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

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

PubMed Central

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

2000-01-01

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

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

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.

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

[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.

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

PubMed

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

2015-11-17

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

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.

Conducting a multicentre and multinational qualitative study on patient transitions.

PubMed

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

2012-12-01

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

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

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

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

PubMed

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

2012-11-01

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

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.

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

PubMed

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

2017-08-25

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

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.

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.

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 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

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.

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

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.

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.

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

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.

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.

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

PubMed

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

2015-12-01

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

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.

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 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.

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.

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.

Live birth after artificial oocyte activation using a ready-to-use ionophore: a prospective multicentre study.

PubMed

Ebner, Thomas; Montag, Markus; Montag, M; Van der Ven, K; Van der Ven, H; Ebner, T; Shebl, O; Oppelt, P; Hirchenhain, J; Krüssel, J; Maxrath, B; Gnoth, C; Friol, K; Tigges, J; Wünsch, E; Luckhaus, J; Beerkotte, A; Weiss, D; Grunwald, K; Struller, D; Etien, C

2015-04-01

Artificial oocyte activation has been proposed as a suitable means to overcome the problem of failed or impaired fertilization after intracytoplasmic sperm injection (ICSI). In a multicentre setting artificial oocyte activation was applied to 101 patients who were diagnosed with fertilization abnormalities (e.g. less than 50% fertilized oocytes) in a previous conventional ICSI cycle. Female gametes were activated for 15 min immediately after ICSI using a ready-to-use Ca(2+)-ionophore solution (A23187). Fertilization, pregnancy and live birth rates were compared with the preceding cycle without activation. The fertilization rate of 48% in the study cycles was significantly higher compared with the 25% in the control cycles (P < 0.001). Further splitting of the historical control group into failed (0%), low (1-30%) and moderate fertilization rate (31-50%) showed that all groups significantly benefitted (P < 0.001) in the ionophore cycle. Fewer patients had their embryo transfer cancelled compared with their previous treatments (1/101 versus 15/101). In total, 99% of the patients had an improved outcome with A23187 application resulting in a 28% live birth rate (35 babies). These data suggest that artificial oocyte activation using a ready-to-use compound is an efficient method. Copyright © 2014 Reproductive Healthcare Ltd. Published by Elsevier Ltd. All rights reserved.

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

PubMed Central

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

2008-01-01

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

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.

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.

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.

Value of Additional Digital Breast Tomosynthesis for Preoperative Staging of Breast Cancer in Dense Breasts.

PubMed

Krammer, Julia; Stepniewski, Kathrin; Kaiser, Clemens G; Brade, Joachim; Riffel, Philipp; Schoenberg, Stefan O; Wasser, Klaus

2017-09-01

This retrospective study was initiated to determine the diagnostic value of additional preoperative breast tomosynthesis (DBT) for breast cancer staging in dense breasts. Sixty-six patients (69 breasts) with findings of American College of Radiology category 3 or 4 with Breast Imaging Reporting and Data System 5, 6 or 0 were included. All patients underwent digital mammography and additional DBT. A total of 40/69 (58%) cancers were detected on both mammography and DBT, 23 (33.3%) were only seen on DBT (p=0.0001); 6/69 (8.7%) carcinomas were not detected by either method, of which three were invasive lobular carcinomas. Sensitivity for multifocal/multicentric disease was significantly higher on DBT (12/19, 63.2%) compared to mammography (4/19, 21.1%) (p=0.02), specificity was comparable (96.0% vs. 90.0%). Multifocal/multicentric disease was not detected on mammography nor DBT in 7/19 (36.8%) patients, including three invasive lobular carcinomas. DBT may significantly improve preoperative breast cancer staging in patients with dense breasts compared to conventional mammography alone. Nevertheless, limitations have to be expected in the case of invasive lobular carcinoma. Copyright© 2017, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.

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.

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.

Asymptomatic population reference values for three knee patient-reported outcomes measures: evaluation of an electronic data collection system and implications for future international, multi-centre cohort studies.

PubMed

McLean, James M; Brumby-Rendell, Oscar; Lisle, Ryan; Brazier, Jacob; Dunn, Kieran; Gill, Tiffany; Hill, Catherine L; Mandziak, Daniel; Leith, Jordan

2018-05-01

The aim was to assess whether the Knee Society Score, Oxford Knee Score (OKS) and Knee Injury and Osteoarthritis Outcome Score (KOOS) were comparable in asymptomatic, healthy, individuals of different age, gender and ethnicity, across two remote continents. The purpose of this study was to establish normal population values for these scores using an electronic data collection system. There is no difference in clinical knee scores in an asymptomatic population when comparing age, gender and ethnicity, across two remote continents. 312 Australian and 314 Canadian citizens, aged 18-94 years, with no active knee pain, injury or pathology in the ipsilateral knee corresponding to their dominant arm, were evaluated. A knee examination was performed and participants completed an electronically administered questionnaire covering the subjective components of the knee scores. The cohorts were age- and gender-matched. Chi-square tests, Fisher's exact test and Poisson regression models were used where appropriate, to investigate the association between knee scores, age, gender, ethnicity and nationality. There was a significant inverse relationship between age and all assessment tools. OKS recorded a significant difference between gender with females scoring on average 1% lower score. There was no significant difference between international cohorts when comparing all assessment tools. An electronic, multi-centre data collection system can be effectively utilized to assess remote international cohorts. Differences in gender, age, ethnicity and nationality should be taken into consideration when using knee scores to compare to pathological patient scores. This study has established an electronic, normal control group for future studies using the Knee society, Oxford, and KOOS knee scores. Diagnostic Level II.

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.

Staff regard towards working with substance users: a European multi-centre study.

PubMed

Gilchrist, Gail; Moskalewicz, Jacek; Slezakova, Silvia; Okruhlica, Lubomir; Torrens, Marta; Vajd, Rajko; Baldacchino, Alex

2011-06-01

To compare regard for working with different patient groups (including substance users) among different professional groups in different health-care settings in eight European countries. A multi-centre, cross-sectional comparative study. Primary care, general psychiatry and specialist addiction services in Bulgaria, Greece, Italy, Poland, Scotland, Slovakia, Slovenia and Spain. A multi-disciplinary convenience sample of 866 professionals (physicians, psychiatrists, psychologists, nurses and social workers) from 253 services. The Medical Condition Regard Scale measured regard for working with different patient groups. Multi-factor between-subjects analysis of variance determined the factors associated with regard for each condition by country and all countries. Regard for working with alcohol (mean score alcohol: 45.35, 95% CI 44.76, 45.95) and drug users (mean score drugs: 43.67, 95% CI 42.98, 44.36) was consistently lower than for other patient groups (mean score diabetes: 50.19, 95% CI 49.71, 50.66; mean score depression: 51.34, 95% CI 50.89, 51.79) across all countries participating in the study, particularly among staff from primary care compared to general psychiatry or specialist addiction services (P<0.001). After controlling for sex of staff, profession and duration of time working in profession, treatment entry point and country remained the only statistically significant variables associated with regard for working with alcohol and drug users. Health professionals appear to ascribe lower status to working with substance users than helping other patient groups, particularly in primary care; the effect is larger in some countries than others. © 2011 The Authors, Addiction © 2011 Society for the Study of Addiction.

The impact of incident fractures on health-related quality of life: 5 years of data from the Canadian Multicentre Osteoporosis Study.

PubMed

Papaioannou, A; Kennedy, C C; Ioannidis, G; Sawka, A; Hopman, W M; Pickard, L; Brown, J P; Josse, R G; Kaiser, S; Anastassiades, T; Goltzman, D; Papadimitropoulos, M; Tenenhouse, A; Prior, J C; Olszynski, W P; Adachi, J D

2009-05-01

Using prospective data from the Canadian Multicentre Osteoporosis Study (CaMos), we compared health utilities index (HUI) scores after 5 years of follow-up among participants (50 years and older) with and without incident clinical fractures. Incident fractures had a negative impact on HUI scores over time. This study examined change in health-related quality of life (HRQL) in those with and without incident clinical fractures as measured by the HUI. The study cohort was 4,820 women and 1,783 men (50 years and older) from the CaMos. The HUI was administered at baseline and year 5. Participants were sub-divided into incident fracture groups (hip, rib, spine, forearm, pelvis, other) and were compared with those without these fractures. The effects of both time and fracture type on HUI scores were examined in multivariable regression analyses. Men and women with hip fractures, compared to those without, had lower HUI measures that ranged from -0.05 to -0.25. Both women and men with spine fractures had significant deficits on the pain attributes (-0.07 to -0.12). In women, self-care (-0.06), mobility and ambulation (-0.05) were also negatively impacted. Women with rib fractures had deficits similar to women with spine fractures, and these effects persisted over time. In men, rib fractures did not significantly affect HUI scores. Pelvic and forearm fractures did not substantially influence HUI scores. The HUI was a sensitive measure of HRQL change over time. These results will inform economic analyses evaluating osteoporosis therapies.

Ethical dilemmas of a large national multi-centre study in Australia: time for some consistency.

PubMed

Driscoll, Andrea; Currey, Judy; Worrall-Carter, Linda; Stewart, Simon

2008-08-01

To examine the impact and obstacles that individual Institutional Research Ethics Committee (IRECs) had on a large-scale national multi-centre clinical audit called the National Benchmarks and Evidence-based National Clinical guidelines for Heart failure management programmes Study. Multi-centre research is commonplace in the health care system. However, IRECs continue to fail to differentiate between research and quality audit projects. The National Benchmarks and Evidence-based National Clinical guidelines for Heart failure management programmes study used an investigator-developed questionnaire concerning a clinical audit for heart failure programmes throughout Australia. Ethical guidelines developed by the National governing body of health and medical research in Australia classified the National Benchmarks and Evidence-based National Clinical guidelines for Heart failure management programmes Study as a low risk clinical audit not requiring ethical approval by IREC. Fifteen of 27 IRECs stipulated that the research proposal undergo full ethical review. None of the IRECs acknowledged: national quality assurance guidelines and recommendations nor ethics approval from other IRECs. Twelve of the 15 IRECs used different ethics application forms. Variability in the type of amendments was prolific. Lack of uniformity in ethical review processes resulted in a six- to eight-month delay in commencing the national study. Development of a national ethics application form with full ethical review by the first IREC and compulsory expedited review by subsequent IRECs would resolve issues raised in this paper. IRECs must change their ethics approval processes to one that enhances facilitation of multi-centre research which is now normative process for health services. The findings of this study highlight inconsistent ethical requirements between different IRECs. Also highlighted are the obstacles and delays that IRECs create when undertaking multi-centre clinical audits. However, in our clinical practice it is vital that clinical audits are undertaken for evaluation purposes. The findings of this study raise awareness of inconsistent ethical processes and highlight the need for expedient ethical review for clinical audits.

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.

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

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.

Multicentric myelolipoma in a dog.

PubMed

Kamiie, Junichi; Fueki, Keisuke; Amagai, Harumi; Ichikawa, Youichiro; Shirota, Kinji

2009-03-01

We report herein a case of multicentric myelolipoma in an 11-year-old beagle dog that presented with vomiting. Laparotomy demonstrated the presence of a large mass adherent to the greater omentum and multiple small white maculae in the spleen. Cytological and histological examinations revealed that the mass and maculae comprised mature adipocytes and hematopoietic elements including granulocytic, erythrocytic and megakaryocytic series in several phases of maturation and macrophages containing hemosiderin deposits, resembling bone marrow. Multicentric myelolipoma was diagnosed. This is first report of multicentric myelolipoma in a dog.

Autofluorescence bronchoscopy with white light bronchoscopy compared with white light bronchoscopy alone for the detection of precancerous lesions: a European randomised controlled multicentre trial.

PubMed

Häussinger, K; Becker, H; Stanzel, F; Kreuzer, A; Schmidt, B; Strausz, J; Cavaliere, S; Herth, F; Kohlhäufl, M; Müller, K-M; Huber, R-M; Pichlmeier, U; Bolliger, Ch T

2005-06-01

The potential of autofluorescence bronchoscopy (AFB) to detect precancerous lesions in the central airways and its role in lung cancer screening is uncertain. A study was undertaken to evaluate the prevalence of moderate/severe dysplasia (dysplasia II-III) and carcinoma in situ (CIS) using a newly developed AFB system in comparison with conventional white light bronchoscopy (WLB) alone. In a prospective randomised multicentre trial, smokers > or = 40 years of age (> or = 20 pack-years) were stratified into four different risk groups and investigated with either WLB+AFB (arm A) or WLB alone (arm B). 1173 patients (916 men) of mean age 58.7 years were included. Overall (arms A and B), preinvasive lesions (dysplasia II-III and CIS) were detected in 3.9% of the patients. The prevalence of patients with preinvasive lesions in the WLB arm was 2.7% compared with 5.1% in the WLB+AFB arm (p = 0.037). For patients with dysplasia II-III, WLB+AFB increased the detection rate by a factor of 2.1 (p = 0.03), while for CIS the factor was only 1.24 (p = 0.75). The biopsy based sensitivity of WLB alone and WLB+AFB for detecting dysplasia II-III and CIS was 57.9% compared with 82.3% (1.42-fold increase). The corresponding specificity was 62.1% compared with 58.4% (0.94-fold decrease). This first randomised study of AFB showed that the combination of WLB+AFB was significantly superior to WLB alone in detecting preneoplastic lesions. Our findings do not support the general use of AFB as a screening tool for lung cancer, but suggest that it may be of use in certain groups. The precise indications await further study.

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.

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.

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.

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.

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.

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

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.

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

PubMed

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

2010-04-28

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

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

PubMed

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

2014-03-12

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

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.

Faecal occult blood testing screening for colorectal cancer and 'missed' interval cancers: are we ignoring the elephant in the room? Results of a multicentre study.

PubMed

George, A T; Aggarwal, S; Dharmavaram, S; Menon, A; Dube, M; Vogler, M; Field, A

2017-05-01

Biennial faecal occult blood testing (FOBT) is used to screen for colorectal cancer throughout the UK. Interval cancers are tumours that develop in patients between screening rounds who have had a negative FOBT. Through a multicentre study, we compared the demographics of patients with interval cancers, FOBT screen detected cancers and cancers that developed in patients who chose not to participate in the screening programme. Five hundred and sixteen colorectal cancers were detected in the screening age group (60-74 years) population in three UK National Health Service hospitals over 2 years. One hundred and twenty seven (25%) were interval cancers, 161 (31%) were screen detected and 228 (44%) were cancers that developed in patients who had declined FOBT. The interval cancer group had a higher incidence of right-sided cancers (38% vs 29% and 24%), a higher proportion of high tumour stages (Dukes C and D) (70% vs 53% and 33%) and a shorter time from diagnosis to death (10 months vs 13 months and 24 months) compared to patients who had declined the FOBT and the FOBT screen detected cancers. Of all the patients studied, those with right-sided interval cancers had the worst outcome. A quarter of the colorectal cancers diagnosed in our study were interval cancers. Patients with right-sided interval cancers had the highest proportion of Dukes C and D tumours coupled with the shortest survival time after diagnosis compared with the other groups. Colorectal Disease © 2016 The Association of Coloproctology of Great Britain and Ireland.

Long-term tolerability of ethinylestradiol 20 μg/drospirenone 3 mg in a flexible extended regimen: results from a randomised, controlled, multicentre study.

PubMed

Klipping, Christine; Duijkers, Ingrid; Fortier, Michel P; Marr, Joachim; Trummer, Dietmar; Elliesen, Jörg

2012-04-01

This study was designed to assess the long-term safety and tolerability of a new flexible extended regimen of ethinylestradiol (EE) 20 μg/drospirenone (DRSP) 3 mg, which allows management of intracyclic (breakthrough) bleeding [flexible management of intracyclic (breakthrough) bleeding (MIB)], in comparison to conventional 28-day and fixed extended regimens. In this Phase III, multicentre, open-label study, women (aged 18-35 years) were randomised to EE/DRSP in the following regimens: flexible(MIB) (24-120 days' active hormonal intake followed by a 4-day tablet-free interval), conventional 28-day (24 days' active hormonal intake followed by a 4-day hormone-free interval) or fixed extended (120 days' uninterrupted active hormonal intake followed by a 4-day tablet-free interval) during a 1-year comparative phase. Thereafter, women entered a 1-year safety extension phase in which the majority received the flexible(MIB) regimen. Safety/tolerability outcomes were measured over 2 years. A separate analysis of certain safety parameters (endometrial, hormonal, lipid, haemostatic and metabolic variables) was conducted at two of the study centres. Results were analysed in 1067 and 783 women in the comparative and safety extension phases. Overall, 56.3% of women experienced ≥1 adverse event (AE) in the safety extension phase. Serious AEs occurred in 3.0%, 1.4% and 3.3% of women receiving the flexible(MIB), conventional and fixed extended regimens, respectively. No unexpected endometrial, hormonal, lipid, haemostatic or metabolic findings occurred with any of the three regimens. EE/DRSP in a flexible extended regimen with management of intracyclic (breakthrough) bleeding is well-tolerated and, when administered for up to 2 years, has a good safety profile comparable to other estrogen/progestogen oral contraceptives.

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

PubMed

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

2011-03-01

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

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

'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.

Pre-trial quality assurance processes for an intensity-modulated radiation therapy (IMRT) trial: PARSPORT, a UK multicentre Phase III trial comparing conventional radiotherapy and parotid-sparing IMRT for locally advanced head and neck cancer.

PubMed

Clark, C H; Miles, E A; Urbano, M T Guerrero; Bhide, S A; Bidmead, A M; Harrington, K J; Nutting, C M

2009-07-01

The purpose of this study was to compare conventional radiotherapy with parotid gland-sparing intensity-modulated radiation therapy (IMRT) using the PARSPORT trial. The validity of such a trial depends on the radiotherapy planning and delivery meeting a defined standard across all centres. At the outset, many of the centres had little or no experience of delivering IMRT; therefore, quality assurance processes were devised to ensure consistency and standardisation of all processes for comparison within the trial. The pre-trial quality assurance (QA) programme and results are described. Each centre undertook exercises in target volume definition and treatment planning, completed a resource questionnaire and produced a process document. Additionally, the QA team visited each participating centre. Each exercise had to be accepted before patients could be recruited into the trial. 10 centres successfully completed the quality assurance exercises. A range of treatment planning systems, linear accelerators and delivery methods were used for the planning exercises, and all the plans created reached the standard required for participation in this multicentre trial. All 10 participating centres achieved implementation of a comprehensive and robust IMRT programme for treatment of head and neck cancer.

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.

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.

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.

A double-blind comparative multicentre study of remoxipride and haloperidol in schizophrenia.

PubMed

Lindström, L H; Wieselgren, I M; Struwe, G; Kristjansson, E; Akselson, S; Arthur, H; Andersen, T; Lindgren, S; Norman, O; Naimell, L

1990-01-01

In a double-blind multicentre study of parallel group design the efficacy and safety of remoxipride and haloperidol were compared in a total of 96 patients with acute episodes of schizophrenic or schizophreniform disorder according to DSM-III. There were 48 patients in each treatment group; 27 men and 21 women in the remoxipride group, 33 men and 15 women in the haloperidol group. The median duration of illness was 7 years in both groups. The mean daily dose was 437 mg for remoxipride and 10.6 mg for haloperidol during the last week of treatment. No statistically significant differences in total BPRS scores were found between remoxipride and haloperidol. The median total BPRS scores at the start of active treatment were 26 in the remoxipride and 27 in the haloperidol group; these were reduced to 16 and 12.5, respectively, at the last rating. According to Clinical Global Impression (CGI), 43% of patients in the remoxipride group and 68% of those in the haloperidol group improved much or very much during treatment. This difference was not statistically significant. Treatment-emergent extrapyramidal side effects such as akathisia, tremor, and rigidity occurred significantly more frequently in the haloperidol group; this group also made more frequent use of anticholinergic drugs. Neither of the trial drugs seriously affected laboratory or cardiovascular variables. It is concluded that remoxipride has an antipsychotic effect in a dose range of 150-600 mg per day comparable to that of haloperidol in doses up to 20 mg per day but with fewer extrapyramidal side effects.

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.

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

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 comparative assessment of the bio-evolution Toxoplasma gondii detection kit with eight laboratory-developed PCR assays for molecular diagnosis of congenital toxoplasmosis.

PubMed

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

2015-01-01

The detection of Toxoplasma gondii in amniotic fluid is an essential tool for the prenatal diagnosis of congenital toxoplasmosis and is currently essentially based on the use of PCR. Although some consensus is emerging, this molecular diagnosis suffers from a lack of standardization and an extreme diversity of laboratory-developed methods. Commercial kits for the detection of T. gondii by PCR were recently developed and offer certain advantages; however, they must be assessed in comparison with optimized reference PCR assays. The present multicentric study aimed to compare the performances of the Bio-Evolution T. gondii detection kit and laboratory-developed PCR assays set up in eight proficient centers in France. The study compared 157 amniotic fluid samples and found concordances of 99% and 100% using 76 T. gondii-infected samples and 81 uninfected samples, respectively. Moreover, taking into account the classification of the European Research Network on Congenital Toxoplasmosis, the overall diagnostic sensitivity of all assays was identical and calculated to be 86% (54/63); specificity was 100% for all assays. Finally, the relative quantification results were in good agreement between the kit and the laboratory-developed assays. The good performances of this commercial kit are probably in part linked to the use of a number of good practices: detection in multiplicate, amplification of the repetitive DNA target rep529, and the use of an internal control for the detection of PCR inhibitors. The only drawbacks noted at the time of the study were the absence of uracil-N-glycosylase and small defects in the reliability of the production of different reagents. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

Multicentric Comparative Assessment of the Bio-Evolution Toxoplasma gondii Detection Kit with Eight Laboratory-Developed PCR Assays for Molecular Diagnosis of Congenital Toxoplasmosis

PubMed Central

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

2014-01-01

The detection of Toxoplasma gondii in amniotic fluid is an essential tool for the prenatal diagnosis of congenital toxoplasmosis and is currently essentially based on the use of PCR. Although some consensus is emerging, this molecular diagnosis suffers from a lack of standardization and an extreme diversity of laboratory-developed methods. Commercial kits for the detection of T. gondii by PCR were recently developed and offer certain advantages; however, they must be assessed in comparison with optimized reference PCR assays. The present multicentric study aimed to compare the performances of the Bio-Evolution T. gondii detection kit and laboratory-developed PCR assays set up in eight proficient centers in France. The study compared 157 amniotic fluid samples and found concordances of 99% and 100% using 76 T. gondii-infected samples and 81 uninfected samples, respectively. Moreover, taking into account the classification of the European Research Network on Congenital Toxoplasmosis, the overall diagnostic sensitivity of all assays was identical and calculated to be 86% (54/63); specificity was 100% for all assays. Finally, the relative quantification results were in good agreement between the kit and the laboratory-developed assays. The good performances of this commercial kit are probably in part linked to the use of a number of good practices: detection in multiplicate, amplification of the repetitive DNA target rep529, and the use of an internal control for the detection of PCR inhibitors. The only drawbacks noted at the time of the study were the absence of uracil-N-glycosylase and small defects in the reliability of the production of different reagents. PMID:25339393

Clinical predictors of rectal lymphogranuloma venereum infection: results from a multicentre case–control study in the UK

PubMed Central

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

2014-01-01

Objective Since 2003, over 2000 cases of lymphogranuloma venereum (LGV) have been diagnosed in the UK in men who have sex with men (MSM). Most cases present with proctitis, but there are limited data on how to differentiate clinically between LGV and other pathology. We analysed the clinical presentations of rectal LGV in MSM to identify clinical characteristics predictive of LGV proctitis and produced a clinical prediction model. Design A prospective multicentre case–control study was conducted at six UK hospitals from 2008 to 2010. Cases of rectal LGV were compared with controls with rectal symptoms but without LGV. Methods Data from 98 LGV cases and 81 controls were collected from patients and clinicians using computer-assisted self-interviews and clinical report forms. Univariate and multivariate logistic regression was used to compare symptoms and signs. Clinical prediction models for LGV were compared using receiver operating curves. Results Tenesmus, constipation, anal discharge and weight loss were significantly more common in cases than controls. In multivariate analysis, tenesmus and constipation alone were suggestive of LGV (OR 2.98, 95% CI 0.99 to 8.98 and 2.87, 95% CI 1.01 to 8.15, respectively) and that tenesmus alone or in combination with constipation was a significant predictor of LGV (OR 6.97, 95% CI 2.71 to 17.92). The best clinical prediction was having one or more of tenesmus, constipation and exudate on proctoscopy, with a sensitivity of 77% and specificity of 65%. Conclusions This study indicates that tenesmus alone or in combination with constipation makes a diagnosis of LGV in MSM presenting with rectal symptoms more likely. PMID:24687130

A randomized multicentre trial to compare revascularization with optimal medical therapy for the treatment of chronic total coronary occlusions.

PubMed

Werner, Gerald S; Martin-Yuste, Victoria; Hildick-Smith, David; Boudou, Nicolas; Sianos, Georgios; Gelev, Valery; Rumoroso, Jose Ramon; Erglis, Andrejs; Christiansen, Evald Høj; Escaned, Javier; di Mario, Carlo; Hovasse, Thomas; Teruel, Luis; Bufe, Alexander; Lauer, Bernward; Bogaerts, Kris; Goicolea, Javier; Spratt, James C; Gershlick, Anthony H; Galassi, Alfredo R; Louvard, Yves

2018-05-02

The clinical value of percutaneous coronary intervention (PCI) for chronic coronary total occlusions (CTOs) is not established by randomized trials. This study should compare the benefit of PCI vs. optimal medical therapy (OMT) on the health status in patients with at least one CTO. Three hundred and ninety-six patients were enrolled in a prospective randomized, multicentre, open-label, and controlled clinical trial to compare the treatment by PCI with OMT with a 2:1 randomization ratio. The primary endpoint was the change in health status assessed by the Seattle angina questionnaire (SAQ) between baseline and 12 months follow-up. Fifty-two percent of patients have multi-vessel disease in whom all significant non-occlusive lesions were treated before randomization. An intention-to-treat analysis was performed including 13.4% failed procedures in the PCI group and 7.3% cross-overs in the OMT group. At 12 months, a greater improvement of SAQ subscales was observed with PCI as compared with OMT for angina frequency [5.23, 95% confidence interval (CI) 1.75; 8.71; P = 0.003], and quality of life (6.62, 95% CI 1.78-11.46; P = 0.007), reaching the prespecified significance level of 0.01 for the primary endpoint. Physical limitation (P = 0.02) was also improved in the PCI group. Complete freedom from angina was more frequent with PCI 71.6% than OMT 57.8% (P = 0.008). There was no periprocedural death or myocardial infarction. At 12 months, major adverse cardiac events were comparable between the two groups. Percutaneous coronary intervention leads to a significant improvement of the health status in patients with stable angina and a CTO as compared with OMT alone. NCT01760083.

Study protocol of a randomised controlled trial of intranasal ketamine compared with intranasal fentanyl for analgesia in children with suspected, isolated extremity fractures in the paediatric emergency department.

PubMed

Reynolds, Stacy L; Studnek, Jonathan R; Bryant, Kathleen; VanderHave, Kelly; Grossman, Eric; Moore, Charity G; Young, James; Hogg, Melanie; Runyon, Michael S

2016-09-08

Fentanyl is the most widely studied intranasal (IN) analgesic in children. IN subdissociative (INSD) ketamine may offer a safe and efficacious alternative to IN fentanyl and may decrease overall opioid use during the emergency department (ED) stay. This study examines the feasibility of a larger, multicentre clinical trial comparing the safety and efficacy of INSD ketamine to IN fentanyl and the potential role for INSD ketamine in reducing total opioid medication usage. This double-blind, randomised controlled, pilot trial will compare INSD ketamine (1 mg/kg) to IN fentanyl (1.5 μg/kg) for analgesia in 80 children aged 4-17 years with acute pain from a suspected, single extremity fracture. The primary safety outcome for this pilot trial will be the frequency of cumulative side effects and adverse events at 60 min after drug administration. The primary efficacy outcome will be exploratory and will be the mean reduction of pain scale scores at 20 min. The study is not powered to examine efficacy. Secondary outcome measures will include the total dose of opioid pain medication in morphine equivalents/kg/hour (excluding study drug) required during the ED stay, number and reason for screen failures, time to consent, and the number and type of protocol deviations. Patients may receive up to 2 doses of study drug. This study was approved by the US Food and Drug Administration, the local institutional review board and the study data safety monitoring board. This study data will be submitted for publication regardless of results and will be used to establish feasibility for a multicentre, non-inferiority trial. NCT02521415. 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/

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.

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.

Treatment of Advanced Glaucoma Study: a multicentre randomised controlled trial comparing primary medical treatment with primary trabeculectomy for people with newly diagnosed advanced glaucoma-study protocol.

PubMed

King, Anthony J; Fernie, Gordon; Azuara-Blanco, Augusto; Burr, Jennifer M; Garway-Heath, Ted; Sparrow, John M; Vale, Luke; Hudson, Jemma; MacLennan, Graeme; McDonald, Alison; Barton, Keith; Norrie, John

2017-10-26

Presentation with advanced glaucoma is the major risk factor for lifetime blindness. Effective intervention at diagnosis is expected to minimise risk of further visual loss in this group of patients. To compare clinical and cost-effectiveness of primary medical management compared with primary surgery for people presenting with advanced open-angle glaucoma (OAG). Design : A prospective, pragmatic multicentre randomised controlled trial (RCT). Twenty-seven UK hospital eye services. Four hundred and forty patients presenting with advanced OAG, according to the Hodapp-Parish-Anderson classification of visual field loss. Participants will be randomised to medical treatment or augmented trabeculectomy (1:1 allocation minimised by centre and presence of advanced disease in both eyes). The primary outcome is vision-related quality of life measured by the National Eye Institute-Visual Function Questionnaire-25 at 24 months. Secondary outcomes include generic EQ-5D-5L, Health Utility Index-3 and glaucoma-related health status (Glaucoma Utility Index), patient experience, visual field measured by mean deviation value, logarithm of the mean angle of resolution visual acuity, intraocular pressure, adverse events, standards for driving and eligibility for blind certification. Incremental cost per quality-adjusted life-year (QALY) based on EQ-5D-5L and glaucoma profile instrument will be estimated. The study will report the comparative effectiveness and cost-effectiveness of medical treatment against augmented trabeculectomy in patients presenting with advanced glaucoma in terms of patient-reported health and visual function, clinical outcomes and incremental cost per QALY at 2 years. Treatment of Advanced Glaucoma Study will be the first RCT reporting outcomes from the perspective of those with advanced glaucoma. ISRCTN56878850, 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.

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

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.

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.

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.

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.

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

Total ankle replacement versus arthrodesis (TARVA): protocol for a multicentre randomised controlled trial

PubMed Central

Goldberg, Andrew J; Zaidi, Razi; Thomson, Claire; Doré, Caroline J; Cro, Suzie; Round, Jeff; Molloy, Andrew; Davies, Mark; Karski, Michael; Kim, Louise; Cooke, Paul

2016-01-01

Introduction Total ankle replacement (TAR) or ankle arthrodesis (fusion) is the main surgical treatments for end-stage ankle osteoarthritis (OA). The popularity of ankle replacement is increasing while ankle fusion rates remain static. Both treatments have efficacy but to date all studies comparing the 2 have been observational without randomisation, and there are no published guidelines as to the most appropriate management. The TAR versus arthrodesis (TARVA) trial aims to compare the clinical and cost-effectiveness of TAR against ankle arthrodesis in the treatment of end-stage ankle OA in patients aged 50–85 years. Methods and analysis TARVA is a multicentre randomised controlled trial that will randomise 328 patients aged 50–85 years with end-stage ankle arthritis. The 2 arms of the study will be TAR or ankle arthrodesis with 164 patients in each group. Up to 16 UK centres will participate. Patients will have clinical assessments and complete questionnaires before their operation and at 6, 12, 26 and 52 weeks after surgery. The primary clinical outcome of the study is a validated patient-reported outcome measure, the Manchester Oxford foot questionnaire, captured preoperatively and 12 months after surgery. Secondary outcomes include quality-of-life scores, complications, revision, reoperation and a health economic analysis. Ethics and dissemination The protocol has been approved by the National Research Ethics Service Committee (London, Bloomsbury 14/LO/0807). This manuscript is based on V.5.0 of the protocol. The trial findings will be disseminated through peer-reviewed publications and conference presentations. Trial registration number NCT02128555. PMID:27601503

Goal-oriented cognitive rehabilitation in early-stage dementia: study protocol for a multi-centre single-blind randomised controlled trial (GREAT)

PubMed Central

2013-01-01

Background Preliminary evidence suggests that goal-oriented cognitive rehabilitation (CR) may be a clinically effective intervention for people with early-stage Alzheimer’s disease, vascular or mixed dementia and their carers. This study aims to establish whether CR is a clinically effective and cost-effective intervention for people with early-stage dementia and their carers. Methods/design In this multi-centre, single-blind randomised controlled trial, 480 people with early-stage dementia, each with a carer, will be randomised to receive either treatment as usual or cognitive rehabilitation (10 therapy sessions over 3 months, followed by 4 maintenance sessions over 6 months). We will compare the effectiveness of cognitive rehabilitation with that of treatment as usual with regard to improving self-reported and carer-rated goal performance in areas identified as causing concern by people with early-stage dementia; improving quality of life, self-efficacy, mood and cognition of people with early-stage dementia; and reducing stress levels and ameliorating quality of life for carers of participants with early-stage dementia. The incremental cost-effectiveness of goal-oriented cognitive rehabilitation compared to treatment as usual will also be examined. Discussion If the study confirms the benefits and cost-effectiveness of cognitive rehabilitation, it will be important to examine how the goal-oriented cognitive rehabilitation approach can most effectively be integrated into routine health-care provision. Our aim is to provide training and develop materials to support the implementation of this approach following trial completion. Trial registration Current Controlled Trials ISRCTN21027481 PMID:23710796

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.

[Multicenter study comparing the efficacy and tolerance of topical ciprofloxacin (0.3%) versus topical gentamicin (0.3%) in the treatment of simple, non-cholesteatomaous chronic otitis media in the suppurative phase].

PubMed

Lorente, J; Sabater, F; Maristany, M; Jiménez, R; Menem, J; Viñas, J; Quesada, P; Traserra, J; Dicenta, M; Abelló, P

1995-01-01

A multicentre double-blind randomized study was carried out to compare topical ciprofloxacin and topical gentamicin in the treatment of simple non-cholesteatomatous purulent chronic otitis media. Three hundred and eight patients were included in the study, 159 treated with ciprofloxacin and 149 treated with gentamicin. The percentage of clinical success (elimination of otorrhoea) was 95% with ciprofloxacin and 94% with gentamicin (ns). Likewise, the percentage of bacteriological erradication was 96% with ciprofloxacin and 93% with gentamicin. Both drugs were well tolerated, without changes in the audiometric values. In these patients, topical ciprofloxacin shows the same efficacy as topical gentamicin without any potential ototoxic effect.

Autofluorescence bronchoscopy with white light bronchoscopy compared with white light bronchoscopy alone for the detection of precancerous lesions: a European randomised controlled multicentre trial

PubMed Central

Haussinger, K; Becker, H; Stanzel, F; Kreuzer, A; Schmidt, B; Strausz, J; Cavaliere, S; Herth, F; Kohlhaufl, M; Muller, K; Huber, R; Pichlmeier, U; Bolliger, C.

2005-01-01

Background: The potential of autofluorescence bronchoscopy (AFB) to detect precancerous lesions in the central airways and its role in lung cancer screening is uncertain. A study was undertaken to evaluate the prevalence of moderate/severe dysplasia (dysplasia II–III) and carcinoma in situ (CIS) using a newly developed AFB system in comparison with conventional white light bronchoscopy (WLB) alone. Methods: In a prospective randomised multicentre trial, smokers ⩾40 years of age (⩾20 pack-years) were stratified into four different risk groups and investigated with either WLB+AFB (arm A) or WLB alone (arm B). Results: 1173 patients (916 men) of mean age 58.7 years were included. Overall (arms A and B), preinvasive lesions (dysplasia II–III and CIS) were detected in 3.9% of the patients. The prevalence of patients with preinvasive lesions in the WLB arm was 2.7% compared with 5.1% in the WLB+AFB arm (p = 0.037). For patients with dysplasia II–III, WLB+AFB increased the detection rate by a factor of 2.1 (p = 0.03), while for CIS the factor was only 1.24 (p = 0.75). The biopsy based sensitivity of WLB alone and WLB+AFB for detecting dysplasia II–III and CIS was 57.9% compared with 82.3% (1.42-fold increase). The corresponding specificity was 62.1% compared with 58.4% (0.94-fold decrease). Conclusions: This first randomised study of AFB showed that the combination of WLB+AFB was significantly superior to WLB alone in detecting preneoplastic lesions. Our findings do not support the general use of AFB as a screening tool for lung cancer, but suggest that it may be of use in certain groups. The precise indications await further study. PMID:15923251

Contact allergy to oxidized geraniol among Swedish dermatitis patients-A multicentre study by the Swedish Contact Dermatitis Research Group.

PubMed

Hagvall, Lina; Bruze, Magnus; Engfeldt, Malin; Isaksson, Marléne; Lindberg, Magnus; Ryberg, Kristina; Stenberg, Berndt; Svedman, Cecilia; Karlberg, Ann-Therese; Bråred Christensson, Johanna

2018-06-21

Geraniol is a widely used fragrance terpene, and is included in fragrance mix I. Geraniol is prone to autoxidation, forming the skin sensitizers geranial, neral, and geraniol-7-hydroperoxide. Oxidized geraniol has previously been patch tested in 1 clinic, giving 1% to 4.6% positive reactions in consecutive patients when tested at 2% to 11%. To compare test reactions to pure and oxidized geraniol, to compare 2 different test concentrations of oxidized geraniol and to investigate the pattern of concomitant reactions to fragrance markers of the baseline series in a multicentre setting. One thousand four hundred and seventy-six consecutive patients referred for patch testing were patch tested with geraniol 6% pet. and oxidized geraniol 6% and 11% pet. Pure geraniol 6% pet., oxidized geraniol 6% pet. and oxidized geraniol 11% pet. gave 1%, 3% and 8% positive patch test reactions and 0.7%, 3% and 5% doubtful reactions, respectively. Approximately 50% of the patients with doubtful reactions to oxidized geraniol 6% pet. had positive reactions to oxidized geraniol 11% pet. Oxidized geraniol 11% pet. provides better detection than oxidized geraniol 6% pet. As most patients reacted only to oxidized geraniol, it is important to explore further whether oxidized geraniol should be included in a baseline patch test series. © 2018 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

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

Tretinoin Nanogel 0.025% Versus Conventional Gel 0.025% in Patients with Acne Vulgaris: A Randomized, Active Controlled, Multicentre, Parallel Group, Phase IV Clinical Trial

PubMed Central

Chandrashekhar, B S; Anitha, M.; Ruparelia, Mukesh; Vaidya, Pradyumna; Aamir, Riyaz; Shah, Sunil; Thilak, S; Aurangabadkar, Sanjeev; Pal, Sandeep; Saraswat, Abir

2015-01-01

Background: Conventional topical tretinoin formulation is often associated with local adverse events. Nanogel formulation of tretinoin has good physical stability and enables good penetration of tretinoin into the pilo-sebaceous glands. Aim: The present study was conducted to assess the efficacy and safety of a nanogel formulation of tretinoin as compared to its conventional gel formulation in the treatment of acne vulgaris of the face. Materials and Methods: This randomized, active controlled, multicentric, phase IV clinical trial evaluated the treatment of patients with acne vulgaris of the face by the two gel formulations locally applied once daily at night for 12 wk. Acne lesion counts (inflammatory, non-inflammatory & total) and severity grading were carried out on the monthly scheduled visits along with the tolerability assessments. Results: A total of 207 patients were randomized in the study. Reductions in the total (72.9% vs. 65.0%; p = 0.03) and inflammatory (78.1% vs. 66.9%; p = 0.02) acne lesions were reported to be significantly greater with the nanogel formulation as compared to the conventional gel formulation. Local adverse events were significantly less (p = 0.04) in the nanogel group (13.3%) as compared to the conventional gel group (24.7%). Dryness was the most common adverse event reported in both the treatment groups while peeling of skin, burning sensation and photosensitivity were reported in patients using the conventional gel only. Conclusion: In the treatment of acne vulgaris of the face, tretinoin nanogel formulation appears to be more effective and better tolerated than the conventional gel formulation. PMID:25738069

A randomised, double-blind, multi-centre trial comparing vasopressin and adrenaline in patients with cardiac arrest presenting to or in the Emergency Department.

PubMed

Ong, Marcus Eng Hock; Tiah, Ling; Leong, Benjamin Sieu-Hon; Tan, Elaine Ching Ching; Ong, Victor Yeok Kein; Tan, Elizabeth Ai Theng; Poh, Bee Yen; Pek, Pin Pin; Chen, Yuming

2012-08-01

To compare vasopressin and adrenaline in the treatment of patients with cardiac arrest presenting to or in the Emergency Department (ED). A randomised, double-blind, multi-centre, parallel-design clinical trial in four adult hospitals. Eligible cardiac arrest patients (confirmed by the absence of pulse, unresponsiveness and apnea) aged >16 (aged>21 for one hospital) were randomly assigned to intravenous adrenaline (1mg) or vasopressin (40 IU) at ED. Patients with traumatic cardiac arrest or contraindication for cardiopulmonary resuscitation (CPR) were excluded. Patients received additional open label doses of adrenaline as per current guidelines. Primary outcome was survival to hospital discharge (defined as participant discharged alive or survival to 30 days post-arrest). The study recruited 727 participants (adrenaline = 353; vasopressin = 374). Baseline characteristics of the two groups were comparable. Eight participants (2.3%) from adrenaline and 11 (2.9%) from vasopressin group survived to hospital discharge with no significant difference between groups (p = 0.27, RR = 1.72, 95% CI = 0.65-4.51). After adjustment for race, medical history, bystander CPR and prior adrenaline given, more participants survived to hospital admission with vasopressin (22.2%) than with adrenaline (16.7%) (p = 0.05, RR = 1.43, 95% CI = 1.02-2.04). Sub-group analysis suggested improved outcomes for vasopressin in participants with prolonged arrest times. Combination of vasopressin and adrenaline did not improve long term survival but seemed to improve survival to admission in patients with prolonged cardiac arrest. Further studies on the effect of vasopressin combined with therapeutic hypothermia on patients with prolonged cardiac arrest are needed. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

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.

Long-term tolerability of ethinylestradiol 20 µg/drospirenone 3 mg in a flexible extended regimen: results from a randomised, controlled, multicentre study

PubMed Central

Klipping, Christine; Duijkers, Ingrid; Fortier, Michel P; Marr, Joachim; Trummer, Dietmar; Elliesen, Jörg

2012-01-01

Background This study was designed to assess the long-term safety and tolerability of a new flexible extended regimen of ethinylestradiol (EE) 20 μg/drospirenone (DRSP) 3 mg, which allows management of intracyclic (breakthrough) bleeding [flexible management of intracyclic (breakthrough) bleeding (MIB)], in comparison to conventional 28-day and fixed extended regimens. Study design In this Phase III, multicentre, open-label study, women (aged 18–35 years) were randomised to EE/DRSP in the following regimens: flexibleMIB (24–120 days' active hormonal intake followed by a 4-day tablet-free interval), conventional 28-day (24 days' active hormonal intake followed by a 4-day hormone-free interval) or fixed extended (120 days' uninterrupted active hormonal intake followed by a 4-day tablet-free interval) during a 1-year comparative phase. Thereafter, women entered a 1-year safety extension phase in which the majority received the flexibleMIB regimen. Safety/tolerability outcomes were measured over 2 years. A separate analysis of certain safety parameters (endometrial, hormonal, lipid, haemostatic and metabolic variables) was conducted at two of the study centres. Results Results were analysed in 1067 and 783 women in the comparative and safety extension phases. Overall, 56.3% of women experienced ≥1 adverse event (AE) in the safety extension phase. Serious AEs occurred in 3.0%, 1.4% and 3.3% of women receiving the flexibleMIB, conventional and fixed extended regimens, respectively. No unexpected endometrial, hormonal, lipid, haemostatic or metabolic findings occurred with any of the three regimens. Conclusions EE/DRSP in a flexible extended regimen with management of intracyclic (breakthrough) bleeding is well-tolerated and, when administered for up to 2 years, has a good safety profile comparable to other estrogen/progestogen oral contraceptives. PMID:22454004

Benefit of particle therapy in re-irradiation of head and neck patients. Results of a multicentric in silico ROCOCO trial.

PubMed

Eekers, Daniëlle B P; Roelofs, Erik; Jelen, Urszula; Kirk, Maura; Granzier, Marlies; Ammazzalorso, Filippo; Ahn, Peter H; Janssens, Geert O R J; Hoebers, Frank J P; Friedmann, Tobias; Solberg, Timothy; Walsh, Sean; Troost, Esther G C; Kaanders, Johannes H A M; Lambin, Philippe

2016-12-01

In this multicentric in silico trial we compared photon, proton, and carbon-ion radiotherapy plans for re-irradiation of patients with squamous cell carcinoma of the head and neck (HNSCC) regarding dose to tumour and doses to surrounding organs at risk (OARs). Twenty-five HNSCC patients with a second new or recurrent cancer after previous irradiation (70Gy) were included. Intensity-modulated proton therapy (IMPT) and ion therapy (IMIT) re-irradiation plans to a second subsequent dose of 70Gy were compared to photon therapy delivered with volumetric modulated arc therapy (VMAT). When comparing IMIT and IMPT to VMAT, the mean dose to all investigated 22 OARs was significantly reduced for IMIT and to 15 out of 22 OARs (68%) using IMPT. The maximum dose to 2% volume (D 2 ) of the brainstem and spinal cord were significantly reduced using IMPT and IMIT compared to VMAT. The data are available on www.cancerdata.org. In this ROCOCO in silico trial, a reduction in mean dose to OARs was achieved using particle therapy compared to photons in the re-irradiation of HNSCC. There was a dosimetric benefit favouring carbon-ions above proton therapy. These dose reductions may potentially translate into lower severe complication rates related to the re-irradiation. Copyright © 2016 The Authors. Published by Elsevier Ireland Ltd.. All rights reserved.

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.

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.

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

Using routine Haemophilia Joint Health Score for international comparisons of haemophilia outcome: standardization is needed.

PubMed

Nijdam, A; Bladen, M; Hubert, N; Pettersson, M; Bartels, B; van der Net, J; Liesner, R; Petrini, P; Kurnik, K; Fischer, K

2016-01-01

Haemophilia Joint Health Score (HJHS) is the most sensitive validated score for physical examination of joint health in haemophilia. HJHS performed at regular intervals can be used for clinical monitoring as well as for comparative outcomes research. To determine whether routinely collected HJHS could be used to compare outcome of three different prophylactic regimens in children with severe haemophilia A (primary) and which parameters caused variability in HJHS (secondary). International retrospective observational multi-centre study comparing routine HJHS in 127 children with severe haemophilia A born from 1995 to 2009, from London, Stockholm and Utrecht centres. Patient and treatment data were collected from the European Paediatric Network for Haemophilia Management registry and patient files. The independent effects of regimens, physiotherapists, age and inhibitor status on HJHS were explored, using multivariable regression analysis. Prophylaxis varied across participating centres, with differences in initial frequency of infusions (1× per week vs. 3× per week), age at reaching infusions ≥3× per week, and dose kg(-1) week(-1) at HJHS assessment. Evaluation at median age of 11 years showed an illogical association of HJHS with treatment regimen: the least intensive regimen had the lowest HJHS. The HJHS increased with age and history of inhibitor, as expected (internal validity). But the comparison of prophylactic regimens was obscured by systematic differences in assessment between physiotherapists, both within and between centres. Inter-physiotherapist discrepancies in routine HJHS hamper comparison of scores between treatment regimens. For multi-centre research, additional inter-observer standardization for HJHS scoring is needed. © 2015 John Wiley & Sons Ltd.

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.

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.

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.

Prevalence and multiplicity of cutaneous beta papilloma viruses in plucked hairs depend on cellular DNA input.

PubMed

Weissenborn, S J; Neale, R; de Koning, M N C; Waterboer, T; Abeni, D; Bouwes Bavinck, J N; Wieland, U; Pfister, H J

2009-11-01

In view of the low loads of beta human papillomaviruses in skin samples, amounts of cellular DNA used in qualitative PCR may become limiting for virus detection and introduce variations in prevalence and multiplicity. This issue was explored within the context of a multicentre study and increasing prevalence and multiplicity was found with increasing input amounts of cellular DNA extracted from hair bulbs. To improve the quality and comparability between different epidemiologic studies ideally equal amounts of cellular DNA should be employed. When cellular DNA input varies this should be clearly taken into account in assessing viral prevalence and multiplicity.

Discontinuation of tofacitinib after achieving low disease activity in patients with rheumatoid arthritis: a multicentre, observational study.

PubMed

Kubo, Satoshi; Yamaoka, Kunihiro; Amano, Koichi; Nagano, Shuji; Tohma, Shigeto; Suematsu, Eiichi; Nagasawa, Hayato; Iwata, Kanako; Tanaka, Yoshiya

2017-08-01

To determine whether tofacitinib can be discontinued in patients with RA who achieve low disease activity (LDA). RA patients with LDA after tofacitinib treatment in a phase III and long-term extension study were enrolled in this multicentre, non-randomized, open, prospective, observational study. The decision of discontinuation or continuation of tofacitinib was determined based on patient-physician decision making with informed consent. The primary endpoint was the proportion of patients who remained tofacitinib-free at post-treatment week 52. Clinical outcome was compared between those who continued and those who discontinued tofacitinib. The last observation carried forward method was used for patients who could not discontinue tofacitinib before week 52. Of 64 patients, 54 discontinued and 10 continued tofacitinib therapy. At post-treatment week 52, 20 of the 54 patients (37%) of the discontinuation group remained tofacitinib-free without disease flare. Disease activity at post-treatment week 52 was higher in the discontinuation group than the continuation group. Among the discontinuation group, the RF titre at baseline was significantly lower in patients who remained tofacitinib-free than those who did not (40 vs 113 U/ml). In fact, a higher proportion of patients with lower RF remained tofacitinib-free at week 52 compared with those with higher RF at baseline. In patients who could not achieve tofacitinib-free status, re-initiation of tofacitinib or other biologics improved disease activity. It is possible to discontinue tofacitinib without flare in about a third of patients with RA. A low RF predicts maintenance of LDA after discontinuation of tofacitinib. © The Author 2017. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For Permissions, please email: journals.permissions@oup.com

Efficacy, safety, and tolerance of the non-ergoline dopamine agonist pramipexole in the treatment of advanced Parkinson's disease: a double blind, placebo controlled, randomised, multicentre study.

PubMed

Pinter, M M; Pogarell, O; Oertel, W H

1999-04-01

Pramipexole, a non-ergot dopamine D2/D3 receptor agonist, was investigated as an add on drug in advanced parkinsonian patients with motor fluctuations to assess efficacy, safety, and tolerance. Seventy eight patients of either sex with advanced Parkinson's disease and treatment complications such as motor fluctuations were enrolled into a double blind, placebo controlled, randomised, multicentre study (phase II) and assigned to add on treatment with pramipexole (n=34) versus placebo (n=44) to a previously stabilised antiparkinsonian medication (7 week dose titration interval, 4 week maintenance period). The primary end point of efficacy was the change from baseline in the total score of the unified Parkinson's disease rating scale (UPDRS) in the on "period" (2 hours after intake of study medication). Safety and tolerability were assessed on the basis of adverse events, vital signs, laboratory measurements, and ECG recordings. There was a significant improvement of the pramipexole group in UPDRS total scores, subscores part II, III (activities of daily living and motor examination), and IV (complications of therapy). Mean UPDRS total score decreased by 37.3% under pramipexole compared with 12.2% under placebo (p<0.001). Patients under pramipexole reported an overall reduction in "off" periods of 12%--resulting in 1.7 more hours "on" time a day--compared with an increase in "off" periods of 2% under placebo. There were no unexpected safety results. The adverse event profile disclosed a high tolerability. The most important adverse events under pramipexole were fatigue, dyskinesia, and vivid dreams. Pramipexole administration is an efficacious and well tolerated add on therapy in patients with advanced Parkinson's disease with an improvement in activities of daily living, motor function, and treatment associated complications.

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

PubMed

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

2018-06-06

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

Efficacy of dosing and re-dosing of two oral fixed combinations of indomethacin, prochlorperazine and caffeine compared with oral sumatriptan in the acute treatment of multiple migraine attacks: a double-blind, double-dummy, randomised, parallel group, multicentre study

PubMed Central

Sandrini, G; Cerbo, R; Del Bene, E; Ferrari, A; Genco, S; Grazioli, I; Martelletti, P; Nappi, G; Pinessi, L; Sarchielli, P; Tamburro, P; Uslenghi, C; Zanchin, G

2007-01-01

Aims and methods: In this double-blind, double-dummy, randomised, parallel group, multicentre study, the efficacy of dosing and re-dosing of a fixed combination of indomethacin, prochlorperazine and caffeine (Indoprocaf) was compared with encapsulated sumatriptan in the acute treatment of two migraine attacks. Additionally, in the group taking Indoprocaf, two different oral formulations were tested: effervescent tablets and encapsulated coated tablets. Results: Of 297 patients randomised (150 assigned to Indoprocaf and 147 to sumatriptan), 281 were included in the intention-to-treat efficacy analysis. The initial dosing of Indoprocaf and sumatriptan was similarly effective with pain-free rates higher than 30% (95% CI of odds-ratio: 0.57–1.28) and headache relief rates of about 60% (95% CI of odds-ratio: 0.82–1.84) with both the drugs. The efficacy of re-dosing of Indoprocaf as rescue medication was more effective than that of sumatriptan with pain-free values of 47% vs. 27% in the total attacks with a statistically significant difference in the first migraine attack in favour of Indoprocaf. The efficacy of re-dosing to treat a recurrence/relapse was very high without differences between the drugs (pain-free: 60% with Indoprocaf and 50% with sumatriptan in the total attacks). Indoprocaf and sumatriptan were well-tolerated. Conclusion: The study demonstrated that the efficacy of the initial dosing of Indoprocaf was not higher than that of sumatriptan, but that the strategy to use the lowest effective dose as soon as the headache occurred, followed by a second dose if the headache has not relieved or to treat a relapse, was very effective, especially with Indoprocaf. PMID:17627707

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.

Use of XenX™, the latest ureteric occlusion device with guide wire utility: results from a prospective multicentric comparative study.

PubMed

Sanguedolce, Francesco; Montanari, Emanuele; Alvarez-Maestro, Mario; Macchione, Nicola; Hruby, Stephan; Papatsoris, Athanasios; Kallidonis, Panagiotis; Villa, Luca; Honeck, Patrick; Traxer, Olivier; Greco, Francesco

2016-11-01

This is a prospective multicentric comparative study evaluating the performance of XenX-a new dual-purpose device for the prevention of stone fragments migration during ureteroscopic lithotripsy (URS). Between March 2014 and January 2015, 41 patients undertaking URS + XenX were matched with 41 patients undergoing standard URS. Patients included had unilateral ureteric stone(s) of 0.5-1.5 cm in maximum size. Demographics, complication rates and surgical outcomes were recorded for comparison. A Likert-like 5-grade scoring system was used for surgeons' evaluation of XenX properties. Cost analysis was performed by comparing weighted mean costs of the relevant procedures. Patients' characteristics between the two groups were comparable. Lasering time was longer for XenX group (13.59 vs. 5.17 min; p = 0.0001) whilst use of basket and need of JJ stent insertion was more frequent in control group (19.5 vs. 97.6 %; p = 0.0001 and 22 vs. 35 %; p = 0.001, respectively). Intra-operative SFR was significantly higher for XenX group (100 vs. 85.4 %; p = 0.0001), but not at 4-week follow-up, after ancillary procedures were needed in 17.1 % of the control group. Surgeons' evaluations for XenX were suboptimal for "Ease of Basketing" (2/5) and "Advancement of double J stent" (3/5). The use of XenX increased costs of procedures, but spared the costs associated to ancillary procedures and stent removals. XenX confirmed to be a safe and effective device especially for the treatment of upper ureteric tract stones; moreover, XenX may reduce the risk for the need of auxiliary procedures and for the insertion of a JJ stent.

Comparison of efficacy and toxicity of doxorubicin and mitoxantrone in combination chemotherapy for canine lymphoma

PubMed Central

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

2016-01-01

Forty-four dogs with multicentric lymphoma were treated using a cyclophosphamide, doxorubicin, vincristine, and prednisolone (CHOP) induction protocol or treated using a cyclophosphamide, mitoxantrone, vincristine, and prednisolone (CMOP) induction protocol. There was no statistical difference in signalment and the presence of historical negative prognostic factors between the groups. The median progression-free survival (PFS) in the CHOP and CMOP groups were 222 d and 162 d, respectively (P = 0.75). The median survival time (MST) of dogs in CHOP and CMOP groups were 318 d and 242 d, respectively (P = 0.63). Anorexia and diarrhea episodes were significantly higher in the CHOP group than in the CMOP group (P = 0.02 and P = 0.01, respectively). These results suggest that the CMOP protocol provides similar PFS, MST and causes fewer side effects compared to the CHOP protocol. Therefore, the CMOP protocol may be another treatment choice for canine multicentric lymphoma. PMID:26933263

Comparison of efficacy and toxicity of doxorubicin and mitoxantrone in combination chemotherapy for canine lymphoma.

PubMed

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

2016-03-01

Forty-four dogs with multicentric lymphoma were treated using a cyclophosphamide, doxorubicin, vincristine, and prednisolone (CHOP) induction protocol or treated using a cyclophosphamide, mitoxantrone, vincristine, and prednisolone (CMOP) induction protocol. There was no statistical difference in signalment and the presence of historical negative prognostic factors between the groups. The median progression-free survival (PFS) in the CHOP and CMOP groups were 222 d and 162 d, respectively (P = 0.75). The median survival time (MST) of dogs in CHOP and CMOP groups were 318 d and 242 d, respectively (P = 0.63). Anorexia and diarrhea episodes were significantly higher in the CHOP group than in the CMOP group (P = 0.02 and P = 0.01, respectively). These results suggest that the CMOP protocol provides similar PFS, MST and causes fewer side effects compared to the CHOP protocol. Therefore, the CMOP protocol may be another treatment choice for canine multicentric lymphoma.

A prospective, randomised, controlled, multi-centre comparative effectiveness study of healing using dehydrated human amnion/chorion membrane allograft, bioengineered skin substitute or standard of care for treatment of chronic lower extremity diabetic ulcers.

PubMed

Zelen, Charles M; Gould, Lisa; Serena, Thomas E; Carter, Marissa J; Keller, Jennifer; Li, William W

2015-12-01

A prospective, randomised, controlled, parallel group, multi-centre clinical trial was conducted at three sites to compare the healing effectiveness of treatment of chronic lower extremity diabetic ulcers with either weekly applications of Apligraf(®) (Organogenesis, Inc., Canton, MA), EpiFix(®) (MiMedx Group, Inc., Marietta, GA), or standard wound care with collagen-alginate dressing. The primary study outcome was the percent change in complete wound healing after 4 and 6 weeks of treatment. Secondary outcomes included percent change in wound area per week, velocity of wound closure and a calculation of the amount and cost of Apligraf or EpiFix used. A total of 65 subjects entered the 2-week run-in period and 60 were randomised (20 per group). The proportion of patients in the EpiFix group achieving complete wound closure within 4 and 6 weeks was 85% and 95%, significantly higher (all adjusted P-values ≤ 0·003) than for patients receiving Apligraf (35% and 45%), or standard care (30% and 35%). After 1 week, wounds treated with EpiFix had reduced in area by 83·5% compared with 53·1% for wounds treated with Apligraf. Median time to healing was significantly faster (all adjusted P-values ≤0·001) with EpiFix (13 days) compared to Apligraf (49 days) or standard care (49 days). The mean number of grafts used and the graft cost per patient were lower in the EpiFix group campared to the Apligraf group, at 2·15 grafts at a cost of $1669 versus 6·2 grafts at a cost of $9216, respectively. The results of this study demonstrate the clinical and resource utilisation superiority of EpiFix compared to Apligraf or standard of care, for the treatment of diabetic ulcers of the lower extremities. © 2014 The Authors. International Wound Journal published by Medicalhelplines.com Inc and John Wiley & Sons 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.

Stapler versus scalpel resection followed by hand-sewn closure of the pancreatic remnant for distal pancreatectomy.

PubMed

Probst, Pascal; Hüttner, Felix J; Klaiber, Ulla; Knebel, Phillip; Ulrich, Alexis; Büchler, Markus W; Diener, Markus K

2015-11-06

Resections of the pancreatic body and tail reaching to the left of the superior mesenteric vein are defined as distal pancreatectomy. Most distal pancreatectomies are elective treatments for chronic pancreatitis, benign or malignant diseases, and they have high morbidity rates of up to 40%. Pancreatic fistula formation is the main source of postoperative morbidity, associated with numerous further complications. Researchers have proposed several surgical resection and closure techniques of the pancreatic remnant in an attempt to reduce these complications. The two most common techniques are scalpel resection followed by hand-sewn closure of the pancreatic remnant and stapler resection and closure. To compare the rates of pancreatic fistula in people undergoing distal pancreatectomy using scalpel resection followed by hand-sewn closure of the pancreatic remnant versus stapler resection and closure. We searched Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE, Biosis and Science Citation Index from database inception to October 2015. We included randomised controlled trials (RCTs) comparing stapler versus scalpel resection followed by hand-sewn closure of the pancreatic remnant for distal pancreatectomy (irrespective of language or publication status). Two authors independently assessed trials for inclusion and extracted the data. Taking into consideration the clinical heterogeneity between the trials (e.g. different endpoint definitions), we analysed data using a random-effects model with Review Manager (RevMan), calculating risk ratio (RR) or mean difference (MD) with 95% confidence intervals (CI). In two eligible trials, a total of 381 participants underwent distal pancreatic resection and were randomised to closure of the pancreatic remnant either with stapler (n = 191) or scalpel resection followed by hand-sewn closure (n = 190). One was a single centre pilot RCT and the other was a multicentre blinded RCT. The single centre pilot RCT evaluated 69 participants in five intervention arms (stapler, hand-sewn, fibrin glue, mesh and pancreaticojejunostomy), although we only assessed the stapler and hand-sewn closure groups (14 and 15 participants, respectively). The multicentre RCT had two interventional arms: stapler (n = 177) and hand-sewn closure (n = 175). The rate of postoperative pancreatic fistula was the main outcome, and it occurred in 79 of 190 participants in the hand-sewn group compared to 65 of 191 participants in the stapler group. Neither the individual trials nor the meta-analysis showed a significant difference between resection techniques (RR 0.90; 95% CI 0.55 to 1.45; P = 0.66). In the same way, postoperative mortality and operation time did not differ significantly. The single centre RCT had an unclear risk of bias in the randomisation, allocation and both blinding domains. However, the much larger multicentre RCT had a low risk of bias in all domains. Due to the small number of events and the wide confidence intervals that cannot exclude clinically important benefit or harm with stapler versus hand-sewn closure, there is a serious possibility of imprecision, making the overall quality of evidence moderate. The quality of evidence is moderate and mainly based on the high weight of the results of one multicentre RCT. Unfortunately, there are no other completed RCTs on this topic except for one relevant ongoing trial. Neither stapler nor scalpel resection followed by hand-sewn closure of the pancreatic remnant for distal pancreatectomy showed any benefit compared to the other method in terms of postoperative pancreatic fistula, overall postoperative mortality or operation time. Currently, the choice of closure is left up to the preference of the individual surgeon and the anatomical characteristics of the patient. Another (non-European) multicentre trial (e.g. with an equality or non-inferiority design) would help to corroborate the findings of this meta-analysis. Future trials assessing novel methods of stump closure should compare them either with stapler or hand-sewn closure as a control group to ensure comparability of results.

Double-blind multicentre UK hospital studies of isoxicam vs naproxen

PubMed Central

Cardoe, N.; Hart, F. Dudley

1986-01-01

1 Two multicentre, parallel group, randomised, double-blind, double-dummy comparison studies were conducted between isoxicam in the usual dose of 200 mg once daily and naproxen 500 mg twice daily. 2 The drugs were administered for 4 weeks to 230 patients suffering from osteoarthritis of the hip and/or knee in the first trial and to 249 patients suffering from rheumatoid arthritis in the second. 3 The studies compared treatments for both safety and overall effectiveness in the relief of pain. 4 In the osteoarthritis trial, overall pain was reduced by both drugs after 2 weeks of therapy but only isoxicam produced further improvement after 4 weeks. 5 Isoxicam produced reductions comparable to those produced by naproxen in pain on standing from the sitting position, pain on walking, and pain on movement of the affected joint, after 2 and 4 weeks. 6 After 4 weeks, isoxicam given once daily in the morning was significantly more effective than naproxen given in the morning and the evening in relieving not only total pain as assessed by a visual analogue scale but, as importantly, night pain. 7 Compared to naproxen therapy, isoxicam therapy was associated with significantly more patients whose disease state was improved at 2 weeks, as assessed by physicians. 8 In the rheumatoid arthritis trial, isoxicam was equally as effective as naproxen in reducing joint tenderness, joint swelling, and pain; at 4 weeks there was a trend in favour of isoxicam in reduction of joint swelling and pain. 9 Isoxicam reduced morning stiffness significantly more than naproxen after 4 weeks; this trend was apparent at 2 weeks. 10 Patients thought that isoxicam was more effective than naproxen, to a significant difference. 11 In both trials, the two drugs were well tolerated and had similar side effects profiles, with the majority of adverse experiences being associated with the digestive system; no side effect was severe. PMID:3620277

A randomised, double-blind, multicentre, parallel-group, prospective study comparing the pharmacokinetics, safety, and efficacy of CT-P13 and innovator infliximab in patients with ankylosing spondylitis: the PLANETAS study.

PubMed

Park, Won; Hrycaj, Pawel; Jeka, Slawomir; Kovalenko, Volodymyr; Lysenko, Grygorii; Miranda, Pedro; Mikazane, Helena; Gutierrez-Ureña, Sergio; Lim, MieJin; Lee, Yeon-Ah; Lee, Sang Joon; Kim, HoUng; Yoo, Dae Hyun; Braun, Jürgen

2013-10-01

To compare the pharmacokinetics (PK), safety and efficacy of innovator infliximab (INX) and CT-P13, a biosimilar to INX, in patients with active ankylosing spondylitis (AS). Phase 1 randomised, double-blind, multicentre, multinational, parallel-group study. Patients were randomised to receive 5 mg/kg of CT-P13 (n=125) or INX (n=125). Primary endpoints were area under the concentration-time curve (AUC) at steady state and observed maximum steady state serum concentration (Cmax,ss) between weeks 22 and 30. Additional PK, efficacy endpoints, including 20% and 40% improvement response according to Assessment in Ankylosing Spondylitis International Working Group criteria (ASAS20 and ASAS40), and safety outcomes were also assessed. Geometric mean AUC was 32 765.8 μgh/ml for CT-P13 and 31 359.3 μgh/ml for INX. Geometric mean Cmax,ss was 147.0 μg/ml for CT-P13 and 144.8 μg/ml for INX. The ratio of geometric means was 104.5% (90% CI 94% to 116%) for AUC and 101.5% (90% CI 95% to 109%) for Cmax,ss. ASAS20 and ASAS40 responses at week 30 were 70.5% and 51.8% for CT-P13 and 72.4% and 47.4% for INX, respectively. In the CT-P13 and INX groups more than one adverse event occurred in 64.8% and 63.9% of patients, infusion reactions occurred in 3.9% and 4.9%, active tuberculosis occurred in 1.6% and 0.8%, and 27.4% and 22.5% of patients tested positive for anti-drug antibodies, respectively. The PK profiles of CT-P13 and INX were equivalent in patients with active AS. CT-P13 was well tolerated, with an efficacy and safety profile comparable to that of INX up to week 30.

Clinical predictors of rectal lymphogranuloma venereum infection: results from a multicentre case-control study in the U.K.

PubMed

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

2014-06-01

Since 2003, over 2000 cases of lymphogranuloma venereum (LGV) have been diagnosed in the U.K. in men who have sex with men (MSM). Most cases present with proctitis, but there are limited data on how to differentiate clinically between LGV and other pathology. We analysed the clinical presentations of rectal LGV in MSM to identify clinical characteristics predictive of LGV proctitis and produced a clinical prediction model. A prospective multicentre case-control study was conducted at six U.K. hospitals from 2008 to 2010. Cases of rectal LGV were compared with controls with rectal symptoms but without LGV. Data from 98 LGV cases and 81 controls were collected from patients and clinicians using computer-assisted self-interviews and clinical report forms. Univariate and multivariate logistic regression was used to compare symptoms and signs. Clinical prediction models for LGV were compared using receiver operating curves. Tenesmus, constipation, anal discharge and weight loss were significantly more common in cases than controls. In multivariate analysis, tenesmus and constipation alone were suggestive of LGV (OR 2.98, 95% CI 0.99 to 8.98 and 2.87, 95% CI 1.01 to 8.15, respectively) and that tenesmus alone or in combination with constipation was a significant predictor of LGV (OR 6.97, 95% CI 2.71 to 17.92). The best clinical prediction was having one or more of tenesmus, constipation and exudate on proctoscopy, with a sensitivity of 77% and specificity of 65%. This study indicates that tenesmus alone or in combination with constipation makes a diagnosis of LGV in MSM presenting with rectal symptoms more likely. 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.

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.

[Multicentre randomized trial comparing triptorelin medical castration versus surgical castration in the treatment of locally advanced or metastatic prostate cancer].

PubMed

Botto, Henry; Rouprêt, Morgan; Mathieu, François; Richard, François

2007-04-01

To report the results of a trial comparing the efficacy of triptorelin and surgical castration in the treatment of locally advanced or metastatic prostate cancer. 80 patients with previously untreated locally advanced or metastatic prostate cancer prostate cancer were included in a one-year multicentre, randomized, prospective, open-label therapeutic trial. Patients either received a monthly injection of triptorelin (group 1; n = 40), or were treated by pulpectomy (group 2; n = 40). Patients were reviewed every 3 months, then every 6 months. The mean age of the patients was 71.22 +/- 8.25 years. At 1 month, 38 patients were castrated (plasma testosterone < 0.5 mg/ml) in the pulpectomy group versus 35 in the triptorelin group. The mean follow-up was 38.8 +/- 26 months in the triptorelin group and 36.3 +/- 25 months in the pulpectomy group. On multivariate analysis, age, impaired performance status and PAP level (> 3.2 ng/ml) were predictive factors of a poor outcome. The median survival was 37.5 +/- 9 months in the triptorelin group and 33 +/- 3 months in the pulpectomy group. At 3 years, no significant difference in specific survival was observed between the 2 groups. At 8 years of follow-up, 63 patients had died. This study demonstrates an equivalent specific survival between patients treated by triptorelin or surgical castration. Castration is rapidly obtained with triptorelin (< 2 months) and is maintained over time throughout the duration of treatment.

Resistant Hypertension: Time to Consider the Best Fifth Anti-Hypertensive Treatment.

PubMed

Pio-Abreu, Andrea; Drager, Luciano F

2018-06-16

Resistant hypertension (RH) is a growing clinical condition worldwide associated with target-organ damage and poor prognosis compared to non-resistant counterparts. The purpose of this review is to perform a critical evaluation of preferable drug choices for managing RH highlighting the evidence that significant proportion of patients remained uncontrolled despite using four anti-hypertensive drugs. Until recently, the fourth drug therapy was main derived from personal opinion or small interventional studies. The recent data derived from two multicentric randomized trials, namely PATHWAY-2 and ReHOT, pointed spironolactone as the preferable fourth drug therapy in patients with confirmed RH as compared to bisoprolol and doxazosin (PATHWAY-2) as well as clonidine (ReHOT). However, significant proportion of patients (especially observed in ReHOT trial that used 24-h ambulatory blood pressure monitoring) did not achieve optimal blood pressure with the fourth drug. This finding underscores the need of new approaches and treatment options in this important research area. The current evidence pointed that significant proportion of RH patients are requiring more than four drugs for controlling BP. This statement is particularly true considering the new criteria proposed by the 2017 Guidelines for diagnosing RH (> 130 × 80 mmHg). New combinations, drugs, or treatments should be tested aiming to reduce the RH burden. Based on the aforementioned multicentric trials, we proposed the first five preferable anti-hypertensive classes in the overall context of RH.

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.

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

Twelve-month short-term safety and visual-acuity results from a multicentre prospective study of epiretinal strontium-90 brachytherapy with bevacizumab for the treatment of subfoveal choroidal neovascularisation secondary to age-related macular degeneration.

PubMed

Avila, M P; Farah, M E; Santos, A; Duprat, J P; Woodward, B W; Nau, J

2009-03-01

This study evaluated the short-term safety and feasibility of epiretinal strontium-90 brachytherapy delivered concomitantly with intravitreal bevacizumab for the treatment of subfoveal CNV due to AMD for 12 months. A 3-year follow-up is planned. In this prospective, non-randomised, multicentre study, 34 treatment-naïve patients with predominantly classic, minimally classic and occult subfoveal CNV lesions received a single treatment with 24 Gy beta radiation (strontium-90) and two injections of the anti-VEGF antibody bevacizumab. Adverse events were observed. BCVA was measured using standard ETDRS vision charts. Twelve months after treatment, no radiation-associated adverse events were observed. In the intent-to-treat (ITT) population, 91% of patients lost <3 lines (15 ETDRS letters) of vision at 12 months, 68% improved or maintained their BCVA at 12 months, and 38% gained >/=3 lines. The mean change in BCVA observed at month 12 was a gain of 8.9 letters. The safety and efficacy of intraocular, epiretinal brachytherapy delivered concomitantly with anti-VEGF therapy for the treatment of subfoveal CNV secondary to AMD were promising in this small study population. Long-term safety will be assessed for 3 years. This regimen is being evaluated in a large, multicentre, phase III study.

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

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.

Efficacy and safety of injection with poly-L-lactic acid compared with hyaluronic acid for correction of nasolabial fold: a randomized, evaluator-blinded, comparative study.

PubMed

Hyun, M Y; Lee, Y; No, Y A; Yoo, K H; Kim, M N; Hong, C K; Chang, S E; Won, C H; Kim, B J

2015-03-01

Hyaluronic acid (HA) fillers and poly-L-lactic acid (PLA) fillers are frequently used to correct facial wrinkles. To compare the efficacy and safety of a novel injectable poly-L-lactic acid (PLA) filler and a well-studied biphasic HA filler for the treatment of moderate to severe nasolabial folds. In this multicentre, randomized, evaluator-blinded, comparative study, subjects were randomized for injections with PLA or HA into both nasolabial folds. Efficacy was determined by calculating the change in Wrinkle Severity Rating Scale (WSRS) relative to baseline. Local safety was assessed by reported adverse events. At week 24, mean improvement in WSRS from baseline was 2.09 ± 0.68 for the PLA side and 1.54 ± 0.65 for the HA side. Both injections were well tolerated, and the adverse reactions were mild and transient in most cases. PLA provides noninferior efficacy compared with HA 6 months after being used to treat moderate to severe nasolabial folds. © 2014 British Association of Dermatologists.

The efficacy and safety of blonanserin compared with haloperidol in acute-phase schizophrenia: a randomized, double-blind, placebo-controlled, multicentre study.

PubMed

Garcia, Esther; Robert, Marta; Peris, Francesc; Nakamura, Hiroshi; Sato, Noriko; Terazawa, Yoshikatsu

2009-01-01

Blonanserin is a novel atypical antipsychotic agent with potent dopamine D(2) and serotonin 5-HT(2) antagonist properties. It may potentially have a lower incidence of adverse events than other antipsychotic agents. To determine the efficacy and safety of three doses of blonanserin compared with placebo and haloperidol in patients with acute-phase schizophrenia. This was a 6-week, randomized, double-blind, placebo- and haloperidol-controlled, international, multicentre study. Patients with an acute exacerbation of their schizophrenia, with a Positive and Negative Syndrome Scale (PANSS) score >/=70 and a Clinical Global Impression - Severity of Illness (CGI-S) score >/=4 ('moderately ill') [with no decrease >/=20% or >/=1 point, respectively, during the wash-out period] were randomized into one of five treatment groups (blonanserin 2.5, 5 or 10 mg, haloperidol 10 mg or placebo once daily). Patients were assessed weekly for clinical efficacy, adverse events, extrapyramidal symptoms (EPS) and drug compliance, and were assessed biweekly for other safety variables. All 307 randomized patients received at least one dose of study medication and 228 (74.3%) completed the study. The mean reduction in PANSS total score at week 6 was significantly greater with all active treatments compared with placebo (-12.58; p < 0.001); blonanserin 10 mg was significantly superior to blonanserin 2.5 mg (-30.18 vs -20.6; p < 0.001), but blonanserin 5 mg (-27.19) and haloperidol 10 mg (-28.16) were not. All active treatments showed greater efficacy against the positive symptoms of schizophrenia, and blonanserin (5 and 10 mg) was more effective against the negative symptoms than haloperidol. Blonanserin was well tolerated at all doses and there was no evidence of clinically important weight gain, orthostatic hypotension, corrected QT interval prolongation or clinically relevant changes in laboratory test results. Haloperidol caused persistent elevation in prolactin levels, but this was not seen with any dose of blonanserin throughout the study period. There was a lower incidence of EPS with blonanserin 10 mg (26.6%) than with haloperidol 10 mg (53.3%). Blonanserin was effective in the treatment of acute schizophrenia and showed greater efficacy in negative symptoms compared with placebo and haloperidol. Blonanserin was well tolerated and its safety profile compared favourably with haloperidol, particularly with respect to prolactin elevation and EPS frequency.

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

PubMed

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

2008-10-01

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

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.

Evaluation of postoperative recovery in day surgery patients using a mobile phone application: a multicentre randomized trial.

PubMed

Jaensson, M; Dahlberg, K; Eriksson, M; Nilsson, U

2017-11-01

Many patients undergoing anaesthesia and surgery experience postoperative complications. Our aim was to investigate whether a systematic follow-up smartphone-based assessment, using recovery assessment by phone points (RAPP) compared with standard care, had a positive effect on day surgery patients' postoperative recovery. We also investigated whether there were differences in women and men's recovery and recovery scores. The study was a single-blind, multicentre randomized controlled trial. A total of 997 patients were randomly allocated to either RAPP or standard care. The Swedish web version of a quality of recovery (SwQoR) questionnaire was used to evaluate the patients' postoperative recovery, either on paper or using an application (RAPP) on postoperative days seven and 14. On postoperative day seven the RAPP group reported significantly better values in seven out of 24 items of the SwQoR: sleeping difficulties; not having a general feeling of wellbeing; having difficulty feeling relaxed/comfortable; and dizziness; headache; pain in the surgical wound; and a swollen surgical wound compared with the control group, implying a good postoperative recovery. Both men and women in the RAPP group reported significantly better values (and, hence good postoperative recovery) compared with the control group in the items sleeping difficulties; not having a general feeling of wellbeing and pain in the surgical wound. Measurement of patient-reported outcomes using a smartphone-based application was associated with decreased discomfort from several postoperative symptoms. Systematic e-assessment can thereby increase patients' quality of recovery and identify key areas for improvement in perioperative care. NCT02492191. © The Author 2017. Published by Oxford University Press on behalf of the British Journal of Anaesthesia.

Moxifloxacin versus ofloxacin plus metronidazole in uncomplicated pelvic inflammatory disease: results of a multicentre, double blind, randomised trial

PubMed Central

Ross, J D C; Cronjé, H S; Paszkowski, T; Rakoczi, I; Vildaite, D; Kureishi, A; Alefelder, M; Arvis, P; Reimnitz, P

2006-01-01

Objective This multinational, multicentre, prospective, randomised, double blind, parallel group, non‐inferiority study compared the efficacy and safety of moxifloxacin monotherapy with ofloxacin plus metronidazole in women with uncomplicated pelvic inflammatory disease. Methods Women from hospitals throughout 13 countries received a 14 day course of either oral moxifloxacin, 400 mg once daily (n = 384), or oral ofloxacin, 400 mg twice daily plus oral metronidazole, 500 mg twice daily (n = 365). Results Of the 741 patients in the intent to treat (ITT) population, 564 (74.2%) were valid for the per protocol (PP) analyses; 112 (19.9%) of these were included in the microbiologically valid population (MBV). Clinical resolution rates in the PP population at the test of cure visit (TOC, 5–24 days post‐therapy, primary efficacy end point) were 90.2% (248/275) for moxifloxacin and 90.7% (262/289) for ofloxacin plus metronidazole (95% CI: −5.7% to 4.0%). At follow up (28–42 days post‐therapy), resolution rates in the PP population were 85.8% (236/275) and 87.9% (254/289) for moxifloxacin and comparator, respectively (95% CI: −8.0% to 3.1%). Bacteriological success rates in the MBV population at TOC were 87.5% (49/56) for moxifloxacin and 82.1% (46/56) for comparator (95% CI: −8.3% to 18.8%). Against Chlamydia trachomatis and Neisseria gonorrhoeae, bacteriological success rates with moxifloxacin were 88.5% (23/26) and 100% (13/13) and for comparator 85.7% (18/21) and 81.8% (18/22), respectively. Drug related adverse events occurred less frequently with moxifloxacin (22.5% (85/378)) versus the comparator (30.9% (112/363)) (p = 0.01). Conclusion In uncomplicated PID, once daily moxifloxacin monotherapy was clinically and bacteriologically as efficacious as twice daily ofloxacin plus metronidazole therapy and was associated with fewer drug related adverse events. PMID:16723364

Issues in conducting cross-cultural research: implementation of an agreed international protocol [corrected] designed by the WHOQOL Group for the conduct of focus groups eliciting the quality of life of older adults.

PubMed

Hawthorne, Graeme; Davidson, Natasha; Quinn, Kathryn; McCrate, Farah; Winkler, Ines; Lucas, Ramona; Kilian, Reinhold; Molzahn, Anita

2006-09-01

Multi-centre and cross-cultural research require the use of common protocols if the results are to be either pooled or compared. All too often adherence to protocols is not discussed in reports and where it is reported poor adherence is frequently noted. This paper discusses the use of international guidelines developed by WHOQOL Field Centres to conduct and report focus groups aimed at eliciting key concepts of quality of life among older adults. This was the first step in the development of the WHOQOL-OLD instrument. Although there was overall adherence to the agreed guidelines, there were some differences in the level of reporting, even after participating Field Centres had the opportunity to explain their reports. The reasons for these discrepancies are reported. It is concluded that because of local situations, it is difficult to achieve identical implementation of multi-centre cross-cultural protocols and that the highest standards of auditing are required if findings are to be compared. Suggestions for how such protocols can be improved are given.

A modified haemagglutination inhibition test for rubella antibodies, using standardized, freeze-dried reagents. Report of a comparative multi-centre trial.

PubMed Central

van Weemen, B.; Kacaki, J.

1976-01-01

A modified haemagglutination inhibition test for rubella antibodies, using standardized freeze-dried reagents, was developed and compared with haemagglutination inhibition tests using fresh erythrocytes. This comparison was made in collaboration with six European laboratories. A total of 4205 serum samples were tested. The results show that: (1) Sensitivity and reliability of the modified test are good; (2) the modified test can be performed in polystyrene microtitration plates. PMID:789763

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

Individualised cognitive functional therapy compared with a combined exercise and pain education class for patients with non-specific chronic low back pain: study protocol for a multicentre randomised controlled trial

PubMed Central

O'Keeffe, Mary; Purtill, Helen; Kennedy, Norelee; O'Sullivan, Peter; Dankaerts, Wim; Tighe, Aidan; Allworthy, Lars; Dolan, Louise; Bargary, Norma; O'Sullivan, Kieran

2015-01-01

Introduction Non-specific chronic low back pain (NSCLBP) is a very common and costly musculoskeletal disorder associated with a complex interplay of biopsychosocial factors. Cognitive functional therapy (CFT) represents a novel, patient-centred intervention which directly challenges pain-related behaviours in a cognitively integrated, functionally specific and graduated manner. CFT aims to target all biopsychosocial factors that are deemed to be barriers to recovery for an individual patient with NSCLBP. A recent randomised controlled trial (RCT) demonstrated the superiority of individualised CFT for NSCLBP compared to manual therapy combined with exercise. However, several previous RCTs have suggested that class-based interventions are as effective as individualised interventions. Therefore, it is important to examine whether an individualised intervention, such as CFT, demonstrates clinical effectiveness compared to a relatively cheaper exercise and education class. The current study will compare the clinical effectiveness of individualised CFT with a combined exercise and pain education class in people with NSCLBP. Methods and analysis This study is a multicentre RCT. 214 participants, aged 18–75 years, with NSCLBP for at least 6 months will be randomised to one of two interventions across three sites. The experimental group will receive individualised CFT and the length of the intervention will be varied in a pragmatic manner based on the clinical progression of participants. The control group will attend six classes which will be provided over a period of 6–8 weeks. Participants will be assessed preintervention, postintervention and after 6 and12 months. The primary outcomes will be functional disability and pain intensity. Non-specific predictors, moderators and mediators of outcome will also be analysed. Ethics and dissemination Ethical approval has been obtained from the Mayo General Hospital Research Ethics Committee (MGH-14-UL). Outcomes will be disseminated through publication according to the SPIRIT statement and will be presented at scientific conferences. Trial registration number (ClinicalTrials.gov NCT02145728). PMID:26033941

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

PubMed

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

2016-01-01

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

Guided Internet-based versus face-to-face clinical care in the management of tinnitus: study protocol for a multi-centre randomised controlled trial.

PubMed

Beukes, Eldré W; Baguley, David M; Allen, Peter M; Manchaiah, Vinaya; Andersson, Gerhard

2017-04-21

Innovative strategies are required to improve access to evidence-based tinnitus interventions. A guided Internet-based cognitive behavioural therapy (iCBT) intervention for tinnitus was therefore developed for a U.K. Initial clinical trials indicated efficacy of iCBT at reducing tinnitus severity and associated comorbidities such as insomnia and depression. The aim of this phase III randomised controlled trial is to compare this new iCBT intervention with an established intervention, namely face-to-face clinical care for tinnitus. This will be a multi-centre study undertaken across three hospitals in the East of England. The design is a randomised, two-arm, parallel-group, non-inferiority trial with a 2-month follow-up. The experimental group will receive the guided iCBT intervention, whereas the active control group will receive the usual face-to-face clinical care. An independent researcher will randomly assign participants, using a computer-generated randomisation schedule, after stratification for tinnitus severity. There will be 46 participants in each group. The primary assessment measure will be the Tinnitus Functional Index. Data analysis will establish whether non-inferiority is achieved using a pre-defined non-inferiority margin. This protocol outlines phase III of a clinical trial comparing a new iCBT with established face-to-face care for tinnitus. If guided iCBT for tinnitus proves to be as effective as the usual tinnitus care, it may be a viable additional management route for individuals with tinnitus. This could increase access to evidence-based effective tinnitus care and reduce the pressures on existing health care systems. ClinicalTrials.gov identifier: NCT02665975 . Registered on 22 January 2016.

Tolerability of the capsaicin 8% patch following pretreatment with lidocaine or tramadol in patients with peripheral neuropathic pain: a multicentre, randomized, assessor-blinded study.

PubMed

Jensen, T S; Høye, K; Fricová, J; Vanelderen, P; Ernault, E; Siciliano, T; Marques, S

2014-10-01

Application of the capsaicin 8% patch is associated with treatment-related discomfort. Consequently, pretreatment for 60 min with anaesthetic cream is recommended; however, this may be uncomfortable and time consuming. We conducted a multicentre, randomized (1:1), assessor-blinded study in patients with peripheral neuropathic pain to assess tolerability of the capsaicin patch following topical lidocaine (4%) or oral tramadol (50 mg) pretreatment. The primary endpoint was the proportion of patients tolerating capsaicin patch application (ability to receive ≥90% of a 60-min application). Numeric Pain Rating Scale (NPRS) scores were assessed before, during and after treatment. Overall, 122 patients were included (61 per arm). The capsaicin patch was tolerated by 121 patients. Tolerability of the capsaicin patch was similar following pretreatment with lidocaine and tramadol. Following patch application, pain levels increased up to 55 min (change from baseline of 1.3 for lidocaine and 1.4 for tramadol). After patch removal, tramadol-treated patients experienced greater pain relief up to the end of day 1; in the evening, mean changes in NPRS scores from baseline were 0 for lidocaine and -1 for tramadol. Proportions of patients reporting increases of ≥2 NPRS points or >33% from baseline at one or more time point(s) on the day of treatment were similar between arms. Adverse event incidence was comparable between arms. Capsaicin 8% patch tolerability was similar in the two arms, with comparable results for most secondary endpoints. Tramadol given 30 min before patch application should be considered as an alternative pretreatment option in patients receiving capsaicin patch treatment. © 2014 The Authors. European Journal of Pain published by John Wiley & Sons Ltd on behalf of European Pain Federation - EFIC®.

Design of a multicentre randomized controlled trial to assess the safety and efficacy of dose titration by specialized nurses in patients with heart failure. ETIFIC study protocol

PubMed Central

García‐Garrido, LLuisa; Nebot Margalef, Magdalena; Lekuona, Iñaki; Comin‐Colet, Josep; Manito, Nicolás; Roure, Julia; Ruiz Rodriguez, Pilar; Enjuanes, Cristina; Latorre, Pedro; Torcal Laguna, Jesús; García‐Gutiérrez, Susana

2017-01-01

Abstract Aims Heart failure (HF) is associated with many hospital admissions and relatively high mortality, rates decreasing with administration of beta‐blockers (BBs), angiotensin‐converting‐enzyme inhibitors, angiotensin II receptor blockers, and mineralocorticoid receptor antagonists. The effect is dose dependent, suboptimal doses being common in clinical practice. The 2012 European guidelines recommend close monitoring and dose titration by HF nurses. Our main aim is to compare BB doses achieved by patients after 4 months in intervention (HF nurse‐managed) and control (cardiologist‐managed) groups. Secondary aims include comparing doses of the other aforementioned drugs achieved after 4 months, adverse events, and outcomes at 6 months in the two groups. Methods We have designed a multicentre (20 hospitals) non‐inferiority randomized controlled trial, including patients with new‐onset HF, left ventricular ejection fraction ≤40%, and New York Heart Association class II–III, with no contraindications to BBs. We will also conduct qualitative analysis to explore potential barriers to and facilitators of dose titration by HF nurses. In the intervention group, HF nurses will implement titration as prescribed by cardiologists, following a protocol. In controls, cardiologists will both prescribe and titrate doses. The study variables are doses of each of the drugs after 4 months relative to the target dose (%), New York Heart Association class, left ventricular ejection fraction, N‐terminal pro B‐type natriuretic peptide levels, 6 min walk distance, comorbidities, renal function, readmissions, mortality, quality of life, and psychosocial characteristics. Conclusions The trial seeks to assess whether titration by HF nurses of drugs recommended in practice guidelines is safe and not inferior to direct management by cardiologists. The results could have an impact on clinical practice. PMID:29154427

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.

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.

Effect of endoscopic transpapillary biliary drainage with/without endoscopic sphincterotomy on post-endoscopic retrograde cholangiopancreatography pancreatitis in patients with biliary stricture (E-BEST): a protocol for a multicentre randomised controlled trial

PubMed Central

Kato, Shin; Kuwatani, Masaki; Sugiura, Ryo; Sano, Itsuki; Kawakubo, Kazumichi; Ono, Kota; Sakamoto, Naoya

2017-01-01

Introduction The effect of endoscopic sphincterotomy prior to endoscopic biliary stenting to prevent post-endoscopic retrograde cholangiopancreatography pancreatitis remains to be fully elucidated. The aim of this study is to prospectively evaluate the non-inferiority of non-endoscopic sphincterotomy prior to stenting for naïve major duodenal papilla compared with endoscopic sphincterotomy prior to stenting in patients with biliary stricture. Methods and analysis We designed a multicentre randomised controlled trial, for which we will recruit 370 patients with biliary stricture requiring endoscopic biliary stenting from 26 high-volume institutions in Japan. Patients will be randomly allocated to the endoscopic sphincterotomy group or the non-endoscopic sphincterotomy group. The main outcome measure is the incidence of pancreatitis within 2 days of initial transpapillary biliary drainage. Data will be analysed on completion of the study. We will calculate the 95% confidence intervals (CIs) of the incidence of pancreatitis in each group and analyse weather the difference in both groups with 95% CIs is within the non-inferiority margin (6%) using the Wald method. Ethics and dissemination This study has been approved by the institutional review board of Hokkaido University Hospital (IRB: 016–0181). Results will be submitted for presentation at an international medical conference and published in a peer-reviewed journal. Trial registration number The University Hospital Medical Information Network ID: UMIN000025727 Pre-results. PMID:28801436

Iron-chelating therapy with deferasirox in transfusion-dependent, higher risk myelodysplastic syndromes: a retrospective, multicentre study.

PubMed

Musto, Pellegrino; Maurillo, Luca; Simeon, Vittorio; Poloni, Antonella; Finelli, Carlo; Balleari, Enrico; Ricco, Alessandra; Rivellini, Flavia; Cortelezzi, Agostino; Tarantini, Giuseppe; Villani, Oreste; Mansueto, Giovanna; Milella, Maria R; Scapicchio, Daniele; Marziano, Gioacchino; Breccia, Massimo; Niscola, Pasquale; Sanna, Alessandro; Clissa, Cristina; Voso, Maria T; Fenu, Susanna; Venditti, Adriano; Santini, Valeria; Angelucci, Emanuele; Levis, Alessandro

2017-06-01

Iron chelation is controversial in higher risk myelodysplastic syndromes (HR-MDS), outside the allogeneic transplant setting. We conducted a retrospective, multicentre study in 51 patients with transfusion-dependent, intermediate-to-very high risk MDS, according to the revised international prognostic scoring system, treated with the oral iron chelating agent deferasirox (DFX). Thirty-six patients (71%) received azacitidine concomitantly. DFX was given at a median dose of 1000 mg/day (range 375-2500 mg) for a median of 11 months (range 0·4-75). Eight patients (16%) showed grade 2-3 toxicities (renal or gastrointestinal), 4 of whom (8%) required drug interruption. Median ferritin levels decreased from 1709 μg/l at baseline to 1100 μg/l after 12 months of treatment (P = 0·02). Seventeen patients showed abnormal transaminase levels at baseline, which improved or normalized under DFX treatment in eight cases. One patient showed a remarkable haematological improvement. At a median follow up of 35·3 months, median overall survival was 37·5 months. The results of this first survey of DFX in HR-MDS are comparable, in terms of safety and efficacy, with those observed in lower-risk MDS. Though larger, prospective studies are required to demonstrate real clinical benefits, our data suggest that DFX is feasible and might be considered in a selected cohort of HR-MDS patients. © 2017 John Wiley & Sons Ltd.

Randomised multicentre trial on safety and efficacy of rivastigmine in cognitively impaired multiple sclerosis patients.

PubMed

Mäurer, M; Ortler, S; Baier, M; Meergans, M; Scherer, P; Hofmann, We; Tracik, F

2013-04-01

Cognitive decline has been recognised as a frequent symptom in multiple sclerosis (MS). Cholinesterase inhibitors (ChEIs) are employed for the treatment of Alzheimer's disease, but there is some evidence that ChEIs might also be effective in MS patients with cognitive deficits, particularly deficits of memory function. The aim of this study was to evaluate efficacy on memory function and safety of the ChEI rivastigmine in MS patients with cognitive deficits as measured by the change from baseline of the total recall score of the selective reminding test (SRT) after 16 weeks of treatment. Efficacy and safety of rivastigmine were analysed in a 16-week, multicentre, double-blind, randomised, placebo-controlled study, followed by an optional one-year open-label treatment phase. Effects of rivastigmine and placebo were compared by an analysis of covariance. In total, 86 patients were enrolled. Patients who received rivastigmine (n = 43) showed a non-significant increase in total recall score (sum of all words immediately recalled over all six trials) over placebo (n = 38) after 16 weeks of treatment (p = 0.2576). Other outcome measures provided no evidence supporting benefits of rivastigmine. Treatment with rivastigmine was well tolerated. With the results of this study, the need for an effective therapy in cognitively impaired MS patients is still required. Thus, intensive and continued clinical research is required to explore therapeutic options for cognitive deficits in MS patients.

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

PubMed

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

2016-05-01

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

Strategies to diagnose ovarian cancer: new evidence from phase 3 of the multicentre international IOTA study.

PubMed

Testa, A; Kaijser, J; Wynants, L; Fischerova, D; Van Holsbeke, C; Franchi, D; Savelli, L; Epstein, E; Czekierdowski, A; Guerriero, S; Fruscio, R; Leone, F P G; Vergote, I; Bourne, T; Valentin, L; Van Calster, B; Timmerman, D

2014-08-12

To compare different ultrasound-based international ovarian tumour analysis (IOTA) strategies and risk of malignancy index (RMI) for ovarian cancer diagnosis using a meta-analysis approach of centre-specific data from IOTA3. This prospective multicentre diagnostic accuracy study included 2403 patients with 1423 benign and 980 malignant adnexal masses from 2009 until 2012. All patients underwent standardised transvaginal ultrasonography. Test performance of RMI, subjective assessment (SA) of ultrasound findings, two IOTA risk models (LR1 and LR2), and strategies involving combinations of IOTA simple rules (SRs), simple descriptors (SDs) and LR2 with and without SA was estimated using a meta-analysis approach. Reference standard was histology after surgery. The areas under the receiver operator characteristic curves of LR1, LR2, SA and RMI were 0.930 (0.917-0.942), 0.918 (0.905-0.930), 0.914 (0.886-0.936) and 0.875 (0.853-0.894). Diagnostic one-step and two-step strategies using LR1, LR2, SR and SD achieved summary estimates for sensitivity 90-96%, specificity 74-79% and diagnostic odds ratio (DOR) 32.8-50.5. Adding SA when IOTA methods yielded equivocal results improved performance (DOR 57.6-75.7). Risk of Malignancy Index had sensitivity 67%, specificity 91% and DOR 17.5. This study shows all IOTA strategies had excellent diagnostic performance in comparison with RMI. The IOTA strategy chosen may be determined by clinical preference.

Itopride and pantoprazole outcomes in diabetic gastroparesis trial (IPOD trial).

PubMed

Venkatesh, Veena; Kulkarni, K P

2008-12-01

The most common cause of gastroparesis is diabetes mellitus. The present study was carried out to asses the combination of itopride and pantoprazole in the treatment of diabetic gastroparesis. The study was an open label, multicentre, conducted in 743 patients with diabetic gastroparesis for a period of 3 weeks. The efficacy parameters included nausea, vomiting, early satiety, bloating, postprandial fullness, epigastric pain and regurgitation. The patients were evaluated based on the frequency and severity of symptoms and compared with the baseline scores. There were significant improvement in severity as well as the frequency of all the symptom parameters of the disease (p<0.001). The physicians' evaluation to the therapy was rated either excellent or good.

A multicentre cohort study assessing day of week effect and outcome from emergency appendicectomy.

PubMed

Ferguson, Henry J M; Hall, Nigel J; Bhangu, Aneel

2014-09-01

There is evidence to suggest that patients undergoing treatment at weekends may be subject to different care processes and outcomes compared with weekdays. This study aimed to determine whether clinical outcomes from weekend appendicectomy are different from those performed on weekdays. Multicentre cohort study during May-June 2012 from 95 centres (89 within the UK). The primary outcome was the 30-day adverse event rate. Multilevel modelling was used to account for clustering within hospitals while adjusting for case mix to produce adjusted ORs and 95% CIs. When compared with Monday, there were no significant differences for other days of the week considering 30-day adverse events in adjusted models. On Sunday, rates of simple appendicitis were highest, and rates of normal (OR 0.62, 95% CI 0.42 to 0.90) and complex appendicitis (OR 0.65, 95% CI 0.46 to 0.93) lowest. This was accompanied by a 43% lower likelihood in use of laparoscopy on Sunday (OR 0.47, 95% CI 0.32 to 0.69), accompanied by the lowest level of consultant presence for the week. When pooling weekends and weekdays, laparoscopy use remained less likely at the weekend (OR 0.68, 95% CI 0.55 to 0.83), with no significant difference for 30-day adverse event rate (OR 1.01, 95% CI 0.80 to 1.29). This study found that weekend appendicectomy was not associated with increased 30-day adverse events. It cannot rule out smaller increases that may be shown by larger studies. It further illustrated that patients operated on at weekends were subject to different care processes, which may expose them to risk. 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.

Protocol of the Australasian Malignant Pleural Effusion (AMPLE) trial: a multicentre randomised study comparing indwelling pleural catheter versus talc pleurodesis

PubMed Central

Fysh, Edward T H; Thomas, Rajesh; Read, Catherine A; Lam, Ben C H; Yap, Elaine; Horwood, Fiona C; Lee, Pyng; Piccolo, Francesco; Shrestha, Ranjan; Garske, Luke A; Lam, David C L; Rosenstengel, Andrew; Bint, Michael; Murray, Kevin; Smith, Nicola A; Lee, Y C Gary

2014-01-01

Introduction Malignant pleural effusion can complicate most cancers. It causes breathlessness and requires hospitalisation for invasive pleural drainages. Malignant effusions often herald advanced cancers and limited prognosis. Minimising time spent in hospital is of high priority to patients and their families. Various treatment strategies exist for the management of malignant effusions, though there is no consensus governing the best choice. Talc pleurodesis is the conventional management but requires hospitalisation (and substantial healthcare resources), can cause significant side effects, and has a suboptimal success rate. Indwelling pleural catheters (IPCs) allow ambulatory fluid drainage without hospitalisation, and are increasingly employed for management of malignant effusions. Previous studies have only investigated the length of hospital care immediately related to IPC insertion. Whether IPC management reduces time spent in hospital in the patients’ remaining lifespan is unknown. A strategy of malignant effusion management that reduces hospital admission days will allow patients to spend more time outside hospital, reduce costs and save healthcare resources. Methods and analysis The Australasian Malignant Pleural Effusion (AMPLE) trial is a multicentred, randomised trial designed to compare IPC with talc pleurodesis for the management of malignant pleural effusion. This study will randomise 146 adults with malignant pleural effusions (1:1) to IPC management or talc slurry pleurodesis. The primary end point is the total number of days spent in hospital (for any admissions) from treatment procedure to death or end of study follow-up. Secondary end points include hospital days specific to pleural effusion management, adverse events, self-reported symptom and quality-of-life scores. Ethics and dissemination The Sir Charles Gairdner Group Human Research Ethics Committee has approved the study as have the ethics boards of all the participating hospitals. The trial results will be published in peer-reviewed journals and presented at scientific conferences. Trial registration numbers Australia New Zealand Clinical Trials Registry—ACTRN12611000567921; National Institutes of Health—NCT02045121. PMID:25377015

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

A Multicentre Audit of Single-Use Surgical Instruments (SUSI) for Tonsillectomy and Adenoidectomy

PubMed Central

O'Flynn, P; Silva, S; Kothari, P; Persaud, R

2007-01-01

INTRODUCTION Prions are resistant to conventional sterilisation procedures and, therefore, could be transmitted iatrogenically through re-usable adenoid and tonsil surgical instruments. Using disposable instruments would avoid the risk of transmission. We present the results of a complete audit loop using BBraun single-use surgical instruments (SUSI). PATIENTS AND METHODS This was a prospective multicentre audit. Surgeons were asked to fill in a standardised questionnaire recording details including postoperative complications, and evaluation of each piece of equipment compared with their own experience of conventional re-usable instruments. In the first cycle, constructive criticisms of the instruments were noted and the manufacturers modified the instruments accordingly. A second cycle of audit was subsequently undertaken. RESULTS A total of 86 patients were audited in the first cycle and 97 in the second cycle. Postoperative haemorrhage rate for both cycles was well within acceptable range. In the first audit cycle, surgeons generally found the Draffin rods, Boyle-Davis gag and bipolar diathermy forceps of poor quality and difficult to use. These were redesigned and, on repeat evaluation during the second audit cycle, were found to be just as good, if not better, than the re-usable instruments. CONCLUSIONS This study suggests that SUSI may be just as good as re-usable instruments. Furthermore, they may be more cost effective. PMID:18201478

Efficacy and tolerability of a fixed-dose combination of metoprolol extended release/amlodipine in patients with mild-to-moderate hypertension: a randomized, parallel-group, multicentre comparison with losartan plus amlodipine.

PubMed

Pareek, Anil; Chandurkar, Nitin B; Sharma, Ravishankar; Tiwari, Dharmendra; Gupta, Bhagwan S

2010-01-01

Epidemiological studies and clinical trials have shown that prevention of cardiovascular disease, the ultimate goal of hypertension treatment, requires a sufficient reduction in blood pressure. The primary objective of this study was to compare the mean decrease in systolic (SBP) and diastolic (DBP) blood pressure between metoprolol extended release (XL)/amlodipine fixed-dose combination and losartan plus amlodipine combination in patients with mild-to-moderate essential hypertension. The secondary objectives of this study were to compare the proportion of responders in the two treatment groups and to evaluate the tolerability of the study medications. This was a randomized, parallel-group, multicentre comparative study conducted at the outpatient departments of three teaching hospitals in India. Patients with mild-to-moderate hypertension (defined as DBP 90-109 mmHg) aged between 18 and 75 years were enrolled in this study and followed up for 12 weeks. Response to study treatments was evaluated in terms of mean decrease in SBP and DBP and the response rate (reduction to SBP <140 mmHg and DBP <90 mmHg). Out of 152 patients who underwent a 1-week placebo washout, 148 eligible patients were randomized to receive either metoprolol XL 25 mg/amlodipine 2.5 mg fixed-dose combination (76 patients) or losartan 25 mg plus amlodipine 2.5 mg (72 patients). The two treatment groups were similar with respect to demographic and baseline characteristics. Non-responders after 4 weeks of therapy were escalated to metoprolol XL 50 mg/amlodipine 5 mg fixed-dose combination or losartan 50 mg plus amlodipine 5 mg, respectively. The study was completed by 66 patients in each group, of whom 43 patients in each group responded to the starting doses. After 4 weeks' therapy, both treatments were associated with significant decreases in SBP and DBP from baseline (p < 0.001) and were comparable with respect to mean decrease in SBP (p = 0.304), mean decrease in DBP (p = 0.630) and response rate (p = 1.0). Also, both the step-up therapies were comparable with respect to mean decrease in SBP (p = 0.484), mean decrease in DBP (p = 0.650) and response rate (p = 0.134) at week 12. Both treatments were well tolerated in the studied population. Metoprolol XL/amlodipine fixed-dose combination was found to be as effective and well tolerated as losartan plus amlodipine in the treatment of essential hypertension.

Theobromine for the treatment of persistent cough: a randomised, multicentre, double-blind, placebo-controlled clinical trial

PubMed Central

McGarvey, Lorcan; Pavord, Ian D.; Higgins, Bernard; Chung, Kian Fan; Birring, Surinder S.

2017-01-01

Background To investigate the effect of BC1036 on health-related quality of life (QOL) in subjects with persistent cough. The secondary objective was to investigate the effect of BC1036 on subjective cough severity. Methods This was a randomised, multicentre, double-blind, placebo-controlled, parallel-group study in 289 subjects with persistent cough. Subjects received BC1036 or placebo twice daily for 14 days. The primary endpoint comprised cough-related QOL assessed using the validated Leicester Cough Questionnaire (LCQ) at Day 14. Secondary endpoints comprised the LCQ scores at Day 7 and Day 28, cough severity VAS scores at each visit and pulmonary function tests. Results At baseline, mean total LCQ score in the BC1036 group was lower (i.e., worse QOL) than placebo (P<0.001), indicating significant between-group heterogeneity. Mean baseline-adjusted change in LCQ score at Day 14 was greater for BC1036 [mean (SD) 2.4±3.5] compared to placebo [mean (SD) score 2.2±3.0], but did not reach statistical significance (P=0.60). Mean cough severity VAS score decreased to a greater extent in the BC1036 group compared to placebo, but again the results were not statistically significant (−12.2±23.28 in BC1036 group and −11.0±21.34 in placebo group at Day 14, P=0.688). There was no significant change in pulmonary function measurements. The adverse event (AE) profile was similar in both groups. Conclusions This study showed that BC1036 was well tolerated and, although the primary endpoint did not achieve statistical significance, the magnitude of improvement was greater with BC1036 compared to placebo with respect to improving QOL and reducing cough severity. Clinical trial registration ClinicalTrials.gov: NCT01656668. PMID:28839984

Viro-immunological response of drug-naive HIV-1-infected patients starting a first-line regimen with viraemia >500,000 copies/ml in clinical practice.

PubMed

Santoro, Maria Mercedes; Di Carlo, Domenico; Armenia, Daniele; Zaccarelli, Mauro; Pinnetti, Carmela; Colafigli, Manuela; Prati, Francesca; Boschi, Andrea; Antoni, Anna Maria Degli; Lagi, Filippo; Sighinolfi, Laura; Gervasoni, Cristina; Andreoni, Massimo; Antinori, Andrea; Mussini, Cristina; Perno, Carlo Federico; Borghi, Vanni; Sterrantino, Gaetana

2017-09-22

Virological success (VS) and immunological reconstitution (IR) of antiretroviral-naive HIV-1-infected patients with pre-therapy viral load (VL) >500,000 copies/ml was assessed after 12 months of treatment according to initial drug-class regimens. An observational multicentre retrospective study was performed. VS was defined as the first VL <50 copies/ml from treatment start. IR was defined as an increase of at least 150 CD4 + T-lymphocytes from treatment start. Survival analysis was used to estimate the probability and predictors of VS and IR by 12 months of therapy. 428 HIV-1-infected patients were analysed. Patients were grouped according to the different first-line drug-classes used: a non-nucleoside reverse transcriptase inhibitor (NNRTI) plus two nucleoside reverse transcriptase inhibitors (NRTIs; NNRTI-group; n=105 [24.5%]); a protease inhibitor (PI) plus two NRTIs (PI-group; n=260 [60.8%]); a four-drug regimen containing a PI-regimen plus an integrase inhibitor (PI+INI-group; n=63 [14.7%]). Patients in the PI-group showed the lowest probability of VS (PI-group: 72.4%; NNRTI-group: 75.5%; PI+INI-group: 81.0%; P<0.0001). By Cox regression, patients in PI+INI and NNRTI-groups showed a higher adjusted hazard ratio (95% CI) of VS compared to those in the PI-group (PI+INI-group: 1.48 [1.08, 2.03]; P=0.014; NNRTI-group: 1.37 [1.06-1.78]; P=0.015). The probability of IR was 76.2%, and was similar among groups. Patients with AIDS showed a lower adjusted hazard ratio (95% CI) of IR compared to non-AIDS presenters (0.70 [0.54, 0.90]; P=0.005). In this multicentre retrospective study, patients with viraemia >500,000 copies/ml who start a first-line regimen containing PI+INI or NNRTI yield a better VS compared to those receiving a PI-based regimen.

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

[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.

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

PubMed

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

2015-03-01

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

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.

Effects of exercise intensity and nutrition advice on myocardial function in obese children and adolescents: a multicentre randomised controlled trial study protocol

PubMed Central

Dias, Katrin A; Coombes, Jeff S; Green, Daniel J; Gomersall, Sjaan R; Keating, Shelley E; Tjonna, Arnt Erik; Hollekim-Strand, Siri Marte; Hosseini, Mansoureh Sadat; Ro, Torstein Baade; Haram, Margrete; Huuse, Else Marie; Davies, Peter S W; Cain, Peter A; Leong, Gary M; Ingul, Charlotte B

2016-01-01

Introduction The prevalence of paediatric obesity is increasing, and with it, lifestyle-related diseases in children and adolescents. High-intensity interval training (HIIT) has recently been explored as an alternate to traditional moderate-intensity continuous training (MICT) in adults with chronic disease and has been shown to induce a rapid reversal of subclinical disease markers in obese children and adolescents. The primary aim of this study is to compare the effects of HIIT with MICT on myocardial function in obese children and adolescents. Methods and analysis Multicentre randomised controlled trial of 100 obese children and adolescents in the cities of Trondheim (Norway) and Brisbane (Australia). The trial will examine the efficacy of HIIT to improve cardiometabolic outcomes in obese children and adolescents. Participants will be randomised to (1) HIIT and nutrition advice, (2) MICT and nutrition advice or (3) nutrition advice. Participants will partake in supervised exercise training and/or nutrition sessions for 3 months. Measurements for study end points will occur at baseline, 3 months (postintervention) and 12 months (follow-up). The primary end point is myocardial function (peak systolic tissue velocity). Secondary end points include vascular function (flow-mediated dilation assessment), quantity of visceral and subcutaneous adipose tissue, myocardial structure and function, body composition, cardiorespiratory fitness, autonomic function, blood biochemistry, physical activity and nutrition. Lean, healthy children and adolescents will complete measurements for all study end points at one time point for comparative cross-sectional analyses. Ethics and dissemination This randomised controlled trial will generate substantial information regarding the effects of exercise intensity on paediatric obesity, specifically the cardiometabolic health of this at-risk population. It is expected that communication of results will allow for the development of more effective evidence-based exercise prescription guidelines in this population while investigating the benefits of HIIT on subclinical markers of disease. Trial registration number NCT01991106. PMID:27044585

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

PubMed Central

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

2017-01-01

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

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.

Urinary lithogenesis risk tests: comparison of a commercial kit and a laboratory prototype test.

PubMed

Grases, Félix; Costa-Bauzá, Antonia; Prieto, Rafel M; Arrabal, Miguel; De Haro, Tomás; Lancina, Juan A; Barbuzano, Carmen; Colom, Sergi; Riera, Joaquín; Perelló, Joan; Isern, Bernat; Sanchis, Pilar; Conte, Antonio; Barragan, Fernando; Gomila, Isabel

2011-11-01

Renal stone formation is a multifactorial process depending in part on urine composition. Other parameters relate to structural or pathological features of the kidney. To date, routine laboratory estimation of urolithiasis risk has been based on determination of urinary composition. This process requires collection of at least two 24 h urine samples, which is tedious for patients. The most important feature of urinary lithogenic risk is the balance between various urinary parameters, although unknown factors may be involved. The objective of this study was to compare data obtained using a commercial kit with those of a laboratory prototype, using a multicentre approach, to validate the utility of these methods in routine clinical practice. A simple new commercial test (NefroPlus®; Sarstedt AG & Co., Nümbrecht, Germany) evaluating the capacity of urine to crystallize calcium salts, and thus permitting detection of patients at risk for stone development, was compared with a prototype test previously described by this group. Urine of 64 volunteers produced during the night was used in these comparisons. The commercial test was also used to evaluate urine samples of 83 subjects in one of three hospitals. Both methods were essentially in complete agreement (98%) with respect to test results. The multicentre data were: sensitivity 94.7%; specificity 76.9%; positive predictive value (lithogenic urine) 90.0%; negative predictive value (non-lithogenic urine) 87.0%; test efficacy 89.2%. The new commercial NefroPlus test offers fast and cheap evaluation of the overall risk of development of urinary calcium-containing calculi.

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

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.

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.

Study for every other day administration of vonoprazan in maintenance treatment of erosive GERD: study protocol for a multicentre randomised cross-over study.

PubMed

Kato, Mototsugu; Ito, Noriko; Demura, Mamiko; Kubo, Kimitoshi; Mabe, Katsuhiro; Harada, Naohiko

2018-01-01

The first drug selected for treatment of gastro-oesophageal reflux disease (GERD) and prevention of the recurrence is a proton pump inhibitor (PPI), but recently, a potassium-competitive acid blocker (P-CAB) was put on the market in Japan. Its onset of effect is faster than PPI, and it takes more than 2 days to recover acid secretion after the withdrawal period. Therefore, unlike PPI, the usefulness of every other day administration or discontinuous administration is expected. This study is a prospective, multicentre, open-label, two-period randomised cross-over study to compare the efficacy and safety of PPI every other day administration and P-CAB every other day administration in 120 patients who receive erosive GERD maintenance therapy with PPI. Patients will be randomly allocated to receive 4 weeks P-CAB or PPI followed by 4 weeks cross over, where those on P-CAB will receive PPI and vice versa. The primary endpoint is proportion of asymptomatic patients. Secondary endpoints are suppressive effect of GERD symptoms, proportion of asymptomatic patients at each time point, safety and cost-saving effect of P-CAB every other day administration, compliance with every other day administration, and proportion of asymptomatic patients at the first month of study drug administration. This study was approved by the National Hospital Organization Central Review Board for Clinical Trials (5 December 2017). If P-CAB every other day administration is established as one of GERD maintenance therapies, there is merit in both medical cost reduction and the safety to alleviate elevation in serum gastrin. UMIN000034701.

Study for every other day administration of vonoprazan in maintenance treatment of erosive GERD: study protocol for a multicentre randomised cross-over study

PubMed Central

Kato, Mototsugu; Ito, Noriko; Demura, Mamiko; Kubo, Kimitoshi; Mabe, Katsuhiro; Harada, Naohiko

2018-01-01

Introduction The first drug selected for treatment of gastro-oesophageal reflux disease (GERD) and prevention of the recurrence is a proton pump inhibitor (PPI), but recently, a potassium-competitive acid blocker (P-CAB) was put on the market in Japan. Its onset of effect is faster than PPI, and it takes more than 2 days to recover acid secretion after the withdrawal period. Therefore, unlike PPI, the usefulness of every other day administration or discontinuous administration is expected. Methods and analysis This study is a prospective, multicentre, open-label, two-period randomised cross-over study to compare the efficacy and safety of PPI every other day administration and P-CAB every other day administration in 120 patients who receive erosive GERD maintenance therapy with PPI. Patients will be randomly allocated to receive 4 weeks P-CAB or PPI followed by 4 weeks cross over, where those on P-CAB will receive PPI and vice versa. The primary endpoint is proportion of asymptomatic patients. Secondary endpoints are suppressive effect of GERD symptoms, proportion of asymptomatic patients at each time point, safety and cost-saving effect of P-CAB every other day administration, compliance with every other day administration, and proportion of asymptomatic patients at the first month of study drug administration. Ethics and dissemination This study was approved by the National Hospital Organization Central Review Board for Clinical Trials (5 December 2017). Discussion If P-CAB every other day administration is established as one of GERD maintenance therapies, there is merit in both medical cost reduction and the safety to alleviate elevation in serum gastrin. Trial registration number UMIN000034701. PMID:29527318

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.

[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.

Outcome of physiotherapy after surgery for cervical disc disease: a prospective randomised multi-centre trial

PubMed Central

2014-01-01

Background Many patients with cervical disc disease require leave from work, due to long-lasting, complex symptoms, including chronic pain and reduced levels of physical and psychological function. Surgery on a few segmental levels might be expected to resolve disc-specific pain and reduce neurological deficits, but not the non-specific neck pain and the frequent illness. No study has investigated whether post-surgery physiotherapy might improve the outcome of surgery. The main purpose of this study was to evaluate whether a well-structured rehabilitation programme might add benefit to the customary post-surgical treatment for cervical disc disease, with respect to function, disability, work capability, and cost effectiveness. Methods/Design This study was designed as a prospective, randomised, controlled, multi-centre study. An independent, blinded investigator will compare two alternatives of rehabilitation. We will include 200 patients of working age, with cervical disc disease confirmed by clinical findings and symptoms of cervical nerve root compression. After providing informed consent, study participants will be randomised to one of two alternative physiotherapy regimes; (A) customary treatment (information and advice on a specialist clinic); or (B) customary treatment plus active physiotherapy. Physiotherapy will follow a standardised, structured programme of neck-specific exercises combined with a behavioural approach. All patients will be evaluated both clinically and subjectively (with questionnaires) before surgery and at 6 weeks, 3 months, 6 months, 12 months, and 24 months after surgery. The main outcome variable will be neck-specific disability. Cost-effectiveness will also be calculated. Discussion We anticipate that the results of this study will provide evidence to support physiotherapeutic rehabilitation applied after surgery for cervical radiculopathy due to cervical disc disease. Trial registration ClinicalTrials.gov identifier: NCT01547611 PMID:24502414

The nutrition-based comprehensive intervention study on childhood obesity in China (NISCOC): a randomised cluster controlled trial.

PubMed

Li, Yanping; Hu, Xiaoqi; Zhang, Qian; Liu, Ailing; Fang, Hongyun; Hao, Linan; Duan, Yifan; Xu, Haiquan; Shang, Xianwen; Ma, Jun; Xu, Guifa; Du, Lin; Li, Ying; Guo, Hongwei; Li, Tingyu; Ma, Guansheng

2010-05-02

Childhood obesity and its related metabolic and psychological abnormalities are becoming serious health problems in China. Effective, feasible and practical interventions should be developed in order to prevent the childhood obesity and its related early onset of clinical cardiovascular diseases. The objective of this paper is to describe the design of a multi-centred random controlled school-based clinical intervention for childhood obesity in China. The secondary objective is to compare the cost-effectiveness of the comprehensive intervention strategy with two other interventions, one only focuses on nutrition education, the other only focuses on physical activity. The study is designed as a multi-centred randomised controlled trial, which included 6 centres located in Beijing, Shanghai, Chongqing, Shandong province, Heilongjiang province and Guangdong province. Both nutrition education (special developed carton style nutrition education handbook) and physical activity intervention (Happy 10 program) will be applied in all intervention schools of 5 cities except Beijing. In Beijing, nutrition education intervention will be applied in 3 schools and physical activity intervention among another 3 schools. A total of 9750 primary students (grade 1 to grade 5, aged 7-13 years) will participate in baseline and intervention measurements, including weight, height, waist circumference, body composition (bioelectrical impendence device), physical fitness, 3 days dietary record, physical activity questionnaire, blood pressure, plasma glucose and plasma lipid profiles. Data concerning investments will be collected in our study, including costs in staff training, intervention materials, teachers and school input and supervising related expenditure. Present study is the first and biggest multi-center comprehensive childhood obesity intervention study in China. Should the study produce comprehensive results, the intervention strategies would justify a national school-based program to prevent childhood obesity in China.

Burnout, psychological morbidity and use of coping mechanisms among palliative care practitioners: A multi-centre cross-sectional study.

PubMed

Koh, Mervyn Yong Hwang; Chong, Poh Heng; Neo, Patricia Soek Hui; Ong, Yew Jin; Yong, Woon Chai; Ong, Wah Ying; Shen, Mira Li Juan; Hum, Allyn Yin Mei

2015-07-01

The prevalence of burnout, psychological morbidity and the use of coping mechanisms among palliative care practitioners in Singapore have not been studied. We aimed to study the prevalence of burnout and psychological morbidity among palliative care practitioners in Singapore and its associations with demographic and workplace factors as well as the use of coping mechanisms. This was a multi-centre, cross-sectional study of all the palliative care providers within the public healthcare sector in Singapore. The study was conducted in hospital palliative care services, home hospice and inpatient hospices in Singapore. The participants were doctors, nurses and social workers. The prevalence of burnout among respondents in our study was 91 of 273 (33.3%) and psychological morbidity was 77 (28.2%). Working >60 h per week was significantly associated with burnout (odds ratio: 9.02, 95% confidence interval: 2.3-35.8, p = 0.002) and psychological morbidity (odds ratio: 7.21, 95% confidence interval: 1.8-28.8, p = 0.005). Home hospice care practitioners (41.5%) were more at risk of developing psychological morbidity compared to hospital-based palliative care (17.5%) or hospice inpatient care (26.0%) (p = 0.007). Coping mechanisms like physical well-being, clinical variety, setting boundaries, transcendental (meditation and quiet reflection), passion for one's work, realistic expectations, remembering patients and organisational activities were associated with less burnout. Our results reveal that burnout and psychological morbidity are significant in the palliative care community and demonstrate a need to look at managing long working hours and promoting the use of coping mechanisms to reduce burnout and psychological morbidity. © The Author(s) 2015.

Diverging effects of diabetes mellitus in patients with peripheral artery disease and abdominal aortic aneurysm and the role of advanced glycation end-products: ARTERY study - protocol for a multicentre cross-sectional study.

PubMed

de Vos, L C; Boersema, J; Hillebrands, J L; Schalkwijk, C G; Meerwaldt, R; Breek, J C; Smit, A J; Zeebregts, C J; Lefrandt, J D

2017-04-11

Diabetes mellitus is a well-defined risk factor for peripheral artery disease (PAD), but protects against the development and growth of abdominal aortic aneurysm (AAA). Diabetes mellitus is associated with arterial stiffening and peripheral arterial media sclerosis. Advanced glycation end-products (AGEs) are increased in diabetes mellitus and cardiovascular disease. AGEs are known to form cross-links between proteins and are associated with arterial stiffness. Whether AGEs contribute to the protective effects of diabetes mellitus in AAA is unknown. Therefore, the ARTERY ( A dvanced glycation end-p R oducts in patients with peripheral ar T ery dis E ase and abdominal ao R tic aneur Y sm) study is designed to evaluate the role of AGEs in the diverging effects of diabetes mellitus on AAA and PAD. This cross-sectional multicentre study will compare the amount, type and location of AGEs in the arterial wall in a total of 120 patients with AAA or PAD with and without diabetes mellitus (n=30 per subgroup). Also, local and systemic vascular parameters, including pulse wave velocity, will be measured to evaluate the association between arterial stiffness and AGEs. Finally, AGEs will be measured in serum, urine, and assessed in skin with skin autofluorescence using the AGE Reader. This study is approved by the Medical Ethics committees of University Medical Center Groningen, Martini Hospital and Medisch Spectrum Twente, the Netherlands. Study results will be disseminated through peer-reviewed journals and scientific events. trialregister.nl NTR 5363. 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/.

Safety and effectiveness of antiretroviral drugs during pregnancy, delivery and breastfeeding for prevention of mother-to-child transmission of HIV-1: the Kesho Bora Multicentre Collaborative Study rationale, design, and implementation challenges.

PubMed

2011-01-01

To evaluate strategies to reduce HIV-1 transmission through breastfeeding, a multicentre study including a nested randomized controlled trial was implemented in five research sites in West, East and South Africa (The Kesho Bora Study). The aim was to optimize the use of antiretroviral (ARV) drugs during pregnancy, delivery and breastfeeding to prevent mother-to-child transmission of HIV-1 (PMTCT) and to preserve the health of the HIV-1-infected mother. The study included long-term ARV treatment for women with advanced disease, and short-course ARV prophylaxis stopped at delivery for women with early disease. Women with intermediate disease participated in a randomized controlled trial to compare safety and efficacy of triple-ARV prophylaxis prolonged during breastfeeding with short-course ARV prophylaxis stopped at delivery. Between January 2005 and August 2008 a total of 1140 women were enrolled. This paper describes the study design, interventions and protocol amendments introduced to adapt to evolving scientific knowledge, international guidelines and availability of ARV treatment. The paper highlights the successes and challenges during the conduct of the trial. The Kesho Bora Study included one of the few randomized controlled trials to assess safety and efficacy of ARV prophylaxis continued during breastfeeding and the only randomized trial to assess maternal prophylaxis started during pregnancy. The findings have been important for informing international and national guidelines on MTCT prevention in developing countries where, due to poverty, lack of reliable and affordable supply of replacement feed and stigma associated with HIV/AIDS, HIV-infected women have little or no option other than to breastfeed their infants. (ISRCTN71468401). Copyright © 2010 Elsevier Inc. All rights reserved.

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

PubMed

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

2017-03-25

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

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

PubMed

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

2012-04-01

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

Immunophenotypic analysis of the Kaposi sarcoma herpesvirus (KSHV; HHV-8)-infected B cells in HIV+ multicentric Castleman disease (MCD).

PubMed

Chadburn, A; Hyjek, E M; Tam, W; Liu, Y; Rengifo, T; Cesarman, E; Knowles, D M

2008-11-01

Kaposi sarcoma herpesvirus (KSHV) is aetiologically related to Kaposi sarcoma, classical and extracavitary primary effusion lymphoma (PEL; EC-PEL) and multicentric Castleman disease (MCD), entities preferentially occurring in HIV-infected individuals. Characterization of HIV-associated PELs/EC-PELs suggests that the KSHV-infected malignant cells originate from a pre-terminal stage of B-cell differentiation. However, only limited phenotypic studies have been performed on HIV+ MCD, including for PR domain containing 1 with zinc finger domain/B lymphocyte-induced maturation protein 1 (PRDM1/BLIMP1), a key regulator of terminal B-cell differentiation. The aim was to characterize KSHV-infected cells in 17 cases of HIV+ MCD. Double immunohistochemistry and immunohistochemistry-in situ hybridization were used to characterize the KSHV-infected cells in MCD; the results were compared with the phenotypic profiles of 39 PELs/EC-PELs and seven PEL cell lines. Whereas the immunophenotype of KSHV-infected cells in MCD and malignant KSHV+ PEL cells was similar (PAX5, Bcl-6-; PRDM1/BLIMP1, IRF4/MUM1+; Ki67+), the MCD KSHV-infected cells differed, as they expressed OCT2, cytoplasmic lambda immunoglobulin; variably expressed CD27; lacked CD138; and were Epstein-Barr virus negative. Although both PEL and MCD originate from KSHV-infected pre-terminally differentiated B cells, these findings, with previously reported genetic studies, indicate HIV+ MCD may arise from extrafollicular B cells, whereas PELs may originate from cells that have traversed the germinal centre.

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.

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

PubMed Central

2010-01-01

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

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.

Effects of closed-loop stimulation vs. DDD pacing on haemodynamic variations and occurrence of syncope induced by head-up tilt test in older patients with refractory cardioinhibitory vasovagal syncope: the Tilt test-Induced REsponse in Closed-loop Stimulation multicentre, prospective, single blind, randomized study.

PubMed

Palmisano, Pietro; Dell'Era, Gabriele; Russo, Vincenzo; Zaccaria, Maria; Mangia, Rolando; Bortnik, Miriam; De Vecchi, Federica; Giubertoni, Ailia; Patti, Fabiana; Magnani, Andrea; Nigro, Gerardo; Rago, Anna; Occhetta, Eraldo; Accogli, Michele

2018-05-01

Closed-loop stimulation (CLS) seemed promising in preventing the recurrence of vasovagal syncope (VVS) in patients with a cardioinhibitory response to head-up tilt test (HUTT) compared with conventional pacing. We hypothesized that the better results of this algorithm are due to its quick reaction in high-rate pacing delivered in the early phase of vasovagal reflex, which increase the cardiac output and the blood pressure preventing loss of consciousness. This prospective, randomized, single-blind, multicentre study was designed as an intra-patient comparison and enrolled 30 patients (age 62.2 ± 13.5 years, males 60.0%) with cardioinhibitory VVS, carrying a dual-chamber pacemaker incorporating CLS algorithm. Two HUTTs were performed one week apart: one during DDD-CLS 60-130/min pacing and the other during DDD 60/min pacing; patients were randomly and blindly assigned to two groups: in one the first HUTT was performed in DDD-CLS (n = 15), in the other in DDD (n = 15). Occurrence of syncope and haemodynamic variations induced by HUTT was recorded during the tests. Compared with DDD, DDD-CLS significantly reduced the occurrence of syncope induced by HUTT (30.0% vs. 76.7%; P < 0.001). In the patients who had syncope in both DDD and DDD-CLS mode, DDD-CLS significantly delayed the onset of syncope during HUTT (from 20.8 ± 3.9 to 24.8 ± 0.9 min; P = 0.032). The maximum fall in systolic blood pressure recorded during HUTT was significantly lower in DDD-CLS compared with DDD (43.2 ± 30.3 vs. 65.1 ± 25.8 mmHg; P = 0.004). In patients with cardioinhibitory VVS, CLS reduces the occurrence of syncope induced by HUTT, compared with DDD pacing. When CLS is not able to abort the vasovagal reflex, it seems to delay the onset of syncope.

Non-invasive diagnosis of acute rejection in renal transplant patients using mass spectrometry of urine samples - a multicentre phase 3 diagnostic accuracy study.

PubMed

Zapf, Antonia; Gwinner, Wilfried; Karch, Annika; Metzger, Jochen; Haller, Hermann; Koch, Armin

2015-09-15

Reliable and timely detection of acute rejection in renal transplant patients is important to preserve the allograft function and to prevent premature allograft failure. The current gold standard for the rejection diagnosis is an allograft biopsy which is usually performed upon an unexplained decline in allograft function. Because of the invasiveness of the biopsy, non-invasive tests have been suggested to diagnose acute rejection including mass spectrometry analysis of urine samples. The aim of this study is to examine the diagnostic accuracy of mass spectrometry analysis in urine for the diagnosis of acute rejections using the biopsy as gold-standard. The study is an ongoing prospective, single-arm, multicentre, phase 3 diagnostic accuracy study. It started in October 2011 and will be concluded in December 2015. Patient within the first year after transplantation who are scheduled for a biopsy to clarify unexplained impairment of the allograft are consecutively recruited into the study. The overall sample size (n = 600) was calculated to demonstrate a sensitivity of 83 % and a specificity of 70 % for a one-sided type one error of 2.5 % and a power of 80 % per hypothesis. Biopsy evaluation and mass spectrometry analysis of urine samples (obtained immediately before biopsy) are performed independently by different readers without knowledge from the respective other assessment. The follow-up observation period is 6 months. For the primary analysis, the lower limits of the two-sided 95 % Wald confidence intervals for sensitivity and specificity will be compared with the pre-specified thresholds (83 % for sensitivity and 70 % for specificity). In secondary analyses the predictive values, the diagnostic measures in subgroups, and the clinical course will be assessed. Previous phase 2 diagnostic accuracy studies (in small selected study populations) provided sufficient evidence to suggest mass spectrometry on urine samples as a promising approach to detect acute rejections. This study determines the diagnostic performance of the test in the routine setting of post-transplant patient care, compared to the biopsy-based rejection diagnosis. The next step would be a randomized trial to compare the two diagnostic strategies (including the urine test or not) in relation to patient relevant endpoints. NCT01315067 ; March 14, 2011.

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.

A pragmatic multi-centre randomised controlled trial of fluid loading in high-risk surgical patients undergoing major elective surgery--the FOCCUS study.

PubMed

Cuthbertson, Brian H; Campbell, Marion K; Stott, Stephen A; Elders, Andrew; Hernández, Rodolfo; Boyers, Dwayne; Norrie, John; Kinsella, John; Brittenden, Julie; Cook, Jonathan; Rae, Daniela; Cotton, Seonaidh C; Alcorn, David; Addison, Jennifer; Grant, Adrian

2011-01-01

Fluid strategies may impact on patient outcomes in major elective surgery. We aimed to study the effectiveness and cost-effectiveness of pre-operative fluid loading in high-risk surgical patients undergoing major elective surgery. This was a pragmatic, non-blinded, multi-centre, randomised, controlled trial. We sought to recruit 128 consecutive high-risk surgical patients undergoing major abdominal surgery. The patients underwent pre-operative fluid loading with 25 ml/kg of Ringer's solution in the six hours before surgery. The control group had no pre-operative fluid loading. The primary outcome was the number of hospital days after surgery with cost-effectiveness as a secondary outcome. A total of 111 patients were recruited within the study time frame in agreement with the funder. The median pre-operative fluid loading volume was 1,875 ml (IQR 1,375 to 2,025) in the fluid group compared to 0 (IQR 0 to 0) in controls with days in hospital after surgery 12.2 (SD 11.5) days compared to 17.4 (SD 20.0) and an adjusted mean difference of 5.5 days (median 2.2 days; 95% CI -0.44 to 11.44; P = 0.07). There was a reduction in adverse events in the fluid intervention group (P = 0.048) and no increase in fluid based complications. The intervention was less costly and more effective (adjusted average cost saving: £2,047; adjusted average gain in benefit: 0.0431 quality adjusted life year (QALY)) and has a high probability of being cost-effective. Pre-operative intravenous fluid loading leads to a non-significant reduction in hospital length of stay after high-risk major surgery and is likely to be cost-effective. Confirmatory work is required to determine whether these effects are reproducible, and to confirm whether this simple intervention could allow more cost-effective delivery of care. Prospective Clinical Trials, ISRCTN32188676.

A pragmatic multi-centre randomised controlled trial of fluid loading in high-risk surgical patients undergoing major elective surgery - the FOCCUS study

PubMed Central

2011-01-01

Introduction Fluid strategies may impact on patient outcomes in major elective surgery. We aimed to study the effectiveness and cost-effectiveness of pre-operative fluid loading in high-risk surgical patients undergoing major elective surgery. Methods This was a pragmatic, non-blinded, multi-centre, randomised, controlled trial. We sought to recruit 128 consecutive high-risk surgical patients undergoing major abdominal surgery. The patients underwent pre-operative fluid loading with 25 ml/kg of Ringer's solution in the six hours before surgery. The control group had no pre-operative fluid loading. The primary outcome was the number of hospital days after surgery with cost-effectiveness as a secondary outcome. Results A total of 111 patients were recruited within the study time frame in agreement with the funder. The median pre-operative fluid loading volume was 1,875 ml (IQR 1,375 to 2,025) in the fluid group compared to 0 (IQR 0 to 0) in controls with days in hospital after surgery 12.2 (SD 11.5) days compared to 17.4 (SD 20.0) and an adjusted mean difference of 5.5 days (median 2.2 days; 95% CI -0.44 to 11.44; P = 0.07). There was a reduction in adverse events in the fluid intervention group (P = 0.048) and no increase in fluid based complications. The intervention was less costly and more effective (adjusted average cost saving: £2,047; adjusted average gain in benefit: 0.0431 quality adjusted life year (QALY)) and has a high probability of being cost-effective. Conclusions Pre-operative intravenous fluid loading leads to a non-significant reduction in hospital length of stay after high-risk major surgery and is likely to be cost-effective. Confirmatory work is required to determine whether these effects are reproducible, and to confirm whether this simple intervention could allow more cost-effective delivery of care. Trial registration Prospective Clinical Trials, ISRCTN32188676 PMID:22177541

Multicentre randomized controlled trial comparing ferric(III)carboxymaltose infusion with oral iron supplementation in the treatment of preoperative anaemia in colorectal cancer patients.

PubMed

Borstlap, W A A; Buskens, C J; Tytgat, K M A J; Tuynman, J B; Consten, E C J; Tolboom, R C; Heuff, G; van Geloven, N; van Wagensveld, B A; C A Wientjes, C A; Gerhards, M F; de Castro, S M M; Jansen, J; van der Ven, A W H; van der Zaag, E; Omloo, J M; van Westreenen, H L; Winter, D C; Kennelly, R P; Dijkgraaf, M G W; Tanis, P J; Bemelman, W A

2015-06-28

At least a third of patients with a colorectal carcinoma who are candidate for surgery, are anaemic preoperatively. Preoperative anaemia is associated with increased morbidity and mortality. In general practice, little attention is paid to these anaemic patients. Some will have oral iron prescribed others not. The waiting period prior to elective colorectal surgery could be used to optimize a patients' physiological status. The aim of this study is to determine the efficacy of preoperative intravenous iron supplementation in comparison with the standard preoperative oral supplementation in anaemic patients with colorectal cancer. In this multicentre randomized controlled trial, patients with an M0-staged colorectal carcinoma who are scheduled for curative resection and with a proven iron deficiency anaemia are eligible for inclusion. Main exclusion criteria are palliative surgery, metastatic disease, neoadjuvant chemoradiotherapy (5 × 5 Gy = no exclusion) and the use of Recombinant Human Erythropoietin within three months before inclusion or a blood transfusion within a month before inclusion. Primary endpoint is the percentage of patients that achieve normalisation of the haemoglobin level between the start of the treatment and the day of admission for surgery. This study is a superiority trial, hypothesizing a greater proportion of patients achieving the primary endpoint in favour of iron infusion compared to oral supplementation. A total of 198 patients will be randomized to either ferric(III)carboxymaltose infusion in the intervention arm or ferrofumarate in the control arm. This study will be performed in ten centres nationwide and one centre in Ireland. This is the first randomized controlled trial to determine the efficacy of preoperative iron supplementation in exclusively anaemic patients with a colorectal carcinoma. Our trial hypotheses a more profound haemoglobin increase with intravenous iron which may contribute to a superior optimisation of the patient's condition and possibly a decrease in postoperative morbidity. ClincalTrials.gov: NCT02243735 .

Comparison between repaglinide and glipizide in Type 2 diabetes mellitus: a 1-year multicentre study.

PubMed

Madsbad, S; Kilhovd, B; Lager, I; Mustajoki, P; Dejgaard, A

2001-05-01

To evaluate the long-term effectiveness and safety of repaglinide, a novel prandial glucose regulator, in comparison with glipizide in the treatment of patients with Type 2 diabetes. Diet or tablet-treated patients with Type 2 diabetes (n = 256; age 40-75 years, body mass index (BMI) 20-35 kg/m2, HbA1c 4.2-12.8%), without signs of severe microvascular or macrovascular complications, were included in this double-blind, multicentre, parallel-group comparative trial. Patients were randomized at a 2:1 ratio to repaglinide, 1-4 mg at mealtimes, or glipizide, 5-15 mg daily. Changes in fasting blood glucose (FBG) and HbA1c during the 12 months of treatment showed a significant difference in favour of repaglinide. In oral hypoglycaemic agents (OHA)-naive patients, HbA1c decreased in the repaglinide and glipizide groups by 1.5% and 0.3%, respectively (P < 0.05 between groups). Fasting blood glucose decreased in the repaglinide group by 2.4 mmol/l and increased in the glipizide group by 1.0 mmol/l (P < 0.05 between groups). In the study population as a whole, repaglinide was able to maintain glycaemic control (HbA1c level) during the 1-year study period, whereas control deteriorated significantly with glipizide. Change in HbA1c from baseline was significantly better with repaglinide than with glipizide after 12 months (P < 0.05). In addition, FBG deteriorated significantly in the glipizide group compared with the repaglinide group (P < 0.05). No patients in either group experienced a major hypoglycaemic event; the number of patients experiencing minor hypoglycaemia was similar in the repaglinide and glipizide groups (15% and 19%, respectively). Repaglinide, given as a prandial glucose regulator, is shown to be an effective and safe treatment of patients with Type 2 diabetes, and is better than glipizide in controlling HbA1c and FBG levels, overall, and in OHA-naive patients.

Efficacy of ethinylestradiol 20 μg/drospirenone 3 mg in a flexible extended regimen in women with moderate-to-severe primary dysmenorrhoea: an open-label, multicentre, randomised, controlled study.

PubMed

Strowitzki, Thomas; Kirsch, Bodo; Elliesen, Jörg

2012-04-01

The aim of this Phase III, multicentre, open-label, randomised study was to compare the efficacy and safety of ethinylestradiol (EE)/drospirenone (DRSP) in a new flexible extended regimen that allowed the management of intracyclic (breakthrough) bleeding (MIB) with that of EE/DRSP in a conventional 28-day regimen in women with moderate-to-severe primary dysmenorrhoea. Women (aged 18-40 years) with moderate-to-severe primary dysmenorrhoea-related pain received a flexible extended regimen with MIB (flexible(MIB); minimum 24, maximum 120 days of continuous tablet intake for a flexible number of cycles to reach a treatment duration of at least 140 days with 4-day breaks between cycles) or a conventional 28-day regimen (24 active and four placebo tablets for five cycles) of EE/DRSP. The primary outcome was the number of days with dysmenorrhoeic pain over 140 days. Secondary outcomes included other dysmenorrhoea-related pain outcomes, bleeding profile, satisfaction and safety. Overall, 223 patients received study medication. There were significantly fewer days with dysmenorrhoeic pain with the flexible(MIB) regimen than the conventional regimen (difference -4.2 days, 95% CI -6.5 to -2.0; p=0.0003), as well as considerably fewer days with at least moderate dysmenorrhoeic pain (difference -2.5 days, 95% CI -3.7 to -1.3), dysmenorrhoeic pain that interfered with daily activities (difference -2.2 days, 95% CI -4.2 to -0.1) and pelvic pain (difference -3.4 days, 95% CI -5.9 to -0.9). Adverse events were similar with both regimens. Compared with the conventional regimen, the flexible extended regimen of EE/DRSP with MIB was associated with a significantly greater reduction in days with dysmenorrhoeic pain in women with moderate-to-severe primary dysmenorrhoea. The flexible(MIB) regimen was also associated with greater improvements in dysmenorrhea according to the Clinical Global Impression rating scale and was generally well tolerated.

Strategies to diagnose ovarian cancer: new evidence from phase 3 of the multicentre international IOTA study

PubMed Central

Testa, A; Kaijser, J; Wynants, L; Fischerova, D; Van Holsbeke, C; Franchi, D; Savelli, L; Epstein, E; Czekierdowski, A; Guerriero, S; Fruscio, R; Leone, F P G; Vergote, I; Bourne, T; Valentin, L; Van Calster, B; Timmerman, D

2014-01-01

Background: To compare different ultrasound-based international ovarian tumour analysis (IOTA) strategies and risk of malignancy index (RMI) for ovarian cancer diagnosis using a meta-analysis approach of centre-specific data from IOTA3. Methods: This prospective multicentre diagnostic accuracy study included 2403 patients with 1423 benign and 980 malignant adnexal masses from 2009 until 2012. All patients underwent standardised transvaginal ultrasonography. Test performance of RMI, subjective assessment (SA) of ultrasound findings, two IOTA risk models (LR1 and LR2), and strategies involving combinations of IOTA simple rules (SRs), simple descriptors (SDs) and LR2 with and without SA was estimated using a meta-analysis approach. Reference standard was histology after surgery. Results: The areas under the receiver operator characteristic curves of LR1, LR2, SA and RMI were 0.930 (0.917–0.942), 0.918 (0.905–0.930), 0.914 (0.886–0.936) and 0.875 (0.853–0.894). Diagnostic one-step and two-step strategies using LR1, LR2, SR and SD achieved summary estimates for sensitivity 90–96%, specificity 74–79% and diagnostic odds ratio (DOR) 32.8–50.5. Adding SA when IOTA methods yielded equivocal results improved performance (DOR 57.6–75.7). Risk of Malignancy Index had sensitivity 67%, specificity 91% and DOR 17.5. Conclusions: This study shows all IOTA strategies had excellent diagnostic performance in comparison with RMI. The IOTA strategy chosen may be determined by clinical preference. PMID:24937676

Effect of endoscopic transpapillary biliary drainage with/without endoscopic sphincterotomy on post-endoscopic retrograde cholangiopancreatography pancreatitis in patients with biliary stricture (E-BEST): a protocol for a multicentre randomised controlled trial.

PubMed

Kato, Shin; Kuwatani, Masaki; Sugiura, Ryo; Sano, Itsuki; Kawakubo, Kazumichi; Ono, Kota; Sakamoto, Naoya

2017-08-11

The effect of endoscopic sphincterotomy prior to endoscopic biliary stenting to prevent post-endoscopic retrograde cholangiopancreatography pancreatitis remains to be fully elucidated. The aim of this study is to prospectively evaluate the non-inferiority of non-endoscopic sphincterotomy prior to stenting for naïve major duodenal papilla compared with endoscopic sphincterotomy prior to stenting in patients with biliary stricture. We designed a multicentre randomised controlled trial, for which we will recruit 370 patients with biliary stricture requiring endoscopic biliary stenting from 26 high-volume institutions in Japan. Patients will be randomly allocated to the endoscopic sphincterotomy group or the non-endoscopic sphincterotomy group. The main outcome measure is the incidence of pancreatitis within 2 days of initial transpapillary biliary drainage. Data will be analysed on completion of the study. We will calculate the 95% confidence intervals (CIs) of the incidence of pancreatitis in each group and analyse weather the difference in both groups with 95% CIs is within the non-inferiority margin (6%) using the Wald method. This study has been approved by the institutional review board of Hokkaido University Hospital (IRB: 016-0181). Results will be submitted for presentation at an international medical conference and published in a peer-reviewed journal. The University Hospital Medical Information Network ID: UMIN000025727 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.

Inclusion criteria provide heterogeneity in baseline profiles of patients with mild cognitive impairment: comparison of two prospective cohort studies

PubMed Central

Kawashima, Shoji; Kato, Takashi

2012-01-01

Background Mild cognitive impairment (MCI) is considered to represent a transitional stage between ageing and Alzheimer's disease (AD). To aim at identifying neuroimaging measures associated with cognitive changes in healthy elderly and MCI patients, longitudinal multicentre studies are ongoing in several countries. The patient profiles of each study are based on unique inclusion criteria. Objectives The purpose of the study is to clarify differences in baseline profiles of MCI patients between Studies on Diagnosis of Early Alzheimer's Disease—Japan (SEAD-J) and Alzheimer's Disease Neuroimaging Initiative (ADNI) and to examine the association between baseline profiles and risk of early conversion to AD. Design Prospective cohort study. Setting and participants SEAD-J recruited 114 patients from nine facilities in Japan. A total of 200 patients in ADNI with fluorodeoxyglucose–positron emission tomography (FDG-PET) were enrolled from the USA. Methods Baseline profiles were statistically analysed. For FDG-PET at a time of inclusion, associations between each profile and cerebral metabolic rate for glucose (CMRgl) were examined using SPM5 software. In each study, the ratio of conversion to AD within the 1-year and 2-year period after inclusion was investigated and differences in baseline profiles between AD converters and non-converters were analysed. Results SEAD-J included MCI patients with more severe verbal memory deficits and extracted patients with higher depressive tendencies. These differences were likely to be associated with criteria. SEAD-J exhibited a higher rate of conversion within 1 year compared with ADNI (24.5% vs 13.5%). In FDG-PET analyses of SEAD-J, AD converters within 1 year showed more severe decrease of FDG uptake in bilateral inferior parietal regions compared with non-converters. Conclusions Different inclusion criteria provided differences in baseline profiles. The severity of memory deficit might cause increase of the AD conversion within 1 year. Clinical outcomes of multicentre studies for early diagnosis of AD should be interpreted carefully considering profiles of patients. PMID:22535791

Aniracetam (Ro 13-5057) in the treatment of senile dementia of Alzheimer type (SDAT): results of a placebo controlled multicentre clinical study.

PubMed

Senin, U; Abate, G; Fieschi, C; Gori, G; Guala, A; Marini, G; Villardita, C; Parnetti, L

1991-12-01

One hundred and nine elderly patients suffering from mild to moderate cognitive impairment fulfilling NINCDS-ADRDA criteria for probable dementia of the Alzheimer type were treated for 6 months with a new nootropic drug, aniracetam (Ro 13-5057) in a double-blind randomized study versus placebo. The two treatment groups were comparable at baseline for demographic and behaviourial parameters and symptomatology. Patients underwent clinical, behaviourial and psychometric evaluation every other month. The aniracetam group differed significantly from the placebo group by the end of the study and also showed a statistically significant improvement versus baseline in the psychobehavioural parameters, while in the placebo group a steady deterioration was observed. Tolerability to aniracetam was excellent.

A randomised, double-blind, multicentre, parallel-group, prospective study comparing the pharmacokinetics, safety, and efficacy of CT-P13 and innovator infliximab in patients with ankylosing spondylitis: the PLANETAS study

PubMed Central

Park, Won; Hrycaj, Pawel; Jeka, Slawomir; Kovalenko, Volodymyr; Lysenko, Grygorii; Miranda, Pedro; Mikazane, Helena; Gutierrez-Ureña, Sergio; Lim, MieJin; Lee, Yeon-Ah; Lee, Sang Joon; Kim, HoUng; Yoo, Dae Hyun; Braun, Jürgen

2013-01-01

Objectives To compare the pharmacokinetics (PK), safety and efficacy of innovator infliximab (INX) and CT-P13, a biosimilar to INX, in patients with active ankylosing spondylitis (AS). Methods Phase 1 randomised, double-blind, multicentre, multinational, parallel-group study. Patients were randomised to receive 5 mg/kg of CT-P13 (n=125) or INX (n=125). Primary endpoints were area under the concentration-time curve (AUC) at steady state and observed maximum steady state serum concentration (Cmax,ss) between weeks 22 and 30. Additional PK, efficacy endpoints, including 20% and 40% improvement response according to Assessment in Ankylosing Spondylitis International Working Group criteria (ASAS20 and ASAS40), and safety outcomes were also assessed. Results Geometric mean AUC was 32 765.8 μgh/ml for CT-P13 and 31 359.3 μgh/ml for INX. Geometric mean Cmax,ss was 147.0  μg/ml for CT-P13 and 144.8 μg/ml for INX. The ratio of geometric means was 104.5% (90% CI 94% to 116%) for AUC and 101.5% (90% CI 95% to 109%) for Cmax,ss. ASAS20 and ASAS40 responses at week 30 were 70.5% and 51.8% for CT-P13 and 72.4% and 47.4% for INX, respectively. In the CT-P13 and INX groups more than one adverse event occurred in 64.8% and 63.9% of patients, infusion reactions occurred in 3.9% and 4.9%, active tuberculosis occurred in 1.6% and 0.8%, and 27.4% and 22.5% of patients tested positive for anti-drug antibodies, respectively. Conclusions The PK profiles of CT-P13 and INX were equivalent in patients with active AS. CT-P13 was well tolerated, with an efficacy and safety profile comparable to that of INX up to week 30. PMID:23687259

Open Abdomen Therapy with Vacuum and Mesh Mediated Fascial Traction After Aortic Repair: an International Multicentre Study.

PubMed

Acosta, Stefan; Seternes, Arne; Venermo, Maarit; Vikatmaa, Leena; Sörelius, Karl; Wanhainen, Anders; Svensson, Mats; Djavani, Khatereh; Björck, Martin

2017-12-01

Open abdomen therapy may be necessary to prevent or treat abdominal compartment syndrome (ACS). The aim of the study was to analyse the primary delayed fascial closure (PDFC) rate and complications after open abdomen therapy with vacuum and mesh mediated fascial traction (VACM) after aortic repair and to compare outcomes between those treated with open abdomen after primary versus secondary operation. This was a retrospective cohort, multicentre study in Sweden, Finland, and Norway, including consecutive patients treated with open abdomen and VACM after aortic repair at six vascular centres in 2006-2015. The primary endpoint was PDFC rate. Among 191 patients, 155 were men. The median age was 71 years (IQR 66-76). Ruptured abdominal aortic aneurysm (RAAA) occurred in 69.1%. Endovascular/hybrid and open repairs were performed in 49 and 142 patients, respectively. The indications for open abdomen were inability to close the abdomen (62%) at primary operation and ACS (80%) at secondary operation. Duration of open abdomen was 11 days (IQR 7-16) in 157 patients alive at open abdomen termination. The PDFC rate was 91.8%. Open abdomen initiated at primary (N=103), compared with secondary operation (N=88), was associated with less severe initial open abdomen status (p=.006), less intestinal ischaemia (p=.002), shorter duration of open abdomen (p=.007), and less renal replacement therapy (RRT, p<.001). In hospital mortality was 39.3%, and after entero-atmospheric fistula (N=9) was 88.9%. Seven developed graft infection within 6 months, 1 year mortality was 28.6%. Intestinal ischaemia (OR 3.71, 95% CI 1.55-8.91), RRT (OR 3.62, 95% CI 1.72-7.65), and age (OR 1.12, 95% CI 1.06-1.12), were independent factors associated with in hospital mortality, but not open abdomen initiated at primary versus secondary operation. VACM was associated with a high PDFC rate after prolonged open abdomen therapy following aortic repair. Patient outcomes seemed better when open abdomen was initiated at primary, compared with secondary operation but a selection effect is possible. Copyright © 2017 European Society for Vascular Surgery. Published by Elsevier Ltd. All rights reserved.

Collaborative derivation of reference intervals for major clinical laboratory tests in Japan.

PubMed

Ichihara, Kiyoshi; Yomamoto, Yoshikazu; Hotta, Taeko; Hosogaya, Shigemi; Miyachi, Hayato; Itoh, Yoshihisa; Ishibashi, Midori; Kang, Dongchon

2016-05-01

Three multicentre studies of reference intervals were conducted recently in Japan. The Committee on Common Reference Intervals of the Japan Society of Clinical Chemistry sought to establish common reference intervals for 40 laboratory tests which were measured in common in the three studies and regarded as well harmonized in Japan. The study protocols were comparable with recruitment mostly from hospital workers with body mass index ≤28 and no medications. Age and sex distributions were made equal to obtain a final data size of 6345 individuals. Between-subgroup differences were expressed as the SD ratio (between-subgroup SD divided by SD representing the reference interval). Between-study differences were all within acceptable levels, and thus the three datasets were merged. By adopting SD ratio ≥0.50 as a guide, sex-specific reference intervals were necessary for 12 assays. Age-specific reference intervals for females partitioned at age 45 were required for five analytes. The reference intervals derived by the parametric method resulted in appreciable narrowing of the ranges by applying the latent abnormal values exclusion method in 10 items which were closely associated with prevalent disorders among healthy individuals. Sex- and age-related profiles of reference values, derived from individuals with no abnormal results in major tests, showed peculiar patterns specific to each analyte. Common reference intervals for nationwide use were developed for 40 major tests, based on three multicentre studies by advanced statistical methods. Sex- and age-related profiles of reference values are of great relevance not only for interpreting test results, but for applying clinical decision limits specified in various clinical guidelines. © The Author(s) 2015.

Diversity of Clostridium difficile PCR ribotypes in Europe: results from the European, multicentre, prospective, biannual, point-prevalence study of Clostridium difficile infection in hospitalised patients with diarrhoea (EUCLID), 2012 and 2013.

PubMed

Davies, Kerrie A; Ashwin, Helen; Longshaw, Christopher M; Burns, David A; Davis, Georgina L; Wilcox, Mark H

2016-07-21

Clostridium difficile infection (CDI) is the major cause of infective diarrhoea in healthcare environments. As part of the European, multicentre, prospective, biannual, point-prevalence study of Clostridium difficile infection in hospitalised patients with diarrhoea (EUCLID), the largest C. difficile epidemiological study of its type, PCR ribotype distribution of C. difficile isolates in Europe was investigated. PCR ribotyping was performed on 1,196 C. difficile isolates from diarrhoeal samples sent to the European coordinating laboratory in 2012-13 and 2013 (from two sampling days) by 482 participating hospitals from 19 European countries. A total of 125 ribotypes were identified, of which ribotypes 027 (19%, n =222), 001/072 (11%, n = 134) and 014/020 (10%, n = 119) were the most prevalent. Distinct regional patterns of ribotype distribution were noted. Of 596 isolates from patients with toxin-positive stools (CDI cases), ribotype 027 accounted for 22% (32/144) of infections in cases aged from 18 to less than 65 years, but the prevalence decreased in those aged ≥ 65 years (14% (59/412)) and further decreased in those aged ≥ 81 years (9% (18/195)). The prevalence of ribotype 027 and 176, but not other epidemic strains, was inversely proportional to overall ribotype diversity (R(2) = 0.717). This study highlights an increased diversity of C. difficile ribotypes across Europe compared with previous studies, with considerable intercountry variation in ribotype distribution. Continuous surveillance programmes are necessary to monitor the changing epidemiology of C. difficile. This article is copyright of The Authors, 2016.

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.

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.

Stop or go? Preventive cognitive therapy with guided tapering of antidepressants during pregnancy: study protocol of a pragmatic multicentre non-inferiority randomized controlled trial.

PubMed

Molenaar, Nina M; Brouwer, Marlies E; Bockting, Claudi L H; Bonsel, Gouke J; van der Veere, Christine N; Torij, Hanneke W; Hoogendijk, Witte J G; Duvekot, Johannes J; Burger, Huibert; Lambregtse-van den Berg, Mijke P

2016-03-18

Approximately 6.2 % of women in the USA and 3.7 % of women in the UK, use Selective Serotonin Reuptake Inhibitors (SSRIs) during their pregnancies because of depression and/or anxiety. In the Netherlands, this prevalence is around 2 %. Nonetheless, SSRI use during pregnancy is still controversial. On the one hand SSRIs may be toxic to the intrauterine developing child, while on the other hand relapse or recurrence of depression during pregnancy poses risks for both mother and child. Among patients and professionals there is an urgent need for evidence from randomized studies to make rational decisions regarding continuation or tapering of SSRIs during pregnancy. At present, no such studies exist. 'Stop or Go' is a pragmatic multicentre randomized non-inferiority trial among 200 pregnant women with a gestational age of less than 16 weeks who use SSRIs without clinically relevant depressive symptoms. Women allocated to the intervention group will receive preventive cognitive therapy with gradual, guided discontinuation of SSRIs under medical management (STOP). Women in the control group will continue the use of SSRIs (GO). Primary outcome will be the (cumulative) incidence of relapse or recurrence of maternal depressive disorder (as assessed by the Structured Clinical Interview for DSM disorders) during pregnancy and up to three months postpartum. Secondary outcomes will be child outcome (neonatal outcomes and psychomotor and behavioural outcomes up to 24 months postpartum), and health-care costs. Total study duration for participants will be therefore be 30 months. We specified a non-inferiority margin of 15 % difference in relapse risk. This study is the first to investigate the effect of guided tapering of SSRIs with preventive cognitive therapy from early pregnancy onwards as compared to continuation of SSRIs during pregnancy. We will study the effects on both mother and child with a pragmatic approach. Additionally, the study examines cost effectiveness. If non-inferiority of preventive cognitive therapy with guided tapering of SSRIs compared to intended continuation of SSRIs is demonstrated for the primary outcome, this may be the preferential strategy during pregnancy. Netherlands Trial Register (NTR): NTR4694 ; registration date: 16-jul-2014.

The micronutrient intake profile of a multicentre cohort of Australian LAGB patients.

PubMed

McGrice, Melanie A; Porter, Judi A

2014-03-01

Patients who have undergone bariatric surgery have increased risks of developing micronutrient deficiencies. Translational research investigating the actual micronutrient intake of bariatric patients is limited. We examined the micronutrient intake of a multicentre cohort of laparoscopic adjustable gastric banding patients 1 year post-surgery. These data were compared to micronutrient recommendations for the general population. Consecutive patients from three bariatric surgery facilities in Melbourne, Australia, were invited to participate 12 months post-operatively. A validated food frequency questionnaire was posted to 215 prospective participants. Of the 52 participants, micronutrient intakes from food and fluids alone were below population recommendations for calcium, folate, magnesium, potassium, retinol equivalents, thiamin and vitamin E. Males did not meet the recommended intakes for zinc, and iron intakes in pre-menopausal women were insufficient. Intakes lower than recommended levels for these micronutrients suggest inadequate intake of foods from vegetable, dairy, lean meat (or alternatives) and wholegrains. Micronutrient intakes below recommended levels in this patient group can be further explained by their macronutrient intakes that suggested diets of poor nutrient density. Recommendations for supplementation in this group have wide variations, usually having been developed through the presence of clinical and biochemical deficiencies. Nutritional supplementation should be more extensive in scope and dosage than is currently recommended by some professional guidelines. Further long-term studies are needed to explore both macro- and micronutrient intakes on the morbidity and mortality of this patient population.

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.

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.

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.

Comparison of clinical outcomes and genomic characteristics of single focus and multifocal glioblastoma

PubMed Central

Paulsson, Anna K.; Holmes, Jordan A.; Peiffer, Ann M.; Miller, Lance D.; Liu, Wennuan; Xu, Jianfeng; Hinson, William H.; Lesser, Glenn J.; Laxton, Adrian W.; Tatter, Stephen B.; Debinski, Waldemar

2014-01-01

We investigate the differences in molecular signature and clinical outcomes between multiple lesion glioblastoma (GBM) and single focus GBM in the modern treatment era. Between August 2000 and May 2010, 161 patients with GBM were treated with modern radiotherapy techniques. Of this group, 33 were considered to have multiple lesion GBM (25 multifocal and 8 multicentric). Patterns of failure, time to progression and overall survival were compared based on whether the tumor was considered a single focus or multiple lesion GBM. Genomic groupings and methylation status were also investigated as a possible predictor of multifocality in a cohort of 41 patients with available tissue for analysis. There was no statistically significant difference in overall survival (p < 0.3) between the multiple lesion tumors (8.2 months) and single focus GBM (11 months). Progression free survival was superior in the single focus tumors (7.1 months) as compared to multi-focal (5.6 months, p = 0.02). For patients with single focus, multifocal and multicentric GBM, 81, 76 and 88 % of treatment failures occurred in the 60 Gy volume (p < 0.5), while 54, 72, and 38 % of treatment failures occurred in the 46 Gy volume (p < 0.4). Out of field failures were rare in both single focus and multiple foci GBM (7 vs 3 %). Genomic groupings and methylation status were not found to predict for multifocality. Patterns of failure, survival and genomic signatures for multiple lesion GBM do not appreciably differ when compared to single focus tumors. PMID:24990827

Is bleach-sedimented smear microscopy an alternative to direct microscopy under programme conditions in India?

PubMed Central

Vishnu, P. H.; Bansal, A.; Satyanarayana, S.; Alavadi, U.; Ohri, B. S.; Shrinivas, M. S. Rao; Desikan, P.; Jaju, J.; Rao, V. G.; Moonan, P. K.

2013-01-01

This cross-sectional multi-centric study compared the yield of and potential benefit for detecting smear-positive pulmonary tuberculosis (PTB) by bleach sedimentation (2% sodium-hypochlorite) versus direct microscopy under programme conditions in India. Among 3168 PTB suspects, 684 (21.6%) were detected by bleach sedimentation vs. 625 (19.7%) by direct microscopy, with a proportional overall agreement of 96% (κ = 0.88). While 594 patients were smear-positive with both methods, 31 patients detected by direct microscopy were missed and an additional 90 patients were detected by bleach sedimentation. Overall, bleach sedimentation increased the yield of smear-positive TB detection; however; it also increased the time to results. PMID:26392991

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

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.

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

Healthcare use, costs and quality of life in patients with end-stage kidney disease receiving conservative management: results from a multi-centre observational study (PACKS).

PubMed

Phair, Glenn; Agus, Ashley; Normand, Charles; Brazil, Kevin; Burns, Aine; Roderick, Paul; Maxwell, Alexander P; Thompson, Colin; Yaqoob, Magdi; Noble, Helen

2018-05-01

Previous research has explored the cost of providing renal replacement therapies in patients with end-stage kidney disease and their quality of life. This is the first study to examine the healthcare costs of patients receiving conservative care without dialysis for end-stage kidney disease. This alternative to dialysis is an option for patients who prefer a supportive and palliative care approach. Descriptive cost and quality of life analyses alongside a UK-based multi-centre observational study in patients receiving conservative management for end-stage kidney disease. Health service use was recorded up to 12 months after making the decision to receive conservative management. Mean costs were calculated for each 3-month time period. The annual cost was calculated in two ways: by using only patients with complete cost data and by using all available data weighted by the number of patients at each time point. In total, 42 patients who opted for conservative management over dialysis were recruited. Mean costs were £1622 (0-3 months), £1008 (3-6 months), £554 (6-9 months) and £2626 (9-12 months). Mean annual cost based on complete data ( n = 8) was £5511, and the weighted mean annual cost was £5620. The importance of this study is twofold. First, it provides substantive new information for health and social care planning of conservative management by demonstrating where demand exists for services, in both the United Kingdom and other countries with a comparable health service structure. Second, methodologically, it indicates that it is feasible to collect service use data directly from this patient population.

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

PubMed

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

2016-09-01

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

Risk and protective factors for falls on stairs in young children: multicentre case–control study

PubMed Central

Kendrick, D; Zou, K; Ablewhite, J; Watson, M; Coupland, C; Kay, B; Hawkins, A; Reading, R

2016-01-01

Aim To investigate risk and protective factors for stair falls in children aged <5 years. Methods Multicentre case–control study at hospitals, minor injury units and general practices in and around four UK study centres. Cases were children with medically attended stair fall injuries. Controls were matched on age, sex, calendar time and study centre. A total of 610 cases and 2658 controls participated. Results Cases’ most common injuries were bangs on the head (66%), cuts/grazes not requiring stitches (14%) and fractures (12%). Parents of cases were significantly more likely not to have stair gates (adjusted OR (AOR) 2.50, 95% CI 1.90 to 3.29; population attributable fraction (PAF) 21%) or to leave stair gates open (AOR 3.09, 95% CI 2.39 to 4.00; PAF 24%) both compared with having closed stair gates. They were more likely not to have carpeted stairs (AOR 1.52, 95% CI 1.09 to 2.10; PAF 5%) and not to have a landing part-way up their stairs (AOR 1.34, 95% CI 1.08 to 1.65; PAF 18%). They were more likely to consider their stairs unsafe to use (AOR 1.46, 95% CI 1.07 to 1.99; PAF 5%) or to be in need of repair (AOR 1.71, 95% CI 1.16 to 2.50; PAF 5%). Conclusion Structural factors including having landings part-way up the stairs and keeping stairs in good repair were associated with reduced stair fall injury risk. Family factors including having stair gates, not leaving gates open and having stair carpets were associated with reduced injury risk. If these associations are causal, addressing these factors in housing policy and routine child health promotion could reduce stair fall injuries. PMID:26662926

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.

Feasibility study from a randomized controlled trial of standard closure of a stoma site vs biological mesh reinforcement.

PubMed

2016-09-01

Hernia formation occurs at closed stoma sites in up to 30% of patients. The Reinforcement of Closure of Stoma Site (ROCSS) randomized controlled trial is evaluating whether placement of biological mesh during stoma closure safely reduces hernia rates compared with closure without mesh, without increasing surgical or wound complications. This paper aims to report recruitment, deliverability and safety from the internal feasibility study. A multicentre, patient and assessor blinded, randomized controlled trial, delivered through surgical trainee research networks. A 90-patient internal feasibility study assessed recruitment, randomization, deliverability and early (30 day) safety of the novel surgical technique (ClinicalTrials.gov registration number NCT02238964). The feasibility study recruited 90 patients from the 104 considered for entry (45 to mesh, 45 to no mesh). Seven of eight participating centres randomized patients within 30 days of opening. Overall, 41% of stomas were created for malignant disease and 73% were ileostomies. No mesh-specific complications occurred. Thirty-one postoperative adverse events were experienced by 31 patients, including surgical site infection (9%) and postoperative ileus (6%). One mesh was removed for re-access to the abdominal cavity, for reasons unrelated to the mesh. Independent review by the Data Monitoring and Ethics Committee of adverse event data by treatment allocation found no safety concerns. Multicentre randomization to this trial of biological mesh is feasible, with no early safety concerns. Progression to the full Phase III trial has continued. ROCSS shows that trainee research networks can efficiently develop and deliver complex interventional surgical trials. Colorectal Disease © 2016 The Association of Coloproctology of Great Britain and Ireland.

Risk and protective factors for falls on one level in young children: multicentre case-control study.

PubMed

Benford, P; Young, B; Coupland, C; Watson, M; Hindmarch, P; Hayes, M; Goodenough, T; Majsak-Newman, G; Kendrick, D

2015-12-01

Childhood falls are an important global public health problem, but there is lack of evidence about their prevention. Falls on one level result in considerable morbidity and they are costly to health services. To estimate ORs for falls on one level in children aged 0-4 years for a range of safety behaviours, safety equipment use and home hazards. Multicentre case-control study at hospitals, minor injury units and general practices in and around four UK study centres. Participants included 582 children less than 5 years of age with a medically attended fall injury occurring at home and 2460 controls matched on age, sex, calendar time and study centre. Fall on one level. Cases' most common injuries were bangs on the head (52%), cuts or grazes not needing stitches (29%) or cuts or grazes needing stitches (17%). Comparing cases to community controls in the adjusted analyses, significant findings were observed for only two exposures. Injured children were significantly less likely to live in a household without furniture corner covers (adjusted OR (AOR) 0.72, 95% CI 0.55 to 0.95), or without rugs and carpets firmly fixed to the floor (AOR 0.76, 95% CI 0.59 to 0.98). We did not find any safety practices, use of safety equipment or home hazards associated with a reduced risk of fall on one level. Our findings do not provide evidence to support changes to current injury prevention practice. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

The CLOSED trial; CLOnidine compared with midazolam for SEDation of paediatric patients in the intensive care unit: study protocol for a multicentre randomised controlled trial

PubMed Central

Neubert, Antje; Baarslag, Manuel Alberto; van Dijk, Monique; van Rosmalen, Joost; Standing, Joseph F; Sheng, Yucheng; Rascher, Wolfgang; Roberts, Deborah; Winslade, Jackie; Rawcliffe, Louise; Hanning, Sara M; Metsvaht, Tuuli; Giannuzzi, Viviana; Larsson, Peter; Pokorná, Pavla; Simonetti, Alessandra; Tibboel, Dick

2017-01-01

Introduction Sedation is an essential part of paediatric critical care. Midazolam, often in combination with opioids, is the current gold standard drug. However, as it is a far-from-ideal agent, clonidine is increasingly being used in children. This drug is prescribed off-label for this indication, as many drugs in paediatrics are. Therefore, the CLOSED trial aims to provide data on the pharmacokinetics, safety and efficacy of clonidine for the sedation of mechanically ventilated patients in order to obtain a paediatric-use marketing authorisation. Methods and analysis The CLOSED study is a multicentre, double-blind, randomised, active-controlled non-inferiority trial with a 1:1 randomisation between clonidine and midazolam. Both treatment groups are stratified according to age in three groups with the same size: <28 days (n=100), 28 days to <2 years (n=100) and 2–18 years (n=100). The primary end point is defined as the occurrence of sedation failure within the study period. Secondary end points include a pharmacokinetic/pharmacodynamic relationship, pharmacogenetics, occurrence of delirium and withdrawal syndrome, opioid consumption and neurodevelopment in the neonatal age group. Logistic regression will be used for the primary end point, appropriate statistics will be used for the secondary end points. Ethics Written informed consent will be obtained from the parents/caregivers. Verbal or deferred consent will be used in the sites where national legislation allows. The study has institutional review board approval at recruiting sites. The results will be published in a peer-reviewed journal and shared with the worldwide medical community. Trial Registration EudraCT: 2014-003582-24; Clinicaltrials.gov: NCT02509273; pre-results. PMID:28637741

A multicentre, double blind, randomised, placebo controlled trial of anakinra (Kineret), a recombinant interleukin 1 receptor antagonist, in patients with rheumatoid arthritis treated with background methotrexate

PubMed Central

Cohen, S; Moreland, L; Cush, J; Greenwald, M; Block, S; Shergy, W; Hanrahan, P; Kraishi, M; Patel, A; Sun, G; Bear, M

2004-01-01

Objective: To assess the efficacy and safety of 100 mg daily anakinra (Kineret), a recombinant form of the naturally occurring interleukin 1 receptor antagonist, plus methotrexate (MTX) in reducing the signs and symptoms of rheumatoid arthritis (RA). Methods: Patients with active RA (n = 506) despite current treatment with MTX were enrolled in this multicentre, double blind, randomised, placebo controlled study. Patients received subcutaneous injections of anakinra 100 mg/day or placebo. They were assessed monthly for 6 months for improvement in signs and symptoms of RA and for adverse events. The primary efficacy measure was the percentage of patients attaining ACR20 response at week 24. Results: Significantly greater proportions of patients treated with anakinra compared with placebo achieved ACR20 (38% v 22%; p<0.001), ACR50 (17% v 8%; p<0.01), and ACR70 (6% v 2%; p<0.05) responses. The response to anakinra was rapid; the proportion of patients with an ACR20 response at the first study assessment (4 weeks) was twice as high with anakinra as with placebo (p<0.005). Clinically meaningful and statistically significant responses were also seen in individual components of the ACR response (for example, Health Assessment Questionnaire, pain, C reactive protein levels, and erythrocyte sedimentation rate). Anakinra was well tolerated, with a safety profile, similar to that of placebo with one exception: mild to moderate injection site reactions were more common with anakinra than with placebo (65% v 24%). Conclusions: This study confirms previous observations from a dose-ranging study showing that anakinra, in combination with MTX, is an effective and safe treatment for patients with RA who have inadequate responses to MTX alone. PMID:15082469

Etiology and prognosis of acute viral encephalitis and meningitis in Chinese children: a multicentre prospective study.

PubMed

Ai, Junhong; Xie, Zhengde; Liu, Gang; Chen, Zongbo; Yang, Yong; Li, Yuning; Chen, Jing; Zheng, Guo; Shen, Kunling

2017-07-14

In China, there were few studies about the pathogens of acute viral encephalitis and meningitis in children in recent years. The aims of this study were to characterize the etiology and prognosis of acute viral encephalitis and meningitis in Chinese children. This was a multicentre prospective study. Two hundred and sixty one viral encephalitis patients and 285 viral meningitis patients were enrolled. The mean age of viral encephalitis and meningitis were 5.88 ± 3.60 years and 6.39 ± 3.57 years, respectively. Real-time reverse transcription PCR and multiplex PCR were used to detect human enteroviruses and herpes viruses in cerebrospinal fluid (CSF) of patients with encephalitis or meningitis. The enzyme-linked immune absorbent assay (ELISA) was used for detecting IgM antibody against Japanese encephalitis virus (JEV) in CSF and against mumps virus, tick-borne encephalitis virus (TBEV), dengue virus and rubella virus in acute serum. The clinical and outcome data were collected during patients' hospitalization. The etiology of viral encephalitis was confirmed in 52.5% patients. The primary pathogen was human enteroviruses (27.7%) in viral encephalitis. The incidence of sequelae and the fatality rate of viral encephalitis with confirmed etiology were 7.5% and 0.8%, respectively. The etiology of viral meningitis was identified in 42.8% cases. The leading pathogen was also human enteroviruses (37.7%) in viral meningitis. The prognosis of viral meningitis was favorable with only 0.7% patients had neurological sequelae. Human enteroviruses were the leading cause both in acute viral encephalitis and viral meningitis in children. The incidence of sequelae and fatality rate of viral encephalitis with confirmed etiology were 7.5% and 0.8%, respectively. The prognosis of viral meningitis was favorable compared to viral encephalitis.

Effects of SofZia-preserved travoprost and benzalkonium chloride-preserved latanoprost on the ocular surface -- a multicentre randomized single-masked study.

PubMed

Aihara, Makoto; Oshima, Hiromi; Araie, Makoto

2013-02-01

To assess the effect of SofZia-preserved travoprost on ocular surface conditions in comparison with benzalkonium chloride (BAK)-preserved latanoprost. A prospective randomized multicentre single-masked comparative study. Patients with open-angle glaucoma or ocular hypertension who had been treated with BAK-preserved latanoprost 0.005% (Xalatan(®) ) monotherapy for at least 3 months. Patients were enrolled at 23 facilities. Patients were randomly divided into the X-X group, continuous use of Xalatan(®) , or the X-T group, switching from Xalatan(®) to SofZia-preserved travoprost 0.004% (TravatanZ(®) ), and followed for 3 months. The superficial punctate keratopathy (SPK), conjunctival epitheliopathy, hyperaemia, tear break-up time (TBUT) and intraocular pressure (IOP) were examined for each patient in a masked manner. Changes in the frequency of keratoconjunctival epitheliopathy were evaluated 3 months after study initiation. Intra- and intergroup comparisons of changes in SPK, conjunctival epitheliopathy, hyperaemia, TBUT and IOP were also carried out. Two hundred twenty patients participated and 215 completed the 3-month study. The frequency of keratoconjunctival epitheliopathy significantly decreased in the X-T group (p = 0.036) and the intergroup difference was also significant (p = 0.001). SPK scores and TBUT were significantly improved in the X-T group (p = 0.034, 0.049), also with significant intergroup differences in the cornea excluding the inferior area and TBUT. There were no significant intergroup differences in changes of the hyperaemia scores and the IOP reduction. Switching to SofZia-preserved travoprost after BAK-preserved latanoprost resulted in a lower incidence of keratoconjunctival epitheliopathy, especially in the cornea, with no clinically relevant changes in hyperaemia and IOP. © 2012 The Authors. Acta Ophthalmologica © 2012 Acta Ophthalmologica Scandinavica Foundation.

Multi-centre evaluation of mass spectrometric identification of anaerobic bacteria using the VITEK® MS system.

PubMed

Garner, O; Mochon, A; Branda, J; Burnham, C-A; Bythrow, M; Ferraro, M; Ginocchio, C; Jennemann, R; Manji, R; Procop, G W; Richter, S; Rychert, J; Sercia, L; Westblade, L; Lewinski, M

2014-04-01

Accurate and timely identification of anaerobic bacteria is critical to successful treatment. Classic phenotypic methods for identification require long turnaround times and can exhibit poor species level identification. Matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF MS) is an identification method that can provide rapid identification of anaerobes. We present a multi-centre study assessing the clinical performance of the VITEK(®) MS in the identification of anaerobic bacteria. Five different test sites analysed a collection of 651 unique anaerobic isolates comprising 11 different genera. Multiple species were included for several of the genera. Briefly, anaerobic isolates were applied directly to a well of a target plate. Matrix solution (α-cyano-4-hydroxycinnamic acid) was added and allowed to dry. Mass spectra results were generated with the VITEK(®) MS, and the comparative spectral analysis and organism identification were determined using the VITEK(®) MS database 2.0. Results were confirmed by 16S rRNA gene sequencing. Of the 651 isolates analysed, 91.2% (594/651) exhibited the correct species identification. An additional eight isolates were correctly identified to genus level, raising the rate of identification to 92.5%. Genus-level identification consisted of Actinomyces, Bacteroides and Prevotella species. Fusobacterium nucleatum, Actinomyces neuii and Bacteroides uniformis were notable for an increased percentage of no-identification results compared with the other anaerobes tested. VITEK(®) MS identification of clinically relevant anaerobes is highly accurate and represents a dramatic improvement over other phenotypic methods in accuracy and turnaround time. © 2013 The Authors Clinical Microbiology and Infection © 2013 European Society of Clinical Microbiology and Infectious Diseases.

A randomised controlled multicentre trial of women's and men's satisfaction with two models of antenatal education.

PubMed

Bergström, Malin; Kieler, Helle; Waldenström, Ulla

2011-12-01

To study women's and men's satisfaction with two models of antenatal education: natural childbirth preparation with psychoprophylaxis, and standard antenatal education including preparation for childbirth and parenthood but no psychoprophylaxis. Randomised controlled multicentre trial. 15 Antenatal clinics in Sweden between January 2006 and May 2007. 1087 Nulliparous women and 1064 of their partners. Both models had four two-hour sessions during pregnancy and one session post partum. The natural model was manual-based and focused on childbirth preparation, including psychoprophylaxis. In the standard care model, the group leader was free to choose her teaching approach, with an equal amount of time allocated to preparation for childbirth and for parenthood. Women's and men's evaluation of antenatal education at three months post partum. The proportion of women and men in each model that expressed satisfaction with the education were compared using χ(2) test. More women and men in the natural groups were satisfied with the education compared with the standard care groups: women 76% versus 68% (p = 0.03) and men 73% versus 65% (p = 0.03). The figures were similar for satisfaction with the childbirth preparation component: 78% and 62% in women (p < 0.001), and 79% and 67% in men (p < 0.001) in the natural and standard care groups, respectively. Fewer participants were satisfied with the parenthood preparation component, but the proportions were higher in the standard care groups: women 37% versus 32% (p < 0.001) and men 23% versus 20% (p < 0.001). A structured manual-based model of antenatal education which focuses on childbirth preparation with psychoprophylaxis may better meet expectant parents' expectations than standard antenatal education in Sweden. Copyright © 2010 Elsevier Ltd. All rights reserved.

Validating Variational Bayes Linear Regression Method With Multi-Central Datasets.

PubMed

Murata, Hiroshi; Zangwill, Linda M; Fujino, Yuri; Matsuura, Masato; Miki, Atsuya; Hirasawa, Kazunori; Tanito, Masaki; Mizoue, Shiro; Mori, Kazuhiko; Suzuki, Katsuyoshi; Yamashita, Takehiro; Kashiwagi, Kenji; Shoji, Nobuyuki; Asaoka, Ryo

2018-04-01

To validate the prediction accuracy of variational Bayes linear regression (VBLR) with two datasets external to the training dataset. The training dataset consisted of 7268 eyes of 4278 subjects from the University of Tokyo Hospital. The Japanese Archive of Multicentral Databases in Glaucoma (JAMDIG) dataset consisted of 271 eyes of 177 patients, and the Diagnostic Innovations in Glaucoma Study (DIGS) dataset includes 248 eyes of 173 patients, which were used for validation. Prediction accuracy was compared between the VBLR and ordinary least squared linear regression (OLSLR). First, OLSLR and VBLR were carried out using total deviation (TD) values at each of the 52 test points from the second to fourth visual fields (VFs) (VF2-4) to 2nd to 10th VF (VF2-10) of each patient in JAMDIG and DIGS datasets, and the TD values of the 11th VF test were predicted every time. The predictive accuracy of each method was compared through the root mean squared error (RMSE) statistic. OLSLR RMSEs with the JAMDIG and DIGS datasets were between 31 and 4.3 dB, and between 19.5 and 3.9 dB. On the other hand, VBLR RMSEs with JAMDIG and DIGS datasets were between 5.0 and 3.7, and between 4.6 and 3.6 dB. There was statistically significant difference between VBLR and OLSLR for both datasets at every series (VF2-4 to VF2-10) (P < 0.01 for all tests). However, there was no statistically significant difference in VBLR RMSEs between JAMDIG and DIGS datasets at any series of VFs (VF2-2 to VF2-10) (P > 0.05). VBLR outperformed OLSLR to predict future VF progression, and the VBLR has a potential to be a helpful tool at clinical settings.

A multicentre, randomized, placebo- and active-controlled trial comparing the efficacy and safety of topical ketoprofen in Transfersome gel (IDEA-033) with ketoprofen-free vehicle (TDT 064) and oral celecoxib for knee pain associated with osteoarthritis.

PubMed

Conaghan, Philip G; Dickson, John; Bolten, Wolfgang; Cevc, Gregor; Rother, Matthias

2013-07-01

To assess the efficacy and safety of 12-week treatment with ketoprofen in ultradeformable phospholipid vesicles in patients with OA knee pain and to compare the efficacy with that of ketoprofen-free vehicle and celecoxib. METHODS; A multicentre, double-blind controlled study in which patients with knee OA and moderate pain were randomized to one of the six arms: topical ketoprofen 50 or 100 mg in ultradeformable vesicles (IDEA-033), 2.2 or 4.4 g ketoprofen-free vehicle (TDT 064), oral celecoxib 100 mg or matching oral placebo, all bd. The primary outcome was change from baseline in the WOMAC pain subscale at week 12. A total of 1395 patients received treatment. Baseline mean WOMAC pain scores ranged from 4.7 to 4.8 across groups. The mean reduction in WOMAC pain score at week 12 was -1.9 (-40.8%) for ketoprofen 50 mg, -1.9 (-40.9%) for ketoprofen 100 mg, -1.9 (-39.8%) for 2.2 g TDT 064, -1.8 (-37.8%) for 4.4 g TDT 064, -1.9 (-40.4%) for celecoxib and -1.4 (-29.3%) for oral placebo. IDEA-033 was not statistically superior to TDT 064. All topical treatments were statistically superior to oral placebo and non-inferior to celecoxib. The most frequent types of treatment-related adverse events reported were gastrointestinal for oral (15.9% for celecoxib) and dermal for topical applications (12.2% for ketoprofen 100 mg). IDEA-033 was not superior to ketoprofen-free vehicle, but both formulations were superior to oral placebo and non-inferior to celecoxib in reducing OA knee pain. ClinicalTrials.gov, http://clinicaltrials.gov/, NCT00716547.

A multicentre, randomised, double-blind, single-dose study assessing the efficacy of AMC/DCBA Warm lozenge or AMC/DCBA Cool lozenge in the relief of acute sore throat

PubMed Central

2011-01-01

Background Clinically proven over-the-counter (OTC) treatment options are becoming increasingly important in the self-management of acute sore throat. The aim of this study was to determine the analgesic and sensorial benefits of two different amylmetacresol/2,4-dichlorobenzyl alcohol (AMC/DCBA) throat lozenge formulation variants, AMC/DCBA Warm lozenge and AMC/DCBA Cool lozenge, compared with an unflavoured, non-medicated placebo lozenge in the relief of acute sore throat due to upper respiratory tract infections. Methods In this multicentre, randomised, double-blind, single-dose study, 225 adult patients with acute sore throat were randomly assigned to receive either one AMC/DCBA Warm lozenge (n = 77), one AMC/DCBA Cool lozenge (n = 74) or one unflavoured, non-medicated lozenge (matched for size, shape and demulcency; n = 74). After baseline assessments, patients received their assigned lozenge and completed four rating assessments at 11 timepoints from 1 to 120 minutes post dose. Analgesic properties were assessed by comparing severity of throat soreness and sore throat relief ratings. Difficulty in swallowing, throat numbness, functional, sensorial and emotional benefits were also assessed. Results Both the AMC/DCBA Warm and AMC/DCBA Cool lozenge induced significant analgesic, functional, sensorial and emotional effects compared with the unflavoured, non-medicated lozenge. Sore throat relief, improvements in throat soreness and difficulty in swallowing, and throat numbness were observed as early as 1-5 minutes, and lasted up to 2 hours post dose. Sensorial benefits of warming and cooling associated with the AMC/DCBA Warm and AMC/DCBA Cool lozenge, respectively, were experienced soon after first dose, and in the case of the latter, it lasted long after the lozenge had dissolved. Emotional benefits of feeling better, happier, less distracted and less frustrated were reported in those taking either of the AMC/DCBA throat lozenge variants, with no differences in adverse events compared with the unflavoured, non-medicated lozenge. Conclusions AMC/DCBA Warm and AMC/DCBA Cool lozenges are well-tolerated and effective OTC treatment options, offering functional, sensorial and emotional benefits to patients with acute sore throat, over and above that of the rapid efficacy effects provided. Trial registration ISRCTN: ISRCTN00003567 PMID:21332976

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.

Catheter ablation in patients with persistent atrial fibrillation

PubMed Central

Kirchhof, Paulus; Calkins, Hugh

2017-01-01

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

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

PubMed

Yokode, Masataka; Yamashita, Yukimasa; Zen, Yoh

2017-03-01

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

Posterior chamber phakic intraocular lens implantation: comparative, multicentre study in 351 eyes with low-to-moderate or high myopia.

PubMed

Kamiya, Kazutaka; Shimizu, Kimiya; Igarashi, Akihito; Kitazawa, Yoshihiro; Kojima, Takashi; Nakamura, Tomoaki; Oka, Yoshitaka; Matsumoto, Rei

2018-02-01

To compare the clinical outcomes of posterior chamber phakic intraocular lens implantation with a central hole (Hole Implantable Collamer Lens (ICL), STAAR Surgical) for low-to-moderate myopia and for high myopia. This multicentre retrospective case series comprised 351 eyes of 351 consecutive patients undergoing ICL implantation. Eyes were divided into groups based on preoperative degree of myopia: group 1; 57 eyes, manifest spherical equivalent less than -6 dioptres (D), and group 2; 294 eyes, -6 D or more. Safety, efficacy, predictability, stability and adverse events were compared preoperatively; and at 1 day, 1 week and 1, 3, 6 and 12 months postoperatively, RESULTS: Uncorrected and corrected visual acuities were -0.17±0.14 and -0.21±0.10 logMAR in group 1, and -0.16±0.09 and -0.21±0.08 logMAR in group 2, 1 year postoperatively. In groups 1 and 2, 98% and 99% of eyes were within 1.0 D of the targeted correction. Manifest refraction changes of -0.12±0.34 D (group 1) and -0.18±0.43 D (group 2) occurred from 1 day to 1 year. ICL exchanges were necessary in two eyes (0.7%) in group 2. No vision-threatening complications occurred at any time. The ICL performed well for the correction of both low-to-moderate myopia and high myopia throughout the 1-year observation period. The clinical outcomes of ICL implantation for low-to-moderate myopia are essentially equivalent to those for high myopia. © 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.

Cement augmentation of the Proximal Femoral Nail Antirotation (PFNA) - A multicentre randomized controlled trial.

PubMed

Kammerlander, Christian; Hem, Einar S; Klopfer, Tim; Gebhard, Florian; Sermon, An; Dietrich, Michael; Bach, Olaf; Weil, Yoram; Babst, Reto; Blauth, Michael

2018-04-22

New implant designs like the Proximal Femoral Nail Antirotation (PFNA) were developed to reduce failure rates in unstable pertrochanteric fractures in the elderly. Standardized implant augmentation with up to 6 mL of polymethylmethacrylate (PMMA) cement has been introduced to enhance implant anchorage by increasing the implant-bone interface in osteoporotic bone conditions. Biomechanically, loads to failure were significantly higher with augmentation. The primary objective of this study was to compare the mobility of patients with closed unstable trochanteric fractures treated by PFNA either with or without cement augmentation. A prospective multicentre, randomized, patient-blinded trial was conducted with ambulatory patients aged 75 or older who sustained a closed, unstable trochanteric fracture. Surgical fixation had to be performed within 72 h after admission. Outcomes were evaluated at baseline, during surgery, 3 to 14 days after surgery, 3 months, 6 months, and 12 months after surgery. To evaluate the primary objective, patients' walking speed was assessed by the Timed Up and Go (TUG) test. Secondary objectives included the analysis of implant migration assessed on radiographs, quality of life measured by the Barthel Index, mobility measured by the Parker Mobility Score, and complications. Of 253 randomized patients, 223 patients were eligible: 105 patients were allocated to the PFNA Augmentation group and 118 to PFNA group. At 3 to 14 days after surgery, there was no statistical significant difference in mean walking speed between the treatment groups. For the secondary objectives, also no statistical significant differences were found. However, no patient in the PFNA Augmentation group had a reoperation due to mechanical failure or symptomatic implant migration compared to 6 patients in the PFNA group. Augmentation of the PFNA blade did not improve patients' walking ability compared to the use of a non-augmented PFNA but might have the potential to prevent reoperations by strengthening the osteosynthesis construct. Copyright © 2018 The Authors. Published by Elsevier Ltd.. All rights reserved.

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.

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

PubMed

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

2016-06-01

Damage to the cerebral tissue structural connectivity associated with amyotrophic lateral sclerosis (ALS), which extends beyond the motor pathways, can be visualised by diffusion tensor imaging (DTI). The effective translation of DTI metrics as biomarker requires its application across multiple MRI scanners and patient cohorts. A multicentre study was undertaken to assess structural connectivity in ALS within a large sample size. 442 DTI data sets from patients with ALS (N=253) and controls (N=189) were collected for this retrospective study, from eight international ALS-specialist clinic sites. Equipment and DTI protocols varied across the centres. Fractional anisotropy (FA) maps of the control participants were used to establish correction matrices to pool data, and correction algorithms were applied to the FA maps of the control and ALS patient groups. Analysis of data pooled from all centres, using whole-brain-based statistical analysis of FA maps, confirmed the most significant alterations in the corticospinal tracts, and captured additional significant white matter tract changes in the frontal lobe, brainstem and hippocampal regions of the ALS group that coincided with postmortem neuropathological stages. Stratification of the ALS group for disease severity (ALS functional rating scale) confirmed these findings. This large-scale study overcomes the challenges associated with processing and analysis of multiplatform, multicentre DTI data, and effectively demonstrates the anatomical fingerprint patterns of changes in a DTI metric that reflect distinct ALS disease stages. This success paves the way for the use of DTI-based metrics as read-out in natural history, prognostic stratification and multisite disease-modifying studies in ALS. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

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.

Variable expression of molecular markers in juvenile nasopharyngeal angiofibroma.

PubMed

Mishra, A; Pandey, A; Mishra, S C

2017-09-01

Molecular categorisation may explain the wide variation in the clinical characteristics of juvenile nasopharyngeal angiofibroma. Variations in molecular markers in juvenile nasopharyngeal angiofibroma in an Indian population were investigated and compared with global reports. Variable molecular marker expression was demonstrated at the regional and global levels. A wide variation in molecular characteristics is evident. Molecular data have been reported for only 11 countries, indicating a clear geographical bias. Only 58 markers have been studied, and most are yet to be validated. Research into the molecular epidemiology of juvenile nasopharyngeal angiofibroma is still in its infancy. Although the molecular variation is not well understood, data obtained so far have prompted important research questions. Hence, multicentre collaborative molecular studies are needed to establish the aetiopathogenesis and establish molecular surrogates for clinical characteristics.

[The transrectus sheath preperitoneal procedure: a safe, effective and cheap surgical approach to inguinal hernia?].

PubMed

Prins, M W Wiesje; Voropai, D A Dasha; van Laarhoven, C J H M Kees; Akkersdijk, Willem L

2013-01-01

The main complication of surgery for inguinal hernia is chronic postoperative pain. This is often reported following the Lichtenstein procedure. A new, open surgical technique for the repair of inguinal hernia has been developed. This procedure is called the transrectus sheath preperitoneal procedure (TREPP). At TREPP a lightweight mesh with a ring made of memory metal is introduced into the preperitoneal space through the transrectus sheath. The first results of this operative technique are very promising: short operation time, short learning curve and not many patients with chronic postoperative pain. In a randomised, multi-centre study which will start mid-2013 (ISRCTN18591339), the TREPP procedure is compared with the transinguinal preperitoneal procedure. The primary outcome measure of this study is chronic postoperative pain.

DEAE-Dextran in the treatment of primary hypercholesterolemia and/or hypercholesterolemia combined with hypertriglyceridemia. A multicentric randomized study on the efficacy of DEAE-Dextran compared with Cholestyramine.

PubMed

Fedele, F

2003-01-01

This study was carried out to verify the therapeutic homogeneity between DEAE-Dextran and Cholestyramine. Blood levels of total cholesterol, HDL, LDL and triglycerides were evaluated in 202 patients affected by dyslipidemia and treated with DEAD-D at 2.5 g/day or with Cholestyramine at 12 g/day for 30 days. At the end of treatment both drugs caused significant reduction of total cholesterol, LDL and triglycerides blood levels; DEAD-D was generally more effective than Cholestyramine, in particular on triglycerides values (30.6% and 13.7% of reduction respectively), and produced also a significant increase in HDL cholesterol, differently from Cholestyramine that was ineffective on this parameter.

Supporting clinical rules engine in the adjustment of medication (SCREAM): protocol of a multicentre, prospective, randomised study.

PubMed

Mestres Gonzalvo, Carlota; de Wit, Hugo A J M; van Oijen, Brigit P C; Hurkens, Kim P G M; Janknegt, Rob; Schols, Jos M G A; Mulder, Wubbo J; Verhey, Frans R; Winkens, Bjorn; van der Kuy, Paul-Hugo M

2017-01-26

In the nursing home population, it is estimated that 1 in every 3 patients is polymedicated and given their considerable frailty, these patients are especially prone to adverse drug reactions. Clinical pharmacist-led medication reviews are considered successful interventions to improve medication safety in the inpatient setting. Due to the limited available evidence concerning the benefits of medication reviews performed in the nursing home setting, we propose a study aiming to demonstrate a positive effect that a clinical decision support system, as a health care intervention, may have on the target population. The primary objective of this study is to reduce the number of patients with at least one event when using the clinical decision support system compared to the regular care. These events consist of hospital referrals, delirium, falls, and/or deaths. This study is a multicentre, prospective, randomised study with a cluster group design. The randomisation will be per main nursing home physician and stratified per ward (somatic and psychogeriatric). In the intervention group the clinical decision support system will be used to screen medication list, laboratory values and medical history in order to obtain potential clinical relevant remarks. The remarks will be sent to the main physician and feedback will be provided whether the advice was followed or not. In the control group regular care will be applied. We strongly believe that by using a clinical decision support system, medication reviews are performed in a standardised way which leads to comparable results between patients. In addition, using a clinical decision support system eliminates the time factor to perform medication reviews as the major problems related to medication, laboratory values, indications and/or established patient characteristics will be directly available. In this way, and in order to make the medication review process complete, consultation within healthcare professionals and/or the patient itself will be time effective and the medication surveillance could be performed around the clock. The Netherlands National Trial Register NTR5165 . Registered 2nd April 2015.

Protocol of the Australasian Malignant Pleural Effusion (AMPLE) trial: a multicentre randomised study comparing indwelling pleural catheter versus talc pleurodesis.

PubMed

Fysh, Edward T H; Thomas, Rajesh; Read, Catherine A; Kwan, Ben C H; Lam, Ben C H; Yap, Elaine; Horwood, Fiona C; Lee, Pyng; Piccolo, Francesco; Shrestha, Ranjan; Garske, Luke A; Lam, David C L; Rosenstengel, Andrew; Bint, Michael; Murray, Kevin; Smith, Nicola A; Lee, Y C Gary

2014-11-06

Malignant pleural effusion can complicate most cancers. It causes breathlessness and requires hospitalisation for invasive pleural drainages. Malignant effusions often herald advanced cancers and limited prognosis. Minimising time spent in hospital is of high priority to patients and their families. Various treatment strategies exist for the management of malignant effusions, though there is no consensus governing the best choice. Talc pleurodesis is the conventional management but requires hospitalisation (and substantial healthcare resources), can cause significant side effects, and has a suboptimal success rate. Indwelling pleural catheters (IPCs) allow ambulatory fluid drainage without hospitalisation, and are increasingly employed for management of malignant effusions. Previous studies have only investigated the length of hospital care immediately related to IPC insertion. Whether IPC management reduces time spent in hospital in the patients' remaining lifespan is unknown. A strategy of malignant effusion management that reduces hospital admission days will allow patients to spend more time outside hospital, reduce costs and save healthcare resources. The Australasian Malignant Pleural Effusion (AMPLE) trial is a multicentred, randomised trial designed to compare IPC with talc pleurodesis for the management of malignant pleural effusion. This study will randomise 146 adults with malignant pleural effusions (1:1) to IPC management or talc slurry pleurodesis. The primary end point is the total number of days spent in hospital (for any admissions) from treatment procedure to death or end of study follow-up. Secondary end points include hospital days specific to pleural effusion management, adverse events, self-reported symptom and quality-of-life scores. The Sir Charles Gairdner Group Human Research Ethics Committee has approved the study as have the ethics boards of all the participating hospitals. The trial results will be published in peer-reviewed journals and presented at scientific conferences. Australia New Zealand Clinical Trials Registry-ACTRN12611000567921; National Institutes of Health-NCT02045121. 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.

[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.

Efficacy of maropitant for preventing vomiting associated with motion sickness in dogs.

PubMed

Benchaoui, H A; Siedek, E M; De La Puente-Redondo, V A; Tilt, N; Rowan, T G; Clemence, R G

2007-09-29

Maropitant is a neurokinin-1 inhibitor that acts to prevent and treat vomiting by blocking stimuli to the final common pathway in the emetic centre of the brain. The field efficacy and safety of a single oral dose of maropitant were investigated for the prevention of vomiting in dogs with a history of motion sickness resulting from transportation by car in two blinded, placebo-controlled studies. In an exploratory study designed as a two-way crossover trial with 17 dogs, 10 of the dogs given the placebo vomited during a car journey but only three of the dogs vomited under maropitant treatment. In a larger multicentred parallel design study, 69 of 105 dogs treated with the placebo vomited during the journey compared with 15 of 106 dogs treated with maropitant (P < 0.0001).

Prognostic value of coronary computed tomographic angiography findings in asymptomatic individuals: a 6-year follow-up from the prospective multicentre international CONFIRM study.

PubMed

Cho, Iksung; Al'Aref, Subhi J; Berger, Adam; Ó Hartaigh, Bríain; Gransar, Heidi; Valenti, Valentina; Lin, Fay Y; Achenbach, Stephan; Berman, Daniel S; Budoff, Matthew J; Callister, Tracy Q; Al-Mallah, Mouaz H; Cademartiri, Filippo; Chinnaiyan, Kavitha; Chow, Benjamin J W; DeLago, Augustin; Villines, Todd C; Hadamitzky, Martin; Hausleiter, Joerg; Leipsic, Jonathon; Shaw, Leslee J; Kaufmann, Philipp A; Feuchtner, Gudrun; Kim, Yong-Jin; Maffei, Erica; Raff, Gilbert; Pontone, Gianluca; Andreini, Daniele; Marques, Hugo; Rubinshtein, Ronen; Chang, Hyuk-Jae; Min, James K

2018-03-14

The long-term prognostic benefit of coronary computed tomographic angiography (CCTA) findings of coronary artery disease (CAD) in asymptomatic populations is unknown. From the prospective multicentre international CONFIRM long-term study, we evaluated asymptomatic subjects without known CAD who underwent both coronary artery calcium scoring (CACS) and CCTA (n = 1226). Coronary computed tomographic angiography findings included the severity of coronary artery stenosis, plaque composition, and coronary segment location. Using the C-statistic and likelihood ratio tests, we evaluated the incremental prognostic utility of CCTA findings over a base model that included a panel of traditional risk factors (RFs) as well as CACS to predict long-term all-cause mortality. During a mean follow-up of 5.9 ± 1.2 years, 78 deaths occurred. Compared with the traditional RF alone (C-statistic 0.64), CCTA findings including coronary stenosis severity, plaque composition, and coronary segment location demonstrated improved incremental prognostic utility beyond traditional RF alone (C-statistics range 0.71-0.73, all P < 0.05; incremental χ2 range 20.7-25.5, all P < 0.001). However, no added prognostic benefit was offered by CCTA findings when added to a base model containing both traditional RF and CACS (C-statistics P > 0.05, for all). Coronary computed tomographic angiography improved prognostication of 6-year all-cause mortality beyond a set of conventional RF alone, although, no further incremental value was offered by CCTA when CCTA findings were added to a model incorporating RF and CACS.

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

PubMed

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

2001-04-01

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

Laboratory heterogeneity of the lupus anticoagulant: a multicentre study using different clotting assays on a panel of 78 samples. Hemostasis Committee of the "Société Française de Biologie Clinique".

PubMed

1992-05-15

The laboratory heterogeneity of the lupus anticoagulant (LA) was investigated in a multicentre study using a panel of 78 plasma samples diagnosed as containing a LA. Consecutive samples were collected by 12 participants using various screening tests, and sent to 7 laboratories which performed one or more clotting assays among the following: activated partial thromboplastin time (APTT), dilute Russell viper venom time, kaolin clotting time (KCT), dilute tissue thromboplastin time (dTTI) and a platelet neutralization test. For APTT and dTTI, 10 versions of these tests including standard and mixing procedures were carried out. They varied by reagents, phospholipid concentration or methodology. Cut-off times were determined for each test by comparing the results of the panel to those of a control population. When the data of all clotting assays were pooled, 70 of the 78 selected plasmas were considered to contain LA, 15 of them having a low-titer inhibitor. Sensitivity, defined as the proportion of positive results among LA-containing plasmas, varied from 62 to 100% and was positively related to responsiveness (defined as the mean ratio of clotting time to cut-off time). Laboratory heterogeneity of LA-containing plasma was illustrated by a star symbol plot analysis. Different populations of samples, with LA preferentially recognized by one assay (or group of assays) irrespective of the overall sensitivity of this assay, were identified. Multiple component analysis demonstrated the heterogeneity of low-titer inhibitors, which complicates their recognition in routine laboratory investigation.

Prognostic indicators in primary plasma cell leukaemia: a multicentre retrospective study of 117 patients.

PubMed

Jurczyszyn, Artur; Radocha, Jakub; Davila, Julio; Fiala, Mark A; Gozzetti, Alessandro; Grząśko, Norbert; Robak, Paweł; Hus, Iwona; Waszczuk-Gajda, Anna; Guzicka-Kazimierczak, Renata; Atilla, Erden; Mele, Giuseppe; Sawicki, Waldemar; Jayabalan, David S; Charliński, Grzegorz; Szabo, Agoston G; Hajek, Roman; Delforge, Michel; Kopacz, Agnieszka; Fantl, Dorotea; Waage, Anders; Avivi, Irit; Rodzaj, Marek; Leleu, Xavier; Richez, Valentine; Knopińska-Posłuszny, Wanda; Masternak, Anna; Yee, Andrew J; Barchnicka, Agnieszka; Druzd-Sitek, Agnieszka; Guerrero-Garcia, Thomas; Liu, Jieqi; Vesole, David H; Castillo, Jorge J

2018-03-01

We report a multicentre retrospective study that analysed clinical characteristics and outcomes in 117 patients with primary plasma cell leukaemia (pPCL) treated at the participating institutions between January 2006 and December 2016. The median age at the time of pPCL diagnosis was 61 years. Ninety-eight patients were treated with novel agents, with an overall response rate of 78%. Fifty-five patients (64%) patients underwent upfront autologous stem cell transplantation (ASCT). The median follow-up time was 50 months (95% confidence interval [CI] 33; 76), with a median overall survival (OS) for the entire group of 23 months (95% CI 15; 34). The median OS time in patients who underwent upfront ASCT was 35 months (95% CI 24·3; 46) as compared to 13 months (95% CI 6·3; 35·8) in patients who did not receive ASCT (P = 0·001). Multivariate analyses identified age ≥60 years, platelet count ≤100 × 10 9 /l and peripheral blood plasma cell count ≥20 × 10 9 /l as independent predictors of worse survival. The median OS in patients with 0, 1 or 2-3 of these risk factors was 46, 27 and 12 months, respectively (P < 0·001). Our findings support the use of novel agents and ASCT as frontline treatment in patients with pPCL. The constructed prognostic score should be independently validated. © 2018 John Wiley & Sons Ltd.

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.

Temozolomide alone or in combination with doxorubicin as a rescue agent in 37 cases of canine multicentric lymphoma.

PubMed

Treggiari, E; Elliott, J W; Baines, S J; Blackwood, L

2018-06-01

Temozolomide (TMZ) is an alkylating agent previously used in conjunction with doxorubicin (DOX) to treat dogs with relapsed lymphoma. However, there are very limited data for this drug when used as single agent. The aim of this retrospective study was to evaluate the efficacy and toxicity of TMZ in dogs with relapsed multicentric lymphoma that failed multi-agent chemotherapy protocols, and compare the outcome to a group of dogs receiving the same drug in combination with DOX. Twenty-six patients were included in the TMZ group and 11 in the TMZ/DOX group. Responses were evaluated via retrospective review of the medical records. The overall median survival time (MST) for both groups was 40 days (range 1-527 days). For the TMZ group, median time to progression (TTP) was 15 days (range 1-202 days) and MST 40 days (range 1-527 days), with an overall response rate (ORR) of 32% and 46% recorded toxicities. For the TMZ/DOX group, median TTP was 19 days (range 2-87 days) and MST 24 days (range 3-91 days), with an ORR of 60% and 63% recorded toxicities. However, a proportion of haematological toxicoses may have gone undetected due to the absence of associated clinical signs. The difference in MST and TTP between the 2 groups was not statistically significant. Similarly, no negative prognostic factors were identified. Although responses were generally short lived, this study suggests that TMZ may achieve similar efficacy to TMZ/DOX whilst being associated with a lower frequency of recorded toxicities. © 2017 John Wiley & Sons Ltd.

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.

Xyloglucan for the treatment of acute diarrhea: results of a randomized, controlled, open-label, parallel group, multicentre, national clinical trial.

PubMed

Gnessi, Lucio; Bacarea, Vladimir; Marusteri, Marius; Piqué, Núria

2015-10-30

There is a strong rationale for the use of agents with film-forming protective properties, like xyloglucan, for the treatment of acute diarrhea. However, few data from clinical trials are available. A randomized, controlled, open-label, parallel group, multicentre, clinical trial was performed to evaluate the efficacy and safety of xyloglucan, in comparison with diosmectite and Saccharomyces in adult patients with acute diarrhea due to different causes. Patients were randomized to receive a 3-day treatment. Symptoms (stools type, nausea, vomiting, abdominal pain and flatulence) were assessed by a self-administered ad-hoc questionnaire 1, 3, 6, 12, 24, 48 and 72 h following the first dose administration. Adverse events were also recorded. A total of 150 patients (69.3 % women and 30.7 % men, mean age 47.3 ± 14.7 years) were included (n = 50 in each group). A faster onset of action was observed in the xyloglucan group compared with the diosmectite and S. bouliardii groups. At 6 h xyloglucan produced a statistically significant higher decrease in the mean number of type 6 and 7 stools compared with diosmectite (p = 0.031). Xyloglucan was the most efficient treatment in reducing the percentage of patients with nausea throughout the study period, particularly during the first hours (from 26 % at baseline to 4 % after 6 and 12 h). An important improvement of vomiting was observed in all three treatment groups. Xyloglucan was more effective than diosmectite and S. bouliardii in reducing abdominal pain, with a constant improvement observed throughout the study. The clinical evolution of flatulence followed similar patterns in the three groups, with continuous improvement of the symptom. All treatments were well tolerated, without reported adverse events. Xyloglucan is a fast, efficacious and safe option for the treatment of acute diarrhea. EudraCT number 2014-001814-24 (date: 2014-04-28) ISRCTN number: 90311828.

Short-term risk of liver and renal injury in hospitalized patients using micafungin: a multicentre cohort study.

PubMed

Schneeweiss, Sebastian; Carver, Peggy L; Datta, Kausik; Galar, Alicia; Johnson, Melissa D; Johnson, Matthew G; Marty, Francisco M; Nagel, Jerod; Najdzinowicz, Maryann; Saul, Melissa; Shoham, Shmuel; Silveira, Fernanda P; Varughese, Christy A; Wilck, Marissa; Weatherby, Lisa; Auton, Tim; Walker, Alexander M

2016-10-01

Although echinocandins are generally well tolerated, there is little information on the frequency with which renal and hepatic adverse effects occur during use of micafungin or other parenteral antifungal (PAF) agents in clinical practice. MYCOS is a multicentre cohort study of adult and paediatric patients who received micafungin or other PAFs between 2005 and 2012 at seven tertiary care hospitals from six centres in the USA. PAF cohort controls were selected through propensity score (PS) matching to micafungin recipients using clinical characteristics, other treatments, procedures and hospital service where PAF treatment was initiated. Analysis was restricted to patients without chronic liver and kidney conditions at the time of cohort entry. Treatment-emergent hepatic and renal injury was documented by changes in liver enzymes or estimated glomerular filtration rate through 30 days following completion of PAF treatment. Comparisons were quantified using the HR from a proportional hazards analysis. There were 2970 micafungin recipients PS matched to 6726 recipients of comparator PAFs. Balance was achieved in all baseline covariates between treatment groups. There were similar rates of hepatic injury (micafungin, 13 events per 100 patients and other PAF, 12 per 100; HR = 0.99; 95% CI 0.86-1.14) and lower rates of renal injury (micafungin, 63 events per 100 patients and other PAF, 65 per 100; HR = 0.93; 95% CI 0.87-0.99) for micafungin recipients versus PAF comparators. For a wide spectrum of underlying conditions, we observed no increase in liver injury by micafungin and possibly a reduced risk of renal dysfunction in comparison with other PAF medications. © The Author 2016. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

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

PubMed

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

2016-03-31

To compare the clinical effectiveness of the intravesical administration of combined hyaluronic acid and chondroitin sulfate (HA+CS) versus current standard management in adult women with recurrent urinary tract infections (RUTIs). A European Union-based multicentre, retrospective nested case-control study. 276 adult women treated for RUTIs starting from 2009 to 2013. Patients treated with either intravesical administration of HA+CS or standard of care (antimicrobial/immunoactive prophylaxis/probiotics/cranberry). The primary outcome was occurrence of bacteriologically confirmed recurrence within 12 months. Secondary outcomes were time to recurrence, total number of recurrences, health-related quality of life and healthcare resource consumption. Crude and adjusted results for unbalanced characteristics are presented. 181 patients treated with HA+CS and 95 patients treated with standard of care from 7 centres were included. The crude and adjusted ORs (95% CI) for the primary end point were 0.77 (0.46 to 1.28) and 0.51 (0.27 to 0.96), respectively. However, no evidence of improvement in terms of total number of recurrences (incidence rate ratio (95% CI), 0.99 (0.69 to 1.43)) or time to first recurrence was seen (HR (95% CI), 0.99 (0.61 to 1.61)). The benefit of intravesical HA+CS therapy improves when the number of instillations is ≥ 5. Our results show that bladder instillations of combined HA+CS reduce the risk of bacteriologically confirmed recurrences compared with the current standard management of RUTIs. Total incidence rates and hazard rates were instead non-significantly different between the 2 groups after adjusting for unbalanced factors. In contrast to what happens with antibiotic prophylaxis, the effectiveness of the HA+CS reinstatement therapy improves over time. NCT02016118. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

Wide-neck bifurcation aneurysms of the middle cerebral artery and basilar apex treated by endovascular techniques: a multicentre, core lab adjudicated study evaluating safety and durability of occlusion (BRANCH).

PubMed

De Leacy, Reade A; Fargen, Kyle M; Mascitelli, Justin R; Fifi, Johanna; Turkheimer, Lena; Zhang, Xiangnan; Patel, Aman B; Koch, Matthew J; Pandey, Aditya S; Wilkinson, D Andrew; Griauzde, Julius; James, Robert F; Fortuny, Enzo M; Cruz, Aurora; Boulos, Alan; Nourollah-Zadeh, Emad; Paul, Alexandra; Sauvageau, Eric; Hanel, Ricardo; Aguilar-Salinas, Pedro; Novakovic, Roberta L; Welch, Babu G; Almardawi, Ranyah; Jindal, Gaurav; Shownkeen, Harish; Levy, Elad I; Siddiqui, Adnan H; Mocco, J

2018-06-01

BRANCH (wide-neck bifurcation aneurysms of the middle cerebral artery and basilar apex treated by endovascular techniques) is a multicentre, retrospective study comparing core lab evaluation of angiographic outcomes with self-reported outcomes. Consecutive patients were enrolled from 10 US centres, aged between 18 and 85 with unruptured wide-neck middle cerebral artery (MCA) or basilar apex aneurysms treated endovascularly. Patient demographics, aneurysm morphology, procedural information, mortality and morbidity data and core lab and self-reported modified Raymond Roy (RR) outcomes were obtained. 115 patients met inclusion criteria. Intervention-related mortality and significant morbidity rates were 1.7% (2/115) and 5.8% (6/103) respectively. Core lab adjudicated RR1 and 2 occlusion rates at follow-up were 30.6% and 32.4% respectively. The retreatment rate within the follow-up window was 10/115 (8.7%) and in stent stenosis at follow-up was 5/63 (7.9%). Self-reporting shows a statistically significant direction to angiographic RR one outcomes at follow-up compared with core lab evaluation, with OR 1.75 (95% CI 1.08 to 2.83). Endovascular treatment of wide-neck MCA and basilar apex aneurysms resulted in a core lab adjudicated RR1 occlusion rate of 30.6%. Self-reported results at follow-up favour better angiographic outcomes, with OR 1.75 (95% CI 1.08 to 2.83). These data demonstrate the need for novel endovascular devices specifically designed to treat complex intracranial aneurysms, as well as the importance of core lab adjudication in assessing outcomes in such a trial. © 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.

Design of a multicentre randomized controlled trial to assess the safety and efficacy of dose titration by specialized nurses in patients with heart failure. ETIFIC study protocol.

PubMed

Oyanguren, Juana; García-Garrido, LLuisa; Nebot Margalef, Magdalena; Lekuona, Iñaki; Comin-Colet, Josep; Manito, Nicolás; Roure, Julia; Ruiz Rodriguez, Pilar; Enjuanes, Cristina; Latorre, Pedro; Torcal Laguna, Jesús; García-Gutiérrez, Susana

2017-11-01

Heart failure (HF) is associated with many hospital admissions and relatively high mortality, rates decreasing with administration of beta-blockers (BBs), angiotensin-converting-enzyme inhibitors, angiotensin II receptor blockers, and mineralocorticoid receptor antagonists. The effect is dose dependent, suboptimal doses being common in clinical practice. The 2012 European guidelines recommend close monitoring and dose titration by HF nurses. Our main aim is to compare BB doses achieved by patients after 4 months in intervention (HF nurse-managed) and control (cardiologist-managed) groups. Secondary aims include comparing doses of the other aforementioned drugs achieved after 4 months, adverse events, and outcomes at 6 months in the two groups. We have designed a multicentre (20 hospitals) non-inferiority randomized controlled trial, including patients with new-onset HF, left ventricular ejection fraction ≤40%, and New York Heart Association class II-III, with no contraindications to BBs. We will also conduct qualitative analysis to explore potential barriers to and facilitators of dose titration by HF nurses. In the intervention group, HF nurses will implement titration as prescribed by cardiologists, following a protocol. In controls, cardiologists will both prescribe and titrate doses. The study variables are doses of each of the drugs after 4 months relative to the target dose (%), New York Heart Association class, left ventricular ejection fraction, N-terminal pro B-type natriuretic peptide levels, 6 min walk distance, comorbidities, renal function, readmissions, mortality, quality of life, and psychosocial characteristics. The trial seeks to assess whether titration by HF nurses of drugs recommended in practice guidelines is safe and not inferior to direct management by cardiologists. The results could have an impact on clinical practice. © 2017 The Authors. ESC Heart Failure published by John Wiley & Sons Ltd on behalf of the European Society of Cardiology.

Twelve-month results of a prospective, multicentre trial to assess the everolimus-eluting coronary stent system (PROMUS Element): the PLATINUM PLUS all-comers randomised trial.

PubMed

Fajadet, Jean; Neumann, Franz-Josef; Hildick-Smith, David; Petronio, Sonia; Zaman, Azfar; Spence, Mark; Wöhrle, Jochen; Elhadad, Simon; Roberts, David; Hovasse, Thomas; Valdés, Mariano; Silber, Sigmund

2017-01-20

The aim of the study was to compare the safety and efficacy of the platinum-chromium-based everolimus-eluting stent (EES) with a cobalt-chromium EES. We performed a prospective, multicentre, single-blind non-inferiority all-comers study randomising patients with stable or unstable coronary artery disease (2:1) to treatment with the platinum-chromium EES (n=1,952) or the control cobalt-chromium EES (n=1,028) in Europe (PLATINUM PLUS trial). The primary endpoint was target vessel failure (TVF) at 12 months, a composite of target vessel-related cardiac death, myocardial infarction (MI), and ischaemia-driven target vessel revascularisation (TVR). Among 2,980 patients, 33% presented with acute coronary syndromes, and 48% with multivessel disease. At 12 months, the intention-to-treat analysis determined that the platinum-chromium EES was non-inferior to the cobalt-chromium EES for the primary endpoint (86 [4.6%] patients vs. 32 [3.2%], absolute difference 1.4%, 95% confidence interval [CI]: -0.1-2.9; upper limit of the one-sided 95% CI: 2.57%; non-inferiority p=0.012; superiority analysis: hazard ratio [HR] 1.44, 95% CI: 0.96-2.16, p=0.08). In the per protocol analysis, however, the primary endpoint was significantly more common in the platinum-chromium EES (HR 1.64, 95% CI: 1.05-2.55, p=0.03). There were no significant differences in the rates of cardiac death (1.1% vs. 1.0%, p=0.78), MI (1.6% vs. 0.8%, p=0.09), or ischaemia-driven TLR (2.0% vs. 1.6%, p=0.49). The rates of ARC definite or probable stent thrombosis were comparable between platforms (0.8% vs. 0.5%, p=0.44). At one year, the platinum-chromium EES satisfied the pre-specified criteria for non-inferiority relative to the control cobalt-chromium EES in this all-comers trial.

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

PubMed

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

2006-06-01

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

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

PubMed Central

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

2015-01-01

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

Physiotherapy and occupational therapy interventions for people with benign joint hypermobility syndrome: a systematic review of clinical trials.

PubMed

Smith, Toby O; Bacon, Holly; Jerman, Emma; Easton, Vicky; Armon, Kate; Poland, Fiona; Macgregor, Alex J

2014-01-01

This study assessed the literature to determine the efficacy and effectiveness of physiotherapy and occupational therapy interventions in the treatment of people with benign joint hypermobility syndrome (BJHS). Published literature databases including: AMED, CINAHL, MEDLINE, EMBASE, PubMed and the Cochrane Library, in addition to unpublished databases and trial registries were searched to October 2012. All clinical trials comparing the clinical outcomes of Occupational Therapy and Physiotherapy interventions compared to non-treatment or control intervention for people with BJHS were included. Of the 126 search results, 3 clinical studies satisfied the eligibility criteria. The data provides limited support for the use of wrist/hand splints for school children. While there is some support for exercise-based intervention, there is insufficient research to determine the optimal mode, frequency, dosage or type of exercise which should be delivered. The current evidence-base surrounding Occupational Therapy and Physiotherapy in the management of BJHS is limited in size and quality. There is insufficient research exploring the clinical outcomes of a number of interventions including sensory integration, positioning and posture management and education. Longer term, rigorous multi-centre randomised controlled trials are warranted to begin to assess the clinical and cost-effectiveness of interventions for children and adults with BJHS. Implications for Rehabilitation There is an evidence-base to support clinician's use of proprioceptive-based exercises in adults, and either tailored or generalised physiotherapy regimes for children with BJHS. Clinicians should be cautious when considering the prescription of hand/wrist splints for school age children with BJHS, based on the current research. Until further multi-centre trials are conducted assessing the clinical and cost-effectiveness of interventions for children and adult with BJHS, clinical decision-making should be based on theoretical rather than evidence-based grounds for this population.

Efficacy and Safety of the Biosimilar Infliximab CT-P13 Treatment in Inflammatory Bowel Diseases: A Prospective, Multicentre, Nationwide Cohort.

PubMed

Gecse, Krisztina B; Lovász, Barbara D; Farkas, Klaudia; Banai, János; Bene, László; Gasztonyi, Beáta; Golovics, Petra Anna; Kristóf, Tünde; Lakatos, László; Csontos, Ágnes Anna; Juhász, Márk; Nagy, Ferenc; Palatka, Károly; Papp, Mária; Patai, Árpád; Lakner, Lilla; Salamon, Ágnes; Szamosi, Tamás; Szepes, Zoltán; Tóth, Gábor T; Vincze, Áron; Szalay, Balázs; Molnár, Tamás; Lakatos, Péter L

2016-02-01

Biosimilar infliximab CT-P13 is approved for all indications of the originator product in Europe. Prospective data on its efficacy, safety, and immunogenicity in inflammatory bowel diseases are lacking. A prospective, nationwide, multicentre, observational cohort was designed to examine the efficacy, safety, and immunogenicity of CT-P13 infliximab biosimilar in the induction treatment of Crohn's disease [CD] and ulcerative colitis [UC]. Demographic data were collected and a harmonised monitoring strategy was applied. Early clinical remission, response, and early biochemical response were evaluated at Week 14, steroid-free clinical remission was evaluated at Week 30. Therapeutic drug level was monitored using a conventional enzyme-linked immunosorbent assay. In all, 210 consecutive inflammatory bowel disease [126 CD and 84 UC] patients were included in the present cohort. At Week 14, 81.4% of CD and 77.6% of UC patients showed clinical response and 53.6% of CD and 58.6% of UC patients were in clinical remission. Clinical remission rates at Week 14 were significantly higher in CD and UC patients who were infliximab naïve, compared with those with previous exposure to the originator compound [p < 0.05]. Until Week 30, adverse events were experienced in 17.1% of all patients. Infusion reactions and infectious adverse events occurred in 6.6% and 5.7% of all patients, respectively. This prospective multicentre cohort shows that CT-P13 is safe and effective in the induction of clinical remission and response in both CD and UC. Patients with previous infliximab exposure exhibited decreased response rates and were more likely to develop allergic reactions. Copyright © 2015 European Crohn’s and Colitis Organisation (ECCO). Published by Oxford University Press. All rights reserved. For permissions, please email: journals.permissions@oup.com.

A pragmatic, multicentre, randomised controlled trial comparing stapled haemorrhoidopexy to traditional excisional surgery for haemorrhoidal disease (eTHoS): study protocol for a randomised controlled trial.

PubMed

Watson, Angus J M; Bruhn, Hanne; MacLeod, Kathleen; McDonald, Alison; McPherson, Gladys; Kilonzo, Mary; Norrie, John; Loudon, Malcolm A; McCormack, Kirsty; Buckley, Brian; Brown, Steven; Curran, Finlay; Jayne, David; Rajagopal, Ramesh; Cook, Jonathan A

2014-11-11

Current interventions for haemorrhoidal disease include traditional haemorrhoidectomy (TH) and stapled haemorrhoidopexy (SH) surgery. However, uncertainty remains as to how they compare from a clinical, quality of life (QoL) and economic perspective. The study is therefore designed to determine whether SH is more effective and more cost-effective, compared with TH. eTHoS (either Traditional Haemorrhoidectomy or Stapled Haemorrhoidopexy for Haemorrhoidal Disease) is a pragmatic, multicentre, randomised controlled trial. Currently, 29 secondary care centres are open to recruitment. Patients, aged 18 year or older, with circumferential haemorrhoids grade II to IV, are eligible to take part. The primary clinical and economic outcomes are QoL profile (area under the curve derived from the EuroQol Group's 5 Dimension Health Status Questionnaire (EQ-5D) at all assessment points) and incremental cost per quality adjusted life year (QALY) based on the responses to the EQ-5D at 24 months. The secondary outcomes include a comparison of the SF-36 scores, pain and symptoms sub-domains, disease recurrence, complication rates and direct and indirect costs to the National Health Service (NHS). A sample size of n =338 per group has been calculated to provide 90% power to detect a difference in the mean area under the curve (AUC) of 0.25 standard deviations derived from EQ-5D score measurements, with a two-sided significance level of 5%. Allowing for non-response, 400 participants will be randomised per group. Randomisation will utilise a minimisation algorithm that incorporates centre, grade of haemorrhoidal disease, baseline EQ-5D score and gender. Blinding of participants and outcome assessors is not attempted. This is one of the largest trials of its kind. In the United Kingdom alone, 29,000 operations for haemorrhoidal disease are done annually. The trial is therefore designed to give robust evidence on which clinicians and health service managers can base management decisions and, more importantly, patients can make informed choices. Current Controlled Trials ISRCTN80061723 (assigned 8 March 2010).

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

PubMed

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

2018-04-16

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

A 12-month, open-label, comparative study of quetiapine and risperidone in the acute and long-term treatment of schizophrenia.

PubMed

Perez, Victor; Cañas, Fernando; Tafalla, Monica

2008-05-01

This multicentre, observational, prospective, nonrandomized study compared the effectiveness and tolerability of quetiapine and risperidone in the acute and long-term treatment of schizophrenia in a clinical setting. Patients admitted to an acute unit with schizophrenia, schizophreniform or schizoaffective disorder (DSM-IV), who were prescribed quetiapine or risperidone (3 : 1 ratio) within the first week of treatment, according to the physician's usual practice, were recruited. In total, 492 patients (quetiapine: 367; risperidone: 125) were followed up at weeks 1 and 2, discharge and 6 and 12 months thereafter. Mean doses at 12 months were: quetiapine 718.5 mg/day and risperidone 7.0 mg/day. Efficacy measures (Brief Psychiatric Rating Scale, Clinical Global Impression Severity of Illness and Improvement) indicated similar results for both agents. No difference was found in rehospitalization rate with either drug. In terms of tolerability, orthostatic hypotension was more frequent with quetiapine, but extrapyramidal symptoms and male sexual dysfunction were more frequent with risperidone. In conclusion, quetiapine and risperidone had comparable effectiveness, but there were differences between treatments in their side effect profile.

Cost-efficiency of specialist inpatient rehabilitation for working-aged adults with complex neurological disabilities: a multicentre cohort analysis of a national clinical data set.

PubMed

Turner-Stokes, Lynne; Williams, Heather; Bill, Alan; Bassett, Paul; Sephton, Keith

2016-02-24

To evaluate functional outcomes, care needs and cost-efficiency of specialist rehabilitation for a multicentre cohort of inpatients with complex neurological disability, comparing different diagnostic groups across 3 levels of dependency. A multicentre cohort analysis of prospectively collected clinical data from the UK Rehabilitation Outcomes Collaborative (UKROC) national clinical database, 2010-2015. All 62 specialist (levels 1 and 2) rehabilitation services in England. Working-aged adults (16-65 years) with complex neurological disability. all episodes with length of stay (LOS) 8-400 days and complete outcome measures recorded on admission and discharge. Total N=5739: acquired brain injury n=4182 (73%); spinal cord injury n=506 (9%); peripheral neurological conditions n=282 (5%); progressive conditions n=769 (13%). Specialist inpatient multidisciplinary rehabilitation. Dependency and care costs: Northwick Park Dependency Scale/Care Needs Assessment (NPDS/NPCNA). Functional independence: UK Functional Assessment Measure (UK Functional Independence Measure (FIM)+FAM). Cost-efficiency: (1) time taken to offset rehabilitation costs by savings in NPCNA-estimated costs of ongoing care, (2) FIM efficiency (FIM gain/LOS days), (3) FIM+FAM efficiency (FIM+FAM gain/LOS days). Patients were analysed in 3 groups of dependency. Mean LOS 90.1 (SD 66) days. All groups showed significant reduction in dependency between admission and discharge on all measures (paired t tests: p<0.001). Mean reduction in 'weekly care costs' was greatest in the high-dependency group at £760/week (95% CI 726 to 794)), compared with the medium-dependency (£408/week (95% CI 370 to 445)), and low-dependency (£130/week (95% CI 82 to 178)), groups. Despite longer LOS, time taken to offset the cost of rehabilitation was 14.2 (95% CI 9.9 to 18.8) months in the high-dependency group, compared with 22.3 (95% CI 16.9 to 29.2) months (medium dependency), and 27.7 (95% CI 15.9 to 39.7) months (low dependency). FIM efficiency appeared greatest in medium-dependency patients (0.54), compared with the low-dependency (0.37) and high-dependency (0.38) groups. Broadly similar patterns were seen across all 4 diagnostic groups. Specialist rehabilitation can be highly cost-efficient for all neurological conditions, producing substantial savings in ongoing care costs, especially in high-dependency patients. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

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

PubMed

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

2014-09-01

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

Anrukinzumab, an anti-interleukin 13 monoclonal antibody, in active UC: efficacy and safety from a phase IIa randomised multicentre study.

PubMed

Reinisch, Walter; Panés, Julián; Khurana, Sunil; Toth, Gabor; Hua, Fei; Comer, Gail M; Hinz, Michelle; Page, Karen; O'Toole, Margot; Moorehead, Tara McDonnell; Zhu, Hua; Sun, YanHui; Cataldi, Fabio

2015-06-01

Interleukin 13 (IL-13) is thought to play a key role as an effector cytokine in UC. Anrukinzumab, a humanised antibody that inhibits human IL-13, was evaluated for the treatment of UC. In a multicentre, randomised, double-blind, placebo-controlled study, patients with active UC (Mayo score ≥4 and <10) were randomised to anrukinzumab 200, 400 or 600 mg or placebo. Patients received five intravenous administrations over 14 weeks. The primary endpoint was fold change from baseline in faecal calprotectin (FC) at Week 14. Secondary endpoints included safety, pharmacokinetics and IL-13 levels. The modified intention-to-treat population included 84 patients (21 patients/arm). Fold change of FC from baseline at Week 14 was not significantly different for any treatment groups compared with the placebo. The study had a high dropout rate, in part, related to lack of efficacy. The exploratory comparisons of each dose were not significantly different from placebo in terms of change from baseline in total Mayo score, clinical response, clinical remission and proportion of subjects with mucosal healing. An increase in serum total IL-13 (free and bound to anrukinzumab) was observed for all anrukinzumab groups but not with placebo. This suggests significant binding of anrukinzumab to IL-13. The safety profile was not different between the anrukinzumab and placebo groups. A statistically significant therapeutic effect of anrukinzumab could not be demonstrated in patients with active UC in spite of binding of anrukinzumab to IL-13. ClinicalTrials.gov number NCT01284062. 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.

Add-on levetiracetam in children and adolescents with refractory epilepsy: results of an open-label multi-centre study.

PubMed

Callenbach, Petra M C; Arts, Willem Frans M; ten Houten, Robert; Augustijn, Paul; Gunning, W Boudewijn; Peeters, Els A J; Weber, Alma M; Stroink, Hans; Geerts, Yvette; Geerts, Ada T; Brouwer, Oebele F

2008-07-01

To study the efficacy and tolerability of add-on levetiracetam in children and adolescents with refractory epilepsy. In this prospective multi-centre, open-label, add-on study, 33 children aged 4-16 years (median 8.5 years) with epilepsy refractory to at least two antiepileptic drugs were treated with levetiracetam in addition to their present treatment regimen with a follow-up of 26 weeks. The starting dose of 10 mg/kg/day was increased with 2-week steps of 10 mg/kg/day, if necessary, up to a maximum dose of 60 mg/kg/day. Retention rate was 69.7% after 26 weeks on a median levetiracetam dosage of 22 mg/kg/day. Four children dropped-out because levetiracetam was ineffective, four because seizure frequency increased and/or seizures became more severe, and two because they developed aggressive behaviour. Compared to their baseline seizure frequency, 13 children (39.4%) had a >50% seizure reduction 12 weeks after initiation of levetiracetam, and 17 children (51.5%) at 26 weeks. At 26 weeks, nine children (27.3%) had been seizure-free for at least the last 4 weeks, terminal remission ranged from 0 to 187 days (mean 46 days). Levetiracetam was effective in both partial and primary generalized seizures, but had most effect in partial seizures. Most reported side effects were hyperactivity (48.5%), somnolence (36.4%), irritability (33.3%) and aggressive behaviour (27.3%). Severity of most side effects was mild. Five children had a serious adverse event, which all concerned hospital admissions that were not related to levetiracetam use. Levetiracetam proved to be an effective and well-tolerated add-on treatment in this group of children with refractory epilepsy.

The Prevalence and Characteristics of Primary Headache and Dream-Enacting Behaviour in Japanese Patients with Narcolepsy or Idiopathic Hypersomnia: A Multi-Centre Cross-Sectional Study.

PubMed

Suzuki, Keisuke; Miyamoto, Masayuki; Miyamoto, Tomoyuki; Inoue, Yuichi; Matsui, Kentaro; Nishida, Shingo; Hayashida, Kenichi; Usui, Akira; Ueki, Yoichiro; Nakamura, Masaki; Murata, Momoyo; Numao, Ayaka; Watanabe, Yuji; Suzuki, Shiho; Hirata, Koichi

2015-01-01

Because the prevalence and characteristics of primary headache have yet to be thoroughly studied in patients with hypersomnia disorders, including narcolepsy and idiopathic hypersomnia, we examined these parameters in the Japanese population. In a multicentre cross-sectional survey, among 576 consecutive outpatients with sleep disorders, 68 narcolepsy patients and 35 idiopathic hypersomnia patients were included. Additionally, 61 healthy control subjects participated. Semi-structured headache questionnaires were administered to all participants. The patients with narcolepsy (52.9%) and idiopathic hypersomnia (77.1%) more frequently experienced headache than the healthy controls (24.6%; p<0.0001). The prevalence rates were 23.5%, 41.2% and 4.9% for migraine (p<0.0001) and 16.2%, 23.5% and 14.8% (p = 0.58) for tension-type headache among the narcolepsy patients, the idiopathic hypersomnia patients and the control subjects, respectively. Those who experienced migraine more frequently experienced excessive daytime sleepiness, defined as an Epworth Sleepiness Scale score of ≥10, than those who did not experience headache among the patients with narcolepsy (93.8% vs. 65.6%, p = 0.040) and idiopathic hypersomnia (86.7% vs. 37.5%, p = 0.026). Dream-enacting behaviour (DEB), as evaluated by the rapid eye movement sleep disorders questionnaire, was more frequently observed in the narcolepsy patients than in the idiopathic hypersomnia patients and the control subjects. An increased DEB frequency was observed in the narcolepsy patients with migraines compared to those without headache. Migraines were frequently observed in patients with narcolepsy and idiopathic hypersomnia. DEB is a characteristic of narcolepsy patients. Further studies are required to assess the factors that contribute to migraines in narcolepsy and idiopathic hypersomnia patients.

The Prevalence and Characteristics of Primary Headache and Dream-Enacting Behaviour in Japanese Patients with Narcolepsy or Idiopathic Hypersomnia: A Multi-Centre Cross-Sectional Study

PubMed Central

Suzuki, Keisuke; Miyamoto, Masayuki; Miyamoto, Tomoyuki; Inoue, Yuichi; Matsui, Kentaro; Nishida, Shingo; Hayashida, Kenichi; Usui, Akira; Ueki, Yoichiro; Nakamura, Masaki; Murata, Momoyo; Numao, Ayaka; Watanabe, Yuji; Suzuki, Shiho; Hirata, Koichi

2015-01-01

Background Because the prevalence and characteristics of primary headache have yet to be thoroughly studied in patients with hypersomnia disorders, including narcolepsy and idiopathic hypersomnia, we examined these parameters in the Japanese population. Methods In a multicentre cross-sectional survey, among 576 consecutive outpatients with sleep disorders, 68 narcolepsy patients and 35 idiopathic hypersomnia patients were included. Additionally, 61 healthy control subjects participated. Semi-structured headache questionnaires were administered to all participants. Results The patients with narcolepsy (52.9%) and idiopathic hypersomnia (77.1%) more frequently experienced headache than the healthy controls (24.6%; p<0.0001). The prevalence rates were 23.5%, 41.2% and 4.9% for migraine (p<0.0001) and 16.2%, 23.5% and 14.8% (p = 0.58) for tension-type headache among the narcolepsy patients, the idiopathic hypersomnia patients and the control subjects, respectively. Those who experienced migraine more frequently experienced excessive daytime sleepiness, defined as an Epworth Sleepiness Scale score of ≥10, than those who did not experience headache among the patients with narcolepsy (93.8% vs. 65.6%, p = 0.040) and idiopathic hypersomnia (86.7% vs. 37.5%, p = 0.026). Dream-enacting behaviour (DEB), as evaluated by the rapid eye movement sleep disorders questionnaire, was more frequently observed in the narcolepsy patients than in the idiopathic hypersomnia patients and the control subjects. An increased DEB frequency was observed in the narcolepsy patients with migraines compared to those without headache. Conclusions Migraines were frequently observed in patients with narcolepsy and idiopathic hypersomnia. DEB is a characteristic of narcolepsy patients. Further studies are required to assess the factors that contribute to migraines in narcolepsy and idiopathic hypersomnia patients. PMID:26418536

Tumour stage and gender predict recurrence and second primary malignancies in head and neck cancer: a multicentre study within the INHANCE consortium.

PubMed

Leoncini, Emanuele; Vukovic, Vladimir; Cadoni, Gabriella; Giraldi, Luca; Pastorino, Roberta; Arzani, Dario; Petrelli, Livia; Wünsch-Filho, Victor; Toporcov, Tatiana Natasha; Moyses, Raquel Ayub; Matsuo, Keitaro; Bosetti, Cristina; La Vecchia, Carlo; Serraino, Diego; Simonato, Lorenzo; Merletti, Franco; Boffetta, Paolo; Hashibe, Mia; Lee, Yuan-Chin Amy; Boccia, Stefania

2018-05-19

Recurrence and second primary cancer (SPC) continue to represent major obstacles to long-term survival in head and neck cancer (HNC). Our aim was to evaluate whether established demographics, lifestyle-related risk factors for HNC and clinical data are associated with recurrence and SPC in HNC. We conducted a multicentre study by using data from five studies members of the International Head and Neck Cancer Epidemiology consortium-Milan, Rome, Western Europe, Sao Paulo, and Japan, totalling 4005 HNC cases with a median age of 59 (interquartile range 52-67). Multivariate hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated for recurrence and SPC. During follow-up, 1161 (29%) patients had recurrence and 343 (8.6%) developed SPC. Advanced tumour stage was associated with increased risk of recurrence in HNC overall (HR = 1.76, 95% CI 1.41-2.19). Women with laryngeal cancer had a reduced risk of recurrence compared to men (HR = 0.39, 95% CI: 0.24-0.74). Concerning predictors of SPC, advanced age (HR = 1.02; 95% CI: 1.00-1.04) and alcohol consumption (> 1 drink per day, HR = 2.11; 95% CI: 1.13-3.94) increased the risk of SPC among patients with laryngeal cancer. Additionally, women were at higher risk of SPC, in HNC overall group (HR = 1.68; 95% CI: 1.13-2.51) and oropharyngeal cancer group (HR = 1.74; 95% CI: 1.02-2.98). Tumour stage and male gender (larynx only) were positive predictors of cancer recurrence in HNC patients. Predictors of SPC were advanced age and alcohol use among laryngeal cancer cases, and female gender for oropharyngeal and HNC overall.

Simulation-based team training for multi-professional obstetric care teams to improve patient outcome: a multicentre, cluster randomised controlled trial.

PubMed

Fransen, A F; van de Ven, J; Schuit, E; van Tetering, Aac; Mol, B W; Oei, S G

2017-03-01

To investigate whether simulation-based obstetric team training in a simulation centre improves patient outcome. Multicentre, open, cluster randomised controlled trial. Obstetric units in the Netherlands. Women with a singleton pregnancy beyond 24 weeks of gestation. Random allocation of obstetric units to a 1-day, multi-professional, simulation-based team training focusing on crew resource management (CRM) in a simulation centre or to no such team training. Intention-to-treat analyses were performed at the cluster level, including a measurement 1 year prior to the intervention. Primary outcome was a composite outcome of obstetric complications during the first year post-intervention, including low Apgar score, severe postpartum haemorrhage, trauma due to shoulder dystocia, eclampsia and hypoxic-ischaemic encephalopathy. Maternal and perinatal mortality were also registered. Each study group included 12 units with a median unit size of 1224 women, combining for a total of 28 657 women. In total, 471 medical professionals received the training course. The composite outcome of obstetric complications did not differ between study groups [odds ratio (OR) 1.0, 95% confidence interval (CI) 0.80-1.3]. Team training reduced trauma due to shoulder dystocia (OR 0.50, 95% CI 0.25-0.99) and increased invasive treatment for severe postpartum haemorrhage (OR 2.2, 95% CI 1.2-3.9) compared with no intervention. Other outcomes did not differ between study groups. A 1-day, off-site, simulation-based team training, focusing on teamwork skills, did not reduce a composite of obstetric complications. 1-day, off-site, simulation-based team training did not reduce a composite of obstetric complications. © 2016 Royal College of Obstetricians and Gynaecologists.

Blunt Cardiac Injury in the Severely Injured – A Retrospective Multicentre Study

PubMed Central

Hanschen, Marc; Kanz, Karl-Georg; Kirchhoff, Chlodwig; Khalil, Philipe N.; Wierer, Matthias; van Griensven, Martijn; Laugwitz, Karl-Ludwig; Biberthaler, Peter; Lefering, Rolf; Huber-Wagner, Stefan

2015-01-01

Background Blunt cardiac injury is a rare trauma entity. Here, we sought to evaluate the relevance and prognostic significance of blunt cardiac injury in severely injured patients. Methods In a retrospective multicentre study, using data collected from 47,580 patients enrolled to TraumaRegister DGU (1993-2009), characteristics of trauma, prehospital / hospital trauma management, and outcome analysis were correlated to the severity of blunt cardiac injury. The severity of cardiac injury was assessed according to the abbreviated injury score (AIS score 1-6), the revised injury severity score (RISC) allowed comparison of expected outcome with injury severity-dependent outcome. N = 1.090 had blunt cardiac trauma (AIS 1-6) (2.3% of patients). Results Predictors of blunt cardiac injury could be identified. Sternal fractures indicate a high risk of the presence of blunt cardiac injury (AIS 0 [control]: 3.0%; AIS 1: 19.3%; AIS 2-6: 19.1%). The overall mortality rate was 13.9%, minor cardiac injury (AIS 1) and severe cardiac injury (AIS 2-6) are associated with higher rates. Severe blunt cardiac injury (AIS 4 and AIS 5-6) is associated with a higher mortality (OR 2.79 and 4.89, respectively) as compared to the predicted average mortality (OR 2.49) of the study collective. Conclusion Multiple injured patients with blunt cardiac trauma are at high risk to be underestimated. Careful evaluation of trauma patients is able to predict the presence of blunt cardiac injury. The severity of blunt cardiac injury needs to be stratified according to the AIS score, as the patients’ outcome is dependent on the severity of cardiac injury. PMID:26136126

Differences in acute retroviral syndrome by HIV-1 subtype in a multicentre cohort study in Africa

PubMed Central

Sanders, Eduard J.; Price, Matthew A.; Karita, Etienne; Kamali, Anatoli; Kilembe, William; Bekker, Linda-Gail; Lakhi, Shabir; Inambao, Mubiana; Anzala, Omu; Fast, Patricia E.; Gilmour, Jill; Powers, Kimberly A.

2017-01-01

Objective: Symptoms of acute retroviral syndrome (ARS) may be used to identify patients with acute HIV-1 infection who seek care. ARS symptoms in African adults differ by region. We assessed whether reporting of ARS was associated with HIV-1 subtype in a multicentre African cohort study representing countries with predominant HIV-1 subtypes A, C, and D. Methods: ARS symptoms were assessed in adults enrolling at least 6 weeks after the estimated date of infection in an acute and early HIV-1 infection cohort study. HIV-1 subtype was determined by POL genotyping. We used log-binomial regression to compare ARS symptom prevalence among those with subtype A vs. C or D, adjusting for sex, time since enrolment, and enrolment viral load. Results: Among 183 volunteers ascertained within 6 weeks after estimated date of infection, 77 (42.0%) had subtype A, 83 (45.4%) subtype C, and 23 (12.6%) subtype D infection. Individuals with subtype A were 1.40 (95% confidence interval: 1.17, 1.68) times as likely as individuals with subtypes C or D to report any ARS symptoms; each individual symptom other than rash was also more prevalent in subtype A than in subtype C or D, with prevalence ratios ranging from 1.94 (1.40, 2.70) for headache to 4.92 (2.24, 10.78) for lymphadenopathy. Conclusion: Individuals with subtype A were significantly more likely than individuals with subtypes C or D to report any ARS symptoms. HIV-1 subtypes may help explain differences in ARS that have been observed across regions in Africa, and may impact the yield of symptom-based screening strategies for acute HIV infection detection. PMID:29028659

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

PubMed

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

2018-03-01

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

Patient satisfaction with switching to esomeprazole from existing proton pump inhibitor therapy for gastro-oesophageal reflux disease: an observational, multicentre study.

PubMed

Hoogendoorn, Robert J; Groeneveld, Lex; Kwee, J Andy

2009-01-01

To determine treatment satisfaction in patients with gastro-oesophageal reflux disease (GORD) when switched to esomeprazole. This observational, multicentre study conducted in the Netherlands included primary-care patients being treated with a proton pump inhibitor (PPI) [omeprazole, pantoprazole, rabeprazole or lansoprazole] for GORD who were switched to esomeprazole by their physician. After a median of 28 days' esomeprazole therapy, patients' satisfaction was assessed using a questionnaire. Patients self-rated whether they were 'more satisfied', felt there was 'no difference' or were 'less satisfied' with esomeprazole compared with previous PPI therapy. Symptom control, concomitant medication use and tolerability were also assessed. Overall, 4929 patients were included in this study; of these, only 21.9% were satisfied with PPI treatment at consultation (i.e. prior to switching to esomeprazole). Following switching to esomeprazole therapy, 88.0% of patients were satisfied with therapy and only 26.9% of patients were still experiencing symptoms (vs 84.0% at consultation); 71.3% were more satisfied with esomeprazole than with their previous PPI, most frequently because they had fewer or no symptoms. Among patients who had been using concomitant therapy to control GORD symptoms, 62.0% were no longer using any such medication. Of the 1069 patients who had been satisfied with their previous PPI therapy, 39.4% were even more satisfied with esomeprazole. Esomeprazole was well tolerated; the most commonly reported adverse events were nausea/vomiting and headache, and no treatment-related serious adverse events occurred. Among primary-care patients receiving PPI therapy for GORD, switching to esomeprazole therapy impacts positively on treatment satisfaction and symptom control.

Comparison of intravenous versus combined oral and intravenous antimicrobial prophylaxis (COMBINE) for the prevention of surgical site infection in elective colorectal surgery: study protocol for a multicentre, double-blind, randomised controlled clinical trial

PubMed Central

Vignaud, Marie; Paugam-Burtz, Catherine; Garot, Matthias; Jaber, Samir; Slim, Karem; Panis, Yves; Lucet, Jean-Christophe; Bourdier, Justine; Morand, Dominique; Pereira, Bruno; Futier, Emmanuel

2018-01-01

Introduction Surgical site infections (SSIs) account for 30% of all healthcare-associated infections, with reported rates ranging from 8% and 30% after colorectal surgery and are associated with increased morbidity and mortality rates, length of hospital stay and costs in healthcare. Administration of systemic antimicrobial prophylaxis before surgery is recommended to reduce the risk of SSI, but the optimal regimen remains unclear. We aim to evaluate whether a combined oral and intravenous antimicrobial prophylaxis could be more effective to reduce the incidence of SSI after colorectal surgery, as compared with the standard practice of intravenous antimicrobial prophylaxis alone. Methods and analysis Comparison of intravenous versus combined oral and intravenous antimicrobial prophylaxis (COMBINE) trial is a randomised, placebo-controlled, parallel, double-blind, multicentre study of 960 patients undergoing elective colorectal surgery. Patients will be randomly allocated in a 1:1 ratio to receive either combined oral and intravenous antimicrobial prophylaxis or intravenous antibiotic prophylaxis alone, stratified by centre, the surgical procedure (laparoscopic or open surgery) and according to the surgical skin antisepsis (chlorexidine–alcohol or povidione-iodine alcoholic solution). The primary endpoint is the rate of SSI by day 30 following surgery, with SSI defined by the criteria developed by the Centers for Disease Control and Prevention. Data will be analysed on the intention-to-treat principle and a per-protocol basis. Ethics and dissemination COMBINE trial has been approved by an independent ethics committee for all study centres. Participant recruitment began in May 2016. Results will be published in international peer-reviewed medical journals. Trial registration number EudraCT 2015-002559-84; NCT02618720. PMID:29654027

Lifestyle correlates of self-reported sleep duration among Saudi adolescents: a multicentre school-based cross-sectional study.

PubMed

Al-Hazzaa, H M; Musaiger, A O; Abahussain, N A; Al-Sobayel, H I; Qahwaji, D M

2014-07-01

Lifestyle factors are important determinants of adequate sleep among adolescents. However, findings on sleep duration relative to lifestyle factors are conflicting. Therefore, this study examined the association of self-reported sleep duration with physical activity, sedentary behaviours and dietary habits among Saudi adolescents. A multicentre school-based cross-sectional study was conducted in three major cities in Saudi Arabia. The sample included 2868 secondary-school students (51.9% girls) aged 15-19 years, randomly selected using a multistage stratified cluster sampling technique. In addition to anthropometric measurements, sleep duration, physical activity, sedentary behaviours and dietary habits were assessed using self-reported questionnaire. Several lifestyle factors were associated with sleep duration in adolescents. While controlling for some potential confounders, the findings showed that high screen time [>5 h/day; adjusted odds ratio (aOR) = 1.505, 95% confidence interval (CI) = 1.180-1.920, P = 0.001] and low (aOR = 1.290, 95% CI = 1.064-1.566, P = 0.010) to medium (aOR = 1.316, 95% CI = 1.075-1.611, P = 0.008) physical activity levels were significantly related to daily sleep of 8 h or longer. Furthermore, having low intake of breakfast (<3 day/week compared with 5 days or more per week) decreased the odd of having adequate sleep duration by a factor of 0.795 (95% CI = 0.667-0.947, P < 0.010). Short sleep duration (<8 h/day) among Saudi adolescents 15-19 year olds was significantly associated with several lifestyle factors. Intervention programs aiming for improving sleeping habits among adolescents need to consider such potential association of lifestyle variables with sleep duration. © 2013 John Wiley & Sons Ltd.

The effect of Helicobacter pylori infection and eradication in patients with gastro-oesophageal reflux disease: A parallel-group, double-blind, placebo-controlled multicentre study.

PubMed

Schwizer, Werner; Menne, Dieter; Schütze, Kurt; Vieth, Michael; Goergens, Reiner; Malfertheiner, Peter; Leodolter, Andreas; Fried, Michael; Fox, Mark R

2013-08-01

This study aimed to resolve controversy regarding the effects of Helicobacter pylori eradication therapy and H. pylori infection in gastro-oesophageal reflux disease. A randomized, double-blind, multicentre trial was performed in patients presenting with reflux symptoms. H. pylori-positive patients were randomized to receive either antibiotics or placebo for 7 days. H. pylori-negative patient controls received placebo. All received esomeprazole 20 mg b.d. for 7 days, followed by 40 mg o.d. to complete an 8-week course, and were followed up for 32 weeks by telephone. In this study, 198/589 (34%) patients were H. pylori-positive and 113 H. pylori-negative patients served as controls. Baseline endoscopy revealed 63% Los Angeles grade 0A and 37% Los Angeles grade BCD oesophagitis with no difference between patient groups. Symptom improvement on esomeprazole was seen in 89%. H. pylori eradication was successful in 82%. H. pylori eradication had no effect on symptomatic relapse (hazard ratio 1.15, 95% CI 0.74-1.8; p = 0.5). Overall, H. pylori-positive patients had a lower probability of relapse compared to H. pylori-negative controls (hazard ratio 0.6, 95% CI 0.43-0.85; p = 0.004). Relapse hazard was modulated also by oesophagitis grade (BCD vs. 0A, hazard ratio 2.1, 95% CI 1.5-3.0). Relapse of gastro-oesophageal reflux disease symptoms after a course of high dose acid suppression took longer for H. pylori-positive patients than H. pylori-negative controls; however eradication therapy had no effect on the risk of relapse; ClincialTrials.gov number, NCT00574925.

The effect of Helicobacter pylori infection and eradication in patients with gastro-oesophageal reflux disease: A parallel-group, double-blind, placebo-controlled multicentre study

PubMed Central

Menne, Dieter; Schütze, Kurt; Vieth, Michael; Goergens, Reiner; Malfertheiner, Peter; Leodolter, Andreas; Fried, Michael; Fox, Mark R

2013-01-01

Objectives This study aimed to resolve controversy regarding the effects of Helicobacter pylori eradication therapy and H. pylori infection in gastro-oesophageal reflux disease. Design A randomized, double-blind, multicentre trial was performed in patients presenting with reflux symptoms. H. pylori-positive patients were randomized to receive either antibiotics or placebo for 7 days. H. pylori-negative patient controls received placebo. All received esomeprazole 20 mg b.d. for 7 days, followed by 40 mg o.d. to complete an 8-week course, and were followed up for 32 weeks by telephone. Results In this study, 198/589 (34%) patients were H. pylori-positive and 113 H. pylori-negative patients served as controls. Baseline endoscopy revealed 63% Los Angeles grade 0A and 37% Los Angeles grade BCD oesophagitis with no difference between patient groups. Symptom improvement on esomeprazole was seen in 89%. H. pylori eradication was successful in 82%. H. pylori eradication had no effect on symptomatic relapse (hazard ratio 1.15, 95% CI 0.74–1.8; p = 0.5). Overall, H. pylori-positive patients had a lower probability of relapse compared to H. pylori-negative controls (hazard ratio 0.6, 95% CI 0.43–0.85; p = 0.004). Relapse hazard was modulated also by oesophagitis grade (BCD vs. 0A, hazard ratio 2.1, 95% CI 1.5–3.0). Conclusion Relapse of gastro-oesophageal reflux disease symptoms after a course of high dose acid suppression took longer for H. pylori-positive patients than H. pylori-negative controls; however eradication therapy had no effect on the risk of relapse; ClincialTrials.gov number, NCT00574925. PMID:24917966

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.

Efficacy and safety of a non-acetylated salicylate, choline magnesium trisalicylate, in the treatment of rheumatoid arthritis.

PubMed

Rothwell, K G

1983-01-01

The results of three double-blind, multicentre trials are reviewed to compare the efficacy of acetysalicylic acid (ASA) and a non-acetylated salicylate, choline magnesium trisalicylate (CMT), in the treatment of rheumatoid arthritis. In each trial, patients were randomly assigned to receive comparable doses of salicylate as either ASA or CMT. Mean values for clinical indicators of rheumatoid arthritis (number of painful joints, articular index, number of swollen joints, swelling index, duration of morning stiffness) showed similar or greater improvement among groups of patients receiving CMT, compared to those receiving ASA. In addition, the incidence of gastro-intestinal side-effects was lower among patients receiving CMT.

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.

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.

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.

Multicentre prospective cohort study of body mass index and postoperative complications following gastrointestinal surgery.

PubMed

2016-08-01

There is currently conflicting evidence surrounding the effects of obesity on postoperative outcomes. Previous studies have found obesity to be associated with adverse events, but others have found no association. The aim of this study was to determine whether increasing body mass index (BMI) is an independent risk factor for development of major postoperative complications. This was a multicentre prospective cohort study across the UK and Republic of Ireland. Consecutive patients undergoing elective or emergency gastrointestinal surgery over a 4-month interval (October-December 2014) were eligible for inclusion. The primary outcome was the 30-day major complication rate (Clavien-Dindo grade III-V). BMI was grouped according to the World Health Organization classification. Multilevel logistic regression models were used to adjust for patient, operative and hospital-level effects, creating odds ratios (ORs) and 95 per cent confidence intervals (c.i.). Of 7965 patients, 2545 (32·0 per cent) were of normal weight, 2673 (33·6 per cent) were overweight and 2747 (34·5 per cent) were obese. Overall, 4925 (61·8 per cent) underwent elective and 3038 (38·1 per cent) emergency operations. The 30-day major complication rate was 11·4 per cent (908 of 7965). In adjusted models, a significant interaction was found between BMI and diagnosis, with an association seen between BMI and major complications for patients with malignancy (overweight: OR 1·59, 95 per cent c.i. 1·12 to 2·29, P = 0·008; obese: OR 1·91, 1·31 to 2·83, P = 0·002; compared with normal weight) but not benign disease (overweight: OR 0·89, 0·71 to 1·12, P = 0·329; obese: OR 0·84, 0·66 to 1·06, P = 0·147). Overweight and obese patients undergoing surgery for gastrointestinal malignancy are at increased risk of major postoperative complications compared with those of normal weight. © 2016 The Authors. BJS published by John Wiley & Sons Ltd on behalf of BJS Society Ltd.

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

Effects of exercise intensity and nutrition advice on myocardial function in obese children and adolescents: a multicentre randomised controlled trial study protocol.

PubMed

Dias, Katrin A; Coombes, Jeff S; Green, Daniel J; Gomersall, Sjaan R; Keating, Shelley E; Tjonna, Arnt Erik; Hollekim-Strand, Siri Marte; Hosseini, Mansoureh Sadat; Ro, Torstein Baade; Haram, Margrete; Huuse, Else Marie; Davies, Peter S W; Cain, Peter A; Leong, Gary M; Ingul, Charlotte B

2016-04-04

The prevalence of paediatric obesity is increasing, and with it, lifestyle-related diseases in children and adolescents. High-intensity interval training (HIIT) has recently been explored as an alternate to traditional moderate-intensity continuous training (MICT) in adults with chronic disease and has been shown to induce a rapid reversal of subclinical disease markers in obese children and adolescents. The primary aim of this study is to compare the effects of HIIT with MICT on myocardial function in obese children and adolescents. Multicentre randomised controlled trial of 100 obese children and adolescents in the cities of Trondheim (Norway) and Brisbane (Australia). The trial will examine the efficacy of HIIT to improve cardiometabolic outcomes in obese children and adolescents. Participants will be randomised to (1) HIIT and nutrition advice, (2) MICT and nutrition advice or (3) nutrition advice. Participants will partake in supervised exercise training and/or nutrition sessions for 3 months. Measurements for study end points will occur at baseline, 3 months (postintervention) and 12 months (follow-up). The primary end point is myocardial function (peak systolic tissue velocity). Secondary end points include vascular function (flow-mediated dilation assessment), quantity of visceral and subcutaneous adipose tissue, myocardial structure and function, body composition, cardiorespiratory fitness, autonomic function, blood biochemistry, physical activity and nutrition. Lean, healthy children and adolescents will complete measurements for all study end points at one time point for comparative cross-sectional analyses. This randomised controlled trial will generate substantial information regarding the effects of exercise intensity on paediatric obesity, specifically the cardiometabolic health of this at-risk population. It is expected that communication of results will allow for the development of more effective evidence-based exercise prescription guidelines in this population while investigating the benefits of HIIT on subclinical markers of disease. NCT01991106. 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/

Association of tobacco use and other determinants with pregnancy outcomes: a multicentre hospital-based case-control study in Karachi, Pakistan.

PubMed

Rozi, Shafquat; Butt, Zahid Ahmad; Zahid, Nida; Wasim, Saba; Shafique, Kashif

2016-09-20

The study aimed to identify the effects of maternal tobacco consumption during pregnancy and other factors on birth outcomes and obstetric complications in Karachi, Pakistan. A multicentre hospital-based case-control study. Four leading maternity hospitals of Karachi. A random sample of 1275 women coming to the gynaecology and obstetric department of selected hospitals for delivery was interviewed within 48 hours of delivery from wards. Cases were women with adverse birth outcomes and obstetric complications, while controls were women who had normal uncomplicated delivery. Adverse birth outcomes (preterm delivery, low birth weight, stillbirth, low Apgar score) and obstetric complications (antepartum haemorrhage, caesarean section, etc). Final multiple logistic regression analysis revealed that with every 1 year increase in age the odds of being a case was 1.03 times as compared with being a control. Tobacco use (adjusted OR (aOR): 2.24; 95% CI 1.56 to 3.23), having no slits in the kitchen (proxy indicator for indoor air pollution) (aOR=1.90; 95% CI 1.05 to 3.43), gravidity (aOR=0.83; 95% CI 0.73 to 0.93), non-booked hospital cases (aOR=1.87; 95% CI 1.38 to 2.74), history of stillbirth (aOR=4.06; 95% CI 2.36 to 6.97), miscarriages (aOR=1.91; 95% CI 1.27 to 2.85) and preterm delivery (aOR=6.04; 95% CI 2.52 to 14.48) were significantly associated with being a case as compared with control. This study suggests that women who had adverse pregnancy outcomes were more likely to have exposure to tobacco, previous history of adverse birth outcomes and were non-booked cases. Engagement of stakeholders in tobacco control for providing health education, incorporating tobacco use in women in the tobacco control policy and designing interventions for tobacco use cessation is warranted. Prenatal care and health education might help in preventing such adverse events. 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/

Supplemental parenteral nutrition in critically ill patients: a study protocol for a phase II randomised controlled trial.

PubMed

Ridley, Emma J; Davies, Andrew R; Parke, Rachael; Bailey, Michael; McArthur, Colin; Gillanders, Lyn; Cooper, David J; McGuinness, Shay

2015-12-24

Nutrition is one of the fundamentals of care provided to critically ill adults. The volume of enteral nutrition received, however, is often much less than prescribed due to multiple functional and process issues. To deliver the prescribed volume and correct the energy deficit associated with enteral nutrition alone, parenteral nutrition can be used in combination (termed "supplemental parenteral nutrition"), but benefits of this method have not been firmly established. A multi-centre, randomised, clinical trial is currently underway to determine if prescribed energy requirements can be provided to critically ill patients by using a supplemental parenteral nutrition strategy in the critically ill. This prospective, multi-centre, randomised, stratified, parallel-group, controlled, phase II trial aims to determine whether a supplemental parenteral nutrition strategy will reliably and safely increase energy intake when compared to usual care. The study will be conducted for 100 critically ill adults with at least one organ system failure and evidence of insufficient enteral intake from six intensive care units in Australia and New Zealand. Enrolled patients will be allocated to either a supplemental parenteral nutrition strategy for 7 days post randomisation or to usual care with enteral nutrition. The primary outcome will be the average energy amount delivered from nutrition therapy over the first 7 days of the study period. Secondary outcomes include protein delivery for 7 days post randomisation; total energy and protein delivery, antibiotic use and organ failure rates (up to 28 days); duration of ventilation, length of intensive care unit and hospital stay. At both intensive care unit and hospital discharge strength and health-related quality of life assessments will be undertaken. Study participants will be followed up for health-related quality of life, resource utilisation and survival at 90 and 180 days post randomisation (unless death occurs first). This trial aims to determine if provision of a supplemental parenteral nutrition strategy to critically ill adults will increase energy intake compared to usual care in Australia and New Zealand. Trial outcomes will guide development of a subsequent larger randomised controlled trial. NCT01847534 (First registered 5 February 2013, last updated 14 October 2015).

Design and rationale of the ATHENA study--A 12-month, multicentre, prospective study evaluating the outcomes of a de novo everolimus-based regimen in combination with reduced cyclosporine or tacrolimus versus a standard regimen in kidney transplant patients: study protocol for a randomised controlled trial.

PubMed

Sommerer, Claudia; Suwelack, Barbara; Dragun, Duska; Schenker, Peter; Hauser, Ingeborg A; Nashan, Björn; Thaiss, Friedrich

2016-02-17

Immunosuppression with calcineurin inhibitors remains the mainstay of treatment after kidney transplantation; however, long-term use of these drugs may be associated with nephrotoxicity. In this regard, the current approach is to optimise available immunosuppressive regimens to reduce the calcineurin inhibitor dose while protecting renal function without affecting the efficacy. The ATHENA study is designed to evaluate renal function in two regimens: an everolimus and reduced calcineurin inhibitor-based regimen versus a standard treatment protocol with mycophenolic acid and tacrolimus in de novo kidney transplant recipients. ATHENA is a 12-month, multicentre, open-label, prospective, randomised, parallel-group study in de novo kidney transplant recipients (aged 18 years or older) receiving renal allografts from deceased or living donors. Eligible patients are randomised (1:1:1) prior to transplantation to one of the following three treatment arms: everolimus (starting dose 1.5 mg/day; C0 3-8 ng/mL) with cyclosporine or everolimus (starting dose 3 mg/day; C0 3-8 ng/mL) with tacrolimus or mycophenolic acid (enteric-coated mycophenolate sodium at 1.44 g/day or mycophenolate mofetil at 2 g/day) with tacrolimus; in combination with corticosteroids. All patients receive induction therapy with basiliximab. The primary objective is to demonstrate non-inferiority of renal function (eGFR by the Nankivell formula) in one of the everolimus arms compared with the standard group at month 12 post transplantation. The key secondary objective is to assess the incidence of treatment failure, defined as biopsy-proven acute rejection, graft loss, or death, among the treatment groups. Other objectives include assessment of the individual components of treatment failure, incidence and severity of viral infections, incidence and duration of delayed graft function, incidence of indication biopsies, slow graft function and wound healing complications, and overall safety and tolerability. Exploratory objectives include evaluation of left ventricular hypertrophy assessed by the left ventricular mass index, evolution of human leukocyte antigen and non-human leukocyte antigen antibodies, and a cytomegalovirus substudy. As one of the largest European multicentre kidney transplant studies, ATHENA will determine whether a de novo everolimus-based regimen can preserve renal function versus the standard of care. This study further assesses a number of clinical issues which impact long-term outcomes post transplantation; hence, its results will have a major clinical impact. Clinicaltrials.gov: NCT01843348, date of registration--18 April 2013; EUDRACT number: 2011-005238-21, date of registration--20 March 2012.

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

Adverse Events With Ketamine Versus Ketofol for Procedural Sedation on Adults: A Double-blind, Randomized Controlled Trial.

PubMed

Lemoel, Fabien; Contenti, Julie; Giolito, Didier; Boiffier, Mathieu; Rapp, Jocelyn; Istria, Jacques; Fournier, Marc; Ageron, François-Xavier; Levraut, Jacques

2017-12-01

The goal of our study was to compare the frequency and severity of recovery reactions between ketamine and ketamine-propofol 1:1 admixture ("ketofol"). We performed a multicentric, randomized, double-blind trial in which adult patients received emergency procedural sedations with ketamine or ketofol. Our primary outcome was the proportion of unpleasant recovery reactions. Other outcomes were frequency of interventions required by these recovery reactions, rates of respiratory or hemodynamic events, emesis, and satisfaction of patients as well as providers. A total of 152 patients completed the study, 76 in each arm. Compared with ketamine, ketofol determined a 22% reduction in recovery reactions incidence (p < 0.01) and less clinical and pharmacologic interventions required by these reactions. There was no serious adverse event in both groups. Rates in hemodynamic or respiratory events as well as satisfaction scores were similar. Significantly fewer patients experienced emesis with ketofol, with a threefold reduction in incidence compared with ketamine. We found a significant reduction in recovery reactions and emesis frequencies among adult patients receiving emergency procedural sedations with ketofol, compared with ketamine. © 2017 by the Society for Academic Emergency Medicine.

The impact of study design and diagnostic approach in a large multi-centre ADHD study: Part 2: Dimensional measures of psychopathology and intelligence.

PubMed

Müller, Ueli C; Asherson, Philip; Banaschewski, Tobias; Buitelaar, Jan K; Ebstein, Richard P; Eisenberg, Jaques; Gill, Michael; Manor, Iris; Miranda, Ana; Oades, Robert D; Roeyers, Herbert; Rothenberger, Aribert; Sergeant, Joseph A; Sonuga-Barke, Edmund Js; Thompson, Margaret; Faraone, Stephen V; Steinhausen, Hans-Christoph

2011-04-07

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 ADHD and 1446 unselected siblings. The aim was to describe and analyse questionnaire data and IQ measures from all probands and siblings. In particular, to investigate the influence of age, gender, family status (proband vs. sibling), informant, and centres on sample homogeneity in psychopathological measures. Conners' Questionnaires, Strengths and Difficulties Questionnaires, and Wechsler Intelligence Scores were used to describe the phenotype of the sample. Data were analysed by use of robust statistical multi-way procedures. Besides main effects of age, gender, informant, and centre, there were considerable interaction effects on questionnaire data. The larger differences between probands and siblings at home than at school may reflect contrast effects in the parents. Furthermore, there were marked gender by status effects on the ADHD symptom ratings with girls scoring one standard deviation higher than boys in the proband sample but lower than boys in the siblings sample. The multi-centre design is another important source of heterogeneity, particularly in the interaction with the family status. To a large extent the centres differed from each other with regard to differences between proband and sibling scores. When ADHD probands are diagnosed by use of fixed symptom counts, the severity of the disorder in the proband sample may markedly differ between boys and girls and across age, particularly in samples with a large age range. A multi-centre design carries the risk of considerable phenotypic differences between centres and, consequently, of additional heterogeneity of the sample even if standardized diagnostic procedures are used. These possible sources of variance should be counteracted in genetic analyses either by using age and gender adjusted diagnostic procedures and regional normative data or by adjusting for design artefacts by use of covariate statistics, by eliminating outliers, or by other methods suitable for reducing heterogeneity.

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

PubMed

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

2015-04-01

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

The Clinical Research Office of the Endourological Society (CROES) Multicentre Randomised Trial of Narrow Band Imaging-Assisted Transurethral Resection of Bladder Tumour (TURBT) Versus Conventional White Light Imaging-Assisted TURBT in Primary Non-Muscle-invasive Bladder Cancer Patients: Trial Protocol and 1-year Results.

PubMed

Naito, Seiji; Algaba, Ferran; Babjuk, Marko; Bryan, Richard T; Sun, Ying-Hao; Valiquette, Luc; de la Rosette, Jean

2016-09-01

White light (WL) is the established imaging modality for transurethral resection of bladder tumour (TURBT). Narrow band imaging (NBI) is a promising addition. To compare 12-mo recurrence rates following TURBT using NBI versus WL guidance. The Clinical Research Office of the Endourological Society (CROES) conducted a prospective randomised single-blind multicentre study. Patients with primary non-muscle-invasive bladder cancer (NMIBC) were randomly assigned 1:1 to TURBT guided by NBI or WL. TURBT for NMIBC using NBI or WL. Twelve-month recurrence rates were compared by chi-square tests and survival analyses. Of the 965 patients enrolled in the study, 481 patients underwent WL-assisted TURBT and 484 patients received NBI-assisted TURBT. Of these, 294 and 303 patients, respectively, completed 12-mo follow-up, with recurrence rates of 27.1% and 25.4%, respectively (p=0.585, intention-to-treat [ITT] analysis). In patients at low risk for disease recurrence, recurrence rates at 12 mo were significantly higher in the WL group compared with the NBI group (27.3% vs 5.6%; p=0.002, ITT analysis). Although TURBT took longer on average with NBI plus WL compared with WL alone (38.1 vs 35.0min, p=0.039, ITT; 39.1 vs 35.7min, p=0.047, per protocol [PP] analysis), lesions were significantly more often visible with NBI than with WL (p=0.033). Frequency and severity of adverse events were similar in both treatment groups. Possible limitations were lack of uniformity of surgical resection, data on smoking status, central pathology review, and specific data regarding adjuvant intravesical instillation therapy. NBI and WL guidance achieved similar overall recurrence rates 12 mo after TURBT in patients with NMIBC. NBI-assisted TURBT significantly reduced the likelihood of disease recurrence in low-risk patients. Use of a narrow band imaging technique might provide greater detection of bladder tumours and subsequent treatment leading to reduced recurrence in low-risk patients. Copyright © 2016 European Association of Urology. Published by Elsevier B.V. All rights reserved.

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.

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.

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.

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.

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

PubMed

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

2017-04-01

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

Paroxetine and fluoxetine in pregnancy: a prospective, multicentre, controlled, observational study

PubMed Central

Diav-Citrin, Orna; Shechtman, Svetlana; Weinbaum, Dafna; Wajnberg, Rebecka; Avgil, Meytal; Di Gianantonio, Elena; Clementi, Maurizio; Weber-Schoendorfer, Corinna; Schaefer, Christof; Ornoy, Asher

2008-01-01

WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT In recent years there has been concern regarding the possibility that selective serotonin reuptake inhibitors (SSRIs) cause an increased rate of congenital cardiovascular anomalies. As of today, there is still debate in the literature as to the possible effects of paroxetine and fluoxetine on the embryonic cardiovascular system. WHAT THIS STUDY ADDS Based on prospective data from three Teratogen Information Services, we have demonstrated an increased rate of congenital cardiovascular anomalies among the offspring of fluoxetine- and paroxetine-treated mothers. AIMS Recent studies have suggested a possible association between maternal use of selective serotonin reuptake inhibitors (SSRIs) in early pregnancy and cardiovascular anomalies. The aim of the present study was to evaluate the teratogenic risk of paroxetine and fluoxetine. METHODS This multicentre, prospective, controlled study evaluated the rate of major congenital anomalies after first-trimester gestational exposure to paroxetine, fluoxetine or nonteratogens. RESULTS We followed up 410 paroxetine, 314 fluoxetine first-trimester exposed pregnancies and 1467 controls. After exclusion of genetic and cytogenetic anomalies, there was a higher rate of major anomalies in the SSRI groups compared with the controls [paroxetine 18/348 (5.2%), fluoxetine 12/253 (4.7%) and controls 34/1359 (2.5%)]. The main risk applied to cardiovascular anomalies [paroxetine 7/348 (2.0%), crude odds ratio (OR) 3.47, 95% confidence interval (CI) 1.13, 10.58; fluoxetine 7/253 (2.8%), crude OR, 4.81 95% CI 1.56, 14.71; and controls 8/1359 (0.6%)]. On logistic regression analysis only cigarette smoking of ≥10 cigarettes day−1 and fluoxetine exposure were significant variables for cardiovascular anomalies. The adjusted ORs for paroxetine and fluoxetine were 2.66 (95% CI 0.80, 8.90) and 4.47 (95% CI 1.31, 15.27), respectively. CONCLUSION This study suggests a possible association between cardiovascular anomalies and first-trimester exposure to fluoxetine. PMID:18754846

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.

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.

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

A multicenter study of viable PCR using propidium monoazide to detect Legionella in water samples.

PubMed

Scaturro, Maria; Fontana, Stefano; Dell'eva, Italo; Helfer, Fabrizia; Marchio, Michele; Stefanetti, Maria Vittoria; Cavallaro, Mario; Miglietta, Marilena; Montagna, Maria Teresa; De Giglio, Osvalda; Cuna, Teresa; Chetti, Leonarda; Sabattini, Maria Antonietta Bucci; Carlotti, Michela; Viggiani, Mariagabriella; Stenico, Alberta; Romanin, Elisa; Bonanni, Emma; Ottaviano, Claudio; Franzin, Laura; Avanzini, Claudio; Demarie, Valerio; Corbella, Marta; Cambieri, Patrizia; Marone, Piero; Rota, Maria Cristina; Bella, Antonino; Ricci, Maria Luisa

2016-07-01

Legionella quantification in environmental samples is overestimated by qPCR. Combination with a viable dye, such as Propidium monoazide (PMA), could make qPCR (named then vPCR) very reliable. In this multicentre study 717 artificial water samples, spiked with fixed concentrations of Legionella and interfering bacterial flora, were analysed by qPCR, vPCR and culture and data were compared by statistical analysis. A heat-treatment at 55 °C for 10 minutes was also performed to obtain viable and not-viable bacteria. When data of vPCR were compared with those of culture and qPCR, statistical analysis showed significant differences (P < 0.001). However, although the heat-treatment caused an abatement of CFU/mL ≤1 to 1 log10 unit, the comparison between untreated and heat-treated samples analysed by vPCR highlighted non-significant differences (P > 0.05). Overall this study provided a good experimental reproducibility of vPCR but also highlighted limits of PMA in the discriminating capability of dead and live bacteria, making vPCR not completely reliable. Copyright © 2016 Elsevier Inc. All rights reserved.

Oxidative Stress Induced in Nurses by Exposure to Preparation and Handling of Antineoplastic Drugs in Mexican Hospitals: A Multicentric Study

PubMed Central

Gómez-Oliván, Leobardo Manuel; Miranda-Mendoza, Gerardo Daniel; Cabrera-Galeana, Paula Anel; Galar-Martínez, Marcela; Islas-Flores, Hariz; SanJuan-Reyes, Nely; Neri-Cruz, Nadia; García-Medina, Sandra

2014-01-01

The impact of involuntary exposure to antineoplastic drugs (AD) was studied in a group of nurses in diverse hospitals in Mexico. The results were compared with a group of unexposed nurses. Anthropometric characteristics and the biochemical analysis were analyzed in both groups. Also, lipid peroxidation level (LPX), protein carbonyl content (PCC), and activity of the antioxidant enzymes superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx) were evaluated in blood of study participants as oxidative stress (OS) biomarkers. The group of occupationally exposed (OE) nurses consisted of 30 individuals ranging in age from 25 to 35 years. The control group included 30 nurses who were not occupationally exposed to the preparation and handling of AD and whose anthropometric and biochemical characteristics were similar to those of the OE group. All biomarkers evaluated were significantly increased (P < 0.5) in OE nurses compared to the control group. Results show that the assessment of OS biomarkers is advisable in order to evaluate exposure to AD in nurses. PMID:24719678

Oxidative stress induced in nurses by exposure to preparation and handling of antineoplastic drugs in Mexican hospitals: a multicentric study.

PubMed

Gómez-Oliván, Leobardo Manuel; Miranda-Mendoza, Gerardo Daniel; Cabrera-Galeana, Paula Anel; Galar-Martínez, Marcela; Islas-Flores, Hariz; Sanjuan-Reyes, Nely; Neri-Cruz, Nadia; García-Medina, Sandra

2014-01-01

The impact of involuntary exposure to antineoplastic drugs (AD) was studied in a group of nurses in diverse hospitals in Mexico. The results were compared with a group of unexposed nurses. Anthropometric characteristics and the biochemical analysis were analyzed in both groups. Also, lipid peroxidation level (LPX), protein carbonyl content (PCC), and activity of the antioxidant enzymes superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx) were evaluated in blood of study participants as oxidative stress (OS) biomarkers. The group of occupationally exposed (OE) nurses consisted of 30 individuals ranging in age from 25 to 35 years. The control group included 30 nurses who were not occupationally exposed to the preparation and handling of AD and whose anthropometric and biochemical characteristics were similar to those of the OE group. All biomarkers evaluated were significantly increased (P < 0.5) in OE nurses compared to the control group. Results show that the assessment of OS biomarkers is advisable in order to evaluate exposure to AD in nurses.

Efficacy and safety of artemisinin-naphthoquine versus dihydroartemisinin-piperaquine in adult patients with uncomplicated malaria: a multi-centre study in Indonesia

PubMed Central

2012-01-01

Background A practical and simple regimen for all malaria species is needed towards malaria elimination in Indonesia. It is worth to compare the efficacy and safety of a single dose of artemisinin-naphthoquine (AN) with a three-day regimen of dihydroartemisinin-piperaquine (DHP), the existing programme drug, in adults with uncomplicated symptomatic malaria. Methods This is a phase III, randomized, open label using sealed envelopes, multi-centre, comparative study between a single dose of AN and a three-day dose of DHP in Jayapura and Maumere. The modified WHO inclusion and exclusion criteria for efficacy study were used in this trial. A total of 401 eligible adult malaria subjects were hospitalized for three days and randomly treated with AN four tablets single dose on day 0 or DHP three to four tablets single daily dose for three days, and followed for 42 days for physical examination, thick and thin smears microscopy, and other necessary tests. The efficacy of drug was assessed by polymerase chain reaction (PCR) uncorrected and corrected. Results There were 153 Plasmodium falciparum, 158 Plasmodium vivax and 90 P. falciparum/P. vivax malaria. Mean of fever clearance times were similar, 13.0 ± 10.3 hours in AN and 11.3 ± 7.3 hours in DHP groups. The mean of parasite clearance times were longer in AN compared with DHP (28.0 ± 11.7 hours vs 25.5 ± 12.2 hours, p = 0.04). There were only 12 PCR-corrected P. falciparum late treatment failures: seven in AN and five in DHP groups. The PCR uncorrected and corrected on day −42 of adequate clinical and parasitological responses for treatment of any malaria were 93.7% (95% Cl: 90.3–97.2) and 96.3% (95% Cl: 93.6–99.0) in AN, 96.3% (95% Cl: 93.5–99.0) and 97.3% (95% Cl: 95.0–99.6) in DHP groups. Few and mild adverse events were reported. All the abnormal haematology and blood chemistry values had no clinical abnormality. Conclusion AN and DHP are confirmed very effective, safe and tolerate for treatment of any malaria. Both drugs are promising for multiple first-line therapy policies in Indonesia. PMID:22554203

Outcomes comparison of different surgical strategies for the management of severe aortic valve stenosis: study protocol of a prospective multicentre European registry (E-AVR registry)

PubMed Central

Onorati, Francesco; Gherli, Riccardo; Mariscalco, Giovanni; Girdauskas, Evaldas; Quintana, Eduardo; Santini, Francesco; De Feo, Marisa; Sponga, Sandro; Tozzi, Piergiorgio; Bashir, Mohamad; Perrotti, Andrea; Pappalardo, Aniello; Ruggieri, Vito Giovanni; Santarpino, Giuseppe; Rinaldi, Mauro; Ronaldo, Silva; Nicolini, Francesco

2018-01-01

Introduction Traditional and transcatheter surgical treatments of severe aortic valve stenosis (SAVS) are increasing in parallel with the improved life expectancy. Recent randomised controlled trials (RCTs) reported comparable or non-inferior mortality with transcatheter treatments compared with traditional surgery. However, RCTs have the limitation of being a mirror of the predefined inclusion/exclusion criteria, without reflecting the ‘real clinical world’. Technological improvements have recently allowed the development of minimally invasive surgical accesses and the use of sutureless valves, but their impact on the clinical scenario is difficult to assess because of the monocentric design of published studies and limited sample size. A prospective multicentre registry including all patients referred for a surgical treatment of SAVS (traditional, through full sternotomy; minimally invasive; or transcatheter; with both ‘sutured’ and ‘sutureless’ valves) will provide a ‘real-world’ picture of available results of current surgical options and will help to clarify the ‘grey zones’ of current guidelines. Methods and analysis European Aortic Valve Registry is a prospective observational open registry designed to collect all data from patients admitted for SAVS, with or without coronary artery disease, in 16 cardiac surgery centres located in six countries (France, Germany, Italy, Spain, Switzerland and UK). Patients will be enrolled over a 2-year period and followed up for a minimum of 5 years to a maximum of 10 years after enrolment. Outcome definitions are concordant with Valve Academic Research Consortium-2 criteria and established guidelines. Primary outcome is 5-year all-cause mortality. Secondary outcomes aim at establishing ‘early’ 30-day all-cause and cardiovascular mortality, as well as major morbidity, and ‘late’ cardiovascular mortality, major morbidity, structural and non-structural valve complications, quality of life and echocardiographic results. Ethics and dissemination The study protocol is approved by local ethics committees. Any formal presentation or publication of data will be considered as a joint publication by the participating physician(s) and will follow the recommendations of the International Committee of Medical Journal Editors for authorship. Trial registration number NCT03143361; Pre-results. PMID:29440154

Efficacy of ethinylestradiol 20 µg/drospirenone 3 mg in a flexible extended regimen in women with moderate-to-severe primary dysmenorrhoea: an open-label, multicentre, randomised, controlled study

PubMed Central

Strowitzki, Thomas; Kirsch, Bodo; Elliesen, Jörg

2012-01-01

Objectives The aim of this Phase III, multicentre, open-label, randomised study was to compare the efficacy and safety of ethinylestradiol (EE)/drospirenone (DRSP) in a new flexible extended regimen that allowed the management of intracyclic (breakthrough) bleeding (MIB) with that of EE/DRSP in a conventional 28-day regimen in women with moderate-to-severe primary dysmenorrhoea. Methods Women (aged 18–40 years) with moderate-to-severe primary dysmenorrhoea-related pain received a flexible extended regimen with MIB (flexibleMIB; minimum 24, maximum 120 days of continuous tablet intake for a flexible number of cycles to reach a treatment duration of at least 140 days with 4-day breaks between cycles) or a conventional 28-day regimen (24 active and four placebo tablets for five cycles) of EE/DRSP. The primary outcome was the number of days with dysmenorrhoeic pain over 140 days. Secondary outcomes included other dysmenorrhoea-related pain outcomes, bleeding profile, satisfaction and safety. Results Overall, 223 patients received study medication. There were significantly fewer days with dysmenorrhoeic pain with the flexibleMIB regimen than the conventional regimen (difference −4.2 days, 95% CI −6.5 to −2.0; p=0.0003), as well as considerably fewer days with at least moderate dysmenorrhoeic pain (difference −2.5 days, 95% CI −3.7 to −1.3), dysmenorrhoeic pain that interfered with daily activities (difference −2.2 days, 95% CI −4.2 to −0.1) and pelvic pain (difference −3.4 days, 95% CI −5.9 to −0.9). Adverse events were similar with both regimens. Conclusions Compared with the conventional regimen, the flexible extended regimen of EE/DRSP with MIB was associated with a significantly greater reduction in days with dysmenorrhoeic pain in women with moderate-to-severe primary dysmenorrhoea. The flexibleMIB regimen was also associated with greater improvements in dysmenorrhea according to the Clinical Global Impression rating scale and was generally well tolerated. PMID:22454006

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.

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.

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.

Study design and rationale for Optimal aNtiplatelet pharmacotherapy guided by bedSIDE genetic or functional TESTing in elective percutaneous coronary intervention patients (ONSIDE TEST): a prospective, open-label, randomised parallel-group multicentre trial (NCT01930773).

PubMed

Kołtowski, Łukasz; Aradi, Daniel; Huczek, Zenon; Tomaniak, Mariusz; Sibbing, Dirk; Filipiak, Krzysztof J; Kochman, Janusz; Balsam, Paweł; Opolski, Grzegorz

2016-01-01

High platelet reactivity (HPR) and presence of CYP2C19 loss-of-function alleles are associated with higher risk for periprocedural myocardial infarction in clopidogrel-treated patients undergoing percutaneous coronary intervention (PCI). It is unknown whether personalised treatment based on platelet function testing or genotyping can prevent such complications. The ONSIDE-TEST is a multicentre, prospective, open-label, randomised controlled clinical trial aiming to assess if optimisation of antiplatelet therapy based on either phenotyping or genotyping is superior to conventional care. Patients will be randomised into phenotyping, genotyping, or control arms. In the phenotyping group, patients will be tested with the VerifyNow P2Y12 assay before PCI, and patients with a platelet reactivity unit greater than 208 will be switched over to prasugrel, while others will continue on clopidogrel therapy. In the genotyping group, carriers of the *2 loss-of-function allele will receive prasugrel for PCI, while wild-type subjects will be treated with clopidogrel. Patients in the control arm will be treated with standard-dose clopidogrel. The primary endpoint of the study is the prevalence of periprocedural myocardial injury within 24 h after PCI in the controls as compared to the phenotyping and genotyping group. Secondary endpoints include cardiac death, myocardial infarction, definite or probable stent thrombosis, or urgent repeat revascularisation within 30 days of PCI. Primary safety outcome is Bleeding Academic Research Consortium (BARC) type 3 and 5 bleeding during 30 days of PCI. The ONSIDE TEST trial is expected to verify the clinical utility of an individualised antiplatelet strategy in preventing periprocedural myocardial injury by either phenotyping or genotyping. ClinicalTrials.gov: NCT01930773.

Diclofenac patch for topical treatment of acute impact injuries: a randomised, double blind, placebo controlled, multicentre study

PubMed Central

Predel, H; Koll, R; Pabst, H; Dieter, R; Gallacchi, G; Giannetti, B; Bulitta, M; Heidecker, J; Mueller, E

2004-01-01

Objectives: To investigate the clinical efficacy and safety of a newly developed diclofenac patch in the topical treatment of blunt impact injuries. Methods: This was a randomised, placebo controlled, double blind, multicentre study in 120 patients with traumatic blunt soft tissue injury. Within 3 h of the injury participants of sport competitions and training camps were enrolled and treated twice daily with the diclofenac or a placebo patch over a period of 7 days. Patients were randomised (1:1) to two parallel groups. Tenderness produced by pressure was measured twice daily during the first 3 days after enrolment as well as at day 7. Tenderness was defined as the amount of pressure (measured by a calibrated caliper at the centre of the injury) that first produced a pain reaction as reported by the patient. Results: The primary efficacy variable was the area under the curve for tenderness over the first 3 days. The diclofenac patch was significantly more effective than placebo (p<0.0001). The treatment effect was 64.7 kp h/cm2 (95% confidence interval 48.7 to 80.9) between diclofenac and placebo patches. These results were supported by all secondary efficacy variables. The diclofenac patch produced rapid pain relief as reflected by the time to reach resolution of pain at the injured site which was significantly shorter compared to placebo (p<0.0001). The diclofenac patch was well tolerated. The most frequently observed adverse events were local cutaneous adverse reactions (pruritus, rash) of minor severity occurring with the same frequency as in the placebo group. Conclusions: A newly developed diclofenac patch is effective and safe for the treatment of blunt impact injuries. PMID:15155436

Coexistence of IgM antihepatitis A virus and IgM antihepatitis E virus in acute viral hepatitis: a prospective, multicentre study in Korea.

PubMed

Jang, J-H; Jung, Y M; Kim, J S; Lee, S H; Kim, J-W; Hwang, S G; Rim, K S; Park, S J; Park, Y M; Kang, S-K; Lee, H S; Yun, H; Kim, J-H; Jeong, S-H

2011-10-01

This study investigated the clinical, serological and molecular characteristics of coexistence of both immunoglobulin M (IgM) antihepatitis A virus (HAV) and IgM antihepatitis E virus (HEV) in acute viral hepatitis using a prospective, multicentre design. Among a total of 771 symptomatic cases with acute viral hepatitis enrolled in a Korean city from September 2006 to August 2008, coexistence of IgM anti-HAV and IgM anti-HEV was found in 43 patients (A+E group; 6%), while the existence of IgM anti-HAV alone was found in 595 patients (A group; 77%) and that of IgM anti-HEV alone in 14 patients (E group; 2%). Clinical data analysis and measurement of IgM and IgG anti-HEV were performed using two different commercial kits, and HAV RNA and HEV RNA were detected in available serum or stool samples. The clinical features of the A+E group were similar to those of the A group. HAV RNA detection rates in the A+E and A group were similar, while HEV RNA was detected only in the stool samples of the E group, not in the A+E group. Comparative testing of anti-HEV using two different ELISA kits showed markedly discordant results for IgM anti-HEV positivity and consistently low positivity for IgG anti-HEV in the A+E group. Coexistence of IgM anti-HEV measured by the Genelabs ELISA kit in the setting of hepatitis A appears to yield false-positive results in nonendemic areas of HEV infection. Diagnosis of hepatitis E using IgM anti-HEV should be made with caution. © 2011 Blackwell Publishing Ltd.

Design and rationale of the MR-INFORM study: stress perfusion cardiovascular magnetic resonance imaging to guide the management of patients with stable coronary artery disease.

PubMed

Hussain, Shazia T; Paul, Matthias; Plein, Sven; McCann, Gerry P; Shah, Ajay M; Marber, Michael S; Chiribiri, Amedeo; Morton, Geraint; Redwood, Simon; MacCarthy, Philip; Schuster, Andreas; Ishida, Masaki; Westwood, Mark A; Perera, Divaka; Nagel, Eike

2012-09-19

In patients with stable coronary artery disease (CAD), decisions regarding revascularisation are primarily driven by the severity and extent of coronary luminal stenoses as determined by invasive coronary angiography. More recently, revascularisation decisions based on invasive fractional flow reserve (FFR) have shown improved event free survival. Cardiovascular magnetic resonance (CMR) perfusion imaging has been shown to be non-inferior to nuclear perfusion imaging in a multi-centre setting and superior in a single centre trial. In addition, it is similar to invasively determined FFR and therefore has the potential to become the non-invasive test of choice to determine need for revascularisation. The MR-INFORM study is a prospective, multi-centre, randomised controlled non-inferiority, outcome trial. The objective is to compare the efficacy of two investigative strategies for the management of patients with suspected CAD. Patients presenting with stable angina are randomised into two groups: 1) The FFR-INFORMED group has subsequent management decisions guided by coronary angiography and fractional flow reserve measurements. 2) The MR-INFORMED group has decisions guided by stress perfusion CMR. The primary end-point will be the occurrence of major adverse cardiac events (death, myocardial infarction and repeat revascularisation) at one year. Clinical trials.gov identifier NCT01236807. MR INFORM will assess whether an initial strategy of CMR perfusion is non-inferior to invasive angiography supplemented by FFR measurements to guide the management of patients with stable coronary artery disease. Non-inferiority of CMR perfusion imaging to the current invasive reference standard (FFR) would establish CMR perfusion imaging as an attractive non-invasive alternative to current diagnostic pathways.

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).

Addition of Granulocyte/Monocyte Apheresis to Oral Prednisone for Steroid-dependent Ulcerative Colitis: A Randomized Multicentre Clinical Trial.

PubMed

Domènech, Eugeni; Panés, Julián; Hinojosa, Joaquín; Annese, Vito; Magro, Fernando; Sturniolo, Giacomo Carlo; Bossa, Fabrizio; Fernández, Francisco; González-Conde, Benito; García-Sánchez, Valle; Dignass, Axel; Herrera, José Manuel; Cabriada, José Luis; Guardiola, Jordi; Vecchi, Maurizio; Portela, Francisco; Ginard, Daniel

2018-05-25

Steroid-dependency occurs in up to 30% of patients with ulcerative colitis [UC]. In this setting, few drugs have demonstrated efficacy in inducing steroid-free remission. The aim of this study was to evaluate the efficacy and safety of adding granulocyte/monocyte apheresis [GMA] to oral prednisone in patients with steroid-dependent UC. This was a randomized, multicentre, open trial comparing 7 weekly sessions of GMA plus oral prednisone [40 mg/day and tapering] with prednisone alone, in patients with active, steroid-dependent UC [Mayo score 4-10 and inability to withdraw corticosteroids in 3 months or relapse within the first 3 months after discontinuation]. Patients were stratified by concomitant use of thiopurines at inclusion. A 9-week tapering schedule of prednisone was pre-established in both study groups. The primary endpoint was steroid-free remission [defined as a total Mayo score ≤2, with no subscore >1] at Week 24, with no re-introduction of corticosteroids. In all 123 patients were included [63 GMA group, 62 prednisone alone]. In the intention-to-treat analysis, steroid-free remission at Week 24 was achieved in 13% (95% confidence interval [CI] 6-24) in the GMA group and 7% [95% CI 2-16] in the control group [p = 0.11]. In the GMA group, time to relapse was significantly longer (hazard ratio [HR] 1.7 [1.16-2.48], P = 0.005) and steroid-related adverse events were significantly lower [6% vs 20%, P < 0.05]. In a randomized trial, the addition of 7 weekly sessions of GMA to a conventional course of oral prednisone did not increase the proportion of steroid-free remissions in patients with active steroid-dependent UC, though it delayed clinical relapse.

Preference, satisfaction and critical errors with Genuair and Breezhaler inhalers in patients with COPD: a randomised, cross-over, multicentre study

PubMed Central

Pascual, Sergi; Feimer, Jan; De Soyza, Anthony; Sauleda Roig, Jaume; Haughney, John; Padullés, Laura; Seoane, Beatriz; Rekeda, Ludmyla; Ribera, Anna; Chrystyn, Henry

2015-01-01

Background: The specific attributes of inhaler devices can influence patient use, satisfaction and treatment compliance, and may ultimately impact on clinical outcomes in patients with chronic obstructive pulmonary disease (COPD). Aims: To assess patient preference, satisfaction and critical inhaler technique errors with Genuair (a multidose inhaler) and Breezhaler (a single-dose inhaler) after 2 weeks of daily use. Methods: Patients with COPD and moderate to severe airflow obstruction were randomised in a cross-over, open-label, multicentre study to consecutive once-daily inhalations of placebo via Genuair and Breezhaler, in addition to current COPD medication. The primary end point was the proportion of patients who preferred Genuair versus Breezhaler after 2 weeks (Patient Satisfaction and Preference Questionnaire). Other end points included overall satisfaction and correct use of the inhalers after 2 weeks, and willingness to continue with each device. Results: Of the 128 patients enrolled, 127 were included in the safety population (male n=91; mean age 67.6 years). Of the 110 of the 123 patients in the intent-to-treat population who indicated an inhaler preference, statistically significantly more patients preferred Genuair than Breezhaler (72.7 vs. 27.3%; P<0.001). Mean overall satisfaction scores were also greater for Genuair than for Breezhaler (5.9 vs. 5.3, respectively; P<0.001). After 2 weeks, there was no statistically significant difference in the number of patients who made ⩾1 critical inhaler technique error with Breezhaler than with Genuair (7.3 vs. 3.3%, respectively). Conclusions: Patient overall preference and satisfaction was significantly higher with Genuair compared with Breezhaler. The proportion of patients making critical inhaler technique errors was low with Genuair and Breezhaler. PMID:25927321

Associations between individual characteristics and incontinence-associated dermatitis: a secondary data analysis of a multi-centre prevalence study.

PubMed

Kottner, Jan; Blume-Peytavi, Ulrike; Lohrmann, Christa; Halfens, Ruud

2014-10-01

Incontinent patients are at risk for incontinence-associated dermatitis. Prolonged exposures of the skin to urine and/or stool are causal factors but the exact aetiology and pathophysiology are not fully understood. The aim of the current investigation was to identify person and health-related variables most strongly associated with incontinence-associated dermatitis development. Secondary data analysis of a multicentre-prevalence study in 2012. Hospitals, nursing homes, home care in Austria and the Netherlands. Nursing home residents, hospital patients, home care clients who completed an incontinence assessment and who were incontinent (n = 3713). Mean age 81.2 (SD 11.2) years. Demographic, functional and physiological parameters were compared between subjects with incontinence-associated dermatitis and without. A logistic regression model predicting incontinence-associated dermatitis was build. Subjects with incontinence-associated dermatitis were statistically significantly more often male, had more often diabetes mellitus, had a higher BMI, were less often affected by urinary but more often by faecal incontinence and showed higher degrees of functional and psychical impairments. Being faecal incontinent (OR 1.70; 95% CI 1.14-2.55), having diabetes mellitus (OR 1.46; 95% CI 1.03-2.06) and having "friction and shear" problems (OR 0.65; 95% CI 0.51-0.81) according to the Braden scale item were the strongest covariates for the presence of incontinence-associated dermatitis. It is recommended to target special preventive skin care interventions especially to persons who are faecal incontinent and who have moist perineal skin, who have higher BMIs, who are diabetics, and who need increased assistance in moving. Copyright © 2014 Elsevier Ltd. All rights reserved.

Haplo-identical transplantation for acquired severe aplastic anaemia in a multicentre prospective study.

PubMed

Xu, Lan-Ping; Wang, Shun-Qing; Wu, De-Pei; Wang, Jian-Min; Gao, Su-Jun; Jiang, Ming; Wang, Cun-Bang; Zhang, Xi; Liu, Qi-Fa; Xia, Ling-Hui; Wang, Xin; Huang, Xiao-Jun

2016-10-01

We conducted a prospective, multicentre study to confirm the feasibility of haplo-identical transplantation in treatment of severe aplastic anaemia (SAA) as salvage therapy, by analysing the outcomes of 101 patients who received haplo-identical transplantation between June 2012 and October 2015. All cases surviving for more than 28 d achieved donor myeloid engraftment. The median time for myeloid engraftment was 12 (range, 9-25) days and 15 (range, 7-101) days for platelets, with a cumulative platelet engraftment incidence of 94·1 ± 0·1%. With a median follow-up of 18·3 (3·0-43·6) months, recipients from haplo-identical transplantation had more cumulative incidence of grade II-IV acute graft-versus-host disease (aGVHD, 33·7% vs. 4·2%, P < 0·001), more chronic GVHD (22·4% vs. 6·6%, P = 0·014) at 1 year, but similar grade III-IV aGVHD (7·9% vs. 2·1%, P = 0·157), 3-year estimated overall survival (OS, 89·0% vs. 91·0%, P = 0·555) and failure-free survival (FFS, 86·8% vs. 80·3%, P = 0·659) when compared with 48 patients who received contemporaneous transplantation from matched related donors. Multivariate analysis showed no significant difference in engraftment and survival between the two cohorts. Both OS and FFS for the entire population correlated significantly with grades III-IV aGVHD. In conclusion, haplo-identical transplantation is a feasible choice for SAA with favourable outcomes. © 2016 John Wiley & Sons Ltd.

The influence of aminotransferase levels on liver stiffness assessed by Acoustic Radiation Force Impulse Elastography: a retrospective multicentre study.

PubMed

Bota, Simona; Sporea, Ioan; Peck-Radosavljevic, Markus; Sirli, Roxana; Tanaka, Hironori; Iijima, Hiroko; Saito, Hidetsugu; Ebinuma, Hirotoshi; Lupsor, Monica; Badea, Radu; Fierbinteanu-Braticevici, Carmen; Petrisor, Ana; Friedrich-Rust, Mireen; Sarrazin, Christoph; Takahashi, Hirokazu; Ono, Naofumi; Piscaglia, Fabio; Marinelli, Sara; D'Onofrio, Mirko; Gallotti, Anna; Salzl, Petra; Popescu, Alina; Danila, Mirela

2013-09-01

Acoustic Radiation Force Impulse Elastography is a new method for non-invasive evaluation of liver fibrosis. To evaluate the impact of elevated alanine aminotransferase levels on liver stiffness assessment by Acoustic Radiation Force Impulse Elastography. A multicentre retrospective study including 1242 patients with chronic liver disease, who underwent liver biopsy and Acoustic Radiation Force Impulse. Transient Elastography was also performed in 512 patients. The best Acoustic Radiation Force Impulse cut-off for predicting significant fibrosis was 1.29 m/s in cases with normal alanine aminotransferase levels and 1.44 m/s in patients with alanine aminotransferase levels>5 × the upper limit of normal. The best cut-off for predicting liver cirrhosis were 1.59 and 1.75 m/s, respectively. Acoustic Radiation Force Impulse cut-off for predicting significant fibrosis and cirrhosis were relatively similar in patients with normal alanine aminotransferase and in those with alanine aminotransferase levels between 1.1 and 5 × the upper limit of normal: 1.29 m/s vs. 1.36 m/s and 1.59 m/s vs. 1.57 m/s, respectively. For predicting cirrhosis, the Transient Elastography cut-offs were significantly higher in patients with alanine aminotransferase levels between 1.1 and 5 × the upper limit of normal compared to those with normal alanine aminotransferase: 12.3 kPa vs. 9.1 kPa. Liver stiffness values assessed by Acoustic Radiation Force Impulse and Transient Elastography are influenced by high aminotransferase levels. Transient Elastography was also influenced by moderately elevated aminotransferase levels. Copyright © 2013 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.

Fibrinogen concentrate as a treatment for postpartum haemorrhage-induced coagulopathy: A study protocol for a randomised multicentre controlled trial. The fibrinogen in haemorrhage of DELivery (FIDEL) trial.

PubMed

Ducloy-Bouthors, Anne-Sophie; Mignon, Alexandre; Huissoud, Cyril; Grouin, Jean-Marie; Mercier, Frédéric J

2016-08-01

Postpartum haemorrhage (PPH) remains the leading cause for maternal mortality worldwide. Hypofibrinogenaemia has been identified as a major risk factor for progress towards severe PPH. The efficacy of fibrinogen concentrate supplementation in PPH has been shown in various clinical settings but the level of evidence is not sufficient to prove the benefit, evaluate the risks, and determine the value, timing and dose of fibrinogen supplementation in PPH. The FIDEL trial objective is to evaluate the impact of a therapeutic strategy based on the early administration of human fibrinogen concentrate compared to the current practice based on late administration in severe PPH patients requiring second line uterotonics. This is a prospective multicentre, randomised, double-blind, placebo-controlled trial. A total of 412 patients will be randomised if they meet the following criteria: female patients≥18 years old, vaginal delivery, PPH requiring IV administration of prostaglandins (sulprostone) after 20 to 30minutes of oxytocin failure. The participants are assigned to receive either fibrinogen 3g or placebo infusions. The primary endpoint is a composite endpoint defined as the percentage of patients losing at least 4g/dL of Hb, and/or requiring a transfusion of at least 2 units of packed red blood cells, within the 48hours following fibrinogen administration. The purpose of this study is to demonstrate the efficacy and safety of an early fibrinogen concentrate infusion in uncontrolled active PPH. Copyright © 2016 Société française d'anesthésie et de réanimation (Sfar). Published by Elsevier Masson SAS. All rights reserved.

Whole genome sequencing discriminates hepatocellular carcinoma with intrahepatic metastasis from multi-centric tumors.

PubMed

Furuta, Mayuko; Ueno, Masaki; Fujimoto, Akihiro; Hayami, Shinya; Yasukawa, Satoru; Kojima, Fumiyoshi; Arihiro, Koji; Kawakami, Yoshiiku; Wardell, Christopher P; Shiraishi, Yuichi; Tanaka, Hiroko; Nakano, Kaoru; Maejima, Kazuhiro; Sasaki-Oku, Aya; Tokunaga, Naoki; Boroevich, Keith A; Abe, Tetsuo; Aikata, Hiroshi; Ohdan, Hideki; Gotoh, Kunihito; Kubo, Michiaki; Tsunoda, Tatsuhiko; Miyano, Satoru; Chayama, Kazuaki; Yamaue, Hiroki; Nakagawa, Hidewaki

2017-02-01

Patients with hepatocellular carcinoma (HCC) have a high-risk of multi-centric (MC) tumor occurrence due to a strong carcinogenic background in the liver. In addition, they have a high risk of intrahepatic metastasis (IM). Liver tumors withIM or MC are profoundly different in their development and clinical outcome. However, clinically or pathologically discriminating between IM and MC can be challenging. This study investigated whether IM or MC could be diagnosed at the molecular level. We performed whole genome and RNA sequencing analyses of 49 tumors including two extra-hepatic metastases, and one nodule-in-nodule tumor from 23 HCC patients. Sequencing-based molecular diagnosis using somatic single nucleotide variation information showed higher sensitivity compared to previous techniques due to the inclusion of a larger number of mutation events. This proved useful in cases, which showed inconsistent clinical diagnoses. In addition, whole genome sequencing offered advantages in profiling of other genetic alterations, such as structural variations, copy number alterations, and variant allele frequencies, and helped to confirm the IM/MCdiagnosis. Divergent alterations between IM tumors with sorafenib treatment, long time-intervals, or tumor-in-tumor nodules indicated high intra-tumor heterogeneity, evolution, and clonal switching of liver cancers. It is important to analyze the differences between IM tumors, in addition to IM/MC diagnosis, before selecting a therapeutic strategy for multiple tumors in the liver. Whole genome sequencing of multiple liver tumors enabled the accuratediagnosis ofmulti-centric occurrence and intrahepatic metastasis using somatic single nucleotide variation information. In addition, genetic discrepancies between tumors help us to understand the physical changes during recurrence and cancer spread. Copyright © 2016 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.

Prevalence, antenatal management and perinatal outcomes of monochorionic monoamniotic twin pregnancies: a collaborative multicentre study in England, 2000-2013.

PubMed

Glinianaia, Svetlana V; Rankin, Judith; Khalil, Asma; Binder, Julia; Waring, Gareth; Sturgiss, Stephen N; Thilaganathan, Basky; Hannon, Therese

2018-06-13

To determine the prevalence of monochorionic monoamniotic (MCMA) twin pregnancies and to describe perinatal outcomes and clinical management of these pregnancies. This multicentre cohort study used population-based data on MCMA twin pregnancies from 11 Northern Survey of Twin and Multiple Pregnancy (NorSTAMP) maternity units for the prevalence estimation of MCMA twinning. Pregnancy outcomes at <24 weeks' gestation, antenatal parameters and perinatal outcomes (from ≥24 weeks to the first 28 days of life) were analysed using combined data on pregnancies with confirmed MCMA chorionicity from the NorSTAMP and the Southwest Thames Region of London Obstetric Research Collaborative (STORK) multiple pregnancy cohort for 2000-2013. The estimated total prevalence of MCMA twin pregnancies in the North of England was 8.2 per 1000 total twin pregnancies (59/7170), the birth prevalence was 0.08 per 1000 all (singleton and multiple) pregnancies. The rate of a spontaneous or iatrogenic fetal death at <24 weeks' gestation was 31.8% (54/170); the overall perinatal mortality was 14.7% (17/116), ranging from 69.2% at <30 weeks to 4.5% at ≥33 weeks' gestation. MCMA twins who survived in utero beyond 24 weeks were delivered, usually by caesarean section, at a median of 33 weeks of gestation (interquartile range=32-34). In MCMA twins surviving beyond 24 weeks of gestation, there was a higher survival rate compared to previous decades presumably due to early diagnosis, close surveillance and elective birth around 32-34 weeks of gestation. High perinatal mortality at early gestations was mainly attributed to extreme prematurity due to preterm spontaneous labour. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

Non-hypervascular hypointense nodules detected by Gd-EOB-DTPA-enhanced MRI are a risk factor for recurrence of HCC after hepatectomy.

PubMed

Toyoda, Hidenori; Kumada, Takashi; Tada, Toshifumi; Niinomi, Takuro; Ito, Takanori; Sone, Yasuhiro; Kaneoka, Yuji; Maeda, Atsuyuki

2013-06-01

The gadolinium-ethoxybenzyl-diethylenetriamine pentaacetic acid (Gd-EOB-DTPA)-enhanced magnetic resonance imaging (MRI) often depicts non-hypervascular hypointense hepatic nodules during the hepatobiliary phase in patients with hepatocellular carcinoma (HCC). It is unclear whether the presence of these nodules is associated with HCC recurrence after hepatectomy. We conducted a prospective observational study to investigate the impact of the presence of non-hypervascular hypointense hepatic nodules on the hepatobiliary phase of Gd-EOB-DTPA-enhanced MRI on the recurrence of HCC after hepatectomy. A total of 77 patients who underwent hepatectomy for primary, non-recurrent, hypervascular HCC were prospectively followed up after hepatectomy. Post-operative recurrence rates were compared according to the presence of non-hypervascular hypointense nodules on preoperative Gd-EOB-DTPA-enhanced MRI. Recurrence rates after hepatectomy were higher in patients with non-hypervascular hypointense nodules (risk ratio 1.9396 [1.3615-2.7222]) and the presence of non-hypervascular hypointense nodules was an independent factor associated with postoperative recurrence (risk ratio 2.1767 [1.5089-3.1105]) along with HCC differentiation and portal vein invasion. While no differences were found in the rate of intrahepatic metastasis recurrence based on the preoperative presence of non-hypervascular hypointense hepatic nodules, the rate of multicentric recurrence was significantly higher in patients with preoperative non-hypervascular hypointense hepatic nodules. Patients with preoperative non-hypervascular hypointense hepatic nodules detected during the hepatobiliary phase of Gd-EOB-DTPA-enhanced MRI are at higher risk of HCC recurrence after hepatectomy, mainly due to multicentric recurrence. Copyright © 2013 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.

The PACT trial: PAtient Centered Telerehabilitation: effectiveness of software-supported and traditional mirror therapy in patients with phantom limb pain following lower limb amputation: protocol of a multicentre randomised controlled trial.

PubMed

Rothgangel, Andreas Stefan; Braun, Susy; Schulz, Ralf Joachim; Kraemer, Matthias; de Witte, Luc; Beurskens, Anna; Smeets, Rob Johannes

2015-01-01

Non-pharmacological interventions such as mirror therapy are gaining increased recognition in the treatment of phantom limb pain; however, the evidence in people with phantom limb pain is still weak. In addition, compliance to self-delivered exercises is generally low. The aim of this randomised controlled study is to investigate the effectiveness of mirror therapy supported by telerehabilitation on the intensity, duration and frequency of phantom limb pain and limitations in daily activities compared to traditional mirror therapy and care as usual in people following lower limb amputation. A three-arm multi-centre randomised controlled trial will be performed. Participants will be randomly assigned to care as usual, traditional mirror therapy or mirror therapy supported by telerehabilitation. During the first 4 weeks, at least 10 individual sessions will take place in every group. After the first 4 weeks, participants will be encouraged to perform self-delivered exercises over a period of 6 weeks. Outcomes will be assessed at 4 and 10 weeks after baseline and at 6 months follow-up. The primary outcome measure is the average intensity of phantom limb pain during the last week. Secondary outcome measures include the different dimensions of phantom limb pain, pain-related limitations in daily activities, global perceived effect, pain-specific self-efficacy, and quality of life. Several questions concerning the study design that emerged during the preparation of this trial will be discussed. This will include how these questions were addressed and arguments for the choices that were made. Copyright © 2014 Australian Physiotherapy Association. Published by Elsevier B.V. All rights reserved.

Diagnosis of prosthetic joint infection with alpha-defensin using a lateral flow device: a multicentre study.

PubMed

Berger, P; Van Cauter, M; Driesen, R; Neyt, J; Cornu, O; Bellemans, J

2017-09-01

The purpose of this current multicentre study is to analyse the presence of alpha-defensin proteins in synovial fluid using the Synovasure lateral flow device and to determine its diagnostic reliability and accuracy compared with the prosthetic joint infection (PJI) criteria produced by the Musculoskeletal Infection Society (MSIS). A cohort of 121 patients comprising 85 total knee arthroplasties and 36 total hip arthroplasties was prospectively evaluated between May 2015 and June 2016 in three different orthopaedic centres. The tests were performed on patients with a chronically painful prosthesis undergoing a joint aspiration in a diagnostic pathway or during revision surgery. Based on the MSIS criteria, 34 patients (28%) would have had a PJI, and 87 patients had no PJI. Testing with the lateral flow device had a sensitivity of 97.1% (95% confidence intervals (CI) 84.5 to 99.9) and a specificity of 96.6% (95% CI 90.3 to 99.2). The positive predictive value was 91.7% (95% CI 77.7% to 98.3), and the negative predictive value was 98.8% (95% CI 93.6 to 99.9). Receiver operator characteristics analysis demonstrated an area under the curve for the Synovasure test of 0.97 (95% CI 0.93 to 1.00). Our findings suggest that the Synovasure test has an excellent diagnostic performance to confirm or reject the diagnosis of a PJI. The results are promising for the care of the painful or problematic knee and hip joint arthroplasty and the test should be considered as part of the diagnostic toolbox for PJIs. Cite this article: Bone Joint J 2017;99-B:1176-82. ©2017 The British Editorial Society of Bone & Joint Surgery.

Does cataract surgery alleviate poverty? Evidence from a multi-centre intervention study conducted in Kenya, the Philippines and Bangladesh.

PubMed

Kuper, Hannah; Polack, Sarah; Mathenge, Wanjiku; Eusebio, Cristina; Wadud, Zakia; Rashid, Mamunur; Foster, Allen

2010-11-09

Poverty and blindness are believed to be intimately linked, but empirical data supporting this purported relationship are sparse. The objective of this study is to assess whether there is a reduction in poverty after cataract surgery among visually impaired cases. A multi-centre intervention study was conducted in three countries (Kenya, Philippines, Bangladesh). Poverty data (household per capita expenditure--PCE, asset ownership and self-rated wealth) were collected from cases aged ≥50 years who were visually impaired due to cataract (visual acuity<6/24 in the better eye) and age-sex matched controls with normal vision. Cases were offered free/subsidised cataract surgery. Approximately one year later participants were re-interviewed about poverty. 466 cases and 436 controls were examined at both baseline and follow-up (Follow up rate: 78% for cases, 81% for controls), of which 263 cases had undergone cataract surgery ("operated cases"). At baseline, operated cases were poorer compared to controls in terms of PCE (Kenya: $22 versus £35 p = 0.02, Bangladesh: $16 vs $24 p = 0.004, Philippines: $24 vs 32 p = 0.0007), assets and self-rated wealth. By follow-up PCE had increased significantly among operated cases in each of the three settings to the level of controls (Kenya: $30 versus £36 p = 0.49, Bangladesh: $23 vs $23 p = 0.20, Philippines: $45 vs $36 p = 0.68). There were smaller increases in self-rated wealth and no changes in assets. Changes in PCE were apparent in different socio-demographic and ocular groups. The largest PCE increases were apparent among the cases that were poorest at baseline. This study showed that cataract surgery can contribute to poverty alleviation, particularly among the most vulnerable members of society. This study highlights the need for increased provision of cataract surgery to poor people and shows that a focus on blindness may help to alleviate poverty and achieve the Millennium Development Goals.

A multicentre phase III randomised controlled single-masked clinical trial evaluating the clinical efficacy and safety of light-masks at preventing dark-adaptation in the treatment of early diabetic macular oedema (CLEOPATRA): study protocol for a randomised controlled trial.

PubMed

Sivaprasad, Sobha; Arden, Geoffrey; Prevost, A Toby; Crosby-Nwaobi, Roxanne; Holmes, Helen; Kelly, Joanna; Murphy, Caroline; Rubin, Gary; Vasconcelos, Joanna; Hykin, Philip

2014-11-22

This study will evaluate hypoxia, as a novel concept in the pathogenesis of diabetic macular oedema (DMO). As the oxygen demand of the eye is maximum during dark-adaptation, we hypothesize that wearing light-masks during sleep will cause regression and prevent the development and progression of DMO. The study protocol comprises both an efficacy and mechanistic evaluation to test this hypothesis. This is a phase III randomised controlled single-masked multicentre clinical trial to test the clinical efficacy of light-masks at preventing dark-adaptation in the treatment of non-central DMO. Three hundred patients with non-centre-involving DMO in at least one eye will be randomised 1:1 to light-masks and control masks (with no light) to be used during sleep at night for a period of 24 months. The primary outcome is regression of non-central oedema by assessing change in the zone of maximal retinal thickness at baseline on optical coherence tomography (SD-OCT). Secondary outcomes will evaluate the prevention of development and progression of DMO by assessing changes in retinal thickness in different regions of the macula, macular volume, refracted visual acuity and level of retinopathy. Safety parameters will include sleep disturbance. Adverse events and measures of compliance will be assessed over 24 months. Participants recruited to the mechanistic sub-study will have additional retinal oximetry, multifocal electroretinography (ERG) and microperimetry to evaluate the role of hypoxia by assessing and comparing changes induced by supplemental oxygen and the light-masks at 12 months. The outcomes of this study will provide insight into the pathogenesis of DMO and provide evidence on whether a simple, non-invasive device in the form of a light-mask can help prevent the progression to centre-involving DMO and visual impairment in people with diabetes.

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.

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

PubMed

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

2017-08-01

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

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.

High fat consumption in children with celiac disease.

PubMed

Ferrara, P; Cicala, M; Tiberi, E; Spadaccio, C; Marcella, L; Gatto, A; Calzolari, P; Castellucci, G

2009-01-01

The purpose of this study was to estimate the caloric intake and fat consumption in children with celiac disease (CD) following a gluten-free diet (GFD). This study enrolled 100 subjects, including 50 children with CD on a gluten-free diet and a control group of 50 healthy children. Statistical analysis to compare groups was performed using one-way ANOVA. A significant increase in fat consumption was observed in children with CD as compared to healthy children. The daily fat intake was 72.5 +/- 37.2 g per 100 g of food in the CD group and 52.9 +/- 35.4 g per 100 g of food in the control group (p < 0.008). A significant difference in fat intake was found between celiac and healthy females (10.21 +/- 3.15 g/100 g in the celiac group vs 7.46 +/- 2.91 g/100 g in the control group), p = 0.004. This study describes a significantly higher fat consumption in patients with CD on GFD as compared to controls. This increase was more pronounced in females and during the puberal age. Based on these interesting preliminary results we estimate that further investigations are necessary, such as a randomized multicentre study on the long-term effects of GFD with particular attention to the imbalance in daily fat intake.

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.

Pregnancy outcomes in Lebanese women with multiple sclerosis (the LeMS study): a prospective multicentre study

PubMed Central

Fares, Jawad; Nassar, Anwar H; Gebeily, Souheil; Kobeissy, Firas; Fares, Youssef

2016-01-01

Objective The Lebanese Multiple Sclerosis (LeMS) study aims to assess the influence of pregnancy and delivery on the clinical course of multiple sclerosis (MS) in Lebanese women. Setting This prospective multicentre study took place in three MS referral university medical centres in Lebanon. Participants Included were 29 women over 18 years who had been diagnosed with MS according to the McDonald criteria, and became pregnant between 1995 and 2015. Participating women should have stopped treatment 3 months before conception and become pregnant after the onset of MS. Women were followed up from 1 year preconceptionally and for 4 years postpartum. Main outcome measures The annualised relapse rates per participant during each 3-month period during pregnancy and each year postpartum were compared with the relapse rate during the year before pregnancy using the paired two-tailed t test. p Values <0.05 were considered statistically significant for all analyses (95% CI). Results 64 full-term pregnancies were recorded. All pregnancies (100%) resulted in live births, with no complications or other diseases. In comparison with the prepregnancy year, in which the mean relapse rate±SE was 0.17±0.07, there was a significant reduction in the relapse rate during pregnancy and in the first year postpartum (p=0.02), but an increase in the rate in the second year postpartum (0.21±0.08). Thereafter, from the third year postpartum through the following fourth year, the annualised relapse rate fell slightly but did not differ from the annualised relapse rate recorded in the prepregnancy year (0.17±0.07). Conclusions Pregnancy in Lebanese women with MS does not seem to increase the risk of complications. No relapses were observed during pregnancy and in the first year postpartum; however, relapses rebounded in the second year postpartum, and over the long term, returned to the levels that preceded pregnancy. PMID:27178979

The CLOSED trial; CLOnidine compared with midazolam for SEDation of paediatric patients in the intensive care unit: study protocol for a multicentre randomised controlled trial.

PubMed

Neubert, Antje; Baarslag, Manuel Alberto; Dijk, Monique van; Rosmalen, Joost van; Standing, Joseph F; Sheng, Yucheng; Rascher, Wolfgang; Roberts, Deborah; Winslade, Jackie; Rawcliffe, Louise; Hanning, Sara M; Metsvaht, Tuuli; Giannuzzi, Viviana; Larsson, Peter; Pokorná, Pavla; Simonetti, Alessandra; Tibboel, Dick

2017-06-21

Sedation is an essential part of paediatric critical care. Midazolam, often in combination with opioids, is the current gold standard drug. However, as it is a far-from-ideal agent, clonidine is increasingly being used in children. This drug is prescribed off-label for this indication, as many drugs in paediatrics are. Therefore, the CLOSED trial aims to provide data on the pharmacokinetics, safety and efficacy of clonidine for the sedation of mechanically ventilated patients in order to obtain a paediatric-use marketing authorisation. The CLOSED study is a multicentre, double-blind, randomised, active-controlled non-inferiority trial with a 1:1 randomisation between clonidine and midazolam. Both treatment groups are stratified according to age in three groups with the same size: <28 days (n=100), 28 days to <2 years (n=100) and 2-18 years (n=100). The primary end point is defined as the occurrence of sedation failure within the study period. Secondary end points include a pharmacokinetic/pharmacodynamic relationship, pharmacogenetics, occurrence of delirium and withdrawal syndrome, opioid consumption and neurodevelopment in the neonatal age group. Logistic regression will be used for the primary end point, appropriate statistics will be used for the secondary end points. Written informed consent will be obtained from the parents/caregivers. Verbal or deferred consent will be used in the sites where national legislation allows. The study has institutional review board approval at recruiting sites. The results will be published in a peer-reviewed journal and shared with the worldwide medical community. EudraCT: 2014-003582-24; Clinicaltrials.gov: NCT02509273; 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.

Prehospital endotracheal intubation and chest tubing does not prolong the overall resuscitation time of severely injured patients: a retrospective, multicentre study of the Trauma Registry of the German Society of Trauma Surgery.

PubMed

Kulla, Martin; Helm, Matthias; Lefering, Rolf; Walcher, Felix

2012-06-01

The aim of this study was to determine whether prehospital endotracheal intubation (ETI) and chest tube placement is unnecessarily time consuming in severely injured patients. A retrospective, multicentre study including all adult patients (ISS ≥9; 2002-7) of the Trauma Registry of the German Society of Trauma Surgery who were not secondarily transferred to a trauma centre and received a definitive airway and a chest tube. Creating four groups: AA (n=963) receiving ETI and chest tube on scene, AB (n=1547) ETI performed in the prehospital setting but chest tubing later in the emergency department (ED) and BB (n=640) receiving both procedures in the ED. The BA collective (ETI performed in the ED, but chest tubing on scene) was excluded from the study because of the small sample size (n=41). The trauma resuscitation time (TRT), demographic data, injuries, treatment and outcome of the remaining three collectives were compared. The prehospital TRT of the AA collective was longer than the AB and BB subgroups (80±37 min vs 77±44 min 65±46 min; p<0.01). Although the AA and AB subgroups were more severely injured (ISS 35±15 vs 38±15 vs 31±12; p<0.01) and showed poorer vital parameters on scene, the overall TRT (accident until end of ED treatment) were equal for all three groups (152±59 min vs 151±62 min vs 148±68 min; p=0.07). The TRISS adjusted mortality was also equal in all three groups. In a physician-based emergency medical service, prehospital ETI and chest tube placement do not prolong the total TRT of severely injured patients.

Efficacy and safety of renal denervation for Chinese patients with resistant hypertension using a microirrigated catheter: study design and protocol for a prospective multicentre randomised controlled trial.

PubMed

Liu, Zongjun; Shen, Li; Huang, Weijian; Zhao, Xianxian; Fang, Weiyi; Wang, Changqian; Yin, Zhaofang; Wang, Jianan; Fu, Guosheng; Liu, Xuebo; Jiang, Jianjun; Zhang, Zhihui; Li, Jingbo; Lu, Yingmin; Ge, Junbo

2017-09-01

Available data show that approximately 8%-18% of patients with primary hypertension will develop resistant hypertension. In recent years, catheter-based renal denervation (RDN) has emerged as a potential treatment option for resistant hypertension. A number of observational studies and randomised controlled trials among non-Chinese patients have demonstrated its potential safety and efficacy. This is a multicentre, randomised, open-label, parallel-group, active controlled trial that will investigate the efficacy and safety of a 5F saline-irrigated radiofrequency ablation (RFA) used for RDN in the treatment of Chinese patients with resistant hypertension. A total of 254 patients who have failed pharmacological therapy will be enrolled. Eligible subjects will be randomised in a 1:1 ratio to undergo RDN using the RFA plus antihypertensive medication or to receive treatment with antihypertensive medication alone. The primary outcome measure is the change in 24 hours average ambulatory systolic blood pressure from baseline to 3 months, comparing the RDN-plus-medication group with the medication-alone group. Important secondary endpoints include the change in office blood pressure from baseline to 6 months after randomisation. Safety endpoints such as changes in renal function will also be evaluated. The full analysis set, according to the intent-to-treat principle, will be established as the primary analysis population. All participants will provide informed consent; the study protocol has been approved by the Independent Ethics Committee for each site. This study is designed to investigate the efficacy and safety of RDN using a 5F saline microirrigated RFA. Findings will be shared with participating hospitals, policymakers and the academic community to promote the clinical management of resistant hypertension in China. ClinicalTrials.gov ID: NCT02900729; 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.

Unicompartmental knee arthroplasty modes of failure: wear is not the main reason for failure: a multicentre study of 418 failed knees.

PubMed

Epinette, J-A; Brunschweiler, B; Mertl, P; Mole, D; Cazenave, A

2012-10-01

This study originated from a symposium held by the French Hip and Knee Society (Société française de la hanche et du genou [SFHG]) and was carried out to better assess the distribution of causes of unicompartmental knee arthroplasty (UKA) failures, as well as cause-specific delay to onset. Our working hypothesis was that most failures were traceable to wear occurring over a period of many years. A multicentre retrospective study (25 centres) was conducted in 418 failed UKAs performed between 1978 and 2009. We determined the prevalence and time to onset of the main reasons for revision surgery based upon available preoperative findings. Additional intraoperative findings were analysed. The results were compared to those of nation wide registries to evaluate the representativeness of our study population. Times to revision surgery were short: 19% of revisions occurred within the first year and 48.5% within the first 5 years. Loosening was the main reason for failure (45%), followed by osteoarthritis progression (15%) and, finally, by wear (12%). Other reasons were technical problems in 11.5% of cases, unexplained pain in 5.5%, and failure of the supporting bone in 3.6%. The infection rate was 1.9%. Our results were consistent with those of Swedish and Australian registries. Our hypothesis was not confirmed. The short time to failure in most cases suggests a major role for surgical technique issues. Morbidity related to the implant per se may be seen as moderate and not greater than with total knee prostheses. The good agreement between our data and those of nationwide registries indicates that our population was representative. A finer analysis is needed, indicating that the establishment of a French registry would be of interest. Copyright © 2012. Published by Elsevier Masson SAS.

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.

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…

Effect of the type of maternal pushing during the second stage of labour on obstetric and neonatal outcome: a multicentre randomised trial-the EOLE study protocol.

PubMed

Barasinski, Chloé; Vendittelli, Françoise

2016-12-20

The scientific data currently available do not allow any definitive conclusion to be reached about what type of pushing should be recommended to women during the second stage of labour. The objective of this trial is to assess and compare the effectiveness of directed open-glottis pushing versus directed closed-glottis pushing. Secondary objectives are to assess, according to the type of pushing: immediate maternal and neonatal morbidity, intermediate-term maternal pelvic floor morbidity, uncomplicated birth, and women's satisfaction at 4 weeks post partum. This multicentre randomised clinical trial compares directed closed-glottis pushing (Valsalva) versus directed open-glottis pushing during the second stage of labour in 4 hospitals of France. The study population includes pregnant women who received instruction in both types of pushing, have no previous caesarean delivery, are at term and have a vaginal delivery planned. Randomisation takes place during labour once cervical dilation ≥7 cm. The principal end point is assessed by a composite criterion: spontaneous delivery without perineal lesion (no episiotomy or spontaneous second-degree, third-degree or fourth-degree lacerations). We will need to recruit 125 women per group. The primary analysis will be by intention-to-treat analysis, with the principal results reported as crude relative risks (RRs) with their 95% CIs. A multivariate analysis will be performed to take prognostic and confounding factors into account to obtain adjusted RRs. This study was approved by a French Institutional Review Board (Comité de Protection des Personnes Sud Est 6:N°AU1168). Results will be reported in peer-reviewed journals and at scientific meetings. This study will make it possible to assess the effectiveness of 2 types of directed pushing used in French practice and to assess their potential maternal, fetal and neonatal effects. Findings from the study will be useful for counselling pregnant women before and during labour. Agence national de sécurité du médicament et des produits de santé (ANSM): 150099B-22 and IDRCB: 2014-A01920-47. ClinicalTrials.gov: NCT02474745. Pre-result stage. 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/.

Effect of the type of maternal pushing during the second stage of labour on obstetric and neonatal outcome: a multicentre randomised trial—the EOLE study protocol

PubMed Central

Barasinski, Chloé; Vendittelli, Françoise

2016-01-01

Introduction The scientific data currently available do not allow any definitive conclusion to be reached about what type of pushing should be recommended to women during the second stage of labour. The objective of this trial is to assess and compare the effectiveness of directed open-glottis pushing versus directed closed-glottis pushing. Secondary objectives are to assess, according to the type of pushing: immediate maternal and neonatal morbidity, intermediate-term maternal pelvic floor morbidity, uncomplicated birth, and women's satisfaction at 4 weeks post partum. Methods and analysis This multicentre randomised clinical trial compares directed closed-glottis pushing (Valsalva) versus directed open-glottis pushing during the second stage of labour in 4 hospitals of France. The study population includes pregnant women who received instruction in both types of pushing, have no previous caesarean delivery, are at term and have a vaginal delivery planned. Randomisation takes place during labour once cervical dilation ≥7 cm. The principal end point is assessed by a composite criterion: spontaneous delivery without perineal lesion (no episiotomy or spontaneous second-degree, third-degree or fourth-degree lacerations). We will need to recruit 125 women per group. The primary analysis will be by intention-to-treat analysis, with the principal results reported as crude relative risks (RRs) with their 95% CIs. A multivariate analysis will be performed to take prognostic and confounding factors into account to obtain adjusted RRs. Ethics and dissemination This study was approved by a French Institutional Review Board (Comité de Protection des Personnes Sud Est 6:N°AU1168). Results will be reported in peer-reviewed journals and at scientific meetings. This study will make it possible to assess the effectiveness of 2 types of directed pushing used in French practice and to assess their potential maternal, fetal and neonatal effects. Findings from the study will be useful for counselling pregnant women before and during labour. Trial registration number Agence national de sécurité du médicament et des produits de santé (ANSM): 150099B-22 and IDRCB: 2014-A01920-47. ClinicalTrials.gov: NCT02474745. Pre-result stage. PMID:27998899

The Laser in Glaucoma and Ocular Hypertension (LiGHT) trial. A multicentre randomised controlled trial: baseline patient characteristics.

PubMed

Konstantakopoulou, Evgenia; Gazzard, Gus; Vickerstaff, Victoria; Jiang, Yuzhen; Nathwani, Neil; Hunter, Rachael; Ambler, Gareth; Bunce, Catey

2018-05-01

The laser in glaucoma and ocular hypertension (LiGHT) trial aims to establish whether initial treatment with selective laser trabeculoplasty (SLT) is superior to initial treatment with topical medication for primary open angle glaucoma (POAG) or ocular hypertension (OHT). LiGHT is a prospective unmasked, multicentre, pragmatic, randomised controlled trial (RCT). 718 previously untreated patients with POAG or OHT were recruited at 6 UK centres between 2012 and 2014. Patients were randomised to initial SLT followed by medical therapy or medical therapy without laser. Participants will be monitored for 3 years, according to routine clinical practice. The primary outcome is EQ-5D-5L. Secondary outcomes are treatment pathway cost and cost-effectiveness, Glaucoma Utility Index (GUI), Glaucoma Symptom Scale, Glaucoma Quality of Life (GQL), pathway effectiveness, visual function, safety and concordance. A total of 555 patients had POAG and 163 OHT; 518 patients had both eyes eligible. The mean age for patients with POAG was 64 years and for OHT 58 years. 70% of all participants were white. Median IOP for OHT eyes was 26 mm Hg and 23 mm Hg for POAG eyes. Median baseline visual field mean deviation was -0.81 dB for OHT eyes and -2.82 dB for POAG eyes. There was no difference between patients with POAG and patients with OHT on the EQ-5D-5DL; the difference between OHT and POAG on the GUI was -0.02 and 1.23 on the GQL. The LiGHT trial is the first RCT to compare the two treatment options in a real-world setting. The baseline characteristics of the LiGHT cohort compare well with other landmark glaucoma studies. ISRCTN32038223, Pre-results. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

The Effectiveness of Alcohol Screening and Brief Intervention in Emergency Departments: A Multicentre Pragmatic Cluster Randomized Controlled Trial

PubMed Central

Drummond, Colin; Deluca, Paolo; Coulton, Simon; Bland, Martin; Cassidy, Paul; Crawford, Mike; Dale, Veronica; Gilvarry, Eilish; Godfrey, Christine; Heather, Nick; McGovern, Ruth; Myles, Judy; Newbury-Birch, Dorothy; Oyefeso, Adenekan; Parrott, Steve; Patton, Robert; Perryman, Katherine; Phillips, Tom; Shepherd, Jonathan; Touquet, Robin; Kaner, Eileen

2014-01-01

Background Alcohol misuse is common in people attending emergency departments (EDs) and there is some evidence of efficacy of alcohol screening and brief interventions (SBI). This study investigated the effectiveness of SBI approaches of different intensities delivered by ED staff in nine typical EDs in England: the SIPS ED trial. Methods and Findings Pragmatic multicentre cluster randomized controlled trial of SBI for hazardous and harmful drinkers presenting to ED. Nine EDs were randomized to three conditions: a patient information leaflet (PIL), 5 minutes of brief advice (BA), and referral to an alcohol health worker who provided 20 minutes of brief lifestyle counseling (BLC). The primary outcome measure was the Alcohol Use Disorders Identification Test (AUDIT) status at 6 months. Of 5899 patients aged 18 or more presenting to EDs, 3737 (63·3%) were eligible to participate and 1497 (40·1%) screened positive for hazardous or harmful drinking, of whom 1204 (80·4%) gave consent to participate in the trial. Follow up rates were 72% (n = 863) at six, and 67% (n = 810) at 12 months. There was no evidence of any differences between intervention conditions for AUDIT status or any other outcome measures at months 6 or 12 in an intention to treat analysis. At month 6, compared to the PIL group, the odds ratio of being AUDIT negative for brief advice was 1·103 (95% CI 0·328 to 3·715). The odds ratio comparing BLC to PIL was 1·247 (95% CI 0·315 to 4·939). A per protocol analysis confirmed these findings. Conclusions SBI is difficult to implement in typical EDs. The results do not support widespread implementation of alcohol SBI in ED beyond screening followed by simple clinical feedback and alcohol information, which is likely to be easier and less expensive to implement than more complex interventions. Trial Registration Current Controlled Trials ISRCTN 93681536 PMID:24963731

Multicentre clinical evaluation of the new highly sensitive Elecsys® thyroglobulin II assay in patients with differentiated thyroid carcinoma.

PubMed

Trimboli, P; Imperiali, M; Piccardo, A; CampennÌ, A; Giordani, I; Ruggeri, R M; Baldari, S; Orlandi, F; Giovanella, L

2018-02-01

A highly sensitive thyroglobulin assay (Elecsys® Tg II, Roche Diagnostics, Penzberg, Germany) has become available for monitoring patients with differentiated thyroid cancer (DTC). Here, we evaluated the clinical performance of Elecsys® Tg II assay in a multicentre patients series and compare it with the established Access® Tg assay (Beckman Coulter, Brea, CA, USA). Retrospective analysis on prospectively selected patients in four thyroid cancer referral centres with uniform DTC management. All DTC cases diagnosed, treated and followed up in four tertiary referral centres for thyroid cancer since January 2005 (n = 1456) were retrieved, and predefined selection criteria were applied to prevent relevant enrolment biases. A series of 204 patients was finally selected for this study. Samples had been stored at -80°C. Tg was measured by fully automated immunometric Elecsys® Tg II and Access® Tg assays in a centralized laboratory. Two hundred and four DTC were finally included. Of these, 10.8% had structural recurrence (sREC), and 81.4% showed no evidence of disease (NED) at the end of follow-up. There was a significant analytical bias between methods that cannot be used interchangeably. Using ROC curve analysis, the best basal and rhTSH-stimulated Tg cut-offs to detect sREC were 0.41 μg/L and 1.82 μg/L for Elecsys® and 0.36 μg/L and 1.62 μg/L for Access® assay, respectively. Using Cox proportional hazard regression, Tg was the only independent predictor of cancer relapse. Using appropriate assay-specific cut-offs, the clinical performance of the Elecsys® Tg II assay was comparable to that provided by the well-established Access® Tg assay. © 2017 John Wiley & Sons Ltd.

Stepwise radical endoscopic resection versus radiofrequency ablation for Barrett's oesophagus with high-grade dysplasia or early cancer: a multicentre randomised trial.

PubMed

van Vilsteren, Frederike G I; Pouw, Roos E; Seewald, Stefan; Alvarez Herrero, Lorenza; Sondermeijer, Carine M T; Visser, Mike; Ten Kate, Fiebo J W; Yu Kim Teng, Karl C; Soehendra, Nib; Rösch, Thomas; Weusten, Bas L A M; Bergman, Jacques J G H M

2011-06-01

After focal endoscopic resection (ER) of high-grade dysplasia (HGD) or early cancer (EC) in Barrett's oesophagus (BO), eradication of all remaining BO reduces the recurrence risk. The aim of this study was to compare the safety of stepwise radical ER (SRER) versus focal ER followed by radiofrequency ablation (RFA) for complete eradication of BO containing HGD/EC. A multicentre randomised clinical trial was carried out in three tertiary centres. Patients with BO ≤ 5 cm containing HGD/EC were randomised to SRER or ER/RFA. Patients in the SRER group underwent piecemeal ER of 50% of BO followed by serial ER. Patients in the ER/RFA group underwent focal ER for visible lesions followed by serial RFA. Follow-up endoscopy with biopsies (four-quadrant/2 cm BO) was performed at 6 and 12 months and then annually. The main outcome measures were: stenosis rate; complications; complete histological response for neoplasia (CR-neoplasia); and complete histological response for intestinal metaplasia (CR-IM). CR-neoplasia was achieved in 25/25 (100%) SRER and in 21/22 (96%) ER/RFA patients. CR-IM was achieved in 23 (92%) SRER and 21 (96%) ER/RFA patients. The stenosis rate was significantly higher in SRER (88%) versus ER/RFA (14%; p<0.001), resulting in more therapeutic sessions in SRER (6 vs 3; p<0.001) due to dilations. After median 24 months follow-up, one SRER patient had recurrence of EC, requiring ER. In patients with BO ≤ 5 cm containing HGD/EC, SRER and ER/RFA achieved comparably high rates of CR-IM and CR-neoplasia. However, SRER was associated with a higher number of complications and therapeutic sessions. For these patients, a combined endoscopic approach of focal ER followed by RFA may thus be preferred over SRER. Clinical trial number NTR1337.

Efficacy and safety of epicutaneous ketoprofen in Transfersome (IDEA‐033) versus oral celecoxib and placebo in osteoarthritis of the knee: multicentre randomised controlled trial

PubMed Central

Rother, Matthias; Lavins, Bernard J; Kneer, Werner; Lehnhardt, Klaus; Seidel, Egbert J; Mazgareanu, Stefan

2007-01-01

Objective To compare epicutaneous ketoprofen in Transfersome (ultra‐deformable vesicles, IDEA‐033) versus oral celecoxib and placebo for relief of signs and symptoms in knee osteoarthritis. Methods This was a multicentre, randomised, double‐blind, controlled trial; 397 patients with knee osteoarthritis participated and 324 completed the trial. They were randomly assigned 110 mg epicutaneous ketoprofen in 4.8 g Transfersome plus oral placebo (n = 138), 100 mg oral celecoxib plus placebo gel (n = 132), or both placebo formulations (n = 127) twice daily for 6 weeks. Primary efficacy outcome measures were the changes from baseline to end of the study on the Western Ontario and McMaster Universities (WOMAC) Osteoarthritis Index pain subscale, physical function subscale and patient global assessment (PGA) of response. Results The mean WOMAC pain subscale scores in the intent to treat population were reduced by 18.2 (95% confidence interval −22.1 to −14.3), 20.3 (−24.3 to −16.2) and 9.9 (−13.9 to −5.8) in the IDEA‐033, celecoxib and placebo groups, respectively, and the physical function subscale score by 14.6 (−18.1 to −11.0), 16.6 (−20.2 to −13.0) and 10.2 (−13.8 to −6.6), respectively. The mean PGA of response scores were 1.8 (1.6 to 2.1), 1.7 (1.5 to 1.9) and 1.3 (1.1 to 1.5), respectively. The differences in change between IDEA‐033 and placebo were statistically significant for pain subscale (p<0.01) and PGA of response (p<0.01). Gastrointestinal adverse events for IDEA‐033 were similar to placebo. Conclusion IDEA‐033 is superior to placebo and comparable with celecoxib in relieving pain associated with an acute flare of knee osteoarthritis. PMID:17363401

Targeted therapeutic mild hypercapnia after cardiac arrest: A phase II multi-centre randomised controlled trial (the CCC trial).

PubMed

Eastwood, Glenn M; Schneider, Antoine G; Suzuki, Satoshi; Peck, Leah; Young, Helen; Tanaka, Aiko; Mårtensson, Johan; Warrillow, Stephen; McGuinness, Shay; Parke, Rachael; Gilder, Eileen; Mccarthy, Lianne; Galt, Pauline; Taori, Gopal; Eliott, Suzanne; Lamac, Tammy; Bailey, Michael; Harley, Nerina; Barge, Deborah; Hodgson, Carol L; Morganti-Kossmann, Maria Cristina; Pébay, Alice; Conquest, Alison; Archer, John S; Bernard, Stephen; Stub, Dion; Hart, Graeme K; Bellomo, Rinaldo

2016-07-01

In intensive care observational studies, hypercapnia after cardiac arrest (CA) is independently associated with improved neurological outcome. However, the safety and feasibility of delivering targeted therapeutic mild hypercapnia (TTMH) for such patients is untested. In a phase II safety and feasibility multi-centre, randomised controlled trial, we allocated ICU patients after CA to 24h of targeted normocapnia (TN) (PaCO2 35-45mmHg) or TTMH (PaCO2 50-55mmHg). The primary outcome was serum neuron specific enolase (NSE) and S100b protein concentrations over the first 72h assessed in the first 50 patients surviving to day three. Secondary end-points included global measure of function assessment at six months and mortality for all patients. We enrolled 86 patients. Their median age was 61 years (58, 64 years) and 66 (79%) were male. Of these, 50 patients (58%) survived to day three for full biomarker assessment. NSE concentrations increased in the TTMH group (p=0.02) and TN group (p=0.005) over time, with the increase being significantly more pronounced in the TN group (p(interaction)=0.04). S100b concentrations decreased over time in the TTMH group (p<0.001) but not in the TN group (p=0.68). However, the S100b change over time did not differ between the groups (p(interaction)=0.23). At six months, 23 (59%) TTMH patients had good functional recovery compared with 18 (46%) TN patients. Hospital mortality occurred in 11 (26%) TTMH patients and 15 (37%) TN patients (p=0.31). In CA patients admitted to the ICU, TTMH was feasible, appeared safe and attenuated the release of NSE compared with TN. These findings justify further investigation of this novel treatment. Copyright © 2016. Published by Elsevier Ireland Ltd.

An integrated approach to consumer representation and involvement in a multicentre randomized controlled trial.

PubMed

Langston, Anne L; McCallum, Marilyn; Campbell, Marion K; Robertson, Clare; Ralston, Stuart H

2005-01-01

Although, consumer involvement in individual studies is often limited, their involvement in guiding health research is generally considered to be beneficial. This paper outlines our experiences of an integrated relationship between the organisers of a clinical trial and a consumer organisation. The PRISM trial is a UK multicentre, randomized controlled trial comparing treatment strategies for Paget's disease of the bone. The National Association for the Relief of Paget's Disease (NARPD) is the only UK support group for sufferers of Paget's disease and has worked closely with the PRISM team from the outset. NARPD involvement is integral to the conduct of the trial and specific roles have included: peer-review; trial steering committee membership; provision of advice to participants, and promotion of the trial amongst Paget's disease patients. The integrated relationship has yielded benefits to both the trial and the consumer organisation. The benefits for the trial have included: recruitment of participants via NARPD contacts; well-informed participants; unsolicited patient advocacy of the trial; and interested and pro-active collaborators. For the NARPD and Paget's disease sufferers, benefits have included: increased awareness of Paget's disease; increased access to relevant health research; increased awareness of the NARPD services; and wider transfer of diagnosis and management knowledge to/from health care professionals. Our experience has shown that an integrated approach between a trial team and a consumer organisation is worthwhile. Adoption of such an approach in other trials may yield significant improvements in recruitment and quality of participant information flow. There are, however, resource implications for both parties.

Effects of pimecrolimus cream 1% in the treatment of patients with atopic dermatitis who demonstrate a clinical insensitivity to topical corticosteroids: a randomized, multicentre vehicle-controlled trial.

PubMed

Leung, D Y M; Hanifin, J M; Pariser, D M; Barber, K A; Langley, R G; Schlievert, P M; Abrams, B; Hultsch, T

2009-08-01

Colonization with Staphylococcus aureus in atopic dermatitis (AD) is often associated with worsening of clinical symptoms. Staphylococcus aureus produces superantigens that contribute to cutaneous inflammation and corticosteroid (CS) resistance. To investigate the relationship between CS insensitivity, S. aureus colonization and superantigen production in AD, and to explore the efficacy of pimecrolimus cream in CS-insensitive AD. This was a randomized, double-blind, vehicle-controlled, multicentre, parallel-group study. Seventy-three patients with AD, aged 2-49 years, who had a documented clinical insensitivity to topical CS, were recruited. The primary efficacy parameters combined laboratory (including S. aureus colonization, superantigens) and clinical assessments [including Eczema Area and Severity Index (EASI), whole body Investigator's Global Assessment (IGA), pruritus assessment score, patient's assessment score of disease control]. An increase in S. aureus counts correlated with worsening of clinical score (week 6 vs. baseline) when assessed by IGA, pruritus severity and patient assessment. The presence of superantigens correlated with this worsening. During the 6-week double-blind phase, disease improvement in the pimecrolimus cream group was demonstrated by decreasing EASI scores compared with vehicle. Mean EASI scores for the head and neck showed greater improvement in the pimecrolimus cream group than in the vehicle group at all observed time points. In a cohort of patients with clinical insensitivity to CS there was a significant positive correlation between S. aureus and disease severity. Results suggest that for some of these patients, treatment with pimecrolimus cream 1% is useful, especially in the head/neck area.

Impact of treatment delay on mortality in ST-segment elevation myocardial infarction (STEMI) patients presenting with and without haemodynamic instability: results from the German prospective, multicentre FITT-STEMI trial.

PubMed

Scholz, Karl Heinrich; Maier, Sebastian K G; Maier, Lars S; Lengenfelder, Björn; Jacobshagen, Claudius; Jung, Jens; Fleischmann, Claus; Werner, Gerald S; Olbrich, Hans G; Ott, Rainer; Mudra, Harald; Seidl, Karlheinz; Schulze, P Christian; Weiss, Christian; Haimerl, Josef; Friede, Tim; Meyer, Thomas

2018-04-01

The aim of this study was to investigate the effect of contact-to-balloon time on mortality in ST-segment elevation myocardial infarction (STEMI) patients with and without haemodynamic instability. Using data from the prospective, multicentre Feedback Intervention and Treatment Times in ST-Elevation Myocardial Infarction (FITT-STEMI) trial, we assessed the prognostic relevance of first medical contact-to-balloon time in n = 12 675 STEMI patients who used emergency medical service transportation and were treated with primary percutaneous coronary intervention (PCI). Patients were stratified by cardiogenic shock (CS) and out-of-hospital cardiac arrest (OHCA). For patients treated within 60 to 180 min from the first medical contact, we found a nearly linear relationship between contact-to-balloon times and mortality in all four STEMI groups. In CS patients with no OHCA, every 10-min treatment delay resulted in 3.31 additional deaths in 100 PCI-treated patients. This treatment delay-related increase in mortality was significantly higher as compared to the two groups of OHCA patients with shock (2.09) and without shock (1.34), as well as to haemodynamically stable patients (0.34, P < 0.0001). In patients with CS, the time elapsing from the first medical contact to primary PCI is a strong predictor of an adverse outcome. This patient group benefitted most from immediate PCI treatment, hence special efforts to shorten contact-to-balloon time should be applied in particular to these high-risk STEMI patients. NCT00794001.

Rehabilitation of traumatic brain injury in Italy: a multi-centred study.

PubMed

Zampolini, M; Zaccaria, B; Tolli, V; Frustaci, A; Franceschini, M

2012-01-01

The aims of this study were to analyse TBI rehabilitation in Italy, identifying the main factors conditioning motor and functional recovery and destination upon discharge of traumatic severe acquired brain injury (sABI) patients who had undergone intensive rehabilitative treatment. An observational prospective study of 863 consecutive patients admitted to 52 Rehabilitation Centres from January 2001 to December 2003. The main cause of trauma was road accidents (79.8%), the mean length of stay was 87.31 ± 77.26 days and 40.4% access to rehabilitation facilities after a month. Pressure sore rates fell from 26.1% to 6.6% during the rehabilitation programme. After discharge 615 patients returned home, whilst 212 were admitted to other health facilities. This study highlights some major criticisms of rehabilitation of TBI. The delay of admission and evitable complications such as pressure sores are correlated to a worse outcome. While LOS causes a problem of cost-effectiveness, the rate of home discharge is prevalent and very high compared with other studies.

A headache not to be sneezed at.

PubMed

Garry, D; Forrest-Hay, A

2009-05-01

A 32-year-old male patient presented to the emergency department (ED) complaining of a headache and vertigo precipitated by sneezing. He had a recent history of neck trauma. Examination revealed horizontal nystagmus and a gait that veered to the left, exacerbated by heel to toe walking. A diagnosis of vertebral artery dissection (VAD) was suspected. A bleed was ruled out in the ED by computerised tomography, after which the patient was loaded with aspirin. The diagnosis was confirmed by magnetic resonance imaging and magnetic resonance angiography. Although optimal treatment for VAD is unknown, the Cervical Artery Dissection in Stroke Study (CADISS) is an ongoing randomised multicentre prospective study comparing antiplatelet therapy with anticoagulation for patients with both carotid artery dissection and VAD. Headache is a very common presentation to the ED and a full neurological examination is essential if rarer causes are not to be missed.

Randomised double-blind study comparing tropisetron alone and in combination with dexamethasone in the prevention of acute and delayed cisplatin-induced emesis.

PubMed

Garcia-del-Muro, X; Vadell, C; Pérez Manga, G; Bover, I; Rifá, J; Beltrán, M; Barros, M M; Germá, J R; Fabregat, X; Moreno, V; Salvador, A; Viladiu, P

1998-01-01

In a randomised, double-blind and parallel-design multicentre study, 282 chemotherapy-naive cancer patients received tropisetron 5 mg intravenously (i.v.) before high-dose cisplatin on day 1, and oral tropisetron 5 mg daily on days 2-6, in combination with either placebo (n = 143) or dexamethasone (n = 135), given i.v. on day 1 and orally on days 2-6. Complete protection from acute vomiting/nausea was achieved in 76.3%/79.3% of patients receiving the combination and in 55.2%/61.5% of those receiving tropisetron alone. Complete protection on days 2-6 from delayed vomiting/nausea was obtained in 60%/60% and 39.2%/40.6%, respectively. Tropisetron in combination with dexamethasone is safe and more effective than tropisetron alone in the prevention of both acute and delayed cisplatin-induced emesis.

Rococo study: a real-world evaluation of an over-the-counter medicine in acute cough (a multicentre, randomised, controlled study)

PubMed Central

Birring, S S; Brew, J; Kilbourn, A; Edwards, V; Wilson, R; Morice, A H

2017-01-01

Objectives To investigate the efficacy and safety of CS1002, an over-the-counter cough treatment containing diphenhydramine, ammonium chloride and levomenthol in a cocoa-based demulcent. Design A multicentre, randomised, parallel group, controlled, single-blinded study in participants with acute upper respiratory tract infection-associated cough. Setting 4 general practitioner (GP) surgeries and 14 pharmacies in the UK. Participants Participants aged ≥18 years who self-referred to a GP or pharmacist with acute cough of <7 days' duration. Participant inclusion criterion was cough severity ≥60 mm on a 0–100 mm visual analogue scale (VAS). Exclusion criteria included current smokers or history of smoking within the past 12 months (including e-cigarettes). 163 participants were randomised to the study (mean participant age 38 years, 57% females). Interventions Participants were randomised to CS1002 (Unicough) or simple linctus (SL), a widely used cough treatment, and treatment duration was 7 days or until resolution of cough. Main outcome measures The primary analysis was intention-to-treat (157 participants) and comprised cough severity assessed using a VAS after 3 days' treatment (prespecified primary end point at day 4). Cough frequency, sleep disruption, health status (Leicester Cough Questionnaire (LCQ-acute)) and cough resolution were also assessed. Results At day 4 (primary end point), the adjusted mean difference (95% CI) in cough severity VAS between CS1002 and SL was −5.9 mm (−14.4 to 2.7), p=0.18. At the end of the study (day 7) the mean difference in cough severity VAS was −4.2 mm (−12.2 to 3.9), p=0.31. CS1002 was associated with a greater reduction in cough sleep disruption (mean difference −11.6 mm (−20.6 to 2.7), p=0.01) and cough frequency (mean difference −8.1 mm (−16.2 to 0.1), p=0.05) compared with SL. There was greater improvement in LCQ-acute quality of life scores with CS1002 compared with SL: mean difference (95% CI) 1.2 (0.05 to 2.36), p=0.04 after 5 days' treatment. More participants prematurely stopped treatment due to cough improvement in the CS1002 group (24.4%) compared with SL (10.7%; p=0.02). Adverse events (AEs) were comparable between CS1002 (20.5%) and SL (27.6%) and largely related to the study indication. 6 participants (7%) in the CS1002 group reduced the dose of medication due to drowsiness/tiredness, which subsequently resolved. These events were not reported by participants as AEs. Conclusions Although the primary end point was not achieved, CS1002 was associated with greater reductions in cough frequency, sleep disruption and improved health status compared with SL. Trial registration number EudraCT number 2014-004255-31. PMID:28093442

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

PubMed

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

2015-09-23

Over 70% of all hospital admissions have a peripheral intravenous device (PIV) inserted; however, the failure rate of PIVs is unacceptably high, with up to 69% of these devices failing before treatment is complete. Failure can be due to dislodgement, phlebitis, occlusion/infiltration and/or infection. This results in interrupted medical therapy; painful phlebitis and reinsertions; increased hospital length of stay, morbidity and mortality from infections; and wasted medical/nursing time. Appropriate PIV dressing and securement may prevent many cases of PIV failure, but little comparative data exist regarding the efficacy of various PIV dressing and securement methods. This trial will investigate the clinical and cost-effectiveness of 4 methods of PIV dressing and securement in preventing PIV failure. A multicentre, parallel group, superiority randomised controlled trial with 4 arms, 3 experimental groups (tissue adhesive, bordered polyurethane dressing, sutureless securement device) and 1 control (standard polyurethane dressing) is planned. There will be a 3-year recruitment of 1708 adult patients, with allocation concealment until randomisation by a centralised web-based service. The primary outcome is PIV failure which includes any of: dislodgement, occlusion/infiltration, phlebitis and infection. Secondary outcomes include: types of PIV failure, PIV dwell time, costs, device colonisation, skin colonisation, patient and staff satisfaction. Relative incidence rates of device failure per 100 devices and per 1000 device days with 95% CIs will summarise the impact of each dressing, and test differences between groups. Kaplan-Meier survival curves (with log-rank Mantel-Cox test) will compare device failure over time. p Values of <0.05 will be considered significant. Secondary end points will be compared between groups using parametric or non-parametric techniques appropriate to level of measurement. Ethical approval has been received from Queensland Health (HREC/11/QRCH/152) and Griffith University (NRS/46/11/HREC). Results will be published according to the CONSORT statement and presented at relevant conferences. Australian New Zealand Clinical Trial Registry (ACTRN); 12611000769987. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

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

PubMed Central

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

2015-01-01

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

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/

Pregnancy outcomes after maternal varenicline use; analysis of surveillance data collected by the European Network of Teratology Information Services.

PubMed

Richardson, J L; Stephens, S; Yates, L M; Diav-Citrin, O; Arnon, J; Beghin, D; Kayser, A; Kennedy, D; Cupitt, D; Te Winkel, B; Peltonen, M; Kaplan, Y C; Thomas, S H L

2017-01-01

Varenicline is a smoking cessation aid for which limited data exist concerning safety during human pregnancy. This multicentre prospective observational comparative cohort study was undertaken using surveillance data collected by the European Network of Teratology Information Services. The study sample consisted of 89 varenicline exposed pregnancies and two matched comparator groups; 267 non-teratogen exposed (NTE) controls and 78 exposed to nicotine replacement therapy or bupropion (NRT/B) for smoking cessation. For all exposed pregnancies, varenicline use only occurred in the first trimester, with a considerable proportion discontinuing use in the very early stages of pregnancy. The major congenital malformation rate (n=2/89, 2.25%) was in keeping with the expected background rate (2-4%), and was not significantly increased for first trimester varenicline-exposed infants in comparison with non-exposed controls (vs. NTE: OR 2.02, 95%CI 0.166 to 17.9, vs. OR 0.874, 95%CI 0.0620 to 12.3). However, the small sample size produced very imprecise risk estimates. Copyright © 2016 Elsevier Inc. All rights reserved.

[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 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.

A multicentre audit of HDR/PDR brachytherapy absolute dosimetry in association with the INTERLACE trial (NCT015662405).

PubMed

Díez, P; Aird, E G A; Sander, T; Gouldstone, C A; Sharpe, P H G; Lee, C D; Lowe, G; Thomas, R A S; Simnor, T; Bownes, P; Bidmead, M; Gandon, L; Eaton, D; Palmer, A L

2017-11-09

A UK multicentre audit to evaluate HDR and PDR brachytherapy has been performed using alanine absolute dosimetry. This is the first national UK audit performing an absolute dose measurement at a clinically relevant distance (20 mm) from the source. It was performed in both INTERLACE (a phase III multicentre trial in cervical cancer) and non-INTERLACE brachytherapy centres treating gynaecological tumours. Forty-seven UK centres (including the National Physical Laboratory) were visited. A simulated line source was generated within each centre's treatment planning system and dwell times calculated to deliver 10 Gy at 20 mm from the midpoint of the central dwell (representative of Point A of the Manchester system). The line source was delivered in a water-equivalent plastic phantom (Barts Solid Water) encased in blocks of PMMA (polymethyl methacrylate) and charge measured with an ion chamber at 3 positions (120° apart, 20 mm from the source). Absorbed dose was then measured with alanine at the same positions and averaged to reduce source positional uncertainties. Charge was also measured at 50 mm from the source (representative of Point B of the Manchester system). Source types included 46 HDR and PDR 192 Ir sources, (7 Flexisource, 24 mHDR-v2, 12 GammaMed HDR Plus, 2 GammaMed PDR Plus, 1 VS2000) and 1 HDR 60 Co source, (Co0.A86). Alanine measurements when compared to the centres' calculated dose showed a mean difference (±SD) of  +1.1% (±1.4%) at 20 mm. Differences were also observed between source types and dose calculation algorithm. Ion chamber measurements demonstrated significant discrepancies between the three holes mainly due to positional variation of the source within the catheter (0.4%-4.9% maximum difference between two holes). This comprehensive audit of absolute dose to water from a simulated line source showed all centres could deliver the prescribed dose to within 5% maximum difference between measurement and calculation.

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

Piracetam relieves symptoms in progressive myoclonus epilepsy: a multicentre, randomised, double blind, crossover study comparing the efficacy and safety of three dosages of oral piracetam with placebo

PubMed Central

Koskiniemi, M.; Van Vleymen, B.; Hakamies, L.; Lamusuo, S.; Taalas, J.

1998-01-01

OBJECTIVE—To compare the efficacy, tolerability, and safety of three daily dosage regimens of oral piracetam in patients with progressive myoclonus epilepsy.
METHODS—Twenty patients (12 men, eight women), aged 17-43 years, with classical Unverricht-Lundborg disease were enrolled in a multicentre, randomised, double blind trial of crossover design in which the effects of daily doses of 9.6 g, 16.8 g, and 24 g piracetam, given in two divided doses, were compared with placebo. The crossover design was such that patients received placebo and two of the three dosage regimens of piracetam, each for two weeks, for a total treatment period of six weeks and thus without wash out between each treatment phase. The primary outcome measure was a sum score representing the adjusted total of the ratings of six components of a myoclonus rating scale in which stimulus sensitivity, motor impairment, functional disability, handwriting, and global assessments by investigators and patients were scored. Sequential clinical assessments were made by the same neurologist in the same environment at the same time of day.
RESULTS—Treatment with 24 g/day piracetam produced significant and clinically relevant improvement in the primary outcome measure of mean sum score (p=0.005) and in the means of its subtests of motor impairment (p=0.02), functional disability (p=0.003), and in global assessments by both investigator (p=0.002) and patient (p=0.01). Significant improvement in functional disability was also found with daily doses of 9.6 g and 16.8 g. The dose-effect relation was linear and significant. More patients showed clinically relevant improvement with the highest dosage and, in individual patients, increasing the dose improved response. Piracetam was well tolerated and adverse effects were few, mild, and transient.
CONCLUSIONS—This study provides further evidence that piracetam is an effective and safe medication in patients with Unverricht-Lundborg disease. In addition, it shows that a dose of 24 g is highly beneficial, more effective than lower doses and that a dose-effect relation exists. There is considerable variation in optimal individual dosage.

 PMID:9527146

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

PubMed

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

2017-04-11

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

Intragastric acid control in non-steroidal anti-inflammatory drug users: comparison of esomeprazole, lansoprazole and pantoprazole.

PubMed

Goldstein, J L; Miner, P B; Schlesinger, P K; Liu, S; Silberg, D G

2006-04-15

Studies to date have not directly compared the pharmacodynamic efficacies of different proton pump inhibitors in controlling intragastric acidity in patients treated with non-steroidal anti-inflammatory drugs. To compare acid suppression with once-daily esomeprazole 40 mg, lansoprazole 30 mg and pantoprazole 40 mg in patients receiving non-selective or cyclo-oxygenase-2-selective non-steroidal anti-inflammatory drug therapy. In this multicentre, open-label, comparative, three-way crossover study, adult patients (n = 90) receiving non-steroidal anti-inflammatory drugs were randomized to one of six treatment sequences. At the study site, patients were administered esomeprazole 40 mg, lansoprazole 30 mg and pantoprazole 40 mg for 5 days each, with a washout period of > or =10 days between each treatment. Twenty-four-hour pH testing was performed on day 5 of each dosing period. The mean percentage of time during the 24-h pH monitoring period that gastric pH was >4.0 was significantly greater with esomeprazole (74.2%) compared with lansoprazole (66.5%; P < 0.001) and pantoprazole (60.8%; P < 0.001), and significantly greater with esomeprazole (P < 0.05) than with the comparators regardless of whether using non-selective vs. cyclo-oxygenase-2-selective non-steroidal anti-inflammatory drugs. At the doses studied, esomeprazole treatment provides significantly greater gastric acid suppression than lansoprazole or pantoprazole in patients receiving non-selective or cyclo-oxygenase-2-selective non-steroidal anti-inflammatory drugs.

Exploring the Use of Actigraphy to Investigate Sleep Problems in Older People with Intellectual Disability

ERIC Educational Resources Information Center

van Dijk, E.; Hilgenkamp, T. I. M.; Evenhuis, H. M.; Echteld, M. A.

2012-01-01

Background: The aim of this study was to explore the use of actigraphy to investigate sleep problems in a convenience sample of clients of Dutch intellectual disability (ID) care providers. Based on data obtained in a large multi-centre study on healthy ageing in people with ID, research questions were: "To what degree are actigraphic…

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.

The HubBLe trial: haemorrhoidal artery ligation (HAL) versus rubber band ligation (RBL) for haemorrhoids.

PubMed

Tiernan, Jim; Hind, Daniel; Watson, Angus; Wailoo, Allan J; Bradburn, Michael; Shephard, Neil; Biggs, Katie; Brown, Steven

2012-10-25

Haemorrhoids (piles) are a very common condition seen in surgical clinics. After exclusion of more sinister causes of haemorrhoidal symptoms (rectal bleeding, perianal irritation and prolapse), the best option for treatment depends upon persistence and severity of the symptoms. Minor symptoms often respond to conservative treatment such as dietary fibre and reassurance. For more severe symptoms treatment such as rubber band ligation may be therapeutic and is a very commonly performed procedure in the surgical outpatient setting. Surgery is usually reserved for those who have more severe symptoms, as well as those who do not respond to non-operative therapy; surgical techniques include haemorrhoidectomy and haemorrhoidopexy. More recently, haemorrhoidal artery ligation has been introduced as a minimally invasive, non destructive surgical option.There are substantial data in the literature concerning efficacy and safety of 'rubber band ligation including multiple comparisons with other interventions, though there are no studies comparing it to haemorrhoidal artery ligation. A recent overview has been carried out by the National Institute for Health and Clinical Excellence which concludes that current evidence shows haemorrhoidal artery ligation to be a safe alternative to haemorrhoidectomy and haemorrhoidopexy though it also highlights the lack of good quality data as evidence for the advantages of the technique. The aim of this study is to establish the clinical effectiveness and cost effectiveness of haemorrhoidal artery ligation compared with conventional rubber band ligation in the treatment of people with symptomatic second or third degree (Grade II or Grade III) haemorrhoids. A multi-centre, parallel group randomised controlled trial. The primary outcome is patient-reported symptom recurrence twelve months following the intervention. Secondary outcome measures relate to symptoms, complications, health resource use, health related quality of life and cost effectiveness following the intervention. 350 patients with grade II or grade III haemorrhoids will be recruited in surgical departments in up to 14 NHS hospitals. A multi-centre, parallel group randomised controlled trial. Block randomisation by centre will be used, with 175 participants randomised to each group. The results of the research will help inform future practice for the treatment of grade II and III haemorrhoids. ISRCTN41394716.

Efficacy and tolerability of pale sulfonated shale oil cream 4% in the treatment of mild to moderate atopic eczema in children: a multicentre, randomized vehicle-controlled trial.

PubMed

Korting, H C; Schöllmann, C; Cholcha, W; Wolff, L

2010-10-01

Reports on controlled trials on the efficacy and tolerability of sulfonated shale oils in atopic eczema are not available so far. The aim of this study was to investigate whether topically applied, specially prepared pale sulfonated shale oil (PSSO) cream is capable of improving symptoms/signs of mild to moderate atopic eczema in children more efficaciously than a corresponding vehicle cream. A total of 99 children suffering from mild to moderate atopic eczema were enrolled in this multicentre, randomized, vehicle-controlled study. Verum or vehicle cream was applied to the affected skin area three times a day over 4 weeks. As the primary outcome parameter served the reduction of the total score after 4 weeks of treatment, compared with the initial examination. Secondary outcome parameters were addressed as well. Tolerability was judged by investigators and patients/parents, and adverse events were documented. After 4 weeks of treatment, the total score declined from 13.4 ± 3.7 to 4.5 ± 7.4 score points in the verum group and from 13.0 ± 3.1 to 11.7 ± 8.6 score points in the vehicle group (P < 0.0001). The superiority of verum regarding total score was already apparent after a treatment period of 1 week (reduction by 5.6 ± 4.3 vs. 1.3 ± 5.9 score points; P < 0.0001). Tolerability was found superior at the end of the treatment in the verum when compared with the control group--both by investigators (P < 0.0001) and patients/parents (P = 0.0051). Pale sulfonated shale oil cream 4% is capable to treat mild to moderate atopic eczema in children more efficaciously than vehicle and is well tolerated. PSSO thus represents a valuable addition to our therapeutic armamentarium. PSSO should be considered in particular when valid alternatives for topical glucocorticoids are sought for. © 2010 The Authors. Journal of the European Academy of Dermatology and Venereology © 2010 European Academy of Dermatology and Venereology.

Design of an international multicentre RCT on group schema therapy for borderline personality disorder.

PubMed

Wetzelaer, Pim; Farrell, Joan; Evers, Silvia M A A; Jacob, Gitta A; Lee, Christopher W; Brand, Odette; van Breukelen, Gerard; Fassbinder, Eva; Fretwell, Heather; Harper, R Patrick; Lavender, Anna; Lockwood, George; Malogiannis, Ioannis A; Schweiger, Ulrich; Startup, Helen; Stevenson, Teresa; Zarbock, Gerhard; Arntz, Arnoud

2014-11-18

Borderline personality disorder (BPD) is a severe and highly prevalent mental disorder. Schema therapy (ST) has been found effective in the treatment of BPD and is commonly delivered through an individual format. A group format (group schema therapy, GST) has also been developed. GST has been found to speed up and amplify the treatment effects found for individual ST. Delivery in a group format may lead to improved cost-effectiveness. An important question is how GST compares to treatment as usual (TAU) and what format for delivery of schema therapy (format A; intensive group therapy only, or format B; a combination of group and individual therapy) produces the best outcomes. An international, multicentre randomized controlled trial (RCT) will be conducted with a minimum of fourteen participating centres. Each centre will recruit multiple cohorts of at least sixteen patients. GST formats as well as the orders in which they are delivered to successive cohorts will be balanced. Within countries that contribute an uneven number of sites, the orders of GST formats will be balanced within a difference of one. The RCT is designed to include a minimum of 448 patients with BPD. The primary clinical outcome measure will be BPD severity. Secondary clinical outcome measures will include measures of BPD and general psychiatric symptoms, schemas and schema modes, social functioning and quality of life. Furthermore, an economic evaluation that consists of cost-effectiveness and cost-utility analyses will be performed using a societal perspective. Lastly, additional investigations will be carried out that include an assessment of the integrity of GST, a qualitative study on patients' and therapists' experiences with GST, and studies on variables that might influence the effectiveness of GST. This trial will compare GST to TAU for patients with BPD as well as two different formats for the delivery of GST. By combining an evaluation of clinical effectiveness, an economic evaluation and additional investigations, it will contribute to an evidence-based understanding of which treatment should be offered to patients with BPD from clinical, economic, and stakeholders' perspectives. Netherlands Trial Register NTR2392. Registered 25 June 2010.

Contraceptive efficacy and tolerability of ethinylestradiol 20 μg/drospirenone 3 mg in a flexible extended regimen: an open-label, multicentre, randomised, controlled study.

PubMed

Klipping, Christine; Duijkers, Ingrid; Fortier, Michel P; Marr, Joachim; Trummer, Dietmar; Elliesen, Jörg

2012-04-01

The contraceptive efficacy and tolerability of a new flexible extended regimen of ethinylestradiol (EE) 20 μg/drospirenone (DRSP) 3 mg to extend the menstrual cycle and enable management of intracyclic (breakthrough) bleeding (flexible(MIB)) was investigated and the bleeding pattern compared with a conventional 28-day regimen and a fixed extended 124-day regimen. This Phase III, 2-year, multicentre, open-label study randomly (4:1:1) allocated women (aged 18-35 years) to the following regimens: flexible(MIB) (24-120 days' active hormonal intake with 4-day tablet-free intervals); conventional (24 days' active hormonal intake followed by a 4-day hormone-free interval); or fixed extended (120 days' uninterrupted active hormonal intake followed by a 4-day tablet-free interval). Primary outcomes included the number of bleeding/spotting days during Year 1 (all regimens) and the number of observed unintended pregnancies over 2 years (flexible(MIB) only). Results were analysed in 1067 women (full analysis set). The mean number of bleeding/spotting days was lower with the flexible(MIB) vs the conventional regimen [41.0±29.1 (95% CI 38.8-43.3) vs 65.8±27.0 (95% CI 62.2-69.4) days, p<0.0001; treatment difference -24.8 (95% CI -29.2 to -20.3) days]. The corresponding value for the fixed extended regimen was 60.9±51.1 (95% CI 53.9-67.9) days. The Pearl Index for the flexible(MIB) regimen was 0.64 (95% CI 0.28-1.26). All regimens had comparable tolerability profiles. EE 20 μg/DRSP 3 mg administered as a flexible extended regimen with MIB is effective, well tolerated and is associated with statistically significantly fewer bleeding/spotting days and fewer withdrawal bleeding episodes vs EE/DRSP in a conventional 28-day regimen. The flexible(MIB) also provided statistically significantly fewer spotting days vs EE/DRSP in a fixed extended 124-day regimen (post hoc evaluation). The flexible(MIB) regimen allows women to extend their menstrual cycle and manage their intracyclic (breakthrough) bleeding.

Is Single-stage Revision Safe Following Infected Total Knee Arthroplasty? A Critical Review.

PubMed

Vaishya, Raju; Agarwal, Amit Kumar; Rawat, Sudheer K; Singh, Harsh; Vijay, Vipul

2017-08-30

With the improvement in outcomes and modern prosthesis design, total knee arthroplasty (TKA) has now become a commonly performed surgery. It is postulated that a total of 2-5% of the primary and revision TKA becomes infected every year, requiring a revision procedure which to date is the conventional two-stage revision. The diagnosis and treatment of these periprosthetic infections is a major and challenging task, as it requires precise identification of the pathogen, meticulous debridement, and postoperative rehabilitation. To date, there have been very few studies in existing literature comparing the outcomes of single-stage versus two-stage procedure in infected TKA. The aim of the review was to provide the clinicians an insight into the outcome of the single-stage procedure compared to two-stage procedures and to suggest ways to improve the results further. In the following critical review, a total of 669 cases that underwent either a single or two-stage revision for infected TKA were studied. The postoperative functional scores were comparable in most studies during the early postoperative period. Our data supports the use of a single-stage revision surgery in infected TKA as an alternative to a conventional two-stage procedure. However, larger prospective and multicentric trials are required to validate our findings.

Stigma experienced by patients with severe mental disorders: A nationwide multicentric study from India.

PubMed

Grover, Sandeep; Avasthi, Ajit; Singh, Aakanksha; Dan, Amitava; Neogi, Rajarshi; Kaur, Darpan; Lakdawala, Bhavesh; Rozatkar, Abhijit R; Nebhinani, Naresh; Patra, Suravi; Sivashankar, Priya; Subramanyam, Alka A; Tripathi, Adarsh; Gania, Ab Majid; Singh, Gurvinder Pal; Behere, Prakash

2017-11-01

This study aimed to evaluate the stigma and its correlates among patients with severe mental disorders. Patients with diagnosis of schizophrenia (N = 707), bipolar disorder (N = 344) and recurrent depressive disorder (N = 352) currently in clinical remission from 14 participating centres were assessed on Internalized Stigma of Mental Illness Scale (ISMIS). Patients with diagnosis of schizophrenia experienced higher level of alienation, sterotype endorsement, discrimination experience and total stigma when compared to patients with bipolar disorder and recurrent depressive disorder. Patients with bipolar disorder experienced higher stigma than those with recurrent depressive disorder in the domain of stigma resistance only. Overall compared to affective disorder groups, higher proportion of patients with schizophrenia reported stigma in all the domains of ISMIS. In general in all the 3 diagnostic groups' stigma was associated with shorter duration of illness, shorter duration of treatment and younger age of onset. To conclude, this study suggests that compared to affective disorder, patients with schizophrenia experience higher self stigma. Higher level of stigma is experienced during the early phase of illness. Stigma intervention programs must focus on patients during the initial phase of illness in order to reduce the negative consequences of stigma. Copyright © 2017 Elsevier B.V. All rights reserved.

Pattern of Drug Use and Associated Behaviors Among Female Injecting Drug Users From Northeast India: A Multi-Centric, Cross-Sectional, Comparative Study.

PubMed

Ambekar, Atul; Rao, Ravindra; Agrawal, Alok; Goyal, Shrigopal; Mishra, Ashwani; Kishore, Kunal; Mukherjee, Debashis; Albertin, Cristina

2015-01-01

Studies from developed countries document the presence of injecting drug use among females and significantly higher vulnerabilities and risks as compared with male injecting drug users (IDUs). Studies comparing vulnerabilities and drug use patterns between female and male IDUs are not available for developing countries. The aim of the study was to assess the drug use pattern and related HIV vulnerabilities among female IDUs and compare these findings with those from male IDUs from four states of Northeast India. The study used data collected as part of a nationwide study of drug use pattern and related HIV vulnerabilities among IDUs. Ninety-eight female and 202 male IDUs accessing services from harm reduction sites across the four states of Northeast region of India were chosen through random sampling methodology. Drug use pattern, injecting practices, and knowledge of HIV were assessed using a structured questionnaire. Significantly higher proportion of female IDUs was uneducated, unemployed, reported their occupation as sex workers, and switched to injecting drug use faster as compared with male IDUs. Female IDUs practicing sex work differed significantly from those who did not with respect to frequency of daily injections, choice of drugs injected, and concomitant use of non-injecting drugs. More than half of female IDUs initiated sharing within the first month of injecting. The study demonstrates that female IDUs differ from male IDUs in their drug use pattern, initiation into injection as well as injecting behavior, which would be an important consideration during designing of female-specific interventions.

Outcomes from pandemic influenza A H1N1 infection in recipients of solid-organ transplants: a multicentre cohort study.

PubMed

Kumar, Deepali; Michaels, Marian G; Morris, Michele I; Green, Michael; Avery, Robin K; Liu, Catherine; Danziger-Isakov, Lara; Stosor, Valentina; Estabrook, Michele; Gantt, Soren; Marr, Kieren A; Martin, Stanley; Silveira, Fernanda P; Razonable, Raymund R; Allen, Upton D; Levi, Marilyn E; Lyon, G Marshall; Bell, Lorraine E; Huprikar, Shirish; Patel, Gopi; Gregg, Kevin S; Pursell, Kenneth; Helmersen, Doug; Julian, Kathleen G; Shiley, Kevin; Bono, Bartholomew; Dharnidharka, Vikas R; Alavi, Gelareh; Kalpoe, Jayant S; Shoham, Shmuel; Reid, Gail E; Humar, Atul

2010-08-01

There are few data on the epidemiology and outcomes of influenza infection in recipients of solid-organ transplants. We aimed to establish the outcomes of pandemic influenza A H1N1 and factors leading to severe disease in a cohort of patients who had received transplants. We did a multicentre cohort study of adults and children who had received organ transplants with microbiological confirmation of influenza A infection from April to December, 2009. Centres were identified through the American Society of Transplantation Influenza Collaborative Study Group. Demographics, clinical presentation, treatment, and outcomes were assessed. Severity of disease was measured by admission to hospital and intensive care units (ICUs). The data were analysed with descriptive statistics. Proportions were compared by use of chi(2) tests. We used univariate analysis to identify factors leading to pneumonia, admission to hospital, and admission to an ICU. Multivariate analysis was done by use of a stepwise logistic regression model. We analysed deaths with Kaplan-Meier survival analysis. We assessed 237 cases of medically attended influenza A H1N1 reported from 26 transplant centres during the study period. Transplant types included kidney, liver, heart, lung, and others. Both adults (154 patients; median age 47 years) and children (83; 9 years) were assessed. Median time from transplant was 3.6 years. 167 (71%) of 237 patients were admitted to hospital. Data on complications were available for 230 patients; 73 (32%) had pneumonia, 37 (16%) were admitted to ICUs, and ten (4%) died. Antiviral treatment was used in 223 (94%) patients (primarily oseltamivir monotherapy). Seven (8%) patients given antiviral drugs within 48 h of symptom onset were admitted to an ICU compared with 28 (22.4%) given antivirals later (p=0.007). Children who received transplants were less likely to present with pneumonia than adults, but rates of admission to hospital and ICU were similar. Influenza A H1N1 caused substantial morbidity in recipients of solid-organ transplants during the 2009-10 pandemic. Starting antiviral therapy early is associated with clinical benefit as measured by need for ICU admission and mechanical ventilation. None. 2010 Elsevier Ltd. All rights reserved.

Effectiveness of a programme of exercise on physical function in survivors of critical illness following discharge from the ICU: study protocol for a randomised controlled trial (REVIVE)

PubMed Central

2014-01-01

Background Following discharge home from the ICU, patients often suffer from reduced physical function, exercise capacity, health-related quality of life and social functioning. There is usually no support to address these longer term problems, and there has been limited research carried out into interventions which could improve patient outcomes. The aim of this study is to investigate the effectiveness and cost-effectiveness of a 6-week programme of exercise on physical function in patients discharged from hospital following critical illness compared to standard care. Methods/Design The study design is a multicentre prospective phase II, allocation-concealed, assessor-blinded, randomised controlled clinical trial. Participants randomised to the intervention group will complete three exercise sessions per week (two sessions of supervised exercise and one unsupervised session) for 6 weeks. Supervised sessions will take place in a hospital gymnasium or, if this is not possible, in the participants home and the unsupervised session will take place at home. Blinded outcome assessment will be conducted at baseline after hospital discharge, following the exercise intervention, and at 6 months following baseline assessment (or equivalent time points for the standard care group). The primary outcome measure is physical function as measured by the physical functioning subscale of the Short-Form-36 health survey following the exercise programme. Secondary outcomes are health-related quality of life, exercise capacity, anxiety and depression, self efficacy to exercise and healthcare resource use. In addition, semi-structured interviews will be conducted to explore participants’ perceptions of the exercise programme, and the feasibility (safety, practicality and acceptability) of providing the exercise programme will be assessed. A within-trial cost-utility analysis to assess the cost-effectiveness of the intervention compared to standard care will also be conducted. Discussion If the exercise programme is found to be effective, this study will improve outcomes that are meaningful to patients and their families. It will inform the design of a future multicentre phase III clinical trial of exercise following recovery from critical illness. It will provide useful information which will help the development of services for patients after critical illness. Trial registration ClinicalTrials.gov NCT01463579 PMID:24767671

Effectiveness of a programme of exercise on physical function in survivors of critical illness following discharge from the ICU: study protocol for a randomised controlled trial (REVIVE).

PubMed

O'Neill, Brenda; McDowell, Kathryn; Bradley, Judy; Blackwood, Bronagh; Mullan, Brian; Lavery, Gavin; Agus, Ashley; Murphy, Sally; Gardner, Evie; McAuley, Daniel F

2014-04-27

Following discharge home from the ICU, patients often suffer from reduced physical function, exercise capacity, health-related quality of life and social functioning. There is usually no support to address these longer term problems, and there has been limited research carried out into interventions which could improve patient outcomes. The aim of this study is to investigate the effectiveness and cost-effectiveness of a 6-week programme of exercise on physical function in patients discharged from hospital following critical illness compared to standard care. The study design is a multicentre prospective phase II, allocation-concealed, assessor-blinded, randomised controlled clinical trial. Participants randomised to the intervention group will complete three exercise sessions per week (two sessions of supervised exercise and one unsupervised session) for 6 weeks. Supervised sessions will take place in a hospital gymnasium or, if this is not possible, in the participants home and the unsupervised session will take place at home. Blinded outcome assessment will be conducted at baseline after hospital discharge, following the exercise intervention, and at 6 months following baseline assessment (or equivalent time points for the standard care group). The primary outcome measure is physical function as measured by the physical functioning subscale of the Short-Form-36 health survey following the exercise programme. Secondary outcomes are health-related quality of life, exercise capacity, anxiety and depression, self efficacy to exercise and healthcare resource use. In addition, semi-structured interviews will be conducted to explore participants' perceptions of the exercise programme, and the feasibility (safety, practicality and acceptability) of providing the exercise programme will be assessed. A within-trial cost-utility analysis to assess the cost-effectiveness of the intervention compared to standard care will also be conducted. If the exercise programme is found to be effective, this study will improve outcomes that are meaningful to patients and their families. It will inform the design of a future multicentre phase III clinical trial of exercise following recovery from critical illness. It will provide useful information which will help the development of services for patients after critical illness. ClinicalTrials.gov NCT01463579.

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/.

Efficacy and safety of Postoperative Intravenous Parecoxib sodium Followed by ORal CElecoxib (PIPFORCE) post-total knee arthroplasty in patients with osteoarthritis: a study protocol for a multicentre, double-blind, parallel-group trial

PubMed Central

Zhuang, Qianyu; Bian, Yanyan; Wang, Wei; Jiang, Jingmei; Feng, Bin; Sun, Tiezheng; Lin, Jianhao; Zhang, Miaofeng; Yan, Shigui; Shen, Bin; Pei, Fuxing; Weng, Xisheng

2016-01-01

Introduction Total knee arthroplasty (TKA) has been regarded as a most painful orthopaedic surgery. Although many surgeons sequentially use parecoxib and celecoxib as a routine strategy for postoperative pain control after TKA, high quality evidence is still lacking to prove the effect of this sequential regimen, especially at the medium-term follow-up. The purpose of this study, therefore, is to evaluate efficacy and safety of postoperative intravenous parecoxib sodium followed by oral celecoxib in patients with osteoarthritis (OA) undergoing TKA. The hypothesis is that compared to placebo with opioids as rescue treatment, sequential use of parecoxib and celecoxib can achieve less morphine consumption over the postoperative 2 weeks, as well as better pain control, quicker functional recovery in the postoperative 6 weeks and less opioid-related adverse events during the 12-week recovery phase. Methods and analysis This study is designed as a multicentre, randomised, double-blind, parallel-group and placebo-controlled trial. The target sample size is 246. All participants who meet the study inclusion and exclusion criteria will be randomly assigned in a 1:1 ratio to either the parecoxib/celecoxib group or placebo group. The randomisation and allocation will be study site based. The study will consist of three phases: an initial screening phase; a 6-week double-blind treatment phase; and a 6-week follow-up phase. The primary end point is cumulative opioid consumption during 2 weeks postoperation. Secondary end points consist of the postoperative visual analogue scale score, knee joint function, quality of life, local skin temperature, erythrocyte sedimentation rate, C reactive protein, cytokines and blood coagulation parameters. Safety end points will be monitored too. Ethics and dissemination Ethics approval for this study has been obtained from the Ethics Committee, Peking Union Medical College Hospital, China (Protocol number: S-572) Study results will be available as published manuscripts and presentations at national and international meetings. Trial registration number NCT02198924. PMID:27609846

Efficacy and safety of Postoperative Intravenous Parecoxib sodium Followed by ORal CElecoxib (PIPFORCE) post-total knee arthroplasty in patients with osteoarthritis: a study protocol for a multicentre, double-blind, parallel-group trial.

PubMed

Zhuang, Qianyu; Bian, Yanyan; Wang, Wei; Jiang, Jingmei; Feng, Bin; Sun, Tiezheng; Lin, Jianhao; Zhang, Miaofeng; Yan, Shigui; Shen, Bin; Pei, Fuxing; Weng, Xisheng

2016-09-08

Total knee arthroplasty (TKA) has been regarded as a most painful orthopaedic surgery. Although many surgeons sequentially use parecoxib and celecoxib as a routine strategy for postoperative pain control after TKA, high quality evidence is still lacking to prove the effect of this sequential regimen, especially at the medium-term follow-up. The purpose of this study, therefore, is to evaluate efficacy and safety of postoperative intravenous parecoxib sodium followed by oral celecoxib in patients with osteoarthritis (OA) undergoing TKA. The hypothesis is that compared to placebo with opioids as rescue treatment, sequential use of parecoxib and celecoxib can achieve less morphine consumption over the postoperative 2 weeks, as well as better pain control, quicker functional recovery in the postoperative 6 weeks and less opioid-related adverse events during the 12-week recovery phase. This study is designed as a multicentre, randomised, double-blind, parallel-group and placebo-controlled trial. The target sample size is 246. All participants who meet the study inclusion and exclusion criteria will be randomly assigned in a 1:1 ratio to either the parecoxib/celecoxib group or placebo group. The randomisation and allocation will be study site based. The study will consist of three phases: an initial screening phase; a 6-week double-blind treatment phase; and a 6-week follow-up phase. The primary end point is cumulative opioid consumption during 2 weeks postoperation. Secondary end points consist of the postoperative visual analogue scale score, knee joint function, quality of life, local skin temperature, erythrocyte sedimentation rate, C reactive protein, cytokines and blood coagulation parameters. Safety end points will be monitored too. Ethics approval for this study has been obtained from the Ethics Committee, Peking Union Medical College Hospital, China (Protocol number: S-572) Study results will be available as published manuscripts and presentations at national and international meetings. NCT02198924. 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/

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.

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.

Efficacy and safety of saxagliptin in combination with metformin as initial therapy in Chinese patients with type 2 diabetes: Results from the START study, a multicentre, randomized, double-blind, active-controlled, phase 3 trial.

PubMed

Dou, Jingtao; Ma, Jianhua; Liu, Jun; Wang, Changjiang; Johnsson, Eva; Yao, Hui; Zhao, June; Pan, Changyu

2018-03-01

To assess the efficacy and safety of saxagliptin plus metformin over 24 weeks in pharmacotherapy-naïve Chinese patients with type 2 diabetes mellitus and inadequate glycaemic control (HbA1c, 8.0%-12.0%). In this multicentre, double-blind, active-controlled study (The START study: NCT02273050, clinicaltrials.gov), patients were randomized (1:1:1) to saxagliptin 5 mg plus metformin, saxagliptin 5 mg plus placebo or metformin plus placebo. Saxagliptin was taken once daily; metformin was taken once/twice daily and was titrated from 500 mg to a maximum of 2000 mg/d over 8 weeks. The primary end point was change in HbA1c from baseline to Week 24. Data from 630 patients (66.5% men; mean age, 50.1 years; mean body mass index, 26.6 kg/m 2 ; mean HbA1c, 9.4%; mean diabetes duration, 0.81 years) were analysed. Mean reduction in HbA1c was greater with saxagliptin plus metformin (-3.0%) than with saxagliptin plus placebo (-2.1%; P < .001) or metformin plus placebo (-2.8%; P = .034). Changes in mean fasting plasma glucose, 120-minute postprandial glucose, and 180-minute postprandial glucose area under the curve were greater, and more patients achieved a therapeutic glycaemic response, with saxagliptin plus metformin than with either monotherapy. Hypoglycaemic events were infrequent (<2%). Incidence of adverse events was similar among groups; upper respiratory tract infection and diarrhoea were most common. Saxagliptin 5 mg plus metformin significantly improved glycaemic control compared with either monotherapy in treatment-naïve Chinese patients with type 2 diabetes, and was well tolerated. © 2017 John Wiley & Sons Ltd.

Distinct features distinguishing IgG4-related disease from multicentric Castleman’s disease

PubMed Central

Sasaki, Takanori; Akiyama, Mitsuhiro; Kaneko, Yuko; Mori, Takehiko; Yasuoka, Hidekata; Suzuki, Katsuya; Yamaoka, Kunihiro; Okamoto, Shinichiro; Takeuchi, Tsutomu

2017-01-01

Objectives Differentiating IgG4-related disease (IgG4-RD) from multicentric Castleman’s disease (MCD) is challenging because both diseases present high serum IgG4. The objective of this study is to clarify the differences in characteristics and identify a clinically useful approach to differentiate these two diseases. Methods Forty-five consecutive patients with untreated active IgG4-RD and 33 patients with MCD were included in this study, who visited our institution from January 2000 to August 2016. The clinical and laboratory findings for the patients of the two diseases were compared. Various combinations of the distinctive findings were evaluated to identify the most efficient differentiating features between IgG4-RD and MCD. Results The levels of serum IgG4 were not different between the two diseases. Orbits, lacrimal glands, salivary glands or pancreas were involved in 88.9% of IgG4-RD cases and only in 3.0% of MCD cases. All MCD cases involved lymph nodes. Atopic history was characteristic for IgG4-RD. The levels of C reactive protein (CRP) with a cut-off of 0.80 mg/dL and IgA with a cut-off of 330 mg/dL were the most distinctive. The combination of ‘Orbits, lacrimal glands, salivary glands or pancreas involvement, atopic history, or non-involvement of lymph node’ and ‘CRP ≤ 0.8 mg/dL or IgA ≤ 330 mg/dL’ yielded the probability of 97.8% in IgG4-RD, while that of 3.0 % in patients with MCD. Conclusions Our study revealed distinct features between IgG4-RD and MCD. Differentiating between the diseases based on those distinct features, including distribution of organ involvement, atopic history, levels of IgA and CRP, was a useful approach. PMID:28959455

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.

Glucocorticoids predict 10-year fragility fracture risk in a population-based ambulatory cohort of men and women: Canadian Multicentre Osteoporosis Study (CaMos)

PubMed Central

Pallan, Shelley; Papaioannou, Alexandra; Mulgund, Manisha; Rios, Lorena; Ma, Jinhui; Thabane, Lehana; Davison, Kenneth S.; Josse, Robert G.; Kovacs, Christopher S.; Kreiger, Nancy; Olszynski, Wojciech P.; Prior, Jerilynn C.; Towheed, Tanveer; Adachi, Jonathan D.

2016-01-01

Summary We determined the prospective 10-year association among incident fragility fractures and four glucocorticoid (GC) treatment groups (Never GC, Prior GC, Baseline GC, and Ever GC). Results showed that GC treatment is associated with increased 10-year incident fracture risk in ambulatory men and women across Canada. Purpose Using the Canadian Multicentre Osteoporosis Study dataset, we determined the prospective 10-year association between incident fragility fractures and GC treatment. Methods We conducted a 10-year prospective observational cohort study at nine sites across Canada. A total of 9,263 ambulatory men and women 25 years of age and older were included in the analysis. Multivariable Cox proportional hazards analyses were conducted to determine the relationship among GC treatment groups in four levels that included Never GC, Prior GC, Baseline GC, and Ever GC (combined baseline and prior groups) and time to fracture. Results In each of the Never GC, Prior GC, Baseline GC, and Ever GC treatment groups, the number of participants were 8,832 (95.4 %), 303 (3.3 %), 128 (1.4 %), and 431 (4.7 %), respectively. Of the 9,263 individuals enrolled, incident fragility non-spine, hip, spine, and any fractures were experienced by a total of 896 (9.67 %), 157 (1.69 %), 130 (1.40 %), and 1,102 (11.90 %) over 10-years, respectively. For men and women combined, prior GC treatment was associated with a higher hazard ratio (HR) for time to incident non-vertebral (HR=1.5, 95 % confidence interval [CI]=1.1, 2.0), hip (HR=2.1, 95 % CI=1.1, 4.0), and any fracture (HR=1.4, 95 % CI=1.0, 1.8) compared with never GC treatment. Conclusions GC treatment is associated with increased 10-year incident fracture risk; this highlights the importance of considering therapy to prevent GC-induced fractures for patients who are using GC for various medical conditions. PMID:24577853

Colonoscopic full-thickness resection using an over-the-scope device: a prospective multicentre study in various indications.

PubMed

Schmidt, Arthur; Beyna, Torsten; Schumacher, Brigitte; Meining, Alexander; Richter-Schrag, Hans-Juergen; Messmann, Helmut; Neuhaus, Horst; Albers, David; Birk, Michael; Thimme, Robert; Probst, Andreas; Faehndrich, Martin; Frieling, Thomas; Goetz, Martin; Riecken, Bettina; Caca, Karel

2017-08-10

Endoscopic full-thickness resection (EFTR) is a novel treatment of colorectal lesions not amenable to conventional endoscopic resection. The aim of this prospective multicentre study was to assess the efficacy and safety of the full-thickness resection device. 181 patients were recruited in 9 centres with the indication of difficult adenomas (non-lifting and/or at difficult locations), early cancers and subepithelial tumours (SET). Primary endpoint was complete en bloc and R0 resection. EFTR was technically successful in 89.5%, R0 resection rate was 76.9%. In 127 patients with difficult adenomas and benign histology, R0 resection rate was 77.7%. In 14 cases, lesions harboured unsuspected cancer, another 15 lesions were primarily known as cancers. Of these 29 cases, R0 resection was achieved in 72.4%; 8 further cases had deep submucosal infiltration >1000 µm. Therefore, curative resection could only be achieved in 13/29 (44.8%). In the subgroup with SET (n=23), R0 resection rate was 87.0%. In general, R0 resection rate was higher with lesions ≤2 cm vs >2 cm (81.2% vs 58.1%, p=0.0038). Adverse event rate was 9.9% with a 2.2% rate of emergency surgery. Three-month follow-up was available from 154 cases and recurrent/residual tumour was evident in 15.3%. EFTR has a reasonable technical efficacy especially in lesions ≤2 cm with acceptable complication rates. Curative resection rate for early cancers was too low to recommend its primary use in this indication. Further comparative studies have to show the clinical value and long-term outcome of EFTR in benign colorectal lesions. NCT02362126; Results. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Whole body vibration for older persons: an open randomized, multicentre, parallel, clinical trial

PubMed Central

2011-01-01

Background Institutionalized older persons have a poor functional capacity. Including physical exercise in their routine activities decreases their frailty and improves their quality of life. Whole-body vibration (WBV) training is a type of exercise that seems beneficial in frail older persons to improve their functional mobility, but the evidence is inconclusive. This trial will compare the results of exercise with WBV and exercise without WBV in improving body balance, muscle performance and fall prevention in institutionalized older persons. Methods/Design An open, multicentre and parallel randomized clinical trial with blinded assessment. 160 nursing home residents aged over 65 years and of both sexes will be identified to participate in the study. Participants will be centrally randomised and allocated to interventions (vibration or exercise group) by telephone. The vibration group will perform static/dynamic exercises (balance and resistance training) on a vibratory platform (Frequency: 30-35 Hz; Amplitude: 2-4 mm) over a six-week training period (3 sessions/week). The exercise group will perform the same exercise protocol but without a vibration stimuli platform. The primary outcome measure is the static/dynamic body balance. Secondary outcomes are muscle strength and, number of new falls. Follow-up measurements will be collected at 6 weeks and at 6 months after randomization. Efficacy will be analysed on an intention-to-treat (ITT) basis and 'per protocol'. The effects of the intervention will be evaluated using the "t" test, Mann-Witney test, or Chi-square test, depending on the type of outcome. The final analysis will be performed 6 weeks and 6 months after randomization. Discussion This study will help to clarify whether WBV training improves body balance, gait mobility and muscle strength in frail older persons living in nursing homes. As far as we know, this will be the first study to evaluate the efficacy of WBV for the prevention of falls. Trial Registration ClinicalTrials.gov: NCT01375790 PMID:22192313

The MUK five protocol: a phase II randomised, controlled, parallel group, multi-centre trial of carfilzomib, cyclophosphamide and dexamethasone (CCD) vs. cyclophosphamide, bortezomib (Velcade) and dexamethasone (CVD) for first relapse and primary refractory multiple myeloma.

PubMed

Brown, Sarah; Hinsley, Samantha; Ballesteros, Mónica; Bourne, Sue; McGarry, Paul; Sherratt, Debbie; Flanagan, Louise; Gregory, Walter; Cavenagh, Jamie; Owen, Roger; Williams, Cathy; Kaiser, Martin; Low, Eric; Yong, Kwee

2016-01-01

Multiple myeloma is a plasma cell tumour with an annual incidence in the UK of approximately 40-50 per million i.e. about 4500 new cases per annum. The triple combination cyclophosphamide, bortezomib (Velcade®) and dexamethasone (CVD) is an effective regimen at relapse and has emerged in recent years as the standard therapy at first relapse in the UK. Carfilzomib has good activity as a single agent in the relapsed setting, and it is expected that efficacy will be improved when used in combination with dexamethasone and cyclophosphamide. MUK Five is a phase II open label, randomised, controlled, parallel group, multi-centre trial that will compare the activity of carfilzomib, cyclophosphamide and dexamethasone (CCD) with that of CVD, given over an equivalent treatment period (24 weeks), in participants with multiple myeloma at first relapse, or refractory to no more than 1 line of treatment. In addition, the study also aims to assess the utility of a maintenance schedule of carfilzomib in these participants. The primary objective of the trial is to assess whether CCD provides non-inferior activity in terms of ≥ VGPR rates at 24 weeks, and whether the addition of maintenance treatment with carfilzomib to CCD provides superior activity in terms of progression-free survival, as compared to CCD with no maintenance. Secondary objectives include comparing toxicity profiles, further summarizing and comparing the activity of the different treatment arms and analysis of the effect of each treatment arm on minimal residual disease status. The development of carfilzomib offers the opportunity to further explore the anti-tumour efficacy of proteasome inhibition and, based on the available evidence, it is important and timely to obtain data on the activity, toxicity and tolerability of this drug. In contrast to ongoing phase III trials, this phase II trial has a unique subset of participants diagnosed with multiple myeloma at first relapse or refractory to no more than 1 line of treatment and will also evaluate the utility of maintenance with carfilzomib for up to 18 months and investigate minimal residual disease status to provide information on depth of response and the prognostic impact thereof. The trial is registered under ISRCTN17354232, December 2012.

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

PubMed

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

2012-03-23

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

Balneotherapy Together with a Psychoeducation Program for Benzodiazepine Withdrawal: A Feasibility Study

PubMed Central

De Maricourt, P.; Hergueta, Th.; Galinowski, A.; Salamon, R.; Diallo, A.; Vaugeois, C.; Lépine, J. P.; Olié, J. P.

2016-01-01

Benzodiazepines should be prescribed on a short-term basis, but a significant proportion of patients (%) use them for more than 6 months, constituting a serious public health issue. Indeed, few strategies are effective in helping patients to discontinue long-term benzodiazepine treatments. The aim of this study was to assess the feasibility and the impact of a program including cognitive behavioural therapy, psychoeducation, and balneotherapy in a spa resort to facilitate long-term discontinuation of benzodiazepines. We conducted a prospective multicentre cohort study. Patients with long-term benzodiazepine use were recruited with the aim of anxiolytic withdrawal by means of a psychoeducational program and daily balneotherapy during 3 weeks. The primary efficacy outcome measure was benzodiazepine use 6 months after the program, compared to use at baseline. A total of 70 subjects were enrolled. At 6 months, overall benzodiazepine intake had decreased by 75.3%, with 41.4% of patients completely stopping benzodiazepine use. The results also suggest a significantly greater improvement in anxiety and depression symptoms among patients who discontinued benzodiazepines compared to patients who only reduced their use. Our findings suggest that balneotherapy in association with a psychoeducative program is efficient in subjects with benzodiazepine addiction. PMID:27956923

[Multicentric study of thrombosis prevention in upper-extremity microsurgery. Survey at the Fesum centers].

PubMed

Dumont, L-A; Rongières, M; Tchénio, P; Gangloff, D; Garrido-Stowhas, I

2010-04-01

Thrombosis is still the first cause of microsurgery failure. Lots of publications have been made but no consensus exists. We first analysed the results of our study in 53 French expert surgeons, then we compared them with the last published datas, most of all, with the similar surveys. If a big majority (81 %) of the surgeons use a preventing method, we observed majors variations between them and also compared to the anglosaxons surgeons habits. This survey permits to make the point on today's practice and to show that some of them are based on low proof level and something even done without any medical references. After datas analysis, we observed that none of the medical treatments proved efficiency on preventing vascular thrombosis. The low molecular weight heparins (LMWH) could be used on postops without increase bleeding but not to lower specially the microvascular thrombosis rate. Aspirin did not improve the positive rates and its adjonction to LMWH increased the bleeding. Until scientific studies prove efficacy of a treatment, the surgeon has to make a personal choice: keeping habits or following evidence-based medicine. Copyright 2010 Elsevier Masson SAS. All rights reserved.

[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.

A multicentre randomized controlled trial of an empowerment-inspired intervention for adolescents starting continuous subcutaneous insulin infusion--a study protocol.

PubMed

Brorsson, Anna Lena; Leksell, Janeth; Viklund, Gunnel; Lindholm Olinder, Anna

2013-12-20

Continuous subcutaneous insulin infusion (CSII) treatment among children with type 1 diabetes is increasing in Sweden. However, studies evaluating glycaemic control in children using CSII show inconsistent results. The distribution of responsibility for diabetes self-management between children and parents is often unclear and needs clarification. There is much published support for continued parental involvement and shared diabetes management during adolescence. Guided Self-Determination (GSD) is an empowerment-based, person-centred, reflection and problem solving method intended to guide the patient to become self-sufficient and develop life skills for managing difficulties in diabetes self-management. This method has been adapted for adolescents and parents as Guided Self-Determination-Young (GSD-Y). This study aims to evaluate the effect of an intervention with GSD-Y in groups of adolescents starting on insulin pumps and their parents on diabetes-related family conflicts, perceived health and quality of life (QoL), and metabolic control. Here, we describe the protocol and plans for study enrollment. This study is designed as a randomized, controlled, prospective, multicentre study. Eighty patients between 12-18 years of age who are planning to start CSII will be included. All adolescents and their parents will receive standard insulin pump training. The education intervention will be conducted when CSII is to be started and at four appointments in the first 4 months after starting CSII. The primary outcome is haemoglobin A1c levels. Secondary outcomes are perceived health and QoL, frequency of blood glucose self-monitoring and bolus doses, and usage of carbohydrate counting. The following instruments will be used: Disabkids, 'Check your health', the Diabetes Family Conflict Scale and the Swedish Diabetes Empowerment Scale. Outcomes will be evaluated within and between groups by comparing data at baseline, and at 6 and 12 months after starting treatment. In this study, we will assess the effect of starting an CSII together with the model of GSD to determine whether this approach leads to retention of improved glycaemic control, QoL, responsibility distribution and reduced diabetes-related conflicts in the family.

Measurement of Exercise Tolerance before Surgery (METS) study: a protocol for an international multicentre prospective cohort study of cardiopulmonary exercise testing prior to major non-cardiac surgery.

PubMed

Wijeysundera, Duminda N; Pearse, Rupert M; Shulman, Mark A; Abbott, Tom E F; Torres, Elizabeth; Croal, Bernard L; Granton, John T; Thorpe, Kevin E; Grocott, Michael P W; Farrington, Catherine; Myles, Paul S; Cuthbertson, Brian H

2016-03-11

Preoperative functional capacity is considered an important risk factor for cardiovascular and other complications of major non-cardiac surgery. Nonetheless, the usual approach for estimating preoperative functional capacity, namely doctors' subjective assessment, may not accurately predict postoperative morbidity or mortality. 3 possible alternatives are cardiopulmonary exercise testing; the Duke Activity Status Index, a standardised questionnaire for estimating functional capacity; and the serum concentration of N-terminal pro-B-type natriuretic peptide (NT pro-BNP), a biomarker for heart failure and cardiac ischaemia. The Measurement of Exercise Tolerance before Surgery (METS) Study is a multicentre prospective cohort study of patients undergoing major elective non-cardiac surgery at 25 participating study sites in Australia, Canada, New Zealand and the UK. We aim to recruit 1723 participants. Prior to surgery, participants undergo symptom-limited cardiopulmonary exercise testing on a cycle ergometer, complete the Duke Activity Status Index questionnaire, undergo blood sampling to measure serum NT pro-BNP concentration and have their functional capacity subjectively assessed by their responsible doctors. Participants are followed for 1 year after surgery to assess vital status, postoperative complications and general health utilities. The primary outcome is all-cause death or non-fatal myocardial infarction within 30 days after surgery, and the secondary outcome is all-cause death within 1 year after surgery. Both receiver-operating-characteristic curve methods and risk reclassification table methods will be used to compare the prognostic accuracy of preoperative subjective assessment, peak oxygen consumption during cardiopulmonary exercise testing, Duke Activity Status Index scores and serum NT pro-BNP concentration. The METS Study has received research ethics board approval at all sites. Participant recruitment began in March 2013, and 1-year follow-up is expected to finish in 2016. Publication of the results of the METS Study is anticipated to occur in 2017. 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/

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.

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

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.

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.

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.

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.

A pilot study of spatial patterns in referrals to a multicentre cancer genetics service.

PubMed

Tempest, Vanessa; Higgs, Gary; McDonald, Kevin; Iredale, Rachel; Bater, Tony; Gray, Jonathon

2005-01-01

To analyse spatial and temporal patterns in patients referred to a cancer genetics service in order to monitor service utilization and accessibility. Postcodes of patients during a 4-year period were used to examine spatial patterns using a Geographical Information System (GIS). Referral rates were compared visually and statistically to explore yearly variation for administrative areas in Wales. There has been a four-fold increase in actual referrals to the service over the period of study. The variance between unitary authority referral rates has decreased from the inception of the service from an almost ten-fold difference between lowest and highest in year 1 to less than a three-fold difference in year 4. This study shows the potential of GIS to highlight spatial variations in referral rates across Wales. Although the disparity in referral rates has decreased, trends in referral rates are not consistent. Ongoing research will examine those referral and referrer characteristics affecting uptake. Copyright 2005 S. Karger AG, Basel.

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.

Two doses of rivaroxaban versus aspirin for prevention of recurrent venous thromboembolism. Rationale for and design of the EINSTEIN CHOICE study.

PubMed

Weitz, Jeffrey I; Bauersachs, Rupert; Beyer-Westendorf, Jan; Bounameaux, Henri; Brighton, Timothy A; Cohen, Alexander T; Davidson, Bruce L; Holberg, Gerlind; Kakkar, Ajay; Lensing, Anthonie W A; Prins, Martin; Haskell, Lloyd; van Bellen, Bonno; Verhamme, Peter; Wells, Philip S; Prandoni, Paolo

2015-08-31

Patients with unprovoked venous thromboembolism (VTE) are at high risk for recurrence. Although rivaroxaban is effective for extended VTE treatment at a dose of 20 mg once daily, use of the 10 mg dose may further improve its benefit-to-risk ratio. Low-dose aspirin also reduces rates of recurrent VTE, but has not been compared with anticoagulant therapy. The EINSTEIN CHOICE study is a multicentre, randomised, double-blind, active-controlled, event-driven study comparing the efficacy and safety of two once daily doses of rivaroxaban (20 and 10 mg) with aspirin (100 mg daily) for the prevention of recurrent VTE in patients who completed 6-12 months of anticoagulant therapy for their index acute VTE event. All treatments will be given for 12 months. The primary efficacy objective is to determine whether both doses of rivaroxaban are superior to aspirin for the prevention of symptomatic recurrent VTE, while the principal safety outcome is the incidence of major bleeding. The trial is anticipated to enrol 2,850 patients from 230 sites in 31 countries over a period of 27 months. In conclusion, the EINSTEIN CHOICE study will provide new insights into the optimal antithrombotic strategy for extended VTE treatment by comparing two doses of rivaroxaban with aspirin (clinicaltrials.gov NCT02064439).

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 .

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

Libertas: rationale and study design of a multicentre, Phase II, double-blind, randomised, placebo-controlled investigation to evaluate the efficacy, safety and tolerability of locally applied NRL001 in patients with faecal incontinence.

PubMed

Siproudhis, L; Jones, D; Shing, R Ng Kwet; Walker, D; Scholefield, J H

2014-03-01

Faecal incontinence affects up to 8% of adults. Associated social isolation and subsequent depression can have devastating effects on quality of life (QoL). Faecal incontinence is an underreported health problem as the social isolation and stigma that patients experience makes it difficult for sufferers to discuss their condition with a physician. There have been few well-designed, placebo-controlled clinical trials of treatment for faecal incontinence and little clinical evidence is available to inform the most appropriate management strategies. Libertas, a robustly designed study will investigate the efficacy and safety of NRL001 (1R,2S-methoxamine), an α1 -adrenoceptor agonist, in the treatment of faecal incontinence. Libertas is a multicentre, Phase II, double-blind, randomised, placebo-controlled, parallel group study. Patient recruitment took place across 55 study centres in Europe. Patients suffering with faecal incontinence were randomised into four groups (approximately 110 each) to receive once daily self-administered doses of NRL001 (5, 7.5 or 10 mg or placebo in a suppository formulation) for 8 weeks. The primary objective of Libertas is to assess the impact of once daily administration of NRL001 on the severity and frequency of incontinence episodes as assessed by the Wexner score at 4 weeks, compared with placebo. Secondary outcomes include measures of efficacy of NRL001 compared with placebo following 8 weeks treatment; safety and tolerability; evaluation of plasma pharmacokinetics; establishment of any pharmacokinetic/pharmacodynamic relationship to adverse events; dose-response relationship; the efficacy of NRL001 therapy at 4 and 8 weeks assessed by the Vaizey score; and QoL using the Faecal Incontinence Quality of Life and the EQ-5D-5L Healthcare Questionnaires following 4 and 8 weeks NRL001 therapy. Overall patient satisfaction with the treatment will also be evaluated. This is the first randomised controlled study to investigate the efficacy and safety of a selective α1 -adrenoceptor agonist for the treatment of faecal incontinence. Furthermore, this is the first time the impact of NRL001 on assessments of QoL, health outcomes and patient satisfaction will be assessed. Innovative strategies were developed to meet the challenge of recruiting patients for this study, for example, media advertising, posters and mailshots as allowed by each study centre. Colorectal Disease © 2014 The Association of Coloproctology of Great Britain and Ireland.

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

PubMed Central

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

2015-01-01

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

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

Association of dietary soy genistein intake with lung function and asthma control: a post-hoc analysis of patients enrolled in a prospective multicentre clinical trial

PubMed Central

Bime, Christian; Wei, Christine Y; Holbrook, Janet; Smith, Lewis J; Wise, Robert A

2013-01-01

Background Broad dietary patterns have been linked to asthma but the relative contribution of specific nutrients is unclear. Soy genistein has important anti-inflammatory and other biological effects that might be beneficial in asthma. A positive association was previously reported between soy genistein intake and lung function but not with asthma exacerbations. Aims To conduct a post-hoc analysis of patients with inadequately controlled asthma enrolled in a prospective multicentre clinical trial to replicate this association. Methods A total of 300 study participants were included in the analysis. Dietary soy genistein intake was measured using the Block Soy Foods Screener. The level of soy genistein intake (little or no intake, moderate intake, or high intake) was compared with baseline lung function (pre-bronchodilator forced expiratory volume in 1 second (FEV1)) and asthma control (proportion of participants with an episode of poor asthma control (EPAC) and annualised rates of EPACs over a 6-month follow-up period. Results Participants with little or no genistein intake had a lower baseline FEV1 than those with a moderate or high intake (2.26L vs. 2.53L and 2.47L, respectively; p=0.01). EPACs were more common among those with no genistein intake than in those with a moderate or high intake (54% vs. 35% vs. 40%, respectively; p<0.001). These findings remained significant after adjustment for patient demographics and body mass index. Conclusions In patients with asthma, consumption of a diet with moderate to high amounts of soy genistein is associated with better lung function and better asthma control. PMID:22885561

Multidisciplinary rehabilitation treatment versus cognitive behavioural therapy for patients with chronic fatigue syndrome: a randomized controlled trial.

PubMed

Vos-Vromans, D C W M; Smeets, R J E M; Huijnen, I P J; Köke, A J A; Hitters, W M G C; Rijnders, L J M; Pont, M; Winkens, B; Knottnerus, J A

2016-03-01

The aim of this trial was to evaluate the difference in treatment effect, at 26 and 52 weeks after the start of treatment, between cognitive behavioural therapy (CBT) and multidisciplinary rehabilitation treatment (MRT) for patients with chronic fatigue syndrome (CFS). Multicentre, randomized controlled trial of patients with CFS. Participants were randomly assigned to MRT or CBT. Four rehabilitation centres in the Netherlands. A total of 122 patients participated in the trial. Primary outcomes were fatigue measured by the fatigue subscale of the Checklist Individual Strength and health-related quality of life measured by the Short-Form 36. Outcomes were assessed prior to treatment and at 26 and 52 weeks after treatment initiation. A total of 114 participants completed the assessment at 26 weeks, and 112 completed the assessment at 52 weeks. MRT was significantly more effective than CBT in reducing fatigue at 52 weeks. The estimated difference in fatigue between the two treatments was -3.02 [95% confidence interval (CI) -8.07 to 2.03; P = 0.24] at 26 weeks and -5.69 (95% CI -10.62 to -0.76; P = 0.02) at 52 weeks. Patients showed an improvement in quality of life over time, but between-group differences were not significant. This study provides evidence that MRT is more effective in reducing long-term fatigue severity than CBT in patients with CFS. Although implementation in comparable populations can be recommended based on clinical effectiveness, it is advisable to analyse the cost-effectiveness and replicate these findings in another multicentre trial. © 2015 The Association for the Publication of the Journal of Internal Medicine.

Effectiveness of a standardised exercise programme for recurrent neck and low back pain: a multicentre, randomised, two-arm, parallel group trial across 34 fitness clubs in Finland.

PubMed

Suni, Jaana H; Rinne, Marjo; Tokola, Kari; Mänttäri, Ari; Vasankari, Tommi

2017-01-01

Neck and low back pain (LBP) are common in office workers. Exercise trials to reduce neck and LBP conducted in sport sector are lacking. We investigated the effectiveness of the standardised Fustra20Neck&Back exercise program for reducing pain and increasing fitness in office workers with recurrent non-specific neck and/or LBP. Volunteers were recruited through newspaper and Facebook. The design is a multi-centre randomised, two-arm, parallel group trial across 34 fitness clubs in Finland. Eligibility was determined by structured telephone interview. Instructors were specially educated professionals. Neuromuscular exercise was individually guided twice weekly for 10 weeks. Webropol survey, and objective measurements of fitness, physical activity, and sedentary behavior were conducted at baseline, and at 3 and 12 months. Mean differences between study groups (Exercise vs Control) were analysed using a general linear mixed model according to the intention-to-treat principle. At least moderate intensity pain (≥40 mm) in both the neck and back was detected in 44% of participants at baseline. Exercise compliance was excellent: 92% participated 15-20 times out of 20 possible. Intensity and frequency of neck pain, and strain in neck/shoulders decreased significantly in the Exercise group compared with the Control group. No differences in LBP and strain were detected. Neck/shoulder and trunk flexibility improved, as did quality of life in terms of pain and physical functioning. The Fustra20Neck&Back exercise program was effective for reducing neck/shoulder pain and strain, but not LBP. Evidence-based exercise programs of sports clubs have potential to prevent persistent, disabling musculoskeletal problems.

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

PubMed

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

2009-09-19

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

Technetium-99m tetrofosmin rest/stress myocardial SPET with a same-day 2-hour protocol: comparison with coronary angiography. A Spanish-Portuguese multicentre clinical trial.

PubMed

Montz, R; Perez-Castejón, M J; Jurado, J A; Martín-Comín, J; Esplugues, E; Salgado, L; Ventosa, A; Cantinho, G; Sá, E P; Fonseca, A T; Vieira, M R

1996-06-01

Technetium-99m tetrofosmin (Myoview) has unique properties for myocardial perfusion imaging very early after injection of the tracer. We used a very short same-day rest/stress protocol, to be performed within 2 h and evaluated its diagnostic accuracy. The study included 144 patients from seven Spanish and four Portuguese centres with a diagnosis of uncomplicated coronary artery disease (CAD); 78 patients (54%) had no history of prior myocardial infarction. Patients were injected with /=50%) was achieved with a sensitivity of 64% for the left anterior descending artery, 49% for the left circumflex artery and 86% for the right coronary artery, and an accuracy of 71%, 72% and 73% respectively. Concordance of SPET and CA was 62% for single-vessel disease and 68% for multivessel disease. In conclusion, this Spanish-Portuguese multicentre clinical trial confirmed, in a considerable number of patients who underwent coronary angiography, the feasibility of 99mTc tetrofosmin (Myoview) rest/stress myocardial SPET using a very short protocol (2 h).

Banding versus bonding of first permanent molars: a multi-centre randomized controlled trial.

PubMed

Nazir, Mariyah; Walsh, Tanya; Mandall, Nicky A; Matthew, Susie; Fox, Dee

2011-06-01

To assess the effectiveness of banding versus bonding of first permanent molars during fixed appliance treatment; in terms of attachment failure, patient discomfort and post-treatment enamel demineralization. Multi-centre randomized clinical trial. One District General Hospital Orthodontic Department and two Specialist Orthodontic Practices. Orthodontic patients aged between 10 and 18 years old, randomly allocated to either receive molar bands (n=40) or molar bonds (n=40). Bands were cemented with a conventional glass ionomer cement and tubes were bonded with light-cured composite to all four first permanent molar teeth for each subject. Attachments were reviewed at each recall appointment to assess loosening or loss. The clinical end point of the trial was the day of appliance debond. Enamel demineralization at debond was assessed using the modified International Caries Assessment and Detection System (ICDAS). The first time failure rate for molar bonds was 18·4% and 2·6% for molar bands (P=0·0002). Survival analysis demonstrated molar bonds were more likely to fail compared with molar bands. First permanent molars with bonded tubes experienced more demineralization than those with cemented bands (P=0·027). There was no statistically significant difference in discomfort experienced by patients after banding or bonding first permanent molars (P>0·05). This study shows that as part of fixed appliance therapy, American Orthodontics photoetched first permanent molar bands cemented with 3M ESPE Ketac-Cem perform better than American Orthodontics low profile photo-etched and mesh-based first permanent molar tubes bonded with 3M Unitek Transbond XT in terms of failure behaviour and molar enamel demineralization.

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.

A multicentre, randomized, single-blind, parallel-group study comparing the efficacy and tolerability of benzoyl peroxide 3%/clindamycin 1% with azelaic acid 20% in the topical treatment of mild-to-moderate acne vulgaris.

PubMed

Schaller, M; Sebastian, M; Ress, C; Seidel, D; Hennig, M

2016-06-01

Mild-to-moderate acne vulgaris is treated with a range of mono- and combination therapies; however, clinical evidence is still required to optimize treatment recommendations. To compare the efficacy, tolerability and safety of a combination of benzoyl peroxide 3% and clindamycin 1% (BPO + CLN) with azelaic acid 20% (AzA) for the topical treatment of mild-to-moderate acne vulgaris. This was a randomized, assessor-blinded, parallel-group, multicentre study conducted in Germany. Patients with a confirmed diagnosis of acne vulgaris, aged 12-45 years, were randomized 1 : 1 to once-daily BPO + CLN gel or twice-daily AzA cream for up to 12 weeks. The primary endpoint was the percentage change in inflammatory lesions from baseline at Week 4. Secondary endpoints included total and inflammatory lesion counts and tolerability assessments. For selected secondary endpoints, inductive statistical analysis was performed post hoc. Patient safety was assessed by adverse event (AE) monitoring. Efficacy was assessed in the modified intent-to-treat (mITT) population [patients using ≥1 dose of study medication (ITT), plus baseline and ≥1 post-baseline lesion count (n = 215)]. There was a statistically significant difference in the primary endpoint, with a median decrease of -52.6% for BPO + CLN (n = 107) vs.-38.8% for AzA (n = 108; P = 0.0004). There was also a greater difference in secondary lesion endpoints at Week 12, with a median decrease in inflammatory lesions of -78.8% and -65.3% and total lesions of -69.0% and -53.9% with BPO + CLN and AzA, respectively (both P < 0.0001). Tolerability was acceptable for both treatments. Overall, 55.6% (BPO + CLN) and 69.7% (AzA) of patients reported treatment-emergent AEs, and 15.7% and 35.8% of patients experienced application site reactions with BPO + CLN (24 events; 17 patients) and AzA (60 events; 39 patients) treatment, respectively (ITT population). BPO + CLN demonstrated greater efficacy than AzA in the treatment of mild-to-moderate acne vulgaris and has a positive tolerability and safety profile. © 2016 European Academy of Dermatology and Venereology.

A multi-centre randomised controlled trial of rehabilitation aimed at improving outdoor mobility for people after stroke: Study protocol for a randomised controlled trial

PubMed Central

2012-01-01

Background Up to 42% of all stroke patients do not get out of the house as much as they would like. This can impede a person’s quality of life. This study is testing the clinical effectiveness and cost effectiveness of a new outdoor mobility rehabilitation intervention by comparing it to usual care. Methods/design This is a multi-centre parallel group individually randomised, controlled trial. At least 506 participants will be recruited through 15 primary and secondary care settings and will be eligible if they are over 18 years of age, have had a stroke and wish to get out of the house more often. Participants are being randomly allocated to either the intervention group or the control group. Intervention group participants receive up to 12 rehabilitation outdoor mobility sessions over up to four months. The main component of the intervention is repeated practice of outdoor mobility with a therapist. Control group participants are receiving the usual intervention for outdoor mobility limitations: verbal advice and provision of leaflets provided over one session. Outcome measures are being collected using postal questionnaires, travel calendars and by independent assessors. The primary outcome measure is the Social Function domain of the SF36v2 quality of life assessment six months after recruitment. The secondary outcome measures include: functional ability, mobility, the number of journeys (monthly travel diaries), satisfaction with outdoor mobility, mood, health-related quality of life, resource use of health and social care. Carer mood information is also being collected. The mean Social Function score of the SF-36v2 will be compared between treatment arms using a multiple membership form of mixed effects multiple regression analysis adjusting for centre (as a fixed effect), age and baseline Social Function score as covariates and therapist as a multiple membership random effect. Regression coefficients and 95% confidence intervals will be presented. Discussion This study protocol describes a pragmatic randomised controlled trial that will hopefully provide robust evidence of the benefit of outdoor mobility interventions after stroke for clinicians working in the community. The results will be available towards the end of 2012. Trial registration ISRCTN58683841 PMID:22721452

Contraceptive efficacy and tolerability of ethinylestradiol 20 µg/drospirenone 3 mg in a flexible extended regimen: an open-label, multicentre, randomised, controlled study

PubMed Central

Klipping, Christine; Duijkers, Ingrid; Fortier, Michel P; Marr, Joachim; Trummer, Dietmar; Elliesen, Jörg

2012-01-01

Background The contraceptive efficacy and tolerability of a new flexible extended regimen of ethinylestradiol (EE) 20 μg/drospirenone (DRSP) 3 mg to extend the menstrual cycle and enable management of intracyclic (breakthrough) bleeding (flexibleMIB) was investigated and the bleeding pattern compared with a conventional 28-day regimen and a fixed extended 124-day regimen. Study design This Phase III, 2-year, multicentre, open-label study randomly (4:1:1) allocated women (aged 18–35 years) to the following regimens: flexibleMIB (24–120 days' active hormonal intake with 4-day tablet-free intervals); conventional (24 days' active hormonal intake followed by a 4-day hormone-free interval); or fixed extended (120 days' uninterrupted active hormonal intake followed by a 4-day tablet-free interval). Primary outcomes included the number of bleeding/spotting days during Year 1 (all regimens) and the number of observed unintended pregnancies over 2 years (flexibleMIB only). Results Results were analysed in 1067 women (full analysis set). The mean number of bleeding/spotting days was lower with the flexibleMIB vs the conventional regimen [41.0±29.1 (95% CI 38.8–43.3) vs 65.8±27.0 (95% CI 62.2–69.4) days, p<0.0001; treatment difference −24.8 (95% CI −29.2 to −20.3) days]. The corresponding value for the fixed extended regimen was 60.9±51.1 (95% CI 53.9–67.9) days. The Pearl Index for the flexibleMIB regimen was 0.64 (95% CI 0.28–1.26). All regimens had comparable tolerability profiles. Conclusions EE 20 μg/DRSP 3 mg administered as a flexible extended regimen with MIB is effective, well tolerated and is associated with statistically significantly fewer bleeding/spotting days and fewer withdrawal bleeding episodes vs EE/DRSP in a conventional 28-day regimen. The flexibleMIB also provided statistically significantly fewer spotting days vs EE/DRSP in a fixed extended 124-day regimen (post hoc evaluation). The flexibleMIB regimen allows women to extend their menstrual cycle and manage their intracyclic (breakthrough) bleeding. PMID:22454003

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…

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.

Randomized comparison of operator radiation exposure comparing transradial and transfemoral approach for percutaneous coronary procedures: rationale and design of the minimizing adverse haemorrhagic events by TRansradial access site and systemic implementation of angioX - RAdiation Dose study (RAD-MATRIX).

PubMed

Sciahbasi, Alessandro; Calabrò, Paolo; Sarandrea, Alessandro; Rigattieri, Stefano; Tomassini, Francesco; Sardella, Gennaro; Zavalloni, Dennis; Cortese, Bernardo; Limbruno, Ugo; Tebaldi, Matteo; Gagnor, Andrea; Rubartelli, Paolo; Zingarelli, Antonio; Valgimigli, Marco

2014-06-01

Radiation absorbed by interventional cardiologists is a frequently under-evaluated important issue. Aim is to compare radiation dose absorbed by interventional cardiologists during percutaneous coronary procedures for acute coronary syndromes comparing transradial and transfemoral access. The randomized multicentre MATRIX (Minimizing Adverse Haemorrhagic Events by TRansradial Access Site and Systemic Implementation of angioX) trial has been designed to compare the clinical outcome of patients with acute coronary syndromes treated invasively according to the access site (transfemoral vs. transradial) and to the anticoagulant therapy (bivalirudin vs. heparin). Selected experienced interventional cardiologists involved in this study have been equipped with dedicated thermoluminescent dosimeters to evaluate the radiation dose absorbed during transfemoral or right transradial or left transradial access. For each access we evaluate the radiation dose absorbed at wrist, at thorax and at eye level. Consequently the operator is equipped with three sets (transfemoral, right transradial or left transradial access) of three different dosimeters (wrist, thorax and eye dosimeter). Primary end-point of the study is the procedural radiation dose absorbed by operators at thorax. An important secondary end-point is the procedural radiation dose absorbed by operators comparing the right or left radial approach. Patient randomization is performed according to the MATRIX protocol for the femoral or radial approach. A further randomization for the radial approach is performed to compare right and left transradial access. The RAD-MATRIX study will probably consent to clarify the radiation issue for interventional cardiologist comparing transradial and transfemoral access in the setting of acute coronary syndromes. Copyright © 2014 Elsevier Inc. All rights reserved.

A prospective randomized multicentre study of the impact of gallium-68 prostate-specific membrane antigen (PSMA) PET/CT imaging for staging high-risk prostate cancer prior to curative-intent surgery or radiotherapy (proPSMA study): clinical trial protocol.

PubMed

Hofman, Michael S; Murphy, Declan G; Williams, Scott G; Nzenza, Tatenda; Herschtal, Alan; Lourenco, Richard De Abreu; Bailey, Dale L; Budd, Ray; Hicks, Rodney J; Francis, Roslyn J; Lawrentschuk, Nathan

2018-05-03

Accurate staging of patients with prostate cancer (PCa) is important for therapeutic decision-making. Relapse after surgery or radiotherapy of curative intent is not uncommon and, in part, represents a failure of staging with current diagnostic imaging techniques to detect disease spread. Prostate-specific membrane antigen (PSMA) positron-emission tomography (PET)/computed tomography (CT) is a new whole-body scanning technique that enables visualization of PCa with high contrast. The hypotheses of this study are that: (i) PSMA-PET/CT has improved diagnostic performance compared with conventional imaging; (ii) PSMA-PET/CT should be used as a first-line diagnostic test for staging; (iii) the improved diagnostic performance of PSMA-PET/CT will result in significant management impact; and (iv) there are economic benefits if PSMA-PET/CT is incorporated into the management algorithm. The proPSMA trial is a prospective, multicentre study in which patients with untreated high-risk PCa will be randomized to gallium-68-PSMA-11 PET/CT or conventional imaging, consisting of CT of the abdomen/pelvis and bone scintigraphy with single-photon emission CT/CT. Patients eligible for inclusion are those with newly diagnosed PCa with select high-risk features, defined as International Society of Urological Pathology grade group ≥3 (primary Gleason grade 4, or any Gleason grade 5), prostate-specific antigen level ≥20 ng/mL or clinical stage ≥T3. Patients with negative, equivocal or oligometastatic disease on first line-imaging will cross over to receive the other imaging arm. The primary objective is to compare the accuracy of PSMA-PET/CT with that of conventional imaging for detecting nodal or distant metastatic disease. Histopathological, imaging and clinical follow-up at 6 months will define the primary endpoint according to a predefined scoring system. Secondary objectives include comparing management impact, the number of equivocal studies, the incremental value of second-line imaging in patients who cross over, the cost of each imaging strategy, radiation exposure, inter-observer agreement and safety of PSMA-PET/CT. Longer-term follow-up will also assess the prognostic value of a negative PSMA-PET/CT. This trial will provide data to establish whether PSMA-PET/CT should replace conventional imaging in the primary staging of select high-risk localized PCa, or whether it should be used to provide incremental diagnostic information in selected cases. © 2018 The Authors BJU International © 2018 BJU International Published by John Wiley & Sons Ltd.

A paradigm shift in the surgical reconstruction of extra-articular distal humeral fractures: single-column plating.

PubMed

Meloy, Gregory M; Mormino, Matthew A; Siska, Peter A; Tarkin, Ivan S

2013-11-01

The study aimed (1) to examine if there are equivalent results in terms of union, alignment and elbow functionally comparing single- to dual-column plating of AO/OTA 13A2 and A3 distal humeral fractures and (2) if there are more implant-related complications in patients managed with bicolumnar plating compared to single-column plate fixation. This was a multi-centred retrospective comparative study. The study was conducted at two academic level 1 trauma centres. A total of 105 patients were identified to have surgical management of extra-articular distal humeral fractures Arbeitsgemeinschaft für Osteosynthesefragen/Orthopaedic Trauma Association (AO/OTA) 13A2 and AO/OTA 13A3). Patients were treated with traditional dual-column plating or a single-column posterolateral small-fragment pre-contoured locking plate used as a neutralisation device with at least five screws in the short distal segment. The patients' elbow functionality was assessed in terms of range of motion, union and alignment. In addition, the rate of complications between the groups including radial nerve palsy, implant-related complications (painful prominence and/or ulnar nerve neuritis) and elbow stiffness were compared. Patients treated with single-column plating had similar union rates and alignment. However, single-column plating resulted in a significantly better range of motion with less complications. The current study suggests that exposure/instrumentation of only the lateral column is a reliable and preferred technique. This technique allows for comparable union rates and alignment with increased elbow functionality and decreased number of complications. Copyright © 2013 Elsevier Ltd. All rights reserved.

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

Suitability Of Nitisinone In Alkaptonuria 1 (SONIA 1): an international, multicentre, randomised, open-label, no-treatment controlled, parallel-group, dose-response study to investigate the effect of once daily nitisinone on 24-h urinary homogentisic acid excretion in patients with alkaptonuria after 4 weeks of treatment.

PubMed

Ranganath, Lakshminarayan R; Milan, Anna M; Hughes, Andrew T; Dutton, John J; Fitzgerald, Richard; Briggs, Michael C; Bygott, Helen; Psarelli, Eftychia E; Cox, Trevor F; Gallagher, James A; Jarvis, Jonathan C; van Kan, Christa; Hall, Anthony K; Laan, Dinny; Olsson, Birgitta; Szamosi, Johan; Rudebeck, Mattias; Kullenberg, Torbjörn; Cronlund, Arvid; Svensson, Lennart; Junestrand, Carin; Ayoob, Hana; Timmis, Oliver G; Sireau, Nicolas; Le Quan Sang, Kim-Hanh; Genovese, Federica; Braconi, Daniela; Santucci, Annalisa; Nemethova, Martina; Zatkova, Andrea; McCaffrey, Judith; Christensen, Peter; Ross, Gordon; Imrich, Richard; Rovensky, Jozef

2016-02-01

Alkaptonuria (AKU) is a serious genetic disease characterised by premature spondyloarthropathy. Homogentisate-lowering therapy is being investigated for AKU. Nitisinone decreases homogentisic acid (HGA) in AKU but the dose-response relationship has not been previously studied. Suitability Of Nitisinone In Alkaptonuria 1 (SONIA 1) was an international, multicentre, randomised, open-label, no-treatment controlled, parallel-group, dose-response study. The primary objective was to investigate the effect of different doses of nitisinone once daily on 24-h urinary HGA excretion (u-HGA24) in patients with AKU after 4 weeks of treatment. Forty patients were randomised into five groups of eight patients each, with groups receiving no treatment or 1 mg, 2 mg, 4 mg and 8 mg of nitisinone. A clear dose-response relationship was observed between nitisinone and the urinary excretion of HGA. At 4 weeks, the adjusted geometric mean u-HGA24 was 31.53 mmol, 3.26 mmol, 1.44 mmol, 0.57 mmol and 0.15 mmol for the no treatment or 1 mg, 2 mg, 4 mg and 8 mg doses, respectively. For the most efficacious dose, 8 mg daily, this corresponds to a mean reduction of u-HGA24 of 98.8% compared with baseline. An increase in tyrosine levels was seen at all doses but the dose-response relationship was less clear than the effect on HGA. Despite tyrosinaemia, there were no safety concerns and no serious adverse events were reported over the 4 weeks of nitisinone therapy. In this study in patients with AKU, nitisinone therapy decreased urinary HGA excretion to low levels in a dose-dependent manner and was well tolerated within the studied dose range. EudraCT number: 2012-005340-24. Registered at ClinicalTrials.gov: NCTO1828463. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

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

PubMed

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

2014-11-11

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

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

PubMed

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

2016-06-01

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

Study protocol for a randomised controlled trial: harmonising optimal strategy for treatment of coronary artery stenosis - coronary intervention with next-generation drug-eluting stent platforms and abbreviated dual antiplatelet therapy (HOST-IDEA) trial.

PubMed

Kim, Chi-Hoon; Han, Jung-Kyu; Yang, Han-Mo; Park, Kyung Woo; Lee, Hae-Young; Kang, Hyun-Jae; Koo, Bon-Kwon; Lee, Namho; Cha, Tae-Joon; Yang, Tae-Hyun; Jeong, Myung-Ho; Yoon, Myeong-Ho; Lee, Seung Uk; Lee, Seung Jin; Kim, Jin Won; Cho, Jin-Man; Han, Kyoo-Rok; Pyun, Wook Bum; Kim, Hyo-Soo

2017-10-11

We have recently seen the introduction of newer generation drug-eluting stents with ultrathin struts that use advanced polymer technologies. However, the efficacy and safety of these newest stents have not yet been fully explored. In addition, there are still controversies over the optimal duration of dual antiplatelet therapy (DAPT) after stent implantation, particularly for ultrathin stents with the newest polymer technologies. The HOST-IDEA trial is a randomised, open-label, multicentre, non-inferiority trial and the first study to directly compare two of these ultrathin sirolimus-eluting stents: Orsiro stent with biodegradable polymer, and polymer-free Coroflex ISAR (CX-ISAR) stent. This study has a scheme of 2×2 factorial design according to the stent type and DAPT duration (3 vs 12 months). A total of 2152 patients will be randomised and stratified to demonstrate the non-inferiority of CX-ISAR to Orsiro, or of the abbreviated DAPT duration to the conventional 12 months (both in 1:1 ratio). For the comparison of stent type, the primary endpoint is target lesion failure (TLF), which is a composite of cardiac death, target vessel-related myocardial infarction and clinically driven target lesion revascularisation. For the comparison of DAPT duration, the net adverse clinical event is the coprimary endpoint, which is defined as a composite of TLF, definite/probable stent thrombosis and major bleeding. All the institutions involved in this study are required to have ethical approval prior to patient enrolment. This multicentre study will recruit patients through competitive registration, but institutions that have not yet obtained ethical approvals have made it impossible to enrol patients in a centralised web database. The final results will be presented at relevant international conferences and will be materialised in the form of papers. NCT02601157; 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.

Multicolumn spinal cord stimulation for significant low back pain in failed back surgery syndrome: design of a national, multicentre, randomized, controlled health economics trial (ESTIMET Study).

PubMed

Roulaud, M; Durand-Zaleski, I; Ingrand, P; Serrie, A; Diallo, B; Peruzzi, P; Hieu, P D; Voirin, J; Raoul, S; Page, P; Fontaine, D; Lantéri-Minet, M; Blond, S; Buisset, N; Cuny, E; Cadenne, M; Caire, F; Ranoux, D; Mertens, P; Naous, H; Simon, E; Emery, E; Gadan, B; Regis, J; Sol, J-C; Béraud, G; Debiais, F; Durand, G; Guetarni Ging, F; Prévost, A; Brandet, C; Monlezun, O; Delmotte, A; d'Houtaud, S; Bataille, B; Rigoard, P

2015-03-01

Many studies have demonstrated the efficacy of spinal cord stimulation (SCS) for chronic neuropathic radicular pain over recent decades, but despite global favourable outcomes in failed back surgery syndrome (FBSS) with leg pain, the back pain component remains poorly controlled by neurostimulation. Technological and scientific progress has led to the development of new SCS leads, comprising a multicolumn design and a greater number of contacts. The efficacy of multicolumn SCS lead configurations for the treatment of the back pain component of FBSS has recently been suggested by pilot studies. However, a randomized controlled trial must be conducted to confirm the efficacy of new generation multicolumn SCS. Évaluation médico-économique de la STImulation MEdullaire mulTi-colonnes (ESTIMET) is a multicentre, randomized study designed to compare the clinical efficacy and health economics aspects of mono- vs. multicolumn SCS lead programming in FBSS patients with radicular pain and significant back pain. FBSS patients with a radicular pain VAS score≥50mm, associated with a significant back pain component were recruited in 14 centres in France and implanted with multicolumn SCS. Before the lead implantation procedure, they were 1:1 randomized to monocolumn SCS (group 1) or multicolumn SCS (group 2). Programming was performed using only one column for group 1 and full use of the 3 columns for group 2. Outcome assessment was performed at baseline (pre-implantation), and 1, 3, 6 and 12months post-implantation. The primary outcome measure was a reduction of the severity of low back pain (bVAS reduction≥50%) at the 6-month visit. Additional outcome measures were changes in global pain, leg pain, paraesthesia coverage mapping, functional capacities, quality of life, neuropsychological aspects, patient satisfaction and healthcare resource consumption. Trial recruitment started in May 2012. As of September 2013, all 14 study centres have been initiated and 112/115 patients have been enrolled. Preliminary results are expected to be published in 2015. Clinical trial registration information-URL: www.clinicaltrials.gov. Unique identifier NCT01628237. Copyright © 2014 Elsevier Masson SAS. All rights reserved.

Protocol for the specialist supervised individualised multifactorial treatment of new clinically diagnosed type 2 diabetes in general practice (IDA): a prospective controlled multicentre open-label intervention study

PubMed Central

Stidsen, Jacob Volmer; Nielsen, Jens Steen; Henriksen, Jan Erik; Friborg, Søren Gunnar; Olesen, Thomas Bastholm; Olsen, Michael Hecht; Beck-Nielsen, Henning

2017-01-01

Introduction We present the protocol for a multifactorial intervention study designed to test whether individualised treatment, based on pathophysiological phenotyping and individualised treatment goals, improves type 2 diabetes (T2D) outcomes. Methods and analysis We will conduct a prospective controlled multicentre open-label intervention study, drawing on the longitudinal cohort of the Danish Centre for Strategic Research in Type 2 Diabetes (DD2). New clinically diagnosed patients with T2D in the intervention group will be assigned to receive individualised treatment by their general practitioner. Intervention patients will be compared with a matched control cohort of DD2 patients receiving routine clinical care. Among intervention patients, we will first do pathophysiological phenotyping to classify patients into WHO-defined T2D or other specific types of diabetes (monogenic diabetes, secondary diabetes etc). Patients with WHO-defined T2D will then be further subcharacterised by their beta-cell function (BCF) and insulin sensitivity (IS), using the revised homeostatic assessment model, as having either insulinopaenic T2D (high IS and low BCF), classical T2D (low IS and low BCF) or hyperinsulinaemic T2D (low IS and high BCF). For each subtype, a specific treatment algorithm will target the primary pathophysiological defect. Similarly, antihypertensive treatment will be targeted at the specific underlying pathophysiology, characterised by impedance cardiography (relative importance of vascular resistance, intravascular volume and cardiac inotropy). All treatment goals will be based on individual patient assessment of expected positive versus adverse effects. Web-based and face-to-face individualised lifestyle intervention will also be implemented to empower patients to make a sustainable improvement in daily physical activity and to change to a low-carbohydrate diet. Ethics and dissemination The study will use well-known pharmacological agents according to their labels; patient safety is therefore considered high. Study results will be published in international peer-reviewed journals. Trial registration number NCT02015130; Pre-results. PMID:29229652

Rococo study: a real-world evaluation of an over-the-counter medicine in acute cough (a multicentre, randomised, controlled study).

PubMed

Birring, S S; Brew, J; Kilbourn, A; Edwards, V; Wilson, R; Morice, A H

2017-01-16

To investigate the efficacy and safety of CS1002, an over-the-counter cough treatment containing diphenhydramine, ammonium chloride and levomenthol in a cocoa-based demulcent. A multicentre, randomised, parallel group, controlled, single-blinded study in participants with acute upper respiratory tract infection-associated cough. 4 general practitioner (GP) surgeries and 14 pharmacies in the UK. Participants aged ≥18 years who self-referred to a GP or pharmacist with acute cough of <7 days' duration. Participant inclusion criterion was cough severity ≥60 mm on a 0-100 mm visual analogue scale (VAS). Exclusion criteria included current smokers or history of smoking within the past 12 months (including e-cigarettes). 163 participants were randomised to the study (mean participant age 38 years, 57% females). Participants were randomised to CS1002 (Unicough) or simple linctus (SL), a widely used cough treatment, and treatment duration was 7 days or until resolution of cough. The primary analysis was intention-to-treat (157 participants) and comprised cough severity assessed using a VAS after 3 days' treatment (prespecified primary end point at day 4). Cough frequency, sleep disruption, health status (Leicester Cough Questionnaire (LCQ-acute)) and cough resolution were also assessed. At day 4 (primary end point), the adjusted mean difference (95% CI) in cough severity VAS between CS1002 and SL was -5.9 mm (-14.4 to 2.7), p=0.18. At the end of the study (day 7) the mean difference in cough severity VAS was -4.2 mm (-12.2 to 3.9), p=0.31. CS1002 was associated with a greater reduction in cough sleep disruption (mean difference -11.6 mm (-20.6 to 2.7), p=0.01) and cough frequency (mean difference -8.1 mm (-16.2 to 0.1), p=0.05) compared with SL. There was greater improvement in LCQ-acute quality of life scores with CS1002 compared with SL: mean difference (95% CI) 1.2 (0.05 to 2.36), p=0.04 after 5 days' treatment. More participants prematurely stopped treatment due to cough improvement in the CS1002 group (24.4%) compared with SL (10.7%; p=0.02). Adverse events (AEs) were comparable between CS1002 (20.5%) and SL (27.6%) and largely related to the study indication. 6 participants (7%) in the CS1002 group reduced the dose of medication due to drowsiness/tiredness, which subsequently resolved. These events were not reported by participants as AEs. Although the primary end point was not achieved, CS1002 was associated with greater reductions in cough frequency, sleep disruption and improved health status compared with SL. EudraCT number 2014-004255-31. 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/.

Open randomised prospective comparative multi-centre intervention study of patients with cystic fibrosis and early diagnosed diabetes mellitus

PubMed Central

2014-01-01

Background Diabetes mellitus may be present in patients with cystic fibrosis starting in the second decade of life. The prevalence increases rapidly with increasing age. As life-expectancy increases in cystic fibrosis, cystic fibrosis related diabetes will be diagnosed more frequently in the future. Up to date, no data are available to answer the question if cystic fibrosis related diabetes should always initially be treated by insulin therapy. Missing data regarding oral antidiabetic treatment of newly diagnosed cystic fibrosis related diabetes are an important reason to recommend insulin treatment. Several centres report the successful management of cystic fibrosis related diabetes using oral anti-diabetic drugs at least for some years. Oral therapies would be less invasive for a patient group which is highly traumatized by a very demanding therapy. Based on an initiative of the German Mukoviszidosis-Foundation, the present study tries to answer the question, whether oral therapy with repaglinide is as effective as insulin therapy in cystic fibrosis patients with early diagnosed diabetes mellitus. Methods/Design In all cystic fibrosis patients with an age of 10 years or older, an oral glucose tolerance test is recommended. The result of this test is classified according to the WHO cut off values. It is required to have two diabetes positive oral glucose tolerance tests for the diagnosis of diabetes mellitus. This study is a multi-national, multicentre, open labelled, randomized and prospective controlled parallel group’s trial, with 24 months treatment. The primary objective of this trial is to compare the glycaemic control of oral therapy with Repaglinide with insulin injections in patients with cystic fibrosis related diabetes after 2 years of treatment. The trial should include 74 subjects showing cystic fibrosis related diabetes newly diagnosed by oral glucose tolerance test during annual screening for cystic fibrosis related diabetes. Patients are randomised by central fax randomisation. Primary endpoint is mean HbA1c after 24 months of treatment. Secondary endpoints are change in FEV1% predicted and change in BMI-Z-score. Discussion There is only one prospective study comparing oral antidiabetic drugs to insulin in the treatment of CFRD without fasting hyperglycaemia. The results regarding BMI after 6 months and 12 months showed an improvement for the insulin treated patients and were inconsistent for those treated with repaglinide. HbA1c and lung function (FEV1%pred) were unchanged for either group. The authors compared the changes -12 months to baseline and baseline to +12 months separately for each group. Therefore a direct comparison of the effect of repaglinide versus insulin on BMI, HbA1c and FEV1%pred was not presented. According to our protocol, we will directly compare treatment effects (HbA1c, BMI, FEV1%pred) in between both groups. The actual Cochrane report regarding “Insulin and oral agents for managing CFRD” stated that further studies are needed to establish whether there is clear benefit for hypoglycemic agents. We expect that the results of our study will help to address this clinical need. Trial registration ClinicalTrials.gov Identifier: NCT00662714 PMID:24620855

[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.

Clinical efficacy and safety of imepitoin in comparison with phenobarbital for the control of idiopathic epilepsy in dogs.

PubMed

Tipold, A; Keefe, T J; Löscher, W; Rundfeldt, C; de Vries, F

2015-04-01

The anticonvulsant activity and safety of imepitoin, a novel antiepileptic drug licensed in the European Union, were evaluated in a multicentre field efficacy study as well as in a safety study under laboratory conditions. Efficacy of imepitoin was compared with phenobarbital in 226 client-owned dogs in a blinded parallel group design. The administration of imepitoin twice daily in incremental doses of 10, 20 or 30 mg/kg demonstrated comparable efficacy to phenobarbital in controlling seizures in dogs. The frequency of adverse events including somnolence/sedation, polydipsia and increased appetite was significantly higher in the phenobarbital group. In phenobarbital-treated dogs, significantly increased levels of alkaline phosphatase, gamma-glutamyl-transferase and other liver enzymes occurred, while no such effect was observed in the imepitoin group. In a safety study under laboratory conditions, healthy beagle dogs were administered 0, 30, 90 or 150 mg/kg imepitoin twice daily for 26 weeks. A complete safety evaluation including histopathology was included in the study. A no-observed-adverse-event level of 90 mg/kg twice daily was determined. These results indicate that imepitoin is a potent and safe antiepileptic drug for dogs. © 2014 The Authors. Journal of Veterinary Pharmacology and Therapeutics Published by John Wiley & Sons Ltd.

Lifestyle and dietary habits of patients with gout followed in rheumatology settings.

PubMed

Manara, M; Carrara, G; Scirè, C A; Cimmino, M A; Govoni, M; Montecucco, C; Matucci-Cerinic, M; Minisola, G; Study Group, The King

2015-12-23

Diet and lifestyles modification are core aspects of the non-pharmacological management of gout, but a poor consistency with suggested guidelines is reported. This study aimed to investigate dietary and lifestyle habits of patients with gout followed in rheumatology settings. Data were retrieved from the baseline dataset of the KING study, a multicentre cohort study of patients with gout followed in rheumatology settings. Dietary habits were assessed with the Italian National Institute of Statistics (ISTAT) food-frequency questionnaire and compared with reported data about general population. The relative increase of exposure was estimated by standardized prevalence ratios adjusted for gender, age and geographical distribution. The study population included 446 patients, with a mean age of 63.9 years and a M/F ratio of 9:1. Compared to the Italian population, gouty patients showed a higher prevalence of obesity [1.82 (1.52-2.18)] and a higher consumption of wine [1.85 (1.48-2.32)] and beer [2.21 (1.68-2.90)], but a lower prevalence of smoking and a lower intake of liquor. They showed a lower intake of red meat [0.80 (0.71-0.91)], but a similar intake of other tested dietary factors. Gouty patients' lifestyle is still partially different from the recommended.

The HubBLe Trial: haemorrhoidal artery ligation (HAL) versus rubber band ligation (RBL) for symptomatic second- and third-degree haemorrhoids: a multicentre randomised controlled trial and health-economic evaluation.

PubMed

Brown, Steven; Tiernan, Jim; Biggs, Katie; Hind, Daniel; Shephard, Neil; Bradburn, Mike; Wailoo, Allan; Alshreef, Abualbishr; Swaby, Lizzie; Watson, Angus; Radley, Simon; Jones, Oliver; Skaife, Paul; Agarwal, Anil; Giordano, Pasquale; Lamah, Marc; Cartmell, Mark; Davies, Justin; Faiz, Omar; Nugent, Karen; Clarke, Andrew; MacDonald, Angus; Conaghan, Phillip; Ziprin, Paul; Makhija, Rohit

2016-11-01

Optimal surgical intervention for low-grade haemorrhoids is unknown. Rubber band ligation (RBL) is probably the most common intervention. Haemorrhoidal artery ligation (HAL) is a novel alternative that may be more efficacious. The comparison of HAL with RBL for the treatment of grade II/III haemorrhoids. A multicentre, parallel-group randomised controlled trial. UK NHS and Personal Social Services. 17 NHS Trusts. Patients aged ≥ 18 years presenting with grade II/III (second- and third-degree) haemorrhoids, including those who have undergone previous RBL. HAL with Doppler probe compared with RBL. Primary outcome - recurrence at 1 year post procedure; secondary outcomes - recurrence at 6 weeks; haemorrhoid severity score; European Quality of Life-5 Dimensions, 5-level version (EQ-5D-5L); Vaizey incontinence score; pain assessment; complications; and cost-effectiveness. A total of 370 participants entered the trial. At 1 year post procedure, 30% of the HAL group had evidence of recurrence compared with 49% after RBL [adjusted odds ratio (OR) = 2.23, 95% confidence interval (CI) 1.42 to 3.51; p  = 0.0005]. The main reason for the difference was the number of extra procedures required to achieve improvement/cure. If a single HAL is compared with multiple RBLs then only 37.5% recurred in the RBL arm (adjusted OR 1.35, 95% CI 0.85 to 2.15; p  = 0.20). Persistence of significant symptoms at 6 weeks was lower in both arms than at 1 year (9% HAL and 29% RBL), suggesting significant deterioration in both groups over the year. Symptom score, EQ-5D-5L and Vaizey score improved in both groups compared with baseline, but there was no difference between interventions. Pain was less severe and of shorter duration in the RBL group; most of the HAL group who had pain had mild to moderate pain, resolving by 3 weeks. Complications were low frequency and not significantly different between groups. It appeared that HAL was not cost-effective compared with RBL. In the base-case analysis, the difference in mean total costs was £1027 higher for HAL. Quality-adjusted life-years (QALYs) were higher for HAL; however, the difference was very small (0.01) resulting in an incremental cost-effectiveness ratio of £104,427 per additional QALY. At 1 year, although HAL resulted in fewer recurrences, recurrence was similar to repeat RBL. Symptom scores, complications, EQ-5D-5L and continence score were no different, and patients had more pain in the early postoperative period after HAL. HAL is more expensive and unlikely to be cost-effective in terms of incremental cost per QALY. Blinding of participants and site staff was not possible. The incidence of recurrence may continue to increase with time. Further follow-up would add to the evidence regarding long-term clinical effectiveness and cost-effectiveness. The polysymptomatic nature of haemorrhoidal disease requires a validated scoring system, and the data from this trial will allow further assessment of validity of such a system. These data add to the literature regarding treatment of grade II/III haemorrhoids. The results dovetail with results from the eTHoS study [Watson AJM, Hudson J, Wood J, Kilonzo M, Brown SR, McDonald A, et al. Comparison of stapled haemorrhoidopexy with traditional excisional surgery for haemorrhoidal disease (eTHoS): a pragmatic, multicentre, randomised controlled trial. Lancet 2016, in press.] comparing stapled haemorrhoidectomy with excisional haemorrhoidectomy. Combined results will allow expansion of analysis, allowing surgeons to tailor their treatment options to individual patients. Current Controlled Trials ISRCTN41394716. This project was funded by the NIHR Health Technology Assessment programme and will be published in full in Health Technology Assessment ; Vol. 20, No. 88. See the NIHR Journals Library website for further project information.