this multicentre, randomised controlled trial in ten tertiary and nine teaching hospitals in the Netherlands and Belgium. Women with threatened preterm birth (gestational age 25-34 weeks) were randomly assigned (1:1) to either oral nifedipine or intravenous atosiban for 48 h. An independent data manager used a web-based computerised programme to randomly assign women in permuted block sizes of four, with groups stratified by centre. Clinicians, outcome assessors, and women were not masked to treatment group. The primary outcome was a composite of adverse perinatal outcomes, which included perinatal mortality, bronchopulmonary dysplasia, sepsis, intraventricular haemorrhage, periventricular leukomalacia, and necrotising enterocolitis. Analysis was done in all women and babies with follow-up data. The study is registered at the Dutch Clinical Trial Registry, number NTR2947. Between July 6, 2011, and July 7, 2014, we randomly assigned 254 women to nifedipine and 256 to atosiban. Primary outcome data were available for 248 women and 297 babies in the nifedipine group and 255 women and 294 babies in the atosiban group. The primary outcome occurred in 42 babies (14%) in the nifedipine group and in 45 (15%) in the atosiban group (relative risk [RR] 0·91, 95% CI 0·61-1·37). 16 (5%) babies died in the nifedipine group and seven (2%) died in the atosiban group (RR 2·20, 95% CI 0·91-5·33); all deaths were deemed unlikely to be related to the study drug. Maternal adverse events did not differ between groups. In women with threatened preterm birth, 48 h of tocolysis with nifedipine or atosiban results in similar perinatal outcomes. Future clinical research should focus on large placebo-controlled trials, powered for perinatal outcomes. ZonMw (the Netherlands Organisation for Health Research and Development). Copyright © 2016 Elsevier Ltd. All rights reserved.

A multicentre molecular analysis of hepatitis B and blood-borne virus coinfections in Viet Nam.

PubMed

Dunford, Linda; Carr, Michael J; Dean, Jonathan; Nguyen, Linh Thuy; Ta Thi, Thu Hong; Nguyen, Binh Thanh; Connell, Jeff; Coughlan, Suzie; Nguyen, Hien Tran; Hall, William W; Thi, Lan Anh Nguyen

2012-01-01

Hepatitis B (HBV) infection is endemic in Viet Nam, with up to 8.4 million individuals estimated to be chronically infected. We describe results of a large, multicentre seroepidemiological and molecular study of the prevalence of HBV infection and blood-borne viral coinfections in Viet Nam. Individuals with varying risk factors for infection (n = 8654) were recruited from five centres; Ha Noi, Hai Phong, Da Nang, Khanh Hoa and Can Tho. A mean prevalence rate of 10.7% was observed and levels of HBsAg were significantly higher in injecting drug users (IDUs) (17.4%, n = 174/1000) and dialysis patients (14.3%, n = 82/575) than in lower-risk groups (9.4%; p<0.001). Coinfection with HIV was seen in 28% of HBV-infected IDUs (n = 49/174) and 15.2% of commercial sex workers (CSWs; n = 15/99). HCV infection was present in 89.8% of the HBV-HIV coinfected IDUs (n = 44/49) and 40% of HBV-HIV coinfected CSWs (n = 16/40). Anti-HDV was detected in 10.7% (n = 34/318) of HBsAg positive individuals. Phylogenetic analysis of HBV S gene (n = 187) showed a predominance of genotype B4 (82.6%); genotypes C1 (14.6%), B2 (2.7%) and C5 (0.5%) were also identified. The precore mutation G1896A was identified in 35% of all specimens, and was more frequently observed in genotype B (41%) than genotype C (3%; p<0.0001). In the immunodominant 'a' region of the surface gene, point mutations were identified in 31% (n = 58/187) of sequences, and 2.2% (n = 4/187) and 5.3% (n = 10/187) specimens contained the major vaccine escape mutations G145A/R and P120L/Q/S/T, respectively. 368 HBsAg positive individuals were genotyped for the IL28B SNP rs12979860 and no significant association between the IL28B SNP and clearance of HBsAg, HBV viral load or HBeAg was observed. This study confirms the high prevalence of HBV infection in Viet Nam and also highlights the significant levels of blood-borne virus coinfections, which have important implications for hepatitis-related morbidity and development of effective management strategies.

A Multicentre Molecular Analysis of Hepatitis B and Blood-Borne Virus Coinfections in Viet Nam

PubMed Central

Dunford, Linda; Carr, Michael J.; Dean, Jonathan; Nguyen, Linh Thuy; Ta Thi, Thu Hong; Nguyen, Binh Thanh; Connell, Jeff; Coughlan, Suzie; Nguyen, Hien Tran; Hall, William W.; Thi, Lan Anh Nguyen

2012-01-01

Hepatitis B (HBV) infection is endemic in Viet Nam, with up to 8.4 million individuals estimated to be chronically infected. We describe results of a large, multicentre seroepidemiological and molecular study of the prevalence of HBV infection and blood-borne viral coinfections in Viet Nam. Individuals with varying risk factors for infection (n = 8654) were recruited from five centres; Ha Noi, Hai Phong, Da Nang, Khanh Hoa and Can Tho. A mean prevalence rate of 10.7% was observed and levels of HBsAg were significantly higher in injecting drug users (IDUs) (17.4%, n = 174/1000) and dialysis patients (14.3%, n = 82/575) than in lower-risk groups (9.4%; p<0.001). Coinfection with HIV was seen in 28% of HBV-infected IDUs (n = 49/174) and 15.2% of commercial sex workers (CSWs; n = 15/99). HCV infection was present in 89.8% of the HBV-HIV coinfected IDUs (n = 44/49) and 40% of HBV-HIV coinfected CSWs (n = 16/40). Anti-HDV was detected in 10.7% (n = 34/318) of HBsAg positive individuals. Phylogenetic analysis of HBV S gene (n = 187) showed a predominance of genotype B4 (82.6%); genotypes C1 (14.6%), B2 (2.7%) and C5 (0.5%) were also identified. The precore mutation G1896A was identified in 35% of all specimens, and was more frequently observed in genotype B (41%) than genotype C (3%; p<0.0001). In the immunodominant ‘a’ region of the surface gene, point mutations were identified in 31% (n = 58/187) of sequences, and 2.2% (n = 4/187) and 5.3% (n = 10/187) specimens contained the major vaccine escape mutations G145A/R and P120L/Q/S/T, respectively. 368 HBsAg positive individuals were genotyped for the IL28B SNP rs12979860 and no significant association between the IL28B SNP and clearance of HBsAg, HBV viral load or HBeAg was observed. This study confirms the high prevalence of HBV infection in Viet Nam and also highlights the significant levels of blood-borne virus coinfections, which have important implications for hepatitis-related morbidity and development of effective management strategies. PMID:22720022

Open three-stage transthoracic oesophagectomy versus minimally invasive thoraco-laparoscopic oesophagectomy for oesophageal cancer: protocol for a multicentre prospective, open and parallel, randomised controlled trial.

PubMed

Mu, Juwei; Gao, Shugeng; Mao, Yousheng; Xue, Qi; Yuan, Zuyang; Li, Ning; Su, Kai; Yang, Kun; Lv, Fang; Qiu, Bin; Liu, Deruo; Chen, Keneng; Li, Hui; Yan, Tiansheng; Han, Yongtao; Du, Ming; Xu, Rongyu; Wen, Zhaoke; Wang, Wenxiang; Shi, Mingxin; Xu, Quan; Xu, Shun; He, Jie

2015-11-17

Oesophageal cancer is the eighth most common cause of cancer worldwide. In 2009 in China, the incidence and death rate of oesophageal cancer was 22.14 per 100 000 person-years and 16.77 per 100 000 person-years, respectively, the highest in the world. Minimally invasive oesophagectomy (MIO) was introduced into clinical practice with the aim of reducing the morbidity rate. The mechanisms of MIO may lie in minimising the reaction to surgical injury and inflammation. There are some randomised trials regarding minimally invasive versus open oesophagectomy, with 100-850 subjects enrolled. To date, no large randomised controlled trial comparing minimally invasive versus open oesophagectomy has been reported in China, where squamous cell carcinoma predominated over adenocarcinoma of the oesophagus. This is a 3 year multicentre, prospective, randomised, open and parallel controlled trial, which aims to compare the effectiveness of minimally invasive thoraco-laparoscopic oesophagectomy to open three-stage transthoracic oesophagectomy for resectable oesophageal cancer. Group A patients receive MIO which involves thoracoscopic oesophagectomy and laparoscopic gastric mobilisation with cervical anastomosis. Group B patients receive the open three-stage transthoracic oesophagectomy which involves a right thoracotomy and laparotomy with cervical anastomosis. Primary endpoints include respiratory complications within 30 days after operation. The secondary endpoints include other postoperative complications, influences on pulmonary function, intraoperative data including blood loss, operative time, the number and location of lymph nodes dissected, and mortality in hospital, the length of hospital stay, total expenses in hospital, mortality within 30 days, survival rate after 2 years, postoperative pain, and health-related quality of life (HRQoL). Three hundred and twenty-four patients in each group will be needed and a total of 648 patients will finally be enrolled into the study. The study protocol has been approved by the Institutional Ethics Committees of all participating institutions. The findings of this trial will be disseminated to patients and through peer-reviewed publications and international presentations. NCT02355249. 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/

Outcomes after resection of occupational cholangiocarcinoma.

PubMed

Kubo, Shoji; Takemura, Shigekazu; Tanaka, Shogo; Shinkawa, Hiroji; Kinoshita, Masahiko; Hamano, Genya; Ito, Tokuji; Koda, Masaki; Aota, Takanori; Yamamoto, Takatsugu; Terajima, Hiroaki; Tachiyama, Gorou; Yamada, Terumasa; Nakamori, Shoji; Arimoto, Akira; Fujikawa, Masahiro; Tomimaru, Yoshito; Sugawara, Yasuhiko; Nakagawa, Kei; Unno, Michiaki; Mizuguchi, Toru; Takenaka, Kenji; Kimura, Koichi; Shirabe, Ken; Saiura, Akio; Uesaka, Katsuhiko; Taniguchi, Hiroki; Fukuda, Akira; Chong, Ja-Mun; Kuwae, Yuko; Ohsawa, Masahiko; Sato, Yasunori; Nakanuma, Yasuni

2016-09-01

Cholangiocarcinoma caused by exposure to 1,2-dichloropropane and/or dichloromethane is recognized as occupational cholangiocarcinoma. The aim of this study was to investigate the outcomes after resection of occupational cholangiocarcinoma to establish a treatment strategy for this disease. Clinicopathological findings and outcomes after surgical intervention in 20 patients with occupational cholangiocarcinoma were investigated. Of 20 the patients, curative resection was performed in 16 patients. Three patients underwent radiation at the stump of the bile ducts. Adjuvant chemotherapy was performed in 12 patients. Biliary intraepithelial neoplasia, intraductal papillary neoplasm of the bile duct, and/or chronic bile duct injury was detected in most subjects. Intraabdominal infection developed after surgery in nine patients. Cholangiocarcinoma recurred in 12 of the 20 patients. The recurrent tumors in five patients developed at a different part of the bile duct from the primary tumor and a second resection was performed in four of these five patients. The incidence of postoperative complications including intraabdominal infection was high in patients with occupational cholangiocarcinoma. Multicentric recurrence occurred not infrequently after surgery because the bile ducts had a high potential for the development of carcinoma. The aggressive treatment including second resection for the multicentric recurrence appeared to be effective. © 2016 Japanese Society of Hepato-Biliary-Pancreatic Surgery.

Clinical evaluation study of the German network of disorders of sex development (DSD)/intersexuality: study design, description of the study population, and data quality

PubMed Central

Lux, Anke; Kropf, Siegfried; Kleinemeier, Eva; Jürgensen, Martina; Thyen, Ute

2009-01-01

Background The German Network of Disorders of Sex Development (DSD)/Intersexuality carried out a large scale clinical evaluation study on quality of life, gender identity, treatment satisfaction, coping, and problems associated with diagnoses and therapies in individuals with disorders of sex development (DSD). DSD are a heterogeneous group of various genetic disorders of sex determination or sex differentiation, all of which are rare conditions. In about half of all cases the molecular genetic diagnosis is unknown and diagnosis rests on clinical features. Methods and design The multi-centre clinical evaluation study includes short-term follow-up in some and cross-sectional assessments in all age and diagnostic groups fitting the criteria of DSD. Recruitment was from January 2005 until December 2007 in whole Germany and, additionally, in 2007 in Austria and German-speaking Switzerland. The study consists of a psychosocial inquiry for children, adolescents and their parents, and adults with standardized instruments and the collection of DSD-specific medical data by the attending physician. The main goal was the description of clinical outcomes and the health-care situation of individuals with DSD using a broad generic definition of DSD including all conditions with a mismatch of chromosomal, gonadal and phenotypical sex. 439 children and adolescents, their parents and adults with DSD participated. Discussion The clinical evaluation study represents the most comprehensive study in this clinical field. The paper discusses the study protocol, the data management and data quality as well as the classification used, and it describes the study population. Given the lack of large datasets in rare conditions such as DSD and often biased results from small scale clinical case series, the study aims to generate concrete hypotheses for evidence-based guidelines, which should be tested in further studies. PMID:19383134

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

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.

Endoscopic Stenting as Bridge to Surgery versus Emergency Resection for Left-Sided Malignant Colorectal Obstruction: An Updated Meta-Analysis

PubMed Central

Ceresoli, Marco; Fugazzola, Paola; Ansaloni, Luca

2017-01-01

Introduction Emergency resection represents the traditional treatment for left-sided malignant obstruction. However, the placement of self-expanding metallic stents and delayed surgery has been proposed as an alternative approach. The aim of the current meta-analysis was to review the available evidence, with particular interest for the short-term outcomes, including a recent multicentre RCT. Methods We considered randomized controlled trials comparing stenting as a bridge to surgery and emergency surgery for the management of left-sided malignant large bowel obstruction, performing a systematic review in MEDLINE, PubMed database, and the Cochrane libraries. Results We initially identified a total of 2543 studies. After the elimination of duplicates and the screening of titles and abstracts, seven studies, for a total of 448 patients, were considered. The current meta-analysis revealed no difference in the mortality rate between the stent group and the emergency surgery group; the postoperative complication rate (37.84% versus 54.87%, P = 0.02), the stoma rate (28.8% versus 46.02%, P < 0.0001), and the incidence of wound infection (8.11% versus 15.49%, P = 0.01) were reduced after stent as a bridge to surgery. Conclusion Colonic stenting as a bridge to surgery appears to be a safe approach to malignant large bowel obstruction. Possible advantages of this treatment can be identified in a reduced incidence of postoperative complications and a lower stoma rate. Further RCTs considering long-term outcomes and cost-effectiveness analysis are needed. PMID:28761765

The prevalence of metabolic syndrome in Latin America: a systematic review.

PubMed

Márquez-Sandoval, F; Macedo-Ojeda, G; Viramontes-Hörner, D; Fernández Ballart, J D; Salas Salvadó, J; Vizmanos, B

2011-10-01

To assess the available data on the prevalence of metabolic syndrome (MS) in Latin-American countries. Systematic review. Searches were carried out in PubMed, ISIWeb, SCielo and Redalyc, using 'metabolic syndrome x' and 'prevalence' as keywords for titles and/or abstracts. Articles selected were cross-sectional studies in Latin-American countries, whose main objective was to study MS and whose study population is described below. MS must be determined using Adult Treatment Panel III criteria. Twelve studies with these criteria were selected, one of which was multi-centric. Latin America. Apparently healthy subjects aged 18-65 years (including young adult, mature adult and elderly populations) of both genders. The general prevalence (weighted mean) of MS in Latin-American countries was 24·9 (range: 18·8-43·3) %. MS was slightly more frequent in women (25·3 %) than in men (23·2 %), and the age group with the highest prevalence of MS consisted of those over 50 years of age. The most frequent components of MS were low HDL cholesterol levels (62·9 %) and abdominal obesity (45·8 %). Similar outcomes were obtained from the multi-centre study on Latin-American populations analysed. The present review brings us closer to an understanding of the prevalence of MS in Latin-American countries. However, it is not possible to know the full scope of the problem, partly because data from some countries are not available, and because the methodological differences among the studies published up to the present limit a joint analysis of their results.

Reference intervals: current status, recent developments and future considerations.

PubMed

Ozarda, Yesim

2016-01-01

Reliable and accurate reference intervals (RIs) for laboratory analyses are an integral part of the process of correct interpretation of clinical laboratory test results. RIs given in laboratory reports have an important role in aiding the clinician in interpreting test results in reference to values for healthy populations. Since the 1980s, the International Federation of Clinical Chemistry (IFCC) has been proactive in establishing recommendations to clarify the true significance of the term 'RIs, to select the appropriate reference population and statistically analyse the data. The C28-A3 guideline published by the Clinical and Laboratory Standards Institute (CLSI) and IFCC is still the most widely-used source of reference in this area. In recent years, protocols additional to the Guideline have been published by the IFCC, Committee on Reference Intervals and Decision Limits (C-RIDL), including all details of multicenter studies on RIs to meet the requirements in this area. Multicentric RIs studies are the most important development in the area of RIs. Recently, the C-RIDL has performed many multicentric studies to obtain common RIs. Confusion of RIs and clinical decision limits (CDLs) remains an issue and pediatric and geriatric age groups are a significant problem. For future studies of RIs, the genetic effect would seem to be the most challenging area. 
The aim of the review is to present the current theory and practice of RIs, with special emphasis given to multicenter RIs studies, RIs studies for pediatric and geriatric age groups, clinical decision limits and partitioning by genetic effects on RIs.

Reference intervals: current status, recent developments and future considerations

PubMed Central

Ozarda, Yesim

2016-01-01

Reliable and accurate reference intervals (RIs) for laboratory analyses are an integral part of the process of correct interpretation of clinical laboratory test results. RIs given in laboratory reports have an important role in aiding the clinician in interpreting test results in reference to values for healthy populations. Since the 1980s, the International Federation of Clinical Chemistry (IFCC) has been proactive in establishing recommendations to clarify the true significance of the term ‘RIs, to select the appropriate reference population and statistically analyse the data. The C28-A3 guideline published by the Clinical and Laboratory Standards Institute (CLSI) and IFCC is still the most widely-used source of reference in this area. In recent years, protocols additional to the Guideline have been published by the IFCC, Committee on Reference Intervals and Decision Limits (C-RIDL), including all details of multicenter studies on RIs to meet the requirements in this area. Multicentric RIs studies are the most important development in the area of RIs. Recently, the C-RIDL has performed many multicentric studies to obtain common RIs. Confusion of RIs and clinical decision limits (CDLs) remains an issue and pediatric and geriatric age groups are a significant problem. For future studies of RIs, the genetic effect would seem to be the most challenging area.
The aim of the review is to present the current theory and practice of RIs, with special emphasis given to multicenter RIs studies, RIs studies for pediatric and geriatric age groups, clinical decision limits and partitioning by genetic effects on RIs. PMID:26981015

Impact of intrapatient variability (IPV) in tacrolimus trough levels on long-term renal transplant function: multicentre collaborative retrospective cohort study protocol

PubMed Central

Goldsmith, Petra M; Bottomley, Matthew J; Okechukwu, Okidi; Ross, Victoria C; Ghita, Ryan; Wandless, David; Falconer, Stuart J; Papachristos, Stavros; Nash, Philip; Androshchuk, Vitaliy; Clancy, Marc

2017-01-01

Introduction High intrapatient variability (IPV) in tacrolimus trough levels has been shown to be associated with higher rates of renal transplant failure. There is no consensus on what level of IPV constitutes a risk of graft loss. The establishment of such a threshold could help to guide clinicians in identifying at-risk patients to receive targeted interventions to improve IPV and thus outcomes. Methods and analysis A multicentre Transplant Audit Collaborative has been established to conduct a retrospective study examining tacrolimus IPV and renal transplant outcomes. Patients in receipt of a renal transplant at participating centres between 2009 and 2014 and fulfilling the inclusion criteria will be included in the study. The aim is to recruit a minimum of 1600 patients with follow-up spanning at least 2 years in order to determine a threshold IPV above which a renal transplant recipient would be considered at increased risk of graft loss. The study also aims to determine any national or regional trends in IPV and any demographic associations. Ethics and dissemination Consent will not be sought from patients whose data are used in this study as no additional procedures or information will be required from participants beyond that which would normally take place as part of clinical care. The study will be registered locally in each participating centre in line with local research and development protocols. It is anticipated that the results of this audit will be disseminated locally, in participating NHS Trusts, through national and international meetings and publications in peer-reviewed journals. PMID:28756385

Multicentric squamous cell carcinona in a paca (Agouti paca) resembling Bowen's disease.

PubMed

Luppi, Marcela M; Malta, Marcelo C C; Costa, Maria E L T; Motta, Rafael O C; Santos, Renato L

2008-06-01

An 8-yr-old female paca (Agouti paca) was admitted at the Veterinary Hospital of the Belo Horizonte Zoo (Brazil) with an ulcerated cutaneous nodule of approximately 1.5 cm in diameter in the left ear. One week later, other cutaneous nodules were detected in various body locations. The animal died during a surgical procedure to remove the tumors. All cutaneous nodules were histologically similar with features of squamous cell carcinoma. Considering the predominant in situ nature of the lesion as well as its multicentric localization, the disease reported here closely resembles Bowen's disease, which has been described in humans and which has been identified as a rare neoplastic disease of cats, with one single report in a dog. This is the first report of a neoplastic disease in Agouti

Prevalence of Helicobacter Pylori-Negative, Non-Steroidal Anti-Inflammatory Drug Related Peptic Ulcer Disease in Patients Referred to Afzalipour Hospital.

PubMed

Seyed Mirzaei, Seyed Mahdi; Zahedi, Mohammad Javad; Shafiei Pour, Sara

2015-10-01

BACKGROUND Although Helicobacter pylori and non-steroidal anti-inflammatory drugs (NSAIDs) are the main causes of peptic ulcers disease (PUD), recently the prevalence of idiopathic peptic ulcer (IPU) is increasing in most parts of the world. The aim of this study was to assess the prevalence of IPU in Kerman, the center of largest province in south-east Iran. METHODS We included 215 patients with peptic ulcer in our study. Combined methods rapid urease test (RUT), histology, and real time polymerase chain reaction (PCR) was performed on endoscopic samples of peptic ulcers. NSAID use was determined by medical history. SPSS software version 16 was used for data analysis. p value<0.05 was considered as statistically significant. RESULTS Of 215 consecutive patients with peptic ulcer, four (1.8%) had H.pylorinegative and NSAID-negative PUD. There were not significant differences between patients with IPU and patients with peptic ulcer associated with H.pylori or NSAIDs regarding the sex, age, cigarette smoking, and opioid abuse. CONCLUSION Our study showed that in contrast to other reports from western and some Asian countries, the prevalence of IPU is low in Kerman and H.pylori infection is still the major cause of PUD. We recommend a large and multi-central study to determine the prevalence of IPU in Iran.

Regional variation in asthma symptom prevalence in Latin American children.

PubMed

Mallol, Javier; Solé, Dirceu; Baeza-Bacab, Manuel; Aguirre-Camposano, Viviana; Soto-Quiros, Manuel; Baena-Cagnani, Carlos

2010-08-01

This study investigates the distribution pattern of asthma symptom prevalence in Latin American children aged 13-14 years. A randomized, cross-sectional and multicentric study on the prevalence and severity of asthma symptoms (lifetime asthma, current wheezing, and frequent sleep disturbance by wheezing) was conducted in 165,917 schoolchildren from 56 centers in 17 Latin American countries, as part of the International Study of Asthma and Allergies in Childhood (ISAAC), Phase Three. The prevalence of lifetime asthma prevalence ranged from 1.2% to 33.1%, whereas current wheezing went from 3.9% to 30.8% and frequent sleep disturbance from 0.6% to 6.1%. An important proportion of centers (55%) reported a prevalence of asthma symptoms over 15%. There was no significant correlation between asthma symptom prevalence and latitude, altitude, or tropical setting. At country level, the prevalence of asthma was not associated with gross national income (GNI), proportion of population under the poverty line, or ancestry. This study suggests that ecological interactions, probably typical for each locality, may be the main determinants for the large variability of asthma prevalence in Latin America. The high prevalence of asthma symptoms found in children living in areas with low socioeconomic development would challenge the protective role against asthma of factors related to low hygiene and poverty; contrarily, in this region they would act as risk factors.

Migraine and subclinical atherosclerosis in the Brazilian Longitudinal Study of Adult Health (ELSA-Brasil).

PubMed

Goulart, Alessandra C; Santos, Itamar S; Bittencourt, Márcio S; Lotufo, Paulo A; Benseñor, Isabela M

2016-08-01

The relationship between migraine and coronary heart disease (CHD) remains controversial. We aimed to investigate the association of subclinical atherosclerosis and migraine with or without aura compared to a non-migraine subgroup (reference) in a large Brazilian multicentric cohort study, the Brazilian Longitudinal Study of Adult Health (ELSA-Brasil). Migraine diagnostic was based on International Headache Society criteria, and aura symptoms were validated by a medical doctor in a sub-sample of the ELSA-Brasil, who also underwent coronary artery calcium score (CAC) and carotid intima-media thickness (C-IMT) evaluations. Subclinical atherosclerosis indexes (CAC and C-IMT) were analyzed as dependent variables and migraine (all, with aura, without aura) as an independent variable in the linear and multinomial logistic regression models adjusted for possible confounders. Of 3217 ELSA participants free from CVD at baseline, we found a migraine frequency of 11.9% (5.1% with aura and 6.8% without aura). Overall, migraineurs were mostly women, younger and had lower frequency of CV risk factors, such as hypertension, diabetes and low HDL-cholesterol, compared to non-migraineurs. The strongest inverse correlation between migraine and subclinical atherosclerosis was verified with CAC score. However, all associations lost their significance after multivariate adjustment. In this cross-sectional evaluation of the ELSA study, migraine was not associated with subclinical atherosclerosis, regardless of aura symptoms. © International Headache Society 2015.

Impact of study design on recruitment of patients to a primary care trial: an observational time series analysis of the Birmingham Atrial Fibrillation Treatment of the Aged (BAFTA) study.

PubMed

Fletcher, K; Mant, J; Roalfe, A; Hobbs, F D R

2010-12-01

recruitment targets to randomized controlled trials (RCTs) are often not met. Many interventions are used to improve recruitment but there is little empirical evidence on whether these approaches work. to examine whether changes to the design and conduct of a primary care-based RCT were associated with changes in patient recruitment. an observational time series analysis of recruitment to a primary care-based multi-centre RCT of aspirin versus warfarin for stroke prevention, which involved 330 practices. Several changes to the trial protocol and procedures were made over the 4 years of patient recruitment. For each quarter throughout the recruitment period, the recruitment rate per 1000 total population in active practices was calculated. the recruitment target of 930 patients was exceeded. Fluctuations in recruitment rate occurred during the recruitment period. Following protocol changes aimed to reduce clinical workload, there was a significant increase in recruitment during the final 6 months of the study, during a period when there was not a similarly large increase in the total population available. these findings suggest that the conduct of a trial is an important consideration if studies are to recruit successfully. Expanding the number of centres may not be the most effective way to improve recruitment.

Validation of genetic modifiers for Duchenne muscular dystrophy: a multicentre study assessing SPP1 and LTBP4 variants.

PubMed

van den Bergen, Janneke C; Hiller, Monika; Böhringer, Stefan; Vijfhuizen, Linda; Ginjaar, Hendrika B; Chaouch, Amina; Bushby, Kate; Straub, Volker; Scoto, Mariacristina; Cirak, Sebahattin; Humbertclaude, Véronique; Claustres, Mireille; Scotton, Chiara; Passarelli, Chiara; Lochmüller, Hanns; Muntoni, Francesco; Tuffery-Giraud, Sylvie; Ferlini, Alessandra; Aartsma-Rus, Annemieke M; Verschuuren, Jan J G M; 't Hoen, Peter Ac; Spitali, Pietro

2015-10-01

Duchenne muscular dystrophy (DMD) is characterised by progressive muscle weakness. It has recently been reported that single nucleotide polymorphisms (SNPs) located in the SPP1 and LTBP4 loci can account for some of the inter-individual variability observed in the clinical disease course. The validation of genetic association in large independent cohorts is a key process for rare diseases in order to qualify prognostic biomarkers and stratify patients in clinical trials. Duchenne patients from five European neuromuscular centres were included. Information about age at wheelchair dependence and steroid use was gathered. Melting curve analysis of PCR fragments or Sanger sequencing were used to genotype SNP rs28357094 in the SPP1 gene in 336 patients. The genotype of SNPs rs2303729, rs1131620, rs1051303 and rs10880 in the LTBP4 locus was determined in 265 patients by mass spectrometry. For both loci, a multivariate analysis was performed, using genotype/haplotype, steroid use and cohort as covariates. We show that corticosteroid treatment and the IAAM haplotype of the LTBP4 gene are significantly associated with prolonged ambulation in patients with DMD. There was no significant association between the SNP rs28357094 in the SPP1 gene and the age of ambulation loss. This study underlines the importance of replicating genetic association studies for rare diseases in large independent cohorts to identify the most robust associations. We anticipate that genotyping of validated genetic associations will become important for the design and interpretation of clinical trials. 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.

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.

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

A multi-centre cohort study of short term outcomes of hospital treatment for anorexia nervosa in the UK

PubMed Central

2013-01-01

Background Individual, family and service level characteristics and outcomes are described for adult and adolescent patients receiving specialist inpatient or day patient treatment for anorexia nervosa (AN). Potential predictors of treatment outcome are explored. Method Admission and discharge data were collected from patients admitted at 14 UK hospital treatment units for AN over a period of three years (adult units N = 12; adolescent N = 2) (patients N = 177). Results One hundred and seventy-seven patients with a severe and enduring illness with wide functional impairment took part in the study. Following inpatient care, physical improvement was moderate/good with a large increase in BMI, although most patients continued to have a clinical level of eating disorder symptoms at discharge. The potentially modifiable predictors of outcome included confidence to change, social functioning and carer expressed emotion and control. Conclusions Overall, the response to inpatient treatment was modest particularly in the group with a severe enduring form of illness. Adolescents had a better response. Although inpatient treatment produces an improvement in physical health there was less improvement in other eating disorder and mood symptoms. As predicted by the carer interpersonal maintenance model, carer behaviour may influence the response to inpatient care, as may improved social functioning and confidence to change. PMID:24200194

Acute respiratory distress syndrome.

PubMed

Confalonieri, Marco; Salton, Francesco; Fabiano, Francesco

2017-06-30

Since its first description, the acute respiratory distress syndrome (ARDS) has been acknowledged to be a major clinical problem in respiratory medicine. From July 2015 to July 2016 almost 300 indexed articles were published on ARDS. This review summarises only eight of them as an arbitrary overview of clinical relevance: definition and epidemiology, risk factors, prevention and treatment. A strict application of definition criteria is crucial, but the diverse resource-setting scenarios foster geographic variability and contrasting outcome data. A large international multicentre prospective cohort study including 50 countries across five continents reported that ARDS is underdiagnosed, and there is potential for improvement in its management. Furthermore, epidemiological data from low-income countries suggest that a revision of the current definition of ARDS is needed in order to improve its recognition and global clinical outcome. In addition to the well-known risk-factors for ARDS, exposure to high ozone levels and low vitamin D plasma concentrations were found to be predisposing circumstances. Drug-based preventive strategies remain a major challenge, since two recent trials on aspirin and statins failed to reduce the incidence in at-risk patients. A new disease-modifying therapy is awaited: some recent studies promised to improve the prognosis of ARDS, but mortality and disabling complications are still high in survivors in intensive care. Copyright ©ERS 2017.