Differences in Investigator-Initiated Trials between Japan and Other Countries: Analyses of Clinical Trials Sponsored by Academia and Government in the ClinicalTrials.gov Registry and in the Three Japanese Registries.

PubMed

Ito, Tatsuya

2016-01-01

Following the amendment of the Pharmaceutical Affairs Law in Japan in 2003 researchers were permitted to begin investigator-initiated trials (IITs). In subsequent years, however, the number of IITs remained low. In other countries in Asia as well as in Europe, North America, and South Africa, the number of IITs has increased over the past decade. The differences in the characteristics of IITs between Japan and other countries are unknown. Some studies have analyzed the characteristics of all clinical trials according to registry databases, but there has been less research focusing on IITs. The purpose of this study is to analyze the characteristics of IITs in the ClinicalTrials.gov registry and in the three Japanese registries, to identify differences in IITs between Japan and other countries. Using Thomson Reuters Pharma™, trials sponsored by academia and government as IITs in 2010 and registered in ClinicalTrials.gov were identified. IITs from 2004 to 2012 in Japan were identified in the three Japanese registries: the University Hospital Medical Information Network Clinical Trials Registry, the Japan Pharmaceutical Information Center Clinical Trials Information, and the Japan Medical Association Center for Clinical Trials, Clinical Trials Registry. Characterization was made of the trial purposes, phases, participants, masking, arms, design, controls, and other data. New and revised IITs registered in ClinicalTrials.gov during 2010 averaged about 40% of all sponsor-identified trials. IITs were nearly all early-phase studies with small numbers of participants. A total of 56 Japanese IITs were found over a period of 8 years, and these were also almost nearly all early-phase studies with small numbers of participants. There appear to be no great differences between Japan and other countries in terms of characteristics of IITs. These results should prompt a new review of the IIT environment in Japan.

High Mortality without ESCAPE: The Registry of Heart Failure Patients Receiving Pulmonary Artery Catheters without Randomization

PubMed Central

Allen, Larry A.; Rogers, Joseph G.; Warnica, J. Wayne; DiSalvo, Thomas G.; Tasissa, Gudaye; Binanay, Cynthia; O’Connor, Christopher M.; Califf, Robert M.; Leier, Carl V.; Shah, Monica R.; Stevenson, Lynne W.

2008-01-01

Background In ESCAPE, there was no difference in days alive and out of the hospital for patients with decompensated heart failure (HF) randomly assigned to therapy guided by pulmonary artery catheter (PAC) plus clinical assessment versus clinical assessment alone. The external validity of these findings is debated. Methods and Results ESCAPE sites enrolled 439 patients receiving PAC without randomization in a prospective registry. Baseline characteristics, pertinent trial exclusion criteria, reasons for PAC use, hemodynamics, and complications were collected. Survival was determined from the National Death Index and the Alberta Registry. On average, registry patients had lower blood pressure, worse renal function, less neurohormonal antagonist therapy, and higher use of intravenous inotropes as compared with trial patients. Although clinical assessment anticipated less volume overload and greater hypoperfusion among the registry population, measured filling pressures were similarly elevated in the registry and trial, while measured perfusion was slightly higher among registry patients. Registry patients had longer hospitalization (13 vs. 6 days, p <0.001) and higher 6-month mortality (34% vs. 20%, p < 0.001) than trial patients. Conclusions The decision to use PAC without randomization identified a population with higher disease severity and risk of mortality. This prospective registry highlights the complex context of patient selection for randomized trials. PMID:18926438

Stroke Trials Registry

MedlinePlus

... Trials News About Neurology Image Library Search The Internet Stroke Center Trials Registry Clinical Trials Interventions Conditions ... UT Southwestern Medical Center. Copyright © 1997-2011 - The Internet Stroke Center. All rights reserved. The information contained ...

A methodological approach for assessing the uptake of core outcome sets using ClinicalTrials.gov: findings from a review of randomised controlled trials of rheumatoid arthritis.

PubMed

Kirkham, Jamie J; Clarke, Mike; Williamson, Paula R

2017-05-17

Objective  To assess the uptake of the rheumatoid arthritis core outcome set using a new assessment method of calculating uptake from data in clinical trial registry entries. Design  Review of randomised trials. Setting  ClinicalTrials.gov. Subjects  273 randomised trials of drug interventions for the treatment of rheumatoid arthritis and registered in ClinicalTrials.gov between 2002 and 2016. Full publications were identified for completed studies from information in the trial registry or from an internet search using Google and the citation database Web of Science. Main outcome measure  The percentage of trials reporting or planning to measure the rheumatoid arthritis core outcome set calculated from the information presented in the trial registry and compared with the percentage reporting the rheumatoid arthritis core outcome set in the resulting trial publications. Results  The full rheumatoid arthritis core outcome set was reported in 81% (116/143) of trials identified on the registry as completed (or terminated) for which results were found in either the published literature or the registry. For trials identified on the registry as completed (or terminated), using information only available in the registry gives an estimate for uptake of 77% (145/189). Conclusions  The uptake of the rheumatoid arthritis core outcome set in clinical trials has continued to increase over time. Using the information on outcomes listed for completed or terminated studies in a trial registry provides a reasonable estimate of the uptake of a core outcome set and is a more efficient and up-to-date approach than examining the outcomes in published trial reports. The method proposed may provide an efficient approach for an up-to-date assessment of the uptake of the 300 core outcome sets already published. 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.

Rare malignant pediatric tumors registered in the German Childhood Cancer Registry 2001-2010.

PubMed

Brecht, Ines B; Bremensdorfer, Claudia; Schneider, Dominik T; Frühwald, Michael C; Offenmüller, Sonja; Mertens, Rolf; Vorwerk, Peter; Koscielniak, Ewa; Bielack, Stefan S; Benesch, Martin; Hero, Barbara; Graf, Norbert; von Schweinitz, Dietrich; Kaatsch, Peter

2014-07-01

The German Childhood Cancer Registry (GCCR) annually registers approximately 2,000 children diagnosed with a malignant disease (completeness of registration >95%). While most pediatric cancer patients are diagnosed and treated according to standardized cooperative protocols of the German Society for Pediatric Oncology and Hematology (GPOH), patients with rare tumors are at risk of not being integrated in the network including trials and reference centers. A retrospective analysis of all rare extracranial solid tumors reported to the GCCR 2001-2010 (age <18 years) was undertaken using a combination of the International Classification of Childhood Cancer (ICCC-3) and the International Classification of Diseases-Oncology (ICD-O-3). Tumors accounting for <0.3% of all malignancies were defined as rare (approx. 6 cases/year and registered malignancy). According to this definition 1,189 rare extracranial solid tumors (18.2% of all malignant extracranial solid tumors) were registered, among these 232 patients (19.5% of rare tumor cases), were not included in preexisting GPOH studies/registries. Within 10 years, the number of registered non-GPOH-trial patients with a rare tumor increased. Though most of the GCCR-registered patients with rare malignant tumors are treated within GPOH trials, there is a considerable number of patients that have been diagnosed and treated outside the structures of the GPOH. These patients should be reported to the recently founded German Pediatric Rare Tumor Registry (STEP). Active data accrual and the development of appropriate structures will allow for better registration and improvement of medical care in these patients. © 2014 Wiley Periodicals, Inc.

Inadequate safety reporting in pre-eclampsia trials: a systematic evaluation.

PubMed

Duffy, Jmn; Hirsch, M; Pealing, L; Showell, M; Khan, K S; Ziebland, S; McManus, R J

2018-06-01

Randomised trials and their syntheses in meta-analyses offer a unique opportunity to assess the frequency and severity of adverse reactions. To assess safety reporting in pre-eclampsia trials. Systematic search using bibliographic databases, including Cochrane Central Register of Controlled Trials, Embase, and MEDLINE, from inception to August 2017. Randomised trials evaluating anticonvulsant or antihypertensive medication for pre-eclampsia. Descriptive statistics appraising the adequacy of adverse reaction and toxicity reporting. We included 60 randomised trials. Six trials (10%) were registered with the International Clinical Trials Registry Platform, two registry records referred to adverse reactions, stating 'safety and toleration' and 'possible side effects' would be collected. Twenty-six trials (43%) stated the frequency of withdrawals within each study arm, and five trials (8%) adequately reported these withdrawals. Adverse reactions were inconsistently reported across eligible trials: 24 (40%) reported no serious adverse reactions and 36 (60%) reported no mild adverse reactions. The methods of definition or measurement of adverse reactions were infrequently reported within published trial reports. Pre-eclampsia trials regularly omit critical information related to safety. Despite the paucity of reporting, randomised trials collect an enormous amount of safety data. Developing and implementing a minimum data set could help to improve safety reporting, permitting a more balanced assessment of interventions by considering the trade-off between the benefits and harms. National Institute for Health Research (DRF-2014-07-051), UK; Maternity Forum, Royal Society of Medicine, UK. Developing @coreoutcomes could help to improve safety reporting in #preeclampsia trials. @NIHR_DC. © 2017 Royal College of Obstetricians and Gynaecologists.

Survival of Patients Receiving a Primary Prevention Implantable Cardioverter-Defibrillator in Clinical Practice vs Clinical Trials

PubMed Central

Al-Khatib, Sana M.; Hellkamp, Anne; Bardy, Gust H.; Hammill, Stephen; Jackson Hall, W.; Mark, Daniel B.; Anstrom, Kevin J.; Curtis, Jeptha; Al-Khalidi, Hussein; Curtis, Lesley H.; Heidenreich, Paul; Peterson, Eric D.; Sanders, Gillian; Clapp-Channing, Nancy; Lee, Kerry L.; Moss, Arthur J.

2013-01-01

Importance Randomized clinical trials have shown that implantable cardioverter-defibrillator (ICD) therapy saves lives. Whether the survival of patients who received an ICD in primary prevention clinical trials differs from that of trial-eligible patients receiving a primary prevention ICD in clinical practice is unknown. Objective To determine whether trial-eligible patients who received a primary prevention ICD as documented in a large national registry have a survival rate that differs from the survival rate of similar patients who received an ICD in the 2 largest primary prevention clinical trials, MADIT-II (n=742) and SCD-HeFT (n=829). Design, Setting, and Patients Retrospective analysis of data for patients enrolled in the National Cardiovascular Data Registry ICD Registry between January 1, 2006, and December 31, 2007, meeting the MADIT-II criteria (2464 propensity score–matched patients) or the SCD-HeFT criteria (3352 propensity score–matched patients). Mortality data for the registry patients were collected through December 31, 2009. Main Outcome Measures Cox proportional hazards models were used to compare mortality from any cause. Results The median follow-up time in MADIT-II, SCD-HeFT, and the ICD Registry was 19.5, 46.1, and 35.2 months, respectively. Compared with patients enrolled in the clinical trials, patients in the ICD Registry were significantly older and had a higher burden of comorbidities. In the matched cohorts, there was no significant difference in survival between MADIT-II–like patients in the registry and MADIT-II patients randomized to receive an ICD (2-year mortality rates: 13.9% and 15.6%, respectively; adjusted ICD Registry vs trial hazard ratio, 1.06; 95% CI, 0.85–1.31; P=.62). Likewise, the survival among SCD-HeFT–like patients in the registry was not significantly different from survival among patients randomized to receive ICD therapy in SCD-HeFT (3-year mortality rates: 17.3% and 17.4%, respectively; adjusted registry vs trial hazard ratio, 1.16; 95% CI, 0.97–1.38; P=.11). Conclusions and Relevance There was no significant difference in survival between clinical trial patients randomized to receive an ICD and a similar group of clinical registry patients who received a primary prevention ICD. Our findings support the continued use of primary prevention ICDs in similar patients seen in clinical practice. Trial Registration clinicaltrials.gov Identifier: NCT00000609 PMID:23280225

Review of the registration of clinical trials in UMIN-CTR from 2 June 2005 to 1 June 2010 - focus on Japan domestic, academic clinical trials

PubMed Central

2013-01-01

Background Established on 1 June 2005, the University Hospital Medical Information Network Clinical Trials Registry (UMIN-CTR) is the largest clinical trial registry in Japan, and joined the World Health Organization (WHO) registry network in October 2008. Our aim was to understand the registration trend and overall characteristics of Japan domestic, academic (non-industry-funded) clinical trials, which constitute the main body of registrations in UMIN-CTR. In addition, we aimed to investigate the accessibility of clinical trials in UMIN-CTR to people worldwide, as well as the accessibility of clinical trials conducted in Japan but registered abroad to Japanese people in the Japanese language. Methods We obtained the data for registrations in UMIN-CTR from the UMIN Center, and extracted Japan domestic, academic clinical trials to analyze their registration trend and overall characteristics. We also investigated how many of the trials registered in UMIN-CTR could be accessed from the International Clinical Trials Registry Platform (ICTRP). Finally, we searched ClinicalTrials.gov for all clinical trials conducted in Japan and investigated how many of them were also registered in Japanese registries. All of the above analyses included clinical trials registered from 2 June 2005 to 1 June 2010. Results During the period examined, the registration trend showed an obvious peak around September 2005 and rapid growth from April 2009. Of the registered trials, 46.4% adopted a single-arm design, 34.5% used an active control, only 10.9% were disclosed before trial commencement, and 90.0% did not publish any results. Overall, 3,063 of 3,064 clinical trials registered in UMIN-CTR could be accessed from ICTRP. Only 8.7% of all clinical trials conducted in Japan and registered in ClinicalTrials.gov were also registered in Japanese registries. Conclusions The International Committee of Medical Journal Editors (ICMJE) announcements about clinical trial registration and the Ethical Guidelines for Clinical Research published by the Japanese government are considered to have promoted clinical trial registration in UMIN-CTR. However, problems associated with trial design, retrospective registration, and publication of trial results need to be addressed in future. Almost all clinical trials registered in UMIN-CTR are accessible to people worldwide through ICTRP. However, many trials conducted in Japan but registered abroad cannot be accessed from Japanese registries in Japanese. PMID:24124926

Understanding long-term protection of human papillomavirus vaccination against cervical carcinoma: Cancer registry-based follow-up.

PubMed

Rana, Muhammad Mohsin; Huhtala, Heini; Apter, Dan; Eriksson, Tiina; Luostarinen, Tapio; Natunen, Kari; Paavonen, Jorma; Pukkala, Eero; Lehtinen, Matti

2013-06-15

Phase III clinical trials of human papilloma virus (HPV) vaccination have shown ≥95% efficacy against HPV16/18 associated cervical intraepithelial neoplasia (CIN) Grade 2/3. Long-term surveillance is, however, needed to determine the overall vaccine efficacy (VE) against CIN3 and invasive cervical carcinoma (ICC). During population-based recruitment between September 2002 and March 2003, 1,749 16- to 17-year old Finns participated in a multi-national randomized Phase III HPV6/11/16/18 vaccine (FUTURE II) trial for the determination of VE against HPV16/18 positive CIN2/3. The passive follow-up started at the country-wide, population-based Finnish Cancer Registry (FCR) six months after the active follow-up and voluntary cross-vaccination in April 2007. A cluster randomized, population-based reference cohort of 15,744 unvaccinated, originally 18-19 year old Finns was established in two phases in 2003 and 2005 after the FUTURE II recruitment. We linked these cohorts with the FCR in 2007-2011 (HPV vaccine and placebo cohorts) and 2006-2010 and 2008-2012 (unvaccinated reference cohorts 1 and 2) to compare their incidences of CIN3 and ICC. The four years passive follow-up resulted in 3,464, 3,444 and 62,876 person years for the HPV6/11/16/18, original placebo and reference cohorts, after excluding cases discovered during the clinical follow-up and individuals not at risk. The numbers of CIN3 and ICC cases identified were 0 and 0, 3 and 0, 59 and 3 for the HPV6/11/16/18, placebo and the unvaccinated reference cohorts. The corresponding CIN3 incidence rates were 0/100,000 (95% confidence interval 0.0-106.5), 87.1/100,000 (95% CI 17.9-254.5) and 93.8/100,000 (95% CI 71.4-121), respectively. Long-term surveillance up to 8 years (and longer) post vaccination of the HPV6/11/16/18 vaccine and placebo cohorts, and the unvaccinated reference cohort (not exposed to interventions) for the most stringent efficacy end-points by passive cancer registry-based follow-up is feasible. Copyright © 2012 UICC.

Published intimate partner violence studies often differ from their trial registration records.

PubMed

Madden, Kim; Tai, Kerry; Ali, Zak; Schneider, Patricia; Singh, Mahip; Ghert, Michelle; Bhandari, Mohit

2017-12-27

Registering study protocols in a trial registry is important for methodologic transparency and reducing selective reporting bias. The objective of this investigation was to determine whether published studies of intimate partner violence (IPV) that had been registered matched the registration record on key study design elements. We systematically searched three trial registries to identify registered IPV studies and the published literature for the associated publication. Two authors independently determined for each study whether key study elements in the registry matched those in the published paper. We included 66 studies published between 2006 and 2017. Nearly half (29/66, 44%) were registered after study completion. Many (26/66, 39%) had discrepancies regarding the primary outcome, and nearly two-thirds (42/66, 64%) had discrepancies in secondary outcomes. Discrepancies in study design were less frequent (13/66, 20%). However, large changes in sample size (26/66, 39%) and discrepancies in funding source (28/66, 42%) were frequently observed. Trial registries are important tools for research transparency and identifying and preventing outcome switching and selective outcome reporting bias. Published IPV studies often differ from their records in trial registries. Researchers should pay close attention to the accuracy of trial registry records.

Utilization of Clinical Trials Registries in Obstetrics and Gynecology Systematic Reviews.

PubMed

Bibens, Michael E; Chong, A Benjamin; Vassar, Matt

2016-02-01

To evaluate the use of clinical trials registries in published obstetrics and gynecologic systematic reviews and meta-analyses. We performed a metaepidemiologic study of systematic reviews between January 1, 2007, and December 31, 2015, from six obstetric and gynecologic journals (Obstetrics & Gynecology, Obstetrical & Gynecological Survey, Human Reproduction Update, Gynecologic Oncology, British Journal of Obstetrics and Gynaecology, and American Journal of Obstetrics & Gynecology). All systematic reviews included after exclusions were independently reviewed to determine whether clinical trials registries had been included as part of the search process. Studies that reported using a trials registry were further examined to determine whether trial data were included in the analysis of these systematic reviews. Our initial search resulted in 292 articles, which was narrowed to 256 after exclusions. Of the 256 systematic reviews meeting our selection criteria, 47 (18.4%) used a clinical trials registry. Eleven of the 47 (23.4%) systematic reviews found unpublished data and two included unpublished data in their results. A majority of systematic reviews in clinical obstetrics and gynecology journals do not conduct searches of clinical trials registries or do not make use of data obtained from these searches. Failure to make use of such data may lead to an inaccurate summary of available evidence and may contribute to an overrepresentation of published, statistically significant outcomes.

Comparison of noninferiority margins reported in protocols and publications showed incomplete and inconsistent reporting.

PubMed

Dekkers, Olaf M; Cevallos, Myriam; Bührer, Jonas; Poncet, Antoine; Ackermann Rau, Sabine; Perneger, Thomas V; Egger, Matthias

2015-05-01

To compare noninferiority margins defined in study protocols and trial registry records with margins reported in subsequent publications. Comparison of protocols of noninferiority trials submitted 2001 to 2005 to ethics committees in Switzerland and The Netherlands with corresponding publications and registry records. We searched MEDLINE via PubMed, the Cochrane Controlled Trials Register (Cochrane Library issue 01/2012), and Google Scholar in September 2013 to identify published reports, and the International Clinical Trials Registry Platform of the World Health Organization in March 2013 to identify registry records. Two readers recorded the noninferiority margin and other data using a standardized data-abstraction form. The margin was identical in study protocol and publication in 43 (80%) of 54 pairs of study protocols and articles. In the remaining pairs, reporting was inconsistent (five pairs, 9%), or the noninferiority margin was either not reported in the publication (five pairs, 9%) or not defined in the study protocol (one pair). The confidence interval or the exact P-value required to judge whether the result was compatible with noninferior, inferior, or superior efficacy was reported in 43 (80%) publications. Complete and consistent reporting of both noninferiority margin and confidence interval (or exact P-value) was present in 39 (72%) protocol-publication pairs. Twenty-nine trials (54%) were registered in trial registries, but only one registry record included the noninferiority margin. The reporting of noninferiority margins was incomplete and inconsistent with study protocols in a substantial proportion of published trials, and margins were rarely reported in trial registries. Copyright © 2015 Elsevier Inc. All rights reserved.

Review of U.S. registries for psoriasis.

PubMed

Amin, Mina; No, Daniel J; Wu, Jashin J

2017-12-01

Patient registries are databases comprised of standardized clinical data for a specific population of patients with a particular disease or medical condition. Information from patient registries allows clinicians to assess long-lasting outcomes in patients with a specific disease, such as psoriasis. Our primary objective was to identify available psoriasis registries in the United States (U.S.) and evaluate the application of patient registries compared to clinical trials. We searched Google, the Registry of Patient Registries, Orphanet and ClinicalTrials.gov to create a list of U.S. psoriasis registries. We also performed a literature review on the application of psoriasis registries using PubMed. We identified 6 psoriasis patient registries in the United States. Patient registries are frequently used for psoriasis in the U.S. and provide important information about the safety, efficacy and long-term effects of systemic therapies.

[Realization of design regarding experimental research in the clinical real-world research].

PubMed

He, Q; Shi, J P

2018-04-10

Real world study (RWS), a further verification and supplement for explanatory randomized controlled trial to evaluate the effectiveness of intervention measures in real clinical environment, has increasingly become the focus in the field of research on medical and health care services. However, some people mistakenly equate real world study with observational research, and argue that intervention and randomization cannot be carried out in real world study. In fact, both observational and experimental design are the basic designs in real world study, while the latter usually refers to pragmatic randomized controlled trial and registry-based randomized controlled trial. Other nonrandomized controlled and adaptive designs can also be adopted in the RWS.

Metadata registry and management system based on ISO 11179 for cancer clinical trials information system

PubMed Central

Park, Yu Rang; Kim*, Ju Han

2006-01-01

Standardized management of data elements (DEs) for Case Report Form (CRF) is crucial in Clinical Trials Information System (CTIS). Traditional CTISs utilize organization-specific definitions and storage methods for Des and CRFs. We developed metadata-based DE management system for clinical trials, Clinical and Histopathological Metadata Registry (CHMR), using international standard for metadata registry (ISO 11179) for the management of cancer clinical trials information. CHMR was evaluated in cancer clinical trials with 1625 DEs extracted from the College of American Pathologists Cancer Protocols for 20 major cancers. PMID:17238675

Moving toward the reduction of publication/reporting biases in clinical trials using a new international standard.

PubMed

Doi, Yuriko

2016-01-01

Evidence-based medicine (EBM) is fundamental to ensuring high-quality medical care. It requires systematic reviews and meta-analyses to synthesize diverse information available from individual clinical studies. However, the literature reviewed may represent an incomplete and selective set of research findings, which could lead to publication/reporting biases and distort the true picture of research as a whole. Prospective registry of all clinical trials in the world is mandatory to reduce the biases, which have been disclosed on the International Clinical Trials Registry Platform (ICTRP) of the World Health Organization (WHO) since 2007. The Japan Primary Registries Network (JPRN) is included in the ICTRP. ClinicalTrials.gov, the U.S. clinical trial registry, reports the standardized data of registered trials and offers access to submitted outcomes online. However, the JPRN does not systematically include the outcomes. On April 14, 2015, the WHO published a new statement online on the public disclosure of clinical trial results, which requires researchers to define the timeframes of reporting main findings and key outcomes, to call for results-reporting older, but still unpublished trials, and to outline steps to improve linkages between clinical trial registry entries and their published results. The WHO's new position will facilitate global efforts to reduce publication/reporting biases in clinical trials. Japan will have to actively participate in these efforts as well.

Discrepancies between ClinicalTrials.gov recruitment status and actual trial status: a cross-sectional analysis.

PubMed

Jones, Christopher W; Safferman, Michelle R; Adams, Amanda C; Platts-Mills, Timothy F

2017-10-11

To determine the accuracy of the recruitment status listed on ClinicalTrials.gov as compared with the actual trial status. Cross-sectional analysis. Random sample of interventional phase 2-4 clinical trials registered between 2010 and 2012 on ClinicalTrials.gov. For each trial which was listed within ClinicalTrials.gov as ongoing, two investigators performed a comprehensive literature search for evidence that the trial had actually been completed. For each trial listed as completed or terminated early by ClinicalTrials.gov, we compared the date that the trial was actually concluded with the date the registry was updated to reflect the study's conclusion status. Among the 405 included trials, 92 had a registry status indicating that study activity was either ongoing or the recruitment status was unknown. Of these, published results were available for 34 (37%). Among the 313 concluded trials, the median delay between study completion and a registry update reflecting that the study had ended was 141 days (IQR 48-419), with delays of over 1 year present for 29%. In total, 125 trials (31%) either had a listed recruitment status which was incorrect or had a delay of more than 1 year between the time the study was concluded and the time the registry recruitment status was updated. At present, registry recruitment status information in ClinicalTrials.gov is often outdated or wrong. This inaccuracy has implications for the ability of researchers to identify completed trials and accurately characterise all available medical knowledge on a given subject. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

The pooling of manpower and resources through the establishment of European reference networks and rare disease patient registries is a necessary area of collaboration for rare renal disorders.

PubMed

Parker, Samantha

2014-09-01

This review aims to provide guidance on emerging concepts and policy related to European reference networks (ERNs) for rare diseases (RDs) and the development and management of RD patient registries. A major problem facing many RDs including rare renal disorders is that patients do not have a specialist centre that they can attend where clinicians, working as a multidisciplinary team, are experts in the particular disease. Furthermore, for most RDs, no single centre, and in many cases no single country, has sufficient numbers of patients and resources to fully understand the natural history or to conduct clinical and translational research. Therefore, the pooling of manpower and resources through the establishment of ERN and RD patient registries is a common and necessary area of collaboration. The concept of European networks for RDs dates back to the early 2000s and the Commission launch of a call for European pilot reference networks for RDs. These networks of expert centres have been brought together through the desire for further knowledge and innovation in RD areas. Networks demand a holistic approach and long-term vision with close collaboration between clinicians, diagnostic laboratories, scientists, patients and their families. The development of legal measures for ERNs is in progress at the Commission and these networks will be a shared responsibility of the Commission and member states. In the context of ERNs, an essential activity is the patient registries. Patient registries are organized databases where patient information, including demographic, medical and family history, are collected, stored and available for retrieval via standardized and secure methods. Patient registries are increasingly recognized as crucial tools for RD research for which international collaboration is absolutely essential to understand the pathogenesis of rare genotypes, achieve a unified collection of phenotypic data, foster natural history studies providing the foundation for successful orphan drug development, facilitate studies to identify appropriate clinical endpoints or biomarkers, identify participants for research and clinical trials and support discussions with regulators including the safety and efficacy evaluation of potential therapies. Furthermore, patient registries are often used as part of regulatory decisions and post-marketing surveillance requirements. Data can be entered into a registry by patients, clinicians, researchers or directly imported from patient's health records. The major concern in maintaining the dynamic of these networks and registries is sustainability, as the infrastructures and coordination have a cost. © The Author 2014. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved.

Trials, tricks and transparency: how disclosure rules affect clinical knowledge.

PubMed

Dahm, Matthias; González, Paula; Porteiro, Nicolás

2009-12-01

Scandals of selective reporting of clinical trial results by pharmaceutical firms have underlined the need for more transparency in clinical trials. We provide a theoretical framework which reproduces incentives for selective reporting and yields three key implications concerning regulation. First, a compulsory clinical trial registry complemented through a voluntary clinical trial results database can implement full transparency (the existence of all trials as well as their results is known). Second, full transparency comes at a price. It has a deterrence effect on the incentives to conduct clinical trials, as it reduces the firms' gains from trials. Third, in principle, a voluntary clinical trial results database without a compulsory registry is a superior regulatory tool; but we provide some qualified support for additional compulsory registries when medical decision-makers cannot anticipate correctly the drug companies' decisions whether to conduct trials.

A web-based, patient driven registry for Angelman syndrome: the global Angelman syndrome registry.

PubMed

Napier, Kathryn R; Tones, Megan; Simons, Chloe; Heussler, Helen; Hunter, Adam A; Cross, Meagan; Bellgard, Matthew I

2017-08-01

Angelman syndrome (AS) is a rare neurodevelopmental disorder that is characterised by severe global developmental delays, ataxia, loss of speech, epilepsy, sleep disorders, and a happy disposition. There is currently no cure for AS, though several pharmaceutical companies are anticipating drug trials for new therapies to treat AS. The Foundation for Angelman Therapeutics (FAST) Australia therefore identified a need for a global AS patient registry to identify patients for recruitment for clinical trials.The Global AS Registry was deployed in September 2016 utilising the Rare Disease Registry Framework, an open-source tool that enables the efficient creation and management of patient registries. The Global AS Registry is web-based and allows parents and guardians worldwide to register, provide informed consent, and enter data on individuals with AS. 286 patients have registered in the first 8 months since deployment.We demonstrate the successful deployment of the first patient-driven global registry for AS. The data generated from the Global AS Registry will be crucial in identifying patients suitable for clinical trials and in informing research that will identify treatments for AS, and ultimately improve the lives of individuals and their families living with AS.

Global outcomes of ST-elevation myocardial infarction: comparisons of the Enoxaparin and Thrombolysis Reperfusion for Acute Myocardial Infarction Treatment-Thrombolysis In Myocardial Infarction study 25 (ExTRACT-TIMI 25) registry and trial.

PubMed

Steinberg, Benjamin A; Moghbeli, Nazanin; Buros, Jacqueline; Ruda, Mikhail; Parkhomenko, Alexander; Raju, B Soma; García-Castillo, Armando; Janion, Marianna; Nicolau, José C; Fox, Keith A A; Morrow, David A; Gibson, C Michael; Antman, Elliott M

2007-07-01

Outcomes in patients with ST-elevation myocardial infarction (STEMI) differ between those in clinical trials and those in routine practice, as well as across different regions. We hypothesized that adjustment for baseline risk would minimize such variations. The Enoxaparin and Thrombolysis Reperfusion for Acute Myocardial Infarction Treatment-Thrombolysis In Myocardial Infarction (ExTRACT-TIMI) 25 registry was an observational study of patients with STEMI presenting to hospitals participating in the ExTRACT-TIMI 25 randomized clinical trial. Consecutive patients with STEMI who were not enrolled in the trial were entered into the registry. Demographics, in-hospital therapies, and in-hospital events were collected. Baseline risk was assessed using the TIMI Risk Index for STEMI. To adjust for differences among the countries from which the patients presented, the gross national income per annum per capita (GNI) was used. A total of 3726 patients were registered from 109 sites in 25 countries. Patients in the registry had a higher baseline risk than those in the trial; they had more extensive prior cardiac histories and more comorbidities. Unadjusted in-hospital mortality was higher in the registry (8.3%) than in the trial (6.6%) (hazard ratio, 1.30; P < .001); however, after adjusting for TIMI Risk Index, mortality was similar (hazard ratio(adj), 1.00; P = .97). The GNI was not significantly predictive of in-hospital mortality in the multivariable model of the registry. Patients in the registry had higher mortality than those in the trial. This difference could be explained by the higher baseline risk of patients in the registry. After adjusting for baseline risk, the GNI of the country in which the patient presented did not contribute to predicting in-hospital mortality.

Current situation and challenge of registry in China.

PubMed

Zhang, Yang; Feng, Yuji; Qu, Zhi; Qi, Yali; Zhan, Siyan

2014-09-01

Increasing emphasis has been placed on registries for an organized system used in developing clinical research to improve health care. China has sufficient data that can be applied broadly, but the heterogeneity and irregularity of registries limit their applicability. This article aims to describe the status of registries in China and the related challenges. Patient registries for observational studies were retrieved from the International Clinical Trials Registry to quantitatively evaluate the number of comparatively high-quality registries in China. A literature search was also performed to provide support and updates. A total of 64 patient registries were retrieved from ClinicalTrials.gov using disease, product, and health service as criteria. The sample sizes ranged from 15 to 30,400, with only 12 registries marked as completed. This article describes and compares the detailed information in many aspects. The efficient use of registries has already made considerable progress in China; however, registries still require standardization, high-quality transition, and coordinated development.

Clinical disease registries in acute myocardial infarction.

PubMed

Ashrafi, Reza; Hussain, Hussain; Brisk, Robert; Boardman, Leanne; Weston, Clive

2014-06-26

Disease registries, containing systematic records of cases, have for nearly 100 years been valuable in exploring and understanding various aspects of cardiology. This is particularly true for myocardial infarction, where such registries have provided both epidemiological and clinical information that was not readily available from randomised controlled trials in highly-selected populations. Registries, whether mandated or voluntary, prospective or retrospective in their analysis, have at their core a common study population and common data definitions. In this review we highlight how registries have diversified to offer information on epidemiology, risk modelling, quality assurance/improvement and original research-through data mining, transnational comparisons and the facilitation of enrolment in, and follow-up during registry-based randomised clinical trials.

Core outcome sets and trial registries.

PubMed

Clarke, Mike; Williamson, Paula

2015-05-14

Some reasons for registering trials might be considered as self-serving, such as satisfying the requirements of a journal in which the researchers wish to publish their eventual findings or publicising the trial to boost recruitment. Registry entries also help others, including systematic reviewers, to know about ongoing or unpublished studies and contribute to reducing research waste by making it clear what studies are ongoing. Other sources of research waste include inconsistency in outcome measurement across trials in the same area, missing data on important outcomes from some trials, and selective reporting of outcomes. One way to reduce this waste is through the use of core outcome sets: standardised sets of outcomes for research in specific areas of health and social care. These do not restrict the outcomes that will be measured, but provide the minimum to include if a trial is to be of the most use to potential users. We propose that trial registries, such as ISRCTN, encourage researchers to note their use of a core outcome set in their entry. This will help people searching for trials and those worried about selective reporting in closed trials. Trial registries can facilitate these efforts to make new trials as useful as possible and reduce waste. The outcomes section in the entry could prompt the researcher to consider using a core outcome set and facilitate the specification of that core outcome set and its component outcomes through linking to the original core outcome set. In doing this, registries will contribute to the global effort to ensure that trials answer important uncertainties, can be brought together in systematic reviews, and better serve their ultimate aim of improving health and well-being through improving health and social care.

Defibrillator implantations for primary prevention in the United States: Inappropriate care or inadequate documentation: Insights from the National Cardiovascular Data ICD Registry.

PubMed

Kaiser, Daniel W; Tsai, Vivian; Heidenreich, Paul A; Goldstein, Mary K; Wang, Yongfei; Curtis, Jeptha; Turakhia, Mintu P

2015-10-01

Prior studies have reported that more than 20% of implantable cardioverter-defibrillator (ICD) implantations in the United States do not adhere to trial-based criteria. We sought to investigate the patient characteristics associated with not meeting the inclusion criteria of the clinical trials that have demonstrated the efficacy of primary prevention ICDs. Using data from the National Cardiovascular Data Registry's ICD Registry, we identified patients who received ICDs for primary prevention from January 2006 to December 2008. We determined whether patients met the inclusion criteria of at least 1 of the 4 ICD primary prevention trials: Multicenter Automatic Defibrillator Implantation Trial (MADIT), MADIT-II, Sudden Cardiac Death in Heart Failure Trial (SCD-HeFT), and the Multicenter Unsustained Tachycardia Trial (MUSTT). Among 150,264 patients, 86% met criteria for an ICD implantation based on trial data. The proportion of patients who did not meet trial-based criteria increased as age decreased. In multivariate analysis, the significant predictors for not meeting trial criteria included prior cardiac transplantation (odds ratio [OR] 2.1), pediatric electrophysiology operator (OR 2.0), and high-grade atrioventricular conduction disease (OR 1.4). Among National Cardiovascular Data Registry registrants receiving first-time ICDs for primary prevention, the majority met trial-based criteria. Multivariate analyses suggested that many patients who did not meet the trial-based criteria may have had clinical circumstances that warranted ICD implantation. These findings caution against the use of trial-based indications to determine site quality metrics that could penalize sites that care for younger patients. The planned incorporation of appropriate use criteria into the ICD registry may better characterize patient- and site-level quality and performance. Published by Elsevier Inc.

Design and rationale for the Influenza vaccination After Myocardial Infarction (IAMI) trial. A registry-based randomized clinical trial.

PubMed

Fröbert, Ole; Götberg, Matthias; Angerås, Oskar; Jonasson, Lena; Erlinge, David; Engstrøm, Thomas; Persson, Jonas; Jensen, Svend E; Omerovic, Elmir; James, Stefan K; Lagerqvist, Bo; Nilsson, Johan; Kåregren, Amra; Moer, Rasmus; Yang, Cao; Agus, David B; Erglis, Andrejs; Jensen, Lisette O; Jakobsen, Lars; Christiansen, Evald H; Pernow, John

2017-07-01

Registry studies and case-control studies have demonstrated that the risk of acute myocardial infarction (AMI) is increased following influenza infection. Small randomized trials, underpowered for clinical end points, indicate that future cardiovascular events can be reduced following influenza vaccination in patients with established cardiovascular disease. Influenza vaccination is recommended by international guidelines for patients with cardiovascular disease, but uptake is varying and vaccination is rarely prioritized during hospitalization for AMI. The Influenza vaccination After Myocardial Infarction (IAMI) trial is a double-blind, multicenter, prospective, registry-based, randomized, placebo-controlled, clinical trial. A total of 4,400 patients with ST-segment elevation myocardial infarction (STEMI) or non-STEMI undergoing coronary angiography will randomly be assigned either to in-hospital influenza vaccination or to placebo. Baseline information is collected from national heart disease registries, and follow-up will be performed using both registries and a structured telephone interview. The primary end point is a composite of time to all-cause death, a new AMI, or stent thrombosis at 1 year. The IAMI trial is the largest randomized trial to date to evaluate the effect of in-hospital influenza vaccination on death and cardiovascular outcomes in patients with STEMI or non-STEMI. The trial is expected to provide highly relevant clinical data on the efficacy of influenza vaccine as secondary prevention after AMI. Copyright © 2017 The Author(s). Published by Elsevier Inc. All rights reserved.

Clinical Trial Registries Are of Minimal Use for Identifying Selective Outcome and Analysis Reporting

ERIC Educational Resources Information Center

Norris, Susan L.; Holmer, Haley K.; Fu, Rongwei; Ogden, Lauren A.; Viswanathan, Meera S.; Abou-Setta, Ahmed M.

2014-01-01

Objective: This study aimed to examine selective outcome reporting (SOR) and selective analysis reporting (SAR) in randomized controlled trials (RCTs) and to explore the usefulness of trial registries for identifying SOR and SAR. Study Design and Setting: We selected one "index outcome" for each of three comparative effectiveness reviews…

Transatlantic Comparison of CT Radiation Doses in the Era of Radiation Dose-Tracking Software.

PubMed

Parakh, Anushri; Euler, Andre; Szucs-Farkas, Zsolt; Schindera, Sebastian T

2017-12-01

The purpose of this study is to compare diagnostic reference levels from a local European CT dose registry, using radiation-tracking software from a large patient sample, with preexisting European and North American diagnostic reference levels. Data (n = 43,761 CT scans obtained over the course of 2 years) for the European local CT dose registry were obtained from eight CT scanners at six institutions. Means, medians, and interquartile ranges of volumetric CT dose index (CTDI vol ), dose-length product (DLP), size-specific dose estimate, and effective dose values for CT examinations of the head, paranasal sinuses, thorax, pulmonary angiogram, abdomen-pelvis, renal-colic, thorax-abdomen-pelvis, and thoracoabdominal angiogram were obtained using radiation-tracking software. Metrics from this registry were compared with diagnostic reference levels from Canada and California (published in 2015), the American College of Radiology (ACR) dose index registry (2015), and national diagnostic reference levels from local CT dose registries in Switzerland (2010), the United Kingdom (2011), and Portugal (2015). Our local registry had a lower 75th percentile CTDI vol for all protocols than did the individual internationally sourced data. Compared with our study, the ACR dose index registry had higher 75th percentile CTDI vol values by 55% for head, 240% for thorax, 28% for abdomen-pelvis, 42% for thorax-abdomen-pelvis, 128% for pulmonary angiogram, 138% for renal-colic, and 58% for paranasal sinus studies. Our local registry had lower diagnostic reference level values than did existing European and North American diagnostic reference levels. Automated radiation-tracking software could be used to establish and update existing diagnostic reference levels because they are capable of analyzing large datasets meaningfully.

Current challenges for clinical trials of cardiovascular medical devices.

PubMed

Zannad, Faiez; Stough, Wendy Gattis; Piña, Ileana L; Mehran, Roxana; Abraham, William T; Anker, Stefan D; De Ferrari, Gaetano M; Farb, Andrew; Geller, Nancy L; Kieval, Robert S; Linde, Cecilia; Redberg, Rita F; Stein, Kenneth; Vincent, Alphons; Woehrle, Holger; Pocock, Stuart J

2014-07-15

Several features of cardiovascular devices raise considerations for clinical trial conduct. Prospective, randomized, controlled trials remain the highest quality evidence for safety and effectiveness assessments, but, for instance, blinding may be challenging. In order to avoid bias and not confound data interpretation, the use of objective endpoints and blinding patients, study staff, core labs, and clinical endpoint committees to treatment assignment are helpful approaches. Anticipation of potential bias should be considered and planned for prospectively in a cardiovascular device trial. Prospective, single-arm studies (often referred to as registry studies) can provide additional data in some cases. They are subject to selection bias even when carefully designed; thus, they are generally not acceptable as the sole basis for pre-market approval of high risk cardiovascular devices. However, they complement the evidence base and fill the gaps unanswered by randomized trials. Registry studies present device safety and effectiveness in day-to-day clinical practice settings and detect rare adverse events in the post-market period. No single research design will be appropriate for every cardiovascular device or target patient population. The type of trial, appropriate control group, and optimal length of follow-up will depend on the specific device, its potential clinical benefits, the target patient population and the existence (or lack) of effective therapies, and its anticipated risks. Continued efforts on the part of investigators, the device industry, and government regulators are needed to reach the optimal approach for evaluating the safety and performance of innovative devices for the treatment of cardiovascular disease. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

Registration status and outcome reporting of trials published in core headache medicine journals.

PubMed

Rayhill, Melissa L; Sharon, Roni; Burch, Rebecca; Loder, Elizabeth

2015-11-17

To evaluate randomized controlled trial (RCT) registration and outcome reporting compliance in core headache medicine journals. We identified RCTs published in core journals (Headache, Cephalalgia, and the Journal of Headache and Pain) from 2005 through 2014. We searched articles for trial registration numbers, which were verified in the corresponding trial registry. We categorized trial funding sources as industry, academic, government, or mixed. We contacted corresponding authors to assess reasons for nonregistration. We evaluated whether primary outcomes in trial registries matched those in corresponding publications. The journals published 225 RCTs over the study period. Fifty-eight of 225 (26%) reported a trial registration number in the article that could be linked to a corresponding registry entry. Trial registration rates increased over the 9 years of the study. Forty-six of 118 (39%) of industry-funded studies were registered compared with 27% of academic and 0% of government-funded studies. Only 5% of RCTs were prospectively registered, reported primary outcomes identical to those in the trial registry, and did not report unacknowledged post hoc outcomes. The most common reason for nonregistration was lack of awareness. Only about a quarter of the articles published in the core headache medicine journals are compliant with trial registration, but compliance has increased over time. Selective reporting of outcomes remains a problem, and very few trials met all 3 reporting standards assessed in this study. Efforts to improve the quality of trial reporting in the headache literature should continue. © 2015 American Academy of Neurology.

Glocal clinical registries: pacemaker registry design and implementation for global and local integration--methodology and case study.

PubMed

da Silva, Kátia Regina; Costa, Roberto; Crevelari, Elizabeth Sartori; Lacerda, Marianna Sobral; de Moraes Albertini, Caio Marcos; Filho, Martino Martinelli; Santana, José Eduardo; Vissoci, João Ricardo Nickenig; Pietrobon, Ricardo; Barros, Jacson V

2013-01-01

The ability to apply standard and interoperable solutions for implementing and managing medical registries as well as aggregate, reproduce, and access data sets from legacy formats and platforms to advanced standard formats and operating systems are crucial for both clinical healthcare and biomedical research settings. Our study describes a reproducible, highly scalable, standard framework for a device registry implementation addressing both local data quality components and global linking problems. We developed a device registry framework involving the following steps: (1) Data standards definition and representation of the research workflow, (2) Development of electronic case report forms using REDCap (Research Electronic Data Capture), (3) Data collection according to the clinical research workflow and, (4) Data augmentation by enriching the registry database with local electronic health records, governmental database and linked open data collections, (5) Data quality control and (6) Data dissemination through the registry Web site. Our registry adopted all applicable standardized data elements proposed by American College Cardiology / American Heart Association Clinical Data Standards, as well as variables derived from cardiac devices randomized trials and Clinical Data Interchange Standards Consortium. Local interoperability was performed between REDCap and data derived from Electronic Health Record system. The original data set was also augmented by incorporating the reimbursed values paid by the Brazilian government during a hospitalization for pacemaker implantation. By linking our registry to the open data collection repository Linked Clinical Trials (LinkedCT) we found 130 clinical trials which are potentially correlated with our pacemaker registry. This study demonstrates how standard and reproducible solutions can be applied in the implementation of medical registries to constitute a re-usable framework. Such approach has the potential to facilitate data integration between healthcare and research settings, also being a useful framework to be used in other biomedical registries.

Severe chronic heart failure in patients considered for heart transplantation in Poland.

PubMed

Korewicki, Jerzy; Leszek, Przemysław; Zieliński, Tomasz; Rywik, Tomasz; Piotrowski, Walerian; Kurjata, Paweł; Kozar-Kamińska, Katarzyna; Kodziszewska, Katarzyna

2012-01-01

Based on the results of clinical trials, the prognosis for patients with severe heart failure (HF) has improved over the last 20 years. However, clinical trials do not reflect 'real life' due to patient selection. Thus, the aim of the POLKARD-HF registry was the analysis of survival of patients with refractory HF referred for orthotopic heart transplantation (OHT). Between 1 November 2003 and 31 October 2007, 983 patients with severe HF, referred for OHT in Poland, were included into the registry. All patients underwent routine clinical and hemodynamic evaluation, with NT-proBNP and hsCRP assessment. Death or an emergency OHT were assumed as the endpoints. The average observation period was 601 days. Kaplan-Meier curves with log-rank and univariate together with multifactor Cox regression model the stepwise variable selection method were used to determine the predictive value of analyzed variables. Among the 983 patients, the probability of surviving for one year was approximately 80%, for two years 70%, and for three years 67%. Etiology of the HF did not significantly influence the prognosis. The patients in NYHA class IV had a three-fold higher risk of death or emergency OHT. The univariate/multifactor Cox regression analysis revealed that NYHA IV class (HR 2.578, p < 0.0001), HFSS score (HR 2.572, p < 0.0001) and NT-proBNP plasma level (HR 1.600, p = 0.0200), proved to influence survival without death or emergency OHT. Despite optimal treatment, the prognosis for patients with refractory HF is still not good. NYHA class IV, NT-proBNP and HFSS score can help define the highest risk group. The results are consistent with the prognosis of patients enrolled into the randomized trials.

European Prevention of Alzheimer's Dementia Registry: Recruitment and prescreening approach for a longitudinal cohort and prevention trials.

PubMed

Vermunt, Lisa; Veal, Colin D; Ter Meulen, Lea; Chrysostomou, Charalambos; van der Flier, Wiesje; Frisoni, Giovanni B; Guessous, Idris; Kivipelto, Miia; Marizzoni, Moira; Martinez-Lage, Pablo; Molinuevo, José Luis; Porteous, David; Ritchie, Karen; Scheltens, Philip; Ousset, Pierre-Jean; Ritchie, Craig W; Luscan, Gerald; Brookes, Anthony J; Visser, Pieter Jelle

2018-06-01

It is a challenge to find participants for Alzheimer's disease (AD) prevention trials within a short period of time. The European Prevention of Alzheimer's Dementia Registry (EPAD) aims to facilitate recruitment by preselecting subjects from ongoing cohort studies. This article introduces this novel approach. A virtual registry, with access to risk factors and biomarkers for AD through minimal data sets of ongoing cohort studies, was set up. To date, ten cohorts have been included in the EPAD. Around 2500 participants have been selected, using variables associated with the risk for AD. Of these, 15% were already recruited in the EPAD longitudinal cohort study, which serves as a trial readiness cohort. This study demonstrates that a virtual registry can be used for the preselection of participants for AD studies. Copyright © 2018 the Alzheimer's Association. Published by Elsevier Inc. All rights reserved.

Glocal Clinical Registries: Pacemaker Registry Design and Implementation for Global and Local Integration – Methodology and Case Study

PubMed Central

da Silva, Kátia Regina; Costa, Roberto; Crevelari, Elizabeth Sartori; Lacerda, Marianna Sobral; de Moraes Albertini, Caio Marcos; Filho, Martino Martinelli; Santana, José Eduardo; Vissoci, João Ricardo Nickenig; Pietrobon, Ricardo; Barros, Jacson V.

2013-01-01

Background The ability to apply standard and interoperable solutions for implementing and managing medical registries as well as aggregate, reproduce, and access data sets from legacy formats and platforms to advanced standard formats and operating systems are crucial for both clinical healthcare and biomedical research settings. Purpose Our study describes a reproducible, highly scalable, standard framework for a device registry implementation addressing both local data quality components and global linking problems. Methods and Results We developed a device registry framework involving the following steps: (1) Data standards definition and representation of the research workflow, (2) Development of electronic case report forms using REDCap (Research Electronic Data Capture), (3) Data collection according to the clinical research workflow and, (4) Data augmentation by enriching the registry database with local electronic health records, governmental database and linked open data collections, (5) Data quality control and (6) Data dissemination through the registry Web site. Our registry adopted all applicable standardized data elements proposed by American College Cardiology / American Heart Association Clinical Data Standards, as well as variables derived from cardiac devices randomized trials and Clinical Data Interchange Standards Consortium. Local interoperability was performed between REDCap and data derived from Electronic Health Record system. The original data set was also augmented by incorporating the reimbursed values paid by the Brazilian government during a hospitalization for pacemaker implantation. By linking our registry to the open data collection repository Linked Clinical Trials (LinkedCT) we found 130 clinical trials which are potentially correlated with our pacemaker registry. Conclusion This study demonstrates how standard and reproducible solutions can be applied in the implementation of medical registries to constitute a re-usable framework. Such approach has the potential to facilitate data integration between healthcare and research settings, also being a useful framework to be used in other biomedical registries. PMID:23936257

Constructing a Local Potential Participant Registry to Improve Alzheimer's Disease Clinical Research Recruitment.

PubMed

Grill, Joshua D; Hoang, Dan; Gillen, Daniel L; Cox, Chelsea G; Gombosev, Adrijana; Klein, Kirsten; O'Leary, Steve; Witbracht, Megan; Pierce, Aimee

2018-01-01

Potential participant registries are tools to address the challenge of slow recruitment to clinical research. In particular, registries may aid recruitment to secondary prevention clinical trials for Alzheimer's disease (AD), which enroll cognitively normal older individuals meeting specific genetic or biomarker criteria. Evidence of registry effectiveness is sparse, as is guidance on optimal designs or methods of conduct. We report our experiences of developing a novel local potential participant registry that implemented online enrollment and data collection. In the first year of operation, 957 individuals submitted email addresses to the registry, of whom 592 self-reported demographic, family history, and medical data. In addition, registrants provided information related to their interest and willingness to be contacted about studies. Local earned media and community education were the most effective methods of recruitment into the registry. Seventy-six (26%) of 298 registrants contacted about studies in the first year enrolled in those studies. One hundred twenty-nine registrants were invited to enroll in a preclinical AD trial, of whom 25 (18%) screened and 6 were randomized. These results indicate that registries can aid recruitment and provide needed guidance for investigators initiating new local registries.

Publication proportions for registered breast cancer trials: before and following the introduction of the ClinicalTrials.gov results database.

PubMed

Asiimwe, Innocent Gerald; Rumona, Dickson

2016-01-01

To limit selective and incomplete publication of the results of clinical trials, registries including ClinicalTrials.gov were introduced. The ClinicalTrials.gov registry added a results database in 2008 to enable researchers to post the results of their trials as stipulated by the Food and Drug Administration Amendment Act of 2007. This study aimed to determine the direction and magnitude of any change in publication proportions of registered breast cancer trials that occurred since the inception of the ClinicalTrials.gov results database. A cross-sectional study design was employed using ClinicalTrials.gov, a publicly available registry/results database as the primary data source. Registry contents under the subcategories 'Breast Neoplasms' and 'Breast Neoplasms, Male' were downloaded on 1 August 2015. A literature search for included trials was afterwards conducted using MEDLINE and DISCOVER databases to determine publication status of the registered breast cancer trials. Nearly half (168/340) of the listed trials had been published, with a median time to publication of 24 months (Q1 = 14 months, Q3 = 42 months). Only 86 trials were published within 24 months of completion. There was no significant increase in publication proportions of trials that were completed before the introduction of the results database compared to those completed after (OR = 1.00, 95 % CI = .61 to 1.63; adjusted OR = 0.84, 95 % CI = .51 to 1.39). Characteristics associated with publication included trial type (observational versus interventional adjusted OR = .28, 95 % CI = .10 to .74) and completion/termination status (terminated versus completed adjusted OR = .22, 95 % CI = .09 to .51). Less than a half of breast cancer trials registered in ClinicalTrials.gov are published in peer-reviewed journals.

A dose response randomised controlled trial of docosahexaenoic acid (DHA) in preterm infants.

PubMed

Collins, C T; Sullivan, T R; McPhee, A J; Stark, M J; Makrides, M; Gibson, R A

2015-08-01

Thirty one infants born less than 30 weeks׳ gestational age were randomised to receive either 40 (n=11), 80 (n=9) or 120 (n=11) mg/kg/day of docosahexaenoic acid (DHA) respectively as an emulsion, via the feeding tube, commenced within 4 days of the first enteral feed. Twenty three infants were enroled in non-randomised reference groups; n=11 who had no supplementary DHA and n=12 who had maternal DHA supplementation. All levels of DHA in the emulsion were well tolerated with no effect on number of days of interrupted feeds or days to full enteral feeds. DHA levels in diets were directly related to blood DHA levels but were unrelated to arachidonic acid (AA) levels. All randomised groups and the maternal supplementation reference group prevented the drop in DHA levels at study end that was evident in infants not receiving supplementation. Australian New Zealand Clinical Trials Registry: ACTRN12610000382077. Copyright © 2015 Elsevier Ltd. All rights reserved.

Result Publication of Chinese Trials in World Health Organization Primary Registries

PubMed Central

Xuemei, Liu; Youping, Li; Senlin, Yin; Shangqi, Song

2010-01-01

Background Result publication is the key step to improve the transparency of clinical trials. Objective To investigate the result publication rate of Chinese trials registered in World Health Organization (WHO) primary registries. Method We searched 11 WHO primary registries for Chinese trials records. The progress of each trial was analyzed. We searched for the full texts of result publications cited in the registration records. For completed trials without citations, we searched PubMed, Embase, Chinese Biomedical Literature Database (Chinese), China Knowledge Resource Integrated Database, and Chinese Science and Technology Periodicals Database for result publications. The search was conducted on July 14, 2009. We also called the investigators of completed trials to ask about results publication. Results We identified 1294 Chinese trials records (428 in ChiCTR,743 in clinicaltrials.gov,55 in ISRCTN, 21 in ACTRN). A total of 443 trials had been completed. The publication rate of the Chinese trials in WHO primary registries is 35.2%(156/443).The publication rate of Chinese trials in clinicaltrials.gov, ChiCTR, ISRCTN, and ACRTN was 36.5% (53/145), 36.3% (89/245), 26.0%(9/44), and 55.6%(5/9), respectively. The publication rate of trials sponsored by industry(23.8%) was lower than that of sponsored by central and local government(31.7%), hospital(35.1%), and universities (40.7%). The publication rate for randomized trials was higher than that of cohort study and case-control study (33.2% versus 16.7%, 22.2%). The publication rate for interventional studies and observational studies was similar(33.4% versus 33.3%). Conclusion The publication rate of the registered Chinese trials was low, with no significant difference between ChiCTR and clinicaltrials.gov. An effective mechanism is needed to promote publication of results for registered trials in China. PMID:20856888

[Prehospital thrombolysis: A national perspective. Pharmaco-invasive strategy for early reperfusion of STEMI in Mexico].

PubMed

Arriaga-Nava, Roberto; Valencia-Sánchez, Jesús-Salvador; Rosas-Peralta, Martin; Garrido-Garduño, Martin; Calderón-Abbo, Moisés

2015-01-01

To review the existing evidence on the role of prehospital thrombolysis in patients with ST-segment elevation acute myocardial infarction (STEMI) as part of a strategy of cutting edge to reduce the time of coronary reperfusion and as a consequence improves both the survival and function. We used the technique of exploration-reduction-evaluation-analysis and synthesis of related studies, with an overview of current recommendations, data from controlled clinical trials and from the national and international registries about the different strategies for STEMI reperfusion. In total, we examined 186 references on prehospital thrombolysis, 130 references in times door-treatment, 139 references in STEMI management and national and international registries as well as 135 references on rescue and primary percutaneous coronary intervention for STEMI. Finally the 48 references that were more relevant and informative were retained. The «time» factor is crucial in the success of early reperfusion in STEMI especially if thrombolysis is applied correctly during the prehospital time. The primary percutaneous coronary intervention is contingent upon its feasibility before 120 min from the onset of symptoms. In our midst to internationally, thrombolysis continues to be a strategy with great impact on their expectations of life and function of patients. Telecommunication systems should be incorporate in real time to the priority needs of catastrophic diseases such as STEMI where life is depending on time. Copyright © 2014 Instituto Nacional de Cardiología Ignacio Chávez. Published by Masson Doyma México S.A. All rights reserved.

Existing data sources for clinical epidemiology: Aarhus University Clinical Trial Candidate Database, Denmark.

PubMed

Nørrelund, Helene; Mazin, Wiktor; Pedersen, Lars

2014-01-01

Denmark is facing a reduction in clinical trial activity as the pharmaceutical industry has moved trials to low-cost emerging economies. Competitiveness in industry-sponsored clinical research depends on speed, quality, and cost. Because Denmark is widely recognized as a region that generates high quality data, an enhanced ability to attract future trials could be achieved if speed can be improved by taking advantage of the comprehensive national and regional registries. A "single point-of-entry" system has been established to support collaboration between hospitals and industry. When assisting industry in early-stage feasibility assessments, potential trial participants are identified by use of registries to shorten the clinical trial startup times. The Aarhus University Clinical Trial Candidate Database consists of encrypted data from the Danish National Registry of Patients allowing an immediate estimation of the number of patients with a specific discharge diagnosis in each hospital department or outpatient specialist clinic in the Central Denmark Region. The free access to health care, thorough monitoring of patients who are in contact with the health service, completeness of registration at the hospital level, and ability to link all databases are competitive advantages in an increasingly complex clinical trial environment.

Characteristics and temporal trends in patient registries: focus on the life sciences industry, 1981–2012

PubMed Central

Travers, Karin; Sallum, Rachel H; Burns, Meghan D; Barr, Charles E; Beattie, Mary S; Pashos, Chris L; Luce, Bryan R

2015-01-01

Purpose Patient registries are used to monitor safety, examine real-world effectiveness, and may potentially contribute to comparative effectiveness research. To our knowledge, life sciences industry (LSI)-sponsored registries have not been systematically categorized. This study represents a first step toward understanding such registries over time. Methods Studies described as registries were identified in the ClinicalTrials.gov database. Characteristics from these registry records were abstracted and analyzed. Results Of 1202 registries identified, approximately 47% reported LSI sponsorship. These 562 LSI registries varied in focus: medical devices (n = 193, 34%), specific drugs (n = 173, 31%), procedures (n = 29, 5%), or particular diseases (n = 139, 25%). Thirty-three registries (<6%) evaluated pregnancy outcomes. The most common therapeutic area was cardiovascular (n = 234, 42%); others included endocrinology, immunology, oncology, musculoskeletal disorders, and neurology. The two most often measured outcomes were clinical effectiveness and safety, each of which appeared in 363/562 (65%) of LSI registries. Other outcomes included real-world clinical practice patterns (n = 122, 22%), patient-reported outcomes (n = 106, 19%), disease epidemiology/natural history (n = 69, 12%), and economic outcomes (n = 30, 5%). The number of LSI registries and their geographic diversity has increased over time. Conclusions The LSI registries represent a substantial proportion of all patient registries documented in ClinicalTrials.gov. These prospective studies are growing in number and encompass diverse therapeutic areas and geographic regions. Most registries measure multiple outcomes and capture real-world data that may be unavailable through other study designs. This classification of LSI registries documents their use for studying heterogeneity of diseases, examining treatment patterns, measuring patient-reported outcomes, examining economic outcomes, and performing comparative effectiveness research. © 2014 The Authors. Pharmacoepidemiology and Drug Safety published by John Wiley & Sons, Ltd. PMID:25079108

Outcomes from the Body & Soul Clinical Trials Project: A university-church partnership to improve African American enrollment in a clinical trial registry

PubMed Central

Langford, Aisha T.; Resnicow, Ken; Beasley, Derrick D.

2014-01-01

Objectives Historically, African Americans have been underrepresented in clinical trials (CTs) compared to whites. A growing number of research institutions have created CT registries to match volunteers with appropriate studies. In a sample of 745 African Americans from 16 churches, we tested the impact of a culturally tailored intervention aimed at increasing enrollment in a university-based CT registry. Methods Half of the churches received a culturally tailored CT education program (intervention) and half of the churches received a program about healthy eating (comparison). The main outcomes were the odds of posttest self-reported enrollment and verified enrollment. Using linear regression, posttest willingness to participate in a CT was also assessed. Results Odds of verified enrollment were higher in the intervention than comparison group (OR= 2.95, 95% CI: 1.33–6.5, p=0.01). Posttest self-reported enrollment in the registry was also higher among the intervention group than comparison group members (OR=1.94, 95% CI: 1.08–3.47, p=0.03). Willingness to participate in a future CT was higher in the intervention group (β=0.74, p=0.02). Conclusions A culturally tailored education program about CTs can increase enrollment of African Americans in a university-based clinical trials registry. Practice implications Community engagement and health education workshops may improve minority CT enrollment over time. PMID:25468392

Registry Assessment of Peripheral Interventional Devices (RAPID)　- Registry Assessment of Peripheral Interventional Devices Core Data Elements.

PubMed

Jones, W Schuyler; Krucoff, Mitchell W; Morales, Pablo; Wilgus, Rebecca W; Heath, Anne H; Williams, Mary F; Tcheng, James E; Marinac-Dabic, J Danica; Malone, Misti L; Reed, Terrie L; Fukaya, Rie; Lookstein, Robert; Handa, Nobuhiro; Aronow, Herbert D; Bertges, Daniel J; Jaff, Michael R; Tsai, Thomas T; Smale, Joshua A; Zaugg, Margo J; Thatcher, Robert J; Cronenwett, Jack L; Nc, Durham; Md, Silver Spring; Japan, Tokyo; Ny, New York; Ri, Providence; Vt, Burlington; Mass, Newton; Colo, Denver; Ariz, Tempe; Calif, Santa Clara; Minn, Minneapolis; Nh, Lebanon

2018-01-25

The current state of evaluating patients with peripheral artery disease and more specifically of evaluating medical devices used for peripheral vascular intervention (PVI) remains challenging because of the heterogeneity of the disease process, the multiple physician specialties that perform PVI, the multitude of devices available to treat peripheral artery disease, and the lack of consensus about the best treatment approaches. Because PVI core data elements are not standardized across clinical care, clinical trials, and registries, aggregation of data across different data sources and physician specialties is currently not feasible.Methods and Results:Under the auspices of the U.S. Food and Drug Administration's Medical Device Epidemiology Network initiative-and its PASSION (Predictable and Sustainable Implementation of the National Registries) program, in conjunction with other efforts to align clinical data standards-the Registry Assessment of Peripheral Interventional Devices (RAPID) workgroup was convened. RAPID is a collaborative, multidisciplinary effort to develop a consensus lexicon and to promote interoperability across clinical care, clinical trials, and national and international registries of PVI. The current manuscript presents the initial work from RAPID to standardize clinical data elements and definitions, to establish a framework within electronic health records and health information technology procedural reporting systems, and to implement an informatics-based approach to promote the conduct of pragmatic clinical trials and registry efforts in PVI. Ultimately, we hope this work will facilitate and improve device evaluation and surveillance for patients, clinicians, health outcomes researchers, industry, policymakers, and regulators.

Utility of registries for post-marketing evaluation of medicines. A survey of Swedish health care quality registries from a regulatory perspective.

PubMed

Feltelius, Nils; Gedeborg, Rolf; Holm, Lennart; Zethelius, Björn

2017-06-01

The aim of this study was to describe content and procedures in some selected Swedish health care quality registries (QRs) of relevance to regulatory decision-making. A workshop was organized with participation of seven Swedish QRs which subsequently answered a questionnaire regarding registry content on drug treatments and outcomes. Patient populations, coverage, data handling and quality control, as well as legal and ethical aspects are presented. Scientific publications from the QRs are used as a complementary measure of quality and scientific relevance. The registries under study collect clinical data of high relevance to regulatory and health technology agencies. Five out of seven registries provide information on the drug of interest. When applying external quality criteria, we found a high degree of fulfillment, although information on medication was not sufficient to answer all questions of regulatory interest. A notable strength is the option for linkage to the Prescribed Drug Registry and to information on education and socioeconomic status. Data on drugs used during hospitalization were also collected to some extent. Outcome measures collected resemble those used in relevant clinical trials. All registries collected patient-reported outcome measures. The number of publications from the registries was substantial, with studies of appropriate design, including randomized registry trials. Quality registries may provide a valuable source of post-marketing data on drug effectiveness, safety, and cost-effectiveness. Closer collaboration between registries and regulators to improve quality and usefulness of registry data could benefit both regulatory utility and value for health care providers.

Utility of registries for post-marketing evaluation of medicines. A survey of Swedish health care quality registries from a regulatory perspective

PubMed Central

Feltelius, Nils; Gedeborg, Rolf; Holm, Lennart; Zethelius, Björn

2017-01-01

Aim The aim of this study was to describe content and procedures in some selected Swedish health care quality registries (QRs) of relevance to regulatory decision-making. Methods A workshop was organized with participation of seven Swedish QRs which subsequently answered a questionnaire regarding registry content on drug treatments and outcomes. Patient populations, coverage, data handling and quality control, as well as legal and ethical aspects are presented. Scientific publications from the QRs are used as a complementary measure of quality and scientific relevance. Results The registries under study collect clinical data of high relevance to regulatory and health technology agencies. Five out of seven registries provide information on the drug of interest. When applying external quality criteria, we found a high degree of fulfillment, although information on medication was not sufficient to answer all questions of regulatory interest. A notable strength is the option for linkage to the Prescribed Drug Registry and to information on education and socioeconomic status. Data on drugs used during hospitalization were also collected to some extent. Outcome measures collected resemble those used in relevant clinical trials. All registries collected patient-reported outcome measures. The number of publications from the registries was substantial, with studies of appropriate design, including randomized registry trials. Conclusions Quality registries may provide a valuable source of post-marketing data on drug effectiveness, safety, and cost-effectiveness. Closer collaboration between registries and regulators to improve quality and usefulness of registry data could benefit both regulatory utility and value for health care providers. PMID:28276780

Effects of the length of central cancer registry operations on identification of subsequent cancers and on survival estimates.

PubMed

Qiao, Baozhen; Schymura, Maria J; Kahn, Amy R

2016-10-01

Population-based cancer survival analyses have traditionally been based on the first primary cancer. Recent studies have brought this practice into question, arguing that varying registry reference dates affect the ability to identify earlier cancers, resulting in selection bias. We used a theoretical approach to evaluate the extent to which the length of registry operations affects the classification of first versus subsequent cancers and consequently survival estimates. Sequence number central was used to classify tumors from the New York State Cancer Registry, diagnosed 2001-2010, as either first primaries (value=0 or 1) or subsequent primaries (≥2). A set of three sequence numbers, each based on an assumed reference year (1976, 1986 or 1996), was assigned to each tumor. Percent of subsequent cancers was evaluated by reference year, cancer site and age. 5-year relative survival estimates were compared under four different selection scenarios. The percent of cancer cases classified as subsequent primaries was 15.3%, 14.3% and 11.2% for reference years 1976, 1986 and 1996, respectively; and varied by cancer site and age. When only the first primary was included, shorter registry operation time was associated with slightly lower 5-year survival estimates. When all primary cancers were included, survival estimates decreased, with the largest decreases seen for the earliest reference year. Registry operation length affected the identification of subsequent cancers, but the overall effect of this misclassification on survival estimates was small. Survival estimates based on all primary cancers were slightly lower, but might be more comparable across registries. Copyright © 2016 Elsevier Ltd. All rights reserved.

Reference Standards for Cardiorespiratory Fitness Measured With Cardiopulmonary Exercise Testing Using Cycle Ergometry: Data From the Fitness Registry and the Importance of Exercise National Database (FRIEND) Registry.

PubMed

Kaminsky, Leonard A; Imboden, Mary T; Arena, Ross; Myers, Jonathan

2017-02-01

The importance of cardiorespiratory fitness (CRF) is well established. This report provides newly developed standards for CRF reference values derived from cardiopulmonary exercise testing (CPX) using cycle ergometry in the United States. Ten laboratories in the United States experienced in CPX administration with established quality control procedures contributed to the "Fitness Registry and the Importance of Exercise: A National Database" (FRIEND) Registry from April 2014 through May 2016. Data from 4494 maximal (respiratory exchange ratio, ≥1.1) cycle ergometer tests from men and women (20-79 years) from 27 states, without cardiovascular disease, were used to develop these references values. Percentiles of maximum oxygen consumption (VO 2max ) for men and women were determined for each decade from age 20 years through age 79 years. Comparisons of VO 2max were made to reference data established with CPX data from treadmill data in the FRIEND Registry and previously published reports. As expected, there were significant differences between sex and age groups for VO 2max (P<.01). For cycle tests within the FRIEND Registry, the 50th percentile VO 2max of men and women aged 20 to 29 years declined from 41.9 and 31.0 mLO 2 /kg/min to 19.5 and 14.8 mLO 2 /kg/min for ages 70 to 79 years, respectively. The rate of decline in this cohort was approximately 10% per decade. The FRIEND Registry reference data will be useful in providing more accurate interpretations for the US population of CPX-measured VO 2max from exercise tests using cycle ergometry compared with previous approaches based on estimations of standard differences from treadmill testing reference values. Copyright © 2016 Mayo Foundation for Medical Education and Research. All rights reserved.

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

Examining the challenges of family recruitment to behavioral intervention trials: factors associated with participation and enrollment in a multi-state colonoscopy intervention trial

PubMed Central

2013-01-01

Background Colonoscopy is one of the most effective methods of cancer prevention and detection, particularly for individuals with familial risk. Recruitment of family members to behavioral intervention trials remains uniquely challenging, owing to the intensive process required to identify and contact them. Recruiting at-risk family members involves contacting the original cancer cases and asking them to provide information about their at-risk relatives, who must then be contacted for study enrollment. Though this recruitment strategy is common in family trials, few studies have compared influences of patient and relative participation to nonparticipation. Furthermore, although use of cancer registries to identify initial cases has increased, to our knowledge no study has examined the relationship between registries and family recruitment outcomes. Methods This study assessed predictors of case participation and relative enrollment in a recruitment process that utilized state cancer registries. Participation characteristics were analyzed with separate multivariable logistic regressions in three stages: (1) cancer registry-contacted colorectal cancer (CRC) cases who agreed to study contact; (2) study-contacted CRC cases who provided at-risk relative information; and (3) at-risk relatives contacted for intervention participation. Results Cancer registry source was predictive of participation for both CRC cases and relatives, though relative associations (odds ratios) varied across registries. Cases were less likely to participate if they were Hispanic or nonwhite, and were more likely to participate if they were female or younger than 50 at cancer diagnosis. At-risk relatives were more likely to participate if they were from Utah, if another family member was also participating in the study, or if they had previously had a colonoscopy. The number of eligible cases who had to be contacted to enroll one eligible relative varied widely by registry, from 7 to 81. Conclusions Family recruitment utilizing cancer registry-identified cancer cases is feasible, but highly dependent on both the strategies and protocols of those who are recruiting and on participant characteristics such as sex, race, or geography. Devising comprehensive recruitment protocols that specifically target those less likely to enroll may help future research meet recruitment goals. Trial registration Family Colorectal Cancer Awareness and Risk Education Project NCT01274143. PMID:23782890

Innovative Telemonitoring Enhanced Care Programme for Chronic Heart Failure (ITEC-CHF) to improve guideline compliance and collaborative care: protocol of a multicentre randomised controlled trial

PubMed Central

Jayasena, Rajiv; Maiorana, Andrew; Dowling, Alison; Chen, Sheau Huey; Karunanithi, Mohan; Layland, Jamie; Edwards, Iain

2017-01-01

Introduction Chronic heart failure (CHF) is a life-threatening chronic disease characterised by periodic exacerbations and recurrent hospitalisations. In the management of CHF, patient compliance with evidence-based clinical guidelines is essential, but remains difficult practically. The objective of this study is to examine whether an Innovative Telemonitoring Enhanced Care Programme for CHF (ITEC-CHF) improves patients’ compliance, and associated health and economic outcomes. Methods and analysis An open multicentre randomised controlled trial has been designed. Patients will be recruited and randomised to receive either ITEC-CHF (n=150) or usual care CHF (n=150) for at least 6 months. ITEC-CHF combines usual care and an additional telemonitoring service including remote weight monitoring, structured telephone support and nurse-led collaborative care. The primary outcomes are the compliance rates with the best-practice guidelines for daily weight monitoring. The secondary outcomes include the compliance with other guideline recommendations (health maintenance, medication, diet and exercise), health (health-related quality of life, risk factors, functional capacity and psychological states) and economic outcomes related to the use of healthcare resources such as hospital readmissions and general practitioner/emergency department visits. Ethics and dissemination The clinical trial has been approved by Peninsula Health Human Research Ethics Committee (HREC Reference: HREC/14/PH/27), Royal Perth Hospital Human Research Ethics Committee (Reference: 15-081) and the Curtin University Human Research Ethics Committee (Reference: HR 181/2014). We will disseminate the final results to the public via conferences and journal publications. A final study report will also be provided to the ethics committees. Trial registration number Registered with Australian New Zealand Clinical Trial Registry (ACTRN12614000916640). PMID:28993389

National Dyslipidemia Registry of the Spanish Arteriosclerosis Society: Current status.

PubMed

Pérez-Calahorra, Sofía; Sánchez-Hernández, Rosa M; Plana, Núria; Valdivielso, Pedro; Civeira, Fernando

Clinical registries are a very effective tool to verify the usual clinical practice, to compare clinical strategies and to improve the knowledge of diagnostic and therapeutic new procedures. The National Registry of Dyslipemias of the Spanish Society of Arteriosclerosis (SEA) is an on-line, retrospective and prospective database where the different Spanish lipid units accredited by the SEA introduce data from patients with disorders of lipid metabolism. The registry was created in 2013, and since then clinical, analytical, genetic and evolutionary data of 4,449 patients have been introduced until June 2017. In the last year the registry has given rise to a considerable number of international publications and there are several more in progress. An ambitious incentive plan for inclusion of patients has been initiated to get the SEA registry as a global reference that helps to improve the knowledge and clinical management of these patients. From the coordinating group of the registry we encourage all SEA partners to collaborate in the multiple forms that the registry allows, and to make it an international scientific reference. Copyright © 2017. Publicado por Elsevier España, S.L.U.

Registry Assessment of Peripheral Interventional Devices (RAPID): Registry assessment of peripheral interventional devices core data elements.

PubMed

Jones, W Schuyler; Krucoff, Mitchell W; Morales, Pablo; Wilgus, Rebecca W; Heath, Anne H; Williams, Mary F; Tcheng, James E; Marinac-Dabic, J Danica; Malone, Misti L; Reed, Terrie L; Fukaya, Rie; Lookstein, Robert A; Handa, Nobuhiro; Aronow, Herbert D; Bertges, Daniel J; Jaff, Michael R; Tsai, Thomas T; Smale, Joshua A; Zaugg, Margo J; Thatcher, Robert J; Cronenwett, Jack L

2018-02-01

The current state of evaluating patients with peripheral artery disease and more specifically of evaluating medical devices used for peripheral vascular intervention (PVI) remains challenging because of the heterogeneity of the disease process, the multiple physician specialties that perform PVI, the multitude of devices available to treat peripheral artery disease, and the lack of consensus about the best treatment approaches. Because PVI core data elements are not standardized across clinical care, clinical trials, and registries, aggregation of data across different data sources and physician specialties is currently not feasible. Under the auspices of the U.S. Food and Drug Administration's Medical Device Epidemiology Network initiative-and its PASSION (Predictable and Sustainable Implementation of the National Registries) program, in conjunction with other efforts to align clinical data standards-the Registry Assessment of Peripheral Interventional Devices (RAPID) workgroup was convened. RAPID is a collaborative, multidisciplinary effort to develop a consensus lexicon and to promote interoperability across clinical care, clinical trials, and national and international registries of PVI. The current manuscript presents the initial work from RAPID to standardize clinical data elements and definitions, to establish a framework within electronic health records and health information technology procedural reporting systems, and to implement an informatics-based approach to promote the conduct of pragmatic clinical trials and registry efforts in PVI. Ultimately, we hope this work will facilitate and improve device evaluation and surveillance for patients, clinicians, health outcomes researchers, industry, policymakers, and regulators. Copyright © 2017 Society for Vascular Surgery. All rights reserved.

Proposal for the development of biologics in pediatric rheumatology.

PubMed

Mori, Masaaki; Nakagawa, Masao; Tsuchida, Nao; Kawada, Kou; Sato, Junko; Sakiyama, Michiyo; Hirano, Shinya; Sato, Katsuaki; Nakamura, Hidefumi

2018-02-01

In order to assess the development, approval and early introduction into clinical practice of biologics in the pediatric field, we herein describe the current status of the development to approval of biologics as anti-rheumatic agents for children in Japan, discuss the present problems and provide a proposal for the future. It has become apparent that the duration of the review period required for the preparation of clinical trials and Pharmaceuticals and Medical Devices Agency approval is clearly reduced compared with the past. Thus, it was speculated that a rate-limiting step in the process from development to approval was the duration of clinical trials from start to end. Hence, we focused on the following key words with regard to promotion of the development of biologics and their early practical use: "registry", "centralization", and "global cooperation", all of which are related to the reduction of duration of a clinical trial. In conclusion, to reduce the duration of a clinical trial, it is essential to complete a world-scale registry system by developing the registry system established by the Pediatric Rheumatology Association of Japan. The next step is then to carefully plan to participate in the international network using the world-scale registry system, and develop global cooperative trials in which we can ensure a sufficient number of entries from Japan. © 2017 Japan Pediatric Society.

Selection of Patients in Ongoing Clinical Trials on Lung Cancer.

PubMed

Schulkes, Karlijn J G; Nguyen, Cindy; van den Bos, Frederiek; van Elden, Leontine J R; Hamaker, Marije E

2016-12-01

Lung cancer is predominantly a disease of the elderly: half of all newly diagnosed patients are over 70 years old. Older patients and those with comorbidities are underrepresented in clinical trials; scientific communities have addressed this issue since the end of the 20th century. We set out to determine the characteristics of the selection of patients in lung cancer trials that are currently recruiting. We searched The United States National Institutes of Health (NIH) clinical trial registry ( www.clinicaltrials.gov ) on April 23, 2015 for currently recruiting phase I, II, or III clinical trials in lung cancer. Trial characteristics and study objectives were extracted from the registry website. Of the 419 trails selected in this overview, 88 % explicitly or implicitly excluded elderly patients. Patients were excluded based on stringent organ selection in 76 % of the trials, based on performance status (57 %) and based on age (13 %). The median number of placed restrictions per trial was seven. In the 2 % of the trials that were exclusively designed for elderly patients only fit patients were included. In this overview of current lung cancer trials registered in the NIH clinical trial registry, we found that elderly patients and those with comorbidities are often excluded from participation in clinical trials. Therefore, it is difficult for physicians and their frail patients to properly evaluate the efficacy and safety of current treatment options. More research that includes the elderly and those with comorbidities is urgently needed.

Can rheumatoid arthritis (RA) registries provide contextual safety data for modern RA clinical trials? The case for mortality and cardiovascular disease.

PubMed

Michaud, Kaleb; Berglind, Niklas; Franzén, Stefan; Frisell, Thomas; Garwood, Christopher; Greenberg, Jeffrey D; Ho, Meilien; Holmqvist, Marie; Horne, Laura; Inoue, Eisuke; Nyberg, Fredrik; Pappas, Dimitrios A; Reed, George; Symmons, Deborah; Tanaka, Eiichi; Tran, Trung N; Verstappen, Suzanne M M; Wesby-van Swaay, Eveline; Yamanaka, Hisashi; Askling, Johan

2016-10-01

We implemented a novel method for providing contextual adverse event rates for a randomised controlled trial (RCT) programme through coordinated analyses of five RA registries, focusing here on cardiovascular disease (CVD) and mortality. Each participating registry (Consortium of Rheumatology Researchers of North America (CORRONA) (USA), Swedish Rheumatology Quality of Care Register (SRR) (Sweden), Norfolk Arthritis Register (NOAR) (UK), CORRONA International (East Europe, Latin America, India) and Institute of Rheumatology, Rheumatoid Arthritis (IORRA) (Japan)) defined a main cohort from January 2000 onwards. To address comparability and potential bias, we harmonised event definitions and defined several subcohorts for sensitivity analyses based on disease activity, treatment, calendar time, duration of follow-up and RCT exclusions. Rates were standardised for age, sex and, in one sensitivity analysis, also HAQ. The combined registry cohorts included 57 251 patients with RA (234 089 person-years)-24.5% men, mean (SD) baseline age 58.2 (13.8) and RA duration 8.2 (11.7) years. Standardised registry mortality rates (per 100 person-years) varied from 0.42 (CORRONA) to 0.80 (NOAR), with 0.60 for RCT patients. Myocardial infarction and major adverse cardiovascular events (MACE) rates ranged from 0.09 and 0.31 (IORRA) to 0.39 and 0.77 (SRR), with RCT rates intermediate (0.18 and 0.42), respectively. Additional subcohort analyses showed small and mostly consistent changes across registries, retaining reasonable consistency in rates across the Western registries. Additional standardisation for HAQ returned higher mortality and MACE registry rates. This coordinated approach to contextualising RA RCT safety data demonstrated reasonable differences and consistency in rates for mortality and CVD across registries, and comparable RCT rates, and may serve as a model method to supplement clinical trial analyses for drug development programmes. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

Review of patient registries in dermatology.

PubMed

DiMarco, Gabriella; Hill, Dane; Feldman, Steven R

2016-10-01

Patient registries are datasets containing information on patients with a particular disease or patients who are undergoing a specific treatment. Our objective was to search for and catalog the types of registries being used in dermatology and investigate their characteristics and uses. We searched Google, the Registry of Patient Registries, Orphanet, and ClinicalTrials.gov to compile a list of dermatology disease registries. We also conducted a literature review on the uses of dermatology registries using PubMed. We identified 48 dermatology patient registries, with 23 distinct diseases represented. We also identified 11 registries used for postmarketing surveillance of skin disease. Our search was limited to registries in English. Registries are commonly used for the study of rare dermatologic diseases and for postsurveillance monitoring of systemic therapies in more common dermatologic diseases, such as psoriasis. Copyright © 2016 American Academy of Dermatology, Inc. Published by Elsevier Inc. All rights reserved.

Registry-based randomized controlled trials merged the strength of randomized controlled trails and observational studies and give rise to more pragmatic trials.

PubMed

Mathes, Tim; Buehn, Stefanie; Prengel, Peggy; Pieper, Dawid

2018-01-01

The objective of this study was to analyze the features of registry-based randomized trials (rRCTs). We systematically searched PubMed for rRCTs. Study selection was performed independently by two reviewers. We extracted all data in standardized tables and prepared descriptive summary statistics. The search resulted in 1,202 hits. We included 71 rRCTs. Most rRCTs were from Denmark and Sweden. Chronic conditions were considered in 82.2%. A preventive intervention was examined in 45.1%. The median of included patients was 2,000 (range: 69-246,079). Definition of the study population was mostly broad. Study procedures were regularly little standardized. The number of included and analyzed patients was the same in 82.1%. In half of the rRCTs, more than one registry was utilized. Various linkage techniques were used. In median, two outcomes were collected from the registry/ies. The median follow-up of the rRCTs was 5.3 years (range: 6 weeks to 27 years). Information on quality of registry data was reported in 11.3%. rRCTs can provide valid (randomization, low lost-to-follow-up rates, generalizable) patient important long-term comparative-effectiveness data for relative little effort. Researchers planning an RCT should always check whether existing registries can be used for data collection. Reporting on data quality must be improved for use in evidence synthesis. Copyright © 2017 Elsevier Inc. All rights reserved.

Transparency and public accessibility of clinical trial information in Croatia: how it affects patient participation in clinical trials.

PubMed

Šolić, Ivana; Stipčić, Ana; Pavličević, Ivančica; Marušić, Ana

2017-06-15

Despite increased visibility of clinical trials through international trial registries, patients often remain uninformed of their existence, especially if they do not have access to adequate information about clinical research, including the language of the information. The aim of this study was to describe the context for transparency of clinical trials in Croatia in relation to countries in Central and Eastern Europe, and to assess how informed Croatian patients are about clinical trials and their accessibility. We assessed the transparency of clinical trials from the data available in the public domain. We also conducted an anonymous survey on a convenience sample of 257 patients visiting two family medicine offices or an oncology department in south Croatia, and members of national patients' associations. Despite legal provisions for transparency of clinical trials in Croatia, they are still not sufficiently visible in the public domain. Among countries from Central and Eastern Europe, Croatia has the fewest number of registered trials in the EU Clinical Trials Registry. 66% of the patients in the survey were aware of the existence of clinical trials but only 15% were informed about possibilities of participating in a trial. Although 58% of the respondents were willing to try new treatments, only 6% actually participated in a clinical trial. Only 2% of the respondents were aware of publicly available trial registries. Our study demonstrates that there is low transparency of clinical trials in Croatia, and that Croatian patients are not fully aware of clinical trials and the possibilities of participating in them, despite reported availability of Internet resources and good communication with their physicians. There is a need for active policy measures to increase the awareness of and access to clinical trials to patients in Croatia, particularly in their own language.

CTRI – Clicking to greater transparency and accountability

PubMed Central

George, Bobby

2012-01-01

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

ClinicalTrials.gov as a data source for semi-automated point-of-care trial eligibility screening.

PubMed

Pfiffner, Pascal B; Oh, JiWon; Miller, Timothy A; Mandl, Kenneth D

2014-01-01

Implementing semi-automated processes to efficiently match patients to clinical trials at the point of care requires both detailed patient data and authoritative information about open studies. To evaluate the utility of the ClinicalTrials.gov registry as a data source for semi-automated trial eligibility screening. Eligibility criteria and metadata for 437 trials open for recruitment in four different clinical domains were identified in ClinicalTrials.gov. Trials were evaluated for up to date recruitment status and eligibility criteria were evaluated for obstacles to automated interpretation. Finally, phone or email outreach to coordinators at a subset of the trials was made to assess the accuracy of contact details and recruitment status. 24% (104 of 437) of trials declaring on open recruitment status list a study completion date in the past, indicating out of date records. Substantial barriers to automated eligibility interpretation in free form text are present in 81% to up to 94% of all trials. We were unable to contact coordinators at 31% (45 of 146) of the trials in the subset, either by phone or by email. Only 53% (74 of 146) would confirm that they were still recruiting patients. Because ClinicalTrials.gov has entries on most US and many international trials, the registry could be repurposed as a comprehensive trial matching data source. Semi-automated point of care recruitment would be facilitated by matching the registry's eligibility criteria against clinical data from electronic health records. But the current entries fall short. Ultimately, improved techniques in natural language processing will facilitate semi-automated complex matching. As immediate next steps, we recommend augmenting ClinicalTrials.gov data entry forms to capture key eligibility criteria in a simple, structured format.

Overview of phase IV clinical trials for postmarket drug safety surveillance: a status report from the ClinicalTrials.gov registry.

PubMed

Zhang, Xinji; Zhang, Yuan; Ye, Xiaofei; Guo, Xiaojing; Zhang, Tianyi; He, Jia

2016-11-23

Phase IV trials are often used to investigate drug safety after approval. However, little is known about the characteristics of contemporary phase IV clinical trials and whether these studies are of sufficient quality to advance medical knowledge in pharmacovigilance. We aimed to determine the fundamental characteristics of phase IV clinical trials that evaluated drug safety using the ClinicalTrials.gov registry data. A data set of 19 359 phase IV clinical studies registered in ClinicalTrials.gov was downloaded. The characteristics of the phase IV trials focusing on safety only were compared with those evaluating both safety and efficacy. We also compared the characteristics of the phase IV trials in three major therapeutic areas (cardiovascular diseases, mental health and oncology). Multivariable logistic regression was used to evaluate factors associated with the use of blinding and randomisation. A total of 4772 phase IV trials were identified, including 330 focusing on drug safety alone and 4392 evaluating both safety and efficacy. Most of the phase IV trials evaluating drug safety (75.9%) had enrolment <300 with 96.5% <3000. Among these trials, 8.2% were terminated or withdrawn. Factors associated with the use of blinding and randomisation included the intervention model, clinical specialty and lead sponsor. Phase IV trials evaluating drug safety in the ClinicalTrials.gov registry were dominated by small trials that might not have sufficient power to detect less common adverse events. An adequate sample size should be emphasised for phase IV trials with safety surveillance as main task. 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 heart failure: perspectives from a randomized trial and a simultaneous registry.

PubMed

Ezekowitz, Justin A; Hu, Jia; Delgado, Diego; Hernandez, Adrian F; Kaul, Padma; Leader, Rolland; Proulx, Guy; Virani, Sean; White, Michel; Zieroth, Shelley; O'Connor, Christopher; Westerhout, Cynthia M; Armstrong, Paul W

2012-11-01

Randomized controlled trials (RCT) are limited by their generalizability to the broader nontrial population. To provide a context for Acute Study of Nesiritide in Decompensated Heart Failure (ASCEND-HF) trial, we designed a complementary registry to characterize clinical characteristics, practice patterns, and in-hospital outcomes of acute heart failure patients. Eligible patients for the registry included those with a principal diagnosis of acute heart failure (ICD-9-CM 402 and 428; ICD-10 I50.x, I11.0, I13.0, I13.2) from 8 sites participating in ASCEND-HF (n=697 patients, 2007-2010). Baseline characteristics, treatments, and hospital outcomes from the registy were compared with ASCEND-HF RCT patients from 31 Canadian sites (n=465, 2007-2010). Patients in the registry were older, more likely to be female, and have chronic respiratory disease, less likely to have diabetes mellitus: they had a similar incidence of ischemic HF, atrial fibrillation, and similar B-type natriuretic peptide levels. Registry patients had higher systolic blood pressure (registry: median 132 mm Hg [interquartile range 115-151 mm Hg]; RCT: median 120 mm Hg [interquartile range 110-135 mm Hg]) and ejection fraction (registry: median 40% [interquartile range 27-58%]; RCT: median 29% [interquartile range 20-40 mm Hg]) than RCT patients. Registry patients presented more often via ambulance and had a similar total length of stay as RCT patients. In-hospital mortality was significantly higher in the registry compared with the RCT patients (9.3% versus 1.3%,P<0.001), and this remained after multivariable adjustment (odds ratio 6.6, 95% CI 2.6-16.8, P<0.001). Patients enrolled in a large RCT of acute heart failure differed significantly based on clinical characteristics, treatments, and inpatient outcomes from contemporaneous patients participating in a registry. These results highlight the need for context of RCTs to evaluate generalizability of results and especially the need to improve clinical outcomes in acute heart failure. URL: http://www.clinicaltrials.gov. Unique identifier: NCT00475852.

[The significance of introducing registry study in the post-marketing safety research for Chinese medicine and pharmacy].

PubMed

Liao, Xing; Xie, Yan-Ming; Yang, Wei; Chang, Yan-Peng

2014-03-01

There is a new research model named 'registry study/patient registry' in Western medicine, which could be referred to by Chinese medicine researchers, such as active safety surveillance. This article will introduce registry study from different aspects as the developing history, features, and application in order to inform Chinese medicine researchers of future studies.

Network meta-analyses could be improved by searching more sources and by involving a librarian.

PubMed

Li, Lun; Tian, Jinhui; Tian, Hongliang; Moher, David; Liang, Fuxiang; Jiang, Tongxiao; Yao, Liang; Yang, Kehu

2014-09-01

Network meta-analyses (NMAs) aim to rank the benefits (or harms) of interventions, based on all available randomized controlled trials. Thus, the identification of relevant data is critical. We assessed the conduct of the literature searches in NMAs. Published NMAs were retrieved by searching electronic bibliographic databases and other sources. Two independent reviewers selected studies and five trained reviewers abstracted data regarding literature searches, in duplicate. Search method details were examined using descriptive statistics. Two hundred forty-nine NMAs were included. Eight used previous systematic reviews to identify primary studies without further searching, and five did not report any literature searches. In the 236 studies that used electronic databases to identify primary studies, the median number of databases was 3 (interquartile range: 3-5). MEDLINE, EMBASE, and Cochrane Central Register of Controlled Trials were the most commonly used databases. The most common supplemental search methods included reference lists of included studies (48%), reference lists of previous systematic reviews (40%), and clinical trial registries (32%). None of these supplemental methods was conducted in more than 50% of the NMAs. Literature searches in NMAs could be improved by searching more sources, and by involving a librarian or information specialist. Copyright © 2014 Elsevier Inc. All rights reserved.

Bridging the gap between the randomised clinical trial world and the real world by combination of population-based registry and electronic health record data: A case study in haemato-oncology.

PubMed

Kibbelaar, R E; Oortgiesen, B E; van der Wal-Oost, A M; Boslooper, K; Coebergh, J W; Veeger, N J G M; Joosten, P; Storm, H; van Roon, E N; Hoogendoorn, M

2017-11-01

Randomised clinical trials (RCTs) are considered the basis of evidence-based medicine. It is recognised more and more that application of RCT results in daily practice of clinical decision-making is limited because the RCT world does not correspond with the clinical real world. Recent strategies aiming at substitution of RCT databases by improved population-based registries (PBRs) or by improved electronic health record (EHR) systems to provide significant data for clinical science are discussed. A novel approach exemplified by the HemoBase haemato-oncology project is presented. In this approach, a PBR is combined with an advanced EHR, providing high-quality data for observational studies and support of best practice development. This PBR + EHR approach opens a perspective on randomised registry trials. Copyright © 2017 Elsevier Ltd. All rights reserved.

ClinicalTrials.gov

MedlinePlus

... Terms and Conditions Disclaimer ClinicalTrials.gov is a database of privately and publicly funded clinical studies conducted ... world. ClinicalTrials.gov is a registry and results database of publicly and privately supported clinical studies of ...

Genetics Home Reference: Pompe disease

MedlinePlus

... Genetic Testing (2 links) Genetic Testing Registry: Glycogen storage disease type II, infantile Genetic Testing Registry: Glycogen storage disease, type II Other Diagnosis and Management Resources ( ...

Is Real-World Evidence Used in P&T Monographs and Therapeutic Class Reviews?

PubMed

Hurwitz, Jason T; Brown, Mary; Graff, Jennifer S; Peters, Loretta; Malone, Daniel C

2017-06-01

Payers are faced with making coverage and reimbursement decisions based on the best available evidence. Often these decisions apply to patient populations, provider networks, and care settings not typically studied in clinical trials. Treatment effectiveness evidence is increasingly available from electronic health records, registries, and administrative claims. However, little is known about when and what types of real-world evidence (RWE) studies inform pharmacy and therapeutic (P&T) committee decisions. To evaluate evidence sources cited in P&T committee monographs and therapeutic class reviews and assess the design features and quality of cited RWE studies. A convenience sample of representatives from pharmacy benefit management, health system, and health plan organizations provided recent P&T monographs and therapeutic class reviews (or references from such documents). Two investigators examined and grouped references into major categories (published studies, unpublished studies, and other/unknown) and multiple subcategories (e.g., product label, clinical trials, RWE, systematic reviews). Cited comparative RWE was reviewed to assess design features (e.g., population, data source, comparators) and quality using the Good ReseArch for Comparative Effectiveness (GRACE) Checklist. Investigators evaluated 565 references cited in 27 monographs/therapeutic class reviews from 6 managed care organizations. Therapeutic class reviews mostly cited published clinical trials (35.3%, 155/439), while single-product monographs relied most on manufacturer-supplied information (42.1%, 53/126). Published RWE comprised 4.8% (21/439) of therapeutic class review references, and none (0/126) of the monograph references. Of the 21 RWE studies, 12 were comparative and assessed patient care settings and outcomes typically not included in clinical trials (community ambulatory settings [10], long-term safety [8]). RWE studies most frequently were based on registry data (6), conducted in the United States (6), and funded by the pharmaceutical industry (5). GRACE Checklist ratings suggested the data and methods of these comparative RWE studies were of high quality. RWE was infrequently cited in P&T materials, even among therapeutic class reviews where RWE is more readily available. Although few P&T materials cited RWE, the comparative RWE studies were generally high quality. More research is needed to understand when and what types of real-world studies can more routinely inform coverage and reimbursement decisions. This project was funded by the National Pharmaceutical Council. Hurwitz, Brown, Peters, and Malone have nothing to disclose. Graff is employed by the National Pharmaceutical Council Part of this study was presented as a poster presentation at the AMCP Managed Care & Specialty Pharmacy 2016 Annual Meeting; April 19-22, 2016; San Francisco, CA. Study concept and design were primarily contributed by Malone and Graff, along with Hurwitz and Brown. All authors participated in data collection, and data interpretation was performed by Malone, Hurwitz, and Graff, with assistance from Brown and Peters. The manuscript was written primarily by Hurwitz and Malone, along with Graff, Brown, and Peters, and revised by Malone, Brown, Peters, Hurwitz, and Graff.

From ClinicalTrials.gov trial registry to an analysis-ready database of clinical trial results.

PubMed

Cepeda, M Soledad; Lobanov, Victor; Berlin, Jesse A

2013-04-01

The ClinicalTrials.gov web site provides a convenient interface to look up study results, but it does not allow downloading data in a format that can be readily used for quantitative analyses. To develop a system that automatically downloads study results from ClinicalTrials.gov and provides an interface to retrieve study results in a spreadsheet format ready for analysis. Sherlock(®) identifies studies by intervention, population, or outcome of interest and in seconds creates an analytic database of study results ready for analyses. The outcome classification algorithms used in Sherlock were validated against a classification by an expert. Having a database ready for analysis that can be updated automatically, dramatically extends the utility of the ClinicalTrials.gov trial registry. It increases the speed of comparative research, reduces the need for manual extraction of data, and permits answering a vast array of questions.

The ClinicalTrials.gov results database--update and key issues.

PubMed

Zarin, Deborah A; Tse, Tony; Williams, Rebecca J; Califf, Robert M; Ide, Nicholas C

2011-03-03

The ClinicalTrials.gov trial registry was expanded in 2008 to include a database for reporting summary results. We summarize the structure and contents of the results database, provide an update of relevant policies, and show how the data can be used to gain insight into the state of clinical research. We analyzed ClinicalTrials.gov data that were publicly available between September 2009 and September 2010. As of September 27, 2010, ClinicalTrials.gov received approximately 330 new and 2000 revised registrations each week, along with 30 new and 80 revised results submissions. We characterized the 79,413 registry and 2178 results of trial records available as of September 2010. From a sample cohort of results records, 78 of 150 (52%) had associated publications within 2 years after posting. Of results records available publicly, 20% reported more than two primary outcome measures and 5% reported more than five. Of a sample of 100 registry record outcome measures, 61% lacked specificity in describing the metric used in the planned analysis. In a sample of 700 results records, the mean number of different analysis populations per study group was 2.5 (median, 1; range, 1 to 25). Of these trials, 24% reported results for 90% or less of their participants. ClinicalTrials.gov provides access to study results not otherwise available to the public. Although the database allows examination of various aspects of ongoing and completed clinical trials, its ultimate usefulness depends on the research community to submit accurate, informative data.

Could the erythrocyte indices or serum ferritin predict the therapeutic response to a trial with oral iron during pregnancy? Results from the Accuracy study for Maternal Anaemia diagnosis (AMA).

PubMed

Bresani Salvi, Cristiane Campello; Braga, Maria Cynthia; Figueirôa, José Natal; Batista Filho, Malaquias

2016-08-12

Treatment of maternal iron-deficiency anaemia can reduce risks of prematurity and low birth weight; hence a reliable diagnosis of maternal iron needs is critical. However, erythrocyte indices and serum ferritin have shown a weak correlation with iron status during pregnancy. This study verified the accuracy of those tests to predict the responsiveness to a therapeutic test with oral iron as reference standard for iron deficiency in pregnant women. A prospective diagnostic study phase 3 was conducted in a single prenatal care center in Northeast Brazil. Between August 2011 and October 2012 a consecutive sampling included 187 women in their 2(nd)-3(rd) trimesters of low-risk pregnancy and having anaemia (haemoglobin <11.0 g/dL). Until December 2012, 139 women completed a trial with daily pills of ferrous sulfate (40 mg of iron), during 23 to 125 days. Haemoglobin (Hb), other erythrocyte indices and ferritin (index-tests) were assessed pre-treatment by automated analyzers. Hb was performed also post-treatment to assess the therapeutic response by its post-pretreatment differences. We estimated sensitivity (Se), specificity (Sp), predictive values (PV), likelihood ratios (LR), diagnostic Odds Ratio (OR), area under Receiver Operating Characteristic curve (AUC), accuracy ratio and agreement coefficient of the index-tests against an increase of at least 0.55 Hb Z-score (reference standard test). We calculated the Z-scores according to the reference population from Centers for Disease Control and Prevention. Hb had a mean increase of 0.24 Z-score after 30 iron pills (p 0.013). All index-tests demonstrated PV- above 70 %, PV+ around 40 %, LR around 1.0, and AUC of 0.5 to 0.6. Hb and haematocrit had Se of 50 % (95 % CI 40 to 70); and Sp of 59 % (95 % CI 43 to 74) and 47 % (95 % CI 38 to 57), respectively. Ferritin, Mean Corpuscular Volume, Mean Corpuscular Haemoglobin, Mean Corpuscular Haemoglobin Concentration and Red blood cell Distribution Width had Se below 40 % with Sp above 70 %. Erythrocyte indices and ferritin could not predict the iron needs of anemic pregnant women. Increases of Hb Z-scores after a short treatment with oral iron may be a reliable therapeutic test. World Health Organization International Clinical Trials Registry Platform U1111-1123-2605; Brazilian Registry of Clinical Trials RBR-237wbg , registered 28 July 2011.

eXtended MetaData Registry

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

2006-10-25

The purpose of the eXtended MetaData Registry (XMDR) prototype is to demonstrate the feasibility and utility of constructing an extended metadata registry, i.e., one which encompasses richer classification support, facilities for including terminologies, and better support for formal specification of semantics. The prototype registry will also serve as a reference implementation for the revised versions of ISO 11179, Parts 2 and 3 to help guide production implementations.

A Model-Driven, Science Data Product Registration Service

NASA Astrophysics Data System (ADS)

Hardman, S.; Ramirez, P.; Hughes, J. S.; Joyner, R.; Cayanan, M.; Lee, H.; Crichton, D. J.

2011-12-01

The Planetary Data System (PDS) has undertaken an effort to overhaul the PDS data architecture (including the data model, data structures, data dictionary, etc.) and to deploy an upgraded software system (including data services, distributed data catalog, etc.) that fully embraces the PDS federation as an integrated system while taking advantage of modern innovations in information technology (including networking capabilities, processing speeds, and software breakthroughs). A core component of this new system is the Registry Service that will provide functionality for tracking, auditing, locating, and maintaining artifacts within the system. These artifacts can range from data files and label files, schemas, dictionary definitions for objects and elements, documents, services, etc. This service offers a single reference implementation of the registry capabilities detailed in the Consultative Committee for Space Data Systems (CCSDS) Registry Reference Model White Book. The CCSDS Reference Model in turn relies heavily on the Electronic Business using eXtensible Markup Language (ebXML) standards for registry services and the registry information model, managed by the OASIS consortium. Registries are pervasive components in most information systems. For example, data dictionaries, service registries, LDAP directory services, and even databases provide registry-like services. These all include an account of informational items that are used in large-scale information systems ranging from data values such as names and codes, to vocabularies, services and software components. The problem is that many of these registry-like services were designed with their own data models associated with the specific type of artifact they track. Additionally these services each have their own specific interface for interacting with the service. This Registry Service implements the data model specified in the ebXML Registry Information Model (RIM) specification that supports the various artifacts above as well as offering the flexibility to support customer-defined artifacts. Key features for the Registry Service include: - Model-based configuration specifying customer-defined artifact types, metadata attributes to capture for each artifact type, supported associations and classification schemes. - A REST-based external interface that is accessible via the Hypertext Transfer Protocol (HTTP). - Federation of Registry Service instances allowing associations between registered artifacts across registries as well as queries for artifacts across those same registries. A federation also enables features such as replication and synchronization if desired for a given deployment. In addition to its use as a core component of the PDS, the generic implementation of the Registry Service facilitates its applicability as a core component in any science data archive or science data system.

Clinical trial transparency: an assessment of the disclosure of results of company-sponsored trials associated with new medicines approved recently in Europe.

PubMed

Rawal, Bina; Deane, Bryan R

2014-03-01

Previous studies have raised concerns around the transparency and disclosure rates of clinical trial results on clinical trial registries and in the scientific literature. The objective of this study was to assess the timely disclosure in the public domain of results of company-sponsored clinical trials related to all new medicines approved by the European Medicines Agency (EMA) over a recent 3 year period. The study surveyed various publicly available information sources for both clinical trial registration and disclosure of results (including clinical trial registries, the International Federation of Pharmaceutical Manufacturers and Associations [IFPMA] Clinical Trials Portal, EMA European Public Assessment Reports and PubMed), searched from 27 December 2012 to 31 January 2013. The study covered all 53 new medicines (except vaccines and fixed-dose combinations) approved for marketing by 34 pharmaceutical companies by the EMA in 2009, 2010 and 2011. It included all completed company-sponsored clinical trials conducted in patients and recorded on a clinical trial registry and/or included in an EPAR. OUTCOME MEASURE AND RESULTS: The main outcome measure was the proportion of trials for which results had been disclosed on a registry or in the scientific literature either within 12 months of the later of either first regulatory approval or trial completion, or by 31 January 2013 (end of survey). Of the completed clinical trials associated with all 53 new medicines approved by the EMA between 2009 and 2011, 77% had results disclosed within 12 months. By 31 January 2013, this had increased to 89%. Rates of results disclosure within 12 months were 71%, 81% and 86% for new medicines approved in 2009, 2010 and 2011 respectively. Disclosure increased to 86%, 93% and 91% respectively by 31 January 2013. Although this was a purely quantitative study which did not aim to assess the content of disclosure against any specific requirements, limitations relating to a number of difficulties in finding all relevant data from multiple sources in the public domain were captured. Results of over three-quarters of all company-sponsored clinical trials related to new medicines recently approved by the EMA were disclosed within a year of completion or regulatory approval, and almost 90% were disclosed by 31 January 2013, suggesting transparency is now better than has sometimes been reported previously.

The quality of the reported sample size calculations in randomized controlled trials indexed in PubMed.

PubMed

Lee, Paul H; Tse, Andy C Y

2017-05-01

There are limited data on the quality of reporting of information essential for replication of the calculation as well as the accuracy of the sample size calculation. We examine the current quality of reporting of the sample size calculation in randomized controlled trials (RCTs) published in PubMed and to examine the variation in reporting across study design, study characteristics, and journal impact factor. We also reviewed the targeted sample size reported in trial registries. We reviewed and analyzed all RCTs published in December 2014 with journals indexed in PubMed. The 2014 Impact Factors for the journals were used as proxies for their quality. Of the 451 analyzed papers, 58.1% reported an a priori sample size calculation. Nearly all papers provided the level of significance (97.7%) and desired power (96.6%), and most of the papers reported the minimum clinically important effect size (73.3%). The median (inter-quartile range) of the percentage difference of the reported and calculated sample size calculation was 0.0% (IQR -4.6%;3.0%). The accuracy of the reported sample size was better for studies published in journals that endorsed the CONSORT statement and journals with an impact factor. A total of 98 papers had provided targeted sample size on trial registries and about two-third of these papers (n=62) reported sample size calculation, but only 25 (40.3%) had no discrepancy with the reported number in the trial registries. The reporting of the sample size calculation in RCTs published in PubMed-indexed journals and trial registries were poor. The CONSORT statement should be more widely endorsed. Copyright © 2016 European Federation of Internal Medicine. Published by Elsevier B.V. All rights reserved.

Stroke/Death Rates Following Carotid Artery Stenting and Carotid Endarterectomy in Contemporary Administrative Dataset Registries: A Systematic Review.

PubMed

Paraskevas, K I; Kalmykov, E L; Naylor, A R

2016-01-01

Randomised trials have reported higher stroke/death rates after carotid artery stenting (CAS) versus carotid endarterectomy (CEA). Despite this, the 2011 American Heart Association (AHA) guidelines expanded CAS indications, partly because of the Carotid Revascularization Endarterectomy versus Stenting Trial, but also because of improving outcomes in industry sponsored CAS Registries. The aim of this systematic review was: (i) to compare stroke/death rates after CAS/CEA in contemporary dataset registries, (ii) to examine whether published stroke/death rates after CAS fall within AHA thresholds, and, (iii) to see if there had been a decline (over time) in procedural risk after CAS/CEA. PubMed/Medline, Embase, and Cochrane databases were systematically searched according to the recommendations of the PRISMA statement from January 1, 2008 until February 23, 2015 for administrative dataset registries reporting outcomes after both CEA and CAS. Twenty-one registries reported outcomes involving more than 1,500,000 procedures. Stroke/death after CAS was significantly higher than after CEA in 11/21 registries (52%) involving "average risk for CEA" asymptomatic patients and in 11/18 registries (61%) involving "average risk for CEA" symptomatic patients. In another five registries, CAS was associated with higher stroke/death rates than CEA for both symptomatic and asymptomatic patients, but formal statistical comparison was not reported. CAS was associated with stroke/death rates that exceeded risk thresholds recommended by the AHA in 9/21 registries (43%) involving "average risk for CEA" asymptomatic patients and in 13/18 registries (72%) involving "average risk for CEA" symptomatic patients. In 5/18 registries (28%), the procedural risk after CAS in "average risk" symptomatic patients exceeded 10%. Data from contemporary administrative dataset registries suggest that stroke/death rates following CAS remain significantly higher than after CEA and often exceed accepted AHA thresholds. There was no evidence of a sustained decline in procedural risk after CAS. Copyright © 2015 European Society for Vascular Surgery. Published by Elsevier Ltd. All rights reserved.

Attitudes of people with osteoarthritis towards their conservative management: a systematic review and meta-ethnography.

PubMed

Smith, Toby O; Purdy, Rachel; Lister, Sarah; Salter, Charlotte; Fleetcroft, Robert; Conaghan, Philip G

2014-03-01

This paper determines the perceptions of people diagnosed with osteoarthritis towards their conservative management strategies. A systematic review of the published (AMED, CINAHL, EMBASE, PsychINFO, SportsDisc, MEDLINE, Cochrane Clinical Trials Registry, PubMed) and unpublished/trial registry databases (WHO International Clinical Trials Registry Platform, Current Controlled Trials, the United States National Institute of Health Trials Registry, NIHR Clinical Research Portfolio Database) searched from their inception to July 2013. Eligible studies included those which presented the attitudes or perceptions of people with osteoarthritis towards non-operative management strategies. Study quality was appraised using the CASP and the Gough's weight of evidence appraisal tools. Data were analysed through a meta-ethnography approach. Thirty-three studies including 1,314 people with osteoarthritis were sampled; the majority diagnosed with knee osteoarthritis. The overarching themes indicated people with osteoarthritis delay their diagnosis, opting for self-management and informal information gathering. This informal rather than health professional-led guidance is sought and maintained as an important resource throughout the care of this population and is valued. Diagnosis is sought at a 'critical point'. Healthcare interventions largely provided are poorly perceived. The period of subsequent self-management is an expectation before the inevitable requirement for joint replacement. There remains uncertainty regarding when this is required, but the expected failure of conservative treatment to manage pain and symptoms is common. In conclusion, patients should be enthused towards the principles of self-management and clinicians should not trivialise osteoarthritis. This may provide a more valuable perception of non-operative management to promote its adoption and adherence in managing osteoarthritis.

Use of health plan combined with registry data to predict clinical trial recruitment.

PubMed

Curtis, Jeffrey R; Wright, Nicole C; Xie, Fenglong; Chen, Lang; Zhang, Jie; Saag, Kenneth G; Bharat, Aseem; Kremer, Joel; Cofield, Stacey; Winthrop, Kevin; Delzell, Elizabeth

2014-02-01

Large pragmatic clinical trials (PCTs) are increasingly used to conduct comparative effectiveness research. In the context of planning a safety PCT of the live herpes zoster vaccine in rheumatoid arthritis (RA) patients aged ≥ 50 years receiving anti-tumor necrosis factor (TNF) therapy, we evaluated the use of health plan combined with registry data to assess the feasibility of recruiting the 4000 patients needed for the trial and to facilitate site selection. Using national US data from Medicare, we identified older RA patients who received anti-TNF therapy in the last quarter of 2009. Extrapolations were made from the Medicare patient population to younger patients and those with other types of insurance using the Consortium of Rheumatology Researchers of North America (CORRONA) disease registry. Patients' treating rheumatologists were grouped into practices and sorted by size from the greatest to the least number of eligible patients. Approximately 50,000 RA patients receiving anti-TNF therapy were identified in the Medicare data, distributed across 1980 physician practices. After augmenting Medicare data with information from CORRONA and extrapolating to younger patients and those with other types of insurance, more than 12,000 potentially eligible study subjects were identified from the 50 largest rheumatology practices. Health plan and registry databases appear useful to assess feasibility of large pragmatic trials and to assist in selection of recruitment sites with the greatest number of potentially eligible patients. This novel approach is applicable to trials with simple inclusion/exclusion criteria that can be readily assessed in these data sources.

Impact of searching clinical trial registries in systematic reviews of pharmaceutical treatments: methodological systematic review and reanalysis of meta-analyses.

PubMed

Baudard, Marie; Yavchitz, Amélie; Ravaud, Philippe; Perrodeau, Elodie; Boutron, Isabelle

2017-02-17

Objective  To evaluate the impact of searching clinical trial registries in systematic reviews. Design  Methodological systematic review and reanalyses of meta-analyses. Data sources  Medline was searched to identify systematic reviews of randomised controlled trials (RCTs) assessing pharmaceutical treatments published between June 2014 and January 2015. For all systematic reviews that did not report a trial registry search but reported the information to perform it, the World Health Organization International Trials Registry Platform (WHO ICTRP search portal) was searched for completed or terminated RCTs not originally included in the systematic review. Data extraction  For each systematic review, two researchers independently extracted the outcomes analysed, the number of patients included, and the treatment effect estimated. For each RCT identified, two researchers independently determined whether the results were available (ie, posted, published, or available on the sponsor website) and extracted the data. When additional data were retrieved, we reanalysed meta-analyses and calculated the weight of the additional RCTs and the change in summary statistics by comparison with the original meta-analysis. Results  Among 223 selected systematic reviews, 116 (52%) did not report a search of trial registries; 21 of these did not report the information to perform the search (key words, search date). A search was performed for 95 systematic reviews; for 54 (57%), no additional RCTs were found and for 41 (43%) 122 additional RCTs were identified. The search allowed for increasing the number of patients by more than 10% in 19 systematic reviews, 20% in 10, 30% in seven, and 50% in four. Moreover, 63 RCTs had results available; the results for 45 could be included in a meta-analysis. 14 systematic reviews including 45 RCTs were reanalysed. The weight of the additional RCTs in the recalculated meta-analyses ranged from 0% to 58% and was greater than 10% in five of 14 systematic reviews, 20% in three, and 50% in one. The change in summary statistics ranged from 0% to 29% and was greater than 10% for five of 14 systematic reviews and greater than 20% for two. However, none of the changes to summary effect estimates led to a qualitative change in the interpretation of the results once the new trials were added. Conclusions  Trial registries are an important source for identifying additional RCTs. The additional number of RCTs and patients included if a search were performed varied across systematic reviews. 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.

Measuring clinical trial transparency: an empirical analysis of newly approved drugs and large pharmaceutical companies

PubMed Central

Miller, Jennifer E; Wilenzick, Marc; Ritcey, Nolan; Ross, Joseph S; Mello, Michelle M

2017-01-01

Objectives To define a series of clinical trial transparency measures and apply them to large pharmaceutical and biotechnology companies and their 2014 FDA-approved drugs. Design Cross-sectional descriptive analysis of all clinical trials supporting 2014 Food and Drugs Administration (FDA)-approved new drug applications (NDAs) for novel drugs sponsored by large companies. Data sources Data from over 45 sources, including Drugs@FDA.gov, ClinicalTrials.gov, corporate and international registries; PubMed, Google Scholar, EMBASE, corporate press releases, Securities and Exchange Commission (SEC) filings and personal communications with drug manufacturers. Outcome measures Trial registration, results reporting, clinical study report (CSR) synopsis sharing, biomedical journal publication, and FDA Amendments Acts (FDAAA) compliance, analysed on the drug level. Results The FDA approved 19 novel new drugs, sponsored by 11 large companies, involving 553 trials, in 2014. We analysed 505 relevant trials. Per drug, a median of 100% (IQR 86%–100%) of trials in patients were registered, 71% (IQR 57%–100%) reported results or shared a CSR synopsis, 80% (70%–100%) were published and 96% (80%–100%) were publicly available in some form by 13 months after FDA approval. Disclosure rates were lower at FDA approval (65%) and improved significantly by 6 months post FDA approval. Per drug, a median of 100% (IQR 75%–100%) of FDAAA-applicable trials were compliant. Half of reviewed drugs had publicly disclosed results for all trials in patients in our sample. One trial was uniquely registered in a corporate registry, and not ClinicalTrials.gov; 0 trials were uniquely registered in international registries. Conclusions Among large pharmaceutical companies and new drugs, clinical trial transparency is high based on several standards, although opportunities for improvement remain. Transparency is markedly higher for trials in patients than among all trials supporting drug approval, including trials in healthy volunteers. Ongoing efforts to publicly track companies’ transparency records and recognise exemplary companies may encourage further progress. PMID:29208616

Prospective registration of clinical trials in India: strategies, achievements & challenges.

PubMed

Tharyan, Prathap

2009-02-01

This paper traces the development of the Clinical Trial Registry-India (CTRI) against the backdrop of the inequities in healthcare and the limitations in the design, conduct, regulation, oversight and reporting of clinical trials in India. It describes the scope and goals of the CTRI, the data elements it seeks and the process of registering clinical trials. It reports progress in trial registration in India and discusses the challenges in ensuring that healthcare decisions are informed by all the evidence. A descriptive survey of developments in clinical trial registration in India from publications in the Indian medical literature supplemented by first hand knowledge of these developments and an evaluation of how well clinical trials registered in the CTRI up to 10 January, 2009 comply with the requirements of the CTRI and the World Health Organization's International Clinical Trial Registry (WHO ICTRP). Considerable inequities exist within the Indian health system. Deficiencies in healthcare provision and uneven regulation of, and access to, affordable healthcare co-exists with a large private health system of uneven quality. India is now a preferred destination for outsourced clinical trials but is plagued by poor ethical oversight of the many trial sites and scant information of their existence. The CTRI's vision of conforming to international requirements for transparency and accountability but also using trial registration as a means of improving trial design, conduct and reporting led to the selection of registry-specific dataset items in addition to those endorsed by the WHO ICTRP. Compliance with these requirements is good for the trials currently registered but these trials represent only a fraction of the trials in progress in India. Prospective trial registration is a reality in India. The challenges facing the CTRI include better engagement with key stakeholders to ensure increased prospective registration of clinical trials and utilization of existing legislative opportunities to complement these efforts. © 2009 Blackwell Publishing Asia Pty Ltd and Chinese Cochrane Center, West China Hospital of Sichuan University.

Exclusion of Older Patients From Ongoing Clinical Trials for Hematological Malignancies: An Evaluation of the National Institutes of Health Clinical Trial Registry

PubMed Central

Stauder, Reinhard; van Munster, Barbara C.

2014-01-01

Introduction. Cancer societies, research cooperatives, and countless publications have urged the development of clinical trials that facilitate the inclusion of older patients and those with comorbidities. We set out to determine the characteristics of currently recruiting clinical trials with hematological patients to assess their inclusion and exclusion of elderly patients. Methods. The NIH clinical trial registry was searched on July 1, 2013, for currently recruiting phase I, II or III clinical trials with hematological malignancies. Trial characteristics and study objectives were extracted from the registry website. Results. Although 5% of 1,207 included trials focused exclusively on elderly or unfit patients, 69% explicitly or implicitly excluded older patients. Exclusion based on age was seen in 27% of trials, exclusion based on performance status was seen in 16%, and exclusion based on stringent organ function restrictions was noted in 51%. One-third of the studies that excluded older patients based on age allowed inclusion of younger patients with poor performance status; 8% did not place any restrictions on organ function. Over time, there was a shift from exclusion based on age (p value for trend <.001) toward exclusion based on organ function (p = .2). Industry-sponsored studies were least likely to exclude older patients (p < .001). Conclusion. Notably, 27% of currently recruiting clinical trials for hematological malignancies use age-based exclusion criteria. Although physiological reserves diminish with age, the heterogeneity of the elderly population does not legitimize exclusion based on chronological age alone. Investigators should critically review whether sufficient justification exists for every exclusion criterion before incorporating it in trial protocols. PMID:25170014

Exclusion of older patients from ongoing clinical trials for hematological malignancies: an evaluation of the National Institutes of Health Clinical Trial Registry.

PubMed

Hamaker, Marije E; Stauder, Reinhard; van Munster, Barbara C

2014-10-01

Cancer societies, research cooperatives, and countless publications have urged the development of clinical trials that facilitate the inclusion of older patients and those with comorbidities. We set out to determine the characteristics of currently recruiting clinical trials with hematological patients to assess their inclusion and exclusion of elderly patients. The NIH clinical trial registry was searched on July 1, 2013, for currently recruiting phase I, II or III clinical trials with hematological malignancies. Trial characteristics and study objectives were extracted from the registry website. Although 5% of 1,207 included trials focused exclusively on elderly or unfit patients, 69% explicitly or implicitly excluded older patients. Exclusion based on age was seen in 27% of trials, exclusion based on performance status was seen in 16%, and exclusion based on stringent organ function restrictions was noted in 51%. One-third of the studies that excluded older patients based on age allowed inclusion of younger patients with poor performance status; 8% did not place any restrictions on organ function. Over time, there was a shift from exclusion based on age (p value for trend <.001) toward exclusion based on organ function (p = .2). Industry-sponsored studies were least likely to exclude older patients (p < .001). Notably, 27% of currently recruiting clinical trials for hematological malignancies use age-based exclusion criteria. Although physiological reserves diminish with age, the heterogeneity of the elderly population does not legitimize exclusion based on chronological age alone. Investigators should critically review whether sufficient justification exists for every exclusion criterion before incorporating it in trial protocols. ©AlphaMed Press.

The ClinicalTrials.gov Results Database — Update and Key Issues

PubMed Central

Zarin, Deborah A.; Tse, Tony; Williams, Rebecca J.; Califf, Robert M.; Ide, Nicholas C.

2011-01-01

BACKGROUND The ClinicalTrials.gov trial registry was expanded in 2008 to include a database for reporting summary results. We summarize the structure and contents of the results database, provide an update of relevant policies, and show how the data can be used to gain insight into the state of clinical research. METHODS We analyzed ClinicalTrials.gov data that were publicly available between September 2009 and September 2010. RESULTS As of September 27, 2010, ClinicalTrials.gov received approximately 330 new and 2000 revised registrations each week, along with 30 new and 80 revised results submissions. We characterized the 79,413 registry and 2178 results of trial records available as of September 2010. From a sample cohort of results records, 78 of 150 (52%) had associated publications within 2 years after posting. Of results records available publicly, 20% reported more than two primary outcome measures and 5% reported more than five. Of a sample of 100 registry record outcome measures, 61% lacked specificity in describing the metric used in the planned analysis. In a sample of 700 results records, the mean number of different analysis populations per study group was 2.5 (median, 1; range, 1 to 25). Of these trials, 24% reported results for 90% or less of their participants. CONCLUSIONS ClinicalTrials.gov provides access to study results not otherwise available to the public. Although the database allows examination of various aspects of ongoing and completed clinical trials, its ultimate usefulness depends on the research community to submit accurate, informative data. PMID:21366476

Desmopressin acetate (DDAVP) for preventing and treating acute bleeds during pregnancy in women with congenital bleeding disorders.

PubMed

Karanth, Laxminarayan; Barua, Ankur; Kanagasabai, Sachchithanantham; Nair, Sreekumar

2015-09-09

Congenital bleeding disorders can cause obstetric haemorrhage during pregnancy, labour and following delivery. Desmopressin acetate is found to be an effective drug which can reduce the risk of haemorrhage and can also stop bleeding in certain congenital bleeding disorders. Its use in pregnancy has been controversial. Hence beneficial and adverse effects of desmopressin acetate in these groups of pregnant women should be evaluated.This is an update of a Cochrane review first published in 2013. To determine the efficacy of desmopressin acetate in preventing and treating acute bleeds during pregnancy in women with congenital bleeding disorders. We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group's Coaguopathies Trials Register comprising references identified from comprehensive electronic database searches and handsearches of relevant and abstract books of conferences proceedings. We also searched for any randomised controlled trials in a registry of ongoing trials and the reference lists of relevant articles and reviews.Date of most recent search: 18 June 2015. Randomised and quasi-randomised controlled trials investigating the efficacy of desmopressin acetate versus tranexamic acid or factor VIII or rFactor VII or fresh frozen plasma in preventing and treating congenital bleeding disorders during pregnancy were eligible. No trials matching the selection criteria were eligible for inclusion. No trials matching the selection criteria were eligible for inclusion. The review did not identify any randomised controlled trials investigating the relative effectiveness of desmopressin acetate for bleeding during pregnancy in women with congenital bleeding disorders. In the absence of high quality evidence, clinicians need to use their clinical judgement and lower level evidence (e.g. from observational trials) to decide whether or not to treat women with congenital bleeding disorders with desmopressin acetate.Given the ethical considerations, future randomised controlled trials are unlikely. However, other high quality controlled studies (such as risk allocation designs, sequential design, parallel cohort design) to investigate the risks and benefits of using desmopressin acetate in this population are needed.

Desmopressin acetate (DDAVP) for preventing and treating acute bleeds during pregnancy in women with congenital bleeding disorders.

PubMed

Karanth, Laxminarayan; Barua, Ankur; Kanagasabai, Sachchithanantham; Nair, N S

2013-04-30

Congenital bleeding disorders can cause obstetric haemorrhage during pregnancy, labour and following delivery. Desmopressin acetate is found to be an effective drug which can reduce the risk of haemorrhage and can also stop bleeding in certain congenital bleeding disorders. Its use in pregnancy has been controversial. Hence beneficial and adverse effects of desmopressin acetate in these groups of pregnant women should be evaluated. To determine the efficacy of desmopressin acetate in preventing and treating acute bleeds during pregnancy in women with congenital bleeding disorders. We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group's Coaguopathies Trials Register comprising references identified from comprehensive electronic database searches and handsearches of relevant and abstract books of conferences proceedings. We also searched for any randomised controlled trials in a registry of ongoing trials and the reference lists of relevant articles and reviews.Date of most recent search: 28 February 2013. Randomised and quasi-randomised controlled trials investigating the efficacy of desmopressin acetate versus tranexamic acid or factor VIII or rFactor VII or fresh frozen plasma in preventing and treating congenital bleeding disorders during pregnancy were eligible. No trials matching the selection criteria were eligible for inclusion. No trials matching the selection criteria were eligible for inclusion. The review did not identify any randomised controlled trials investigating the relative effectiveness of desmopressin acetate for bleeding during pregnancy in women with congenital bleeding disorders. In the absence of high quality evidence, clinicians need to use their clinical judgement and lower level evidence (e.g. from observational trials) to decide whether or not to treat women with congenital bleeding disorders with desmopressin acetate.Given the ethical considerations, future randomised controlled trials are unlikely. However, other high quality controlled studies (such as risk allocation designs, sequential design, parallel cohort design) to investigate the risks and benefits of using desmopressin acetate in this population are needed.

A randomized controlled trial of the effectiveness of a pre-recruitment primer letter to increase participation in a study of colorectal screening and surveillance.

PubMed

Paul, Christine; Courtney, Ryan; Sanson-Fisher, Rob; Carey, Mariko; Hill, David; Simmons, Jody; Rose, Shiho

2014-04-01

Recruiting cancer patients is a barrier often encountered in research trials. However, very few randomized trials explore strategies to improve participation rates. The purpose of this study was to evaluate the effectiveness of a pre-recruitment primer letter to recruit persons diagnosed with colorectal cancer for a research trial. Potentially eligible participants were identified by the Victorian Cancer Registry. A total of 1,062 participants were randomized to receive either a mailed explanatory primer letter designed to encourage research participation, or no primer letter. Two weeks after the intervention, the Victorian Cancer Registry sought permission from patients to release their contact details to researchers. Those who agreed were contacted and invited to the study. Pre-recruitment encouragement was not effective at increasing recruitment, with no significant differences demonstrated between experimental groups. Overall, 40% (n = 425) consented to participate, 25% (n = 243) refused and 35% (n = 394) did not respond. While this study demonstrated disappointing outcomes, pre-recruitment letters should not be ruled out as an approach altogether. Rather, future research should explore whether other factors to increase motivation, such as intensity and timing, are feasible and acceptable for contacting cancer patients. Australian and New Zealand Clinical Trials Registry, ACTRN12609000628246.

Genetics Home Reference: Blau syndrome

MedlinePlus

... inherited version of the disorder called early-onset sarcoidosis. Related Information What does it mean if a ... Genetic Testing Registry: Blau syndrome Genetic Testing Registry: Sarcoidosis, early-onset Other Diagnosis and Management Resources (2 ...

Genetics Home Reference: prostate cancer

MedlinePlus

... prostate cancer Genetic Testing Registry: Prostate cancer aggressiveness quantitative trait locus on chromosome 19 Genetic Testing Registry: ... OMIM (25 links) PROSTATE CANCER PROSTATE CANCER AGGRESSIVENESS QUANTITATIVE TRAIT LOCUS ON CHROMOSOME 19 PROSTATE CANCER ANTIGEN ...

Streamlining cardiovascular clinical trials to improve efficiency and generalisability.

PubMed

Zannad, Faiez; Pfeffer, Marc A; Bhatt, Deepak L; Bonds, Denise E; Borer, Jeffrey S; Calvo-Rojas, Gonzalo; Fiore, Louis; Lund, Lars H; Madigan, David; Maggioni, Aldo Pietro; Meyers, Catherine M; Rosenberg, Yves; Simon, Tabassome; Stough, Wendy Gattis; Zalewski, Andrew; Zariffa, Nevine; Temple, Robert

2017-08-01

Controlled trials provide the most valid determination of the efficacy and safety of an intervention, but large cardiovascular clinical trials have become extremely costly and complex, making it difficult to study many important clinical questions. A critical question, and the main objective of this review, is how trials might be simplified while maintaining randomisation to preserve scientific integrity and unbiased efficacy assessments. Experience with alternative approaches is accumulating, specifically with registry-based randomised controlled trials that make use of data already collected. This approach addresses bias concerns while still capitalising on the benefits and efficiencies of a registry. Several completed or ongoing trials illustrate the feasibility of using registry-based controlled trials to answer important questions relevant to daily clinical practice. Randomised trials within healthcare organisation databases may also represent streamlined solutions for some types of investigations, although data quality (endpoint assessment) is likely to be a greater concern in those settings. These approaches are not without challenges, and issues pertaining to informed consent, blinding, data quality and regulatory standards remain to be fully explored. Collaboration among stakeholders is necessary to achieve standards for data management and analysis, to validate large data sources for use in randomised trials, and to re-evaluate ethical standards to encourage research while also ensuring that patients are protected. The rapidly evolving efforts to streamline cardiovascular clinical trials have the potential to lead to major advances in promoting better care and outcomes for patients with cardiovascular disease. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

The Brustkrebs-Studien.de website for breast cancer patients: User acceptance of a German internet portal offering information on the disease and treatment options, and a clinical trials matching service

PubMed Central

2010-01-01

Background The internet portal http://www.brustkrebs-studien.de (BKS) was launched in 2000 by the German Society of Senology (DGS) and the Baden-Württemberg Institute for Women's Health (IFG) to provide expert-written information on breast cancer online and to encourage and facilitate the participation of breast cancer patients in clinical trials. We describe the development of BKS and its applications, and report on website statistics and user acceptance. Methods Existing registries, including ClinicalTrials.gov, were analysed before we designed BKS, which combines a trial registry, a knowledge portal, and an online second opinion service. An advisory board guided the process. Log files and patient enquiries for trial participation and second opinions were analysed. A two-week user satisfaction survey was conducted online. Results During 10/2005-06/2010, the portal attracted 702,655 visitors, generating 15,507,454 page views. By 06/2010, the website's active scientific community consisted of 189 investigators and physicians, and the registry covered 163 clinical trial protocols. In 2009, 143 patients requested trial enrolment and 119 sought second opinions or individual treatment advice from the expert panel. During the two-week survey in 2008, 5,702 BKS visitors submitted 507 evaluable questionnaires. Portal acceptance was high. Respondents trusted information correctness (80%), welcomed self-matching to clinical trials (79%) and planned to use the portal in the future (76%) and recommend it to others (81%). Conclusions BKS is an established and trusted breast cancer information platform offering up-to-date resources and protocols to the growing physician and patient community to encourage participation in clinical trials. Further studies are needed to assess potential increases in trial enrolment by eligibility matching services. PMID:21126358

Genetics Home Reference: mitochondrial complex III deficiency

MedlinePlus

... DNA packaged in chromosomes within the cell nucleus (nuclear DNA). It is not clear why the severity ... deficiency Genetic Testing Registry: Mitochondrial complex III deficiency, nuclear type 2 Genetic Testing Registry: Mitochondrial complex III ...

The use of different reference foods in determining the glycemic index of starchy and non-starchy test foods.

PubMed

Venn, Bernard J; Kataoka, Minako; Mann, Jim

2014-05-31

Glycemic index (GI) is intended to be a property of food but some reports are suggestive that GI is influenced by participant characteristics when glucose is used as a reference. To examine the influence of different reference foods on observed GI. The GIs of five varieties of rice and a sugary beverage (LoGiCane™) were tested in 31 European and 32 Chinese participants using glucose or jasmine rice as reference foods. The GIs of two ready-to-eat breakfast cereals (Kellogg's cornflakes and Sustain) were tested in 20 younger and 60 older people using glucose or Sustain as reference foods. The GIs of rice tended to be higher in the Chinese compared with the Europeans when glucose was used as a reference (jasmine 80 vs 68, P = 0.033; basmati 67 vs 57, P = 0.170; brown 78 vs 65, P = 0.054; Doongara 67 vs 55, P = 0.045; parboiled 72 vs 57, P = 0.011). There were no between-group differences in GI when jasmine rice was the reference. The GIs of breakfast cereals tended to be lower in younger compared with older groups (cornflakes 64 vs 81, P = 0.008; Sustain 56 vs 66, P = 0.054). There was no between-group difference in the GI of cornflakes when Sustain was the reference (cornflakes 115 vs 120, P = 0.64). There was no ethnic difference in GI when glucose was the reference for another sugary food (LoGiCane™ 60 vs 62; P = 0.69). A starchy reference may be more appropriate than a glucose beverage when attempting to derive universally applicable GI values of starchy foods. The Chinese/European trial is registered with the Australian New Zealand Clinical Trials Registry as ACTRN12612000519853.

Rationale and design of a large registry on renal denervation: the Global SYMPLICITY registry.

PubMed

Böhm, Michael; Mahfoud, Felix; Ukena, Christian; Bauer, Axel; Fleck, Eckart; Hoppe, Uta C; Kintscher, Ulrich; Narkiewicz, Krzysztof; Negoita, Manuela; Ruilope, Luis; Rump, L Christian; Schlaich, Markus; Schmieder, Roland; Sievert, Horst; Weil, Joachim; Williams, Bryan; Zeymer, Uwe; Mancia, Giuseppe

2013-08-22

Hypertension is a global healthcare concern associated with a wide range of comorbidities. The recognition that elevated sympathetic drive plays an important role in the pathogenesis of hypertension led to the use of renal artery denervation to interrupt the efferent and afferent sympathetic nerves between the brain and kidneys to lower blood pressure. Clinical trials of the Symplicity™ renal denervation system have demonstrated that radiofrequency ablation of renal artery nerves is safe and significantly lowers blood pressure in patients with severe resistant (systolic BP >160 mmHg) hypertension. Smaller ancillary studies in hypertensive patients suggest a benefit from renal denervation in a variety of conditions such as chronic kidney disease, glucose intolerance, sleep apnoea and heart failure. The Global SYMPLICITY registry, which incorporates the GREAT SYMPLICITY registry initiated in Germany, is being conducted worldwide to evaluate the safety and efficacy of treatment with the Symplicity renal denervation system in real-world uncontrolled hypertensive patients, looking first at subjects with severe resistant hypertension to confirm the results of prior clinical trials, but then also subjects with a wider range of baseline blood pressure and coexisting comorbidities. The rationale, design and first baseline data from the Global SYMPLICITY registry are presented.

Analysis of Existing Guidelines for the Systematic Planning Process of Clinical Registries.

PubMed

Löpprich, Martin; Knaup, Petra

2016-01-01

Clinical registries are a powerful method to observe the clinical practice and natural disease history. In contrast to clinical trials, where guidelines and standardized methods exist and are mandatory, only a few initiatives have published methodological guidelines for clinical registries. The objective of this paper was to review these guidelines and systematically assess their completeness, usability and feasibility according to a SWOT analysis. The results show that each guideline has its own strengths and weaknesses. While one supports the systematic planning process, the other discusses clinical registries in great detail. However, the feasibility was mostly limited and the special requirements of clinical registries, their flexible, expandable and adaptable technological structure was not addressed consistently.

Postmarket studies required by the US Food and Drug Administration for new drugs and biologics approved between 2009 and 2012: cross sectional analysis.

PubMed

Wallach, Joshua D; Egilman, Alexander C; Dhruva, Sanket S; McCarthy, Margaret E; Miller, Jennifer E; Woloshin, Steven; Schwartz, Lisa M; Ross, Joseph S

2018-05-24

To characterize postmarketing requirements for new drugs and biologics approved by the US Food and Drug Administration (FDA), and to examine rates and timeliness of registration, results reporting, and publication of required prospective cohort studies, registries, and clinical trials. Cross sectional analysis. Postmarketing requirements for all new drugs and biologics approved by the FDA between 1 January 2009 and 31 December 2012, with follow-up up to 15 November 2017. Postmarketing requirements and their characteristics known at the time of FDA approval, including FDA authority, study design, and study characteristics. Rates and timeliness of registration and results reporting on ClinicalTrials.gov and publication in peer reviewed journals of required prospective cohort studies, registries, and clinical trials. Between 2009 and 12, the FDA approved 97 new drugs and biologics for 106 indications with at least one postmarketing requirement at the time of first approval, for a total of 437 postmarketing requirements. Postmarket study descriptions were short (median word count 44 (interquartile range 29-71)) and often lacked information to determine an up to date progress (131 (30%)). 220 (50.3%) postmarketing requirements were for new animal or other studies (including pharmacokinetic studies); 134 (30.7%) were for prospective cohort studies, registries, and clinical trials; and 83 (19.0%) were for secondary analyses or follow-up studies. Of 110 clinical trials, 38 (34.5%), 44 (40.0%), 62 (56.4%), 66 (60.0%), and 98 (89.1%) did not report enough information to establish use of randomization, comparator type, allocation, outcome, and number of patients to be enrolled, respectively. Of 134 required prospective cohort studies, registries, and clinical trials, 102 (76.1%) were registered on ClinicalTrials.gov; of 50 registered and completed studies, 36 (72.0%) had reported results on ClinicalTrials.gov. Among 65 completed studies, 47 (72.3%) had either reported results or were published a median of 47 months (interquartile range 32-67) after FDA approval. 32 (68.1%) of these 47 studies did not report results publicly by the time of their original FDA report submission deadline. Postmarketing requirements for new drugs and biologics were often briefly described and did not contain enough information to characterize study designs. Approximately three quarters of postmarketing requirements for prospective cohort studies, registries, and clinical trials were registered on ClinicalTrials.gov, and nearly three quarters of completed studies reported results or were published, suggesting that at least a quarter of these required studies are not being publicly disseminated. 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.

Genetics Home Reference: Fanconi anemia

MedlinePlus

... D1 Genetic Testing Registry: Fanconi anemia, complementation group D2 Genetic Testing Registry: Fanconi anemia, complementation group E ... ANEMIA, COMPLEMENTATION GROUP D1 FANCONI ANEMIA, COMPLEMENTATION GROUP D2 FANCONI ANEMIA, COMPLEMENTATION GROUP E FANCONI ANEMIA, COMPLEMENTATION ...

CNS sites cooperate to detect duplicate subjects with a clinical trial subject registry.

PubMed

Shiovitz, Thomas M; Wilcox, Charles S; Gevorgyan, Lilit; Shawkat, Adnan

2013-02-01

To report the results of the first 1,132 subjects in a pilot project where local central nervous system trial sites collaborated in the use of a subject database to identify potential duplicate subjects. Central nervous system sites in Los Angeles and Orange County, California, were contacted by the lead author to seek participation in the project. CTSdatabase, a central nervous system-focused trial subject registry, was utilized to track potential subjects at pre-screen. Subjects signed an institutional review board-approved authorization prior to participation, and site staff entered their identifiers by accessing a website. Sites were prompted to communicate with each other or with the database administrator when a match occurred between a newly entered subject and a subject already in the database. Between October 30, 2011, and August 31, 2012, 1,132 subjects were entered at nine central nervous system sites. Subjects continue to be entered, and more sites are anticipated to begin participation by the time of publication. Initially, there were concerns at a few sites over patient acceptance, financial implications, and/or legal and privacy issues, but these were eventually overcome. Patient acceptance was estimated to be above 95 percent. Duplicate Subjects (those that matched several key identifiers with subjects at different sites) made up 7.78 percent of the sample and Certain Duplicates (matching identifiers with a greater than 1 in 10 million likelihood of occurring by chance in the general population) accounted for 3.45 percent of pre-screens entered into the database. Many of these certain duplicates were not consented for studies because of the information provided by the registry. The use of a clinical trial subject registry and cooperation between central nervous system trial sites can reduce the number of duplicate and professional subjects entering clinical trials. To be fully effective, a trial subject database could be integrated into protocols across pharmaceutical companies, thereby mandating site participation and increasing the likelihood that duplicate subjects will be removed before they enter (and negatively affect) clinical trials.

Use of ClinicalTrials.gov to estimate condition-specific nocebo effects and other factors affecting outcomes of analgesic trials.

PubMed

Cepeda, M Soledad; Lobanov, Victor; Berlin, Jesse A

2013-04-01

ClinicalTrials.gov is a registry and results database of federally and privately supported clinical trials conducted worldwide. We sought to answer: what are the characteristics of pain trials; how frequently are these trials stopped and why; what is the magnitude of attrition due to lack of efficacy or adverse events; and whether the withdrawal rates depend on pain syndrome. To facilitate this and subsequent studies, we have developed a system called Sherlock that automatically downloads data from ClinicalTrials.gov into a relational database. We included pain interventional trials. To evaluate attrition, we restricted consideration to prospective randomized, parallel, double-blind, placebo-controlled trials. Of the 82,867 trials, 6% reported results and 5.6% terminated before the planned number of subjects was accrued. Of these early terminations, 38% were due to enrollment difficulties. In the placebo arms, 3.8% of participants withdrew due to lack of efficacy and 4.9% due to adverse events, with proportions differing among pain conditions. Compared with migraine trials, in fibromyalgia trials 5.1% more participants withdrew due to lack of efficacy (95% confidence interval [CI], 2.5-7.8%), and 6.4% more withdrew due to adverse events (95% CI, 4.3-8.6%). Nonsteroidal anti-inflammatory drugs were the treatment class with the lowest adverse events withdrawals. Recruitment challenges account for the largest proportion of noncompleted trials. Attrition rates differ across pain conditions. Migraine studies had the lowest withdrawal rate. Tools like Sherlock facilitate conducting research in the ClinicalTrials.gov registry. ClinicalTrials.gov registry enables researchers to get a snapshot of a specific field and observe changes over time in trial design, including numbers of subjects accrued, and it can inform clinical trial design. We learned that recruitment challenges account for the largest proportion of noncompleted trials, attrition rates differed across pain conditions, and migraine studies had the lowest withdrawal rate. Copyright © 2013 American Pain Society. Published by Elsevier Inc. All rights reserved.

Why does primary angioplasty not work in registries? Quantifying the susceptibility of real-world comparative effectiveness data to allocation bias.

PubMed

Sen, Sayan; Davies, Justin E; Malik, Iqbal S; Foale, Rodney A; Mikhail, Ghada W; Hadjiloizou, Nearchos; Hughes, Alun; Mayet, Jamil; Francis, Darrel P

2012-11-01

Meta-analysis of registries (comparative effectiveness research) shows that primary angioplasty and fibrinolysis have equivalent real-world survival. Yet, randomized, controlled trials consistently find primary angioplasty superior. Can unequal allocation of higher-risk patients in registries have masked primary angioplasty benefit? First, we constructed a model to demonstrate the potential effect of allocation bias. We then analyzed published registries (55022 patients) for allocation of higher-risk patients (Killip class ≥1) to determine whether the choice of reperfusion therapy was affected by the risk level of the patient. Meta-regression was used to examine the relationship between differences in allocation of high-risk patient to primary angioplasty or fibrinolysis and mortality. Initial modeling suggested that registry outcomes are sensitive to allocation bias of high-risk patients. Across the registries, the therapy receiving excess high-risk patients had worse mortality. Unequal distribution of high-risk status accounted for most of the between-registry variance (adjusted R(2)(meta)=83.1%). Accounting for differential allocation of higher-risk patients, primary angioplasty gave 22% lower mortality (odds ratio, 0.78; 95% confidence interval, 0.64-0.97; P=0.029). We derive a formula, called the number needed to abolish, highlighting situations in which comparative effectiveness studies are particularly vulnerable to this bias. In ST-segment elevation myocardial infarction, clinicians' preference for management of a few high-risk patients can shift mortality substantially. Comparative effectiveness research in any disease is vulnerable to this, especially diseases with an immediately identifiable high-risk subgroup that clinicians prefer to allocate to 1 therapy. For this reason, preliminary indications from registry-based comparative effectiveness research should be definitively tested by randomized, controlled trials.

Iliac Arteries: How Registries Can Help Improve Outcomes

PubMed Central

Tapping, Charles Ross; Uberoi, Raman

2014-01-01

There are many publications reporting excellent short and long-term results with endovascular techniques. Patients included in trials are often highly selected and may not represent real world practice. Registries are important to interventional radiologists for several reasons; they reflect prevailing practice and can be used to establish real world standards of care and safety profiles. This information allows individuals and centers to evaluate their outcomes compared with national norms. The British Iliac Angioplasty and Stenting (BIAS) registry is an example of a mature registry that has been collecting data since 2000 and has been reporting outcomes since 2001. This article discusses the evidence to support both endovascular and surgical intervention for aortoiliac occlusive disease, the role of registries, and optimal techniques for aortoiliac intervention. PMID:25435659

Measuring clinical trial transparency: an empirical analysis of newly approved drugs and large pharmaceutical companies.

PubMed

Miller, Jennifer E; Wilenzick, Marc; Ritcey, Nolan; Ross, Joseph S; Mello, Michelle M

2017-12-05

To define a series of clinical trial transparency measures and apply them to large pharmaceutical and biotechnology companies and their 2014 FDA-approved drugs. Cross-sectional descriptive analysis of all clinical trials supporting 2014 Food and Drugs Administration (FDA)-approved new drug applications (NDAs) for novel drugs sponsored by large companies. Data from over 45 sources, including Drugs@FDA.gov, ClinicalTrials.gov, corporate and international registries; PubMed, Google Scholar, EMBASE, corporate press releases, Securities and Exchange Commission (SEC) filings and personal communications with drug manufacturers. Trial registration, results reporting, clinical study report (CSR) synopsis sharing, biomedical journal publication, and FDA Amendments Acts (FDAAA) compliance, analysed on the drug level. The FDA approved 19 novel new drugs, sponsored by 11 large companies, involving 553 trials, in 2014. We analysed 505 relevant trials. Per drug, a median of 100% (IQR 86%-100%) of trials in patients were registered, 71% (IQR 57%-100%) reported results or shared a CSR synopsis, 80% (70%-100%) were published and 96% (80%-100%) were publicly available in some form by 13 months after FDA approval. Disclosure rates were lower at FDA approval (65%) and improved significantly by 6 months post FDA approval. Per drug, a median of 100% (IQR 75%-100%) of FDAAA-applicable trials were compliant. Half of reviewed drugs had publicly disclosed results for all trials in patients in our sample. One trial was uniquely registered in a corporate registry, and not ClinicalTrials.gov; 0 trials were uniquely registered in international registries. Among large pharmaceutical companies and new drugs, clinical trial transparency is high based on several standards, although opportunities for improvement remain. Transparency is markedly higher for trials in patients than among all trials supporting drug approval, including trials in healthy volunteers. Ongoing efforts to publicly track companies' transparency records and recognise exemplary companies may encourage further progress. © 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.

How does a clinical trial fit into the real world? The RELAX-AHF study population into the EAHFE registry.

PubMed

Miró, Òscar; Gil, Víctor; Müller, Christian; Mebazaa, Alexander; Bueno, Héctor; Martín-Sánchez, Francisco Javier; Herrero, Pablo; Jacob, Javier; Llorens, Pere

2015-10-01

To test how accurate the recently published RELAX-AHF trial was in recruiting real-world patients with acute-decompensated heart failure (ADHF). We compared clinical and outcome data of patients receiving serelaxin in the RELAX-AHF trial (RELAX group, n = 581) with patients included in the EAHFE registry [5497 ADHF from 29 Spanish emergency departments (EDs)]. The EAHFE registry was split into two groups: EAHFE-non-RELAX (patients not fulfilling the RELAX-AHF inclusion criteria; n = 3205, 58.3 %) and EAHFE-RELAX A (patients fulfilling RELAX-AHF inclusion criteria; n = 2292, 41.7 %). The latter group was further refined by also applying exclusion criteria (EAHFE-RELAX B; n = 964, 17.4 %). Both EAHFE-RELAX groups differed from the EAHFE-non-RELAX group in multiple aspects, with the lower the proportion of patients with implantable cardiac defibrillator and with pulmonary diseases the greater the differences found. The RELAX group, compared with the EAHFE-RELAX groups, significantly included fewer females, younger patients, less in NYHA class I/II, less with implantable cardiac defibrillator and on beta-blocker treatment, and patients had lower systolic blood pressure and cardiac and respiratory rates at ED arrival. The EAHFE-RELAX groups had a significantly lower all-cause mortality than EAHFE-non-RELAX group, and qualitative analysis suggested that EAHFE-RELAX groups had a higher mortality than the RELAX group. Patients included in the RELAX-AHF trial showed unanticipated differences when compared with a population from the EAHFE registry fulfilling very similar inclusion and exclusion criteria.

Safety of the HPV Bivalent and Quadrivalent Vaccines During Pregnancy.

PubMed

Forinash, Alicia B; Yancey, Abigail M; Pitlick, Jamie M; Myles, Thomas D

2011-02-01

To evaluate the safety of the human papillomavirus (HPV) bivalent and quadrivalent vaccines in pregnancy. PubMed (1966-August 2010) was searched using the terms human papillomavirus, human papillomavirus vaccine, and pregnancy. References were reviewed for relevant information. All studies including humans that were published in English with data describing HPV vaccine administration in pregnancy were evaluated. Two combined analyses of 7 Phase 3 efficacy trials have retrospectively evaluated the safety of unintentional administration of either the bivalent (n = 1786) or quadrivalent (n = 2085) HPV vaccine during pregnancy. In addition, postmarketing pregnancy registry surveillance data (prospective, n = 787; retrospective, n = 76) for the quadrivalent HPV vaccine have been published. However, only 279 pregnancies from the studies and 90 pregnancies from the registry occurred within 30 days of receiving the vaccination. Overall, the vaccine does not appear to be associated with an increased risk of spontaneous abortion, fetal malformations, or adverse pregnancy outcomes beyond that found in the general population. Although the data are limited, neither HPV vaccine appears to be associated with an increased risk of adverse pregnancy outcomes. However, limitations of the data include small patient populations, minimal to no adjustments for factors known to influence pregnancy outcomes or malformations, and the majority of the available pregnancy data are from retrospective analysis of Phase 3 efficacy trials. Neither HPV vaccine should be routinely administered during pregnancy. If a pregnancy occurs midseries, the remaining vaccines should be given after pregnancy completion. Further studies are required to determine actual risk. © 2011 SAGE Publications.

Clinical trial resources on the internet must be designed to reach underrepresented minorities.

PubMed

Wilson, John J; Mick, Rosemarie; Wei, S Jack; Rustgi, Anil K; Markowitz, Sanford D; Hampshire, Maggie; Metz, James M

2006-01-01

Internet-based clinical trial information services are being developed to increase recruitment to studies. However, there are limited data that evaluate their ability to reach elderly and underrepresented minority populations. This study was designed to evaluate the ability of an established clinical trials registry to reach these populations based on expected Internet use. This study compares general Internet users to participants who enrolled in an Internet based colorectal cancer clinical trials registry established by OncoLink (www.oncolink.org) and the National Colorectal Cancer Research Alliance. Observed rates of demographic groupings were compared to those established for general Internet users. Two thousand, four hundred and thirty-seven participants from the continental United States used the Internet to register for the database. New England, the Mid-Atlantic region, and the Southeast had the highest relative frequency of participation in the database, whereas the Upper Midwest, California, and the South had the lowest rates. Compared to general Internet users, there was an overrepresentation of women (73% vs. 50%) and participants over 55 years old (27% vs. 14%). However, there was an underrepresentation of minorities (10.3% vs. 22%), particularly African Americans (3.1% vs. 8%) and Hispanics (2.8% vs. 9%). The Internet is a growing medium for registry into clinical trials databases. However, even taking into account the selection bias of Internet accessibility, there are still widely disparate demographics between general Internet users and those registering for clinical trials, particularly the underrepresentation of minorities. Internet-based educational and recruitment services for clinical trials must be designed to reach these underrepresented minorities to avoid selection biases in future clinical trials.

Rare disease registries: a call to action.

PubMed

Lacaze, Paul; Millis, Nicole; Fookes, Megan; Zurynski, Yvonne; Jaffe, Adam; Bellgard, Matthew; Winship, Ingrid; McNeil, John; Bittles, Alan H

2017-09-01

When registries collect accurate clinical data over time, they can act as fundamental support structures for patients and their families and powerful cost-effective instruments to support clinical trials and translational research to improve quality of care, quality of life and survival. Registries are critical for rare diseases (RD) with low prevalence and propensity for variation in treatment and outcomes. Rare Voices Australia is leading a call for action to the research and clinical community to prioritise RD data collection and develop an integrated RD Registry strategy for Australia. Financial, operational and governance challenges exist for establishing and maintaining RD registries. As a multidisciplinary team whose interests converge on RD, we highlight the need for the establishment of an Australian RD Registry Alliance. This 'umbrella' organisation will: (i) bring together existing RD registries across Australia; (ii) establish National RD Registry Standards to support interoperability and cohesion across registries; (iii) develop strategies to attract sustainable funding from government and other sources to maximise the utility of existing RD registries and support the development of new RD registries. The most important role for the Alliance would be to use the RD registries for translational research to address current knowledge gaps about RD and to improve the care for the over 1.4 million Australians estimated to live with RD. © 2017 Royal Australasian College of Physicians.

Mexican registry of pulmonary hypertension: REMEHIP.

PubMed

Sandoval Zarate, Julio; Jerjes-Sanchez, Carlos; Ramirez-Rivera, Alicia; Zamudio, Tomas Pulido; Gutierrez-Fajardo, Pedro; Elizalde Gonzalez, Jose; Leon, Mario Seoane Garcia De; Gamez, Miguel Beltran; Abril, Francisco Moreno Hoyos; Michel, Rodolfo Parra; Aguilar, Humberto Garcia

REMEHIP is a prospective, multicentre registry on pulmonary hypertension. The main objective will be to identify the clinical profile, medical care, therapeutic trends and outcomes in adult and pediatric Mexican patients with well-characterized pulmonary hypertension. REMEHIP a multicenter registry began in 2015 with a planned recruitment time of 12 months and a 4-year follow-up. The study population will comprise a longitudinal cohort study, collecting data on patients with prevalent and incident pulmonary hypertension. Will be included patients of age >2 years and diagnosis of pulmonary hypertension by right heart catheterization within Group 1 and Group 4 of the World Health Organization classification. The structure, data collection and data analysis will be based on quality current recommendations for registries. The protocol has been approved by institutional ethics committees in all participant centers. All patients will sign an informed consent form. Currently in Mexico, there is a need of observational registries that include patients with treatment in the everyday clinical practice so the data could be validated and additional information could be obtained versus the one from the clinical trials. In this way, REMEHIP emerges as a link among randomized clinical trials developed by experts and previous Mexican experience. Copyright © 2016 Instituto Nacional de Cardiología Ignacio Chávez. Publicado por Masson Doyma México S.A. All rights reserved.

Azacitidine for Front-Line Therapy of Patients with AML: Reproducible Efficacy Established by Direct Comparison of International Phase 3 Trial Data with Registry Data from the Austrian Azacitidine Registry of the AGMT Study Group

PubMed Central

Pleyer, Lisa; Döhner, Hartmut; Dombret, Hervé; Seymour, John F.; Schuh, Andre C.; Beach, CL; Swern, Arlene S.; Burgstaller, Sonja; Stauder, Reinhard; Girschikofsky, Michael; Sill, Heinz; Schlick, Konstantin; Thaler, Josef; Halter, Britta; Machherndl Spandl, Sigrid; Zebisch, Armin; Pichler, Angelika; Pfeilstöcker, Michael; Autzinger, Eva M.; Lang, Alois; Geissler, Klaus; Voskova, Daniela; Sperr, Wolfgang R.; Hojas, Sabine; Rogulj, Inga M.; Andel, Johannes; Greil, Richard

2017-01-01

We recently published a clinically-meaningful improvement in median overall survival (OS) for patients with acute myeloid leukaemia (AML), >30% bone marrow (BM) blasts and white blood cell (WBC) count ≤15 G/L, treated with front-line azacitidine versus conventional care regimens within a phase 3 clinical trial (AZA-AML-001; NCT01074047; registered: February 2010). As results obtained in clinical trials are facing increased pressure to be confirmed by real-world data, we aimed to test whether data obtained in the AZA-AML-001 trial accurately represent observations made in routine clinical practice by analysing additional AML patients treated with azacitidine front-line within the Austrian Azacitidine Registry (AAR; NCT01595295; registered: May 2012) and directly comparing patient-level data of both cohorts. We assessed the efficacy of front-line azacitidine in a total of 407 patients with newly-diagnosed AML. Firstly, we compared data from AML patients with WBC ≤ 15 G/L and >30% BM blasts included within the AZA-AML-001 trial treated with azacitidine (“AML-001” cohort; n = 214) with AAR patients meeting the same inclusion criteria (“AAR (001-like)” cohort; n = 95). The current analysis thus represents a new sub-analysis of the AML-001 trial, which is directly compared with a new sub-analysis of the AAR. Baseline characteristics, azacitidine application, response rates and OS were comparable between all patient cohorts within the trial or registry setting. Median OS was 9.9 versus 10.8 months (p = 0.616) for “AML-001” versus “AAR (001-like)” cohorts, respectively. Secondly, we pooled data from both cohorts (n = 309) and assessed the outcome. Median OS of the pooled cohorts was 10.3 (95% confidence interval: 8.7, 12.6) months, and the one-year survival rate was 45.8%. Thirdly, we compared data from AAR patients meeting AZA-AML-001 trial inclusion criteria (n = 95) versus all AAR patients with World Health Organization (WHO)-defined AML (“AAR (WHO-AML)” cohort; n = 193). Within the registry population, median OS for AAR patients meeting trial inclusion criteria versus all WHO-AML patients was 10.8 versus 11.8 months (p = 0.599), respectively. We thus tested and confirmed the efficacy of azacitidine as a front-line agent in patients with AML, >30% BM blasts and WBC ≤ 15 G/L in a routine clinical practice setting. We further show that the efficacy of azacitidine does not appear to be limited to AML patients who meet stringent clinical trial inclusion criteria, but instead appears efficacious as front-line treatment in all patients with WHO-AML. PMID:28212292

Impact of clinical registries on quality of patient care and health outcomes: protocol for a systematic review.

PubMed

Hoque, Dewan Md Emdadul; Kumari, Varuni; Ruseckaite, Rasa; Romero, Lorena; Evans, Sue M

2016-04-26

Many developed countries have regional and national clinical registries aimed at improving health outcomes of patients diagnosed with particular diseases or cared for in particular healthcare settings. Clinical quality registries (CQRs) are clinical registries established with the purpose of monitoring quality of care and providing feedback to improve health outcomes. The aim of this systematic review is to understand the impact of CQRs on (1) mortality/survival; (2) measures of outcome that reflect a process or outcome of healthcare; (3) healthcare utilisation and (4) costs. The PRISMA-P methodology, checklist and standard strategy using predefined inclusion and exclusion criteria and structured data abstraction tools will be followed. A search of the electronic databases MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials (CENTRAL) and CINAHL will be undertaken, in addition to Google Scholar and grey literature, to identify studies in English covering the period January 1980 to December 2014. Case-control, cohort, randomised controlled trials and controlled clinical trials which describe the registry as an intervention will be eligible for inclusion. Narrative synthesis of study findings will be conducted, guided by a conceptual framework developed to analyse the outcome measure of the registry using defined criteria. If sufficient studies are identified with a similar outcome of interest and measure using the same comparator and time of interval, results will be pooled for random-effects meta-analysis. Test for heterogeneity and sensitivity analysis will be conducted. To identify reporting bias, forest plots and funnel plots will be created and, if required, Egger's test will be conducted. Ethical approval is not required as primary data will not be collected. Review results will be published as a part of thesis, peer-reviewed journal and conferences. CRD42015017319. 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/

Precision and negative predictive value of links between ClinicalTrials.gov and PubMed.

PubMed

Huser, Vojtech; Cimino, James J

2012-01-01

One of the goals of translational science is to shorten the time from discovery to clinical use. Clinical trial registries were established to increase transparency in completed and ongoing clinical trials, and they support linking trials with resulting publications. We set out to investigate precision and negative predictive value (NPV) of links between ClinicalTrials.gov (CT.gov) and PubMed. CT.gov has been established to increase transparency in clinical trials and the link to PubMed is crucial for supporting a number of important functions, including ascertaining publication bias. We drew a random sample of trials downloaded from CT.gov and performed manual review of retrieved publications. We characterize two types of links between trials and publications (NCT-link originating from MEDLINE and PMID-link originating from CT.gov).The link precision is different based on type (NCT-link: 100%; PMID-link: 63% to 96%). In trials with no linked publication, we were able to find publications 44% of the time (NPV=56%) by searching PubMed. This low NPV shows that there are potentially numerous publications that should have been formally linked with the trials. Our results indicate that existing trial registry and publisher policies may not be fully enforced. We suggest some automated methods for improving link quality.

Vinpocetine for acute ischaemic stroke.

PubMed

Bereczki, D; Fekete, I

2008-01-23

Vasoactive and neuroprotective drugs such as vinpocetine are used to treat stroke in some countries. To assess the effect of vinpocetine in acute ischaemic stroke. We searched the Cochrane Stroke Group Trials Register (last searched February 2007), MEDLINE (1966 to February 2007) and Scopus (1960 to February 2007). We also searched the Internet Stroke Center Stroke Trials Registry, Google Scholar, the science-specific search engine Scirus and Wanfang Data, the leading information provider in China. We contacted researchers in the field and four pharmaceutical companies that manufacture vinpocetine. Searches were complete to February 2007. Unconfounded randomised trials of vinpocetine compared with placebo, or any other reference treatment, in people with acute ischaemic stroke. We included trials if treatment started no later than 14 days after stroke onset. Two review authors independently applied the inclusion criteria. One review author extracted the data, which was then checked by the second review author. We assessed trial quality. The primary outcome measure was death or dependency. We included two trials, involving a total of 70 participants. Data for 63 participants were reported in the two trials combined. The rate of death or dependency did not differ between the treatment and placebo groups at one and three months. The 95% confidence intervals for the outcome measures were wide and included the possibility of both significant benefit and significant harm. No adverse effects were reported. There is not enough evidence to evaluate the effect of vinpocetine on survival or dependency in patients with acute ischaemic stroke.

IT behind a platform for Translational Cancer Research - concept and objectives.

PubMed

Steffens, Michael; Husmann, Gabriele; Koca, Mithat; Lablans, Martin; Komor, Martina; Zeissig, Sylke; Emrich, Katharina; Brandts, Christian; Serve, Hubert; Blettner, Maria; Uckert, Frank

2012-01-01

The German Consortium for Translational Cancer Research (DKTK) and the Rhine-Main Translational Cancer Research Network (RM-TCRN) are designed to exploit large population cohorts of cancer patients for the purpose of bio-banking, clinical trials, and clinical cancer registration. Hence, the success of these platforms is heavily dependent on the close interlinking of clinical data from cancer patients, information from study registries, and data from bio-banking systems of different laboratories and scientific institutions. This article referring to the poster discusses the main challenges of the platforms from an information technology point of view, legal and data security issues, and outlines an integrative IT-concept concerning a decentralized, distributed search approach where data management and search is in compliance with existing legislative rules.

Functional requirements regarding medical registries--preliminary results.

PubMed

Oberbichler, Stefan; Hörbst, Alexander

2013-01-01

The term medical registry is used to reference tools and processes to support clinical or epidemiologic research or provide a data basis for decisions regarding health care policies. In spite of this wide range of applications the term registry and the functional requirements which a registry should support are not clearly defined. This work presents preliminary results of a literature review to discover functional requirements which form a registry. To extract these requirements a set of peer reviewed articles was collected. These set of articles was screened by using methods from qualitative research. Up to now most discovered functional requirements focus on data quality (e. g. prevent transcription error by conducting automatic domain checks).

ClinicalTrials.gov, stem cells and 'pay-to-participate' clinical studies.

PubMed

Turner, Leigh

2017-09-01

Numerous US businesses that engage in direct-to-consumer advertising of stem cell interventions that are not US FDA-approved also recruit clients by listing 'pay-to-participate' studies listed on ClinicalTrials.gov . Individuals considering enrolling in such studies and NIH officials responsible for overseeing the database need to be aware that some businesses are using the registry to promote unapproved stem cell interventions that study subjects are charged to receive. Inclusion of such studies in ClinicalTrials.gov reveals that the database needs better screening tools. In particular, screening should evaluate whether studies submitted to the registry have been reviewed and permitted to proceed by the FDA in the case of clinical studies requiring FDA clearance in addition to institutional review board approval.

Contemporary roles of registries in clinical cardiology: when do we need randomized trials?

PubMed

Ieva, Francesca; Gale, Chris P; Sharples, Linda D

2014-12-01

Clinical registries are established as tools for auditing clinical standards and benchmarking quality improvement initiatives. They also have an emerging role (as electronic health records) in cardiovascular research and, in particular, the conduct of RCTs. While the RCT is accepted as the most robust experimental design, observational data from clinical registries has become increasingly valuable for RCTs. Data from clinical registries may be used to augment results from RCTs, identify patients for recruitment and as an alternative when randomization is not practically possible or ethically desirable. Here the authors appraise the advantages and disadvantages of both methodologies, with the aim of clarifying when their joint use may be successful.

Prospective registration trends, reasons for retrospective registration and mechanisms to increase prospective registration compliance: descriptive analysis and survey

PubMed Central

Seidler, Anna Lene; Askie, Lisa M

2018-01-01

Objectives To analyse prospective versus retrospective trial registration trends on the Australian New Zealand Clinical Trials Registry (ANZCTR) and to evaluate the reasons for non-compliance with prospective registration. Design Part 1: Descriptive analysis of trial registration trends from 2006 to 2015. Part 2: Online registrant survey. Participants Part 1: All interventional trials registered on ANZCTR from 2006 to 2015. Part 2: Random sample of those who had retrospectively registered a trial on ANZCTR between 2010 and 2015. Main outcome measures Part 1: Proportion of prospective versus retrospective clinical trial registrations (ie, registration before versus after enrolment of the first participant) on the ANZCTR overall and by various key metrics, such as sponsor, funder, recruitment country and sample size. Part 2: Reasons for non-compliance with prospective registration and perceived usefulness of various proposed mechanisms to improve prospective registration compliance. Results Part 1: Analysis of the complete dataset of 9450 trials revealed that compliance with prospective registration increased from 48% (216 out of 446 trials) in 2006 to 63% (723/1148) in 2012 and has since plateaued at around 64%. Patterns of compliance were relatively consistent across sponsor and funder types (industry vs non-industry), type of intervention (drug vs non-drug) and size of trial (n<100, 100–500, >500). However, primary sponsors from Australia/New Zealand were almost twice as likely to register prospectively (62%; 4613/7452) compared with sponsors from other countries with a WHO Network Registry (35%; 377/1084) or sponsors from countries without a WHO Registry (29%; 230/781). Part 2: The majority (56%; 84/149) of survey respondents cited lack of awareness as a reason for not registering their study prospectively. Seventy-four per cent (111/149) stated that linking registration to ethics approval would facilitate prospective registration. Conclusions Despite some progress, compliance with prospective registration remains suboptimal. Linking registration to ethics approval was the favoured strategy among those sampled for improving compliance. PMID:29496896

Current status of registry of vaccine clinical trials conducted by Korean investigators in ClinicalTrials.gov, database of US National Institutes of Health.

PubMed

Cho, Jahyang; Kim, Bo Bae; Bae, Chong-Woo; Cha, Sung-Ho

2013-01-01

PubMed is not only includes international medical journals but also has a registration site for the ongoing clinical trials, such as ClinicalTrials.gov, under the supervision of US National Institutes of Health. We analyzed current status of vaccine clinical trials conducted by Korean investigators in database of ClinicalTrial.gov. As of October 2012, there are total of 72 trials found on registry of vaccine clinical trials conducted by Korean investigators in database of ClinicalTrial.gov. These trials were analyzed and classified by conditions of vaccine clinical trials, biologicals or drugs used in vaccine clinical trials, status of proceeding research, and list of sponsor and collaborators. Total 72 trials of vaccine clinical trials conducted by Korean investigators are classified by groups of infection (64 trials), cancer (4 trials), and others (4 trials). Infections group shown are as follows: poliomyelitis, pertussis, diphtheria, tetanus, and Haemophilus influenzae type b (10), influenza (9), human papillomavirus infection (8), pneumococcal vaccine (6), herpes zoster (4), smallpox (4), hepatitis B (4), etc. One trial of each in lung cancer, breast cancer, prostate cancer, and colorectal cancer are shown in cancer group. One trial of each in Crohn's disease, ulcerative colitis, renal failure, and rheumatoid arthritis are shown in other group. Vaccine clinical trials conducted by Korean investigators in ClinicalTrial.gov reflects the current status of Korean research on vaccine clinical trials at the international level and can indicate research progress. It is hoped that this aids the development of future vaccine clinical trials in Korea.

[Priorities of clinical drug trials in Brazil and neglected diseases of poverty].

PubMed

Santana, Rafael Santos; Leite, Silvana Nair

2016-11-01

To identify clinical drug trials performed in Brazil between 2012 and 2015, with emphasis on those focusing on neglected diseases of poverty. Two clinical trial registries, ReBEC (Brazilian registry) and ClinicalTrials.gov were surveyed. The following aspects were investigated: distribution of clinical trials in relation to the burden of disease in Brazil, distribution of trials regarding their focus on diseases of poverty vs. diseases not linked to poverty, phase of trials, performing institution, and type of funding (private, public, or mixed). The search revealed 866 eligible trials, 88 registered in ReBEC and 778 in ClinicalTrials.gov. Of these, 73 (8.5%) were phase I trials, 610 (70.5%) were phase II and III trials, and 183 (21%) were phase IV trials. There were 38 trials (4%) focusing on neglected diseases of poverty. Regarding the burden of disease, 734 (84.8%) trials focused on noncommunicable diseases, which in fact represent the largest burden of disease in Brazil. Most trials were carried out by pharmaceutical companies (55.3%), with predominance of private funding (57.1%); however, if only the diseases of poverty are considered, 63.1% were financed by public resources. The clinical drug trials carried out in Brazil in the study period are in agreement with the proportional burden of disease for the country. However, the neglected diseases of poverty were not prioritized. More effective action is necessary to redirect clinical research on drug development to meet national needs.

Cost effectiveness of drug-eluting stents as compared with bare metal stents in patients with coronary artery disease.

PubMed

Wisløff, Torbjørn; Atar, Dan; Sønbø Kristiansen, Ivar

2013-01-01

The aim of this study was to estimate the incremental cost effectiveness of replacing bare metal stents (BMS) by drug-eluting stents (DES) when using trial data and registry data. We developed a Markov model (model of cost effectiveness of coronary artery disease) in which 60-year-old patients started by undergoing percutaneous coronary intervention for acute or subacute coronary artery disease. The patients are followed until death or 100 years of age. Data on the occurrence of events (revascularization, acute myocardial infarction, and death) were based on Scandinavian registry data. Separate analyses were conducted with data on effectiveness based on randomized controlled trials and patient registries. On using trial data, it was found that sirolimus-eluting stents (SES) yield 0.003 greater life expectancy and $3300 lower costs than do BMS (dominant strategy). Paclitaxel-eluting stents (PES) yield 0.148 more life years than do SES at additional lifetime costs of $2800 ($21,400 per life year gained). On using registry data, the cost per life year gained was found to be $4900 when replacing BMS with DES. Probabilistic sensitivity analyses, on the other hand, indicate that PES only has a 50%-75% probability of being cost effective, regardless of the type of effectiveness data. DESs are cost effective with current willingness to pay for life year gains. Whether PES or SES is the most effective DES remains uncertain.

Castration-resistant prostate cancer: targeted therapies.

PubMed

Leo, S; Accettura, C; Lorusso, V

2011-01-01

Castration-resistant prostate cancer (CRPC) refers to patients who no longer respond to surgical or medical castration. Standard treatment options are limited. To review the concepts and rationale behind targeted agents currently in late-stage clinical testing for patients with CRPC. Novel targeted therapies in clinical trials were identified from registries. The Medline database was searched for all relevant reports published from 1996 to October 2009. Bibliographies of the retrieved articles and major international meeting abstracts were hand-searched to identify additional studies. Advances in our understanding of the molecular mechanisms underlying prostate cancer (PCa) progression have translated into a variety of treatment approaches. Agents targeting androgen receptor activation and local steroidogenesis, angiogenesis, immunotherapy, apoptosis, chaperone proteins, the insulin-like growth factor (IGF) pathway, RANK ligand, endothelin receptors, and the Src family kinases are entering or have recently completed accrual to phase III trials for patients with CRPC. There has been an increase in the understanding of the mechanisms of progression of CRPC. A number of new agents targeting mechanisms of PCa progression with early promising results are in clinical trials and have the potential to provide novel treatment options for CRPC in the near future. Copyright © 2011 S. Karger AG, Basel.

Tools in a clinical information system supporting clinical trials at a Swiss University Hospital.

PubMed

Weisskopf, Michael; Bucklar, Guido; Blaser, Jürg

2014-12-01

Issues concerning inadequate source data of clinical trials rank second in the most common findings by regulatory authorities. The increasing use of electronic clinical information systems by healthcare providers offers an opportunity to facilitate and improve the conduct of clinical trials and the source documentation. We report on a number of tools implemented into the clinical information system of a university hospital to support clinical research. In 2011/2012, a set of tools was developed in the clinical information system of the University Hospital Zurich to support clinical research, including (1) a trial registry for documenting metadata on the clinical trials conducted at the hospital, (2) a patient-trial-assignment-tool to tag patients in the electronic medical charts as participants of specific trials, (3) medical record templates for the documentation of study visits and trial-related procedures, (4) online queries on trials and trial participants, (5) access to the electronic medical records for clinical monitors, (6) an alerting tool to notify of hospital admissions of trial participants, (7) queries to identify potentially eligible patients in the planning phase as trial feasibility checks and during the trial as recruitment support, and (8) order sets to facilitate the complete and accurate performance of study visit procedures. The number of approximately 100 new registrations per year in the voluntary trial registry in the clinical information system now matches the numbers of the existing mandatory trial registry of the hospital. Likewise, the yearly numbers of patients tagged as trial participants as well as the use of the standardized trial record templates increased to 2408 documented trial enrolments and 190 reports generated/month in the year 2013. Accounts for 32 clinical monitors have been established in the first 2 years monitoring a total of 49 trials in 16 clinical departments. A total of 15 months after adding the optional feature of hospital admission alerts of trial participants, 107 running trials have activated this option, including 48 out of 97 studies (49.5%) registered in the year 2013, generating approximately 85 alerts per month. The popularity of the presented tools in the clinical information system illustrates their potential to facilitate the conduct of clinical trials. The tools also allow for enhanced transparency on trials conducted at the hospital. Future studies on monitoring and inspection findings will have to evaluate their impact on quality and safety. © The Author(s) 2014.

Chemoprophylaxis in Contacts of Patients with Cholera: Systematic Review and Meta-Analysis

PubMed Central

Reveiz, Ludovic; Chapman, Evelina; Ramon-Pardo, Pilar; Koehlmoos, Tracey Perez; Cuervo, Luis Gabriel; Aldighieri, Sylvain; Chambliss, Amy

2011-01-01

Introduction There is a pressing need for effective measures to prevent the spread of cholera. Our systematic review assesses the effects of chemoprophylaxis in preventing cholera among exposed contacts. Methods and Findings We considered published and unpublished reports of studies up to July 2011. For this we searched: PubMed (1966 to July, 2011), Embase (1980 to July 2011), Cochrane Central Register of Controlled Trials (6; 2011), LILACS (1982 to July, 2011), the International Clinical Trials Registry Platform (July 2011) and references of identified publications. We included controlled clinical trials (randomized and non-randomized) in which chemoprophylaxis was used to prevent cholera among patient contacts. The main outcome measures were hospitalization and laboratory diagnosis of cholera in contacts for cholera patients. We assessed the risk of bias. We identified 2638 references and these included 2 randomized trials and 5 controlled trials that added up to a total of 4,154 participants. The risk of bias scored high for most trials. The combined results from two trials found that chemoprophylaxis reduced hospitalization of contacts during the follow-up period by 8–12 days (2826 participants; RR 0.54 95% CI 0.40–0.74;I2 0%). A meta-analysis of five trials found a significant reduction in disease among contacts with at least one positive sample who received chemoprophylaxis during the overall follow-up (range 4–15 days) (1,414 participants; RR 0.35 95% CI 0.18–0.66;I2 74%). A significant reduction in the number of positive samples was also found with chemoprophylaxis (3 CCT; 6,918 samples; RR 0.39 95% CI 0.29–0.51;I2 0%). Conclusion Our findings suggest that chemoprophylaxis has a protective effect among household contacts of people with cholera but the results are based on studies with a high risk of bias. Hence, there is a need for adequate reliable research that allows balancing benefits and harms by evaluating the effects of chemoprophylaxis. PMID:22102873

Patient registries: useful tools for clinical research in myasthenia gravis.

PubMed

Baggi, Fulvio; Mantegazza, Renato; Antozzi, Carlo; Sanders, Donald

2012-12-01

Clinical registries may facilitate research on myasthenia gravis (MG) in several ways: as a source of demographic, clinical, biological, and immunological data on large numbers of patients with this rare disease; as a source of referrals for clinical trials; and by allowing rapid identification of MG patients with specific features. Physician-derived registries have the added advantage of incorporating diagnostic and treatment data that may allow comparison of outcomes from different therapeutic approaches, which can be supplemented with patient self-reported data. We report the demographic analysis of MG patients in two large physician-derived registries, the Duke MG Patient Registry, at the Duke University Medical Center, and the INNCB MG Registry, at the Istituto Neurologico Carlo Besta, as a preliminary study to assess the consistency of the two data sets. These registries share a common structure, with an inner core of common data elements (CDE) that facilitate data analysis. The CDEs are concordant with the MG-specific CDEs developed under the National Institute of Neurological Disorders and Stroke Common Data Elements Project. © 2012 New York Academy of Sciences.

Cost-effectiveness of rituximab as maintenance treatment for relapsed follicular lymphoma: results of a population-based study.

PubMed

Blommestein, Hedwig M; Issa, Djamila E; Pompen, Marjolein; Ten Hoor, Gerhard; Hogendoorn, Mels; Joosten, Peter; Zweegman, Sonja; Huijgens, Peter C; Uyl-de Groot, Carin A

2014-01-01

On the basis of two population-based registries, our study aims to calculate the real-world cost-effectiveness of rituximab maintenance compared with observation in relapsed or refractory follicular lymphoma patients who responded to second-line chemotherapy. Data were obtained from the EORTC20981 trial, the Netherlands Cancer Registry and two population-based registries. A Markov model was developed to calculate cost per life year gained (LYG) and quality-adjusted life years (QALYs) for three scenarios. Our real-world patients were (62 years) 6 to 7 years older and had higher complete response rates to second-line chemotherapy than the trial population. Differences between the real-world rituximab and observation group were observed for second-line chemotherapy and disease progression. Groups were more balanced after using propensity matching. Relying entirely on updated trial results (scenario1) in combination with local cost data resulted in ratios of €11,259 per LYG and €12,655 per QALY. For scenario2, consisting of trial efficacy and matched real-world costs, ratios of €21,202 per LYG and €23,821 per QALY were calculated. Using real-world matched evidence (scenario3) for both effectiveness and costs showed ratios of €10,591 per LYG and €11,245 per QALY. Although differences in real-world and trial population were found, using real-world data as well as results from long-term trial follow-up showed favourable ICERs for rituximab maintenance. Nevertheless, results showed that caution is required with data synthesis, interpretation and generalisability of results. As different scenarios provide answers to different questions, we recommend healthcare decision-makers to recognise the importance of calculating several cost-effectiveness scenarios. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Using Arden Syntax to Identify Registry-Eligible Very Low Birth Weight Neonates from the Electronic Health Record

PubMed Central

Sarkar, Indra Neil; Chen, Elizabeth S.; Rosenau, Paul T.; Storer, Matthew B.; Anderson, Beth; Horbar, Jeffrey D.

2014-01-01

Condition-specific registries are essential resources for supporting epidemiological, quality improvement, and clinical trial studies. The identification of potentially eligible patients for a given registry often involves a manual process or use of ad hoc software tools. With the increased availability of electronic health data, such as within Electronic Health Record (EHR) systems, there is potential to develop healthcare standards based approaches for interacting with these data. Arden Syntax, which has traditionally been used to represent medical knowledge for clinical decision support, is one such standard that may be adapted for the purpose of registry eligibility determination. In this feasibility study, Arden Syntax was explored for its ability to represent eligibility criteria for a registry of very low birth weight neonates. The promising performance (100% recall; 97% precision) of the Arden Syntax approach at a single institution suggests that a standards-based methodology could be used to robustly identify registry-eligible patients from EHRs. PMID:25954412

The pancreatic surgery registry (StuDoQ|Pancreas) of the German Society for General and Visceral Surgery (DGAV) - presentation and systematic quality evaluation.

PubMed

Wellner, Ulrich F; Klinger, Carsten; Lehmann, Kai; Buhr, Heinz; Neugebauer, Edmund; Keck, Tobias

2017-04-05

Pancreatic resections are among the most complex procedures in visceral surgery. While mortality has decreased substantially over the past decades, morbidity remains high. The volume-outcome correlation in pancreatic surgery is among the strongest in the field of surgery. The German Society for General and Visceral Surgery (DGAV) established a national registry for quality control, risk assessment and outcomes research in pancreatic surgery in Germany (DGAV SuDoQ|Pancreas). Here, we present the aims and scope of the DGAV StuDoQ|Pancreas Registry. A systematic assessment of registry quality is performed based on the recommendations of the German network for outcomes research (DNVF). The registry quality was assessed by consensus criteria of the DNVF in regard to the domains Systematics and Appropriateness, Standardization, Validity of the sampling procedure, Validity of data collection, Validity of statistical analysis and reports, and General demands for registry quality. In summary, DGAV StuDoQ|Pancreas meets most of the criteria of a high-quality clinical registry. The DGAV StuDoQ|Pancreas provides a valuable platform for quality assessment, outcomes research as well as randomized registry trials in pancreatic surgery.

Rationale and design of a multidisciplinary national real-world registry on carotid stenting: the Italian Registry for Carotid Stenting (RISC).

PubMed

Biasi, Giorgio M; Deleo, Gaetano; Froio, Alberto; Cremonesi, Alberto; Inglese, Luigi; Lavitrano, Marialuisa; Setacci, Carlo

2006-04-01

The Registro Italiano per lo Stenting Carotideo (RISC, Italian Registry for Carotid Stenting) has been organized by Italian specialists from different disciplines directly involved in the prevention of stroke due to carotid plaques through stenting of carotid lesions. The Registry has been endorsed by the national societies of 4 different specialties: vascular surgery, interventional cardiology, radiology, and neuroradiology. Each society contributed in the planning stage. The basis for the registry is to collect data on carotid stenting procedures performed by different specialists with different techniques in a "real-world" setting without the limitations of a randomized clinical trial. The Registry was funded to enroll at least 1200 patients over a minimum period of 36 months. The results will be analyzed using the intention-to-treat principle and are anticipated in late 2006. Primary endpoints of the registry are the 30-day combined death and stroke rate and the occurrence of restenosis and ipsilateral neurological deficit at 12 and 24 months. Considerable attention has been paid to the registry's quality control program to ensure scientific validation. An online database facilitates the collection of data with speed and accuracy.

Caffeine, Adenosine Receptors and Estrogen in Toxin Models of Parkinson’s Disease

DTIC Science & Technology

2008-10-30

these have advanced molecules to clinical studies.2,3 Thus, the NIH clinical trial registry lists over a dozen actively recruiting or completed trials ...into clinical trials ,4 and multiple other preclinical programs are apparently progressing (including publicly announced programs at Neurocrine5 and...unpublished results). Adenosine A2AR antagonists are currently in clinical trials for PD because of their symptom- improving abilities. The

Agreement in reporting between trial publications and current clinical trial registry in high impact journals: A methodological review.

PubMed

Kosa, Sarah Daisy; Mbuagbaw, Lawrence; Borg Debono, Victoria; Bhandari, Mohit; Dennis, Brittany B; Ene, Gabrielle; Leenus, Alvin; Shi, Daniel; Thabane, Michael; Valvasori, Sara; Vanniyasingam, Thuva; Ye, Chenglin; Yranon, Elgene; Zhang, Shiyuan; Thabane, Lehana

2018-02-01

The primary objective of this systematic survey was to examine the percentage of studies in which there was agreement in the reporting of the primary outcome between the currently updated version of the clinical trial registry and the published paper. We also investigated the factors associated with agreement in reporting of the primary outcome. We searched PubMed for all randomized control trials (RCT)s published in 2012-2015 in the top five general medicine journals (based on the 2014 impact factor). Two hundred abstracts (50 from each year) were randomly selected for data extraction. Agreement in reporting of 11 key study conduct items (e.g., sample size) and study characteristics (e.g., funding, number of sites) were extracted by two independent reviewers. Descriptive analyses were conducted to determine the proportion of studies on which there was agreement in reporting of key study conduct items. Generalized estimating equations were used to explore factors associated with agreement in reporting of the primary outcome. Of the 200 included studies, 87% had agreement in reporting of the primary outcome. After adjusting for other covariates, having greater than 50 sites was associated with an increased likelihood of agreement in reporting of the primary outcome (odds ratio=7.1, 95% confidence interval=1.39, 36.27, p=0.018). We identified substantive disagreement in reporting between publications and current clinical trial registry, which were associated with several study characteristics. Further measures are needed to improve reporting given the potential threats to the quality and integrity of scientific research. Copyright © 2017 Elsevier Inc. All rights reserved.

The impact of neutral-pH peritoneal dialysates with reduced glucose degradation products on clinical outcomes in peritoneal dialysis patients.

PubMed

Cho, Yeoungjee; Johnson, David W; Badve, Sunil V; Craig, Jonathan C; Strippoli, Giovanni F M; Wiggins, Kathryn J

2013-11-01

Neutral-pH peritoneal dialysates, with reduced glucose degradation products (GDPs), have been developed to reduce peritoneal membrane damage. Here our review evaluated the impact of these solutions on clinical outcomes using data from The Cochrane CENTRAL Registry, MEDLINE, Embase, and reference lists for randomized trials of biocompatible solutions. Summary estimates of effect were obtained using a random-effects model of 20 eligible trials encompassing 1383 patients. The quality of studies was generally poor, such that 13 studies had greater than a 20% loss to follow-up and only 3 trials reported adequate concealment of allocation. Use of neutral-pH dialysates with reduced GDPs resulted in larger urine volumes (7 trials; 520 patients; mean difference 126 ml/day, 95% CI 27-226), improved residual renal function after 12 months (6 trials; 360 patients; standardized mean difference 0.31, 95% confidence interval 0.10-0.52), and a trend to reduced inflow pain (1 trial; 58 patients; relative risk 0.51, 95% CI 0.24-1.08). However, there was no significant effect on body weight, hospitalization, peritoneal solute transport rate, peritoneal small-solute clearance, peritonitis, technique failure, patient survival, or adverse events. No significant harms were identified. Thus, based on generally poor quality trials, the use of neutral-pH peritoneal dialysates with reduced GDPs resulted in greater urine volumes and residual renal function after 12 months, but without other clinical benefits. Larger, better-quality studies are needed for accurate evaluation of the impact of these newer dialysates on patient-level hard outcomes.

Post-approval Studies for Rare Disease Treatments and Orphan Drugs.

PubMed

Maier, William C; Christensen, Ronald A; Anderson, Patricia

2017-01-01

Drug development involves a multi-stage process of drug discovery, animal studies and human clinical trials to assess the safety and efficacy of new medications. Rare disease drug development involves a much smaller number of affected patients, a predominance of pediatric patients and more complicated disease presentation. Post-approval studies are designed to address several limitations associated with the rare disease clinical trials.National and international regulatory agencies in the US and Europe have adopted similar approaches to requirements post-approval data for rare diseases and orphan drug indications. The US FDA published guidance in 2011 and the European Medicines Agency in 2015.Post-approval studies for rare diseases include observational studies, pragmatic trials and randomized controlled studies. Observational studies include both original data collection studies and the use of secondary data (retrospective studies). Original data collection can address limitations of retrospective studies resulting from incomplete information in secondary data sources. Disease registries focus on detail about a broad range of patients with a rare disease while product-related registries focus on specific health care outcomes associated with a single product and may incorporate a comparator of an alternative therapy or therapies.Rare disease patients can be difficult to find and enroll in a registry using conventional physician based driven recruitment. The study process also needs to recognize changes in the patient's disease and lifestyle and adapt both the study design and methods over time. Many rare diseases have strong patient advocacy groups that can in aid the design and execution of rare disease registries.

Searching ClinicalTrials.gov and the International Clinical Trials Registry Platform to inform systematic reviews: what are the optimal search approaches?

PubMed

Glanville, Julie M; Duffy, Steven; McCool, Rachael; Varley, Danielle

2014-07-01

Since 2005, International Committee of Medical Journal Editors (ICMJE) member journals have required that clinical trials be registered in publicly available trials registers before they are considered for publication. The research explores whether it is adequate, when searching to inform systematic reviews, to search for relevant clinical trials using only public trials registers and to identify the optimal search approaches in trials registers. A search was conducted in ClinicalTrials.gov and the International Clinical Trials Registry Platform (ICTRP) for research studies that had been included in eight systematic reviews. Four search approaches (highly sensitive, sensitive, precise, and highly precise) were performed using the basic and advanced interfaces in both resources. On average, 84% of studies were not listed in either resource. The largest number of included studies was retrieved in ClinicalTrials.gov and ICTRP when a sensitive search approach was used in the basic interface. The use of the advanced interface maintained or improved sensitivity in 16 of 19 strategies for Clinicaltrials.gov and 8 of 18 for ICTRP. No single search approach was sensitive enough to identify all studies included in the 6 reviews. Trials registers cannot yet be relied upon as the sole means to locate trials for systematic reviews. Trials registers lag behind the major bibliographic databases in terms of their search interfaces. For systematic reviews, trials registers and major bibliographic databases should be searched. Trials registers should be searched using sensitive approaches, and both the registers consulted in this study should be searched.

A comparison of interventional clinical trials in rare versus non-rare diseases: an analysis of ClinicalTrials.gov.

PubMed

Bell, Stuart A; Tudur Smith, Catrin

2014-11-26

To provide a comprehensive characterisation of rare disease clinical trials registered in ClinicalTrials.gov, and compare against characteristics of trials in non-rare diseases. Registry based study of ClinicalTrials.gov registration entries. The ClinicalTrials.gov registry comprised 133,128 studies registered to September 27, 2012. By annotating medical subject heading descriptors to condition terms we could identify rare and non-rare disease trials. A total of 24,088 Interventional trials registered after January 1, 2006, conducted in the United States, Canada and/or the European Union were categorised as rare or non-rare. Characteristics of the respective trials were extracted and summarised with comparative statistics calculated where appropriate. Characteristics of interventional trials reported in the database categorised by rare and non-rare conditions to allow comparison. Of the 24,088 trials categorised 2,759 (11.5%) were classified as rare disease trials and 21,329 (88.5%) related to non-rare conditions. Despite the limitations of the database we found that rare disease trials differed to non-rare disease trials across all characteristics that we examined. Rare disease trials enrolled fewer participants (median 29 vs. 62), were more likely to be single arm (63.0% vs. 29.6%), non-randomised (64.5% vs. 36.1%) and open label (78.7% vs. 52.2%). A higher proportion of rare disease trials were terminated early (13.7% vs. 6.3%) and proportionally fewer rare disease studies were actively pursuing, or waiting to commence, enrolment (15.9% vs. 38.5%). Rare disease interventional trials differ from those in non-rare conditions with notable differences in enrolment, design, blinding and randomisation. However, clinical trials should aim to implement the highest trial design standards possible, regardless of whether diseases are rare or not.

Pediatric Clinical Trials Conducted in South Korea from 2006 to 2015: An Analysis of the South Korean Clinical Research Information Service, US ClinicalTrials.gov and European Clinical Trials Registries.

PubMed

Choi, Sheung-Nyoung; Lee, Ji-Hyun; Song, In-Kyung; Kim, Eun-Hee; Kim, Jin-Tae; Kim, Hee-Soo

2017-12-01

The status of pediatric clinical trials performed in South Korea in the last decade, including clinical trials of drugs with unapproved indications for children, has not been previously examined. The aim was to provide information regarding the current state of pediatric clinical trials and create a basis for future trials performed in South Korea by reviewing three databases of clinical trials registrations. We searched for pediatric clinical studies (participants <18 years old) conducted in South Korea between 2006 and 2015 registered on the Clinical Research Information Service (CRIS), ClinicalTrials.gov, and the European Clinical Trials Registry (EuCTR). Additionally, we reviewed whether unapproved indications were involved in each trial by comparing the trials with a list of authorized trials provided by the Ministry of Food and Drug Safety (MFDS). The primary and secondary outcomes were to determine the change in number of pediatric clinical trials with unapproved indications over time and to assess the status of unauthorized pediatric clinical trials from the MFDS and the publication of articles after these clinical trials, respectively. We identified 342 clinical studies registered in the CRIS (n = 81), ClinicalTrials.gov (n = 225), and EuCTR (n = 36), of which 306 were reviewed after excluding duplicate registrations. Among them, 181 studies were interventional trials dealing with drugs and biological agents, of which 129 (71.3%) involved unapproved drugs. Of these 129 trials, 107 (82.9%) were authorized by the MFDS. Pediatric clinical trials in South Korea aiming to establish the safety and efficacy of drugs in children are increasing; however, non-MFDS-authorized studies remain an issue.

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

PubMed

DiMichele, D M

2006-12-01

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

Influence of morphology on survival for non-Hodgkin lymphoma in Europe and the United States.

PubMed

Sant, Milena; Allemani, Claudia; De Angelis, Roberta; Carbone, Antonino; de Sanjosè, Silvia; Gianni, Alessandro M; Giraldo, Pilar; Marchesi, Francesca; Marcos-Gragera, Rafael; Martos-Jiménez, Carmen; Maynadié, Marc; Raphael, Martine; Berrino, Franco

2008-03-01

We explored the influence of morphology on geographic differences in 5-year survival for non-Hodgkin lymphoma (NHL) diagnosed in 1990-1994 and followed for 5years: 16,955 cases from 27 EUROCARE-3 cancer registries, and 22,713 cases from 9 US SEER registries. Overall 5-year relative survival was 56.1% in EUROCARE west, 47.1% in EUROCARE east and 56.3% in SEER. Relative excess risk (RER) of death was 1.05 (95% confidence interval (CI) 1.01-1.10) in EUROCARE west, 1.52 (95% CI 1.44-1.60) in EUROCARE east (SEER reference). Excess risk of death was significantly above reference (diffuse B lymphoma) for Burkitt's and NOS lymphoma; not different for lymphoblastic and other T-cell; significantly below reference (in the order of decreasing relative excess risk) for NHL NOS, mantle cell/centrocytic, lymphoplasmacytic, follicular, small lymphocytic/chronic lymphocytic leukaemia, other specified NHL and cutaneous morphologies. Interpretation of marked variation in survival with morphology is complicated by classification inconsistencies. The completeness and standardisation of cancer registry morphology data needs to be improved.

A pilot registry of unexplained fatiguing illnesses and chronic fatigue syndrome

PubMed Central

2013-01-01

Background Chronic fatigue syndrome (CFS) has no diagnostic clinical signs or biomarkers, so diagnosis requires ruling out conditions with similar signs and symptoms. We conducted a pilot registry of unexplained fatiguing illnesses and CFS to determine the feasibility of establishing and operating a registry and implementing an education outreach initiative. The pilot registry was conducted in Bibb County, Georgia. Patient referrals were obtained from healthcare providers who were identified by using various education outreach initiatives. These referrals were later supplemented with self-referrals by members of a local CFS support group. All patients meeting referral criteria were invited to participate in a screening interview to determine eligibility. If patients met registry criteria, they were invited to a one-day clinic for physical and laboratory evaluations. We classified patients based on the 1994 case definition. Results We registered 827 healthcare providers. Forty-two providers referred 88 patients, and 58 patients (66%) completed clinical evaluation. Of the 188 CFS support group members, 53 were self-referred and 46 (87%) completed the clinical evaluation. Of the 104 participants completing evaluation, 36% (n = 37) met the criteria for CFS, 17% (n = 18) had insufficient fatigue or symptoms (ISF), and 47% (n = 49) were found to have exclusionary medical or psychiatric illnesses. Classification varied significantly by type of referral but not by previous history of CFS diagnosis. Healthcare providers referred more patients who were classified as CFS as compared to support group referrals in which more exclusionary conditions were identified. Family practice and internal medicine specialties made the most referrals and had the highest number of CFS cases. We conducted three CME events, held three “Meet and Greet” sessions, visited four large clinical health practices and health departments, mailed five registry newsletters, and conducted in-person office visits as part of education outreach, which contributed to patient referrals. Conclusions Referrals from healthcare providers and self-referrals from the patient support group were important to registry enrollment. The number of potentially treatable conditions that were identified highlights the need for continued medical management in this population, as well as the limitations of registries formed without clinical examination. Education initiatives were successful in part because of partnerships with local organizations. PMID:23915640

Rationale and design of a prospective study: Cervical Dystonia Patient Registry for Observation of OnaBotulinumtoxinA Efficacy (CD PROBE)

PubMed Central

2011-01-01

Background A registry of patients with cervical dystonia (Cervical Dystonia Patient Registry for Observation of onaBotulinumtoxinA Efficacy [CD PROBE]) was initiated to capture data regarding physician practices and patient outcomes with onabotulinumtoxinA (BOTOX®, Allergan, Inc., Irvine, CA, USA). Methods and baseline demographics from an interim analysis are provided. Methods/Design This is a prospective, multicenter, clinical registry in the United States enrolling subjects with cervical dystonia (CD) who are toxin naïve and/or new to the physicians' practices, or who had been in a clinical trial but received their last injection ≥ 16 weeks prior to enrollment. Subjects are followed over 3 injection cycles of onabotulinumtoxinA, with assessments at time of injection and 4-6 weeks later. Information on physician's practice, patient demographics, CD disease history, duration of treatment intervals and neurotoxin dose, dilution, use of electromyography, and muscles injected are collected. Outcomes are assessed by physicians and subjects using various questionnaires. Discussion This ongoing registry includes 609 subjects with the following baseline data: 75.9% female, 93.6% Caucasian, mean age 57.6 ± 14.3, age at symptom onset 48.3 ± 16.2, and time to diagnosis 5.4 ± 8.6 years, with an additional 1.0 ± 3.5 years before treatment. Of those employed at the time of diagnosis, 36.6% stopped working as a result of CD. CD PROBE, the largest clinical registry of CD treatment, will provide useful data on current treatment practices with onabotulinumtoxinA, potentially leading to refinements for optimization of outcomes. Trial registration NCT00836017 PMID:22054223

Inception of a national multidisciplinary registry for stereotactic radiosurgery.

PubMed

Sheehan, Jason P; Kavanagh, Brian D; Asher, Anthony; Harbaugh, Robert E

2016-01-01

Stereotactic radiosurgery (SRS) represents a multidisciplinary approach to the delivery of ionizing high-dose radiation to treat a wide variety of disorders. Much of the radiosurgical literature is based upon retrospective single-center studies along with a few randomized controlled clinical trials. More timely and effective evidence is needed to enhance the consistency and quality of and clinical outcomes achieved with SRS. The authors summarize the creation and implementation of a national SRS registry. The American Association of Neurological Surgeons (AANS) through NeuroPoint Alliance, Inc., started a successful registry effort with its lumbar spine initiative. Following a similar approach, the AANS and NeuroPoint Alliance collaborated with corporate partners and the American Society for Radiation Oncology to devise a data dictionary for an SRS registry. Through administrative and financial support from professional societies and corporate partners, a framework for implementation of the registry was created. Initial plans were devised for a 3-year effort encompassing 30 high-volume SRS centers across the country. Device-specific web-based data-extraction platforms were built by the corporate partners. Data uploaders were then used to port the data to a common repository managed by Quintiles, a national and international health care trials company. Audits of the data for completeness and veracity will be undertaken by Quintiles to ensure data fidelity. Data governance and analysis are overseen by an SRS board comprising equal numbers of representatives from the AANS and NeuroPoint Alliance. Over time, quality outcome assessments and post hoc research can be performed to advance the field of SRS. Stereotactic radiosurgery offers a high-technology approach to treating complex intracranial disorders. Improvements in the consistency and quality of care delivered to patients who undergo SRS should be afforded by the national registry effort that is underway.

Validation of a case definition to define chronic dialysis using outpatient administrative data.

PubMed

Clement, Fiona M; James, Matthew T; Chin, Rick; Klarenbach, Scott W; Manns, Braden J; Quinn, Robert R; Ravani, Pietro; Tonelli, Marcello; Hemmelgarn, Brenda R

2011-03-01

Administrative health care databases offer an efficient and accessible, though as-yet unvalidated, approach to studying outcomes of patients with chronic kidney disease and end-stage renal disease (ESRD). The objective of this study is to determine the validity of outpatient physician billing derived algorithms for defining chronic dialysis compared to a reference standard ESRD registry. A cohort of incident dialysis patients (Jan. 1-Dec. 31, 2008) and prevalent chronic dialysis patients (Jan 1, 2008) was selected from a geographically inclusive ESRD registry and administrative database. Four administrative data definitions were considered: at least 1 outpatient claim, at least 2 outpatient claims, at least 2 outpatient claims at least 90 days apart, and continuous outpatient claims at least 90 days apart with no gap in claims greater than 21 days. Measures of agreement of the four administrative data definitions were compared to a reference standard (ESRD registry). Basic patient characteristics are compared between all 5 patient groups. 1,118,097 individuals formed the overall population and 2,227 chronic dialysis patients were included in the ESRD registry. The three definitions requiring at least 2 outpatient claims resulted in kappa statistics between 0.60-0.80 indicating "substantial" agreement. "At least 1 outpatient claim" resulted in "excellent" agreement with a kappa statistic of 0.81. Of the four definitions, the simplest (at least 1 outpatient claim) performed comparatively to other definitions. The limitations of this work are the billing codes used are developed in Canada, however, other countries use similar billing practices and thus the codes could easily be mapped to other systems. Our reference standard ESRD registry may not capture all dialysis patients resulting in some misclassification. The registry is linked to on-going care so this is likely to be minimal. The definition utilized will vary with the research objective.

Compliance with mandatory reporting of clinical trial results on ClinicalTrials.gov: cross sectional study.

PubMed

Prayle, Andrew P; Hurley, Matthew N; Smyth, Alan R

2012-01-03

To examine compliance with mandatory reporting of summary clinical trial results (within one year of completion of trial) on ClinicalTrials.gov for studies that fall under the recent Food and Drug Administration Amendments Act (FDAAA) legislation. Registry based study of clinical trial summaries. ClinicalTrials.gov, searched on 19 January 2011, with cross referencing with Drugs@FDA to determine for which trials mandatory reporting was required within one year. Selection criteria Studies registered on ClinicalTrials.gov with US sites which completed between 1 January and 31 December 2009. Proportion of trials for which results had been reported. The ClinicalTrials.gov registry contained 83,579 entries for interventional trials, of which 5642 were completed within the timescale of interest. We identified trials as falling within the mandatory reporting rules if they were covered by the FDAAA (trials of a drug, device, or biological agent, which have at least one US site, and are of phase II or later) and if they investigated a drug that already had approval from the Food and Drug Administration. Of these, 163/738 (22%) had reported results within one year of completion of the trial compared with 76/727 (10%) trials that were not subject to mandatory reporting (95% confidence interval for the difference in proportions 7.8% to 15.5%; χ(2) test, P = 2.6 × 10(-9)). Later phase trials were more likely to report results (P = 4.4 × 10(-11)), as were industry funded trials (P = 2.2 × 10(-16)). Most trials subject to mandatory reporting did not report results within a year of completion.

Role of preliminary registry data in development of a clinical trial for an innovative device: a small but integral piece of a health policy initiative

PubMed Central

Ricci, Donald R.; de Vries, Joost; Blanc, Raphael

2017-01-01

ABSTRACT Establishing a national health policy at a macro level involves the integration of a series of health initiatives across a spectrum of activities, including clinical care. Evaluation of the safety and efficacy of a new medical device ultimately evolves to testing in humans. The pathway to a formal prospective clinical trial includes a stepwise appreciation of pre-clinical data and detailed analysis of data obtained from preliminary registries, where information about appropriate patient selection and use of the device is obtained. Evaluation of procedural and follow-up efficacy and safety data in a preliminary series of cases, chosen to simulate published data, allows the design and conduct of clinical trials that are required to verify preliminary observations, closing the loop on one aspect of modifying health policy decisions. PMID:28321285

Clinical trials in dentistry in India: Analysis from trial registry.

PubMed

Gowri, S; Kannan, Sridharan

2017-01-01

Evidence-based practice requires clinical trials to be performed. In India, if any clinical trial has to be performed, it has to be registered with clinical trial registry of India. Studies have shown that the report of clinical trials is poor in dentistry. Hence, the present study has been conducted to assess the type and trends of clinical trials being undertaken in dentistry in India over a span of 6 years. All the clinical trials which were registered with the Central Trial Registry of India (CTRI) (www.ctri.nic.in) from January 1, 2007 to March 3, 2014 were evaluated using the keyword "dental." Following information were collected for each of the clinical trials obtained from the search; number of centres (single center/multicentric), type of the institution undertaking the research (government/private/combined), study (observational/interventional), study design (randomized/single blinded/double-blinded), type of health condition, type of participants (healthy/patients), sponsors (academia/commercial), phase of clinical trial (Phase 1/2/3/4), publication details (published/not published), whether it was a postgraduate thesis or not and prospective or retrospective registration of clinical trials, methodological quality (method of randomization, allocation concealment). Descriptive statistics was used for analysis of various categories. Trend analysis was done to assess the changes over a period of time. The search yielded a total of 84 trials of which majority of them were single centered. Considering the study design more than half of the registered clinical trials were double-blinded (47/84 [56%]). With regard to the place of conducting a trial, most of the trials were planned to be performed in private hospitals (56/84 [66.7%]). Most (79/84, 94.1%) of the clinical trials were interventional while only 5/84 (5.9%) were observational. Majority (65/84, 77.4%) of the registered clinical trials were recruiting patients while the rest were being done in healthy participants. From 2011, some of the postgraduate thesis trials had also been registered (2011-8; 2012-8; 2013-13; 2014-6). Inadequacy in reporting the method of randomization and allocation concealment was observed in 37/67 (55.2%) and 31/67 (46.2%) clinical trials respectively. A considerable number of postgraduate theses was also registered with CTRI in dentistry and majority of the clinical trials despite being completed are not yet published. The number of clinical trials in dentistry are low in India, and more focus should be placed by dental investigators regarding the reporting standards. Furthermore, researchers and trial sponsors should aim at publication of the research findings so that it is made publically available for use. A clear-cut need exists for an increase in both the quantity and quality of clinical trials in dentistry.

Evidence-based practice: extending the search to find material for the systematic review

PubMed Central

Helmer, Diane; Savoie, Isabelle; Green, Carolyn; Kazanjian, Arminée

2001-01-01

Background: Cochrane-style systematic reviews increasingly require the participation of librarians. Guidelines on the appropriate search strategy to use for systematic reviews have been proposed. However, research evidence supporting these recommendations is limited. Objective: This study investigates the effectiveness of various systematic search methods used to uncover randomized controlled trials (RCTs) for systematic reviews. Effectiveness is defined as the proportion of relevant material uncovered for the systematic review using extended systematic review search methods. The following extended systematic search methods are evaluated: searching subject-specific or specialized databases (including trial registries), hand searching, scanning reference lists, and communicating personally. Methods: Two systematic review projects were prospectively monitored regarding the method used to identify items as well as the type of items retrieved. The proportion of RCTs identified by each systematic search method was calculated. Results: The extended systematic search methods uncovered 29.2% of all items retrieved for the systematic reviews. The search of specialized databases was the most effective method, followed by scanning of reference lists, communicating personally, and hand searching. Although the number of items identified through hand searching was small, these unique items would otherwise have been missed. Conclusions: Extended systematic search methods are effective tools for uncovering material for the systematic review. The quality of the items uncovered has yet to be assessed and will be key in evaluating the value of the systematic search methods. PMID:11837256

Chronic obstructive pulmonary disease self-management activation research trial (COPD-SMART): results of recruitment and baseline patient characteristics.

PubMed

Russo, Rennie; Coultas, David; Ashmore, Jamile; Peoples, Jennifer; Sloan, John; Jackson, Bradford E; Uhm, Minyong; Singh, Karan P; Blair, Steven N; Bae, Sejong

2015-03-01

To describe the recruitment methods, study participation rate, and baseline characteristics of a representative sample of outpatients with COPD eligible for pulmonary rehabilitation participating in a trial of a lifestyle behavioral intervention to increase physical activity. A patient registry was developed for recruitment using an administrative database from primary care and specialty clinics of an academic medical center in northeast Texas for a parallel group randomized trial. The registry was comprised of 5582 patients and over the course of the 30 month recruitment period 325 patients were enrolled for an overall study participation rate of 35.1%. After a 6-week COPD self-management education period provided to all enrolled patients, 305 patients were randomized into either usual care (UC; n=156) or the physical activity self-management intervention (PASM; n=149). There were no clinically significant differences in demographics, clinical characteristics, or health status indicators between the randomized groups. The results of this recruitment process demonstrate the successful use of a patient registry for enrolling a representative sample of outpatients eligible for pulmonary rehabilitation with COPD from primary and specialty care. Moreover, this approach to patient recruitment provides a model for future studies utilizing administrative databases and electronic health records. Published by Elsevier Inc.

Observational studies: a valuable source for data on the true value of RA therapies.

PubMed

van Vollenhoven, Ronald F; Severens, Johan L

2011-03-01

The validity of observational studies is sometimes questioned because of the limitations of non-randomly assigned controls, various biases such as channeling bias, confounding by indication, and other pitfalls. Yet, (post-marketing) observational data can provide important information regarding not only drug safety but also the effectiveness and appropriate use of agents in the real world, outside of clinical trials. Observational studies also provide data regarding the wider value of these agents in terms of, for example, reducing the need for surgical procedures, reducing absenteeism and increasing productivity. Importantly, data from some observational registry studies have subsequently been confirmed by clinical trials, supporting the overall validity of the registry-based approach. Observational studies also allow measures such as health assessment questionnaire scores, disease activity scores, and glucocorticoid use over time to be monitored for longer periods. Furthermore, observational data in real, less strictly selected patients without the constraints of formal study populations may produce findings not observed in clinical trials but that warrant further investigation in a controlled trial environment. For example, recent data from the Stockholm tumor necrosis factor follow-up registry in Sweden showed increases in the time people worked after initiation of biologics that, surprisingly, continued into the fourth and fifth years of treatment--a finding not observed with standardized outcomes. Observational studies are truly an underappreciated and valuable source of data on the real value of anti-rheumatic therapies, and these data are essential for making sound decisions regarding coverage and reimbursement.

Assessment of Registration Information on Methodological Design of Acupuncture RCTs: A Review of 453 Registration Records Retrieved from WHO International Clinical Trials Registry Platform

PubMed Central

Gu, Jing; Wang, Qi; Wang, Xiaogang; Li, Hailong; Gu, Mei; Ming, Haixia; Dong, Xiaoli; Yang, Kehu; Wu, Hongyan

2014-01-01

Background. This review provides the first methodological information assessment of protocol of acupuncture RCTs registered in WHO International Clinical Trials Registry Platform (ICTRP). Methods. All records of acupuncture RCTs registered in the ICTRP have been collected. The methodological design assessment involved whether the randomization methods, allocation concealment, and blinding were adequate or not based on the information of registration records (protocols of acupuncture RCTs). Results. A total of 453 records, found in 11 registries, were examined. Methodological details were insufficient in registration records; there were 76.4%, 89.0%, and 21.4% records that did not provide information on randomization methods, allocation concealment, and blinding respectively. The proportions of adequate randomization methods, allocation concealment, and blinding were only 107 (23.6%), 48 (10.6%), and 210 (46.4%), respectively. The methodological design improved year by year, especially after 2007. Additionally, methodology of RCTs with ethics approval was clearly superior to those without ethics approval and different among registries. Conclusions. The overall methodological design based on registration records of acupuncture RCTs is not very well but improved year by year. The insufficient information on randomization methods, allocation concealment, and blinding maybe due to the relevant description is not taken seriously in acupuncture RCTs' registration. PMID:24688591

Assessment of Registration Information on Methodological Design of Acupuncture RCTs: A Review of 453 Registration Records Retrieved from WHO International Clinical Trials Registry Platform.

PubMed

Gu, Jing; Wang, Qi; Wang, Xiaogang; Li, Hailong; Gu, Mei; Ming, Haixia; Dong, Xiaoli; Yang, Kehu; Wu, Hongyan

2014-01-01

Background. This review provides the first methodological information assessment of protocol of acupuncture RCTs registered in WHO International Clinical Trials Registry Platform (ICTRP). Methods. All records of acupuncture RCTs registered in the ICTRP have been collected. The methodological design assessment involved whether the randomization methods, allocation concealment, and blinding were adequate or not based on the information of registration records (protocols of acupuncture RCTs). Results. A total of 453 records, found in 11 registries, were examined. Methodological details were insufficient in registration records; there were 76.4%, 89.0%, and 21.4% records that did not provide information on randomization methods, allocation concealment, and blinding respectively. The proportions of adequate randomization methods, allocation concealment, and blinding were only 107 (23.6%), 48 (10.6%), and 210 (46.4%), respectively. The methodological design improved year by year, especially after 2007. Additionally, methodology of RCTs with ethics approval was clearly superior to those without ethics approval and different among registries. Conclusions. The overall methodological design based on registration records of acupuncture RCTs is not very well but improved year by year. The insufficient information on randomization methods, allocation concealment, and blinding maybe due to the relevant description is not taken seriously in acupuncture RCTs' registration.

Prospective registration trends, reasons for retrospective registration and mechanisms to increase prospective registration compliance: descriptive analysis and survey.

PubMed

Hunter, Kylie Elizabeth; Seidler, Anna Lene; Askie, Lisa M

2018-03-01

To analyse prospective versus retrospective trial registration trends on the Australian New Zealand Clinical Trials Registry (ANZCTR) and to evaluate the reasons for non-compliance with prospective registration. Part 1: Descriptive analysis of trial registration trends from 2006 to 2015. Part 2: Online registrant survey. Part 1: All interventional trials registered on ANZCTR from 2006 to 2015. Part 2: Random sample of those who had retrospectively registered a trial on ANZCTR between 2010 and 2015. Part 1: Proportion of prospective versus retrospective clinical trial registrations (ie, registration before versus after enrolment of the first participant) on the ANZCTR overall and by various key metrics, such as sponsor, funder, recruitment country and sample size. Part 2: Reasons for non-compliance with prospective registration and perceived usefulness of various proposed mechanisms to improve prospective registration compliance. Part 1: Analysis of the complete dataset of 9450 trials revealed that compliance with prospective registration increased from 48% (216 out of 446 trials) in 2006 to 63% (723/1148) in 2012 and has since plateaued at around 64%. Patterns of compliance were relatively consistent across sponsor and funder types (industry vs non-industry), type of intervention (drug vs non-drug) and size of trial (n<100, 100-500, >500). However, primary sponsors from Australia/New Zealand were almost twice as likely to register prospectively (62%; 4613/7452) compared with sponsors from other countries with a WHO Network Registry (35%; 377/1084) or sponsors from countries without a WHO Registry (29%; 230/781). Part 2: The majority (56%; 84/149) of survey respondents cited lack of awareness as a reason for not registering their study prospectively. Seventy-four per cent (111/149) stated that linking registration to ethics approval would facilitate prospective registration. Despite some progress, compliance with prospective registration remains suboptimal. Linking registration to ethics approval was the favoured strategy among those sampled for improving compliance. © 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.

Exit interviews to reduce turnover amongst healthcare professionals.

PubMed

Flint, Anndrea; Webster, Joan

2013-03-28

Exit interviews are widely used in healthcare organisations to identify reasons for staff attrition, yet their usefulness in limiting turnover is unclear. To determine the effectiveness of various exit interview strategies in decreasing turnover rates amongst healthcare professionals. We searched the Cochrane EPOC Group Specialised Register; Cochrane Central Register of Controlled Trials (CENTRAL), Issue 11, 2012; MEDLINE, Ovid (1950- ); EMBASE, Ovid (1947- ); CINAHL, EbscoHost (1980- ), and PsycINFO, OVID (1806-) between October 31 and November 6, 2012. We also screened the reference lists of included studies and relevant reviews; and searched trial registries for planned and on-going trials. We did not restrict searches by language or publication date. Randomised controlled trials, controlled clinical trials, controlled before-after studies and interrupted time series studies comparing turnover rates between healthcare professionals who had undergone one form of exit interview with another form of exit interview or with no interview. Two review authors independently assessed trial quality and extracted data. The original search identified 1560 citations, of which we considered 19 potentially relevant. The two authors independently reviewed the abstracts of these studies and retrieved the full texts of eight studies. We excluded all eight following independent assessment; they were either interviews, commentaries on how to do an exit interview or descriptive studies about reasons for leaving. We found no trials that matched our inclusion criteria. For this first update, we screened 2220 citations and identified no new trials. Evidence about the effectiveness of exit interviews to reduce turnover is currently not available. However, exit interviews may provide useful information about the work environment which, in turn, may be useful in the development of interventions to reduce turnover.

Exit interviews to reduce turnover amongst healthcare professionals.

PubMed

Webster, Joan; Flint, Anndrea

2014-03-15

Exit interviews are widely used in healthcare organisations to identify reasons for staff attrition, yet their usefulness in limiting turnover is unclear. To determine the effectiveness of various exit interview strategies in decreasing turnover rates amongst healthcare professionals. We searched the Cochrane EPOC Group Specialised Register; Cochrane Central Register of Controlled Trials (CENTRAL), Issue 11, 2012; MEDLINE, Ovid (1950- ); EMBASE, Ovid (1947- ); CINAHL, EbscoHost (1980- ), and PsycINFO, OVID (1806-) between October 31 and November 6, 2012. We also screened the reference lists of included studies and relevant reviews; and searched trial registries for planned and on-going trials. We did not restrict searches by language or publication date. Randomised controlled trials, controlled clinical trials, controlled before-after studies and interrupted time series studies comparing turnover rates between healthcare professionals who had undergone one form of exit interview with another form of exit interview or with no interview. Two review authors independently assessed trial quality and extracted data. The original search identified 1560 citations, of which we considered 19 potentially relevant. The two authors independently reviewed the abstracts of these studies and retrieved the full texts of eight studies. We excluded all eight following independent assessment; they were either interviews, commentaries on how to do an exit interview or descriptive studies about reasons for leaving. We found no trials that matched our inclusion criteria. For this first update, we screened 2220 citations and identified no new trials. Evidence about the effectiveness of exit interviews to reduce turnover is currently not available. However, exit interviews may provide useful information about the work environment which, in turn, may be useful in the development of interventions to reduce turnover.

Impact of a Primary Care CKD Registry in a US Public Safety-Net Health Care Delivery System: A Pragmatic Randomized Trial.

PubMed

Tuot, Delphine S; McCulloch, Charles E; Velasquez, Alexandra; Schillinger, Dean; Hsu, Chi-Yuan; Handley, Margaret; Powe, Neil R

2018-04-23

Many individuals with chronic kidney disease (CKD) do not receive guideline-concordant care. We examined the impact of a team-based primary care CKD registry on clinical measures and processes of care among patients with CKD cared for in a public safety-net health care delivery system. Pragmatic trial of a CKD registry versus a usual-care registry for 1 year. Primary care providers (PCPs) and their patients with CKD in a safety-net primary care setting in San Francisco. The CKD registry identified at point of care all patients with CKD, those with blood pressure (BP)>140/90mmHg, those without angiotensin-converting enzyme (ACE) inhibitor/angiotensin receptor blocker (ARB) prescription, and those without albuminuria quantification in the past year. It also provided quarterly feedback pertinent to these metrics to promote "outreach" to patients with CKD. The usual-care registry provided point-of-care cancer screening and immunization data. Changes in systolic BP at 12 months (primary outcome), proportion of patients with BP control, prescription of ACE inhibitors/ARBs, quantification of albuminuria, severity of albuminuria, and estimated glomerular filtration rate. The patient population (n=746) had a mean age of 56.7±12.1 (standard deviation) years, was 53% women, and was diverse (8% non-Hispanic white, 35.7% black, 24.5% Hispanic, and 24.4% Asian). Randomization to the CKD registry (30 PCPs, 285 patients) versus the usual-care registry (49 PCPs, 461 patients) was associated with 2-fold greater odds of ACE inhibitor/ARB prescription (adjusted OR, 2.25; 95% CI, 1.45-3.49) and albuminuria quantification (adjusted OR, 2.44; 95% CI, 1.38-4.29) during the 1-year study period. Randomization to the CKD registry was not associated with changes in systolic BP, proportion of patients with uncontrolled BP, or degree of albuminuria or estimated glomerular filtration rate. Potential misclassification of CKD; missing baseline medication data; limited to study of a public safety-net health care system. A team-based safety-net primary care CKD registry did not improve BP parameters, but led to greater albuminuria quantification and more ACE inhibitor/ARB prescriptions after 1 year. Adoption of team-based CKD registries may represent an important step in translating evidence into practice for CKD management. Copyright © 2018 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.

Vascular protection in peripheral artery disease: systematic review and modelling study.

PubMed

Hackam, D G; Sultan, N M; Criqui, M H

2009-07-01

To ascertain the effectiveness of medical therapy for reducing risk in peripheral artery disease (PAD) and to model the potential impact of combining multiple efficacious approaches. 17 electronic databases, reference lists of primary studies, clinical practice guidelines, review articles, trial registries and conference proceedings from cardiology, vascular surgery and atherosclerosis meetings were screened. Eligible studies were randomized trials or meta-analyses of randomized trials of medical therapy for PAD which reported major cardiovascular events (myocardial infarction, stroke and cardiovascular death). Baseline event rates for modelling analyses were derived from published natural history cohorts. Overall, three strategies had persuasive evidence for reducing risk in PAD: antiplatelet agents (pooled RRR 26%, 95% CI 10 to 42), statins (pooled RRR 26%, 95% CI 18 to 33) and angiotensin-converting enzyme inhibitors (individual trial RRR 25%, 95% CI 8 to 39). The estimated cumulative relative risk reduction for all three strategies was 59% (CI 32 to 76). Given a 5-year major cardiovascular event rate of 25%, the corresponding absolute risk reduction and number needed to treat to prevent one event were 15% (CI 8 to 19) and 7 (CI 5 to 12), respectively. Population level analyses suggest that increased uptake of these modalities could prevent more than 200 000 events in patients with PAD each year. The use of multiple efficacious strategies has the potential to substantially reduce the cardiovascular burden of PAD. However, these data should be regarded as hypothetical, since they are based on mathematical modelling rather than factorial randomized trials.

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

PubMed

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

2017-07-26

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

[The role of recombinant activated factor VII in neuro- surgical and neurocritical patients].

PubMed

Rama-Maceiras, P; Ingelmo-Ingelmo, I; Fábregas-Juliá, N; Hernández-Palazón, J

2011-06-01

Central nervous system haemorrhage is a severe pathology, as a small amount of bleeding inside the brain can result in devastating consequences. Haemostatic agents might decrease the consequences of intra- cranial bleeding, whichever spontaneous, traumatic, or anticoagulation treatment etiology. Proacogulant recombinant activated factor VII (rFVIIa) has been given after central nervous system bleeding, with an off-label indication. In this update, we go over the drug mechanism of action, its role in the treatment of central nervous system haemorrhage and the published evidences regarding this subject. We carried out a literature review concerning the treatment with rFVIIa in central nervous system haemorrhage, neurocritical pathologies and neurosurgical procedures, searching in MEDLINE and in clinical trials registry: http://clinicaltrials.gov (last review September 2010), as well as performing a manual analysis of collected articles, looking for aditional references. The results of randomized clinical trials do not support the systematic administration of rFVIIa for spontaneous intracranial cerebral haemorrhage. In other central nervous system related haemorrhages, the current available data consist on retrospective studies, expert opinion or isolated case reports.

Optical reading aids for children and young people with low vision.

PubMed

Barker, Lucy; Thomas, Rachel; Rubin, Gary; Dahlmann-Noor, Annegret

2015-03-04

Low vision in childhood is a significant barrier to learning and development, particularly for reading and education. Optical low vision aids may be used to maximise the child's functional vision. The World Health Organization (WHO) has previously highlighted the importance of the use of low vision aids in managing children with visual impairment across the world. To assess the effect of optical low vision aids on reading in children and young people with low vision. We searched CENTRAL (which contains the Cochrane Eyes and Vision Group Trials Register) (2014, Issue 12), Ovid MEDLINE, Ovid MEDLINE In-Process and Other Non-Indexed Citations, Ovid MEDLINE Daily, Ovid OLDMEDLINE (January 1946 to January 2015), EMBASE (January 1980 to January 2015), the Health Technology Assessment Programme (HTA) (www.hta.ac.uk/), the ISRCTN registry (www.isrctn.com/editAdvancedSearch), ClinicalTrials.gov (www.clinicaltrials.gov) and the World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP) (www.who.int/ictrp/search/en). We did not use any date or language restrictions in the electronic searches for trials. We last searched the electronic databases on 8 January 2015.We also used manual searching to check the references listed in retrieved articles. Manufacturers of low vision aids were contacted to request any information about studies or research regarding their products. We planned to include randomised controlled trials (RCTs) and quasi-RCTs where any optical low vision aid was compared to standard refractive correction in children and young people aged between 5 and 16 years of age with low vision as defined by the WHO. We planned to include within-person design studies where the order of presentation of devices was randomised. Two authors independently reviewed the search results for eligibility . No studies met the inclusion criteria for this review. There is a lack of good quality evidence regarding the use of optical low vision aids in children and young people. As such, no implications for practice can be drawn. We believe future research should include functional outcome measures such as reading speed, accuracy and comprehension, as well as the effect of low vision aids on quality of life, in order to truly assess and compare the effect of these devices on a child's life and development.

Challenges in translating endpoints from trials to observational cohort studies in oncology

PubMed Central

Ording, Anne Gulbech; Cronin-Fenton, Deirdre; Ehrenstein, Vera; Lash, Timothy L; Acquavella, John; Rørth, Mikael; Sørensen, Henrik Toft

2016-01-01

Clinical trials are considered the gold standard for examining drug efficacy and for approval of new drugs. Medical databases and population surveillance registries are valuable resources for post-approval observational research, which are increasingly used in studies of benefits and risk of new cancer drugs. Here, we address the challenges in translating endpoints from oncology trials to observational studies. Registry-based cohort studies can investigate real-world safety issues – including previously unrecognized concerns – by examining rare endpoints or multiple endpoints at once. In contrast to clinical trials, observational cohort studies typically do not exclude real-world patients from clinical practice, such as old and frail patients with comorbidity. The observational cohort study complements the clinical trial by examining the effectiveness of interventions applied in clinical practice and by providing evidence on long-term clinical outcomes, which are often not feasible to study in a clinical trial. Various endpoints can be included in clinical trials, such as hard endpoints, soft endpoints, surrogate endpoints, and patient-reported endpoints. Each endpoint has it strengths and limitations for use in research studies. Endpoints used in oncology trials are often not applicable in observational cohort studies which are limited by the setting of standard clinical practice and by non-standardized endpoint determination. Observational studies can be more helpful moving research forward if they restrict focus to appropriate and valid endpoints. PMID:27354827

[Diagnostic criteria and risk assessment of complications after gastric cancer surgery in western countries].

PubMed

Wu, Zhouqiao; Wang, Qi; Shi, Jinyao; Cherry, Koh; Desiderio, Jacopo; Li, Ziyu; Ji, Jiafu

2017-02-25

Postoperative complications are important outcome measurements for surgical quality and safety control. However, the complication registration has always been problematic due to the lack of definition consensus and the other practical difficulties. This narrative review summarizes the data registry system for single institutional registry, national data registry, international multi-center trial registries in the western world, aiming to share the experience of complication classification and data registration. We interviewed Dr. Koh from Royal Prince Alfred Hospital in Australia for single institutional experience, Dr. van der Wielen and Dr. Desideriofor, from two international multi-center trial(STOMACH) and registry (IMIGASTRIC) respectively, and Prof. Dr. Wijnhoven from the Dutch Upper GI Audit(DUCA). The major questions include which complications are obligated to report in the respective registry, what are the definitions of those complications, who perform the registration, and how are the complications evaluated or classified. Four telephone conferences were initiated to discuss the above-mentioned topics. The DUCA and IMGASTRIC provided the definition of the major complications. The consent definition provided by DUCA was based on the LOW classification which came out after a four-year discussion and consensus meeting among international experts in the according field. However, none of the four registries asked for an obligatory standardization of the diagnostic criteria among the participating centers or surgeons. Instead, all the registries required a detailed recording of the diagnostic strategy and classification of the complications with the Clavien-Dindo scoring system. Most data were registered by surgeons or data managers during or immediately after the hospitalization. The investigators or an independent third party conducted the auditing of the data quality. Standardization of complication diagnosis among different centers is a difficult task, consuming much effort and time. On top of that, standardization of the complication registration is of critical and practical importance. We encourage all centers to register complications with the diagnostic criteria and following intervention. Based on this, the Clavien-Dindo classification can be properly justified, which has been widely accepted by most centers and should be routinely used as the standard evaluation system for postoperative complications in gastric tumor surgery.

Booster dose vaccination for preventing hepatitis B.

PubMed

Poorolajal, Jalal; Hooshmand, Elham

2016-06-07

Antibodies against hepatitis B surface antigen (HBsAg) wane over time following hepatitis B immunisation; hence, it is unclear whether people vaccinated in three-dose or four-dose schedules of the hepatitis B vaccine are still immune when the hepatitis B surface antibody (anti-HBs) level in their body is undetectable, or lower than the level usually considered protective. This question may potentially be answered indirectly by measuring the anamnestic immune response to a booster dose of vaccine. The term 'booster' (or revaccination) refers to an additional dose of hepatitis B vaccine (HBV) given some time post-primary vaccination to induce immune memory and improve protection against hepatitis B virus (HBV) infection. To assess the benefits and harms of booster dose hepatitis B vaccination, more than five years after the primary vaccination, for preventing HBV infection in healthy individuals previously vaccinated with the hepatitis B vaccine, and with hepatitis B surface antibody (anti-HBs) levels below 10 mIU/mL. We searched the Cochrane Hepato-Biliary Group Controlled Trials Register, the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE, Science Citation Index Expanded, conference databases, and reference lists of articles to January 2016. We also contacted authors of articles. In addition, we searched ClinicalTrials.gov and the World Health Organization (WHO) International Clinical Trials Registry Platform for ongoing trials (May 2016). Randomised clinical trials addressing anamnestic immune response to a booster dose of hepatitis B vaccine, more than five years after the primary vaccination, in apparently healthy participants, vaccinated in a three-dose or four-dose schedule of the hepatitis B vaccine during the primary vaccination, without receiving an additional dose or immunoglobulin. Both review authors decided if the identified studies met the inclusion criteria or not. Primary outcomes included the proportion of participants with anamnestic immune response in non-protected participants and signs of HBV infection. Secondary outcomes were the proportion of participants that developed local and systemic adverse events following a booster dose injection. We planned to report the weighted proportion with 95% confidence intervals (CIs). There were no eligible randomised clinical trials fulfilling the inclusion criteria of this review. We were unable to include any randomised clinical trials on the topic; only randomised clinical trials will be able to provide an answer as to whether a booster dose vaccination is able to protect against hepatitis B infection.

International Clinical Trials in Latin American and Caribbean Countries: Research and Development to Meet Local Health Needs

PubMed Central

da Silva, Ricardo E.; Amato, Angélica A.; Guilhem, Dirce B.; de Carvalho, Marta R.; Novaes, Maria R. C. G.

2018-01-01

Introduction: Although international health research involves some benefits for the host countries, such as access to innovative treatments, the research itself may not be aligned with their communities' actual health needs. Objective: To map the global landscape of clinical trials run in Latin American and Caribbean countries and discuss the addressing of local health needs in the agenda of international clinical trials. Methods: The present study is a cross-sectional overview and used data referent to studies registered between 01/01/2014 and 12/31/2014 in the World Health Organization's (WHO) International Clinical Trials Registry Platform (ICTRP). Results: Non-communicable diseases such as diabetes, cancer, and asthma—studies which were financed mainly by industries—were the conditions investigated most in the region of Latin America and the Caribbean. The neglected diseases, on the other hand, such as Chagas disease, and dengue, made up 1% of the total number of studies. Hospitals and nonprofit nongovernmental organizations prioritize resources for investigating new drugs for neglected diseases, such as Chagas disease and dengue. Conclusion: The international multicenter clinical trials for investigating new drugs are aligned with the health needs of the region of Latin America and the Caribbean, when one considers the burden resulting from the non-communicable diseases in this region. However, the transmissible diseases, such as tuberculosis and AIDS, and the neglected diseases, such as Chagas disease and dengue, which have an important impact on public health in this region, continue to arouse little interest among the institutions which finance the clinical trials. PMID:29354059

Methods for increasing upper airway muscle tonus in treating obstructive sleep apnea: systematic review.

PubMed

Valbuza, Juliana Spelta; de Oliveira, Márcio Moysés; Conti, Cristiane Fiquene; Prado, Lucila Bizari F; de Carvalho, Luciane Bizari Coin; do Prado, Gilmar Fernandes

2010-12-01

Treatment of obstructive sleep apnea (OSA) using methods for increasing upper airway muscle tonus has been controversial and poorly reported. Thus, a review of the evidence is needed to evaluate the effectiveness of these methods. The design used was a systematic review of randomized controlled trials. Data sources are from the Cochrane Library, Medline, Embase and Scielo, registries of ongoing trials, theses indexed at Biblioteca Regional de Medicina/Pan-American Health Organization of the World Health Organization and the reference lists of all the trials retrieved. This was a review of randomized or quasi-randomized double-blind trials on OSA. Two reviewers independently applied eligibility criteria. One reviewer assessed study quality and extracted data, and these processes were checked by a second reviewer. The primary outcome was a decrease in the apnea/hypopnea index (AHI) of below five episodes per hour. Other outcomes were subjective sleep quality, sleep quality measured by night polysomnography, quality of life measured subjectively and adverse events associated with the treatments. Three eligible trials were included. Two studies showed improvements through the objective and subjective analyses, and one study showed improvement of snoring, but not of AHI while the subjective analyses showed no improvement. The adverse events were reported and they were not significant. There is no accepted scientific evidence that methods aiming to increase muscle tonus of the stomatognathic system are effective in reducing AHI to below five events per hour. Well-designed randomized controlled trials are needed to assess the efficacy of such methods.

Is Mandatory Prospective Trial Registration Working to Prevent Publication of Unregistered Trials and Selective Outcome Reporting? An Observational Study of Five Psychiatry Journals That Mandate Prospective Clinical Trial Registration.

PubMed

Scott, Amelia; Rucklidge, Julia J; Mulder, Roger T

2015-01-01

To address the bias occurring in the medical literature associated with selective outcome reporting, in 2005, the International Committee of Medical Journal Editors (ICMJE) introduced mandatory trial registration guidelines and member journals required prospective registration of trials prior to patient enrolment as a condition of publication. No research has examined whether these guidelines are impacting psychiatry publications. Our objectives were to determine the extent to which articles published in psychiatry journals adhering to ICMJE guidelines were correctly prospectively registered, whether there was evidence of selective outcome reporting and changes to participant numbers, and whether there was a relationship between registration status and source of funding. Any clinical trial (as defined by ICMJE) published between 1 January 2009 and 31 July 2013 in the top five psychiatry journals adhering to ICMJE guidelines (The American Journal of Psychiatry, Archives of General Psychiatry/JAMA Psychiatry, Biological Psychiatry, Journal of the American Academy of Child and Adolescent Psychiatry, and The Journal of Clinical Psychiatry) and conducted after July 2005 (or 2007 for two journals) was included. For each identified trial, where possible we extracted trial registration information, changes to POMs between publication and registry to assess selective outcome reporting, changes to participant numbers, and funding type. Out of 3305 articles, 181 studies were identified as clinical trials requiring registration: 21 (11.6%) were deemed unregistered, 61 (33.7%) were retrospectively registered, 37 (20.4%) had unclear POMs either in the article or the registry and 2 (1.1%) were registered in an inaccessible trial registry. Only 60 (33.1%) studies were prospectively registered with clearly defined POMs; 17 of these 60 (28.3%) showed evidence of selective outcome reporting and 16 (26.7%) demonstrated a change in participant numbers of 20% or more; only 26 (14.4%) of the 181 the trials were prospectively registered and did not alter their POMs or the time frames at which they were measured. Prospective registration with no changes in POMs occurred more frequently with pharmaceutical funding. Although standards are in place to improve prospective registration and transparency in clinical trials, less than 15% of psychiatry trials were prospectively registered with no changes in POMs. Most trials were either not prospectively registered, changed POMs or the timeframes at some point after registration or changed participant numbers. Authors, journal editors and reviewers need to further efforts to highlight the value of prospective trial registration.

Clinical Trials Network / Building Infrastructure to Accelerate Transfer of Basic Research in Spinal Cord Injury (SCI) to Clinical Practice

DTIC Science & Technology

2015-05-01

Glasgow Coma Scale (GCS) and of associated injuries with the Abbreviated Injury Scale . The American Spinal Injury Association impairment scale (AIS) is...registry protocol includes: the AIS Impairment Scale , and where appropriate, the Functional Independence Measure FIM™, the Spinal Cord Independence...have been achieved with the registry. Enrollment of 762 participants has demonstrated that is feasible to acquire prospective standardized research

Generalizability of EXCEL and NOBLE results to a large registry population with unprotected left main coronary artery disease.

PubMed

Lee, Pil Hyung; Kang, Se Hun; Han, Seungbong; Ahn, Jung-Min; Bae, Jae Seok; Lee, Cheol Hyun; Kang, Soo-Jin; Lee, Seung-Whan; Kim, Young-Hak; Lee, Cheol Whan; Park, Seong-Wook; Park, Duk-Woo; Park, Seung-Jung

2017-12-01

The aim of this study was to determine how trial-based findings of EXCEL and NOBLE might be interpreted and generalizable in 'real-world' settings with comparison of data from the large-scaled, all-comer Interventional Research Incorporation Society-Left MAIN Revascularization (IRIS-MAIN) registry. We compared baseline clinical and procedural characteristics and also determined how the relative treatment effect of percutaneous coronary intervention (PCI) and coronary artery bypass grafting (CABG) was different in EXCEL and NOBLE, compared with those of the multicenter, IRIS-MAIN registry (n=2481). The primary outcome for between-study comparison was a composite of death, myocardial infarction (MI), or stroke. There were between-study differences in patient risk profiles (age, BMI, diabetes, and clinical presentation), lesion complexities, and procedural characteristics (stent type, the use of off-pump surgery, and radial artery); the proportion of diabetes and acute coronary syndrome was particularly lower in NOBLE than in other studies. Although there was interstudy heterogeneity for the protocol definition of MI, the risks for serious composite outcome of death, MI, or stroke were similar between PCI and CABG in EXCEL [hazard ratio (HR): 1.00; 95% confidence interval (CI): 0.79-1.26; P=0.98] and in the matched cohort of IRIS-MAIN (HR: 1.08; 95%CI: 0.85-1.38; P=0.53), whereas it was significantly higher after PCI than after CABG in NOBLE (HR: 1.47; 95%CI: 1.06-2.05; P=0.02), which was driven by more common MI and stroke after PCI. In the comparison of a large-sized, all-comer registry, the EXCEL trial might represent better generalizability with respect to baseline characteristics and observed clinical outcomes compared with the NOBLE trial.

Results of the post-market Registry to Evaluate the HeartWare Left Ventricular Assist System (ReVOLVE).

PubMed

Strueber, Martin; Larbalestier, Robert; Jansz, Paul; Zimpfer, Daniel; Fiane, Arnt E; Tsui, Steven; Simon, André; Schmitto, Jan D; Khaghani, Asghar; Wieselthaler, George M; Najarian, Kevin; Schueler, Stephan

2014-05-01

The post-market Registry to Evaluate the HeartWare Left Ventricular Assist System (ReVOLVE) is an investigator-initiated registry established to collect post-CE Mark Trial clinical data on patients receiving a HeartWare ventricular assist device (HVAD) in the European Union and Australia. The ReVOLVE is a multi-center, prospective, single-arm registry performed at seven centers in Europe and two in Australia. Herein we describe a total of 254 commercial HVAD implants according to labeled indications between February 2009 and November 2012. Summary statistics included patients' demographics, adverse events, length of support and outcomes. Compared with the clinical trial supporting the CE Mark of the HeartWare system, patient selection differed in that patients were older, and there were higher proportions of females and patients with idiopathic cardiomyopathies in the ReVOLVE cohort. Duration of support ranged from 1 to 1,057 days, with a mean of 363 ± 280 days (median 299.5 days). Transplantation was done in 56 patients (22%), explant for recovery was performed in 3 patients (1%), 43 died while on support (17%), and 152 (60%) remain on the device. Success in patients with the HeartWare system was 87% at 6 months, 85% at 1 year, 79% at 2 years and 73% at 3 years. Adverse event rates were low, comparable or improved when compared to the CE Mark Trial. Real-world use of the HeartWare system continues to demonstrate excellent clinical outcomes in patients supported with the device. Copyright © 2014 International Society for Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.

Planning the Safety of Atrial Fibrillation Ablation Registry Initiative (SAFARI) as a Collaborative Pan-Stakeholder Critical Path Registry Model: a Cardiac Safety Research Consortium "Incubator" Think Tank.

PubMed

Al-Khatib, Sana M; Calkins, Hugh; Eloff, Benjamin C; Packer, Douglas L; Ellenbogen, Kenneth A; Hammill, Stephen C; Natale, Andrea; Page, Richard L; Prystowsky, Eric; Jackman, Warren M; Stevenson, William G; Waldo, Albert L; Wilber, David; Kowey, Peter; Yaross, Marcia S; Mark, Daniel B; Reiffel, James; Finkle, John K; Marinac-Dabic, Danica; Pinnow, Ellen; Sager, Phillip; Sedrakyan, Art; Canos, Daniel; Gross, Thomas; Berliner, Elise; Krucoff, Mitchell W

2010-01-01

Atrial fibrillation (AF) is a major public health problem in the United States that is associated with increased mortality and morbidity. Of the therapeutic modalities available to treat AF, the use of percutaneous catheter ablation of AF is expanding rapidly. Randomized clinical trials examining the efficacy and safety of AF ablation are currently underway; however, such trials can only partially determine the safety and durability of the effect of the procedure in routine clinical practice, in more complex patients, and over a broader range of techniques and operator experience. These limitations of randomized trials of AF ablation, particularly with regard to safety issues, could be addressed using a synergistically structured national registry, which is the intention of the SAFARI. To facilitate discussions about objectives, challenges, and steps for such a registry, the Cardiac Safety Research Consortium and the Duke Clinical Research Institute, Durham, NC, in collaboration with the US Food and Drug Administration, the American College of Cardiology, and the Heart Rhythm Society, organized a Think Tank meeting of experts in the field. Other participants included the National Heart, Lung and Blood Institute, the Centers for Medicare and Medicaid Services, the Agency for Healthcare Research and Quality, the Society of Thoracic Surgeons, the AdvaMed AF working group, and additional industry representatives. The meeting took place on April 27 to 28, 2009, at the US Food and Drug Administration headquarters in Silver Spring, MD. This article summarizes the issues and directions presented and discussed at the meeting. Copyright 2010 Mosby, Inc. All rights reserved.

Design of FRESH START: A Randomized Trial of Exercise and Diet among Cancer Survivors.

ERIC Educational Resources Information Center

Demark-Wahnefried, Wendy; Clipp, Elizabeth C.; McBride, Colleen; Lobach, David F.; Lipkus, Isaac; Peterson, Bercedis; Snyder, Denise Clutter; Sloane, Richard; Arbanas, Jennifer; Kraus, William E.

2003-01-01

Fresh Start is a randomized, controlled trial that will test whether personally tailored, distance-medicine-based programs will increase exercise and fruit and vegetable consumption and decrease fat intake among individuals recently diagnosed with breast or prostate cancer. People from hospital cancer registries and oncologic practices will…

The utility of heart failure registries: a descriptive and comparative study of two heart failure registries.

PubMed

Trullàs, Joan Carles; Miró, Òscar; Formiga, Francesc; Martín-Sánchez, Francisco Javier; Montero-Pérez-Barquero, Manuel; Jacob, Javier; Quirós-López, Raúl; Herrero Puente, Pablo; Manzano, Luís; Llorens, Pere

2016-05-01

Registries are useful to address questions that are difficult to answer in clinical trials. The objective of this study was to describe and compare two heart failure (HF) cohorts from two Spanish HF registries. We compared the RICA and EAHFE registries, both of which are prospective multicentre cohort studies including patients with decompensated HF consecutively admitted to internal medicine wards (RICA) or attending the emergency department (EAHFE). From the latter registry we only included patients who were admitted to internal medicine wards. A total of 5137 patients admitted to internal medicine wards were analysed (RICA: 3287 patients; EAHFE: 1850 patients). Both registries included elderly patients (RICA: mean (SD) age 79 (9) years; EAHFE: mean (SD) age 81 (9) years), with a slight predominance of female gender (52% and 58%, respectively, in the RICA and EAHFE registries) and with a high proportion of patients with preserved ejection fraction (58% and 62%, respectively). Some differences in comorbidities were noted, with diabetes mellitus, dyslipidaemia, chronic renal failure and atrial fibrillation being more frequent in the RICA registry while cognitive and functional impairment predominated in the EAHFE registry. The 30-day mortality after discharge was 3.4% in the RICA registry and 4.8% in the EAHFE registry (p<0.05) and the 30-day readmission rate was 7.5% in the RICA registry (readmission to hospital) and 24.0% in the EAHFE registry (readmission to emergency department) (p<0.001). We found differences in the clinical characteristics of patients admitted to Spanish internal medicine wards for decompensated HF depending on inclusion in either the RICA or EAHFE registry. 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/

Comparison of Registered and Reported Outcomes in Randomized Clinical Trials Published in Anesthesiology Journals.

PubMed

Jones, Philip M; Chow, Jeffrey T Y; Arango, Miguel F; Fridfinnson, Jason A; Gai, Nan; Lam, Kevin; Turkstra, Timothy P

2017-10-01

Randomized clinical trials (RCTs) provide high-quality evidence for clinical decision-making. Trial registration is one of the many tools used to improve the reporting of RCTs by reducing publication bias and selective outcome reporting bias. The purpose of our study is to examine whether RCTs published in the top 6 general anesthesiology journals were adequately registered and whether the reported primary and secondary outcomes corresponded to the originally registered outcomes. Following a prespecified protocol, an electronic database was used to systematically screen and extract data from RCTs published in the top 6 general anesthesiology journals by impact factor (Anaesthesia, Anesthesia & Analgesia, Anesthesiology, British Journal of Anaesthesia, Canadian Journal of Anesthesia, and European Journal of Anaesthesiology) during the years 2007, 2010, 2013, and 2015. A manual search of each journal's Table of Contents was performed (in duplicate) to identify eligible RCTs. An adequately registered trial was defined as being registered in a publicly available trials registry before the first patient being enrolled with an unambiguously defined primary outcome. For adequately registered trials, the outcomes registered in the trial registry were compared with the outcomes reported in the article, with outcome discrepancies documented and analyzed by the type of discrepancy. During the 4 years studied, there were 860 RCTs identified, with 102 RCTs determined to be adequately registered (12%). The proportion of adequately registered trials increased over time, with 38% of RCTs being adequately registered in 2015. The most common reason in 2015 for inadequate registration was registering the RCT after the first patient had already been enrolled. Among adequately registered trials, 92% had at least 1 primary or secondary outcome discrepancy. In 2015, 42% of RCTs had at least 1 primary outcome discrepancy, while 90% of RCTs had at least 1 secondary outcome discrepancy. Despite trial registration being an accepted best practice, RCTs published in anesthesiology journals have a high rate of inadequate registration. While mandating trial registration has increased the proportion of adequately registered trials over time, there is still an unacceptably high proportion of inadequately registered RCTs. Among adequately registered trials, there are high rates of discrepancies between registered and reported outcomes, suggesting a need to compare a published RCT with its trial registry entry to be able to fully assess the quality of the study. If clinicians base their decisions on evidence distorted by primary outcome switching, patient care could be negatively affected.

Characterization and utilization of an international neurofibromatosis web-based, patient–entered registry: An observational study

PubMed Central

Korf, Bruce; Rangel Miller, Vanessa; Viskochil, David

2017-01-01

The neurofibromatoses (neurofibromatosis type 1, neurofibromatosis type 2 and schwannomatosis) are rare disorders having clinical manifestations that vary greatly from patient to patient. The rarity and variability of these disorders has made it challenging for investigators to identify sufficient numbers of patients with particular clinical characteristics or specific germline mutations for participation in interventional studies. Similarly, because the natural history of all types of neurofibromatosis (NF) is variable and unique for each individual, it is difficult to identify meaningful clinical outcome measures for potential therapeutic interventions. In 2012, the Children’s Tumor Foundation created a web-based patient-entered database, the NF Registry, to inform patients of research opportunities for which they fit general eligibility criteria and enable patients to contact investigators who are seeking to enroll patients in approved trials. Registrants were recruited through CTF-affiliated NF clinics and conferences, through its website, and by word-of-mouth and social media. Following online consent, demographic information and details regarding manifestations of NF were solicited on the Registry website. Statistical analyses were performed on data from a cohort of 4680 registrants (the number of registrants as of October 9, 2015) who met diagnostic criteria for one of the 3 NF conditions. The analyses support our hypothesis that patient-reported symptom incidences in the NF Registry are congruent with published clinician-sourced data. Between April 26, 2013 and July 8, 2016, the registry has been useful to investigators in recruitment, particularly for observational trials, especially those for development of patient-reported outcomes. PMID:28644838

Characterization and utilization of an international neurofibromatosis web-based, patient-entered registry: An observational study.

PubMed

Seidlin, Mindell; Holzman, Robert; Knight, Pamela; Korf, Bruce; Rangel Miller, Vanessa; Viskochil, David; Bakker, Annette

2017-01-01

The neurofibromatoses (neurofibromatosis type 1, neurofibromatosis type 2 and schwannomatosis) are rare disorders having clinical manifestations that vary greatly from patient to patient. The rarity and variability of these disorders has made it challenging for investigators to identify sufficient numbers of patients with particular clinical characteristics or specific germline mutations for participation in interventional studies. Similarly, because the natural history of all types of neurofibromatosis (NF) is variable and unique for each individual, it is difficult to identify meaningful clinical outcome measures for potential therapeutic interventions. In 2012, the Children's Tumor Foundation created a web-based patient-entered database, the NF Registry, to inform patients of research opportunities for which they fit general eligibility criteria and enable patients to contact investigators who are seeking to enroll patients in approved trials. Registrants were recruited through CTF-affiliated NF clinics and conferences, through its website, and by word-of-mouth and social media. Following online consent, demographic information and details regarding manifestations of NF were solicited on the Registry website. Statistical analyses were performed on data from a cohort of 4680 registrants (the number of registrants as of October 9, 2015) who met diagnostic criteria for one of the 3 NF conditions. The analyses support our hypothesis that patient-reported symptom incidences in the NF Registry are congruent with published clinician-sourced data. Between April 26, 2013 and July 8, 2016, the registry has been useful to investigators in recruitment, particularly for observational trials, especially those for development of patient-reported outcomes.

Comparison between publicly accessible publications, registries, and protocols of phase III trials indicated persistence of selective outcome reporting.

PubMed

Zhang, Sheng; Liang, Fei; Li, Wenfeng

2017-11-01

The decision to make protocols of phase III randomized controlled trials (RCTs) publicly accessible by leading journals was a landmark event in clinical trial reporting. Here, we compared primary outcomes defined in protocols with those in publications describing the trials and in trial registration. We identified phase III RCTs published between January 1, 2012, and June 30, 2015, in The New England Journal of Medicine, The Lancet, The Journal of the American Medical Association, and The BMJ with available protocols. Consistency in primary outcomes between protocols and registries (articles) was evaluated. We identified 299 phase III RCTs with available protocols in this analysis. Out of them, 25 trials (8.4%) had some discrepancy for primary outcomes between publications and protocols. Types of discrepancies included protocol-defined primary outcome reported as nonprimary outcome in publication (11 trials, 3.7%), protocol-defined primary outcome omitted in publication (10 trials, 3.3%), new primary outcome introduced in publication (8 trials, 2.7%), protocol-defined nonprimary outcome reported as primary outcome in publication (4 trials, 1.3%), and different timing of assessment of primary outcome (4 trials, 1.3%). Out of trials with discrepancies in primary outcome, 15 trials (60.0%) had discrepancies that favored statistically significant results. Registration could be seen as a valid surrogate of protocol in 237 of 299 trials (79.3%) with regard to primary outcome. Despite unrestricted public access to protocols, selective outcome reporting persists in a small fraction of phase III RCTs. Only studies from four leading journals were included, which may cause selection bias and limit the generalizability of this finding. Copyright © 2017 Elsevier Inc. All rights reserved.

On-going clinical trials for elderly patients with a hematological malignancy: are we addressing the right end points?

PubMed

Hamaker, M E; Stauder, R; van Munster, B C

2014-03-01

Cancer societies and research cooperative groups worldwide have urged for the development of cancer trials that will address those outcome measures that are most relevant to older patients. We set out to determine the characteristics and study objectives of current clinical trials in hematological patients. The United States National Institutes of Health clinical trial registry was searched on 1 July 2013, for currently recruiting phase I, II or III clinical trials in hematological malignancies. Trial characteristics and study objectives were extracted from the registry website. In the 1207 clinical trials included in this overview, patient-centered outcome measures such as quality of life, health care utilization and functional capacity were only incorporated in a small number of trials (8%, 4% and 0.7% of trials, respectively). Even in trials developed exclusively for older patients, the primary focus lies on standard end points such as toxicity, efficacy and survival, while patient-centered outcome measures are included in less than one-fifth of studies. Currently on-going clinical trials in hematological malignancies are unlikely to significantly improve our knowledge of the optimal treatment of older patients as those outcome measures that are of primary importance to this patient population are still included in only a minority of studies. As a scientific community, we cannot continue to simply acknowledge this issue, but must all participate in taking the necessary steps to enable the delivery of evidence-based, tailor-made and patient-focused cancer care to our rapidly growing elderly patient population.

On-going clinical trials for elderly patients with a hematological malignancy: are we addressing the right end points?†

PubMed Central

Hamaker, M. E.; Stauder, R.; van Munster, B. C.

2014-01-01

Background Cancer societies and research cooperative groups worldwide have urged for the development of cancer trials that will address those outcome measures that are most relevant to older patients. We set out to determine the characteristics and study objectives of current clinical trials in hematological patients. Method The United States National Institutes of Health clinical trial registry was searched on 1 July 2013, for currently recruiting phase I, II or III clinical trials in hematological malignancies. Trial characteristics and study objectives were extracted from the registry website. Results In the 1207 clinical trials included in this overview, patient-centered outcome measures such as quality of life, health care utilization and functional capacity were only incorporated in a small number of trials (8%, 4% and 0.7% of trials, respectively). Even in trials developed exclusively for older patients, the primary focus lies on standard end points such as toxicity, efficacy and survival, while patient-centered outcome measures are included in less than one-fifth of studies. Conclusion Currently on-going clinical trials in hematological malignancies are unlikely to significantly improve our knowledge of the optimal treatment of older patients as those outcome measures that are of primary importance to this patient population are still included in only a minority of studies. As a scientific community, we cannot continue to simply acknowledge this issue, but must all participate in taking the necessary steps to enable the delivery of evidence-based, tailor-made and patient-focused cancer care to our rapidly growing elderly patient population. PMID:24458474

Efficacy of a multimodal physiotherapy treatment program for hip osteoarthritis: a randomised placebo-controlled trial protocol

PubMed Central

2010-01-01

Background Hip osteoarthritis (OA) is a common condition leading to pain, disability and reduced quality of life. There is currently limited evidence to support the use of conservative, non-pharmacological treatments for hip OA. Exercise and manual therapy have both shown promise and are typically used together by physiotherapists to manage painful hip OA. The aim of this randomised controlled trial is to compare the efficacy of a physiotherapy treatment program with placebo treatment in reducing pain and improving physical function. Methods The trial will be conducted at the University of Melbourne Centre for Health, Exercise and Sports Medicine. 128 participants with hip pain greater or equal to 40/100 on visual analogue scale (VAS) and evidence of OA on x-ray will be recruited. Treatment will be provided by eight community physiotherapists in the Melbourne metropolitan region. The active physiotherapy treatment will comprise a semi-structured program of manual therapy and exercise plus education and advice. The placebo treatment will consist of sham ultrasound and the application of non-therapeutic gel. The participants and the study assessor will be blinded to the treatment allocation. Primary outcomes will be pain measured by VAS and physical function recorded on the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) immediately after the 12 week intervention. Participants will also be followed up at 36 weeks post baseline. Conclusions The trial design has important strengths of reproducibility and reflecting contemporary physiotherapy practice. The findings from this randomised trial will provide evidence for the efficacy of a physiotherapy program for painful hip OA. Trial Registration Australian New Zealand Clinical Trials Registry reference: ACTRN12610000439044 PMID:20946621

The effect of whole body vibration on balance, gait performance and mobility in people with stroke: a systematic review and meta-analysis.

PubMed

Yang, Xiaotian; Wang, Pu; Liu, Chuan; He, Chengqi; Reinhardt, Jan D

2015-07-01

To examine the effect of whole body vibration on balance, gait performance and mobility among people with stroke. A systematic review was conducted by two independent reviewers who completed the article search and selection. We included randomized controlled trials published in English examining effects of whole body vibration on balance, gait, mobility, muscle strength and muscle tone in adults with a clinical diagnosis of stroke. Articles were excluded if they were research studies on people with other primary diagnosis, abstracts published in the conferences or books. The Cochrane risk of bias tool was used to assess the methodological quality of the selected studies. Sources included Cochrane Central Register of Controlled Trials, Pubmed, MEDLINE, CINAHL, EMBASE, PEDro, PsycINFO, Science Citation Index, ClinicalTrials.gov, Current Controlled Trials, Stroke Trials Registry, and reference lists of all relevant articles. Eight randomized controlled trials (nine articles) involving 271 participants were included in this meta-analysis. No significant improvement was found regarding Berg balance scale (SMD=-0.08, 95%CI=-1.35 to 1.19, P=0.91), mobility (SMD=0.45, 95%CI=-0.46 to 1.37, P=0.33), maximal isometric contracion of knee extension strength (SMD=0.23, 95%CI=-0.27 to 0.74, P=0.36), and maximal isometric contracion of knee extension strength (SMD=0.09, 95%CI=-0.38 to 0.56, P=0.71). There was no evidence for effects of whole body vibration on balance in people with stroke. Effects of whole body vibration on mobility and gait performance remain inconclusive. More large and high-quality trials are required. © The Author(s) 2014.

The Basilar Artery International Cooperation Study (BASICS): study protocol for a randomised controlled trial

PubMed Central

2013-01-01

Background Despite recent advances in acute stroke treatment, basilar artery occlusion (BAO) is associated with a death or disability rate of close to 70%. Randomised trials have shown the safety and efficacy of intravenous thrombolysis (IVT) given within 4.5 h and have shown promising results of intra-arterial thrombolysis given within 6 h of symptom onset of acute ischaemic stroke, but these results do not directly apply to patients with an acute BAO because only few, if any, of these patients were included in randomised acute stroke trials. Recently the results of the Basilar Artery International Cooperation Study (BASICS), a prospective registry of patients with acute symptomatic BAO challenged the often-held assumption that intra-arterial treatment (IAT) is superior to IVT. Our observations in the BASICS registry underscore that we continue to lack a proven treatment modality for patients with an acute BAO and that current clinical practice varies widely. Design BASICS is a randomised controlled, multicentre, open label, phase III intervention trial with blinded outcome assessment, investigating the efficacy and safety of additional IAT after IVT in patients with BAO. The trial targets to include 750 patients, aged 18 to 85 years, with CT angiography or MR angiography confirmed BAO treated with IVT. Patients will be randomised between additional IAT followed by optimal medical care versus optimal medical care alone. IVT has to be initiated within 4.5 h from estimated time of BAO and IAT within 6 h. The primary outcome parameter will be favourable outcome at day 90 defined as a modified Rankin Scale score of 0–3. Discussion The BASICS registry was observational and has all the limitations of a non-randomised study. As the IAT approach becomes increasingly available and frequently utilised an adequately powered randomised controlled phase III trial investigating the added value of this therapy in patients with an acute symptomatic BAO is needed (clinicaltrials.gov: NCT01717755). PMID:23835026

Involving American Indians and medically underserved rural populations in cancer clinical trials.

PubMed

Guadagnolo, B Ashleigh; Petereit, Daniel G; Helbig, Petra; Koop, David; Kussman, Patricia; Fox Dunn, Emily; Patnaik, Asha

2009-12-01

To assess cancer clinical trial recruitment and reasons for nonaccrual among a rural, medically underserved population served by a community-based cancer care center. We prospectively tracked clinical trial enrollment incidence among all new patients presenting at the Rapid City Regional Cancer Care Institute. Evaluating physicians completed questionnaires for each patient regarding clinical trial enrollment status and primary reasons for nonenrollment. Patients who identified as American Indian were referred to a program where patients were assisted in navigating the medical system by trained, culturally competent staff. Between September 2006 and January 2008, 891 new cancer patients were evaluated. Seventy-eight patients (9%; 95% confidence intervals, 7-11%) were enrolled on a clinical treatment trial. For 73% (95% confidence intervals, 69-75%) of patients (646 of 891) lack of relevant protocol availability or protocol inclusion criteria restrictiveness was the reason for nonenrollment. Only 45 (5%; 95% confidence intervals, 4-7%) patients refused enrollment on a trial. Of the 78 enrolled on a trial, 6 (8%; 95% confidence intervals, 3-16%) were American Indian. Three additional American Indian patients were enrolled under a nontreatment cancer control trial, bringing the total percentage enrolled of the 94 American Indians who presented to the clinic to 10% (95% confidence intervals, 5-17%). Eligibility rates were unable to be calculated and cross validation of the number in the cohort via registries or ICD-9 codes was not performed. Clinical trial participation in this medically underserved population was low overall, but approximately 3-fold higher than reported national accrual rates. Lack of availability of protocols for common cancer sites as well as stringent protocol inclusion criteria were the primary obstacles to clinical trial enrollment. Targeted interventions using a Patient Navigation program were used to engage AI patients and may have resulted in higher clinical trial enrollment among this racial/ethnic group.

Involving American Indians and medically underserved rural populations in cancer clinical trials

PubMed Central

Guadagnolo, B Ashleigh; Petereit, Daniel G; Helbig, Petra; Koop, David; Kussman, Patricia; Dunn, Emily Fox; Patnaik, Asha

2010-01-01

Purpose To assess cancer clinical trial recruitment and reasons for nonaccrual among a rural, medically underserved population served by a community-based cancer care center. Methods We prospectively tracked clinical trial enrollment incidence among all new patients presenting at the Rapid City Regional Cancer Care Institute. Evaluating physicians completed questionnaires for each patient regarding clinical trial enrollment status and primary reasons for nonenrollment. Patients who identified as American Indian were referred to a program where patients were assisted in navigating the medical system by trained, culturally competent staff. Results Between September 2006 and January 2008, 891 new cancer patients were evaluated. Seventy-eight patients (9%; 95% confidence intervals, 7–11%) were enrolled on a clinical treatment trial. For 73% (95% confidence intervals, 69–75%) of patients (646 of 891) lack of relevant protocol availability or protocol inclusion criteria restrictiveness was the reason for nonenrollment. Only 45 (5%; 95% confidence intervals, 4–7%) patients refused enrollment on a trial. Of the 78 enrolled on a trial, 6 (8%; 95% confidence intervals, 3–16%) were American Indian. Three additional American Indian patients were enrolled under a nontreatment cancer control trial, bringing the total percentage enrolled of the 94 American Indians who presented to the clinic to 10% (95% confidence intervals, 5–17%). Limitations Eligibility rates were unable to be calculated and cross validation of the number in the cohort via registries or ICD-9 codes was not performed. Conclusion Clinical trial participation in this medically underserved population was low overall, but approximately 3-fold higher than reported national accrual rates. Lack of availability of protocols for common cancer sites as well as stringent protocol inclusion criteria were the primary obstacles to clinical trial enrollment. Targeted interventions using a Patient Navigation program were used to engage AI patients and may have resulted in higher clinical trial enrollment among this racial/ethnic group. PMID:19933720

Melanoma of the Skin in the Danish Cancer Registry and the Danish Melanoma Database: A Validation Study.

PubMed

Pedersen, Sidsel Arnspang; Schmidt, Sigrun Alba Johannesdottir; Klausen, Siri; Pottegård, Anton; Friis, Søren; Hölmich, Lisbet Rosenkrantz; Gaist, David

2018-05-01

The nationwide Danish Cancer Registry and the Danish Melanoma Database both record data on melanoma for purposes of monitoring, quality assurance, and research. However, the data quality of the Cancer Registry and the Melanoma Database has not been formally evaluated. We estimated the positive predictive value (PPV) of melanoma diagnosis for random samples of 200 patients from the Cancer Registry (n = 200) and the Melanoma Database (n = 200) during 2004-2014, using the Danish Pathology Registry as "gold standard" reference. We further validated tumor characteristics in the Cancer Registry and the Melanoma Database. Additionally, we estimated the PPV of in situ melanoma diagnoses in the Melanoma Database, and the sensitivity of melanoma diagnoses in 2004-2014. The PPVs of melanoma in the Cancer Registry and the Melanoma Database were 97% (95% CI = 94, 99) and 100%. The sensitivity was 90% in the Cancer Registry and 77% in the Melanoma Database. The PPV of in situ melanomas in the Melanoma Database was 97% and the sensitivity was 56%. In the Melanoma Database, we observed PPVs of ulceration of 75% and Breslow thickness of 96%. The PPV of histologic subtypes varied between 87% and 100% in the Cancer Registry and 93% and 100% in the Melanoma Database. The PPVs for anatomical localization were 83%-95% in the Cancer Registry and 93%-100% in the Melanoma Database. The data quality in both the Cancer Registry and the Melanoma Database is high, supporting their use in epidemiologic studies.

Trials with patient-reported outcomes registered on the Australian New Zealand Clinical Trials Registry (ANZCTR).

PubMed

Mercieca-Bebber, Rebecca; Williams, Douglas; Tait, Margaret-Ann; Roydhouse, Jessica; Busija, Lucy; Sundaram, Chindhu Shunmuga; Wilson, Michelle; Langford, Ailsa; Rutherford, Claudia; Roberts, Natasha; King, Madeleine; Vodicka, Elisabeth; Devine, Beth

2018-06-18

It is important to understand the number, types and regions of trials that include patient-reported outcomes (PROs) to appreciate how patient experiences have been considered in studies of health and interventions. Twenty-seven percent of trials registered with ClinicalTrials.gov (2007-2013) included PROs; however, a regional breakdown was not provided and no reviews have been conducted of the Australia New Zealand Clinical Trials Registry (ANZCTR). We aimed to identify trials registered with ANZCTR with PRO endpoints and describe their characteristics. ANZCTR was systematically searched from inception (2005) to 31 March 2017 for trials with PRO endpoints. Search terms included PRO measures listed in Patient-Reported Outcomes Quality of Life Instrument Database and Grid-Enabled Measures, as well as generic PRO terms (e.g. "quality of life" (QOL)). Trial endpoints were individually coded using an established framework to identify trials with PROs for the analysis. Of 13,666 registered trials, 6168 (45.1%) included a PRO. The proportion of studies including PROs increased between 2006 and 2016 (r = 0.74, p = 0.009). Among the 6168 trials, there were 17,961 individual PRO endpoints, including symptoms/functional outcomes/condition-specific QOL (65.6%), generic QOL (13.2%), patient-reported experiences (9.9%), patient-reported behaviours (7.9%). Mental health was the most common category (99.8% included PROs), followed by physical medicine/rehabilitation (65.6%), musculoskeletal (63.5%), public health (63.1%), and cancer (54.2%). Our findings suggest growing use of PROs in the assessment of health and interventions in ANZ. Our review identifies trial categories with limited patient-reported information and provides a basis for future work on the impact of PRO findings in clinical care.

Hyperglycaemia in early pregnancy: the Treatment of Booking Gestational diabetes Mellitus (TOBOGM) study. A randomised controlled trial.

PubMed

Simmons, David; Hague, William M; Teede, Helena J; Cheung, N Wah; Hibbert, Emily J; Nolan, Christopher J; Peek, Michael J; Girosi, Federico; Cowell, Christopher T; Wong, Vincent W-M; Flack, Jeff R; McLean, Mark; Dalal, Raiyomand; Robertson, Annette; Rajagopal, Rohit

2018-05-28

Gestational diabetes mellitus (GDM) causes adverse pregnancy outcomes that can be averted by treatment from 24-28 weeks' gestation. Assessing and treating women for overt diabetes in pregnancy (ODIP) at the first antenatal clinic booking is now recommended in international guidelines. As a consequence, women with milder hyperglycaemia are being diagnosed and treated for early GDM, but randomised controlled trial (RCTs) assessing the benefits and harms of such treatment have not been undertaken. The Treatment Of Booking Gestational diabetes Mellitus (TOBOGM) study is a multi-centre RCT examining whether diagnosing and treating GDM diagnosed at booking improves pregnancy outcomes. Methods and analysis: 4000 adult pregnant women (< 20 weeks' gestation) at risk of ODIP will be recruited from 12 hospital antenatal booking clinics and referred for an oral glucose tolerance test (OGTT). 800 women with hyperglycaemia (ie, booking GDM) according to the 2014 Australasian Diabetes-in-Pregnancy Society criteria for pregnant women at 24-28 weeks' gestation will be randomised to immediate treatment for GDM (intervention) or to no treatment (control), pending the results of a second OGTT at 24-28 weeks' gestation. Antenatal and GDM care will otherwise follow local guidelines. Randomisation will be stratified by site and OGTT glycaemic risk strata. The primary pregnancy outcome is a composite of respiratory distress, phototherapy, birth trauma, birth before 37 weeks' gestation, stillbirth or death, shoulder dystocia, and birthweight ≥ 4.5 kg. The primary neonatal outcome is neonatal lean body mass. The primary maternal outcome is pre-eclampsia. Ethics approval: South Western Sydney Local Health District Research and Ethics Office (reference, 15/LPOOL/551). Dissemination of results: Peer-reviewed publications, scientific meetings, collaboration with research groups undertaking comparable studies, discussions with guideline groups and policy makers. Australian New Zealand Clinical Trials Registry, ACTRN12616000924459.

Costs of revascularization over eight years in the randomized and eligible patients in the Emory Angioplasty versus Surgery Trial (EAST).

PubMed

Weintraub, W S; Becker, E R; Mauldin, P D; Culler, S; Kosinski, A S; King, S B

2000-10-01

The Emory Angioplasty versus Surgery Trial (EAST) was a randomized trial that compared, by intention to treat, the clinical outcome and costs of percutaneous transluminal coronary angioplasty (PTCA) and coronary bypass grafting (CABG) for multivessel coronary artery disease. We present the findings of the economic analysis of EAST through 8 years of follow-up and compare the cost and outcomes of patients randomized in EAST versus patients eligible but not randomized (registry patients). Charges were assessed from hospital UB82 and UB92 bills and professional charges from the Emory Clinic. Hospital charges were reduced to cost through step-down accounting methods. All costs and charges were inflated to 1997 dollars. Costs were assessed for initial hospitalization and for cumulative costs of the initial hospitalization and additional revascularization procedures up to 8 years. Total 8-year costs were $46,548 for CABG and $44,491 for PTCA (p = 0.37). Cost of CABG in the eligible registry group showed a pattern similar to that for randomized patients, but total cost of PTCA was lower for registry patients than for randomized patients. Thus, the primary procedural costs of CABG are more than those for PTCA; this cost advantage, given the limits of measurement, is largely or even completely lost for randomized patients over the course of 8 years because of additional procedures after a first revascularization by PTCA.

[Orange Platform].

PubMed

Toba, Kenji

2017-07-01

The Organized Registration for the Assessment of dementia on Nationwide General consortium toward Effective treatment in Japan (ORANGE platform) is a recently established nationwide clinical registry for dementia. This platform consists of multiple registries of patients with dementia stratified by the following clinical stages: preclinical, mild cognitive impairment, early-stage, and advanced-stage dementia. Patients will be examined in a super-longitudinal fashion, and their lifestyle, social background, genetic risk factors, and required care process will be assessed. This project is also notable because the care registry includes information on the successful, comprehensive management of patients with dementia. Therefore, this multicenter prospective cohort study will contribute participants to all clinical trials for Alzheimer's disease as well as improve the understanding of individuals with dementia.

Design of a framework for the deployment of collaborative independent rare disease-centric registries: Gaucher disease registry model.

PubMed

Bellgard, Matthew I; Napier, Kathryn R; Bittles, Alan H; Szer, Jeffrey; Fletcher, Sue; Zeps, Nikolajs; Hunter, Adam A; Goldblatt, Jack

2018-02-01

Orphan drug clinical trials often are adversely affected by a lack of high quality treatment efficacy data that can be reliably compared across large patient cohorts derived from multiple governmental and country jurisdictions. It is critical that these patient data be captured with limited corporate involvement. For some time, there have been calls to develop collaborative, non-proprietary, patient-centric registries for post-market surveillance of aspects related to orphan drug efficacy. There is an urgent need for the development and sustainable deployment of these 'independent' registries that can capture comprehensive clinical, genetic and therapeutic information on patients with rare diseases. We therefore extended an open-source registry platform, the Rare Disease Registry Framework (RDRF) to establish an Independent Rare Disease Registry (IRDR). We engaged with an established rare disease community for Gaucher disease to determine system requirements, methods of data capture, consent, and reporting. A non-proprietary IRDR model is presented that can serve as autonomous data repository, but more importantly ensures that the relevant data can be made available to appropriate stakeholders in a secure, timely and efficient manner to improve clinical decision-making and the lives of those with a rare disease. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

My Retina Tracker™: An On-line International Registry for People Affected with Inherited Orphan Retinal Degenerative Diseases and their Genetic Relatives - A New Resource.

PubMed

Fisher, Joan K; Bromley, Russell L; Mansfield, Brian C

2016-01-01

My Retina Tracker™ is a new on-line registry for people affected with inherited orphan retinal degenerative diseases, and their unaffected, genetic relatives. Created and supported by the Foundation Fighting Blindness, it is an international resource designed to capture the disease from the perspective of the registry participant and their retinal health care providers. The registry operates under an Institutional Review Board (IRB)-approved protocol and allows sharing of de-identified data with participants, researchers and clinicians. All participants sign an informed consent that includes selecting which data they wish to share. There is no minimum age of participation. Guardians must sign on behalf of minors, and children between the ages of 12 to 17 also sign an informed assent. Participants may compare their disease to others in the registry using graphical interpretations of the aggregate registry data. Researchers and clinicians have two levels of access. The first provides an interface to interrogate all data fields registrants have agreed to share based on their answers in the IRB informed consent. The second provides a route to contact people in the registry who may be eligible for studies or trials, through the Foundation.

Rationale, design and objectives of ARegPKD, a European ARPKD registry study.

PubMed

Ebner, Kathrin; Feldkoetter, Markus; Ariceta, Gema; Bergmann, Carsten; Buettner, Reinhard; Doyon, Anke; Duzova, Ali; Goebel, Heike; Haffner, Dieter; Hero, Barbara; Hoppe, Bernd; Illig, Thomas; Jankauskiene, Augustina; Klopp, Norman; König, Jens; Litwin, Mieczyslaw; Mekahli, Djalila; Ranchin, Bruno; Sander, Anja; Testa, Sara; Weber, Lutz Thorsten; Wicher, Dorota; Yuzbasioglu, Ayse; Zerres, Klaus; Dötsch, Jörg; Schaefer, Franz; Liebau, Max Christoph

2015-02-18

Autosomal recessive polycystic kidney disease (ARPKD) is a rare but frequently severe disorder that is typically characterized by cystic kidneys and congenital hepatic fibrosis but displays pronounced phenotypic heterogeneity. ARPKD is among the most important causes for pediatric end stage renal disease and a leading reason for liver-, kidney- or combined liver kidney transplantation in childhood. The underlying pathophysiology, the mechanisms resulting in the observed clinical heterogeneity and the long-term clinical evolution of patients remain poorly understood. Current treatment approaches continue to be largely symptomatic and opinion-based even in most-advanced medical centers. While large clinical trials for the frequent and mostly adult onset autosomal dominant polycystic kidney diseases have recently been conducted, therapeutic initiatives for ARPKD are facing the challenge of small and clinically variable cohorts for which reliable end points are hard to establish. ARegPKD is an international, mostly European, observational study to deeply phenotype ARPKD patients in a pro- and retrospective fashion. This registry study is conducted with the support of the German Society for Pediatric Nephrology (GPN) and the European Study Consortium for Chronic Kidney Disorders Affecting Pediatric Patients (ESCAPE Network). ARegPKD clinically characterizes long-term ARPKD courses by a web-based approach that uses detailed basic data questionnaires in combination with yearly follow-up visits. Clinical data collection is accompanied by associated biobanking and reference histology, thus setting roots for future translational research. The novel registry study ARegPKD aims to characterize miscellaneous subcohorts and to compare the applied treatment options in a large cohort of deeply characterized patients. ARegPKD will thus provide evidence base for clinical treatment decisions and contribute to the pathophysiological understanding of this severe inherited disorder.

Creating a global rare disease patient registry linked to a rare diseases biorepository database: Rare Disease-HUB (RD-HUB).

PubMed

Rubinstein, Yaffa R; Groft, Stephen C; Bartek, Ronald; Brown, Kyle; Christensen, Ronald A; Collier, Elaine; Farber, Amy; Farmer, Jennifer; Ferguson, John H; Forrest, Christopher B; Lockhart, Nicole C; McCurdy, Kate R; Moore, Helen; Pollen, Geraldine B; Richesson, Rachel; Miller, Vanessa Rangel; Hull, Sara; Vaught, Jim

2010-09-01

A movement to create a global patient registry for as many as 7,000 rare diseases was launched at a workshop, "Advancing Rare Disease Research: The Intersection of Patient Registries, Biospecimen Repositories, and Clinical Data." http://rarediseases.info.nih.gov/PATIENT_REGISTRIES_WORKSHOP/. The workshop was sponsored by the Office of Rare Diseases Research (ORDR). The focus was the building of an infrastructure for an internet-based global registry linking to biorepositories. Such a registry would serve the patients, investigators, and drug companies. To aid researchers the participants suggested the creation of a centralized database of biorepositories for rare biospecimens (RD-HUB)http://biospecimens.ordr.info.nih.gov/ that could be linked to the registry. Over two days of presentations and breakout sessions, several hundred attendees discussed government rules and regulations concerning privacy and patients' rights and the nature and scope of data to be entered into a central registry as well as concerns about how to validate patient and clinician-entered data to ensure data accuracy. Mechanisms for aggregating data from existing registries were also discussed. The attendees identified registry best practices, model coding systems, international systems for recruiting patients into clinical trials and novel ways of using the internet directly to invite participation in research. They also speculated about who would bear ultimate responsibility for the informatics in the registry and who would have access to the information. Hurdles associated with biospecimen collection and how to overcome them were detailed. The development of the recommendations was, in itself, an indication of the commitment of the rare disease community as never before. Published by Elsevier Inc.

Lessons learned in acute heart failure.

PubMed

Cheema, Baljash; Ambrosy, Andrew P; Kaplan, Rachel M; Senni, Michele; Fonarow, Gregg C; Chioncel, Ovidiu; Butler, Javed; Gheorghiade, Mihai

2018-04-01

Acute heart failure (HF) is a global pandemic with more than one million admissions to hospital annually in the US and millions more worldwide. Post-discharge mortality and readmission rates remain unchanged and unacceptably high. Although recent drug development programmes have failed to deliver novel therapies capable of reducing cardiovascular morbidity and mortality in patients hospitalized for worsening chronic HF, hospitalized HF registries and clinical trial databases have generated a wealth of information improving our collective understanding of the HF syndrome. This review will summarize key insights from clinical trials in acute HF and hospitalized HF registries over the last several decades, focusing on improving the management of patients with HF and reduced ejection fraction. © 2017 The Authors. European Journal of Heart Failure © 2017 European Society of Cardiology.

Metamizole-Associated Adverse Events: A Systematic Review and Meta-Analysis

PubMed Central

Fässler, Margrit; Blozik, Eva; Linde, Klaus; Jüni, Peter; Reichenbach, Stephan; Scherer, Martin

2015-01-01

Background Metamizole is used to treat pain in many parts of the world. Information on the safety profile of metamizole is scarce; no conclusive summary of the literature exists. Objective To determine whether metamizole is clinically safe compared to placebo and other analgesics. Methods We searched CENTRAL, MEDLINE, EMBASE, CINAHL, and several clinical trial registries. We screened the reference lists of included trials and previous systematic reviews. We included randomized controlled trials that compared the effects of metamizole, administered to adults in any form and for any indication, to other analgesics or to placebo. Two authors extracted data regarding trial design and size, indications for pain medication, patient characteristics, treatment regimens, and methodological characteristics. Adverse events (AEs), serious adverse events (SAEs), and dropouts were assessed. We conducted separate meta-analyses for each metamizole comparator, using standard inverse-variance random effects meta-analysis to pool the estimates across trials, reported as risk ratios (RRs). We calculated the DerSimonian and Laird variance estimate T2 to measure heterogeneity between trials. The pre-specified primary end point was any AE during the trial period. Results Of the 696 potentially eligible trials, 79 trials including almost 4000 patients with short-term metamizole use of less than two weeks met our inclusion criteria. Fewer AEs were reported for metamizole compared to opioids, RR = 0.79 (confidence interval 0.79 to 0.96). We found no differences between metamizole and placebo, paracetamol and NSAIDs. Only a few SAEs were reported, with no difference between metamizole and other analgesics. No agranulocytosis or deaths were reported. Our results were limited by the mediocre overall quality of the reports. Conclusion For short-term use in the hospital setting, metamizole seems to be a safe choice when compared to other widely used analgesics. High-quality, adequately sized trials assessing the intermediate- and long-term safety of metamizole are needed. PMID:25875821

Brief emergency department interventions for youth who use alcohol and other drugs: a systematic review.

PubMed

Newton, Amanda S; Dong, Kathryn; Mabood, Neelam; Ata, Nicole; Ali, Samina; Gokiert, Rebecca; Vandermeer, Ben; Tjosvold, Lisa; Hartling, Lisa; Wild, T Cameron

2013-05-01

Brief intervention (BI) is recommended for use with youth who use alcohol and other drugs. Emergency departments (EDs) can provide BIs at a time directly linked to harmful and hazardous use. The objective of this systematic review was to determine the effectiveness of ED-based BIs. We searched 14 electronic databases, a clinical trial registry, conference proceedings, and study references. We included randomized controlled trials with youth 21 years or younger. Two reviewers independently selected studies and assessed methodological quality. One reviewer extracted and a second verified data. We summarized findings qualitatively. Two trials with low risk of bias, 2 trials with unclear risk of bias, and 5 trials with high risk of bias were included. Trials evaluated targeted BIs for alcohol-positive (n = 3) and alcohol/other drug-positive youth (n = 1) and universal BIs for youth reporting recent alcohol (n = 4) or cannabis use (n = 1). Few differences were found in favor of ED-based BIs, and variation in outcome measurement and poor study quality precluded firm conclusions for many comparisons. Universal and targeted BIs did not significantly reduce alcohol use more than other care. In one targeted BI trial with high risk of bias, motivational interviewing (MI) that involved parents reduced drinking quantity per occasion and high-volume alcohol use compared with MI that was delivered to youth only. Another trial with high risk of bias reported an increase in abstinence and reduction in physical altercations when youth received peer-delivered universal MI for cannabis use. In 2 trials with unclear risk of bias, MI reduced drinking and driving and alcohol-related injuries after the ED visit. Computer-based MI delivered universally in 1 trial with low risk of bias reduced alcohol-related consequences 6 months after the ED visit. Clear benefits of using ED-based BI to reduce alcohol and other drug use and associated injuries or high-risk behaviours remain inconclusive because of variation in assessing outcomes and poor study quality.

The Italian Registry of Antiphospholipid Antibodies.

PubMed

Finazzi, G

1997-01-01

The clinical importance of antiphospholipid antibodies (APA) derives from their association with a syndrome of venous and arterial thrombosis, recurrent fetal loss and thrombocytopenia known as the antiphospholipid syndrome (APS). The Italian Registry of Antiphospholipid Antibodies was set up in 1989 for the purpose of collecting a large number of patients with lupus anticoagulant (LA) or anticardiolipin antibodies (ACA) for clinical studies in order to obtain more information on the clinical features of APS. The Italian Registry has completed two clinical studies and proposed an international trial on the treatment of APS patients. These activities of the Registry are reviewed herein. Additional information has been obtained from pertinent articles and abstracts published in journals covered by the Science Citation Index and Medline. The first study of the Registry was a retrospective analysis of enrolled patients which showed that: a) the prevalence of thrombosis and thrombocytopenia was similar in cases with idiopathic APA or APA secondary to systemic lupus erythematosus, and b) the rate of thrombosis was significantly reduced in patients with severe thrombocytopenia but not in those with only a mild reduction of the platelet count. The second study was a prospective survey of the natural history of the disease, showing that a) previous thrombosis and ACA titer > 40 units were independent predictors of subsequent vascular complications; b) a history of miscarriage or thrombosis is significantly associated with adverse pregnancy outcome; c) hematological malignancies can develop during follow-up and patients with APA should be considered at increased risk of developing NHL. Thus the possibility of a hematologic neoplastic disease should be borne in mind in the initial evaluation and during the follow-up of these patients. The latest initiative of the Registry was the proposal of an international, randomized clinical trial (WAPS study) aimed at assessing the efficacy and safety of high-dose warfarin in preventing recurrent thrombosis in patients with APA and vascular disease. The study is scheduled to start in March 1997.

WITHDRAWN: Systemic treatments for metastatic cutaneous melanoma.

PubMed

Crosby, Tom; Fish, Reg; Coles, Bernadette; Mason, Malcolm

2018-02-07

Systemic therapies for metastatic cutaneous melanoma, the most aggressive of all skin cancers, remain disappointing. Few lasting remissions are achieved and the therapeutic aim remains one of palliation.Many agents are used alone or in combination with varying degrees of toxicity and cost. It is unclear whether evidence exists to support these complex regimens over best supportive care / placebo. To review the benefits from the use of systemic therapies in metastatic cutaneous melanoma compared to best supportive care/placebo, and to establish whether a 'standard' therapy exists which is superior to other treatments. Randomised controlled trials were identified from the MEDLINE, EMBASE and CCTR/CENTRAL databases. References, conference proceedings, and Science Citation Index/Scisearch were also used to locate trials. Cancer registries and trialists were also contacted. Randomised controlled trials of adults with histologically proven metastatic cutaneous melanoma in which systemic anti-cancer therapy was compared with placebo or supportive care. Study selection was performed by two independent reviewers. Data extraction forms were used for studies which appeared to meet the selection criteria and, where appropriate, full text articles were retrieved and reviewed independently. No randomised controlled trials were found comparing a systemic therapy with placebo or best supportive care in metastatic cutaneous melanoma. There is no evidence from randomised controlled clinical trials to show superiority of systemic therapy over best supportive care / placebo in the treatment of malignant cutaneous melanoma.Given that patients with metastatic melanoma frequently receive systemic therapy, it is our pragmatic view that a future systematic review could compare any systemic treatment, or combination of treatments, to single agent dacarbazine.

Systematic review: probiotics for functional constipation in children.

PubMed

Wojtyniak, Katarzyna; Szajewska, Hania

2017-09-01

We updated our 2010 systematic review on the efficacy of probiotics in the treatment of constipation in children. The MEDLINE, EMBASE, and Cochrane Library databases; clinical trial registries; and reference lists of included studies were searched to February 2017 for randomized controlled trials (RCTs) performed in children, with no language restriction. The primary outcome measure was treatment success, as defined by the investigators. We included seven RCTs with a total of 515 participants. Included trials were heterogeneous with respect to study population, probiotic strains, dosages, study duration, and follow-up. Pooled results of two RCTs showed no significant difference between the Lactobacillus rhamnosus casei Lcr35 and placebo groups with respect to treatment success. Other probiotics were studied in single trials only. There was no significant difference between the probiotic and control groups with respect to treatment success. While some probiotic strains showed some effects on defecation frequency, none of the probiotics had beneficial effects on frequency of fecal incontinence or frequency of abdominal pain. Adverse events were rare and not serious. Limited evidence does not support the use of any of currently evaluated probiotics in the treatment of functional constipation in children. What is Known: • Conventional treatment for functional constipation in children does not always provide satisfying improvement. • Probiotics have been suggested as potential treatment modalities for this condition. What is New: • Probiotics are ineffective for the management of functional constipation in children in terms of treatment success, frequency of fecal incontinence, and frequency of abdominal pain.

The EPIRARE proposal of a set of indicators and common data elements for the European platform for rare disease registration.

PubMed

Taruscio, Domenica; Mollo, Emanuela; Gainotti, Sabina; Posada de la Paz, Manuel; Bianchi, Fabrizio; Vittozzi, Luciano

2014-01-01

The European Union acknowledges the relevance of registries as key instruments for developing rare disease (RD) clinical research, improving patient care and health service (HS) planning and funded the EPIRARE project to improve standardization and data comparability among patient registries and to support new registries and data collections. A reference list of patient registry-based indicators has been prepared building on the work of previous EU projects and on the platform stakeholders' information needs resulting from the EPIRARE surveys and consultations. The variables necessary to compute these indicators have been analysed for their scope and use and then organized in data domains. The reference indicators span from disease surveillance, to socio-economic burden, HS monitoring, research and product development, policy equity and effectiveness. The variables necessary to compute these reference indicators have been selected and, with the exception of more sophisticated indicators for research and clinical care quality, they can be collected as data elements common (CDE) to all rare diseases. They have been organized in data domains characterized by their contents and main goal and a limited set of mandatory data elements has been defined, which allows case notification independently of the physician or the health service. The definition of a set of CDE for the European platform for RD patient registration is the first step in the promotion of the use of common tools for the collection of comparable data. The proposed organization of the CDE contributes to the completeness of case ascertainment, with the possible involvement of patients and patient associations in the registration process.

Designing effective drug and device development programs for hospitalized heart failure: A proposal for pretrial registries

PubMed Central

Greene, Stephen J.; Shah, Ami N.; Butler, Javed; Ambrosy, Andrew P.; Anker, Stefan D.; Chioncel, Ovidiu; Collins, Sean P.; Dinh, Wilfried; Dunnmon, Preston M.; Fonarow, Gregg C.; Lam, Carolyn S. P.; Mentz, Robert J.; Pieske, Burkert; Roessig, Lothar; Rosano, Giuseppe M. C.; Sato, Naoki; Vaduganathan, Muthiah; Gheorghiade, Mihai

2014-01-01

Recent international phase III clinical trials of novel therapies for hospitalized heart failure (HHF) have failed to improve the unacceptably high postdischarge event rate. These large studies have demonstrated notable geographic and site-specific variation in patient profiles and enrollment. Possible contributors to the lack of success in HHF outcome trials include challenges in selecting clinical sites capable of (1) providing adequate numbers of appropriately selected patients and (2) properly executing the study protocol. We propose a “pretrial registry” as a novel tool for improving the efficiency and quality of international HHF trials by focusing on the selection and cultivation of high-quality sites. A pretrial registry may help assess a site’s ability to achieve adequate enrollment of the target patient population, integrate protocol requirements into clinical workflow, and accomplish appropriate follow-up. Although such a process would be associated with additional upfront resource investment, this appropriation may be modest in comparison with the downstream costs associated with maintenance of poorly performing sites, failed clinical trials, and the global health and economic burden of HHF. This review is based on discussions between scientists, clinical trialists, and regulatory representatives regarding methods for improving international HHF trials that took place at the United States Food and Drug Administration on January 12th, 2012. PMID:25066552

Childhood Vesicoureteral Reflux Studies: Registries and Repositories Sources and Nosology

PubMed Central

Chesney, Russell W.; Patters, Andrea B.

2012-01-01

Despite several recent studies, the advisability of antimicrobial prophylaxis and certain imaging studies for urinary tract infections (UTIs) remains controversial. The role of vesicoureteral reflux (VUR) on the severity and re-infection rates for UTIs is also difficult to assess. Registries and repositories of data and biomaterials from clinical studies in children with VUR are valuable. Disease registries are collections of secondary data related to patients with a specific diagnosis, condition or procedure. Registries differ from indices in that they contain more extensive data. A research repository is an entity that receives, stores, processes and/or disseminates specimens (or other materials) as needed. It encompasses the physical location as well as the full range of activities associated with its operation. It may also be referred to as a biorepository. This report provides information about some current registries and repositories that include data and samples from children with VUR. It also describes the heterogeneous nature of the subjects, as some registries and repositories include only data or samples from patients with primary reflux while others also include those from patients with syndromic or secondary reflux. PMID:23044377

Artificial Nutritional Support Registries: systematic review.

PubMed

Castelló-Botía, I; Wanden-Berghe, C; Sanz-Valero, J

2009-01-01

The nutritional registries are data bases through which we obtain the information to understand the nutrition of populations. Several main nutrition societies of the world have these types of registries, outstanding the NADYA (Home artificial and Ambulatory nutrition) group in Spain. The object of this study is to determine by means of a systematic review, the existent scientific production in the international data bases referred to nutritional support registries. Descriptive transversal study of the results of a critical bibliographic research done in the bioscience data bases: MEDLINE, EMBASE, The Cochrane Library, ISI (Web of Sciences), LILACS, CINHAL. A total of 20 original articles related to nutritional registries were found and recovered. Eleven registries of eight countries were identified: Australia, Germany, Italy, Japan, Spain, Sweden, United Status and United Kingdom. The Price Index was of 65% and all the articles were published in the last 20 years. The Price Index highlights the innovativeness of this practice. The articles related to nutritional support are heterogeneous with respect to data and population, which exposes this as a limitation for a combined analysis.

Laboratory Tests

MedlinePlus

... PI CONNECT Research Network USIDNET Patient Registry IDF Survey Research IDF Surveys National Health Insurance Surveys Clinical Trials ... and Fellows Research USIDNET IDF Research Fund IDF Survey Research IDF Surveys Contact Us Search form Search Laboratory ...

14th International Congress on Antiphospholipid Antibodies: task force report on antiphospholipid syndrome treatment trends.

PubMed

Erkan, Doruk; Aguiar, Cassyanne L; Andrade, Danieli; Cohen, Hannah; Cuadrado, Maria J; Danowski, Adriana; Levy, Roger A; Ortel, Thomas L; Rahman, Anisur; Salmon, Jane E; Tektonidou, Maria G; Willis, Rohan; Lockshin, Michael D

2014-06-01

Antiphospholipid Syndrome (APS) is characterized by vascular thrombosis and/or pregnancy morbidity occurring in patients with persistent antiphospholipid antibodies (aPL). The primary objective of the APS Treatment Trends Task Force, created as part of the 14th International Congress on aPL, was to systematically review the potential future treatment strategies for aPL-positive patients. The task force chose as future clinical research directions: a) determining the necessity for controlled clinical trials in venous thromboembolism with the new oral direct thrombin or anti-factor Xa inhibitors pending the results of the ongoing rivaroxaban in APS (RAPS) trial, and designing controlled clinical trials in other forms of thrombotic APS; b) systematically analyzing the literature as well as aPL/APS registries, and creating specific registries for non-warfarin/heparin anticoagulants; c) increasing recruitment for an ongoing primary thrombosis prevention trial, and designing secondary thrombosis and pregnancy morbidity prevention trials with hydroxychloroquine; d) determining surrogate markers to select patients for statin trials; e) designing controlled studies with rituximab and other anti-B-cell agents; f) designing mechanistic and clinical studies with eculizumab and other complement inhibitors; and g) chemically modifying peptide therapy to improve the half-life and minimize immunogenicity. The report also includes recommendations for clinicians who consider using these agents in difficult-to-manage aPL-positive patients. Copyright © 2014 Elsevier B.V. All rights reserved.

Reporting of methods was better in the Clinical Trials Registry-India than in Indian journal publications.

PubMed

Tharyan, Prathap; George, Aneesh Thomas; Kirubakaran, Richard; Barnabas, Jabez Paul

2013-01-01

We sought to evaluate if editorial policies and the reporting quality of randomized controlled trials (RCTs) had improved since our 2004-05 survey of 151 RCTs in 65 Indian journals, and to compare reporting quality of protocols in the Clinical Trials Registry-India (CTRI). An observational study of endorsement of Consolidated Standards for the Reporting of Trials (CONSORT) and International Committee of Medical Journal Editors (ICMJE) requirements in the instructions to authors in Indian journals, and compliance with selected requirements in all RCTs published during 2007-08 vs. our previous survey and between all RCT protocols in the CTRI on August 31, 2010 and published RCTs from both surveys. Journal policies endorsing the CONSORT statement (22/67, 33%) and ICMJE requirements (35/67, 52%) remained suboptimal, and only 4 of 13 CONSORT items were reported in more than 50% of the 145 RCTs assessed. Reporting of ethical issues had improved significantly, and that of methods addressing internal validity had not improved. Adequate methods were reported significantly more frequently in 768 protocols in the CTRI, than in the 296 published trials. The CTRI template facilitates the reporting of valid methods in registered trial protocols. The suboptimal compliance with CONSORT and ICMJE requirements in RCTs published in Indian journals reduces credibility in the reliability of their results. Copyright © 2013 Elsevier Inc. All rights reserved.

Pressure ulcer risk assessment and prevention: a systematic comparative effectiveness review.

PubMed

Chou, Roger; Dana, Tracy; Bougatsos, Christina; Blazina, Ian; Starmer, Amy J; Reitel, Katie; Buckley, David I

2013-07-02

Pressure ulcers are associated with substantial health burdens but may be preventable. To review the clinical utility of pressure ulcer risk assessment instruments and the comparative effectiveness of preventive interventions in persons at higher risk. MEDLINE (1946 through November 2012), CINAHL, the Cochrane Library, grant databases, clinical trial registries, and reference lists. Randomized trials and observational studies on effects of using risk assessment on clinical outcomes and randomized trials of preventive interventions on clinical outcomes. Multiple investigators abstracted and checked study details and quality using predefined criteria. One good-quality trial found no evidence that use of a pressure ulcer risk assessment instrument, with or without a protocolized intervention strategy based on assessed risk, reduces risk for incident pressure ulcers compared with less standardized risk assessment based on nurses' clinical judgment. In higher-risk populations, 1 good-quality and 4 fair-quality randomized trials found that more advanced static support surfaces were associated with lower risk for pressure ulcers compared with standard mattresses (relative risk range, 0.20 to 0.60). Evidence on the effectiveness of low-air-loss and alternating-air mattresses was limited, with some trials showing no clear differences from advanced static support surfaces. Evidence on the effectiveness of nutritional supplementation, repositioning, and skin care interventions versus usual care was limited and had methodological shortcomings, precluding strong conclusions. Only English-language articles were included, publication bias could not be formally assessed, and most studies had methodological shortcomings. More advanced static support surfaces are more effective than standard mattresses for preventing ulcers in higher-risk populations. The effectiveness of formal risk assessment instruments and associated intervention protocols compared with less standardized assessment methods and the effectiveness of other preventive interventions compared with usual care have not been clearly established.

Music for medical indications in the neonatal period: a systematic review of randomised controlled trials.

PubMed

Hartling, L; Shaik, M S; Tjosvold, L; Leicht, R; Liang, Y; Kumar, M

2009-09-01

To conduct a systematic review of the efficacy of music for medical indications in term or preterm neonates. We searched 17 electronic databases, subject bibliographies, reference lists and trials registries. Two reviewers independently screened studies for inclusion, assessed methodological quality, and extracted data. Meta-analysis was not feasible due to heterogeneity in outcomes so a qualitative analysis is presented. Nine randomised trials were included. The methodological quality was generally poor (median Jadad score = 1). The outcomes most commonly reported were physiological measures (heart rate (HR), respiratory rate, oxygen saturation (SaO2)), behavioural state and pain. Six studies evaluated music for the painful procedures circumcision (three trials) and heel prick (three trials). For circumcisions, one high quality pilot study (n = 23) showed benefits of music for the outcomes of HR, SaO2 and pain, while two low quality studies showed no difference. For heel prick, three low quality studies provided some evidence that music may be beneficial primarily for measures of behaviour and pain. The remaining studies evaluated the use of music in preterm infants to improve physiological and behavioural parameters (n = 31; benefits observed for behavioural parameters), to reinforce non-nutritive sucking via use of a pacifier activated lullaby (n = 32; significant increase in feeding rates), and to influence physiological stability and behaviours in infants with chronic lung disease (n = 22; no significant differences for outcomes assessed). The heterogeneity in study populations, interventions and outcomes precludes definitive conclusions around efficacy. There is preliminary evidence for some therapeutic benefits of music for specific indications; however, these findings need to be confirmed in methodologically rigorous trials.

The current state of the creation and modernization of national geodetic and cartographic resources in Poland

NASA Astrophysics Data System (ADS)

Doskocz, Adam

2016-01-01

All official data are currently integrated and harmonized in a spatial reference system. This paper outlines a national geodetic and cartographic resources in Poland. The national geodetic and cartographic resources are an important part of the spatial information infrastructure in the European Community. They also provide reference data for other resources of Spatial Data Infrastructure (SDI), including: main and detailed geodetic control networks, base maps, land and buildings registries, geodetic registries of utilities and topographic maps. This paper presents methods of producing digital map data and technical standards for field surveys, and in addition paper also presents some aspects of building Global and Regional SDI.

The value of patient registries in advancing pediatric surgical care.

PubMed

Skarsgard, Erik D

2018-05-01

Pediatric surgeons treat a variety of conditions that are distinguished by their low occurrence rate, complexity, and need for integrated multidisciplinary care. Although randomized controlled trials (RCTs) are considered the gold standard for generating evidence to inform best practice, they are poorly suited to rare diseases based on the variability of illness severity, unpredictability in clinical course, and the impact limitations of studying a single intervention at a time. An alternative to RCTs for comparative effectiveness research for rare diseases in pediatric surgery is the patient registry, which collects detailed and condition-specific patient level data related to illness severity, treatment, and outcome, and allows a large, disease-specific database to be created for the dual purposes of collaborative research and quality improvement across participating sites. This review discusses the various functions of a patient registry in fulfilling its mandate of evidence-based practice and outcome improvement using examples from a variety of existing pediatric surgical registries. The value proposition of patient registries as sources of knowledge, facilitators of practice standardization, and enablers of continuous quality improvement is discussed. Copyright © 2018 Elsevier Inc. All rights reserved.

Using an International Clinical Registry of Regional Anesthesia to Identify Targets for Quality Improvement

PubMed Central

Sites, Brian D.; Barrington, Michael J.; Davis, Matthew

2014-01-01

Background Despite the widespread use of regional anesthesia, limited information on clinical performance exists. Institutions, therefore, have little knowledge of how they are performing in regards to both safety and effectiveness. In this study, we demonstrate how a medical institution (or physician/physician group) may use data from a multi-center clinical registry of regional anesthesia to inform quality improvement strategies. Methods We analyzed data from the International Registry of Regional Anesthesia that includes prospective data on peripheral regional anesthesia procedures from 19 centers located around the world. Using data from the clinical registry, we present summary statistics of the overall safety and effectiveness of regional anesthesia. Furthermore, we demonstrate, using a variety of performance measures, how these data can be used by hospitals to identify areas for quality improvement. To do so, we compare the performance of one member institution (a United States medical center in New Hampshire) to that of the other 18 member institutions of the clinical registry. Results The clinical registry contained information on 23,271 blocks that were performed between June 1, 2011, and May 1, 2014, on 16,725 patients. The overall success rate was 96.7%, immediate complication rate was 2.2%, and the all-cause 60-day rate of neurological sequelae was 8.3 (95% CI, 7.2–9.7) per 10,000. Registry wide major hospital events included 7 wrong site blocks, 3 seizures, 1 complete heart block, 1 retroperitoneal hematoma, and 3 pneumothoraces. For our reference medical center, we identified areas meriting quality improvement. Specifically, after accounting for differences in the age, sex, and health status of patient populations, the reference medical center appeared to rely more heavily on opioids for post procedure management, had higher patient pain scores, and experienced delayed discharge when compared with other member institutions. Conclusions To our knowledge, this is the first large-scale effort to use a clinical registry to provide comparative outcome rates representing the safety and effectiveness of regional anesthesia. These results can be used to help inform quality improvement strategies. PMID:25275578

Haphazard reporting of deaths in clinical trials: a review of cases of ClinicalTrials.gov records and matched publications-a cross-sectional study.

PubMed

Earley, Amy; Lau, Joseph; Uhlig, Katrin

2013-01-18

A participant death is a serious event in a clinical trial and needs to be unambiguously and publicly reported. To examine (1) how often and how numbers of deaths are reported in ClinicalTrials.gov records; (2) how often total deaths can be determined per arm within a ClinicalTrials.gov results record and its corresponding publication and (3) whether counts may be discordant. Registry-based study of clinical trial results reporting. ClinicalTrials.gov results database searched in July 2011 and matched PubMed publications. A random sample of ClinicalTrials.gov results records. Detailed review of records with a single corresponding publication. ClinicalTrials.gov records reporting number of deaths under participant flow, primary or secondary outcome or serious adverse events. Consistency in reporting of number of deaths between ClinicalTrials.gov records and corresponding publications. In 500 randomly selected ClinicalTrials.gov records, only 123 records (25%) reported a number for deaths. Reporting of deaths across data modules for participant flow, primary or secondary outcomes and serious adverse events was variable. In a sample of 27 pairs of ClinicalTrials.gov records with number of deaths and corresponding publications, total deaths per arm could only be determined in 56% (15/27 pairs) but were discordant in 19% (5/27). In 27 pairs of ClinicalTrials.gov records without any information on number of deaths, 48% (13/27) were discordant since the publications reported absence of deaths in 33% (9/27) and positive death numbers in 15% (4/27). Deaths are variably reported in ClinicalTrials.gov records. A reliable total number of deaths per arm cannot always be determined with certainty or can be discordant with number reported in corresponding trial publications. This highlights a need for unambiguous and complete reporting of the number of deaths in trial registries and publications.

Haphazard reporting of deaths in clinical trials: a review of cases of ClinicalTrials.gov records and matched publications–a cross-sectional study

PubMed Central

Earley, Amy; Lau, Joseph; Uhlig,, Katrin

2013-01-01

Context A participant death is a serious event in a clinical trial and needs to be unambiguously and publicly reported. Objective To examine (1) how often and how numbers of deaths are reported in ClinicalTrials.gov records; (2) how often total deaths can be determined per arm within a ClinicalTrials.gov results record and its corresponding publication and (3) whether counts may be discordant. Design Registry-based study of clinical trial results reporting. Setting ClinicalTrials.gov results database searched in July 2011 and matched PubMed publications. Selection criteria A random sample of ClinicalTrials.gov results records. Detailed review of records with a single corresponding publication. Main outcome measure ClinicalTrials.gov records reporting number of deaths under participant flow, primary or secondary outcome or serious adverse events. Consistency in reporting of number of deaths between ClinicalTrials.gov records and corresponding publications. Results In 500 randomly selected ClinicalTrials.gov records, only 123 records (25%) reported a number for deaths. Reporting of deaths across data modules for participant flow, primary or secondary outcomes and serious adverse events was variable. In a sample of 27 pairs of ClinicalTrials.gov records with number of deaths and corresponding publications, total deaths per arm could only be determined in 56% (15/27 pairs) but were discordant in 19% (5/27). In 27 pairs of ClinicalTrials.gov records without any information on number of deaths, 48% (13/27) were discordant since the publications reported absence of deaths in 33% (9/27) and positive death numbers in 15% (4/27). Conclusions Deaths are variably reported in ClinicalTrials.gov records. A reliable total number of deaths per arm cannot always be determined with certainty or can be discordant with number reported in corresponding trial publications. This highlights a need for unambiguous and complete reporting of the number of deaths in trial registries and publications. PMID:23335556

CKD.QLD: establishment of a chronic kidney disease [CKD] registry in Queensland, Australia.

PubMed

Venuthurupalli, Sree K; Hoy, Wendy E; Healy, Helen G; Cameron, Anne; Fassett, Robert G

2017-06-07

Chronic kidney disease [CKD] is recognised as a global public health problem. Until recently, the majority of information informing on CKD has been generated from renal registries reporting on patients with end-stage kidney disease [ESKD] and on renal replacement therapy [RRT]. There has been a paucity of information on pre-dialysis CKD cohorts, and many issues related to these poorly described populations are unresolved. To this end, international organizations have called for CKD surveillance systems across all countries. In Australia, we have responded by developing the Chronic Kidney Disease in Queensland [CKD.QLD] with three main platforms consisting of CKD Registry, clinical trials and development of biobank. This registry which is the core component of CKD surveillance was conceptualized specifically for the pre-dialysis population in the public health system in Queensland, Australia. Recruitment started in May 2011, and to date the Registry has evolved as one of the largest CKD cohorts in the world with recruitment close to 7000 patients. The Registry has had many outcomes, including being the nidus for Australia's first National Health and Medical Research Council [NHMRC] CKD Centre of Research Excellence [CKD.CRE]. The Registry, with its linkage to Queensland Health datasets, is reporting, and is expected to continue generating, significant information on multiple aspects of CKD, its trajectory, management and patient outcomes. Intent of the CKD.CRE is to facilitate an expanded Registry network that has representation from health services, both public and private, across Australia.

Changes to registration elements and results in a cohort of Clinicaltrials.gov trials were not reflected in published articles.

PubMed

Pranić, Shelly; Marušić, Ana

2016-02-01

To assess effectiveness of legislative initiatives to stimulate public registration of trial results, we assessed adherence to protocol and results reporting, changes to registry, and publication data for randomized controlled trials (RCTs) after introduction of Food and Drug Administration Amendment Act (FDAAA). Observational study of a cohort of ClinicalTrials.gov registered FDAAA-covered RCTs found through ClinicalTrials.gov between 2009 and 2012 and data from corresponding publications. WHO Minimum Data Set items were abstracted by one author and verified by the other author. Among 81 eligible trials, most were industry-funded, with a drug intervention in parallel assignment. Secondary outcomes at the initial and last registration were omitted for 17% and 19.7% of RCTs, respectively. RCT registration changes mostly involved scientific title (18.8%). Inclusion criteria omission was most common (88%) in publications. Inferential statistical methods for primary and secondary outcomes matched between registry and publication for 53.4% and 28.6% of RCTs, respectively. Serious and other adverse events (AEs) that were absent for 23.8% and 4.8% of RCTs, respectively, were published as nonoccurring. Discrepancies remain relatively high between registered and published outcomes, particularly regarding registered omissions in publications and concomitant reporting, nature of statistical method used, and reporting of AEs. This seriously undermines transparency of clinical trials and needs immediate attention of all stakeholders in health research. Copyright © 2016 Elsevier Inc. All rights reserved.

The Kidney Awareness Registry and Education (KARE) study: protocol of a randomized controlled trial to enhance provider and patient engagement with chronic kidney disease.

PubMed

Tuot, Delphine S; Velasquez, Alexandra; McCulloch, Charles E; Banerjee, Tanushree; Zhu, Yunnuo; Hsu, Chi-yuan; Handley, Margaret; Schillinger, Dean; Powe, Neil R

2015-10-22

Chronic kidney disease (CKD) is common and is associated with excess mortality and morbidity. Better management could slow progression of disease, prevent metabolic complications, and reduce cardiovascular outcomes. Low patient awareness of CKD and ineffective patient-provider communication can impede such efforts. We developed provider and patient-directed interventions that harness health information technology to enhance provider recognition of CKD and delivery of guideline concordant care and augment patient understanding and engagement in CKD care. We report the design and protocol of the Kidney Awareness Registry and Education (KARE) Study, a 2x2 factorial randomized controlled trial that examines the impact of a multi-level intervention on health outcomes among low-income English, Spanish and Cantonese-speaking patients with CKD in a safety net system. The intervention includes: (1) implementation of a primary care electronic CKD registry that notifies practice teams of patients' CKD status and employs a patient profile and quarterly feedback to encourage provision of guideline-concordant care at point-of-care and via outreach; and (2) a language-concordant, culturally-sensitive self-management support program that consists of automated telephone modules, provision of low-literacy written patient-educational materials and telephone health coaching. The primary outcomes of the trial are changes in systolic blood pressure (BP) and the proportion of patients with BP control (≤ 140/90 mmHg) after one year. Secondary outcomes include patient understanding of CKD, participation in healthy behaviors, and practice team delivery of guideline-concordant CKD care. Results from the KARE study will provide data on the feasibility, effectiveness, and acceptability of technology-based interventions that support primary care efforts at improving health outcomes among vulnerable patients with CKD. ClinicalTrials.gov, number: NCT01530958.

Immune Deficiency Foundation

MedlinePlus

... PI CONNECT Research Network USIDNET Patient Registry IDF Survey Research IDF Surveys National Health Insurance Surveys Clinical Trials ... and Fellows Research USIDNET IDF Research Fund IDF Survey Research IDF Surveys Contact Us Search form Search Welcome ...

Community engagement in diverse populations for Alzheimer disease prevention trials.

PubMed

Romero, Heather R; Welsh-Bohmer, Kathleen A; Gwyther, Lisa P; Edmonds, Henry L; Plassman, Brenda L; Germain, Cassandra M; McCart, Michelle; Hayden, Kathleen M; Pieper, Carl; Roses, Allen D

2014-01-01

The recruitment of asymptomatic volunteers has been identified as a critical factor that is delaying the development and validation of preventive therapies for Alzheimer disease (AD). Typical recruitment strategies involve the use of convenience samples or soliciting participation of older adults with a family history of AD from clinics and outreach efforts. However, high-risk groups, such as ethnic/racial minorities, are traditionally less likely to be recruited for AD prevention studies, thus limiting the ability to generalize findings for a significant proportion of the aging population. A community-engagement approach was used to create a registry of 2311 research-ready, healthy adult volunteers who reflect the ethnically diverse local community. Furthermore, the registry's actual commitment to research was examined, through demonstrated participation rates in a clinical study. The approach had varying levels of success in establishing a large, diverse pool of individuals who are interested in participating in pharmacological prevention trials and meet the criteria for primary prevention research trials designed to delay the onset of AD. Our efforts suggest that entry criteria for the clinical trials need to be carefully considered to be inclusive of African Americans, and that sustained effort is needed to engage African Americans in pharmacological prevention approaches.

Comparison of pharmacological and non-pharmacological interventions to prevent delirium in critically ill patients: a protocol for a systematic review incorporating network meta-analyses.

PubMed

Burry, L D; Hutton, B; Guenette, M; Williamson, D; Mehta, S; Egerod, I; Kanji, S; Adhikari, N K; Moher, D; Martin, C M; Rose, L

2016-09-08

Delirium is characterized by acute changes in mental status including inattention, disorganized thinking, and altered level of consciousness, and is highly prevalent in critically ill adults. Delirium has adverse consequences for both patients and the healthcare system; however, at this time, no effective treatment exists. The identification of effective prevention strategies is therefore a clinical and research imperative. An important limitation of previous reviews of delirium prevention is that interventions were considered in isolation and only direct evidence was used. Our systematic review will synthesize all existing data using network meta-analysis, a powerful statistical approach that enables synthesis of both direct and indirect evidence. We will search Ovid MEDLINE, CINAHL, Embase, PsycINFO, and Web of Science from 1980 to March 2016. We will search the PROSPERO registry for protocols and the Cochrane Library for published systematic reviews. We will examine reference lists of pertinent reviews and search grey literature and the International Clinical Trials Registry Platform for unpublished studies and ongoing trials. We will include randomized and quasi-randomized trials of critically ill adults evaluating any pharmacological, non-pharmacological, or multi-component intervention for delirium prevention, administered in or prior to (i.e., peri-operatively) transfer to the ICU. Two authors will independently screen search results and extract data from eligible studies. Risk of bias assessments will be completed on all included studies. To inform our network meta-analysis, we will first conduct conventional pair-wise meta-analyses for primary and secondary outcomes using random-effects models. We will generate our network meta-analysis using a Bayesian framework, assuming a common heterogeneity parameter across all comparisons, and accounting for correlations in multi-arm studies. We will perform analyses using WinBUGS software. This systematic review will address the existing knowledge gap regarding best practices for delirium prevention in critically ill adults by synthesizing evidence from trials of pharmacological, non-pharmacological, and multi-component interventions administered in or prior to transfer to the ICU. Use of network meta-analysis will clarify which delirium prevention strategies are most effective in improving clinical outcomes while causing least harm. The network meta-analysis is a novel approach and will provide knowledge users and decision makers with comparisons of multiple interventions of delirium prevention strategies. PROSPERO CRD42016036313.

Respiratory-Related Hospitalizations following Prophylaxis in the Canadian Registry for Palivizumab (2005–2012) Compared to Other International Registries

PubMed Central

Mitchell, Ian; Lanctôt, Krista L.

2013-01-01

Respiratory syncytial virus (RSV) infection occurs commonly in infants aged ≤2 years, and severe infection results in hospitalization with accompanying morbidity and mortality. Palivizumab has been available for prophylaxis for the past 15 years. Prospective data on patients who received palivizumab from 2005 to 2012 has been assembled in the Canadian registry (CARESS) to document utilization, compliance, and health outcomes in both hospital and community settings. Long-term data is necessary to evaluate the impact of palivizumab on the incidence of RSV infections, minimize healthcare resources, and identify which infant subpopulations are receiving prophylaxis. A database search was also conducted for similar information from published registries, and hospitalization rates were compared to results from randomized clinical trials (RCTs).Overall hospitalization rates (percent; range) for respiratory-related illnesses and RSV-specific infection in infants who meet standard indications for prophylaxis were 6.6 (3.3–7.7) and 1.55 (0.3–2.06), respectively, in CARESS, which closely aligns with registry data from 4 other countries, despite the former comprising the largest cohort of complex patients internationally. Overall RSV-related hospitalization rates were lower across registries compared to equivalent patients in RCTs. Registry data provides valuable information regarding real-world experience with palivizumab, while facilitating the genesis of new research themes. PMID:23861694

American College of Chest Physicians

MedlinePlus

... Trials Registry NetWorks What Are NetWorks? FAQs Handbook Leadership Development Get Involved Membership Join Benefits and FAQ ... Provider Members International Membership Trainee Opportunities Member Directory Leadership Opportunities Apply for CHEST Leadership Become an FCCP ...

Interventions for treating oro-antral communications and fistulae due to dental procedures.

PubMed

Kiran Kumar Krishanappa, Salian; Prashanti, Eachempati; Sumanth, Kumbargere N; Naresh, Shetty; Moe, Soe; Aggarwal, Himanshi; Mathew, Rebecca J

2016-05-27

An oro-antral communication is an unnatural opening between the oral cavity and maxillary sinus. When it fails to close spontaneously, it remains patent and is epithelialized to develop into an oro-antral fistula. Various surgical and non-surgical techniques have been used for treating the condition. Surgical procedures include flaps, grafts and other techniques like re-implantation of third molars. Non-surgical techniques include allogenic materials and xenografts. To assess the effectiveness and safety of various interventions for the treatment of oro-antral communications and fistulae due to dental procedures. We searched the Cochrane Oral Health Group's Trials Register (whole database, to 3 July 2015), the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library, 2015, Issue 6), MEDLINE via OVID (1946 to 3 July 2015), EMBASE via OVID (1980 to 3 July 2015), US National Institutes of Health Trials Registry (http://clinicaltrials.gov) (whole database, to 3 July 2015) and the World Health Organization (WHO) International Clinical Trials Registry Platform (http://www.who.int/ictrp/en/) (whole database, to 3 July 2015). We also searched the reference lists of included and excluded trials for any randomised controlled trials (RCTs). We included RCTs evaluating any intervention for treating oro-antral communications or oro-antral fistulae due to dental procedures. We excluded quasi-RCTs and cross-over trials. We excluded studies on participants who had oro-antral communications, fistulae or both related to Caldwell-Luc procedure or surgical excision of tumours. Two review authors independently selected trials. Two review authors assessed trial risk of bias and extracted data independently. We estimated risk ratios (RR) for dichotomous data, with 95% confidence intervals (CI). We assessed the overall quality of the evidence using the GRADE approach. We included only one study in this review, which compared two surgical interventions: pedicled buccal fat pad flap and buccal flap for the treatment of oro-antral communications. The study involved 20 participants. The risk of bias was unclear. The relevant outcome reported in this trial was successful (complete) closure of oro-antral communication.The quality of the evidence for the primary outcome was very low. The study did not find evidence of a difference between interventions for the successful (complete) closure of an oro-antral communication (RR 1.00, 95% Cl 0.83 to 1.20) one month after the surgery. All oro-antral communications in both groups were successfully closed so there were no adverse effects due to treatment failure.We did not find trials evaluating any other intervention for treating oro-antral communications or fistulae due to dental procedures. We found very low quality evidence from a single small study that compared pedicled buccal fat pad and buccal flap. The evidence was insufficient to judge whether there is a difference in the effectiveness of these interventions as all oro-antral communications in the study were successfully closed by one month after surgery. Large, well-conducted RCTs investigating different interventions for the treatment of oro-antral communications and fistulae caused by dental procedures are needed to inform clinical practice.

Embedding a randomized clinical trial into an ongoing registry infrastructure: unique opportunities for efficiency in design of the Study of Access site For Enhancement of Percutaneous Coronary Intervention for Women (SAFE-PCI for Women).

PubMed

Hess, Connie N; Rao, Sunil V; Kong, David F; Aberle, Laura H; Anstrom, Kevin J; Gibson, C Michael; Gilchrist, Ian C; Jacobs, Alice K; Jolly, Sanjit S; Mehran, Roxana; Messenger, John C; Newby, L Kristin; Waksman, Ron; Krucoff, Mitchell W

2013-09-01

Women are at higher risk than men for bleeding and vascular complications after percutaneous coronary intervention (PCI). Compared with femoral access, radial access reduces these complications but may be more challenging in women because of higher rates of radial artery spasm, tortuosity, and occlusion as well as lower rates of procedure success. Whether the safety advantages of radial versus femoral access in women undergoing PCI are outweighed by reduced effectiveness has not been studied. The Study of Access site For Enhancement of PCI for Women is a prospective, randomized clinical trial comparing radial with femoral arterial access in women undergoing PCI. In conjunction with the US Food and Drug Administration's Critical Path Cardiac Safety Research Consortium, this study embeds the randomized clinical trial into the existing infrastructure of the National Cardiovascular Data Registry CathPCI Registry through the National Institute of Health's National Cardiovascular Research Infrastructure. The primary efficacy end point is a composite of bleeding (Bleeding Academic Research Consortium types 2, 3, or 5) or vascular complication requiring intervention occurring at 72 hours after PCI or by hospital discharge. The primary feasibility end point is procedure success. Secondary end points include procedure duration, contrast volume, radiation dose, quality of life, and a composite of 30-day death, vascular complication, or unplanned revascularization. © 2013.

Inpatient management of children with severe acute malnutrition: a review of WHO guidelines

PubMed Central

Tickell, Kirkby D

2016-01-01

Abstract Objective To understand how the World Health Organization’s (WHO’s) guidelines on the inpatient care of children with complicated severe acute malnutrition may be strengthened to improve outcomes. Methods In December 2015, we searched Google scholar and WHO’s website for WHO recommendations on severe acute malnutrition management and evaluated the history and cited evidence behind these recommendations. We systematically searched WHO International Clinical Trials Registry Platform, clinicaltrials.gov and the Controlled Trials metaRegister until 10 August 2015 for recently completed, ongoing, or pending trials. Findings WHO’s guidelines provide 33 recommendations on the topic. However, 16 (48.5%) of these recommendations were based solely on expert opinion – unsupported by published evidence. Another 11 (33.3%) of the recommendations were supported by the results of directly relevant research – i.e. either randomized trials (8) or observational studies (3). The other six recommendations (18.2%) were based on studies that were not conducted among children with complicated severe malnutrition or studies of treatment that were not identical to the recommended intervention. Trials registries included 20 studies related to the topic, including nine trials of alternative feeding regimens. Acute medical management and follow-up care studies were minimally represented. Conclusion WHO’s guidelines on the topic have a weak evidence base and have undergone limited substantive adjustments over the past decades. More trials are needed to make that evidence base more robust. If the mortality associated with severe malnutrition is to be reduced, inpatient and post-discharge management trials, supported by studies on the causes of mortality, are needed. PMID:27708469

Global shortage of neonatal and paediatric antibiotic trials: rapid review

PubMed Central

Thompson, Georgina; Barker, Charlotte I; Folgori, Laura; Bielicki, Julia A; Bradley, John S; Lutsar, Irja; Sharland, Mike

2017-01-01

Objectives There have been few clinical trials (CTs) on antibiotics that inform neonatal and paediatric drug labelling. The rate of unlicensed and off-label prescribing in paediatrics remains high. It is unclear whether the current neonatal and paediatric antibiotic research pipeline is adequate to inform optimal drug dosing. Using the ClinicalTrials.gov registry, this review aims to establish the current global status of antibiotic CTs in children up to 18 years of age. Methods Studies were identified using key word searches of the ClinicalTrials.gov registry and were manually filtered using prespecified inclusion/exclusion criteria. Results 76 registered open CTs of antibiotics in children were identified globally; 23 (30%) were recruiting newborns (only 8 (11%) included preterm neonates), 52 (68%) infants and toddlers, 58 (76%) children and 54 (71%) adolescents. The majority of registered trials were late phase (10 (15%) phase 3 and 23 (35%) phase 4/pharmacovigilance). Two-thirds were sponsored by non-profit organisations, compared with pharmaceutical companies (50 (66%) vs 26 (34%), respectively). A greater proportion of non-profit funded trials were efficacy-based strategic trials (n=34, 68%), in comparison with industry-led trials, which were most often focused on safety or pharmacokinetic data (n=17, 65%). Only 2 of the 37 antibiotics listed on the May 2016 Pew Charitable Trusts antibiotic development pipeline, currently being studied in adults, appear to be currently recruiting in open paediatric CTs. Conclusions This review highlights that very few paediatric antibiotic CTs are being conducted globally, especially in neonates. There is a striking disparity noted between antibiotic drug development programmes in adults and children. PMID:29030411

Sexual counselling for treating or preventing sexual dysfunction in women living with female genital mutilation: A systematic review.

PubMed

Okomo, Uduak; Ogugbue, Miriam; Inyang, Elizabeth; Meremikwu, Martin M

2017-02-01

Female sexual dysfunction is the persistent or recurring decrease in sexual desire or arousal, the difficulty or inability to achieve an orgasm, and/or the feeling of pain during sexual intercourse. Impaired sexual function can occur with all types of female genital mutilation (FGM) owing to the structural changes, pain, or traumatic memories associated with the procedure. To conduct a systematic review of randomized and nonrandomized studies into the effects of sexual counseling with or without genital lubricants on the sexual function of women living with FGM. Cochrane Central Register of Controlled Trials, MEDLINE, African Index Medicus, SCOPUS, LILACS, CINAHL, ClinicalTrials.gov, Pan African Clinical Trials Registry, and other databases were searched to August 2015. The reference lists of retrieved studies were checked for reports of additional studies, and lead authors contacted for additional data. Studies of girls and women living with any type of FGM who received counselling interventions for sexual dysfunction were included. No relevant studies that addressed the objective of the review were identified. Despite a comprehensive search, the authors could not find evidence of the effects of sexual counseling on the sexual function of women living with FGM. Studies assessing this intervention are needed. CRD42015024593. © 2017 International Federation of Gynecology and Obstetrics. The World Health Organization retains copyright and all other rights in the manuscript of this article as submitted for publication.

Proving Value in Radiology: Experience Developing and Implementing a Shareable Open Source Registry Platform Driven by Radiology Workflow.

PubMed

Gichoya, Judy Wawira; Kohli, Marc D; Haste, Paul; Abigail, Elizabeth Mills; Johnson, Matthew S

2017-10-01

Numerous initiatives are in place to support value based care in radiology including decision support using appropriateness criteria, quality metrics like radiation dose monitoring, and efforts to improve the quality of the radiology report for consumption by referring providers. These initiatives are largely data driven. Organizations can choose to purchase proprietary registry systems, pay for software as a service solution, or deploy/build their own registry systems. Traditionally, registries are created for a single purpose like radiation dosage or specific disease tracking like diabetes registry. This results in a fragmented view of the patient, and increases overhead to maintain such single purpose registry system by requiring an alternative data entry workflow and additional infrastructure to host and maintain multiple registries for different clinical needs. This complexity is magnified in the health care enterprise whereby radiology systems usually are run parallel to other clinical systems due to the different clinical workflow for radiologists. In the new era of value based care where data needs are increasing with demand for a shorter turnaround time to provide data that can be used for information and decision making, there is a critical gap to develop registries that are more adapt to the radiology workflow with minimal overhead on resources for maintenance and setup. We share our experience of developing and implementing an open source registry system for quality improvement and research in our academic institution that is driven by our radiology workflow.

Evidence and practice in spine registries

PubMed Central

van Hooff, Miranda L; Jacobs, Wilco C H; Willems, Paul C; Wouters, Michel W J M; de Kleuver, Marinus; Peul, Wilco C; Ostelo, Raymond W J G; Fritzell, Peter

2015-01-01

Background and purpose We performed a systematic review and a survey in order to (1) evaluate the evidence for the impact of spine registries on the quality of spine care, and with that, on patient-related outcomes, and (2) evaluate the methodology used to organize, analyze, and report the “quality of spine care” from spine registries. Methods To study the impact, the literature on all spinal disorders was searched. To study methodology, the search was restricted to degenerative spinal disorders. The risk of bias in the studies included was assessed with the Newcastle-Ottawa scale. Additionally, a survey among registry representatives was performed to acquire information about the methodology and practice of existing registries. Results 4,273 unique references up to May 2014 were identified, and 1,210 were eligible for screening and assessment. No studies on impact were identified, but 34 studies were identified to study the methodology. Half of these studies (17 of the 34) were judged to have a high risk of bias. The survey identified 25 spine registries, representing 14 countries. The organization of these registries, methods used, analytical approaches, and dissemination of results are presented. Interpretation We found a lack of evidence that registries have had an impact on the quality of spine care, regardless of whether intervention was non-surgical and/or surgical. To improve the quality of evidence published with registry data, we present several recommendations. Application of these recommendations could lead to registries showing trends, monitoring the quality of spine care given, and ultimately improving the value of the care given to patients with degenerative spinal disorders. PMID:25909475

Resource implications of preparing individual participant data from a clinical trial to share with external researchers.

PubMed

Tudur Smith, Catrin; Nevitt, Sarah; Appelbe, Duncan; Appleton, Richard; Dixon, Pete; Harrison, Janet; Marson, Anthony; Williamson, Paula; Tremain, Elizabeth

2017-07-17

Demands are increasingly being made for clinical trialists to actively share individual participant data (IPD) collected from clinical trials using responsible methods that protect the confidentiality and privacy of clinical trial participants. Clinical trialists, particularly those receiving public funding, are often concerned about the additional time and money that data-sharing activities will require, but few published empirical data are available to help inform these decisions. We sought to evaluate the activity and resources required to prepare anonymised IPD from a clinical trial in anticipation of a future data-sharing request. Data from two UK publicly funded clinical trials were used for this exercise: 2437 participants with epilepsy recruited from 90 hospital outpatient clinics in the SANAD trial and 146 children with neuro-developmental problems recruited from 18 hospitals in the MENDS trial. We calculated the time and resources required to prepare each anonymised dataset and assemble a data pack ready for sharing. The older SANAD trial (published 2007) required 50 hours of staff time with a total estimated associated cost of £3185 whilst the more recently completed MENDS trial (published 2012) required 39.5 hours of staff time with total estimated associated cost of £2540. Clinical trial researchers, funders and sponsors should consider appropriate resourcing and allow reasonable time for preparing IPD ready for subsequent sharing. This process would be most efficient if prospectively built into the standard operational design and conduct of a clinical trial. Further empirical examples exploring the resource requirements in other settings is recommended. SANAD: International Standard Randomised Controlled Trials Registry: ISRCTN38354748 . Registered on 25 April 2003. EU Clinical Trials Register Eudract 2006-004025-28 . Registered on 16 May 2007. International Standard Randomised Controlled Trials Registry: ISRCTN05534585 /MREC 07/MRE08/43. Registered on 26 January 2007.

A registry-based randomized trial comparing radial and femoral approaches in women undergoing percutaneous coronary intervention: the SAFE-PCI for Women (Study of Access Site for Enhancement of PCI for Women) trial.

PubMed

Rao, Sunil V; Hess, Connie N; Barham, Britt; Aberle, Laura H; Anstrom, Kevin J; Patel, Tejan B; Jorgensen, Jesse P; Mazzaferri, Ernest L; Jolly, Sanjit S; Jacobs, Alice; Newby, L Kristin; Gibson, C Michael; Kong, David F; Mehran, Roxana; Waksman, Ron; Gilchrist, Ian C; McCourt, Brian J; Messenger, John C; Peterson, Eric D; Harrington, Robert A; Krucoff, Mitchell W

2014-08-01

This study sought to determine the effect of radial access on outcomes in women undergoing percutaneous coronary intervention (PCI) using a registry-based randomized trial. Women are at increased risk of bleeding and vascular complications after PCI. The role of radial access in women is unclear. Women undergoing cardiac catheterization or PCI were randomized to radial or femoral arterial access. Data from the CathPCI Registry and trial-specific data were merged into a final study database. The primary efficacy endpoint was Bleeding Academic Research Consortium type 2, 3, or 5 bleeding or vascular complications requiring intervention. The primary feasibility endpoint was access site crossover. The primary analysis cohort was the subgroup undergoing PCI; sensitivity analyses were conducted in the total randomized population. The trial was stopped early for a lower than expected event rate. A total of 1,787 women (691 undergoing PCI) were randomized at 60 sites. There was no significant difference in the primary efficacy endpoint between radial or femoral access among women undergoing PCI (radial 1.2% vs. 2.9% femoral, odds ratio [OR]: 0.39; 95% confidence interval [CI]: 0.12 to 1.27); among women undergoing cardiac catheterization or PCI, radial access significantly reduced bleeding and vascular complications (0.6% vs. 1.7%; OR: 0.32; 95% CI: 0.12 to 0.90). Access site crossover was significantly higher among women assigned to radial access (PCI cohort: 6.1% vs. 1.7%; OR: 3.65; 95% CI: 1.45 to 9.17); total randomized cohort: (6.7% vs. 1.9%; OR: 3.70; 95% CI: 2.14 to 6.40). More women preferred radial access. In this pragmatic trial, which was terminated early, the radial approach did not significantly reduce bleeding or vascular complications in women undergoing PCI. Access site crossover occurred more often in women assigned to radial access. (SAFE-PCI for Women; NCT01406236). Copyright © 2014 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

[Real-world data on novel oral anticoagulants: the added value of registries and observational studies. Focus on apixaban].

PubMed

Pelliccia, Francesco; Tanzilli, Gaetano; Schiariti, Michele; Viceconte, Nicola; Greco, Cesare; Gaudio, Carlo

2016-12-01

Anticoagulant therapy has been used with great effect for decades for the prevention of stroke among patients with atrial fibrillation. In recent years, the therapeutic armamentarium has been strengthened considerably, with the addition of anticoagulants acting through novel pathways. The currently available novel agents are apixaban, rivaroxaban and dabigatran. These novel oral anticoagulants (NOACs) were approved for use on the basis of major clinical trials clearly demonstrating improved risk reductions compared to warfarin for stroke and/or major bleeding events. In these studies, apixaban and dabigatran 150 mg each significantly reduced the risk of stroke, while apixaban and dabigatran 110 mg reduced the risk of major bleeding compared to warfarin. Extrapolating the results of the randomized clinical trials on NOACs to all patients is not possible, as the strict design of clinical trials yields information that is directly applicable to a relatively narrow spectrum of patients. To control for confounding variables, randomized studies restrict enrolment to a prespecified set of criteria that do not necessarily reflect the profiles of all those who could potentially benefit from these agents. Research continues using the trial databases, in an attempt to better identify patient subgroups who do or do not benefit from each of the agents. At the European Society of Cardiology (ESC) annual meetings in London in 2015 and in Rome in 2016, there were several presentations and posters providing this type of evidence. Perhaps more important, as real-world experience with these agents grows, we are beginning to obtain meaningful new information about the NOACs in everyday use. This has involved the study of large databases including patients receiving these medications in clinical situations less stringently defined than in the randomized clinical trials. These include purpose-built registries, observational studies, and analyses of healthcare administrative databases. At both ESC meetings in 2015 and 2016, a wealth of information was presented using these types of sources. In many cases, these new data reinforce the key learnings from the randomized clinical trials. The following report provides highlights of registry and other post-marketing data presented at both ESC meetings in 2015 and 2016.

Vitamin K for upper gastrointestinal bleeding in people with acute or chronic liver diseases.

PubMed

Martí-Carvajal, Arturo J; Solà, Ivan

2015-06-09

Upper gastrointestinal bleeding is one of the most frequent causes of morbidity and mortality in the course of liver cirrhosis. Several treatments are used for upper gastrointestinal bleeding in people with liver diseases. One of them is vitamin K administration, but it is not known whether it benefits or harms people with acute or chronic liver disease and upper gastrointestinal bleeding. This is an update of this Cochrane review. To assess the beneficial and harmful effects of vitamin K for people with acute or chronic liver disease and upper gastrointestinal bleeding. We searched The Cochrane Hepato-Biliary Controlled Trials Register (February 2015), the Cochrane Central Register of Controlled Trials (CENTRAL) (Issue 2 of 12, 2015), MEDLINE (Ovid SP) (1946 to February 2015), EMBASE (Ovid SP) (1974 to February 2015), Science Citation Index EXPANDED (1900 to February 2015), and LILACS (1982 to 25 February 2015). We sought additional randomised trials from two registries of clinical trials: the World Health Organization Clinical Trials Search Portal and the metaRegister of Controlled Trials. We looked through the reference lists of the retrieved publications and review articles. Randomised clinical trials irrespective of blinding, language, or publication status for assessment of benefits and harms. We considered observational studies for assessment of harms only. \\We aimed to summarise data from randomised clinical trials using Standard Cochrane methodology and assess them according to the GRADE approach. We found no randomised trials on vitamin K for upper gastrointestinal bleeding in people with liver diseases assessing benefits and harms of the intervention. We identified no quasi-randomised studies, historically controlled studies, or observational studies assessing harms. This updated review found no randomised clinical trials of vitamin K for upper gastrointestinal bleeding in people with liver diseases. The benefits and harms of vitamin K need to be tested in randomised clinical trials. Until randomised clinical trials are conducted to assess the trade-off between benefits and harms, we cannot recommend or refute the use of vitamin K for upper gastrointestinal bleeding in people with liver diseases.

Chemical mutagenesis in laboratory mammals. A bibliography on the effects of chemicals on germ cells

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

Von Halle, E.S.

1973-09-01

A list of references is presented on chemical mutagenesis in laboratory mammals. The references relate primarily to chemical effects on germ cells. Only references to the use of chemicals or chemicals and radiation are included. The publication includes a citation index, agent index, chemical abstracts registry number index, organism index, KWIC index, author index, and first author index. (ERB)

Utilizing national and international registries to enhance pre-market medical device regulatory evaluation.

PubMed

Yue, Lilly Q; Campbell, Gregory; Lu, Nelson; Xu, Yunling; Zuckerman, Bram

2016-01-01

Regulatory decisions are made based on the assessment of risk and benefit of medical devices at the time of pre-market approval and subsequently, when post-market risk-benefit balance needs reevaluation. Such assessments depend on scientific evidence obtained from pre-market studies, post-approval studies, post-market surveillance studies, patient perspective information, as well as other real world data such as national and international registries. Such registries provide real world evidence and are playing a more and more important role in enhancing the safety and effectiveness evaluation of medical devices. While these registries provide large quantities of data reflecting real world practice and can potentially reduce the cost of clinical trials, challenges arise concerning (1) data quality adequate for regulatory decision-making, (2) bias introduced at every stage and aspect of study, (3) scientific validity of study designs, and (4) reliability and interpretability of study results. This article will discuss related statistical and regulatory challenges and opportunities with examples encountered in medical device regulatory reviews.

Comparison of education group strategies and home visits in type 2 diabetes mellitus: clinical trial.

PubMed

Santos, Jéssica Caroline Dos; Cortez, Daniel Nogueira; Macedo, Maísa Mara Lopes; Reis, Edna Afonso; Reis, Ilka Afonso; Torres, Heloísa Carvalho

2017-12-21

to compare the adherence and empowerment of patients with type 2 diabetes mellitus for self-care practices and glycemic control in group education strategies and home visits. Clinical trial with ten randomized clusters, performed with 238 patients with type 2 diabetes mellitus distributed in group education, home visit, and control group. Socio-demographic data, glycated hemoglobin and those obtained from the self-care and empowerment questionnaires were collected. Statistical analysis was performed separately by educational strategy. the mean age of the patients was 57.8 years old (SD = 9.4 years old), with a predominantly female participation (66.4%). Both strategies presented similar results regarding adherence to self-care practices and patient empowerment. There was also a reduction in glycated hemoglobin levels; however, only in the education group, the difference presented statistical significance (p <0.001). the strategies were effective; however, group education presented better glycemic control results in relation to the home visit. International registry: NCT02132338 and national: RBR-92j38t in the clinical trials registry.

[Side effects of biologic therapies in psoriasis].

PubMed

Altenburg, A; Augustin, M; Zouboulis, C C

2018-04-01

The introduction of biologics has revolutionized the treatment of moderate to severe plaque psoriasis. Due to the continuous expansion of biological therapies for psoriasis, it is particularly important to acknowledge efficacy and safety of the compounds not only in clinical trials but also in long-term registry-based observational studies. Typical side effects and significant risks of antipsoriatic biologic therapies considering psoriatic control groups are presented. A selective literature search was conducted in PubMed and long-term safety studies of the psoriasis registries PsoBest, PSOLAR and BADBIR were evaluated. To assess the long-term safety of biologics, the evaluation of the course of large patient cohorts in long-term registries is of particular medical importance. Newer biologic drugs seem to exhibit a better safety profile than older ones.

Childhood vesicoureteral reflux studies: registries and repositories sources and nosology.

PubMed

Chesney, Russell W; Patters, Andrea B

2013-12-01

Despite several recent studies, the advisability of antimicrobial prophylaxis and certain imaging studies for urinary tract infections (UTIs) remains controversial. The role of vesicoureteral reflux (VUR) on the severity and re-infection rates for UTIs is also difficult to assess. Registries and repositories of data and biomaterials from clinical studies in children with VUR are valuable. Disease registries are collections of secondary data related to patients with a specific diagnosis, condition or procedure. Registries differ from indices in that they contain more extensive data. A research repository is an entity that receives, stores, processes and/or disseminates specimens (or other materials) as needed. It encompasses the physical location as well as the full range of activities associated with its operation. It may also be referred to as a biorepository. This report provides information about some current registries and repositories that include data and samples from children with VUR. It also describes the heterogeneous nature of the subjects, as some registries and repositories include only data or samples from patients with primary reflux while others also include those from patients with syndromic or secondary reflux. Copyright © 2012 Journal of Pediatric Urology Company. All rights reserved.

Novel Multivalent Wound-Healing Ointment Provides Bioburden Control and Moisture Management: A Retrospective Registry Data Analysis.

PubMed

Serena, Thomas; Connell, Heather; McConnell, Sharon; Patel, Keyur; Doner, Bryan; Sabo, Matthew; Miller, Michael; Serena, Laura; Le, Lam T; Goldsmith, David; Chung, Jane

2016-10-01

The purpose of this retrospective registry data analysis was to explore the effectiveness of a novel multivalent topical ointment (Terrasil Infection Control Wound Care Ointment; Aspiera Medical, Woonsocket, Rhode Island), containing a patented mineral complex and 0.2% benzethonium chloride in the treatment of nonhealing acute and chronic wounds. Aspiera Medical designed a registry to capture physician experiences and treatment results with Terrasil Infection Control Wound Care Ointment. Physicians were asked to enter deidentified patient data into an online registry. Wound clinics in the United States were asked to participate in the registry. Physicians at 4 wound clinics treated 30 patients (26 of whom completed the treatment) with various chronic wounds that had persisted for an average of 6 months and entered treatment data into the registry. Patients applied the ointment according to physician orders. Concurrent treatments used by patients included offloading, compression wraps, and dressings, such as collagen and calcium alginate. Patients were treated until complete wound closure or lost to follow-up. Physicians calculated each patient's percentage wound reduction at each visit. Thirty patients were entered into the registry. Pretreatment and posttreatment measurements were available for 26 of them. Patients achieved an average surface area reduction of 84% in a mean of 23 days' treatment. The antimicrobial and moisturizing ointment studied appears to be effective in promoting wound closure in a variety of acute and chronic wounds. Wounds studied included diabetic foot ulcers, venous leg ulcers, venous stasis ulcers, surgical infections, burns, and insect bites. The results of this registry data analysis will be used to inform planned clinical trials.

Statistical controversies in clinical research: comparison of primary outcomes in protocols, public clinical-trial registries and publications: the example of oncology trials.

PubMed

Perlmutter, A S; Tran, V-T; Dechartres, A; Ravaud, P

2017-04-01

Protocols are often unavailable to peer-reviewers and readers. To detect outcome reporting bias (ORB), readers usually have to resort to publicly available descriptions of study design such as public clinical trial registries. We compared primary outcomes in protocols, ClinicalTrials.gov and publications of oncology trials and evaluated the use of ClinicalTrials.gov as compared with protocols in detecting discrepancies between planned and published outcomes. We searched for phase III oncology trials registered in ClinicalTrials.gov and published in the Journal of Clinical Oncology and New England Journal of Medicine between January 2014 and June 2015. We extracted primary outcomes reported in the protocol, ClinicalTrials.gov and the publication. First, we assessed the quality of primary outcome descriptions by using a published framework. Second, we evaluated modifications of primary outcomes between each source. Finally, we evaluated the agreement, specificity and sensitivity of detecting modifications between planned and published outcomes by using protocols or ClinicalTrials.gov. We included 65 trials, with 81 primary outcomes common among the 3 sources. The proportion of primary outcomes reporting all items from the framework was 73%, 22%, and 75% for protocols, ClinicalTrials.gov and publications, respectively. Eight (12%) trials presented a discrepancy between primary outcomes reported in the protocol and in the publication. Twelve (18.5%) trials presented a discrepancy between primary outcomes registered at ClinicalTrials.gov and in publications. We found a moderate agreement in detecting discrepant reporting of outcomes by using protocols or ClinicalTrials.gov [κ = 0.53, 95% confidence interval (0.25-0.81)]. Using ClinicalTrials.gov to detect discrepant reporting of outcomes showed high specificity (89.5%) but lacked sensitivity (75%) as compared with use of protocols. In oncology trials, primary outcome descriptions in ClinicalTrials.gov are often of low quality and may not reflect what is in the protocol, thus limiting the detection of modifications between planned and published outcomes. © The Author 2016. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved. For permissions, please email: journals.permissions@oup.com.

Therapeutic improvements expected in the near future for schizophrenia and schizoaffective disorder: an appraisal of phase III clinical trials of schizophrenia-targeted therapies as found in US and EU clinical trial registries.

PubMed

Garay, Ricardo P; Citrome, Leslie; Samalin, Ludovic; Liu, Chen-Chung; Thomsen, Morten S; Correll, Christoph U; Hameg, Ahcène; Llorca, Pierre-Michel

2016-01-01

In this review, the authors describe medications in phase III of clinical development for schizophrenia and schizoaffective disorder, and provide an opinion on how current treatment can be improved in the near future. Recent (post 2013) phase III clinical trials of schizophrenia-targeted therapies were found in US and EU clinical trial registries. Two hundred fifty-three trials were identified, that included 16 investigational compounds. The antipsychotics brexpiprazole and cariprazine have been approved in the US, and although both are dopamine D2 receptor partial agonists, they differ markedly in their pharmacodynamic profiles. Encenicline and valbenazine are first-in-class candidates for treatment of cognitive impairment associated with schizophrenia (CIAS) and tardive dyskinesia, respectively. Eleven add-on compounds were previously approved for other therapeutic indications and are for the most part being studied at academic medical centers and smaller pharmaceutical companies for negative symptoms and CIAS or for specific populations (comorbidities, antipsychotic-induced obesity). Promising new agents are emerging for schizophrenia and schizoaffective disorder. In addition to better-tolerated antipsychotics that treat positive symptoms, we could see the arrival of the first effective drug for negative symptoms and CIAS, which would strongly facilitate the ultimate goal of recovery in persons with schizophrenia.

[The Murcia Twin Registry. A resource for research on health-related behaviour].

PubMed

Ordoñana, Juan R; Sánchez Romera, Juan F; Colodro-Conde, Lucía; Carrillo, Eduvigis; González-Javier, Francisca; Madrid-Valero, Juan J; Morosoli-García, José J; Pérez-Riquelme, Francisco; Martínez-Selva, José M

Genetically informative designs and, in particular, twin studies, are the most widely used methodology to analyse the relative contribution of genetic and environmental factors to inter-individual variability. These studies basically compare the degree of phenotypical similarity between monozygotic and dizygotic twin pairs. In addition to the traditional estimate of heritability, this kind of registry enables a wide variety of analyses which are unique due to the characteristics of the sample. The Murcia Twin Registry is population-based and focused on the analysis of health-related behaviour. The observed prevalence of health problems is comparable to that of other regional and national reference samples, which guarantees its representativeness. Overall, the characteristics of the Registry facilitate developing various types of research as well as genetically informative designs, and collaboration with different initiatives and consortia. Copyright © 2016 SESPAS. Publicado por Elsevier España, S.L.U. All rights reserved.

Standardization of Questions in Rare Disease Registries: The PRISM Library Project

PubMed Central

Shereff, Denise; Andrews, James Everett

2012-01-01

Background Patient registries are often a helpful first step in estimating the impact and understanding the etiology of rare diseases - both requisites for the development of new diagnostics and therapeutics. The value and utility of patient registries rely on the use of both well-constructed structured research questions and relevant answer sets accompanying them. There are currently no clear standards or specifications for developing registry questions, and there are no banks of existing questions to support registry developers. Objective This paper introduces the [Rare Disease] PRISM (Patient Registry Item Specifications and Metadata for Rare Disease) project, a library of standardized questions covering a broad spectrum of rare diseases that can be used to support the development of new registries, including Internet-based registries. Methods A convenience sample of questions was identified from well-established (>5 years) natural history studies in various diseases and from several existing registries. Face validity of the questions was determined by review by many experts (both terminology experts at the College of American Pathologists (CAP) and research and informatics experts at the University of South Florida (USF)) for commonality, clarity, and organization. Questions were re-worded slightly, as needed, to make the full semantics of the question clear and to make the questions generalizable to multiple diseases where possible. Questions were indexed with metadata (structured and descriptive information) using a standard metadata framework to record such information as context, format, question asker and responder, and data standards information. Results At present, PRISM contains over 2,200 questions, with content of PRISM relevant to virtually all rare diseases. While the inclusion of disease-specific questions for thousands of rare disease organizations seeking to develop registries would present a challenge for traditional standards development organizations, the PRISM library could serve as a platform to liaison between rare disease communities and existing standardized controlled terminologies, item banks, and coding systems. Conclusions If widely used, PRISM will enable the re-use of questions across registries, reduce variation in registry data collection, and facilitate a bottom-up standardization of patient registries. Although it was initially developed to fulfill an urgent need in the rare disease community for shared resources, the PRISM library of patient-directed registry questions can be a valuable resource for registries in any disease – whether common or rare. Trial Registration N/A PMID:23611924

The NordICC Study: Rationale and design of a randomized trial on colonoscopy screening for colorectal cancer

PubMed Central

F.Kaminski, Michal; Bretthauer, Michael; Zauber, Ann G.; Kuipers, Ernst J.; Adami, Hans-Olov; van Ballegooijen, Marjolein; Regula, Jaroslaw; van Leerdam, Monique; Stefansson, Tryggvi; Påhlman, Lars; Dekker, Evelien; Hernán, Miguel A.; Garborg, Kjetil; Hoff, Geir

2017-01-01

Background While colonoscopy screening is widely used in several European countries and the United States, no randomised trials exist to quantify its benefits. The Nordic-European Initiative on Colorectal Cancer (NordICC) is a multinational, randomized controlled trial aiming at investigating the effect of colonoscopy screening on CRC incidence and mortality. This paper describes the rationale and design of the NordICC trial. Material and methods Men and women age 55 to 64 years are drawn from the population registries in the participating countries and randomly assigned to either once-only colonoscopy screening with removal of all detected lesions, or no screening (standard of care in the trial regions). All individuals are followed for 15 years after inclusion using dedicated national registries. Results The primary endpoints of the trial are cumulative CRC-specific death and CRC incidence during 15 years of follow up. We hypothesize a 50% CRC mortality-reducing efficacy of the colonoscopy intervention and predict 50% compliance, yielding a 25% mortality reduction among those invited to screening. For 90% power and a two-sided alpha level of 0.05, using a 2:1 randomisation, 45,600 individuals will be randomised to control, and 22,800 individuals to the colonoscopy group. Interim analyses of the effect of colonoscopy on CRC incidence and mortality will be performed at 10 years follow-up. Conclusions The aim of the NordICC trial is to quantify the effectiveness of population-based colonoscopy screening. This will allow development of evidence-based guidelines for CRC screening in the general population. PMID:22723185

TOPS: Trial Of Prevention Strategies for low back pain in patients recently recovered from low back pain—study rationale and protocol

PubMed Central

Lin, Chung-Wei C; Hancock, Mark J; Latimer, Jane; Buchbinder, Rachelle; Grotle, Margreth; van Tulder, Maurits; New, Charles H; Wisby-Roth, Trish; Maher, Chris G

2016-01-01

Introduction Low back pain (LBP) is the health condition that carries the greatest disability burden worldwide; however, there is only modest support for interventions to prevent LBP. The aim of this trial is to establish the effectiveness and cost-effectiveness of group-based exercise and educational classes compared with a minimal intervention control in preventing recurrence of LBP in people who have recently recovered from an episode of LBP. Methods and analysis TOPS will be a pragmatic comparative effectiveness randomised clinical trial with a parallel economic evaluation combining three separate cohorts (TOPS Workers, TOPS Primary Care, TOPS Defence) with the same methodology. 1482 participants who have recently recovered from LBP will be randomised to either a comprehensive exercise and education programme or a minimal intervention control. Participants will be followed up for a minimum of 1 year. The primary outcome will be days till recurrence of LBP. Effectiveness will be assessed using survival analysis. Cost-effectiveness will be assessed from the societal perspective. Ethics and dissemination This trial has been approved by the University of Sydney Human Research Ethics Committee (HREC) (ref: 2015/728) and prospectively registered with the Australian and New Zealand Clinical Trials Registry (ref: 12615000939594). We will also obtain ethics approval from the Australian Defence Force HREC. The results of this study will be submitted for publication in a prominent journal and widely publicised in the general media. Trial registration number Australian and New Zealand Clinical Trial Registry (ANZCTR) 12615000939594. PMID:27217287

Over the counter (OTC) artificial tear drops for dry eye syndrome.

PubMed

Pucker, Andrew D; Ng, Sueko M; Nichols, Jason J

2016-02-23

Over the counter (OTC) artificial tears historically have been the first line of treatment for dry eye syndrome and dry eye-related conditions like contact lens discomfort, yet currently we know little regarding the overall efficacy of individual, commercially available artificial tears. This review provides a much needed meta-analytical look at all randomized and quasi-randomized clinical trials that have analyzed head-to-head comparisons of OTC artificial tears. To evaluate the effectiveness and toxicity of OTC artificial tear applications in the treatment of dry eye syndrome compared with another class of OTC artificial tears, no treatment, or placebo. We searched CENTRAL (which contains the Cochrane Eyes and Vision Trials Register) (2015, Issue 12), Ovid MEDLINE, Ovid MEDLINE In-Process and Other Non-Indexed Citations, Ovid MEDLINE Daily, Ovid OLDMEDLINE (January 1946 to December 2015), EMBASE (January 1980 to December 2015), Latin American and Caribbean Health Sciences (LILACS) (January 1982 to December 2015), the ISRCTN registry (www.isrctn.com/editAdvancedSearch), ClinicalTrials.gov (www.clinicaltrials.gov), the World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP) (www.who.int/ictrp/search/en) and the US Food and Drugs Administration (FDA) website (www.fda.gov). We did not use any date or language restrictions in the electronic searches for trials. We last searched the electronic databases on 4 December 2015. We searched reference lists of included trials for any additional trials not identified by the electronic searches. This review includes randomized controlled trials with adult participants who were diagnosed with dry eye, regardless of race and gender. We included trials in which the age of participants was not reported, and clinical trials comparing OTC artificial tears with another class of OTC artificial tears, placebo, or no treatment. This review did not consider head-to-head comparisons of artificial tears with another type of dry-eye therapy. We followed the standard methodological procedures expected by Cochrane. Two authors independently screened the search results, reviewed full-text copies for eligibility, examined risk of bias, and extracted data. We performed meta-analysis for trials that compared similar interventions and reported comparable outcomes with sufficient data. We summarized all other included trial results in the text. We included 43 randomized controlled trials (3497 participants with dry eye). Due to the heterogeneity of study characteristics among the included trials with respect to types of diagnostic criteria, interventions, comparisons, and measurements taken, our ability to perform meta-analyses was limited. The review found that, in general, there was uncertainty whether different OTC artificial tears provide similar relief of signs and symptoms when compared with each other or placebo. Nevertheless, we found that 0.2% polyacrylic acid-based artificial tears were consistently more effective at treating dry eye symptoms than 1.4% polyvinyl alcohol-based artificial tears in two trials assessing this comparison (175 participants). All other included artificial tears produced contradictory between-group results or found no between-group differences. Our review also found that OTC artificial tears may be generally safe, but not without adverse events. Overall, we assessed the quality of evidence as low due to high risks of bias among included trials and poor reporting of outcome measures which were insufficient for quantitative analysis. Furthermore, we identified an additional 18 potentially eligible trials that were reported only in clinical trial registers with no associated results or publications. These trials reportedly enrolled 2079 total participants for whom no data are available. Such lack of reporting of trial results represents a high risk of publication bias. OTC artificial tears may be safe and effective means for treating dry eye syndrome; the literature indicates that the majority of OTC artificial tears may have similar efficacies. This conclusion could be greatly skewed by the inconsistencies in study designs and inconsistencies in reporting trial results. Additional research is therefore needed before we can draw robust conclusions about the effectiveness of individual OTC artificial tear formulations.

Exit interviews to reduce turnover amongst healthcare professionals.

PubMed

Webster, Joan; Flint, Anndrea

2014-08-19

Exit interviews are widely used in healthcare organisations to identify reasons for staff attrition, yet their usefulness in limiting turnover is unclear. To determine the effectiveness of various exit interview strategies in decreasing turnover rates amongst healthcare professionals. We searched the Cochrane EPOC Group Specialised Register; Cochrane Central Register of Controlled Trials (CENTRAL), Issue 11, 2012; MEDLINE, Ovid (1950- ); EMBASE, Ovid (1947- ); CINAHL, EbscoHost (1980- ), and PsycINFO, OVID (1806-) between October 31 and November 6, 2012. We also screened the reference lists of included studies and relevant reviews; and searched trial registries for planned and on-going studies. We did not restrict searches by language or publication date. Randomised controlled trials, controlled clinical trials, controlled before-after studies and interrupted time series studies comparing turnover rates between healthcare professionals who had undergone one form of exit interview with another form of exit interview or with no interview. Two review authors independently assessed trial quality and extracted data. The original search identified 1560 citations, of which we considered 19 potentially relevant. The two authors independently reviewed the abstracts of these studies and retrieved the full texts of eight studies. We excluded all eight following independent assessment; they were either interviews, commentaries on how to do an exit interview or descriptive studies about reasons for leaving. We found no studies that matched our inclusion criteria. For this first update, we screened 2220 citations and identified no new studies. Evidence about the effectiveness of exit interviews to reduce turnover is currently not available. However, exit interviews may provide useful information about the work environment which, in turn, may be useful in the development of interventions to reduce turnover.

Meta-analysis of randomized controlled trials on cognitive effects of Bacopa monnieri extract.

PubMed

Kongkeaw, Chuenjid; Dilokthornsakul, Piyameth; Thanarangsarit, Phurit; Limpeanchob, Nanteetip; Norman Scholfield, C

2014-01-01

Bacopa monnieri has a long history in Ayurvedic medicine for neurological and behavioral defects. To assess its efficacy in improving cognitive function. MEDLINE, EMBASE, CINAHL, AMED, Cochrane Central of clinical trial, WHO registry, Thai Medical Index, Index Medicus Siriraj library and www.clinicaltrial.gov were searched from the inception date of each database to June 2013 using scientific and common synonyms of Bacopa monnieri, cognitive performance or memory. The reference lists of retrieved articles were also reviewed. Randomized, placebo controlled human intervention trials on chronic ≥ 12 weeks dosing of standardized extracts of Bacopa monnieri without any co-medication were included in this study. The methodological quality of studies was assessed using Cochrane's risk of bias assessment and Jadad's quality scales. The weighted mean difference and 95% confidence interval (95% CI) were performed using the random-effects model of the Dersimonian-Laird method. Nine studies met the inclusion criteria using 518 subjects. Overall quality of all included trials was low risk of bias and quality of reported information was high. Meta-analysis of 437 eligible subjects showed improved cognition by shortened Trail B test (-17.9 ms; 95% CI -24.6 to -11.2; p<0.001) and decreased choice reaction time (10.6 ms; 95% CI -12.1 to -9.2; p<0.001). This meta-analysis suggests that Bacopa monnieri has the potential to improve cognition, particularly speed of attention but only a large well designed 'head-to-head' trial against an existing medication will provide definitive data on its efficacy on healthy or dementia patients using a standardized preparation. © 2013 Elsevier Ireland Ltd. All rights reserved.

A controlled trial of implementing a complex mental health intervention for carers of vulnerable young people living in out-of-home care: the ripple project.

PubMed

Herrman, Helen; Humphreys, Cathy; Halperin, Stephen; Monson, Katherine; Harvey, Carol; Mihalopoulos, Cathrine; Cotton, Susan; Mitchell, Penelope; Glynn, Tony; Magnus, Anne; Murray, Lenice; Szwarc, Josef; Davis, Elise; Havighurst, Sophie; McGorry, Patrick; Tyano, Sam; Kaplan, Ida; Rice, Simon; Moeller-Saxone, Kristen

2016-12-07

Out-of-home care (OoHC) refers to young people removed from their families by the state because of abuse, neglect or other adversities. Many of the young people experience poor mental health and social function before, during and after leaving care. Rigorously evaluated interventions are urgently required. This publication describes the protocol for the Ripple project and notes early findings from a controlled trial demonstrating the feasibility of the work. The Ripple project is implementing and evaluating a complex mental health intervention that aims to strengthen the therapeutic capacities of carers and case managers of young people (12-17 years) in OoHC. The study is conducted in partnership with mental health, substance abuse and social services in Melbourne, with young people as participants. It has three parts: 1. Needs assessment and implementation of a complex mental health intervention; 2. A 3-year controlled trial of the mental health, social and economic outcomes; and 3. Nested process evaluation of the intervention. Early findings characterising the young people, their carers and case managers and implementing the intervention are available. The trial Wave 1 includes interviews with 176 young people, 52% of those eligible in the study population, 104 carers and 79 case managers. Implementing and researching an affordable service system intervention appears feasible and likely to be applicable in other places and countries. Success of the intervention will potentially contribute to reducing mental ill-health among these young people, including suicide attempts, self-harm and substance abuse, as well as reducing homelessness, social isolation and contact with the criminal justice system. Australian New Zealand Clinical Trials Registry ACTRN12615000501549 . Retrospectively registered 19 May 2015.

Design of case report forms based on a public metadata registry: re-use of data elements to improve compatibility of data.

PubMed

Dugas, Martin

2016-11-29

Clinical trials use many case report forms (CRFs) per patient. Because of the astronomical number of potential CRFs, data element re-use at the design stage is attractive to foster compatibility of data from different trials. The objective of this work is to assess the technical feasibility of a CRF editor with connection to a public metadata registry (MDR) to support data element re-use. Based on the Medical Data Models portal, an ISO/IEC 11179-compliant MDR was implemented and connected to a web-based CRF editor. Three use cases were implemented: re-use at the form, item group and data element levels. CRF design with data element re-use from a public MDR is feasible. A prototypic system is available. The main limitation of the system is the amount of available MDR content.

Warfarin for prevention of thromboembolism in atrial fibrillation: comparison of patient characteristics and outcomes of the "Real-World" Michigan Anticoagulation Quality Improvement Initiative (MAQI2) registry to the RE-LY, ROCKET-AF, and ARISTOTLE trials.

PubMed

Hughey, Andrew B; Gu, Xiaokui; Haymart, Brian; Kline-Rogers, Eva; Almany, Steve; Kozlowski, Jay; Besley, Dennis; Krol, Gregory D; Ahsan, Syed; Kaatz, Scott; Froehlich, James B; Barnes, Geoffrey D

2018-06-14

Randomized controlled trials (RCTs) examining warfarin use for stroke prevention in atrial fibrillation (AF) may not accurately reflect real-world populations. We aimed to determine the representativeness of the RCT populations to real-world patients and to describe differences in the characteristics of trial populations from trial eligible patients in a real-world setting. We hypothesized that a significant fraction of real-world patients would not qualify for the RE-LY, ROCKET-AF, and ARISTOTLE trials and that real-world patients qualifying for the studies may have more strokes and bleeding events. We compared the inclusion and exclusion criteria, patient characteristics, and clinical outcomes from RE-LY, ROCKET-AF, and ARISTOTLE against data from the Michigan Anticoagulation Quality Improvement Initiative (MAQI 2 ), a regional network of six community- and academic-based anticoagulation clinics. Of the 1446 non-valvular AF patients in the MAQI 2 registry taking warfarin, approximately 40-60% would meet the selection criteria used in RE-LY (788, 54.5%), ROCKET-AF (566, 39.1%), and ARISTOTLE (866, 59.9%). The most common reasons for exclusion from one or more trial were anemia (15.1%), other concurrent medications (11.2%), and chronic kidney disease (9.4%). Trial-eligible MAQI 2 patients were older, more frequently female, with a higher rate of paroxysmal AF, and lower rates of congestive heart failure, previous stroke, and previous myocardial infarction than the trial populations. MAQI 2 patients eligible for each trial had a lower rate of stroke and similar rate of major bleeding than was observed in the trials. A sizable proportion of real-world AF patients managed in anticoagulation clinics would not have been eligible for the RE-LY, ROCKET-AF, and ARISOTLE trials. The expected stroke risk reduction and bleeding risk among real-world AF patients on warfarin may not be congruent with published clinical trial data.

Results of the destination therapy post-food and drug administration approval study with a continuous flow left ventricular assist device: a prospective study using the INTERMACS registry (Interagency Registry for Mechanically Assisted Circulatory Support).

PubMed

Jorde, Ulrich P; Kushwaha, Sudhir S; Tatooles, Antone J; Naka, Yoshifumi; Bhat, Geetha; Long, James W; Horstmanshof, Douglas A; Kormos, Robert L; Teuteberg, Jeffrey J; Slaughter, Mark S; Birks, Emma J; Farrar, David J; Park, Soon J

2014-05-06

A post-approval (PA) study for destination therapy (DT) was required by the Food and Drug Administration (FDA) to determine whether results with the HeartMate (HM) II (Thoratec, Pleasanton, California) left ventricular assist device (LVAD) in a commercial setting were comparable to results during the DT multicenter pivotal clinical trial. New device technology developed in the clinical research setting requires validation in a real-world setting. The PA study was a prospective evaluation of the first 247 HM II patients identified pre-operatively as eligible for DT in the national INTERMACS (Interagency Registry for Mechanically Assisted Circulatory Support) registry. Patients were enrolled from January to September 2010 at 61 U.S. centers and followed for 2 years. A historical comparison group included patients (n = 133 at 34 centers) enrolled in the primary data cohort in the DT pivotal trial (TR). Survival rates and adverse events for the PA group were obtained from the INTERMACS registry. Baseline characteristics were similar for PA versus TR. Forty-five percent of PA patients were in INTERMACS profiles 1 to 2 and 28% were in profile 3. Adverse events in the PA group were similar or lower than those in the TR group, including improvements in device-related infection (0.22 vs. 0.47) and post-operative bleeding requiring surgery (0.09 vs. 0.23) events per patient-year. Kaplan-Meier survival at 2 years was 62% (PA group) versus 58% (TR group). PA group survival at 1 and 2 years was 82 ± 5% and 69 ± 6% for INTERMACS profiles 4 to 7 (n = 63) versus 72 ± 3% and 60 ± 4% for profiles 1 to 3 (n = 184). The median length of stay after surgery was reduced by 6 days in the PA group versus the TR group. Results in a commercial patient care setting for the DT population supported the original pivotal clinical trial findings regarding the efficacy and risk profile of the HM II LVAD. Survival was best in patients who were not inotrope-dependent (INTERMACS profiles 4 to 7). Copyright © 2014 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

Completeness of reporting of patient-relevant clinical trial outcomes: comparison of unpublished clinical study reports with publicly available data.

PubMed

Wieseler, Beate; Wolfram, Natalia; McGauran, Natalie; Kerekes, Michaela F; Vervölgyi, Volker; Kohlepp, Petra; Kamphuis, Marloes; Grouven, Ulrich

2013-10-01

Access to unpublished clinical study reports (CSRs) is currently being discussed as a means to allow unbiased evaluation of clinical research. The Institute for Quality and Efficiency in Health Care (IQWiG) routinely requests CSRs from manufacturers for its drug assessments. Our objective was to determine the information gain from CSRs compared to publicly available sources (journal publications and registry reports) for patient-relevant outcomes included in IQWiG health technology assessments (HTAs) of drugs. We used a sample of 101 trials with full CSRs received for 16 HTAs of drugs completed by IQWiG between 15 January 2006 and 14 February 2011, and analyzed the CSRs and the publicly available sources of these trials. For each document type we assessed the completeness of information on all patient-relevant outcomes included in the HTAs (benefit outcomes, e.g., mortality, symptoms, and health-related quality of life; harm outcomes, e.g., adverse events). We dichotomized the outcomes as "completely reported" or "incompletely reported." For each document type, we calculated the proportion of outcomes with complete information per outcome category and overall. We analyzed 101 trials with CSRs; 86 had at least one publicly available source, 65 at least one journal publication, and 50 a registry report. The trials included 1,080 patient-relevant outcomes. The CSRs provided complete information on a considerably higher proportion of outcomes (86%) than the combined publicly available sources (39%). With the exception of health-related quality of life (57%), CSRs provided complete information on 78% to 100% of the various benefit outcomes (combined publicly available sources: 20% to 53%). CSRs also provided considerably more information on harms. The differences in completeness of information for patient-relevant outcomes between CSRs and journal publications or registry reports (or a combination of both) were statistically significant for all types of outcomes. The main limitation of our study is that our sample is not representative because only CSRs provided voluntarily by pharmaceutical companies upon request could be assessed. In addition, the sample covered only a limited number of therapeutic areas and was restricted to randomized controlled trials investigating drugs. In contrast to CSRs, publicly available sources provide insufficient information on patient-relevant outcomes of clinical trials. CSRs should therefore be made publicly available. Please see later in the article for the Editors' Summary.

Global shortage of neonatal and paediatric antibiotic trials: rapid review.

PubMed

Thompson, Georgina; Barker, Charlotte I; Folgori, Laura; Bielicki, Julia A; Bradley, John S; Lutsar, Irja; Sharland, Mike

2017-10-13

There have been few clinical trials (CTs) on antibiotics that inform neonatal and paediatric drug labelling. The rate of unlicensed and off-label prescribing in paediatrics remains high. It is unclear whether the current neonatal and paediatric antibiotic research pipeline is adequate to inform optimal drug dosing. Using the ClinicalTrials.gov registry, this review aims to establish the current global status of antibiotic CTs in children up to 18 years of age. Studies were identified using key word searches of the ClinicalTrials.gov registry and were manually filtered using prespecified inclusion/exclusion criteria. 76 registered open CTs of antibiotics in children were identified globally; 23 (30%) were recruiting newborns (only 8 (11%) included preterm neonates), 52 (68%) infants and toddlers, 58 (76%) children and 54 (71%) adolescents. The majority of registered trials were late phase (10 (15%) phase 3 and 23 (35%) phase 4/pharmacovigilance). Two-thirds were sponsored by non-profit organisations, compared with pharmaceutical companies (50 (66%) vs 26 (34%), respectively). A greater proportion of non-profit funded trials were efficacy-based strategic trials (n=34, 68%), in comparison with industry-led trials, which were most often focused on safety or pharmacokinetic data (n=17, 65%). Only 2 of the 37 antibiotics listed on the May 2016 Pew Charitable Trusts antibiotic development pipeline, currently being studied in adults, appear to be currently recruiting in open paediatric CTs. This review highlights that very few paediatric antibiotic CTs are being conducted globally, especially in neonates. There is a striking disparity noted between antibiotic drug development programmes in adults and children. © 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.

Unloading shoes for osteoarthritis of the knee: protocol for the SHARK randomised controlled trial

PubMed Central

2014-01-01

Background Knee osteoarthritis (OA) is a common and disabling condition. Abnormalities in knee loading play an important role in disease pathogenesis, yet there are few non-surgical treatments for knee OA capable of reducing knee load. This two-arm randomised controlled trial is investigating the efficacy of specially-designed unloading shoes for the treatment of symptoms in people with knee OA. Methods/Design 164 people with symptomatic medial tibiofemoral joint OA will be recruited from the community and randomly allocated to receive either unloading shoes or control shoes. Unloading shoes have a specially-designed triple-density midsole where the medial side is softer than normal and the lateral side harder as well as a lateral wedge between the sole and sock-liner. Control shoes are standard athletic shoes and do not contain these features. Participants will be blinded to shoe allocation and will be instructed to wear the shoes as much as possible every day for 6 months, for a minimum of 4 hours per day. The primary outcomes are knee pain (numerical rating scale) and self-reported physical function (Western Ontario and McMaster Universities Osteoarthritis Index) measured at baseline and 6 months. Secondary outcomes include additional measures of knee pain, knee stiffness, participant global ratings of change in symptoms, quality-of-life and physical activity. Conclusions The findings from this study will help determine whether specially-designed unloading shoes are efficacious in the management of knee OA. Trial registration Australian New Zealand Clinical Trials Registry reference: ACTRN12613000851763. PMID:24555418

Ultrasonic dissection versus electrocautery in mastectomy for breast cancer - a meta-analysis.

PubMed

Currie, A; Chong, K; Davies, G L; Cummins, R S

2012-10-01

Electrocautery has advanced the practice of mastectomy but significant morbidity, such as seroma and blood loss, remains a concern. This has led to newer forms of dissection being introduced including the ultrasonic dissection devices, which are thought to reduce tissue damage. The aim of this systematic review was to compare the outcomes after mastectomy using novel ultrasonic dissection or standard electrocautery in published trials. Medline, Embase, trial registries, conference proceedings and reference lists were searched for comparative trials of ultrasonic dissection versus electrocautery for mastectomy. The primary outcomes were total postoperative drainage, seroma development and intra-operative blood loss. Secondary outcomes were operative time and wound complications. Odds ratios were calculated for categorical outcomes and standardised mean differences for continuous outcomes. Six trials were included in the analysis of 287 mastectomies. There was no effect in total postoperative drainage (pooled analysis weight mean difference: -0.21 (95% CI: -0.70-0.29); p = 0.41) or seroma development (pooled analysis odds ratio: 0.77 (95% CIs 0.43-1.37); p = 0.37). Intra-operative blood was slightly less for ultrasonic dissection compared to standard electrocautery (pooled analysis weight mean difference: -1.04 (95% CI: -2.00 to -0.08); p = 0.03). Ultrasonic dissection and standard electrocautery had similar outcomes with regard to operative time and wound complications. Ultrasonic dissection and standard electrocautery appear to deliver similar results in the mastectomy setting. Further cost-effectiveness analysis may guide surgeon selection in the use of new technologies for mastectomy. Copyright © 2012 Elsevier Ltd. All rights reserved.

Blood pressure targets for vasopressor therapy: a systematic review.

PubMed

D'Aragon, Frederick; Belley-Cote, Emilie P; Meade, Maureen O; Lauzier, François; Adhikari, Neill K J; Briel, Matthias; Lalu, Manoj; Kanji, Salmaan; Asfar, Pierre; Turgeon, Alexis F; Fox-Robichaud, Alison; Marshall, John C; Lamontagne, François

2015-06-01

Physicians often prescribe vasopressors to correct pathological vasodilation and improve tissue perfusion in patients with septic shock, but the evidence to inform practice on vasopressor dosing is weak. We undertook a systematic review of clinical studies evaluating different blood pressure targets for the dosing of vasopressors in septic shock. We searched MEDLINE, EMBASE, CENTRAL (to November 2013), reference lists from included articles, and trial registries for randomized controlled trials (RCTs) and observational and crossover intervention studies comparing different blood pressure targets for vasopressor therapy in septic shock. Two reviewers independently selected eligible studies and extracted data on standardized forms. We identified 2 RCTs and 10 crossover trials but no observational studies meeting our criteria. Only one RCT measured clinical outcomes after comparing mean arterial pressure targets of 80 to 85 mmHg versus 65 to 70 mmHg. There was no effect on 28-day mortality, but confidence intervals were wide (hazard ratio, 95% confidence interval [95% CI] 0.84 - 1.38). In contrast, this intervention was associated with a greater risk of atrial fibrillation (relative risk, 2.36; 95% CI, 1.18 - 4.72) and a lower risk of renal replacement therapy in hypertensive patients (relative risk, 0.75; 95% CI, 0.57 - 1.0). Crossover trials suggest that achieving higher blood pressure targets by increasing vasopressor doses increases heart rate and cardiac index with no effect on serum lactate. Our findings underscore the paucity of clinical evidence to guide the administration of vasopressors in critically ill patients with septic shock. Further rigorous research is needed to establish an evidence base for vasopressor administration in this population.

The risk of elevated prolactin levels in pediatric patients exposed to antipsychotics for the treatment of schizophrenia and schizophrenia spectrum disorders: protocol for a systematic review and meta-analysis

PubMed Central

2014-01-01

Background Antipsychotic medications, particularly second-generation antipsychotics, are increasingly being used to alleviate the symptoms of schizophrenia and other severe mental disorders in the pediatric population. While evidence-based approaches examining efficacy and safety outcomes have been reported, no review has evaluated prolactin-based adverse events for antipsychotic treatments in schizophrenia and schizophrenia spectrum disorders. Methods/design Searches involving MEDLINE, EMBASE, CENTRAL, PsycINFO, and clinical trial registries (ClinicalTrials.gov, Drug Industry Document Archive [DIDA], International Clinical Trials Registry Platform [ICTRP]) will be used to identify relevant studies. Two reviewers will independently screen abstracts and relevant full-text articles of the papers identified by the initial search according to the prospectively defined eligibility criteria. Data extraction will be conducted in duplicate independently. Pairwise random effects meta-analyses and network meta-analyses will be conducted on individual drug and class effects where appropriate. Discussion This systematic review will evaluate prolactin-based adverse events of first- and second-generation antipsychotics in the pediatric population with schizophrenia and schizophrenia spectrum disorders. It will also seek to strengthen the evidence base of the safety of antipsychotics by incorporating both randomized controlled trials and observational studies. Systematic review registration PROSPERO CRD42014009506 PMID:25312992

Health Authorities Data Collection of THC:CBD Oromucosal Spray (L'Agenzia Italiana del Farmaco Web Registry): Figures after 1.5 Years.

PubMed

Patti, Francesco

2016-01-01

In Italy, all prescriptions for THC:CBD oromucosal spray for treatment of multiple sclerosis (MS) spasticity are linked to the official Agenzia Italiana del Farmaco (AIFA) web-based registry, which tracks the effectiveness and tolerability of medications in a prospective and observational manner. AIFA e-registry data for THC:CBD oromucosal spray collected between January 2014 and February 2015 for 1,534 patients from 30 large Italian specialized MS centres were compiled. Patients had a long disease history (17.6 ± 8.6 years) and significant impairment (mean Expanded Disability Status Scale score 6.4 ± 1.2). MS spasticity was evaluated using the 0-10 numerical rating scale (NRS). After the first month titration and trial period, 61.9% of patients achieved sufficient improvement in spasticity (≥20% NRS) to qualify for continued treatment. After 6 months, clinically meaningful ≥30% NRS improvement was recorded in 40.2% of patients continuing with treatment. Spasticity-associated symptoms such as cramps and nocturnal spasms improved in most responding patients. Mean reported doses of THC:CBD oromucosal spray (6.2-6.7 sprays/day) were lower than those reported in clinical trials. Adverse events (mainly mild to moderate) were reported by 15% of patients; no new safety concerns beyond the approved label were identified. The results of the AIFA e-registry analysis align with those of other THC:CBD observational projects and reaffirm the characteristics of this therapeutic option in the management of treatment-resistant MS spasticity, a frequently overlooked symptom. © 2016 S. Karger AG, Basel.

The effectiveness of opioid substitution treatments for patients with opioid dependence: a systematic review and multiple treatment comparison protocol

PubMed Central

2014-01-01

Background Opioids are psychoactive analgesic drugs prescribed for pain relief and palliative care. Due to their addictive potential, effort and vigilance in controlling prescriptions is needed to avoid misuse and dependence. Despite the effort, the prevalence of opioid use disorder continues to rise. Opioid substitution therapies are commonly used to treat opioid dependence; however, there is minimal consensus as to which therapy is most effective. Available treatments include methadone, heroin, buprenorphine, as well as naltrexone. This systematic review aims to assess and compare the effect of all available opioid substitution therapies on the treatment of opioid dependence. Methods/Design The authors will search Medline, EMBASE, PubMed, PsycINFO, Web of Science, Cochrane Library, Cochrane Clinical Trials Registry, World Health Organization International Clinical Trials Registry Platform Search Portal, and the National Institutes for Health Clinical Trials Registry. The title, abstract, and full-text screening will be completed in duplicate. When appropriate, multiple treatment comparison Bayesian meta-analytic methods will be performed to deduce summary statistics estimating the effectiveness of all opioid substitution therapies in terms of retention and response to treatment (as measured through continued opioid abuse). Discussion Using evidence gained from this systematic review, we anticipate disseminating an objective review of the current available literature on the effectiveness of all opioid substitution therapies for the treatment of opioid use disorder. The results of this systematic review are imperative to the further enhancement of clinical practice in addiction medicine. Systematic review registration PROSPERO CRD42013006507. PMID:25239213

How health technology assessment agencies address the issue of unpublished data.

PubMed

Kreis, Julia; Panteli, Dimitra; Busse, Reinhard

2014-01-01

Reporting bias potentially threatens the validity of results in health technology assessment (HTA) reports. Our study aimed to explore policies and practices of HTA agencies regarding strategies to include previously unpublished data in their assessments, focusing on requests to industry for unpublished data. We included international HTA agencies with publicly available methods papers as well as HTA reports. From the methods papers and recent reports we extracted information on requests to industry and on searches in trial registries, regulatory authority Web sites and for conference abstracts. Eighteen HTA agencies and seventy-three reports were included. Agencies' methods papers showed variability regarding requests to industry (requests are routinely carried out in seven cases, not mentioned in six, at the discretion of HTA authors in three, and based on manufacturer applications in two), which were reflected in the reports investigated. As reporting of requests was limited, it often remained unclear whether unpublished data had been received. Searches in trial registries, at regulatory authorities or for conference abstracts are described as a routine or optional part of the search strategy in the methods papers of 9, 11, and 8 included agencies, respectively. A total of 52 percent, 39 percent, and 16 percent of reports described searches in trial registries, at regulatory agencies, and hand searching of conference proceedings. International HTA agencies currently differ considerably in their efforts to address the issue of unpublished data. Requests to industry may constitute one strategy to access and include unpublished data, while agencies can learn from each other concerning successful practice.

The European Cystic Fibrosis Society Patient Registry: valuable lessons learned on how to sustain a disease registry.

PubMed

Viviani, Laura; Zolin, Anna; Mehta, Anil; Olesen, Hanne Vebert

2014-06-07

Disease registries have the invaluable potential to provide an insight into the natural history of the disease under investigation, to provide useful information (e.g. through health indicators) for planning health care services and to identify suitable groups of patients for clinical trials enrolment. However, the establishment and maintenance of disease registries is a burdensome initiative from economical and organisational points of view and experience sharing on registries management is important to avoid waste of resources. The aim of this paper is to discuss the problems embedded in the institution and management of an international disease registry to warn against common mistakes that can derail the best of intentions: we share the experience of the European Cystic Fibrosis Society Patient Registry, which collects data on almost 30,000 patients from 23 countries. We discuss the major problems that researchers often encounter in the creation and management of disease registries: definition of the aims the registry has to reach, definition of the criteria for patients referral to the registry, definition of the information to record, set up of a data quality process, handling of missing data, maintenance of data confidentiality, regulation of data use and dissemination of research results. We give examples on how many crucial aspects were solved by the European Cystic Fibrosis Society Patient Registry regarding objectives, inclusion criteria and variables definition, data management, data quality controls, missing data handling, confidentiality maintenance, data use and results dissemination. We suggest an extensive literature research and discussions in working groups with different stake holders, including patient representatives, on the objectives, inclusion criteria and the information to record. We propose to pilot the recording of few variables and test the applicability of their definition first. The use of a shared electronic platform for data collection that automatically computes derived variables, and automatically performs basic data quality controls is a good data management practice, that also helps in reducing missing data. We found crucial for success the collaboration with existing national and international registries, cystic fibrosis organisations and patients' associations.

The European Cystic Fibrosis Society Patient Registry: valuable lessons learned on how to sustain a disease registry

PubMed Central

2014-01-01

Background Disease registries have the invaluable potential to provide an insight into the natural history of the disease under investigation, to provide useful information (e.g. through health indicators) for planning health care services and to identify suitable groups of patients for clinical trials enrolment. However, the establishment and maintenance of disease registries is a burdensome initiative from economical and organisational points of view and experience sharing on registries management is important to avoid waste of resources. The aim of this paper is to discuss the problems embedded in the institution and management of an international disease registry to warn against common mistakes that can derail the best of intentions: we share the experience of the European Cystic Fibrosis Society Patient Registry, which collects data on almost 30,000 patients from 23 countries. Methods We discuss the major problems that researchers often encounter in the creation and management of disease registries: definition of the aims the registry has to reach, definition of the criteria for patients referral to the registry, definition of the information to record, set up of a data quality process, handling of missing data, maintenance of data confidentiality, regulation of data use and dissemination of research results. Results We give examples on how many crucial aspects were solved by the European Cystic Fibrosis Society Patient Registry regarding objectives, inclusion criteria and variables definition, data management, data quality controls, missing data handling, confidentiality maintenance, data use and results dissemination. Conclusions We suggest an extensive literature research and discussions in working groups with different stake holders, including patient representatives, on the objectives, inclusion criteria and the information to record. We propose to pilot the recording of few variables and test the applicability of their definition first. The use of a shared electronic platform for data collection that automatically computes derived variables, and automatically performs basic data quality controls is a good data management practice, that also helps in reducing missing data. We found crucial for success the collaboration with existing national and international registries, cystic fibrosis organisations and patients’ associations. PMID:24908055

Rationale and design of three observational, prospective cohort studies including biobanking to evaluate and improve diagnostics, management strategies and risk stratification in venous thromboembolism: the VTEval Project

PubMed Central

Frank, Bernd; Ariza, Liana; Lamparter, Heidrun; Grossmann, Vera; Prochaska, Jürgen H; Ullmann, Alexander; Kindler, Florentina; Weisser, Gerhard; Walter, Ulrich; Lackner, Karl J; Espinola-Klein, Christine; Münzel, Thomas; Konstantinides, Stavros V; Wild, Philipp S

2015-01-01

Introduction Venous thromboembolism (VTE) with its two manifestations deep vein thrombosis (DVT) and pulmonary embolism (PE) is a major public health problem. The VTEval Project aims to investigate numerous research questions on diagnosis, clinical management, treatment and prognosis of VTE, which have remained uncertain to date. Methods and analysis The VTEval Project consists of three observational, prospective cohort studies on VTE comprising cohorts of individuals with a clinical suspicion of acute PE (with or without DVT), with a clinical suspicion of acute DVT (without symptomatic PE) and with an incidental diagnosis of VTE (PE or DVT). The VTEval Project expects to enrol a total of approximately 2000 individuals with subsequent active and passive follow-up investigations over a time period of 5 years per participant. Time points for active follow-up investigations are at months 3, 6, 12, 24 and 36 after diagnosis (depending on the disease cohort); passive follow-up investigations via registry offices and the cancer registry are performed 48 and 60 months after diagnosis for all participants. Primary short-term outcome is defined by overall mortality (PE-related death and all other causes of death), primary long-term outcome by symptomatic VTE (PE-related death, recurrence of non-fatal PE or DVT). The VTEval Project includes three ‘all-comer’ studies and involves the standardised acquisition of high-quality data, covering the systematic assessment of VTE including symptoms, risk profile, psychosocial, environmental and lifestyle factors as well as clinical and subclinical disease, and it builds up a large state-of-the-art biorepository containing various materials from serial blood samplings. Ethics and dissemination The VTEval Project has been approved by the local data safety commissioner and the responsible ethics committee (reference no. 837.320.12 (8421-F)). Trial results will be published in peer-reviewed journals and presented at national and international scientific meetings. Trial registration number NCT02156401. PMID:26133379

“Smart” RCTs: Development of a Smartphone App for Fully Automated Nutrition-Labeling Intervention Trials

PubMed Central

Li, Nicole; Dunford, Elizabeth; Eyles, Helen; Crino, Michelle; Michie, Jo; Ni Mhurchu, Cliona

2016-01-01

Background There is substantial interest in the effects of nutrition labels on consumer food-purchasing behavior. However, conducting randomized controlled trials on the impact of nutrition labels in the real world presents a significant challenge. Objective The Food Label Trial (FLT) smartphone app was developed to enable conducting fully automated trials, delivering intervention remotely, and collecting individual-level data on food purchases for two nutrition-labeling randomized controlled trials (RCTs) in New Zealand and Australia. Methods Two versions of the smartphone app were developed: one for a 5-arm trial (Australian) and the other for a 3-arm trial (New Zealand). The RCT protocols guided requirements for app functionality, that is, obtaining informed consent, two-stage eligibility check, questionnaire administration, randomization, intervention delivery, and outcome assessment. Intervention delivery (nutrition labels) and outcome data collection (individual shopping data) used the smartphone camera technology, where a barcode scanner was used to identify a packaged food and link it with its corresponding match in a food composition database. Scanned products were either recorded in an electronic list (data collection mode) or allocated a nutrition label on screen if matched successfully with an existing product in the database (intervention delivery mode). All recorded data were transmitted to the RCT database hosted on a server. Results In total approximately 4000 users have downloaded the FLT app to date; 606 (Australia) and 1470 (New Zealand) users met the eligibility criteria and were randomized. Individual shopping data collected by participants currently comprise more than 96,000 (Australia) and 229,000 (New Zealand) packaged food and beverage products. Conclusions The FLT app is one of the first smartphone apps to enable conducting fully automated RCTs. Preliminary app usage statistics demonstrate large potential of such technology, both for intervention delivery and data collection. Trial Registration Australian New Zealand Clinical Trials Registry ACTRN12614000964617. New Zealand trial: Australian New Zealand Clinical Trials Registry ACTRN12614000644662. PMID:26988128

Acute pancreatitis patient registry to examine novel therapies in clinical experience (APPRENTICE): an international, multicenter consortium for the study of acute pancreatitis.

PubMed

Papachristou, Georgios I; Machicado, Jorge D; Stevens, Tyler; Goenka, Mahesh Kumar; Ferreira, Miguel; Gutierrez, Silvia C; Singh, Vikesh K; Kamal, Ayesha; Gonzalez-Gonzalez, Jose A; Pelaez-Luna, Mario; Gulla, Aiste; Zarnescu, Narcis O; Triantafyllou, Konstantinos; Barbu, Sorin T; Easler, Jeffrey; Ocampo, Carlos; Capurso, Gabriele; Archibugi, Livia; Cote, Gregory A; Lambiase, Louis; Kochhar, Rakesh; Chua, Tiffany; Tiwari, Subhash Ch; Nawaz, Haq; Park, Walter G; de-Madaria, Enrique; Lee, Peter J; Wu, Bechien U; Greer, Phil J; Dugum, Mohannad; Koutroumpakis, Efstratios; Akshintala, Venkata; Gougol, Amir

2017-01-01

We have established a multicenter international consortium to better understand the natural history of acute pancreatitis (AP) worldwide and to develop a platform for future randomized clinical trials. The AP patient registry to examine novel therapies in clinical experience (APPRENTICE) was formed in July 2014. Detailed web-based questionnaires were then developed to prospectively capture information on demographics, etiology, pancreatitis history, comorbidities, risk factors, severity biomarkers, severity indices, health-care utilization, management strategies, and outcomes of AP patients. Between November 2015 and September 2016, a total of 20 sites (8 in the United States, 5 in Europe, 3 in South America, 2 in Mexico and 2 in India) prospectively enrolled 509 AP patients. All data were entered into the REDCap (Research Electronic Data Capture) database by participating centers and systematically reviewed by the coordinating site (University of Pittsburgh). The approaches and methodology are described in detail, along with an interim report on the demographic results. APPRENTICE, an international collaboration of tertiary AP centers throughout the world, has demonstrated the feasibility of building a large, prospective, multicenter patient registry to study AP. Analysis of the collected data may provide a greater understanding of AP and APPRENTICE will serve as a future platform for randomized clinical trials.

A multicentre, randomised controlled, non-inferiority trial, comparing nasal high flow with nasal continuous positive airway pressure as primary support for newborn infants with early respiratory distress born in Australian non-tertiary special care nurseries (the HUNTER trial): study protocol

PubMed Central

Manley, Brett J; Roberts, Calum T; Arnolda, Gaston R B; Wright, Ian M R; Owen, Louise S; Dalziel, Kim M; Foster, Jann P; Davis, Peter G; Buckmaster, Adam G

2017-01-01

Introduction Nasal high-flow (nHF) therapy is a popular mode of respiratory support for newborn infants. Evidence for nHF use is predominantly from neonatal intensive care units (NICUs). There are no randomised trials of nHF use in non-tertiary special care nurseries (SCNs). We hypothesise that nHF is non-inferior to nasal continuous positive airway pressure (CPAP) as primary support for newborn infants with respiratory distress, in the population cared for in non-tertiary SCNs. Methods and analysis The HUNTER trial is an unblinded Australian multicentre, randomised, non-inferiority trial. Infants are eligible if born at a gestational age ≥31 weeks with birth weight ≥1200 g and admitted to a participating non-tertiary SCN, are <24 hours old at randomisation and require non-invasive respiratory support or supplemental oxygen for >1 hour. Infants are randomised to treatment with either nHF or CPAP. The primary outcome is treatment failure within 72 hours of randomisation, as determined by objective oxygenation, apnoea or blood gas criteria or by a clinical decision that urgent intubation and mechanical ventilation, or transfer to a tertiary NICU, is required. Secondary outcomes include incidence of pneumothorax requiring drainage, duration of respiratory support, supplemental oxygen and hospitalisation, costs associated with hospital care, cost-effectiveness, parental stress and satisfaction and nursing workload. Ethics and dissemination Multisite ethical approval for the study has been granted by The Royal Children’s Hospital, Melbourne, Australia (Trial Reference No. 34222), and by each participating site. The trial is currently recruiting in eight centres in Victoria and New South Wales, Australia, with one previous site no longer recruiting. The trial results will be published in a peer-reviewed journal and will be presented at national and international conferences. Trial registration number Australian and New Zealand Clinical Trials Registry (ANZCTR): ACTRN12614001203640; pre-results. PMID:28645982

Using NLP to identify cancer cases in imaging reports drawn from radiology information systems.

PubMed

Patrick, Jon; Asgari, Pooyan; Li, Min; Nguyen, Dung

2013-01-01

A Natural Language processing (NLP) classifier has been developed for the Victorian and NSW Cancer Registries with the purpose of automatically identifying cancer reports from imaging services, transmitting them to the Registries and then extracting pertinent cancer information. Large scale trials conducted on over 40,000 reports show the sensitivity for identifying reportable cancer reports is above 98% with a specificity above 96%. Detection of tumour stream, report purpose, and a variety of extracted content is generally above 90% specificity. The differences between report layout and authoring strategies across imaging services appear to require different classifiers to retain this high level of accuracy. Linkage of the imaging data with existing registry records (hospital and pathology reports) to derive stage and recurrence of cancer has commenced and shown very promising results.

TREatment of ATopic eczema (TREAT) Registry Taskforce: protocol for an international Delphi exercise to identify a core set of domains and domain items for national atopic eczema registries.

PubMed

Gerbens, Louise A A; Boyce, Aaron E; Wall, Dmitri; Barbarot, Sebastien; de Booij, Richard J; Deleuran, Mette; Middelkamp-Hup, Maritza A; Roberts, Amanda; Vestergaard, Christian; Weidinger, Stephan; Apfelbacher, Christian J; Irvine, Alan D; Schmitt, Jochen; Williamson, Paula R; Spuls, Phyllis I; Flohr, Carsten

2017-02-27

Patients with moderate-to-severe atopic eczema (AE) often require photo- or systemic immunomodulatory therapies to induce disease remission and maintain long-term control. The current evidence to guide clinical management is small, despite the frequent and often off-label use of these treatments. Registries of patients on photo- and systemic immunomodulatory therapies could fill this gap, and the collection of a core set concerning these therapies in AE will allow direct comparisons across registries as well as data sharing and pooling. Using an eDelphi approach, the international TREatment of ATopic eczema (TREAT) Registry Taskforce aims to seek consensus between key stakeholders internationally on a core set of domains and domain items for AE patient registries with a research focus that collect data of children and adults on photo- and systemic immunomodulatory therapies. Participants from six stakeholder groups will be invited: doctors, nurses, non-clinical researchers, patients, as well as industry and regulatory body representatives. The eDelphi will comprise three sequential online rounds, requesting participants to rate the importance of each proposed domain and domain items. Participants will be able to add domains and domain items to the proposed list in round 1. A final consensus meeting will be held with representatives of each stakeholder group. Identifying a uniform core set of domains and domain items to be captured by AE patient registries will increase the utility of individual registries, and provide greater insight into the effectiveness, safety and cost-effectiveness of photo- and systemic immunomodulatory therapies to guide clinical management across dermatology centres and country borders. Not applicable. This eDelphi study was registered in the Core Outcome Measures for Effectiveness Trials (COMET) database.

Reducing selection bias in case-control studies from rare disease registries.

PubMed

Cole, J Alexander; Taylor, John S; Hangartner, Thomas N; Weinreb, Neal J; Mistry, Pramod K; Khan, Aneal

2011-09-12

In clinical research of rare diseases, where small patient numbers and disease heterogeneity limit study design options, registries are a valuable resource for demographic and outcome information. However, in contrast to prospective, randomized clinical trials, the observational design of registries is prone to introduce selection bias and negatively impact the validity of data analyses. The objective of the study was to demonstrate the utility of case-control matching and the risk-set method in order to control bias in data from a rare disease registry. Data from the International Collaborative Gaucher Group (ICGG) Gaucher Registry were used as an example. A case-control matching analysis using the risk-set method was conducted to identify two groups of patients with type 1 Gaucher disease in the ICGG Gaucher Registry: patients with avascular osteonecrosis (AVN) and those without AVN. The frequency distributions of gender, decade of birth, treatment status, and splenectomy status were presented for cases and controls before and after matching. Odds ratios (and 95% confidence intervals) were calculated for each variable before and after matching. The application of case-control matching methodology results in cohorts of cases (i.e., patients with AVN) and controls (i.e., patients without AVN) who have comparable distributions for four common parameters used in subject selection: gender, year of birth (age), treatment status, and splenectomy status. Matching resulted in odds ratios of approximately 1.00, indicating no bias. We demonstrated bias in case-control selection in subjects from a prototype rare disease registry and used case-control matching to minimize this bias. Therefore, this approach appears useful to study cohorts of heterogeneous patients in rare disease registries.

Balancing the Optimal and the Feasible: A Practical Guide for Setting Up Patient Registries for the Collection of Real-World Data for Health Care Decision Making Based on Dutch Experiences.

PubMed

de Groot, Saskia; van der Linden, Naomi; Franken, Margreet G; Blommestein, Hedwig M; Leeneman, Brenda; van Rooijen, Ellen; Koos van der Hoeven, J J M; Wouters, Michel W; Westgeest, Hans M; Uyl-de Groot, Carin A

2017-04-01

The aim of this article was to provide practical guidance in setting up patient registries to facilitate real-world data collection for health care decision making. This guidance was based on our experiences and involvement in setting up patient registries in oncology in the Netherlands. All aspects were structured according to 1) mission and goals ("the Why"), 2) stakeholders and funding ("the Who"), 3) type and content ("the What"), and 4) identification and recruitment of patients, data handling, and pharmacovigilance ("the How"). The mission of most patient registries is improving patient health by improving the quality of patient care; monitoring and evaluating patient care is often the primary goal ("the Why"). It is important to align the objectives of the registry and agree on a clear and functional governance structure with all stakeholders ("the Who"). There is often a trade off between reliability, validity, and specificity of data elements and feasibility of data collection ("the What"). Patient privacy should be carefully protected, and address (inter-)national and local regulations. Patient registries can reveal unique safety information, but it can be challenging to comply with pharmacovigilance guidelines ("the How"). It is crucial to set up an efficient patient registry that serves its aims by collecting the right data of the right patient in the right way. It can be expected that patient registries will become the new standard alongside randomized controlled trials due to their unique value. Copyright © 2017 International Society for Pharmacoeconomics and Outcomes Research (ISPOR). Published by Elsevier Inc. All rights reserved.

Genetics Home Reference: acute necrotizing encephalopathy type 1

MedlinePlus

... the signs and symptoms of this condition. The health history of the individual, such as nutritional status and number of prior ... (1 link) Genetic Testing Registry: Encephalopathy, acute, infection- ...

Assessment of immunization registry databases as supplemental sources of data to improve ascertainment of vaccination coverage estimates in the national immunization survey.

PubMed

Khare, Meena; Piccinino, Linda; Barker, Lawrence E; Linkins, Robert W

2006-08-01

To evaluate the use of immunization registry data to supplement missing or incomplete vaccination data reported by immunization providers (referred to as "providers" hereafter) in the National Immunization Survey. Cross-sectional, random-digit-dialing, telephone survey to measure vaccination coverage among children aged 19 to 35 months in the United States. Four sites with mature (with >67% of provider participation in the area) immunization registries. Of the 639 children with complete household interviews, interviewers had consent from the respondents for 569 (89.0%) children to contact their providers and for 556 (87.0%) children to contact both providers and registries. Percentages of children up-to-date for vaccines based on data from providers, registries, and both sources combined. According to provider-reported data, weighted estimates of coverage for the recommended childhood vaccine series 4:3:1:3 at the 4 sites were 65.6%, 78.8%, 81.6%, and 77.0%. According to registry data, these coverage rates were consistently lower: 31.7% (P<.05), 65.4%, 71.9%, and 61.8%, respectively. When all unique vaccine doses were combined from both sources, the pooled 4:3:1:3 coverage rates increased to 72.0%, 92.0%, 88.7%, and 80.2%, respectively. The quality and completeness of vaccination histories from the registries were inconsistent and varied by sites. Vaccination coverage estimates were the lowest when only registry-reported data were used and were the highest when provider- and registry-reported histories were combined. Although registries enrolled and matched more children, vaccination histories were missing, incomplete, and inconsistent. The quality and completeness of the registry data must be improved and must be comparable across all states before further consideration may be given to supplement or replace the provider-reported National Immunization Survey data.

Computerized patient identification for the EMBRACA clinical trial using real-time data from the PRAEGNANT network for metastatic breast cancer patients.

PubMed

Hein, Alexander; Gass, Paul; Walter, Christina Barbara; Taran, Florin-Andrei; Hartkopf, Andreas; Overkamp, Friedrich; Kolberg, Hans-Christian; Hadji, Peyman; Tesch, Hans; Ettl, Johannes; Wuerstlein, Rachel; Lounsbury, Debra; Lux, Michael P; Lüftner, Diana; Wallwiener, Markus; Müller, Volkmar; Belleville, Erik; Janni, Wolfgang; Fehm, Tanja N; Wallwiener, Diethelm; Ganslandt, Thomas; Ruebner, Matthias; Beckmann, Matthias W; Schneeweiss, Andreas; Fasching, Peter A; Brucker, Sara Y

2016-07-01

As breast cancer is a diverse disease, clinical trials are becoming increasingly diversified and are consequently being conducted in very small subgroups of patients, making study recruitment increasingly difficult. The aim of this study was to assess the use of data from a remote data entry system that serves a large national registry for metastatic breast cancer. The PRAEGNANT network is a real-time registry with an integrated biomaterials bank that was designed as a scientific study and as a means of identifying patients who are eligible for clinical trials, based on clinical and molecular information. Here, we report on the automated use of the clinical data documented to identify patients for a clinical trial (EMBRACA) for patients with metastatic breast cancer. The patients' charts were assessed by two independent physicians involved in the clinical trial and also by a computer program that tested patients for eligibility using a structured query language script. In all, 326 patients from two study sites in the PRAEGNANT network were included in the analysis. Using expert assessment, 120 of the 326 patients (37 %) appeared to be eligible for inclusion in the EMBRACA study; with the computer algorithm assessment, a total of 129 appeared to be eligible. The sensitivity of the computer algorithm was 0.87 and its specificity was 0.88. Using computer-based identification of patients for clinical trials appears feasible. With the instrument's high specificity, its application in a large cohort of patients appears to be feasible, and the workload for reassessing the patients is limited.

WALK 2.0: examining the effectiveness of Web 2.0 features to increase physical activity in a 'real world' setting: an ecological trial.

PubMed

Caperchione, Cristina M; Kolt, Gregory S; Savage, Trevor N; Rosenkranz, Richard R; Maeder, Anthony J; Vandelanotte, Corneel; Duncan, Mitch J; Van Itallie, Anetta; Tague, Rhys; Mummery, W Kerry

2014-10-10

Low levels of health-enhancing physical activity require novel approaches that have the potential to reach broad populations. Web-based interventions are a popular approach for behaviour change given their wide reach and accessibility. However, challenges with participant engagement and retention reduce the long-term maintenance of behaviour change. Web 2.0 features present a new and innovative online environment supporting greater interactivity, with the potential to increase engagement and retention. In order to understand the applicability of these innovative interventions for the broader population, 'real-world' interventions implemented under 'everyday conditions' are required. The aim of this study is to investigate the difference in physical activity behaviour between individuals using a traditional Web 1.0 website with those using a novel Web 2.0 website. In this study we will aim to recruit 2894 participants. Participants will be recruited from individuals who register with a pre-existing health promotion website that currently provides Web 1.0 features (http://www.10000steps.org.au). Eligible participants who provide informed consent will be randomly assigned to one of the two trial conditions: the pre-existing 10 000 Steps website (with Web 1.0 features) or the newly developed WALK 2.0 website (with Web 2.0 features). Primary and secondary outcome measures will be assessed by self-report at baseline, 3 months and 12 months, and include: physical activity behaviour, height and weight, Internet self-efficacy, website usability, website usage and quality of life. This study has received ethics approval from the University of Western Sydney Human Research Ethics Committee (Reference Number H8767) and has been funded by the National Health and Medical Research Council (Reference Number 589903). Study findings will be disseminated widely through peer-reviewed publications, academic conferences and local community-based presentations. Australian New Zealand Clinical Trials Registry Number: ACTRN12611000253909, WHO Universal Trial Number: U111-1119-1755. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

The 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 .

Newborn screening for galactosaemia.

PubMed

Lak, Rohollah; Yazdizadeh, Bahareh; Davari, Majid; Nouhi, Mojtaba; Kelishadi, Roya

2017-12-23

Classical galactosaemia is an autosomal recessive inborn error of metabolism caused by a deficiency of the enzyme galactose-1-phosphate uridyltransferase. This is a rare and potentially lethal condition that classically presents in the first week of life once milk feeds have commenced. Affected babies may present with any or all of the following: cataracts; fulminant liver failure; prolonged jaundice; or Escherichia coli sepsis. Once the diagnosis is suspected, feeds containing galactose must be stopped immediately and replaced with a soya-based formula. The majority of babies will recover, however a number will not survive. There are long-term complications of galactosaemia, despite treatment, including learning disabilities and female infertility. It has been postulated that galactosaemia could be detected on newborn screening and this would prevent the immediate severe liver dysfunction and sepsis. To assess whether there is evidence that newborn screening for galactosaemia prevents or reduces mortality and morbidity and improves clinical outcomes in affected neonates and the quality of life in older children. We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group Trials Register comprising references identified from electronic database searches, handsearches of relevant journals and conference abstract books. We also searched online trials registries and the reference lists of relevant articles and reviews.Date of the most recent search of Cochrane Cystic Fibrosis Group's Trials Register: 18 December 2017.Date of the most recent search of additional resources: 11 October 2017. Randomised controlled studies and controlled clinical studies, published or unpublished comparing the use of any newborn screening test to diagnose infants with galactosaemia and presenting a comparison between a screened population versus a non-screened population. No studies of newborn screening for galactosaemia were found. No studies were identified for inclusion in the review. We were unable to identify any eligible studies for inclusion in this review and hence it is not possible to draw any conclusions based on randomised controlled studies. However, we are aware of uncontrolled studies which support the efficacy of newborn screening for galactosaemia. There are a number of reviews and economic analyses of non-trial literature suggesting that screening is appropriate.

Protocol for a randomised controlled trial of 90% kanuka honey versus 5% aciclovir for the treatment of herpes simplex labialis in the community setting

PubMed Central

Singer, Joseph; Shortt, Nicholas; Beasley, Richard; Salih, Shahlaa AL

2017-01-01

Introduction Worldwide, about 90% of people are infected with the herpes simplex virus, 30% of whom will experience recurrent herpes simplex labialis, commonly referred to as ‘cold sores’, which can last up to 10 days. The most common treatment is aciclovir cream which reduces healing time by just half a day compared with no specific treatment. This is a protocol for a randomised controlled trial (RCT) to determine the efficacy of medical grade kanuka honey-based topical treatment (Honevo) in reducing the healing time and pain of cold sores, compared with topical aciclovir treatment (Viraban). Methods and analysis This open-label, parallel-group, active comparator superiority RCT will compare the efficacy of medical grade kanuka honey with 5% aciclovir cream in the treatment of cold sores in the setting of a pharmacy research network of 60 sites throughout New Zealand. Adults presenting with a cold sore (N=950) will be randomised by pharmacy-based investigators. The pharmacy-based investigators will dispense the investigational product to randomised participants and both study groups apply the treatment five times daily until their skin returns to normal or for 14 days, whichever occurs first. In response to a daily SMS message, participants complete an assessment of their cold sore healing, with reference to a visual guide, and transmit it to the investigators by a smartphone eDiary in real time. The primary outcome variable is time (in days) from randomisation to return to normal skin. Secondary endpoints include total healing time stratified by stage of the lesion at onset of treatment, highest pain severity and time to pain resolution. Ethics and dissemination New Zealand Ethics Registration 15/NTB/93. Results will be published in a peer-reviewed medical journal, presented at academic meetings and reported to participants. Trial registration number Australia New Zealand Clinical Trials Registry: ACTRN12615000648527, pre-results. SCOTT Registration: 15/SCOTT/14 Protocol version 4.0 (12 June 2017) PMID:28775197

A Comparison of Patient Characteristics and Outcomes in Selected European and U.S. Rheumatoid Arthritis Registries

PubMed Central

Curtis, Jeffrey R; Jain, Archana; Askling, Johan; Bridges, Lou; Carmona, Loreto; Dixon, William; Finckh, Axel; Hyrich, Kimme; Greenberg, Jeffrey; Kremer, Joel; Listing, Joachim; Michaud, Kaleb; Mikuls, Ted; Shadick, Nancy; Solomon, Daniel H; Wolfe, Fred; Zink, Angela

2010-01-01

Purpose To provide a qualitative comparison of selected US and European rheumatoid arthritis (RA) biologics registries and cohorts including ARTIS, BIOBADASER, BSRBR, BRASS, CLEAR, CORRONA, NDB, RABBIT, SCQM, and VARA. Randomized controlled trials (RCTs) have demonstrated the efficacy of biologic agents in treatment of rheumatic diseases. However, results from RCTs may not be generalizable to clinical practice because of their strict inclusion and exclusion criteria. Assessment of safety using RCT data also is limited by short duration of follow-up and relatively small sample sizes which generally preclude analysis of longer-term outcomes and rare adverse events. In rheumatology, various observational cohorts and registries have been created to complement information obtained from RCTs, some with the primary purpose of monitoring effectiveness and safety of biologic agents. Most registries are either drug based or disease based. These registries include patients with a variety of rheumatic diseases including RA. A careful comparison of these registries, as provided in this article, can provide a basis for understanding the many similarities and differences inherent in their design, as well as societal context and content, all of which can significantly impact their results and comparisons across registers. Summary The increasing use of biologic agents for treatment of rheumatic diseases has raised important questions about cost, safety and effectiveness of these agents. The unique and variable features of patient populations and registry designs in Europe and the U.S. provide valuable and complementary data on comparative effectiveness and safety of biologic agents to what can be derived from RCTs. PMID:20674669

Non-invasive versus invasive management in patients with prior coronary artery bypass surgery with a non-ST segment elevation acute coronary syndrome: study design of the pilot randomised controlled trial and registry (CABG-ACS)

PubMed Central

Lee, Matthew M Y; Petrie, Mark C; Rocchiccioli, Paul; Simpson, Joanne; Jackson, Colette; Brown, Ammani; Corcoran, David; Mangion, Kenneth; McEntegart, Margaret; Shaukat, Aadil; Rae, Alan; Hood, Stuart; Peat, Eileen; Findlay, Iain; Murphy, Clare; Cormack, Alistair; Bukov, Nikolay; Balachandran, Kanarath; Papworth, Richard; Ford, Ian; Briggs, Andrew; Berry, Colin

2016-01-01

Introduction There is an evidence gap about how to best treat patients with prior coronary artery bypass grafts (CABGs) presenting with non-ST segment elevation acute coronary syndromes (NSTE-ACS) because historically, these patients were excluded from pivotal randomised trials. We aim to undertake a pilot trial of routine non-invasive management versus routine invasive management in patients with NSTE-ACS with prior CABG and optimal medical therapy during routine clinical care. Our trial is a proof-of-concept study for feasibility, safety, potential efficacy and health economic modelling. We hypothesise that a routine invasive approach in patients with NSTE-ACS with prior CABG is not superior to a non-invasive approach with optimal medical therapy. Methods and analysis 60 patients will be enrolled in a randomised clinical trial in 4 hospitals. A screening log will be prospectively completed. Patients not randomised due to lack of eligibility criteria and/or patient or physician preference and who give consent will be included in a registry. We will gather information about screening, enrolment, eligibility, randomisation, patient characteristics and adverse events (including post-discharge). The primary efficacy outcome is the composite of all-cause mortality, rehospitalisation for refractory ischaemia/angina, myocardial infarction and hospitalisation for heart failure. The primary safety outcome is the composite of bleeding, stroke, procedure-related myocardial infarction and worsening renal function. Health status will be assessed using EuroQol 5 Dimensions (EQ-5D) assessed at baseline and 6 monthly intervals, for at least 18 months. Trial registration number NCT01895751 (ClinicalTrials.gov). PMID:27110377

Mental health impact of social capital interventions: a systematic review.

PubMed

Flores, Elaine C; Fuhr, Daniela C; Bayer, Angela M; Lescano, Andres G; Thorogood, Nicki; Simms, Victoria

2018-02-01

Mental disorders are a major contributor to the global burden of disease and disability, and can be extremely costly at both individual and community level. Social capital, (SC) defined as an individual's social relationships and participation in community networks, may lower the risk of mental disorders while increasing resilience capacity, adaptation and recovery. SC interventions may be a cost-effective way of preventing and ameliorating these conditions. However, the impact of these SC interventions on mental health still needs research. We conducted a systematic review of SC-based interventions to investigate their effect on mental health outcomes from controlled, quasi-experimental studies or pilot trials. We searched twelve academic databases, three clinical trials registries, hand-searched references and contacted field experts. Studies' quality was assessed with the Cochrane Risk of Bias tools for randomized and non-randomized studies. Seven studies were included in the review, published between 2006 and 2016. There was substantial heterogeneity in the definitions of both SC and mental disorders among the studies, preventing us from calculating pooled effect sizes. The interventions included community engagement and educative programs, cognitive processing therapy and sociotherapy for trauma survivors, and neighbourhood projects. There are paucity of SC interventions investigating the effect on mental health outcomes. This study showed that both SC scores and mental health outcomes improved over time but there was little evidence of benefit compared to control groups in the long term. Further high-quality trials are needed, especially among adverse populations to assess sustainability of effect.

Cochrane systematic reviews are useful to map research gaps for decreasing maternal mortality.

PubMed

Chapman, Evelina; Reveiz, Ludovic; Chambliss, Amy; Sangalang, Stephanie; Bonfill, Xavier

2013-01-01

To use an "evidence-mapping" approach to assess the usefulness of Cochrane reviews in identifying research gaps in the maternal health. The article describes the general mapping, prioritizing, reconciling, and updating approach: (1) identifying gaps in the maternal health research using published systematic reviews and formulating research questions, (2) prioritizing questions using Delphi method, (3) reconciling identified research priorities with the existing literature (i.e., searching of ongoing trials in trials registries), (4) updating the process. A comprehensive search of Cochrane systematic reviews published or updated from January 2006 to March 2011 was performed. We evaluated the "Implications for Research" section to identify gaps in the research. Our search strategy identified 695 references; 178 systematic reviews identifying at least one research gap were used. We formulated 319 research questions, which were classified into 11 different categories based on the direct and indirect causes of maternal mortality: postpartum hemorrhage, abortion, hypertensive disorders, infection/sepsis, caesarean section, diabetes, pregnancy prevention, preterm labor, other direct causes, indirect causes, and health policies and systems. Most research questions concerned the effectiveness of clinical interventions, including drugs (42.6%), nonpharmacologic interventions (16.3%), and health system (14.7%). It is possible to identify gaps in the maternal health research by using this approach. Copyright © 2013 Elsevier Inc. All rights reserved.

From Nonclinical Research to Clinical Trials and Patient-registries: Challenges and Opportunities in Biomedical Research

PubMed Central

de la Torre Hernández, José M.; Edelman, Elazer R.

2018-01-01

The most important challenge faced by human beings is health. The only way to provide better solutions for health care is innovation, true innovation. The only source of true innovation is research, good research indeed. The pathway from a basic science study to a randomized clinical trial is long and not free of bumps and even landmines. These are all the obstacles and barriers that limit the availability of resources, entangle administrative-regulatory processes, and restrain investigators’ initiatives. There is increasing demand for evidence to guide clinical practice but, paradoxically, biomedical research has become increasingly complex, expensive, and difficult to integrate into clinical care with increased barriers to performing the practical aspects of investigation. We face the challenge of increasing the volume of biomedical research and simultaneously improving the efficiency and output of this research. In this article, we review the main stages and methods of biomedical research, from nonclinical studies with animal and computational models to randomized trials and clinical registries, focusing on their limitations and challenges, but also providing alternative solutions to overcome them. Fortunately, challenges are always opportunities in disguise. PMID:28838647

Treatment of inflammatory dilated cardiomyopathy and (peri)myocarditis with immunosuppression and i.v. immunoglobulins.

PubMed

Maisch, Bernhard; Hufnagel, Günther; Kölsch, Susanne; Funck, Rainer; Richter, Annette; Rupp, Heinz; Herzum, Matthias; Pankuweit, Sabine

2004-09-01

Treatment objectives in inflammatory dilated cardiomyopathy (DCMi), myocarditis (M) and peri(myo)carditis are 1) the elimination of inflammatory cells from the myocardium and pericardium, 2) the elimination or (second best) mitigation of B-cell products such as antibodies and immuncomplexes directed against cardiac epitopes such as sarcolemmal, fibrillary and mitochondrial epitopes, and 3) the eradication of the causative viral or microbial agent, if present. A "non-specific" anti-inflammatory treatment in peri(myo)carditis can be carried out with antiphlogistics (NSAIDs preferably colchicine 1-3 mg/d) independent from the presence of the infective agent. In larger virus and bacteria negative effusions we recommend intrapericardial instillation of cristalloid triamcinolon (Volon A) at a dose of 500 mg/m(2), which should be left in place to have a sustained effect over at least 4 weeks. This will effectively prevent recurrences particularly when colchicine is added over a period of at least 3-6 months. Taking into account the 2004 ESC task force recommendations on the management of pericardial diseases the treatment recommendation for NSAIDs and colchicine can be classified as level of evidence A, indication class I, for intrapericardial triamcinolon instillation as level of evidence B, indication class IIa. In (immuno)histologically validated autoreactive (virus negative) myocarditis and DCMi double-blind randomized trials are lacking to demonstrate the superiority of immunosuppression over conventional heart failure management. The only published randomized and double-blind immunosuppression treatment trial (American Myocarditis Treatment Trial) was underpowered and did not distinguish viral from non-viral disease. It showed neither benefit nor harm of a combination of cyclosporin and prednisone. A number of retrospective analyses of immunosuppression in myocarditis showed some benefit of surrogate parameters (ejection fraction, exercise tolerance) but improvement under conventional heart failure treatment cannot be ruled out completely as the main cause for amelioration. ESETCID (European Study on the Epidemiology and Treatment of Cardiac Inflammatory Disease) is a double-blind, randomized, placebo-controled three-armed trial with prednisolone and azathioprine for autoreactive (virus negative) DCMi, interferon alpha for enterovirus positive DCMi, high-dose immunoglobulin for cytomegalovirus and intermediate dose for adeno- and Parvo B19 DCMi. It has now randomized more than 120 patients to the different treatment arms. Its final result has still to be awaited.-Patients not willing to randomize in the trial were included in a registry follow-up, which shows improvement of hemodynamic parameters and elimination of the inflammation in the majority of patients. This is in concordance with several non-randomized trials. Since evidence is conflicting (level of evidence C, indication class IIb; if negative viral etiology is taken into consideration class IIa) treatment with immunosuppression cannot be generally recommended but should be further evaluated in doubleblind randomized clinical trials or at least in controlled trials and registries. This also applies to treatment with interferon for enteroviral or other viral infections in the heart. : The elimination of anticardiac antibodies, which have been associated with DCMi, is a currently discussed concept, which is supported by published registry data and a few very small controlled investigations but not by a randomized double-blind trial with clinical endpoints of relevance. In some studies immunoglobulins have been substituted, so that an additional immunomodulatory effect has to be taken into account. The current proof of concept can be ranked level of evidence C, indication class IIa only. An even more challenging and still more attractive hypothesis is that cardiac inflammation caused by specific circulating beta-adrenoceptor antibodies can be eradicated with the elimination of the beta-receptor antibody thus healing dilated cardiomyopathy. Application of this approach can be ranked level of evidence C, indication class IIb at present only. Therefore these two pathophysiologically attractive concepts have to await further validation by a double-blind, randomized clinical endpoint trial. It has been shown that immunoglobulins have both an antiviral and an anti-inflammatory effect. They may suppress proinflammatory cytokines and reduce oxidative stress. HIGH-DOSE I.V. In biopsy proven CMVmyocarditis a controlled trial demonstrated eradication of inflammation and of the virus (level of evidence B, indication class IIa), which is in accordance with registry data and case reports. In suspected myocarditis (not biopsy proven, no viral etiology established or excluded) conflicting data exist with respect to the improvement of surrogate markers such as the ejection fraction under high-dose immunoglobulins. More evidence can be weighted in favour of a positive treatment effect (level of evidence B, indication class IIb). Importantly there were no detrimental effects of the ivIG reported in these trials. One has to consider the high costs of this treatment, however. A trial taking into account the different etiologies (different viruses assessed separately vs. non-viral/autoreactive vs. placebo) is still lacking. MODERATE-DOSE I.V. Registry data support a positive effect of 20 g i.v. pentaglobin (IgG and IgM) in adenovirus positive myocarditis for clinical improvement, eradication of both the inflammation and the virus. In Parvo B19 myocarditis our own registry data indicate that clinical improvement can be noted, but only inflammation is successfully eliminated, whereas Parvo B19 persistence remains a problem in the majority of patients. In Parvo B19 associated DCMi therefore dose finding studies and randomized trials are needed.

Genetics Home Reference: myasthenia gravis

MedlinePlus

... ventilation assistance. This respiratory failure, called a myasthenic crisis, may be triggered by stresses such as infections ... be inherited? More about Inheriting Genetic Conditions Diagnosis & Management Resources Genetic Testing (2 links) Genetic Testing Registry: ...

Genetics Home Reference: hereditary angioedema

MedlinePlus

... 000 people. Type I is the most common, accounting for 85 percent of cases. Type II occurs ... be inherited? More about Inheriting Genetic Conditions Diagnosis & Management Resources Genetic Testing (3 links) Genetic Testing Registry: ...

Genetics Home Reference: multiminicore disease

MedlinePlus

... are less common than the classic form, together accounting for about 25 percent of all cases. The ... be inherited? More about Inheriting Genetic Conditions Diagnosis & Management Resources Genetic Testing (5 links) Genetic Testing Registry: ...

A multicentre, randomised controlled, non-inferiority trial, comparing nasal high flow with nasal continuous positive airway pressure as primary support for newborn infants with early respiratory distress born in Australian non-tertiary special care nurseries (the HUNTER trial): study protocol.

PubMed

Manley, Brett J; Roberts, Calum T; Arnolda, Gaston R B; Wright, Ian M R; Owen, Louise S; Dalziel, Kim M; Foster, Jann P; Davis, Peter G; Buckmaster, Adam G

2017-06-23

Nasal high-flow (nHF) therapy is a popular mode of respiratory support for newborn infants. Evidence for nHF use is predominantly from neonatal intensive care units (NICUs). There are no randomised trials of nHF use in non-tertiary special care nurseries (SCNs). We hypothesise that nHF is non-inferior to nasal continuous positive airway pressure (CPAP) as primary support for newborn infants with respiratory distress, in the population cared for in non-tertiary SCNs. The HUNTER trial is an unblinded Australian multicentre, randomised, non-inferiority trial. Infants are eligible if born at a gestational age ≥31 weeks with birth weight ≥1200 g and admitted to a participating non-tertiary SCN, are <24 hours old at randomisation and require non-invasive respiratory support or supplemental oxygen for >1 hour. Infants are randomised to treatment with either nHF or CPAP. The primary outcome is treatment failure within 72 hours of randomisation, as determined by objective oxygenation, apnoea or blood gas criteria or by a clinical decision that urgent intubation and mechanical ventilation, or transfer to a tertiary NICU, is required. Secondary outcomes include incidence of pneumothorax requiring drainage, duration of respiratory support, supplemental oxygen and hospitalisation, costs associated with hospital care, cost-effectiveness, parental stress and satisfaction and nursing workload. Multisite ethical approval for the study has been granted by The Royal Children's Hospital, Melbourne, Australia (Trial Reference No. 34222), and by each participating site. The trial is currently recruiting in eight centres in Victoria and New South Wales, Australia, with one previous site no longer recruiting. The trial results will be published in a peer-reviewed journal and will be presented at national and international conferences. Australian and New Zealand Clinical Trials Registry (ANZCTR): ACTRN12614001203640; 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.

The impact of population-based disease management services for selected chronic conditions: the Costs to Australian Private Insurance - Coaching Health (CAPICHe) study protocol

PubMed Central

2012-01-01

Background Recent evidence from a large scale trial conducted in the United States indicates that enhancing shared decision-making and improving knowledge, self-management, and provider communication skills to at-risk patients can reduce health costs and utilisation of healthcare resources. Although this trial has provided a significant advancement in the evidence base for disease management programs it is still left for such results to be replicated and/or generalised for populations in other countries and other healthcare environments. This trial responds to the limited analyses on the effectiveness of providing chronic disease management services through telephone health coaching in Australia. The size of this trial and it's assessment of cost utility with respect to potentially preventable hospitalisations adds significantly to the body of knowledge to support policy and investment decisions in Australia as well as to the international debate regarding the effect of disease management programs on financial outcomes. Methods Intention to treat study applying a prospective randomised design comparing usual care with extensive outreach to encourage use of telephone health coaching for those people identified from a risk scoring algorithm as having a higher likelihood of future health costs. The trial population has been limited to people with one or more of the following selected chronic conditions: namely, low back pain, diabetes, coronary artery disease, heart failure, and chronic obstructive pulmonary disease. This trial will enrol at least 64,835 sourced from the approximately 3 million Bupa Australia private health insured members located across Australia. The primary outcome will be the total (non-maternity) cost per member as reported to the private health insurer (i.e. charged to the insurer) 12 months following entry into the trial for each person. Study recruitment will be completed in early 2012 and the results will be available in late 2013. Discussion If positive, CAPICHe will represent a potentially cost-effective strategy to improve health outcomes in higher risk individuals with a chronic condition, in a private health insurance setting. Trial Registration Australian New Zealand Clinical Trials Registry reference: ACTRN12611000580976 PMID:22325668

The NeuroAiD Safe Treatment (NeST) Registry: a protocol

PubMed Central

Venketasubramanian, Narayanaswamy; Kumar, Ramesh; Soertidewi, Lyna; Abu Bakar, Azizi; Laik, Carine; Gan, Robert

2015-01-01

Introduction NeuroAiD (MLC601, MLC901), a combination of natural products, has been shown to be safe and to aid neurological recovery after brain injuries. The NeuroAiD Safe Treatment (NeST) Registry aims to assess its use and safety in the real-world setting. Methods and analysis The NeST Registry is designed as a product registry that would provide information on the use and safety of NeuroAiD in clinical practice. An online NeST Registry was set up to allow easy entry and retrieval of essential information including demographics, medical conditions, clinical assessments of neurological, functional and cognitive state, compliance, concomitant medications, and side effects, if any, among patients on NeuroAiD. Patients who are taking or have been prescribed NeuroAiD may be included. Participation is voluntary. Data collected are similar to information obtained during standard care and are prospectively entered by the participating physicians at baseline (before initialisation of NeuroAiD) and during subsequent visits. The primary outcome assessed is safety (ie, non-serious and serious adverse event), while compliance and neurological status over time are secondary outcomes. The in-person follow-up assessments are timed with clinical appointments. Anonymised data will be extracted and collectively analysed. Initial target sample size for the registry is 2000. Analysis will be performed after every 500 participants entered with completed follow-up information. Ethics and dissemination Doctors who prescribe NeuroAiD will be introduced to the registry by local partners. The central coordinator of the registry will discuss the protocol and requirements for implementation with doctors who show interest. Currently, the registry has been approved by the Ethics Committees of Universiti Kebangsaan Malaysia (Malaysia) and National Brain Center (Indonesia). In addition, for other countries, Ethics Committee approval will be obtained in accordance with local requirements. Trial registration number NCT02536079. PMID:26567259

Promoting deceased organ and tissue donation registration in family physician waiting rooms (RegisterNow-1 trial): study protocol for a pragmatic, stepped-wedge, cluster randomized controlled registry.

PubMed

Li, Alvin H; Garg, Amit X; Prakash, Versha; Grimshaw, Jeremy M; Taljaard, Monica; Mitchell, Joanna; Matti, Danny; Linklater, Stefanie; Naylor, Kyla L; Dixon, Stephanie; Faulds, Cathy; Bevan, Rachel; Getchell, Leah; Knoll, Greg; Kim, S Joseph; Sontrop, Jessica; Bjerre, Lise M; Tong, Allison; Presseau, Justin

2017-12-21

There is a worldwide shortage of organs available for transplant, leading to preventable mortality associated with end-stage organ disease. While most citizens in many countries with an intent-to-donate "opt-in" system support organ donation, registration rates remain low. In Canada, most Canadians support organ donation but less than 25% in most provinces have registered their desire to donate their organs when they die. The family physician office is a promising yet underused setting in which to promote organ donor registration and address known barriers and enablers to registering for deceased organ and tissue donation. We developed a protocol to evaluate an intervention to promote registration for organ and tissue donation in family physician waiting rooms. This protocol describes a planned, stepped-wedge, cluster randomized registry trial in six family physician offices in Ontario, Canada to evaluate the effectiveness of reception staff providing patients with a pamphlet that addresses barriers and enablers to registration including a description of how to register for organ donation. An Internet-enabled tablet will also be provided in waiting rooms so that interested patients can register while waiting for their appointments. Family physicians and reception staff will be provided with training and/or materials to support any conversations about organ donation with their patients. Following a 2-week control period, the six offices will cross sequentially into the intervention arm in randomized sequence at 2-week intervals until all offices deliver the intervention. The primary outcome will be the proportion of patients visiting the office who are registered organ donors 7 days following their office visit. We will evaluate this outcome using routinely collected registry data from provincial administrative databases. A post-trial qualitative evaluation process will assess the experiences of reception staff and family physicians with the intervention and the stepped-wedge trial design. Promoting registration for organ donation in family physician offices is a potentially useful strategy for increasing registration for organ donation. Increased registration may ultimately help to increase the number of organs available for transplant. The results of this trial will provide important preliminary data on the effectiveness of using family physician offices to promote registration for organ donation. ClinicalTrials.gov, ID: NCT03213171 . Registered on 11 July 2017.

Kangaroo mother care: using formative research to design an acceptable community intervention.

PubMed

Mazumder, Sarmila; Upadhyay, Ravi Prakash; Hill, Zelee; Taneja, Sunita; Dube, Brinda; Kaur, Jasmine; Shekhar, Medha; Ghosh, Runa; Bisht, Shruti; Martines, Jose Carlos; Bahl, Rajiv; Sommerfelt, Halvor; Bhandari, Nita

2018-03-02

Low and middle income countries (LMICs), including India, contribute to a major proportion of low birth weight (LBW) infants globally. These infants require special care. Kangaroo Mother Care (KMC) in hospitals is a cost effective and efficacious intervention. In institutional deliveries, the duration of facility stay is often short. In LMICs, a substantial proportion of deliveries still occur at home and access to health care services is limited. In these circumstances, a pragmatic choice may be to initiate KMC at home for LBW babies. However, evidence is lacking on benefits of community-initiated KMC (cKMC). Promoting KMC at home without an understanding of its acceptability may lead to limited success. We conducted formative research to assess the feasibility, acceptability and adoption of cKMC with the aim of designing an intervention package for a randomised controlled trial in LBW infants in Haryana, India. Qualitative methods included 40 in-depth interviews with recently delivered women and 6 focus group discussions, two each with fathers and grandfathers, grandmothers, and community health workers. A prototype intervention package to promote cKMC was developed and tested in 28 mother-infant pairs (of them, one mother had twins), using Household (HH) trials. We found that most mothers in the community recognized that babies born small required special care. In spite of not being aware of the practice of KMC, respondents felt that creating awareness of KMC benefits will promote practice. They expressed concerns about doing KMC for long periods because mothers needed rest after delivery. However, the cultural practice of recently delivered women not expected to be doing household chores and availability of other family members were identified as enablers. HH trials provided an opportunity to test the intervention package and showed high acceptability for KMC. Most mothers perceived benefits such as weight gain and increased activity in the infant. Community-initiated KMC is acceptable by mothers and adoption rates are high. Formative research is essential for developing a strategy for delivery of an intervention. Trial registration number CTRI/2015/10/006267 . Name of Registry: Clinical Trials Registry - India. URL of Registry: http://ctri.nic.in/Clinicaltrials/login.php Date of Registration: 15/10/2015. Date of enrolment of the first participant to the trial: 18/04/2015.

Clinical trial transparency update: an assessment of the disclosure of results of company-sponsored trials associated with new medicines approved in Europe in 2013.

PubMed

Deane, Bryan R; Sivarajah, Jacintha

2017-03-01

The objective of this study was to assess the timely disclosure of results of company-sponsored clinical trials related to all new medicines approved by the European Medicines Agency (EMA) during 2013. This is an extension of two previously reported studies of trials related to all new medicines approved in Europe in 2009, 2010 and 2011, and in 2012. The original study found that over a three year period over three-quarters of all trials were disclosed within 12 months and almost 90% were disclosed by the end of the study. The extension study (2012 approvals) showed an improvement in results disclosure within 12 months to 90%, and an overall disclosure rate of 92% by the end of the study. The methodology used was exactly as previously reported. Various publicly available information sources were searched for both clinical trial registration and disclosure of results. All completed company-sponsored trials related to each new medicine approved for marketing by the EMA in 2013, carried out in patients and recorded on a clinical trials registry and/or included in an EMA European Public Assessment Report (EPAR), were included. Information sources were searched between 1 May and 31 July 2015. The main outcome measure was the proportion of trials for which results had been disclosed on a registry or in the scientific literature either within 12 months of the later of either first regulatory approval or trial completion, or by 31 July 2015 (end of survey). Of the completed trials associated with 34 new medicines licensed to 24 different companies in 2013, results of 90% (484/539) had been disclosed within 12 months, and results of 93% (500/539) had been disclosed by 31 July 2015. The disclosure rate within 12 months of 90% suggests that industry is continuing to achieve disclosure in a timely manner. The overall disclosure rate at study end of 93% indicates that the improvement in transparency amongst company-sponsored trials has been maintained in the trials associated with new medicines approved in 2013.

Clinical trial transparency update: an assessment of the disclosure of results of company-sponsored trials associated with new medicines approved in Europe in 2014.

PubMed

Deane, Bryan R; Porkess, Sheuli

2018-07-01

The objective of this study was to assess the timely disclosure of results of company-sponsored clinical trials related to all new medicines approved by the European Medicines Agency (EMA) during 2014. This is the final extension of three previously reported studies of trials related to all new medicines approved in Europe in 2009, 2010 and 2011, and in 2012 and 2013. The original study found that over a three-year period over three-quarters of all trials were disclosed within 12 months and almost 90% were disclosed by the end of the study (31 January 2013). The extension studies (2012 and 2013 approvals) both showed an improvement in results disclosure within 12 months to 90%, and an overall disclosure rate of 92% and 93% respectively by the end of the studies. The methodology used was exactly as previously reported. Various publicly available information sources were searched for both clinical trial registration and disclosure of results. All completed company-sponsored trials related to each new medicine approved for marketing by the EMA in 2014, carried out in patients and recorded on a clinical trials registry and/or included in an EMA European Public Assessment Report (EPAR), were included. Information sources were searched between 1 May and 31 July 2016. The main outcome measure was the proportion of trials for which results had been disclosed on a registry or in the scientific literature either within 12 months of the later of either first regulatory approval or trial completion, or by 31 July 2016 (end of survey). Of the completed trials associated with 32 new medicines licensed to 22 different companies in 2014, results of 93% (505/542) had been disclosed within 12 months, and results of 96% (518/542) had been disclosed by 31 July 2016. The disclosure rate within 12 months of 93% suggests that industry is continuing to achieve disclosure in a timely manner. The overall disclosure rate at study end of 96% indicates that the improvement in transparency amongst company-sponsored trials has been maintained in the trials associated with new medicines approved in 2014.

Antibacterial agents in composite restorations for the prevention of dental caries.

PubMed

Pereira-Cenci, Tatiana; Cenci, Maximiliano S; Fedorowicz, Zbys; Azevedo, Marina

2013-12-17

Dental caries is a multifactorial disease in which the fermentation of food sugars by bacteria from the biofilm (dental plaque) leads to localised demineralisation of tooth surfaces, which may ultimately result in cavity formation. Resin composites are widely used in dentistry to restore teeth. These restorations can fail for a number of reasons, such as secondary caries, and restorative material fracture and other minor reasons. From these, secondary caries, which are caries lesions developed adjacent to restorations, is the main cause for restorations replacement. The presence of antibacterials in both the filling material and the bonding systems would theoretically be able to affect the initiation and progression of caries adjacent to restorations. This is an update of the Cochrane review published in 2009. To assess the effects of antibacterial agents incorporated into composite restorations for the prevention of dental caries. We searched the following electronic databases: the Cochrane Oral Health Group's Trials Register (to 23 July 2013), the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2013, Issue 6), MEDLINE via OVID (1946 to 23 July 2013) and EMBASE via OVID (1980 to 23 July 2013). We searched the US National Institutes of Health Trials Register (http://clinicaltrials.gov), the metaRegister of Controlled Trials (www.controlled-trials.com) and the World Health Organization International Clinical Trials Registry platform (www.who.int/trialsearch) for ongoing trials. No restrictions were placed on the language or date of publication when searching the electronic databases. Randomised controlled trials comparing resin composite restorations containing antibacterial agents with composite restorations not containing antibacterial agents. Two review authors conducted screening of studies in duplicate and independently, and although no eligible trials were identified, the two authors had planned to extract data independently and assess trial quality using standard Cochrane Collaboration methodologies. We retrieved 308 references to studies, none of which matched the inclusion criteria for this review and all of which were excluded. We were unable to identify any randomised controlled trials on the effects of antibacterial agents incorporated into composite restorations for the prevention of dental caries. The absence of high level evidence for the effectiveness of this intervention emphasises the need for well designed, adequately powered, randomised controlled clinical trials. Thus, conclusions remain the same as the previously published review, with no included clinical trials.

Ursodeoxycholic acid for cystic fibrosis-related liver disease.

PubMed

Cheng, Katharine; Ashby, Deborah; Smyth, Rosalind L

2017-09-11

Abnormal biliary secretion leads to the thickening of bile and the formation of plugs within the bile ducts; the consequent obstruction and abnormal bile flow ultimately results in the development of cystic fibrosis-related liver disease. This condition peaks in adolescence with up to 20% of adolescents with cystic fibrosis developing chronic liver disease. Early changes in the liver may ultimately result in end-stage liver disease with people needing transplantation. One therapeutic option currently used is ursodeoxycholic acid. This is an update of a previous review. To analyse evidence that ursodeoxycholic acid improves indices of liver function, reduces the risk of developing chronic liver disease and improves outcomes in general in cystic fibrosis. We searched the Cochrane CF and Genetic Disorders Group Trials Register comprising references identified from comprehensive electronic database searches, handsearches of relevant journals and abstract books of conference proceedings. We also contacted drug companies and searched online trial registries.Date of the most recent search of the Group's trials register: 09 April 2017. Randomised controlled trials of the use of ursodeoxycholic acid for at least three months compared with placebo or no additional treatment in people with cystic fibrosis. Two authors independently assessed trial eligibility and quality. The authors used GRADE to assess the quality of the evidence. Twelve trials have been identified, of which four trials involving 137 participants were included; data were only available from three of the trials (118 participants) since one cross-over trial did not report appropriate data. The dose of ursodeoxycholic acid ranged from 10 to 20 mg/kg/day for up to 12 months. The complex design used in two trials meant that data could only be analysed for subsets of participants. There was no significant difference in weight change, mean difference -0.90 kg (95% confidence interval -1.94 to 0.14) based on 30 participants from two trials. Improvement in biliary excretion was reported in only one trial and no significant change after treatment was shown. There were no data available for analysis for long-term outcomes such as death or need for liver transplantation. There are few trials assessing the effectiveness of ursodeoxycholic acid. The quality of the evidence identified ranged from low to very low. There is currently insufficient evidence to justify its routine use in cystic fibrosis.

Delay in Recognition of Pulmonary Arterial Hypertension

PubMed Central

Brown, Lynette M.; Chen, Hubert; Halpern, Scott; Taichman, Darren; McGoon, Michael D.; Farber, Harrison W.; Frost, Adaani E.; Liou, Theodore G.; Turner, Michelle; Feldkircher, Kathy; Miller, Dave P.

2011-01-01

Background: Pulmonary arterial hypertension (PAH) is a progressive and fatal disorder. Despite the emergence of effective therapy, PAH is commonly at an advanced stage when recognized. Factors associated with a prolonged symptomatic period before the recognition of PAH have not been fully evaluated. Methods: The Registry to Evaluate Early and Long-term PAH Disease Management (REVEAL Registry) enrolled 2,967 US adult patients with PAH from March 2006 to September 2007. Patients were considered to have delayed disease recognition if > 2 years elapsed between symptom onset and the patient receiving a PAH diagnosis, starting on PAH-specific therapy, or receiving a diagnosis by right-sided heart catheterization. Results: In 21.1% of patients, symptoms were experienced for > 2 years before PAH was recognized. Patients with onset of PAH symptoms before age 36 years showed the highest likelihood of delayed disease recognition (OR, 3.07; 95% CI, 2.03-4.66). History of obstructive airways disease (OR, 1.93; 95% CI, 1.5-2.47) and sleep apnea (OR, 1.72; 95% CI, 1.33-2.22) were independently associated with delayed PAH recognition. Six-minute walk distance < 250 m (OR, 1.91; 95% CI, 1.16-3.13), right atrial pressure < 10 mm Hg (OR, 1.77; 95% CI, 1.26-2.48), and pulmonary vascular resistance < 10 Wood units (OR, 1.28; 95% CI, 1.02-1.60) were also associated with delayed disease recognition, but sex, race/ethnicity, and geographic region showed no association. Conclusions: One in five patients in the REVEAL Registry who were diagnosed with PAH reported symptoms for > 2 years before their disease was recognized. Younger individuals and patients with histories of common respiratory disorders were most likely to experience delayed PAH recognition. Trial registry: ClinicalTrials.gov; No.: NCT00370214; URL: www.clinicaltrials.gov PMID:21393391

National MS and Parkinson's Disease Registries Act

THOMAS, 111th Congress

Sen. Dorgan, Byron L. [D-ND

2009-06-16

Senate - 06/16/2009 Read twice and referred to the Committee on Health, Education, Labor, and Pensions. (All Actions) Tracker: This bill has the status IntroducedHere are the steps for Status of Legislation:

Genetics Home Reference: otopalatodigital syndrome type 2

MedlinePlus

... Testing (1 link) Genetic Testing Registry: Oto-palato-digital syndrome, type II Other Diagnosis and Management Resources ( ... syndrome FPO OPD syndrome, type 2 oto-palato-digital syndrome, type II Taybi syndrome Related Information How ...

Genetics Home Reference: otopalatodigital syndrome type 1

MedlinePlus

... Testing (1 link) Genetic Testing Registry: Oto-palato-digital syndrome, type I Other Diagnosis and Management Resources ( ... syndrome FPO OPD syndrome, type 1 oto-palato-digital syndrome, type I Taybi syndrome Related Information How ...

Genetics Home Reference: MPV17-related hepatocerebral mitochondrial DNA depletion syndrome

MedlinePlus

... Genetic Testing Registry: Navajo neurohepatopathy Other Diagnosis and Management Resources (2 links) GeneReview: MPV17-Related Hepatocerebral Mitochondrial DNA Maintenance Defect The United Mitochondrial Disease Foundation: Treatments and ...

45 CFR 170.205 - Content exchange standards and implementation specifications for exchanging electronic health...

Code of Federal Regulations, 2014 CFR

2014-10-01

...) (incorporated by reference in § 170.299). Implementation specifications. The Healthcare Information Technology... Guide for Ambulatory Healthcare Provider Reporting to Central Cancer Registries, HL7 Clinical Document...

Genetics Home Reference: combined pituitary hormone deficiency

MedlinePlus

... the most common known cause of this disorder, accounting for an estimated 12 to 55 percent of ... be inherited? More about Inheriting Genetic Conditions Diagnosis & Management Resources Genetic Testing (7 links) Genetic Testing Registry: ...

Genetics Home Reference: Paget disease of bone

MedlinePlus

... genetic cause of classic Paget disease of bone , accounting for 10 to 50 percent of cases that ... be inherited? More about Inheriting Genetic Conditions Diagnosis & Management Resources Genetic Testing (6 links) Genetic Testing Registry: ...

Genetics Home Reference: familial isolated pituitary adenoma

MedlinePlus

... 1,000 people. FIPA, though, is quite rare, accounting for approximately 2 percent of pituitary adenomas. More ... be inherited? More about Inheriting Genetic Conditions Diagnosis & Management Resources Genetic Testing (1 link) Genetic Testing Registry: ...

Genetics Home Reference: Woodhouse-Sakati syndrome

MedlinePlus

... low amounts of hormones that direct sexual development (hypogonadism), which typically becomes apparent during adolescence. Without hormone ... Resources Genetic Testing (1 link) Genetic Testing Registry: Hypogonadism, diabetes mellitus, alopecia, mental retardation and electrocardiographic abnormalities ...

A cluster randomised controlled trial of a comprehensive accreditation intervention to reduce alcohol consumption at community sports clubs: study protocol

PubMed Central

Wolfenden, Luke; Rowland, Bosco C; Tindall, Jennifer; Gillham, Karen E; McElduff, Patrick; Rogerson, John C; Wiggers, John H

2011-01-01

Introduction Excessive alcohol consumption is responsible for considerable harm from chronic disease and injury. Within most developed countries, members of sporting clubs consume alcohol at levels above that of communities generally. Despite the potential benefits of interventions to address alcohol consumption in sporting clubs, there have been no randomised controlled trials to test the effectiveness of these interventions. The aim of this study is to examine the effectiveness of a comprehensive accreditation intervention with community football clubs (Rugby League, Rugby Union, soccer/association football and Australian Rules football) in reducing excessive alcohol consumption by club members. Methods and analysis The study will be conducted in New South Wales, Australia, and employ a cluster randomised controlled trial design. Half of the football clubs recruited to the trial will be randomised to receive an intervention implemented over two and a half winter sporting seasons. The intervention is based on social ecology theory and is comprehensive in nature, containing multiple elements designed to decrease the supply of alcohol to intoxicated members, cease the provision of cheap and free alcohol, increase the availability and cost-attractiveness of non-alcoholic and low-alcoholic beverages, remove high alcohol drinks and cease drinking games. The intervention utilises a three-tiered accreditation framework designed to motivate intervention implementation. Football clubs in the control group will receive printed materials on topics unrelated to alcohol. Outcome data will be collected pre- and postintervention through cross-sectional telephone surveys of club members. The primary outcome measure will be alcohol consumption by club members at the club, assessed using a graduated frequency index and a seven day diary. Ethics and dissemination The study was approved by The University of Newcastle Human Research Ethics Committee (reference: H-2008-0432). Study findings will be disseminated widely through peer-reviewed publications and conference presentations. Trial registration number Australian New Zealand Clinical Trials Registry: ACTRN12609000224224. PMID:22021867

SENIORLAB: a prospective observational study investigating laboratory parameters and their reference intervals in the elderly.

PubMed

Risch, Martin; Nydegger, Urs; Risch, Lorenz

2017-01-01

In clinical practice, laboratory results are often important for making diagnostic, therapeutic, and prognostic decisions. Interpreting individual results relies on accurate reference intervals and decision limits. Despite the considerable amount of resources in clinical medicine spent on elderly patients, accurate reference intervals for the elderly are rarely available. The SENIORLAB study set out to determine reference intervals in the elderly by investigating a large variety of laboratory parameters in clinical chemistry, hematology, and immunology. The SENIORLAB study is an observational, prospective cohort study. Subjectively healthy residents of Switzerland aged 60 years and older were included for baseline examination (n = 1467), where anthropometric measurements were taken, medical history was reviewed, and a fasting blood sample was drawn under optimal preanalytical conditions. More than 110 laboratory parameters were measured, and a biobank was set up. The study participants are followed up every 3 to 5 years for quality of life, morbidity, and mortality. The primary aim is to evaluate different laboratory parameters at age-related reference intervals. The secondary aims of this study include the following: identify associations between different parameters, identify diagnostic characteristics to diagnose different circumstances, identify the prevalence of occult disease in subjectively healthy individuals, and identify the prognostic factors for the investigated outcomes, including mortality. To obtain better grounds to justify clinical decisions, specific reference intervals for laboratory parameters of the elderly are needed. Reference intervals are obtained from healthy individuals. A major obstacle when obtaining reference intervals in the elderly is the definition of health in seniors because individuals without any medical condition and any medication are rare in older adulthood. Reference intervals obtained from such individuals cannot be considered representative for seniors in a status of age-specific normal health. In addition to the established methods for determining reference intervals, this longitudinal study utilizes a unique approach, in that survival and long-term well-being are taken as indicators of health in seniors. This approach is expected to provide robust and representative reference intervals that are obtained from an adequate reference population and not a collective of highly selected individuals. The present study was registered under International Standard Randomized Controlled Trial Number registry: ISRCTN53778569.

Does Age Influence Cardiac Resynchronization Therapy Use and Outcome?

PubMed

Heidenreich, Paul A; Tsai, Vivian; Bao, Haikun; Curtis, Jeptha; Goldstein, Mary; Curtis, Lesley; Hernandez, Adrian; Peterson, Pamela; Turakhia, Mintu P; Masoudi, Frederick A

2015-06-01

This study sought to describe the use of CRT-D and its association with survival for older patients. Many patients who receive cardiac resynchronization therapy with defibrillator (CRT-D) in practice are older than those included in clinical trials. We identified patients undergoing ICD implantation in the National Cardiovascular Disease Registry (NCDR) ICD registry from 2006 to 2009, who also met clinical trial criteria for CRT, including left ventricular ejection fraction (LVEF) ≤35%, QRS ≥120 ms, and New York Heart Association (NYHA) functional class III or IV. NCDR registry data were linked to the social security death index to determine the primary outcome of time to death from any cause. We identified 70,854 patients from 1,187 facilities who met prior trial criteria for CRT-D. The mean age of the 58,147 patients receiving CRT-D was 69.4 years with 6.4% of patients age 85 or older. CRT use was 80% or higher among candidates in all age groups. Follow-up was available for 42,285 patients age ≥65 years at 12 months. Receipt of CRT-D was associated with better survival at 1 year (82.1% vs. 77.1%, respectively) and 4 years (54.0% vs. 46.2% , respectively) than in those receiving only an ICD (p < 0.001). The CRT association with improved survival was not different for different age groups (p = 0.86 for interaction). More than 80% of older patients undergoing ICD implantation who were candidates for a CRT-D received the combined device. Mortality in older patients undergoing ICD implantation was high but was lower for those receiving CRT-D. Copyright © 2015 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

Phenobarbital versus morphine in the management of neonatal abstinence syndrome, a randomized control trial.

PubMed

Nayeri, Fatemeh; Sheikh, Mahdi; Kalani, Majid; Niknafs, Pedram; Shariat, Mamak; Dalili, Hosein; Dehpour, Ahmad-Reza

2015-05-15

Evaluating the efficacy of the loading and tapering dose of Phenobarbital versus oral Morphine in the management of NAS. This randomized, open-label, controlled trial was conducted on 60 neonates born to illicit drugs dependent mothers at Vali-Asr and Akbar-Abadi hospitals, Tehran, Iran, who exhibited NAS requiring medical therapy. The neonates were randomized to receive either: Oral Morphine Sulfate or a loading dose of Phenobarbital followed by a tapering dose. The duration of treatment required for NAS resolution, the total hospital stay and the requirement for additional second line treatment were compared between the treatment groups. The Mean ± Standard Deviation for the duration of treatment required for the resolution of NAS was 8.5 ± 5 days in the Morphine group and 8.5 ± 4 days in the Phenobarbital group (P = 0.9). The duration of total hospital stay was 12.6 ± 5.6 days in the Morphine group and 12.5 ± 5.3 days in the Phenobarbital group (P = 0.7). 3.3 % in the Morphine group versus 6.6 % in the Phenobarbital group required adjunctive treatment (P = 0.5). There were no significant differences in the duration of treatment, duration of hospital stay, and the requirement for adjunctive treatment, between the neonates with NAS who received Morphine Sulfate and neonates who received a loading and tapering dose of Phenobarbital. This study is registered at the Iranian Registry of Clinical Trials ( www.irct.ir ) which is a Primary Registry in the WHO Registry Network. (Registration Number =  IRCT201406239568N8 ).

Background and design of the ACCA-EAPCI registry on ST-segment elevation myocardial infarction of the European Society of Cardiology.

PubMed

Zeymer, Uwe; Ludman, Peter; Danchin, Nicolas; Kala, Petr; Maggioni, Aldo P; Weidinger, Franz

2018-02-01

Treatment of patients with acute ST-segment elevation myocardial infarction has improved over past decades, with reperfusion therapy being the cornerstone in the acute phase. Based on the results of large randomised trials the current ST-segment elevation myocardial infarction guidelines of the European Society of Cardiology (ESC) recommend acute treatments and secondary prevention therapies. However, there are large variations between ESC countries in the treatment of patients presenting with ST-segment elevation myocardial infarction. Therefore the ESC has initiated a prospective registry to evaluate the current treatments and outcomes of these patients with a special focus on adherence to the ESC guidelines and on differences between countries and regions. This paper describes the methodology and design of the ST-segment elevation myocardial infarction registry conducted in collaboration of the Acute Cardiac Care Association and the European Association of Percutaneous Coronary Intervention.

Structures' validation profiles in Transmission of Imaging and Data (TRIAD) for automated National Clinical Trials Network (NCTN) clinical trial digital data quality assurance.

PubMed

Giaddui, Tawfik; Yu, Jialu; Manfredi, Denise; Linnemann, Nancy; Hunter, Joanne; O'Meara, Elizabeth; Galvin, James; Bialecki, Brian; Xiao, Ying

2016-01-01

Transmission of Imaging and Data (TRIAD) is a standard-based system built by the American College of Radiology to provide the seamless exchange of images and data for accreditation of clinical trials and registries. Scripts of structures' names validation profiles created in TRIAD are used in the automated submission process. It is essential for users to understand the logistics of these scripts for successful submission of radiation therapy cases with less iteration. Copyright © 2016 American Society for Radiation Oncology. Published by Elsevier Inc. All rights reserved.

Interventions to Improve the Quality of Outpatient Specialty Referral Requests: A Systematic Review.

PubMed

Hendrickson, Chase D; Lacourciere, Stacy L; Zanetti, Cole A; Donaldson, Patrick C; Larson, Robin J

2016-09-01

Requests for outpatient specialty consultations occur frequently but often are of poor quality because of incompleteness. The authors searched bibliographic databases, trial registries, and references during October 2014 for studies evaluating interventions to improve the quality of outpatient specialty referral requests compared to usual practice. Two reviewers independently extracted data and assessed quality. Findings were qualitatively summarized for completeness of information relayed in a referral request within naturally emerging intervention categories. Of 3495 articles screened, 11 were eligible. All 3 studies evaluating software-based interventions found statistically significant improvements. Among 4 studies evaluating template/pro forma interventions, completeness was uniformly improved but with variable or unreported statistical significance. Of 4 studies evaluating educational interventions, 2 favored the intervention and 2 found no difference. One study evaluating referral management was negative. Current evidence for improving referral request quality is strongest for software-based interventions and templates, although methodological quality varied and findings may be setting specific. © The Author(s) 2015.

Automatic HTS force measurement instrument

DOEpatents

Sanders, Scott T.; Niemann, Ralph C.

1999-01-01

A device for measuring the levitation force of a high temperature superconductor sample with respect to a reference magnet includes a receptacle for holding several high temperature superconductor samples each cooled to superconducting temperature. A rotatable carousel successively locates a selected one of the high temperature superconductor samples in registry with the reference magnet. Mechanism varies the distance between one of the high temperature superconductor samples and the reference magnet, and a sensor measures levitation force of the sample as a function of the distance between the reference magnet and the sample. A method is also disclosed.

The CNDR: collaborating to translate new therapies for Canadians.

PubMed

Korngut, Lawrence; Campbell, Craig; Johnston, Megan; Benstead, Timothy; Genge, Angela; Mackenzie, Alex; McCormick, Anna; Biggar, Douglas; Bourque, Pierre; Briemberg, Hannah; O'Connell, Colleen; Dojeiji, Suzan; Dooley, Joseph; Grant, Ian; Hogan, Gillian; Johnston, Wendy; Kalra, Sanjay; Katzberg, Hans D; Mah, Jean K; McAdam, Laura; McMillan, Hugh J; Melanson, Michel; Selby, Kathryn; Shoesmith, Christen; Smith, Garth; Venance, Shannon L; Wee, Joy

2013-09-01

Patient registries represent an important method of organizing "real world" patient information for clinical and research purposes. Registries can facilitate clinical trial planning and recruitment and are particularly useful in this regard for uncommon and rare diseases. Neuromuscular diseases (NMDs) are individually rare but in aggregate have a significant prevalence. In Canada, information on NMDs is lacking. Barriers to performing Canadian multicentre NMD research exist which can be overcome by a comprehensive and collaborative NMD registry. We describe the objectives, design, feasibility and initial recruitment results for the Canadian Neuromuscular Disease Registry (CNDR). The CNDR is a clinic-based registry which launched nationally in June 2011, incorporates paediatric and adult neuromuscular clinics in British Columbia, Alberta, Ontario, Quebec, New Brunswick and Nova Scotia and, as of December 2012, has recruited 1161 patients from 12 provinces and territories. Complete medical datasets have been captured on 460 "index disease" patients. Another 618 "non-index" patients have been recruited with capture of physician-confirmed diagnosis and contact information. We have demonstrated the feasibility of blended clinic and central office-based recruitment. "Index disease" patients recruited at the time of writing include 253 with Duchenne and Becker muscular dystrophy, 161 with myotonic dystrophy, and 71 with ALS. The CNDR is a new nationwide registry of patients with NMDs that represents an important advance in Canadian neuromuscular disease research capacity. It provides an innovative platform for organizing patient information to facilitate clinical research and to expedite translation of recent laboratory findings into human studies.

United Kingdom Carotid Artery Stent Registry: Short- and Long-Term Outcomes

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

Goode, S. D., E-mail: s.goode@sheffield.ac.uk; Cleveland, T. J.; Gaines, P. A.

Background: Carotid artery stenting (CAS) has evolved to treat carotid artery disease with the intention of prevent stroke. The British Society of Interventional Radiologists developed a voluntary registry to monitor the practice of this novel procedure. We present the data from the United Kingdom (UK) CAS registry for short and long-term outcomes for symptomatic and asymptomatic carotid disease. Methods: The UK CAS registry collected data from 1998 to 2010 from 31 hospitals across the UK for 1,154 patients. All interventions were enrolled in the registry for both asymptomatic and symptomatic patients. Initial entry forms were completed for each patient enteredmore » with data including indications, demographic data, CAS data (including stents and protection device details) and 30-day outcomes. Complications were documented. Follow-up data were collected at yearly intervals. Results: Nine hundred fifty-three (83 %) symptomatic and 201 (17 %) asymptomatic patients were enrolled into the registry. The 30-day all stroke and death rates for symptomatic patients were 5.5 and 2.2 % for those with asymptomatic disease. The 30-day mortality rate was 1.7 % for symptomatic and 0.6 % for asymptomatic patients. For symptomatic patients undergoing CAS, the 7-year all-cause mortality rate was 22.2 % and for asymptomatic patients 18.1 %. The 7-year all-cause mortality and disabling stroke rates were 25.3 and 19.4 %, respectively. Conclusion: These data indicate that outside of the tight constraints of a randomised trial, CAS provides effective prophylaxis against stroke and death.« less

Development of a core outcome set for disease modification trials in mild to moderate dementia: a systematic review, patient and public consultation and consensus recommendations.

PubMed Central

Webster, Lucy; Groskreutz, Derek; Grinbergs-Saull, Anna; Howard, Rob; O'Brien, John T; Mountain, Gail; Banerjee, Sube; Woods, Bob; Perneczky, Robert; Lafortune, Louise; Roberts, Charlotte; McCleery, Jenny; Pickett, James; Bunn, Frances; Challis, David; Charlesworth, Georgina; Featherstone, Katie; Fox, Chris; Goodman, Claire; Jones, Roy; Lamb, Sallie; Moniz-Cook, Esme; Schneider, Justine; Shepperd, Sasha; Surr, Claire; Thompson-Coon, Jo; Ballard, Clive; Brayne, Carol; Burke, Orlaith; Burns, Alistair; Clare, Linda; Garrard, Peter; Kehoe, Patrick; Passmore, Peter; Holmes, Clive; Maidment, Ian; Murtagh, Fliss; Robinson, Louise; Livingston, Gill

2017-01-01

BACKGROUND There is currently no disease-modifying treatment available to halt or delay the progression of the disease pathology in dementia. An agreed core set of the best-available and most appropriate outcomes for disease modification would facilitate the design of trials and ensure consistency across disease modification trials, as well as making results comparable and meta-analysable in future trials. OBJECTIVES To agree a set of core outcomes for disease modification trials for mild to moderate dementia with the UK dementia research community and patient and public involvement (PPI). DATA SOURCES We included disease modification trials with quantitative outcomes of efficacy from (1) references from related systematic reviews in workstream 1; (2) searches of the Cochrane Dementia and Cognitive Improvement Group study register, Cochrane Central Register of Controlled Trials, Cumulative Index to Nursing and Allied Health Literature, EMBASE, Latin American and Caribbean Health Sciences Literature and PsycINFO on 11 December 2015, and clinical trial registries [International Standard Randomised Controlled Trial Number (ISRCTN) and clinicaltrials.gov] on 22 and 29 January 2016; and (3) hand-searches of reference lists of relevant systematic reviews from database searches. REVIEW METHODS The project consisted of four workstreams. (1) We obtained related core outcome sets and work from co-applicants. (2) We systematically reviewed published and ongoing disease modification trials to identify the outcomes used in different domains. We extracted outcomes used in each trial, recording how many used each outcome and with how many participants. We divided outcomes into the domains measured and searched for validation data. (3) We consulted with PPI participants about recommended outcomes. (4) We presented all the synthesised information at a conference attended by the wider body of National Institute for Health Research (NIHR) dementia researchers to reach consensus on a core set of outcomes. RESULTS We included 149 papers from the 22,918 papers screened, referring to 125 individual trials. Eighty-one outcomes were used across trials, including 72 scales [31 cognitive, 12 activities of daily living (ADLs), 10 global, 16 neuropsychiatric and three quality of life] and nine biological techniques. We consulted with 18 people for PPI. The conference decided that only cognition and biological markers are core measures of disease modification. Cognition should be measured by the Mini Mental State Examination (MMSE) or the Alzheimer's Disease Assessment Scale - Cognitive subscale (ADAS-Cog), and brain changes through structural magnetic resonance imaging (MRI) in a subset of participants. All other domains are important but not core. We recommend using the Neuropsychiatric Inventory for neuropsychiatric symptoms: the Disability Assessment for Dementia for ADLs, the Dementia Quality of Life Measure for quality of life and the Clinical Dementia Rating scale to measure dementia globally. LIMITATIONS Most of the trials included participants with Alzheimer's disease, so recommendations may not apply to other types of dementia. We did not conduct economic analyses. The PPI consultation was limited to members of the Alzheimer's Society Research Network. CONCLUSIONS Cognitive outcomes and biological markers form the core outcome set for future disease modification trials, measured by the MMSE or ADAS-Cog, and structural MRI in a subset of participants. FUTURE WORK We envisage that the core set may be superseded in the future, particularly for other types of dementia. There is a need to develop an algorithm to compare scores on the MMSE and ADAS-Cog. STUDY REGISTRATION The project was registered with Core Outcome Measures in Effectiveness Trials [ www.comet-initiative.org/studies/details/819?result=true (accessed 7 April 2016)]. The systematic review protocol is registered as PROSPERO CRD42015027346. FUNDING The National Institute for Health Research Health Technology Assessment programme. PMID:28625273

The First 500 Registrations to the Research Registry®: Advancing Registration of Under-Registered Study Types.

PubMed

Agha, Riaz; Fowler, Alexander J; Limb, Christopher; Al Omran, Yasser; Sagoo, Harkiran; Koshy, Kiron; Jafree, Daniyal J; Anwar, Mohammed Omer; McCullogh, Peter; Orgill, Dennis Paul

2016-01-01

The Declaration of Helsinki 2013 encourages the registration of all research studies involving human participants. However, emphasis has been placed on prospective clinical trials, and it is estimated that only 10% of observational studies are registered. In response, Research Registry ® was launched in February 2015; a retrospectively curated registry that is free and easy to use. Research Registry ® enables prospective or retrospective registration of studies, including those study types that cannot be registered on existing registries. In this study, we describe the first 500 registrations on Research Registry ® . Since the launch of Research Registry ® in February 2015, data of registrations have been collected, including type of studies registered, country of origin, and data curation activity. Inappropriate registrations, such as duplicates, were identified by the data curation process. These were removed from the database or modified as required. A quality score was assigned for each registration, based on Sir Austin Bradford Hill's criteria on what research studies should convey. Changes in quality scores over time were assessed. A total of 500 studies were registered on Research Registry ® from February 2015 to October 2015, with a total of 1.7 million patients enrolled. The most common study types were retrospective cohort studies (37.2%), case series (14.8%), and first-in-man case reports (10.4%). Registrations were received from 57 different countries; the most submissions were received from Turkey, followed by China and the United Kingdom. Retrospective data curation identified 80 studies that were initially registered as the incorrect study type, and were subsequently correct. The Kruskal-Wallis test identified a significant improvement in quality scores for registrations from February 2015 to October 2015 ( p  < 0.0001). Since its conception in February 2015, Research Registry ® has established itself as a new registry that is free, easy to use, and enables the registration of various study types, including observational studies and first-in-man case reports. Going forward, our plan is to continue developing Research Registry ® in line with user feedback and usability studies. We plan to further promote Research Registry ® to advance the cause of registration of research, to increase compliance with the Declaration of Helsinki 2013.

Leflunomide is equally efficacious and safe compared to low dose rituximab in refractory rheumatoid arthritis given in combination with methotrexate: results from a randomized double blind controlled clinical trial.

PubMed

Wijesinghe, Harindu; Galappatthy, Priyadharshini; de Silva, Rajiva; Seneviratne, Suranjith L; Saravanamuttu, Ushagowry; Udagama, Preethi; Hart, Melanie; Kelleher, Peter; Senerath, Upul; Fernandopulle, Rohini; Weerasekera, Lilani P; Wijayaratne, Lalith S

2017-07-19

The standard dose of rituximab used in rheumatoid arthritis (RA) is 1000 mg but recent studies have shown that low dose (500 mg) is also effective. Efficacy of low dose rituximab in rheumatoid arthritis (RA) refractory to first-line non-biologic Disease Modifying Anti Rheumatic Drugs (DMARDs), compared to leflunomide is unknown. In a tertiary care referral setting, we conducted a randomized, double blind controlled clinical trial comparing the efficacy and safety of low-dose rituximab-methotrexate combination with leflunomide-methotrexate combination. Patients on methotrexate (10-20 mg/week) with a Disease Activity Score (DAS) > 3.2 were randomly assigned to rituximab (500 mg on days 1 and 15) or leflunomide (10-20 mg/day). The primary end-point was ACR20 at 24 weeks. Sample of 40 had 70% power to detect a 30% difference. ACR50, ACR70, DAS, EULAR good response, CD3 + (T cell), CD19 + (B cell) and CD19 + CD27+ (memory B cell) counts, tetanus and pneumococcal antibody levels were secondary end points. Baseline characteristics were comparable in the two groups. At week 24, ACR20 was 85% vs 84% (p = 0.93), ACR50 was 60% vs. 64% (p = 0.79) and ACR70 was 35% vs 32% (P = 0.84), in rituximab and in leflunomide groups respectively. Serious adverse events were similar. With rituximab there was significant reduction in B cells (p < 0.001), memory B cells (p < 0.001) and pneumococcal antibody levels (P < 0.05) without significant changes in T cells (p = 0.835) and tetanus antibody levels (p = 0.424) at 24 weeks. With leflunomide, significant reduction in memory B cells (p < 0.01) and pneumococcal antibody levels (p < 0.01) occurred without significant changes in B cells (P > 0.05), T cells (P > 0.05) or tetanus antibody levels (P > 0.05). Leflunomide-methotrexate combination is as efficacious as low-dose rituximab-methotrexate combination at 24 weeks, in RA patient's refractory to initial DMARDs. The high responses seen in both groups have favorable cost implications for patients in developing countries. Changes in immune parameters with leflunomide are novel and need further characterization. The trial was registered with the Sri Lanka Clinical Trials Registry (SLCTR), a publicly accessible primary registry linked to the registry network of the International Clinical Trials Registry Platform of the WHO (WHO-ICTRP) (registration number: SLCTR/2008/008 dated 16th May 2008).

Embedding clinical interventions into observational studies

PubMed Central

Newman, Anne B.; Avilés-Santa, M. Larissa; Anderson, Garnet; Heiss, Gerardo; Howard, Wm. James; Krucoff, Mitchell; Kuller, Lewis H.; Lewis, Cora E.; Robinson, Jennifer G.; Taylor, Herman; Treviño, Roberto P.; Weintraub, William

2017-01-01

Novel approaches to observational studies and clinical trials could improve the cost-effectiveness and speed of translation of research. Hybrid designs that combine elements of clinical trials with observational registries or cohort studies should be considered as part of a long-term strategy to transform clinical trials and epidemiology, adapting to the opportunities of big data and the challenges of constrained budgets. Important considerations include study aims, timing, breadth and depth of the existing infrastructure that can be leveraged, participant burden, likely participation rate and available sample size in the cohort, required sample size for the trial, and investigator expertise. Community engagement and stakeholder (including study participants) support are essential for these efforts to succeed. PMID:26611435

Differences in reporting serious adverse events in industry sponsored clinical trial registries and journal articles on antidepressant and antipsychotic drugs: a cross-sectional study

PubMed Central

Hughes, Shannon; Cohen, David; Jaggi, Rachel

2014-01-01

Objective To examine the degree of concordance in reporting serious adverse events (SAEs) from antidepressant and antipsychotic drug trials among journal articles and clinical trial summaries, and to categorise types of discrepancies. Design Cross-sectional study of summaries of all antidepressant and antipsychotic trials included in an online trial registry and their first associated stand-alone journal articles. Setting Clinicalstudyresults.org, sponsored by Pharmaceutical Research and Manufacturers of America; clinicaltrials.gov, administered by the US National Institutes of Health. Main outcome measure 3 coders extracted data on the numbers and types of SAEs. Results 244 trial summaries for six antidepressant and antipsychotic drugs were retrieved, 142 (58.2%) listing an associated article. Of 1608 SAEs in drug-treated participants according to trial summaries, 694 (43.2%) did not appear in associated articles. Nearly 60% of SAEs counted in articles and 41% in trial summaries had no description. Most cases of death (62.3%) and suicide (53.3%) were not reported in articles. Half or more of the 142 pairs were discordant in reporting the number (49.3%) or description (67.6%) of SAEs. These discrepancies resulted from journal articles’ (1) omission of complete SAE data, (2) reporting acute phase study results only and (3) more restrictive reporting criteria. Trial summaries with zero SAE were 2.35 (95% CI, 1.58 to 3.49; p<0.001) times more likely to be published with no discrepancy in their associated journal article. Since clinicalstudyresults.org was removed from the Internet in 2011, only 7.8% of retrieved trial summaries appear with results on clinicaltrials.gov. Conclusions Substantial discrepancies exist in SAE data found in journal articles and registered summaries of antidepressant and antipsychotic drug trials. Two main scientific sources accessible to clinicians and researchers are limited by incomplete, ambiguous and inconsistent reporting. Access to complete and accurate data from clinical trials of drugs currently in use remains a pressing concern. PMID:25009136

Photorefractive keratectomy (PRK) versus laser assisted in situ keratomileusis (LASIK) for hyperopia correction.

PubMed

Settas, George; Settas, Clare; Minos, Evangelos; Yeung, Ian Yl

2012-06-13

Hyperopia, or hypermetropia (also known as long-sightedness or far-sightedness), is the condition where the unaccommodating eye brings parallel light to a focus behind the retina instead of on it. Hyperopia can be corrected with both non-surgical and surgical methods, among them photorefractive keratectomy (PRK) and laser assisted In situ keratomileusis (LASIK). There is uncertainty as to whether hyperopic-PRK or hyperopic-LASIK is the better method. The objectives of this review were to determine whether PRK or LASIK leads to more reliable, stable and safe results when correcting a hyperopic refractive error. We searched CENTRAL (which contains the Cochrane Eyes and Vision Group Trials Register) (The Cochrane Library 2012, Issue 2), MEDLINE (January 1950 to February 2012), EMBASE (January 1980 to February 2012), Latin American and Caribbean Literature on Health Sciences (LILACS) (January 1982 to February 2012), the metaRegister of Controlled Trials (mRCT) (www.controlled-trials.com), ClinicalTrials.gov (www.clinicaltrials.gov) and the WHO International Clinical Trials Registry Platform (ICTRP) (www.who.int/ictrp/search/en). There were no date or language restrictions in the electronic searches for trials. The electronic databases were last searched on 17 February 2012. When trials are included in the review we will search the reference lists of the studies included in the review for information about further trials. We will use the Science Citation Index to search for papers that cite any studies included in this review. We did not handsearch journals or conference proceedings specifically for this review. We planned to include only randomised controlled trials (RCTs) comparing PRK against LASIK for correction of hyperopia and then perform a sensitivity analysis of pre- and post-millennial trials since this is the mid-point in the history of both PRK and LASIK. We did not identify any studies that met the inclusion criteria for this review. As no studies met the inclusion criteria for this review, we discussed the results of non-randomised trials comparing hyperopic-PRK with hyperopic-LASIK. No robust, reliable conclusions could be reached, but the non-randomised trials reviewed appear to be in agreement that hyperopic-PRK and hyperopic-LASIK are of comparable efficacy. High quality, well-planned open RCTs are needed in order to obtain a robust clinical evidence base.

Acute pancreatitis patient registry to examine novel therapies in clinical experience (APPRENTICE): an international, multicenter consortium for the study of acute pancreatitis

PubMed Central

Papachristou, Georgios I.; Machicado, Jorge D.; Stevens, Tyler; Goenka, Mahesh Kumar; Ferreira, Miguel; Gutierrez, Silvia C.; Singh, Vikesh K.; Kamal, Ayesha; Gonzalez-Gonzalez, Jose A.; Pelaez-Luna, Mario; Gulla, Aiste; Zarnescu, Narcis O.; Triantafyllou, Konstantinos; Barbu, Sorin T.; Easler, Jeffrey; Ocampo, Carlos; Capurso, Gabriele; Archibugi, Livia; Cote, Gregory A.; Lambiase, Louis; Kochhar, Rakesh; Chua, Tiffany; Tiwari, Subhash Ch.; Nawaz, Haq; Park, Walter G.; de-Madaria, Enrique; Lee, Peter J.; Wu, Bechien U.; Greer, Phil J.; Dugum, Mohannad; Koutroumpakis, Efstratios; Akshintala, Venkata; Gougol, Amir

2017-01-01

Background We have established a multicenter international consortium to better understand the natural history of acute pancreatitis (AP) worldwide and to develop a platform for future randomized clinical trials. Methods The AP patient registry to examine novel therapies in clinical experience (APPRENTICE) was formed in July 2014. Detailed web-based questionnaires were then developed to prospectively capture information on demographics, etiology, pancreatitis history, comorbidities, risk factors, severity biomarkers, severity indices, health-care utilization, management strategies, and outcomes of AP patients. Results Between November 2015 and September 2016, a total of 20 sites (8 in the United States, 5 in Europe, 3 in South America, 2 in Mexico and 2 in India) prospectively enrolled 509 AP patients. All data were entered into the REDCap (Research Electronic Data Capture) database by participating centers and systematically reviewed by the coordinating site (University of Pittsburgh). The approaches and methodology are described in detail, along with an interim report on the demographic results. Conclusion APPRENTICE, an international collaboration of tertiary AP centers throughout the world, has demonstrated the feasibility of building a large, prospective, multicenter patient registry to study AP. Analysis of the collected data may provide a greater understanding of AP and APPRENTICE will serve as a future platform for randomized clinical trials. PMID:28042246

EARLY Treatment with azilsartan compared to ACE-inhibitors in anti-hypertensive therapy--rationale and design of the EARLY hypertension registry.

PubMed

Gitt, Anselm K; Baumgart, Peter; Bramlage, Peter; Mahfoud, Felix; Potthoff, Sebastian A; Senges, Jochen; Schneider, Steffen; Buhck, Hartmut; Schmieder, Roland E

2013-07-02

Arterial hypertension is highly prevalent but poorly controlled. Blood pressure (BP) reduction substantially reduces cardiovascular morbidity and mortality. Recent randomized, double-blind clinical trials demonstrated that azilsartan medoxomil (AZM) is more effective in reducing BP than the ubiquitary ACE inhibitor ramipril. Therefore, we aimed to test whether these can be verified under clinical practice conditions. The "Treatment with Azilsartan Compared to ACE-Inhibitors in Anti-Hypertensive Therapy" (EARLY) registry is a prospective, observational, national, multicenter registry with a follow-up of up to 12 months. It will include up to 5000 patients on AZM or ACE-inhibitor monotherapy in a ratio of 7 to 3. A subgroup of patients will undergo 24-hour BP monitoring. EARLY has two co-primary objectives: 1) Description of the safety profile of azilsartan and 2) achievement of BP targets based on recent national and international guidelines for patients treated with azilsartan in comparison to those treated with ACE-inhibitors. The most important secondary endpoints are the determination of persistence with treatment and the documentation of cardiovascular and renal events. Recruitment commenced in January 2012 and will be completed by February 2013. The data obtained will supplement previous results from randomized controlled trials to document the potential value of utilizing azilsartan medoxomil in comparison to ACE-inhibitor treatment for target BP achievement in clinical practice.

Efficacy and safety of mepivacaine compared with lidocaine in local anaesthesia in dentistry: a meta-analysis of randomised controlled trials.

PubMed

Su, Naichuan; Liu, Yan; Yang, Xianrui; Shi, Zongdao; Huang, Yi

2014-04-01

The objective of the study was to assess the efficacy and safety of mepivacaine compared with lidocaine used in local anaesthesia in dentistry. Medline, Cochrane Central Register of Controlled Trials, EMBASE, Chinese BioMedical Literature Database, China National Knowledge Infrastructure and WHO International Clinical Trials Registry Platform were searched electronically. Relevant journals and references of studies included were hand-searched for randomised controlled trials comparing mepivacaine with lidocaine in terms of efficacy and safety. Twenty-eight studies were included, of which 15 had low risk of bias and 13 had moderate risk of bias. In comparison with 2% lidocaine with 1:100,000 adrenaline, 3% mepivacaine showed a lower success rate (P = 0.05), a shorter onset time of pulpal anaesthesia (P = 0.0005), inferior pain control during injection phase and superior inhibition of heart rate increase (P < 0.0001). In contrast, 2% mepivacaine with 1:100,000 adrenaline gave a higher success rate (P < 0.00001), a similar onset time of pulpal anaesthesia (P = 0.34) and superior pain control during injection phase (P < 0.0001); 2% mepivacaine with 1:20,000 levonordefrin had the same success rate (P = 0.69) and similar onset time of pulpal anaesthesia (P = 0.90). In addition, 3% mepivacaine had shorter onset time (P = 0.004), same level of success rate (P = 0.28) and similar pain control during injection and postinjection compared with 2% lidocaine with 1:50,000 adrenaline. Given the efficacy and safety of the two solutions, 2% mepivacaine with vasoconstrictors is better than 2% lidocaine with vasoconstrictors in dental treatment. Meanwhile, 3% plain mepivacaine is better for patients with cardiac diseases. © 2014 FDI World Dental Federation.

Pharmacotherapies for fatigue in chronic liver disease (CLD): a systematic review and meta-analysis (protocol).

PubMed

Effiong, Andem; Kumari, Prerna

2018-02-14

This is the protocol for a systematic review (and meta-analysis) of an intervention. The primary objective of this systematic review will be to assess the benefits and harms of pharmacological therapies (pharmacotherapies) for the management of fatigue in adults with CLD of any etiology. The effects of pharmacological therapies on fatigue in CLD will be compared against those of placebo, no intervention, or non-pharmacological interventions. Specifically, this review will examine whether pharmacological therapies improve CLD-associated fatigue, and if they do, what key elements are associated with their effectiveness. The results of this systematic review will assist clinicians, policy-makers, researchers, and people with CLD in decision-making on how best to manage fatigue and its associated symptoms. MEDLINE, SCOPUS, EMBASE, EU Clinical Trials Register, WHO International Clinical Trials Registry Platform, CENTRAL (The Cochrane Library), ClinicalTrials.gov, reference lists of articles and conference proceedings will be searched for relevant studies. No language or date restrictions will be applied. Eligible studies will include adults with CLD of any etiology. Included studies will be randomized controlled trials. From included studies, data on participant characteristics, study design, setting, research ethics compliance, and intervention outcomes will be extracted. Risk of bias in included studies will be assessed using the Cochrane Risk of Bias Tool. A random-effects meta-analysis will be conducted. If substantial or considerable levels of heterogeneity are detected, analysis will be limited to a narrative synthesis. This systematic review will examine the effectiveness of pharmacological therapies on fatigue reduction in people with CLD. Such therapies may be more effective than non-pharmacological interventions in treating fatigue symptoms in CLD. Evidence derived from the findings of this study will guide future practice, policy, and research. PROSPERO, CRD42017076957.

Meta-analysis of selective serotonin reuptake inhibitors in patients with depression and coronary heart disease.

PubMed

Pizzi, Carmine; Rutjes, Anne Wilhelmina Saskia; Costa, Grazia Maria; Fontana, Fiorella; Mezzetti, Andrea; Manzoli, Lamberto

2011-04-01

The occurrence of depression in patients with coronary heart disease (CHD) substantially increases the likelihood of a poorer cardiovascular prognosis. Although antidepressants are generally effective in decreasing depression, their use in patients with CHD is controversial. We carried out a meta-analysis to evaluate the health effects of selective serotonin reuptake inhibitors (SSRIs) versus placebo or no antidepressants in patients with CHD and depression. Observational studies and randomized controlled trials (RCTs) were searched in MEDLINE, EMBASE, PsycINFO, Cochrane Controlled Clinical Trial Register and other trial registries, and references of relevant articles. Primary outcomes were readmission for CHD (including myocardial infarction, unstable angina, and stroke) and all-cause mortality; the secondary outcome was severity of depression symptoms. Seven articles on 6 RCTs involving 2,461 participants were included. One study incorrectly randomized participants, and another was a reanalysis of RCT data. These were considered observational and analyzed separately. When only properly randomized trials were considered (n = 734 patients), patients on SSRIs showed no significant differences in mortality (risk ratio 0.39, 95% confidence interval 0.08 to 2.01) or CHD readmission rates (0.74, 0.44 to 1.23) compared to controls. Conversely, when all studies were included, SSRI use was associated with a significant decrease in CHD readmission (0.63, 0.46 to 0.86) and mortality rates (0.56, 0.35 to 0.88). A significantly greater improvement in depression symptoms was always apparent in patients on SSRIs with all selected indicators. In conclusion, in patients with CHD and depression, SSRI medication decreases depression symptoms and may improve CHD prognosis. Crown Copyright © 2011. Published by Elsevier Inc. All rights reserved.

Efficacy and safety of bupivacaine versus lidocaine in dental treatments: a meta-analysis of randomised controlled trials.

PubMed

Su, Naichuan; Wang, Hang; Zhang, Shu; Liao, Shuang; Yang, Shuying; Huang, Yi

2014-02-01

The objective of this study was to assess the efficacy and safety of bupivacaine compared with lidocaine in local anaesthesia in dental treatment. Medline, Cochrane Central Register of Controlled Trials, EMBASE, Chinese BioMedical Literature Database, China National Knowledge Infrastructure, and the World Health Organisation (WHO) International Clinical Trials Registry Platform were searched electronically. Relevant journals and references of studies included were hand-searched for randomised controlled trials comparing bupivacaine with lidocaine in terms of efficacy and safety. Sixteen studies were included, of which nine had low, six had moderate and one had high risk of bias. In comparison with 2% lidocaine plus 1:100,000 adrenaline, 0.5% bupivacaine plus 1:200,000 adrenaline showed a higher success rate in inflamed pulp (P = 0.03) but a lower success rate in vital pulp (P < 0.00001), a lower percentage of patients using postoperative analgesics (P < 0.00001), a longer onset times of pulpal anaesthesia and a longer duration of pulpal anaesthesia (P < 0.00001). In comparison with 2% lidocaine plus 1:80,000 adrenaline, 0.75% bupivacaine plus 1:200,000 adrenaline had same level of success rate (P = 0.29), and was better in postoperative pain control (P = 0.001) while 0.75% levobupivacaine had same level of postoperative pain control (P = 0.16); 0.5% levobupivacaine had higher success rate (P = 0.04) and was better in postoperative pain control (P = 0.001) than 2% lidocaine. There was no statistically significance in adverse events between two groups. Given the efficacy and safety, the bupivacaine group is better than the lidocaine group in dental operations that take a relatively long time, especially in endodontic treatments or where there is a need for postoperative pain management. © 2013 FDI World Dental Federation.

Completeness of Reporting of Patient-Relevant Clinical Trial Outcomes: Comparison of Unpublished Clinical Study Reports with Publicly Available Data

PubMed Central

Wieseler, Beate; Wolfram, Natalia; McGauran, Natalie; Kerekes, Michaela F.; Vervölgyi, Volker; Kohlepp, Petra; Kamphuis, Marloes; Grouven, Ulrich

2013-01-01

Background Access to unpublished clinical study reports (CSRs) is currently being discussed as a means to allow unbiased evaluation of clinical research. The Institute for Quality and Efficiency in Health Care (IQWiG) routinely requests CSRs from manufacturers for its drug assessments. Our objective was to determine the information gain from CSRs compared to publicly available sources (journal publications and registry reports) for patient-relevant outcomes included in IQWiG health technology assessments (HTAs) of drugs. Methods and Findings We used a sample of 101 trials with full CSRs received for 16 HTAs of drugs completed by IQWiG between 15 January 2006 and 14 February 2011, and analyzed the CSRs and the publicly available sources of these trials. For each document type we assessed the completeness of information on all patient-relevant outcomes included in the HTAs (benefit outcomes, e.g., mortality, symptoms, and health-related quality of life; harm outcomes, e.g., adverse events). We dichotomized the outcomes as “completely reported” or “incompletely reported.” For each document type, we calculated the proportion of outcomes with complete information per outcome category and overall. We analyzed 101 trials with CSRs; 86 had at least one publicly available source, 65 at least one journal publication, and 50 a registry report. The trials included 1,080 patient-relevant outcomes. The CSRs provided complete information on a considerably higher proportion of outcomes (86%) than the combined publicly available sources (39%). With the exception of health-related quality of life (57%), CSRs provided complete information on 78% to 100% of the various benefit outcomes (combined publicly available sources: 20% to 53%). CSRs also provided considerably more information on harms. The differences in completeness of information for patient-relevant outcomes between CSRs and journal publications or registry reports (or a combination of both) were statistically significant for all types of outcomes. The main limitation of our study is that our sample is not representative because only CSRs provided voluntarily by pharmaceutical companies upon request could be assessed. In addition, the sample covered only a limited number of therapeutic areas and was restricted to randomized controlled trials investigating drugs. Conclusions In contrast to CSRs, publicly available sources provide insufficient information on patient-relevant outcomes of clinical trials. CSRs should therefore be made publicly available. Please see later in the article for the Editors' Summary PMID:24115912

Genetics Home Reference: GM3 synthase deficiency

MedlinePlus

... GM3 synthase deficiency is characterized by recurrent seizures (epilepsy) and problems with brain development. Within the first ... Testing (1 link) Genetic Testing Registry: Amish infantile epilepsy syndrome Other Diagnosis and Management Resources (2 links) ...

Genetics Home Reference: Boucher-Neuhäuser syndrome

MedlinePlus

... the cerebellum ). Affected individuals have an unsteady walking style (gait) and frequent falls. Another key feature of ... be inherited? More about Inheriting Genetic Conditions Diagnosis & Management Resources Genetic Testing (1 link) Genetic Testing Registry: ...

Improvement of the National Program of Cancer Registries Act

THOMAS, 111th Congress

Sen. Sanders, Bernard [I-VT

2009-04-02

Senate - 04/02/2009 Read twice and referred to the Committee on Health, Education, Labor, and Pensions. (All Actions) Tracker: This bill has the status IntroducedHere are the steps for Status of Legislation:

Measuring energy expenditure in the intensive care unit: a comparison of indirect calorimetry by E-sCOVX and Quark RMR with Deltatrac II in mechanically ventilated critically ill patients.

PubMed

Rehal, Martin Sundström; Fiskaare, Erik; Tjäder, Inga; Norberg, Åke; Rooyackers, Olav; Wernerman, Jan

2016-03-05

Indirect calorimetry allows the determination of energy expenditure in critically ill patients by measuring oxygen consumption (VO2) and carbon dioxide production (VCO2). Recent studies have demonstrated variable performance of "breath-by-breath" instruments compared to mixing chamber technology. The aim of this study was to validate two modern devices (E-sCOVX and Quark RMR) against a reference method (Deltatrac II). Measurements of VO2/VCO2 with the test and reference devices were performed simultaneously over a 20-min period in mechanically ventilated adult intensive care unit patients. Accuracy and precision of instruments were analyzed using Bland-Altman plots. Forty-eight measurements in 22 patients were included for analysis. Both E-sCOVX and Quark RMR overestimated VO2 and VCO2 compared to Deltatrac II, corresponding to a 10% higher mean resting energy expenditure. Limits of agreement of resting energy expenditure within ± 2 standard deviations were ± 461 kcal/24 h (± 21% expressed as percentage error) for ΔE-sCOVX-Deltatrac II and ± 465 kcal/24 h (± 22%) for ΔQuark RMR-Deltatrac II. Both test devices overestimate VO2 and VCO2 compared to Deltatrac II. The observed limits of agreement are comparable to those commonly accepted in evaluations of circulatory monitoring, and significantly less than results from predictive equations. We hypothesize that the discrepancy between methods is due to patient/ventilator-related factors that affect the synchronization of gas and spirometry waveforms. Australian New Zealand Clinical Trials Registry, Trial ID ACTRN12615000205538. Date registered 3 March 2015.

The impact of population-based disease management services for selected chronic conditions: the Costs to Australian Private Insurance--Coaching Health (CAPICHe) study protocol.

PubMed

Byrnes, Joshua M; Goldstein, Stan; Venator, Benjamin; Pollicino, Christine; Ng, Shu-Kay; Veroff, David; Bennett, Christine; Scuffham, Paul A

2012-02-10

Recent evidence from a large scale trial conducted in the United States indicates that enhancing shared decision-making and improving knowledge, self-management, and provider communication skills to at-risk patients can reduce health costs and utilisation of healthcare resources. Although this trial has provided a significant advancement in the evidence base for disease management programs it is still left for such results to be replicated and/or generalised for populations in other countries and other healthcare environments. This trial responds to the limited analyses on the effectiveness of providing chronic disease management services through telephone health coaching in Australia. The size of this trial and it's assessment of cost utility with respect to potentially preventable hospitalisations adds significantly to the body of knowledge to support policy and investment decisions in Australia as well as to the international debate regarding the effect of disease management programs on financial outcomes. Intention to treat study applying a prospective randomised design comparing usual care with extensive outreach to encourage use of telephone health coaching for those people identified from a risk scoring algorithm as having a higher likelihood of future health costs. The trial population has been limited to people with one or more of the following selected chronic conditions: namely, low back pain, diabetes, coronary artery disease, heart failure, and chronic obstructive pulmonary disease. This trial will enrol at least 64,835 sourced from the approximately 3 million Bupa Australia private health insured members located across Australia. The primary outcome will be the total (non-maternity) cost per member as reported to the private health insurer (i.e. charged to the insurer) 12 months following entry into the trial for each person. Study recruitment will be completed in early 2012 and the results will be available in late 2013. If positive, CAPICHe will represent a potentially cost-effective strategy to improve health outcomes in higher risk individuals with a chronic condition, in a private health insurance setting. Australian New Zealand Clinical Trials Registry reference: ACTRN12611000580976.

Physiotherapy intervention in Parkinson's disease: systematic review and meta-analysis.

PubMed

Tomlinson, Claire L; Patel, Smitaa; Meek, Charmaine; Herd, Clare P; Clarke, Carl E; Stowe, Rebecca; Shah, Laila; Sackley, Catherine; Deane, Katherine H O; Wheatley, Keith; Ives, Natalie

2012-08-06

To assess the effectiveness of physiotherapy compared with no intervention in patients with Parkinson's disease. Systematic review and meta-analysis of randomised controlled trials. Literature databases, trial registries, journals, abstract books, and conference proceedings, and reference lists, searched up to the end of January 2012. Randomised controlled trials comparing physiotherapy with no intervention in patients with Parkinson's disease were eligible. Two authors independently abstracted data from each trial. Standard meta-analysis methods were used to assess the effectiveness of physiotherapy compared with no intervention. Tests for heterogeneity were used to assess for differences in treatment effect across different physiotherapy interventions used. Outcome measures were gait, functional mobility and balance, falls, clinician rated impairment and disability measures, patient rated quality of life, adverse events, compliance, and economic analysis outcomes. 39 trials of 1827 participants met the inclusion criteria, of which 29 trials provided data for the meta-analyses. Significant benefit from physiotherapy was reported for nine of 18 outcomes assessed. Outcomes which may be clinically significant were speed (0.04 m/s, 95% confidence interval 0.02 to 0.06, P<0.001), Berg balance scale (3.71 points, 2.30 to 5.11, P<0.001), and scores on the unified Parkinson's disease rating scale (total score -6.15 points, -8.57 to -3.73, P<0.001; activities of daily living subscore -1.36, -2.41 to -0.30, P=0.01; motor subscore -5.01, -6.30 to -3.72, P<0.001). Indirect comparisons of the different physiotherapy interventions found no evidence that the treatment effect differed across the interventions for any outcomes assessed, apart from motor subscores on the unified Parkinson's disease rating scale (in which one trial was found to be the cause of the heterogeneity). Physiotherapy has short term benefits in Parkinson's disease. A wide range of physiotherapy techniques are currently used to treat Parkinson's disease, with little difference in treatment effects. Large, well designed, randomised controlled trials with improved methodology and reporting are needed to assess the efficacy and cost effectiveness of physiotherapy for treating Parkinson's disease in the longer term.

A cross-sectional analysis of HIV and hepatitis C clinical trials 2007 to 2010: the relationship between industry sponsorship and randomized study design.

PubMed

Goswami, Neela D; Tsalik, Ephraim L; Naggie, Susanna; Miller, William C; Horton, John R; Pfeiffer, Christopher D; Hicks, Charles B

2014-01-22

The proportion of clinical research sponsored by industry will likely continue to expand as federal funds for academic research decreases, particularly in the fields of HIV/AIDS and hepatitis C (HCV). While HIV and HCV continue to burden the US population, insufficient data exists as to how industry sponsorship affects clinical trials involving these infectious diseases. Debate exists about whether pharmaceutical companies undertake more market-driven research practices to promote therapeutics, or instead conduct more rigorous trials than their non-industry counterparts because of increased resources and scrutiny. The ClinicalTrials.gov registry, which allows investigators to fulfill a federal mandate for public trial registration, provides an opportunity for critical evaluation of study designs for industry-sponsored trials, independent of publication status. As part of a large public policy effort, the Clinical Trials Transformation Initiative (CTTI) recently transformed the ClinicalTrials.gov registry into a searchable dataset to facilitate research on clinical trials themselves. We conducted a cross-sectional analysis of 477 HIV and HCV drug treatment trials, registered with ClinicalTrials.gov from 1 October 2007 to 27 September 2010, to study the relationship of study sponsorship with randomized study design. The likelihood of using randomization given industry (versus non-industry) sponsorship was reported with prevalence ratios (PR). PRs were estimated using crude and stratified tabular analysis and Poisson regression adjusting for presence of a data monitoring committee, enrollment size, study phase, number of study sites, inclusion of foreign study sites, exclusion of persons older than age 65, and disease condition. The crude PR was 1.17 (95% CI 0.94, 1.45). Adjusted Poisson models produced a PR of 1.13 (95% CI 0.82, 1.56). There was a trend toward mild effect measure modification by study phase, but this was not statistically significant. In stratified tabular analysis the adjusted PR was 1.14 (95% CI 0.78, 1.68) among phase 2/3 trials and 1.06 (95% CI 0.50, 2.22) among phase 4 trials. No significant relationship was found between industry sponsorship and use of randomization in trial design in this cross-sectional study. Prospective studies evaluating other aspects of trial design may shed further light on the relationship between industry sponsorship and appropriate trial methodology.

A cross-sectional analysis of HIV and hepatitis C clinical trials 2007 to 2010: the relationship between industry sponsorship and randomized study design

PubMed Central

2014-01-01

Background The proportion of clinical research sponsored by industry will likely continue to expand as federal funds for academic research decreases, particularly in the fields of HIV/AIDS and hepatitis C (HCV). While HIV and HCV continue to burden the US population, insufficient data exists as to how industry sponsorship affects clinical trials involving these infectious diseases. Debate exists about whether pharmaceutical companies undertake more market-driven research practices to promote therapeutics, or instead conduct more rigorous trials than their non-industry counterparts because of increased resources and scrutiny. The ClinicalTrials.gov registry, which allows investigators to fulfill a federal mandate for public trial registration, provides an opportunity for critical evaluation of study designs for industry-sponsored trials, independent of publication status. As part of a large public policy effort, the Clinical Trials Transformation Initiative (CTTI) recently transformed the ClinicalTrials.gov registry into a searchable dataset to facilitate research on clinical trials themselves. Methods We conducted a cross-sectional analysis of 477 HIV and HCV drug treatment trials, registered with ClinicalTrials.gov from 1 October 2007 to 27 September 2010, to study the relationship of study sponsorship with randomized study design. The likelihood of using randomization given industry (versus non-industry) sponsorship was reported with prevalence ratios (PR). PRs were estimated using crude and stratified tabular analysis and Poisson regression adjusting for presence of a data monitoring committee, enrollment size, study phase, number of study sites, inclusion of foreign study sites, exclusion of persons older than age 65, and disease condition. Results The crude PR was 1.17 (95% CI 0.94, 1.45). Adjusted Poisson models produced a PR of 1.13 (95% CI 0.82, 1.56). There was a trend toward mild effect measure modification by study phase, but this was not statistically significant. In stratified tabular analysis the adjusted PR was 1.14 (95% CI 0.78, 1.68) among phase 2/3 trials and 1.06 (95% CI 0.50, 2.22) among phase 4 trials. Conclusions No significant relationship was found between industry sponsorship and use of randomization in trial design in this cross-sectional study. Prospective studies evaluating other aspects of trial design may shed further light on the relationship between industry sponsorship and appropriate trial methodology. PMID:24450313

Massage, reflexology and other manual methods for pain management in labour.

PubMed

Smith, Caroline A; Levett, Kate M; Collins, Carmel T; Jones, Leanne

2012-02-15

Many women would like to avoid pharmacological or invasive methods of pain management in labour, and this may contribute towards the popularity of complementary methods of pain management. This review examined currently available evidence supporting the use of manual healing methods including massage and reflexology for pain management in labour. To examine the effects of manual healing methods including massage and reflexology for pain management in labour on maternal and perinatal morbidity. We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (30 June 2011), the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2011, Issue 2 of 4), MEDLINE (1966 to 30 June 2011), CINAHL (1980 to 30 June 2011), the Australian and New Zealand Clinical Trial Registry (30 June 2011), Chinese Clinical Trial Register (30 June 2011), Current Controlled Trials (30 June 2011), ClinicalTrials.gov, (30 June 2011) ISRCTN Register (30 June 2011), National Centre for Complementary and Alternative Medicine (NCCAM) (30 June 2011) and the WHO International Clinical Trials Registry Platform (30 June 2011). Randomised controlled trials comparing manual healing methods with standard care, no treatment, other non-pharmacological forms of pain management in labour or placebo. Two authors independently assessed trial quality and extracted data. We attempted to contact study authors for additional information. We included six trials, with data reporting on five trials and 326 women in the meta-analysis. We found trials for massage only. Less pain during labour was reported from massage compared with usual care during the first stage of labour (standardised mean difference (SMD) -0.82, 95% confidence interval (CI) -1.17 to -0.47), four trials, 225 women), and labour pain was reduced in one trial of massage compared with music (risk ratio (RR) 0.40, 95% CI 0.18 to 0.89, 101 women). One trial of massage compared with usual care found reduced anxiety during the first stage of labour (MD -16.27, 95% CI -27.03 to -5.51, 60 women). No trial was assessed as being at a low risk of bias for all quality domains. Massage may have a role in reducing pain, and improving women's emotional experience of labour. However, there is a need for further research.

The CRAC cohort model: A computerized low cost registry of interventional cardiology with daily update and long-term follow-up.

PubMed

Rangé, G; Chassaing, S; Marcollet, P; Saint-Étienne, C; Dequenne, P; Goralski, M; Bardiére, P; Beverilli, F; Godillon, L; Sabine, B; Laure, C; Gautier, S; Hakim, R; Albert, F; Angoulvant, D; Grammatico-Guillon, L

2018-05-01

To assess the reliability and low cost of a computerized interventional cardiology (IC) registry to prospectively and systematically collect high-quality data for all consecutive coronary patients referred for coronary angiogram or/and coronary angioplasty. Rigorous clinical practice assessment is a key factor to improve prognosis in IC. A prospective and permanent registry could achieve this goal but, presumably, at high cost and low level of data quality. One multicentric IC registry (CRAC registry), fully integrated to usual coronary activity report software, started in the centre Val-de-Loire (CVL) French region in 2014. Quality assessment of CRAC registry was conducted on five IC CathLab of the CVL region, from January 1st to December 31st 2014. Quality of collected data was evaluated by measuring procedure exhaustivity (comparing with data from hospital information system), data completeness (quality controls) and data consistency (by checking complete medical charts as gold standard). Cost per procedure (global registry operating cost/number of collected procedures) was also estimated. CRAC model provided a high-quality level with 98.2% procedure completeness, 99.6% data completeness and 89% data consistency. The operating cost per procedure was €14.70 ($16.51) for data collection and quality control, including ST-segment elevation myocardial infarction (STEMI) preadmission information and one-year follow-up after angioplasty. This integrated computerized IC registry led to the construction of an exhaustive, reliable and costless database, including all coronary patients entering in participating IC centers in the CVL region. This solution will be developed in other French regions, setting up a national IC database for coronary patients in 2020: France PCI. Copyright © 2018 Elsevier Masson SAS. All rights reserved.

A Comparative Reference Study for the Validation of HLA-Matching Algorithms in the Search for Allogeneic Hematopoietic Stem Cell Donors and Cord Blood Units

DTIC Science & Technology

2016-08-15

HLA ISSN 2059-2302 A comparative reference study for the validation of HLA-matching algorithms in the search for allogeneic hematopoietic stem cell...from different inter- national donor registries by challenging them with simulated input data and subse- quently comparing the output. This experiment...original work is properly cited, the use is non-commercial and no modifications or adaptations are made. Comparative reference validation of HLA

Safety and effectiveness of the INVATEC MO.MA proximal cerebral protection device during carotid artery stenting: results from the ARMOUR pivotal trial.

PubMed

Ansel, Gary M; Hopkins, L Nelson; Jaff, Michael R; Rubino, Paolo; Bacharach, J Michael; Scheinert, Dierk; Myla, Subbarao; Das, Tony; Cremonesi, Alberto

2010-07-01

The multicenter ARMOUR (ProximAl PRotection with the MO.MA Device DUring CaRotid Stenting) trial evaluated the 30-day safety and effectiveness of the MO.MA Proximal Cerebral Protection Device (Invatec, Roncadelle, Italy) utilized to treat high surgical risk patients undergoing carotid artery stenting (CAS). Distal embolic protection devices (EPD) have been traditionally utilized during CAS. The MO.MA device acts as a balloon occlusion "endovascular clamping" system to achieve cerebral protection prior to crossing the carotid stenosis. This prospective registry enrolled 262 subjects, 37 roll-in and 225 pivotal subjects evaluated with intention to treat (ITT) from September 2007 to February 2009. Subjects underwent CAS using the MO.MA device. The primary endpoint, myocardial infarction, stroke, or death through 30 days (30-day major adverse cardiac and cerebrovascular events [MACCE]) was compared to a performance goal of 13% derived from trials utilizing distal EPD. For the ITT population, the mean age was 74.7 years with 66.7% of the cohort being male. Symptomatic patients comprised 15.1% and 28.9% were octogenarians. Device success was 98.2% and procedural success was 93.2%. The 30-day MACCE rate was 2.7% [95% CI (1.0-5.8%)] with a 30-day major stroke rate of 0.9%. No symptomatic patient suffered a stroke during this trial. The ARMOUR trial demonstrated that the MO.MA(R) Proximal Cerebral Protection Device is safe and effective for high surgical risk patients undergoing CAS. The absence of stroke in symptomatic patients is the lowest rate reported in any independently adjudicated prospective multicenter registry trial to date. (c) 2010 Wiley-Liss, Inc.

Funding characteristics of randomised clinical trials supported by the Swiss National Science Foundation: a retrospective cohort study.

PubMed

Amstutz, Alain; Schandelmaier, Stefan; Frei, Roy; Surina, Jakub; Agarwal, Arnav; Alturki, Reem; von Niederhäusern, Belinda; von Elm, Erik; Briel, Matthias; On Behalf Of The MAking Randomized Trials Affordable Marta Group

2018-01-29

Failure to publish publicly funded research represents a waste of scarce research resources across medical disciplines and countries. In Switzerland, about 40% of randomised clinical trials (RCTs) supported by the Swiss National Science Foundation (SNSF) were not published. We aimed to describe funding characteristics of published and unpublished RCTs supported by the SNSF, to quantify the amount of money spent for unpublished studies, and to compare our results to a similar study performed in the UK. We established a retrospective cohort of RCTs funded by the SNSF up to 2015. For each RCT proposal, two investigators independently identified corresponding publications in electronic databases and trial registries. Teams of two investigators independently extracted details from the original SNSF proposal and, if available, from trial registries or publications. In addition, we surveyed principal investigators about trial costs and additional sources of funding. We included 101 RCTs supported by the SNSF between 1986 and 2015. Most were single-centre RCTs with a median of 138 participants (interquartile range [IQR] 76-400). Overall, 67 (67%) principal investigators responded to our main survey questions. Median total costs per RCT were CHF 428 000 (IQR 282 000-900 000) of which the SNSF provided a median CHF 222 000 (67% of total costs, IQR 40-80%). Most investigators (70%) mentioned additional funding, mainly from their own institution or private foundations. A total of CHF 6.7 million was granted to RCTs that remained unpublished. Funding characteristics were similar to publicly funded trials in the UK. A third of the total SNSF grant sum spent on healthcare RCTs between 1986 and 2015 did not result in peer-reviewed scientific publications. New SNSF grant schemes might improve publication outcomes but their effectiveness needs to be evaluated.

A systematic review assessing non-pharmacological conservative treatment studies for people with non-inflammatory multi-joint pain: clinical outcomes and research design considerations.

PubMed

Comer, C; Smith, T O; Drew, B; Raja, R; Kingsbury, S R; Conaghan, Philip G

2018-03-01

To systematically review the evidence to determine the clinical outcomes and the important methodological quality features of interventional studies on adults with non-inflammatory multi-joint pain (MJP). Systematic search of published and unpublished literature using the databases: AMED, CINAHL, MEDLINE, EMBASE, psycINFO, SPORTDiscus, PEDro, OpenGrey, the EU Clinical Trials Register, World Health Organization International Clinical Trial Registry Platform, ClinicalTrials.gov and the ISRCTN registry (search: inception to 19th October 2017). All papers reporting the clinical outcomes of non-pharmacological interventions for people with non-inflammatory MJP were included. Studies were critically appraised using the Downs and Black Critical Appraisal and the TIDieR reporting checklists. Data were analysed using a Best Evidence Synthesis approach. From 3824 citations, four papers satisfied the eligibility criteria. Three studies reported outcomes from multidisciplinary rehabilitation programmes and one study reported the findings of a spa therapy intervention. All interventions significantly improved pain, function and quality of life in the short-term. There was limited reporting of measures for absenteeism, presenteeism and psychosocial outcomes. The evidence was 'weak', and due to a lack of controlled trials, there is limited evidence to ascertain treatment effectiveness. Design consideration for future trials surround improved reporting of participant characteristics, interventions and the standardisation of core outcome measures. There is insufficient high-quality trial data to determine the effectiveness of treatments for non-inflammatory MJP. Given the significant health burden which this condition presents on both individuals and wider society, developing and testing interventions and accurately reporting these, should be a research priority. Registration PROSPERO (CRD42013005888).

Eligibility for clinical trials in primary Sjögren’s syndrome: lessons from the UK Primary Sjögren’s Syndrome Registry

PubMed Central

Oni, Clare; Mitchell, Sheryl; James, Katherine; Ng, Wan-Fai; Griffiths, Bridget; Hindmarsh, Victoria; Price, Elizabeth; Pease, Colin T.; Emery, Paul; Lanyon, Peter; Jones, Adrian; Bombardieri, Michele; Sutcliffe, Nurhan; Pitzalis, Costantino; Hunter, John; Gupta, Monica; McLaren, John; Cooper, Annie; Regan, Marian; Giles, Ian; Isenberg, David; Saravanan, Vadivelu; Coady, David; Dasgupta, Bhaskar; McHugh, Neil; Young-Min, Steven; Moots, Robert; Gendi, Nagui; Akil, Mohammed; Barone, Francesca; Fisher, Ben; Rauz, Saaeha; Richards, Andrea; Bowman, Simon J.

2016-01-01

Abstract Objective: To identify numbers of participants in the UK Primary Sjögren’s Syndrome Registry (UKPSSR) who would fulfil eligibility criteria for previous/current or potential clinical trials in primary SS (pSS) in order to optimize recruitment. Methods: We did a retrospective analysis of UKPSSR cohort data of 688 participants who had pSS with evaluable data. Results: In relation to previous/current trials, 75.2% fulfilled eligibility for the Belimumab in Subjects with Primary Sjögren’s Syndrome study (Belimumab), 41.4% fulfilled eligibility for the Trial of Remicade in primary Sjögren’s syndrome study (Infliximab), 35.4% for the Efficacy of Tocilizumab in Primary Sjögren’s Syndrome study (Tocilizumab), 46.3% for the Tolerance and Efficacy of Rituximab in Sjögren’s Disease study (Rituximab), 26.9% for the Trial of anti-B-cell therapy in pSS study (Rituximab) and 26.6% for the Efficacy and Safety of Abatacept in Patients With Primary Sjögren’s Syndrome study (Abatacept). If recent measures of outcome, such as the EULAR Sjögren’s Syndrome Patient Reported Index (ESSPRI) score ⩾5 (measure of patient symptoms) and the EULAR Sjögren’s Syndrome Disease Activity Index (ESSDAI) score ⩾5 (measure of systemic disease activity) are incorporated into a study design, with requirements for an unstimulated salivary flow >0 and anti-Ro positivity, then the pool of eligible participants is reduced to 14.3%. Conclusion: The UKPSSR identified a number of options for trial design, including selection on ESSDAI ⩾5, ESSPRI ⩾5 and serological and other parameters. PMID:26510429

Eligibility for clinical trials in primary Sjögren's syndrome: lessons from the UK Primary Sjögren's Syndrome Registry.

PubMed

Oni, Clare; Mitchell, Sheryl; James, Katherine; Ng, Wan-Fai; Griffiths, Bridget; Hindmarsh, Victoria; Price, Elizabeth; Pease, Colin T; Emery, Paul; Lanyon, Peter; Jones, Adrian; Bombardieri, Michele; Sutcliffe, Nurhan; Pitzalis, Costantino; Hunter, John; Gupta, Monica; McLaren, John; Cooper, Annie; Regan, Marian; Giles, Ian; Isenberg, David; Saravanan, Vadivelu; Coady, David; Dasgupta, Bhaskar; McHugh, Neil; Young-Min, Steven; Moots, Robert; Gendi, Nagui; Akil, Mohammed; Barone, Francesca; Fisher, Ben; Rauz, Saaeha; Richards, Andrea; Bowman, Simon J

2016-03-01

To identify numbers of participants in the UK Primary Sjögren's Syndrome Registry (UKPSSR) who would fulfil eligibility criteria for previous/current or potential clinical trials in primary SS (pSS) in order to optimize recruitment. We did a retrospective analysis of UKPSSR cohort data of 688 participants who had pSS with evaluable data. In relation to previous/current trials, 75.2% fulfilled eligibility for the Belimumab in Subjects with Primary Sjögren's Syndrome study (Belimumab), 41.4% fulfilled eligibility for the Trial of Remicade in primary Sjögren's syndrome study (Infliximab), 35.4% for the Efficacy of Tocilizumab in Primary Sjögren's Syndrome study (Tocilizumab), 31.6% for the Tolerance and Efficacy of Rituximab in Sjögren's Disease study (Rituximab), 26.9% for the Trial of anti-B-cell therapy in pSS study (Rituximab) and 26.6% for the Efficacy and Safety of Abatacept in Patients With Primary Sjögren's Syndrome study (Abatacept). If recent measures of outcome, such as the EULAR Sjögren's Syndrome Patient Reported Index (ESSPRI) score ⩾5 (measure of patient symptoms) and the EULAR Sjögren's Syndrome Disease Activity Index (ESSDAI) score ⩾5 (measure of systemic disease activity) are incorporated into a study design, with requirements for an unstimulated salivary flow >0 and anti-Ro positivity, then the pool of eligible participants is reduced to 14.3%. The UKPSSR identified a number of options for trial design, including selection on ESSDAI ⩾5, ESSPRI ⩾5 and serological and other parameters. © The Author 2015. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Structures Validation Profiles in Transmission of Imaging and Data (TRIAD) for Automated NCTN Clinical Trial Digital Data Quality Assurance

PubMed Central

Giaddui, Tawfik; Yu, Jialu; Manfredi, Denise; Linnemann, Nancy; Hunter, Joanne; O’Meara, Elizabeth; Galvin, James; Bialecki, Brian; Xiao, Ying

2016-01-01

Transmission of Imaging and Data (TRIAD) is a standard-based system built by the American College of Radiology (ACR) to provide seamless exchange of images and data for accreditation of clinical trials and registries. Scripts of structures’ names validation profiles created in TRIAD are used in the automated submission process. It is essential for users to understand the logistics of these scripts for successful submission of radiotherapy cases with less iteration. PMID:27053498

SPIRIT 2013 Statement: defining standard protocol items for clinical trials.

PubMed

Chan, An-Wen; Tetzlaff, Jennifer M; Altman, Douglas G; Laupacis, Andreas; Gøtzsche, Peter C; Krle A-Jerić, Karmela; Hrobjartsson, Asbjørn; Mann, Howard; Dickersin, Kay; Berlin, Jesse A; Dore, Caroline J; Parulekar, Wendy R; Summerskill, William S M; Groves, Trish; Schulz, Kenneth F; Sox, Harold C; Rockhold, Frank W; Rennie, Drummond; Moher, David

2015-12-01

The protocol of a clinical trial serves as the foundation for study planning, conduct, reporting, and appraisal. However, trial protocols and existing protocol guidelines vary greatly in content and quality. This article describes the systematic development and scope of SPIRIT (Standard Protocol Items: Recommendations for Interventional Trials) 2013, a guideline for the minimum content of a clinical trial protocol. The 33-item SPIRIT checklist applies to protocols for all clinical trials and focuses on content rather than format. The checklist recommends a full description of what is planned; it does not prescribe how to design or conduct a trial. By providing guidance for key content, the SPIRIT recommendations aim to facilitate the drafting of high-quality protocols. Adherence to SPIRIT would also enhance the transparency and completeness of trial protocols for the benefit of investigators, trial participants, patients, sponsors, funders, research ethics committees or institutional review boards, peer reviewers, journals, trial registries, policymakers, regulators, and other key stakeholders.

SPIRIT 2013 Statement: Defining Standard Protocol Items for Clinical Trials

PubMed Central

Chan, An-Wen; Tetzlaff, Jennifer M.; Altman, Douglas G.; Laupacis, Andreas; Gøtzsche, Peter C.; Krleža-Jerić, Karmela; Hróbjartsson, Asbjørn; Mann, Howard; Dickersin, Kay; Berlin, Jesse A.; Doré, Caroline J.; Parulekar, Wendy R.; Summerskill, William S.M.; Groves, Trish; Schulz, Kenneth F.; Sox, Harold C.; Rockhold, Frank W.; Rennie, Drummond; Moher, David

2016-01-01

The protocol of a clinical trial serves as the foundation for study planning, conduct, reporting, and appraisal. However, trial protocols and existing protocol guidelines vary greatly in content and quality. This article describes the systematic development and scope of SPIRIT (Standard Protocol Items: Recommendations for Interventional Trials) 2013, a guideline for the minimum content of a clinical trial protocol. The 33-item SPIRIT checklist applies to protocols for all clinical trials and focuses on content rather than format. The checklist recommends a full description of what is planned; it does not prescribe how to design or conduct a trial. By providing guidance for key content, the SPIRIT recommendations aim to facilitate the drafting of high-quality protocols. Adherence to SPIRIT would also enhance the transparency and completeness of trial protocols for the benefit of investigators, trial participants, patients, sponsors, funders, research ethics committees or institutional review boards, peer reviewers, journals, trial registries, policymakers, regulators, and other key stakeholders. PMID:23295957

SPIRIT 2013 statement: defining standard protocol items for clinical trials.

PubMed

Chan, An-Wen; Tetzlaff, Jennifer M; Altman, Douglas G; Laupacis, Andreas; Gøtzsche, Peter C; Krleža-Jerić, Karmela; Hróbjartsson, Asbjørn; Mann, Howard; Dickersin, Kay; Berlin, Jesse A; Doré, Caroline J; Parulekar, Wendy R; Summerskill, William S M; Groves, Trish; Schulz, Kenneth F; Sox, Harold C; Rockhold, Frank W; Rennie, Drummond; Moher, David

2013-02-05

The protocol of a clinical trial serves as the foundation for study planning, conduct, reporting, and appraisal. However, trial protocols and existing protocol guidelines vary greatly in content and quality. This article describes the systematic development and scope of SPIRIT (Standard Protocol Items: Recommendations for Interventional Trials) 2013, a guideline for the minimum content of a clinical trial protocol.The 33-item SPIRIT checklist applies to protocols for all clinical trials and focuses on content rather than format. The checklist recommends a full description of what is planned; it does not prescribe how to design or conduct a trial. By providing guidance for key content, the SPIRIT recommendations aim to facilitate the drafting of high-quality protocols. Adherence to SPIRIT would also enhance the transparency and completeness of trial protocols for the benefit of investigators, trial participants, patients, sponsors, funders, research ethics committees or institutional review boards, peer reviewers, journals, trial registries, policymakers, regulators, and other key stakeholders.

Trends in Recruitment Rates for Acute Stroke Trials, 1990-2014.

PubMed

Feldman, William B; Kim, Anthony S; Chiong, Winston

2017-03-01

Slow recruitment in acute stroke trials hampers the evaluation of new therapies and delays the adoption of effective therapies into clinical practice. This systematic review evaluates whether recruitment efficiency and rates have increased in acute stroke trials from 1990 to 2014. Acute stroke trials from 2010 to 2014 were identified by a search of PubMed, Medline, the Cochrane Database of Research in Stroke, and the Stroke Trials Registry. These trials were compared to a previously published data set of trials conducted from 1990 to 2004. The median recruitment efficiency of trials from 1990 to 2004 was 0.41 participants/site/month compared with 0.26 participants/site/month from 2010 to 2014 ( P =0.14). The median recruitment rate of trials from 1990 to 2004 was 26.8 participants/month compared with 19.0 participants/month from 2010 to 2014 ( P =0.13). For acute stroke trials, neither recruitment efficiency nor recruitment rates have increased over the past 25 years and, if anything, have declined. © 2017 American Heart Association, Inc.

The Database for Aggregate Analysis of ClinicalTrials.gov (AACT) and Subsequent Regrouping by Clinical Specialty

PubMed Central

Tasneem, Asba; Aberle, Laura; Ananth, Hari; Chakraborty, Swati; Chiswell, Karen; McCourt, Brian J.; Pietrobon, Ricardo

2012-01-01

Background The ClinicalTrials.gov registry provides information regarding characteristics of past, current, and planned clinical studies to patients, clinicians, and researchers; in addition, registry data are available for bulk download. However, issues related to data structure, nomenclature, and changes in data collection over time present challenges to the aggregate analysis and interpretation of these data in general and to the analysis of trials according to clinical specialty in particular. Improving usability of these data could enhance the utility of ClinicalTrials.gov as a research resource. Methods/Principal Results The purpose of our project was twofold. First, we sought to extend the usability of ClinicalTrials.gov for research purposes by developing a database for aggregate analysis of ClinicalTrials.gov (AACT) that contains data from the 96,346 clinical trials registered as of September 27, 2010. Second, we developed and validated a methodology for annotating studies by clinical specialty, using a custom taxonomy employing Medical Subject Heading (MeSH) terms applied by an NLM algorithm, as well as MeSH terms and other disease condition terms provided by study sponsors. Clinical specialists reviewed and annotated MeSH and non-MeSH disease condition terms, and an algorithm was created to classify studies into clinical specialties based on both MeSH and non-MeSH annotations. False positives and false negatives were evaluated by comparing algorithmic classification with manual classification for three specialties. Conclusions/Significance The resulting AACT database features study design attributes parsed into discrete fields, integrated metadata, and an integrated MeSH thesaurus, and is available for download as Oracle extracts (.dmp file and text format). This publicly-accessible dataset will facilitate analysis of studies and permit detailed characterization and analysis of the U.S. clinical trials enterprise as a whole. In addition, the methodology we present for creating specialty datasets may facilitate other efforts to analyze studies by specialty groups. PMID:22438982

The database for aggregate analysis of ClinicalTrials.gov (AACT) and subsequent regrouping by clinical specialty.

PubMed

Tasneem, Asba; Aberle, Laura; Ananth, Hari; Chakraborty, Swati; Chiswell, Karen; McCourt, Brian J; Pietrobon, Ricardo

2012-01-01

The ClinicalTrials.gov registry provides information regarding characteristics of past, current, and planned clinical studies to patients, clinicians, and researchers; in addition, registry data are available for bulk download. However, issues related to data structure, nomenclature, and changes in data collection over time present challenges to the aggregate analysis and interpretation of these data in general and to the analysis of trials according to clinical specialty in particular. Improving usability of these data could enhance the utility of ClinicalTrials.gov as a research resource. The purpose of our project was twofold. First, we sought to extend the usability of ClinicalTrials.gov for research purposes by developing a database for aggregate analysis of ClinicalTrials.gov (AACT) that contains data from the 96,346 clinical trials registered as of September 27, 2010. Second, we developed and validated a methodology for annotating studies by clinical specialty, using a custom taxonomy employing Medical Subject Heading (MeSH) terms applied by an NLM algorithm, as well as MeSH terms and other disease condition terms provided by study sponsors. Clinical specialists reviewed and annotated MeSH and non-MeSH disease condition terms, and an algorithm was created to classify studies into clinical specialties based on both MeSH and non-MeSH annotations. False positives and false negatives were evaluated by comparing algorithmic classification with manual classification for three specialties. The resulting AACT database features study design attributes parsed into discrete fields, integrated metadata, and an integrated MeSH thesaurus, and is available for download as Oracle extracts (.dmp file and text format). This publicly-accessible dataset will facilitate analysis of studies and permit detailed characterization and analysis of the U.S. clinical trials enterprise as a whole. In addition, the methodology we present for creating specialty datasets may facilitate other efforts to analyze studies by specialty groups.

Effectiveness of an annular closure device in a "real-world" population: stratification of registry data using screening criteria from a randomized controlled trial.

PubMed

Kuršumović, Adisa; Rath, Stefan A

2018-01-01

Increased focus has been put on the use of "'real-world" data to support randomized clinical trial (RCT) evidence for clinical decision-making. The objective of this study was to assess the performance of an annular closure device (ACD) after stratifying a consecutive series of "real-world" patients by the screening criteria of an ongoing RCT. This was a single-center registry analysis of 164 subjects who underwent limited discectomy combined with ACD for symptomatic lumbar disc herniation. Patients were stratified into two groups using the selection criteria of a pivotal RCT on the same device: Trial (met inclusion; n=44) or non-Trial (did not meet inclusion; n=120). Patient-reported outcomes, including Oswestry Disability Index (ODI) and visual analog scale (VAS) for leg and back pain, and adverse events were collected from baseline to last follow-up (mean: Trial - 15.6 months; non-Trial - 14.6 months). Statistical analyses were performed with significance set at p <0.05. Patient-reported outcomes were not significantly different between groups at last ( p ≥0.15) and clinical success (≥15-point improvement in ODI score; ≥20-point improvement in VAS scores) was achieved in both the groups. Three non-Trial (2.5%) and three Trial (6.8%) patients experienced symptomatic reherniation ( p =0.34). Rates of reoperation, ACD mesh dislocation/separation, and other radiographic findings were similar between groups ( p =1.00). Outcomes with the ACD appeared advantageous in both the groups, particularly in comparison with historical reherniation rates reported in the same high-risk, large annular defect population. Stratification of this "real-world" series on the basis of RCT screening criteria did not result in significant between-group differences. These findings suggest that the efficacy of the ACD extends beyond the strictly defined patient population being studied in the RCT of this device. Furthermore, reducing the reherniation rate following lumbar discectomy has positive clinical and economic implications.

A method for using real world data in breast cancer modeling.

PubMed

Pobiruchin, Monika; Bochum, Sylvia; Martens, Uwe M; Kieser, Meinhard; Schramm, Wendelin

2016-04-01

Today, hospitals and other health care-related institutions are accumulating a growing bulk of real world clinical data. Such data offer new possibilities for the generation of disease models for the health economic evaluation. In this article, we propose a new approach to leverage cancer registry data for the development of Markov models. Records of breast cancer patients from a clinical cancer registry were used to construct a real world data driven disease model. We describe a model generation process which maps database structures to disease state definitions based on medical expert knowledge. Software was programmed in Java to automatically derive a model structure and transition probabilities. We illustrate our method with the reconstruction of a published breast cancer reference model derived primarily from clinical study data. In doing so, we exported longitudinal patient data from a clinical cancer registry covering eight years. The patient cohort (n=892) comprised HER2-positive and HER2-negative women treated with or without Trastuzumab. The models generated with this method for the respective patient cohorts were comparable to the reference model in their structure and treatment effects. However, our computed disease models reflect a more detailed picture of the transition probabilities, especially for disease free survival and recurrence. Our work presents an approach to extract Markov models semi-automatically using real world data from a clinical cancer registry. Health care decision makers may benefit from more realistic disease models to improve health care-related planning and actions based on their own data. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

Avelumab: A Review of Its Application in Metastatic Merkel Cell Carcinoma.

PubMed

Joseph, Jocelyn; Zobniw, Chrystia; Davis, Jennifer; Anderson, Jaime; Trinh, Van Anh

2018-04-01

To summarize the clinical development of avelumab and its clinical relevance in metastatic Merkel cell carcinoma (MCC). An English-language literature search using PubMed was performed using the terms avelumab, anti-PD-1, anti-PD-L1, and MCC from January of 1950 to March 2018. Data were also obtained from package inserts, meeting abstracts, and clinical registries. All relevant published articles of avelumab were reviewed. Clinical trial registries and meeting abstracts were used for information about ongoing trials. Avelumab is a fully human monoclonal antibody that inhibits programmed death ligand-1, which reverses T-cell exhaustion and induces antitumor responses. Avelumab is safe and effective in previously treated metastatic MCC based on a phase II trial of previously treated patients with objective response rates in 28 of 88 patients, including 10 complete responses and 19 partial responses. Median overall survival (OS) was 12.9 months, and 1-year progression-free survival and OS were 30% and 52%, respectively. Grade 3 treatment-related side effects included lymphopenia (2 patients), serum creatine phosphokinase increase (1 patient), aminotransferase elevation (1 patient), and serum cholesterol increase (1 patient). Relevance to Patient Care and Clinical Practice: This review outlines the pharmacology and clinical trial data for avelumab in metastatic MCC and guides clinicians on avelumab's place in therapy. Avelumab is the first Food and Drug Administration-approved medication for metastatic MCC and provides an advantage of durable responses and possibly improved tolerability compared with traditional platinum-based chemotherapy. Clinical trials are under way to expand its utility into the adjuvant and frontline settings.

Selective outcome reporting and sponsorship in randomized controlled trials in IVF and ICSI.

PubMed

Braakhekke, M; Scholten, I; Mol, F; Limpens, J; Mol, B W; van der Veen, F

2017-10-01

Are randomized controlled trials (RCTs) on IVF and ICSI subject to selective outcome reporting and is this related to sponsorship? There are inconsistencies, independent from sponsorship, in the reporting of primary outcome measures in the majority of IVF and ICSI trials, indicating selective outcome reporting. RCTs are subject to bias at various levels. Of these biases, selective outcome reporting is particularly relevant to IVF and ICSI trials since there is a wide variety of outcome measures to choose from. An established cause of reporting bias is sponsorship. It is, at present, unknown whether RCTs in IVF/ICSI are subject to selective outcome reporting and whether this is related with sponsorship. We systematically searched RCTs on IVF and ICSI published between January 2009 and March 2016 in MEDLINE, EMBASE, the Cochrane Central Register of Controlled Trials and the publisher subset of PubMed. We analysed 415 RCTs. Per included RCT, we extracted data on impact factor of the journal, sample size, power calculation, and trial registry and thereafter data on primary outcome measure, the direction of trial results and sponsorship. Of the 415 identified RCTs, 235 were excluded for our primary analysis, because the sponsorship was not reported. Of the 180 RCTs included in our analysis, 7 trials did not report on any primary outcome measure and 107 of the remaining 173 trials (62%) reported on surrogate primary outcome measures. Of the 114 registered trials, 21 trials (18%) provided primary outcomes in their manuscript that were different from those in the trial registry. This indicates selective outcome reporting. We found no association between selective outcome reporting and sponsorship. We ran additional analyses to include the trials that had not reported sponsorship and found no outcomes that differed from our primary analysis. Since the majority of the trials did not report on sponsorship, there is a risk on sampling bias. IVF and ICSI trials are subject, to a large extent, to selective outcome reporting. Readers should be aware of this to avoid implementation of false or misleading results in clinical practice. No funding received and there are no conflicts of interest. N/A. © The Author 2017. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com

Genetics Home Reference: cystic fibrosis

MedlinePlus

... Foundation) Genetic Testing (1 link) Genetic Testing Registry: Cystic fibrosis Other Diagnosis and Management Resources (5 links) American Society for Reproductive Medicine: Male Infertility Baby's First Test GeneReview: Cystic Fibrosis and Congenital Absence of the Vas Deferens Genomics ...

[WebSurvCa: web-based estimation of death and survival probabilities in a cohort].

PubMed

Clèries, Ramon; Ameijide, Alberto; Buxó, Maria; Vilardell, Mireia; Martínez, José Miguel; Alarcón, Francisco; Cordero, David; Díez-Villanueva, Ana; Yasui, Yutaka; Marcos-Gragera, Rafael; Vilardell, Maria Loreto; Carulla, Marià; Galceran, Jaume; Izquierdo, Ángel; Moreno, Víctor; Borràs, Josep M

2018-01-19

Relative survival has been used as a measure of the temporal evolution of the excess risk of death of a cohort of patients diagnosed with cancer, taking into account the mortality of a reference population. Once the excess risk of death has been estimated, three probabilities can be computed at time T: 1) the crude probability of death associated with the cause of initial diagnosis (disease under study), 2) the crude probability of death associated with other causes, and 3) the probability of absolute survival in the cohort at time T. This paper presents the WebSurvCa application (https://shiny.snpstats.net/WebSurvCa/), whereby hospital-based and population-based cancer registries and registries of other diseases can estimate such probabilities in their cohorts by selecting the mortality of the relevant region (reference population). Copyright © 2017 SESPAS. Publicado por Elsevier España, S.L.U. All rights reserved.

A Standard Nomenclature for Referencing and Authentication of Pluripotent Stem Cells.

PubMed

Kurtz, Andreas; Seltmann, Stefanie; Bairoch, Amos; Bittner, Marie-Sophie; Bruce, Kevin; Capes-Davis, Amanda; Clarke, Laura; Crook, Jeremy M; Daheron, Laurence; Dewender, Johannes; Faulconbridge, Adam; Fujibuchi, Wataru; Gutteridge, Alexander; Hei, Derek J; Kim, Yong-Ou; Kim, Jung-Hyun; Kokocinski, Anja Kolb-; Lekschas, Fritz; Lomax, Geoffrey P; Loring, Jeanne F; Ludwig, Tenneille; Mah, Nancy; Matsui, Tohru; Müller, Robert; Parkinson, Helen; Sheldon, Michael; Smith, Kelly; Stachelscheid, Harald; Stacey, Glyn; Streeter, Ian; Veiga, Anna; Xu, Ren-He

2018-01-09

Unambiguous cell line authentication is essential to avoid loss of association between data and cells. The risk for loss of references increases with the rapidity that new human pluripotent stem cell (hPSC) lines are generated, exchanged, and implemented. Ideally, a single name should be used as a generally applied reference for each cell line to access and unify cell-related information across publications, cell banks, cell registries, and databases and to ensure scientific reproducibility. We discuss the needs and requirements for such a unique identifier and implement a standard nomenclature for hPSCs, which can be automatically generated and registered by the human pluripotent stem cell registry (hPSCreg). To avoid ambiguities in PSC-line referencing, we strongly urge publishers to demand registration and use of the standard name when publishing research based on hPSC lines. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

Herbal medicine for low-back pain.

PubMed

Oltean, Hanna; Robbins, Chris; van Tulder, Maurits W; Berman, Brian M; Bombardier, Claire; Gagnier, Joel J

2014-12-23

Low-back pain (LBP) is a common condition and imposes a substantial economic burden upon people living in industrialized societies. A large proportion of people with chronic LBP use complementary and alternative medicine (CAM), visit CAM practitioners, or both. Several herbal medicines have been purported for use in treating people with LBP. This is an update of a Cochrane Review first published in 2006. To determine the effectiveness of herbal medicine for non-specific LBP. We searched the following electronic databases up to September 2014: MEDLINE, EMBASE, CENTRAL, CINAHL, Clinical Trials.gov, World Health Organization International Clinical Trials Registry Portal and PubMed; checked reference lists in review articles, guidelines and retrieved trials; and personally contacted individuals with expertise in this area. We included randomized controlled trials (RCTs) examining adults (over 18 years of age) suffering from acute, sub-acute, or chronic non-specific LBP. The interventions were herbal medicines which we defined as plants used for medicinal purposes in any form. Primary outcome measures were pain and function. A library scientist with the Cochrane Back Review Group conducted the database searches. One review author contacted content experts and acquired relevant citations. We downloaded full references and abstracts of the identified studies and retrieved a hard copy of each study for final inclusion decisions. Two review authors assessed risk of bias, GRADE criteria (GRADE 2004), and CONSORT compliance and a random subset were compared to assessments by a third individual. Two review authors assessed clinical relevance and resolved any disagreements by consensus. We included 14 RCTs (2050 participants) in this review. One trial on Solidago chilensis M. (Brazilian arnica) (20 participants) found very low quality evidence of reduction in perception of pain and improved flexibility with application of Brazilian arnica-containing gel twice daily as compared to placebo gel. Capsicum frutescens cream or plaster probably produces more favourable results than placebo in people with chronic LBP (three trials, 755 participants, moderate quality evidence). Based on current evidence, it is not clear whether topical capsicum cream is more beneficial for treating people with acute LBP compared to placebo (one trial, 40 participants, low quality evidence). Another trial found equivalence of C. frutescens cream to a homeopathic ointment (one trial, 161 participants, very low quality evidence). Daily doses of Harpagophytum procumbens (devil's claw), standardized to 50 mg or 100 mg harpagoside, may be better than placebo for short-term improvements in pain and may reduce use of rescue medication (two trials, 315 participants, low quality evidence). Another H. procumbens trial demonstrated relative equivalence to 12.5 mg per day of rofecoxib (Vioxx®) but was of very low quality (one trial, 88 participants, very low quality). Daily doses of Salix alba (white willow bark), standardized to 120 mg or 240 mg salicin, are probably better than placebo for short-term improvements in pain and rescue medication (two trials, 261 participants, moderate quality evidence). An additional trial demonstrated relative equivalence to 12.5 mg per day of rofecoxib (one trial, 228 participants) but was graded as very low quality evidence. S. alba minimally affected platelet thrombosis versus a cardioprotective dose of acetylsalicylate (one trial, 51 participants). One trial (120 participants) examining Symphytum officinale L. (comfrey root extract) found low quality evidence that a Kytta-Salbe comfrey extract ointment is better than placebo ointment for short-term improvements in pain as assessed by VAS. Aromatic lavender essential oil applied by acupressure may reduce subjective pain intensity and improve lateral spine flexion and walking time compared to untreated participants (one trial, 61 participants,very low quality evidence). No significant adverse events were noted within the included trials. C. frutescens (Cayenne) reduces pain more than placebo. Although H. procumbens, S. alba, S. officinale L., S. chilensis, and lavender essential oil also seem to reduce pain more than placebo, evidence for these substances was of moderate quality at best. Additional well-designed large trials are needed to test these herbal medicines against standard treatments. In general, the completeness of reporting in these trials was poor. Trialists should refer to the CONSORT statement extension for reporting trials of herbal medicine interventions.

Information provision for people with multiple sclerosis.

PubMed

Köpke, Sascha; Solari, Alessandra; Khan, Fary; Heesen, Christoph; Giordano, Andrea

2014-04-21

People with multiple sclerosis (MS) are confronted with a number of important uncertainties concerning many aspects of the disease. Among others, these include diagnosis, prognosis, disease course, disease-modifying therapies, symptomatic therapies and non-pharmacological interventions. It has been shown that people with MS demand adequate information to be able to actively participate in medical decision making and to self-manage their disease. On the other hand, it has been found that patients' disease-related knowledge is poor. Therefore, guidelines have recommended clear and concise high-quality information at all stages of the disease. Several studies have outlined communication and information deficits in the care of people with MS and, accordingly, a number of information and decision support programmes have been published. To evaluate the effectiveness of information provision interventions for people with MS that aim to promote informed choice and improve patient-relevant outcomes. We searched the Cochrane Multiple Sclerosis and Rare Diseases of the Central Nervous System Group Specialised Register which contains trials from CENTRAL (The Cochrane Library 2013, Issue 6), MEDLINE, EMBASE, CINAHL, LILACS, PEDro and clinical trials registries (12 June 2013) as well as other sources. In addition, we searched PsycINFO, trial registries, and reference lists of identified articles. We also contacted trialists. Randomised controlled trials, cluster randomised controlled trials and quasi-randomised trials comparing information provision for people with MS or suspected MS (intervention groups) with usual care or other types of information provision (control groups) were eligible. Two review authors independently assessed the retrieved articles for relevance and methodological quality, and extracted data. Critical appraisal of studies addressed the risk of selection bias, performance bias, attrition bias and detection bias. We contacted authors of relevant studies for additional information. Ten randomised controlled trials involving a total of 1314 participants met the inclusion criteria and were analysed. The interventions addressed a variety of topics using different approaches for information provision in different settings. Topics included disease-modifying therapy, relapse management, self-care strategies, fatigue management, family planning and general health promotion. The interventions contained decision aids, educational programmes, self-care interventions and personal interviews with physicians. All interventions were complex interventions using more than one active component, but the number and extent of the intervention components differed markedly between studies. The studies had a variable risk of bias. We did not perform meta-analyses due to marked clinical heterogeneity. All four studies assessing MS-related knowledge (524 participants; moderate-quality evidence) detected significant differences between groups as a result of the interventions indicating that information provision may successfully increase participants' knowledge. There were mixed results from four studies reporting effects on decision making (836 participants; low-quality evidence) and from five studies assessing quality of life (605 participants; low-quality evidence). There were no adverse events in the six studies reporting on adverse events. Information provision for people with MS seems to increase disease-related knowledge, with less clear results on decision making and quality of life. There seem to be no negative side effects from informing patients about their disease. Interpretation of study results remains challenging due to the marked heterogeneity of the interventions and outcome measures.

Over the counter (OTC) artificial tear drops for dry eye syndrome

PubMed Central

Pucker, Andrew D; Ng, Sueko M; Nichols, Jason J

2016-01-01

Background Over the counter (OTC) artificial tears historically have been the first line of treatment for dry eye syndrome and dry eye-related conditions like contact lens discomfort, yet currently we know little regarding the overall efficacy of individual, commercially available artificial tears. This review provides a much needed meta-analytical look at all randomized and quasi-randomized clinical trials that have analyzed head-to-head comparisons of OTC artificial tears. Objectives To evaluate the effectiveness and toxicity of OTC artificial tear applications in the treatment of dry eye syndrome compared with another class of OTC artificial tears, no treatment, or placebo. Search methods We searched CENTRAL (which contains the Cochrane Eyes and Vision Trials Register) (2015, Issue 12), Ovid MEDLINE, Ovid MEDLINE In-Process and Other Non-Indexed Citations, Ovid MEDLINE Daily, Ovid OLDMEDLINE (January 1946 to December 2015), EMBASE (January 1980 to December 2015), Latin American and Caribbean Health Sciences (LILACS) (January 1982 to December 2015), the ISRCTN registry (www.isrctn.com/editAdvancedSearch), ClinicalTrials.gov (www.clinicaltrials.gov), the World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP) (www.who.int/ictrp/search/en) and the US Food and Drugs Administration (FDA) website (www.fda.gov). We did not use any date or language restrictions in the electronic searches for trials. We last searched the electronic databases on 4 December 2015. We searched reference lists of included trials for any additional trials not identified by the electronic searches. Selection criteria This review includes randomized controlled trials with adult participants who were diagnosed with dry eye, regardless of race and gender. We included trials in which the age of participants was not reported, and clinical trials comparing OTC artificial tears with another class of OTC artificial tears, placebo, or no treatment. This review did not consider head-to-head comparisons of artificial tears with another type of dry-eye therapy. Data collection and analysis We followed the standard methodological procedures expected by Cochrane. Two authors independently screened the search results, reviewed full-text copies for eligibility, examined risk of bias, and extracted data. We performed meta-analysis for trials that compared similar interventions and reported comparable outcomes with sufficient data. We summarized all other included trial results in the text. Main results We included 43 randomized controlled trials (3497 participants with dry eye). Due to the heterogeneity of study characteristics among the included trials with respect to types of diagnostic criteria, interventions, comparisons, and measurements taken, our ability to perform meta-analyses was limited. The review found that, in general, there was uncertainty whether different OTC artificial tears provide similar relief of signs and symptoms when compared with each other or placebo. Nevertheless, we found that 0.2% polyacrylic acid-based artificial tears were consistently more effective at treating dry eye symptoms than 1.4% polyvinyl alcohol-based artificial tears in two trials assessing this comparison (175 participants). All other included artificial tears produced contradictory between-group results or found no between-group differences. Our review also found that OTC artificial tears may be generally safe, but not without adverse events. Overall, we assessed the quality of evidence as low due to high risks of bias among included trials and poor reporting of outcome measures which were insufficient for quantitative analysis. Furthermore, we identified an additional 18 potentially eligible trials that were reported only in clinical trial registers with no associated results or publications. These trials reportedly enrolled 2079 total participants for whom no data are available. Such lack of reporting of trial results represents a high risk of publication bias. Authors’ conclusions OTC artificial tears may be safe and effective means for treating dry eye syndrome; the literature indicates that the majority of OTC artificial tears may have similar efficacies. This conclusion could be greatly skewed by the inconsistencies in study designs and inconsistencies in reporting trial results. Additional research is therefore needed before we can draw robust conclusions about the effectiveness of individual OTC artificial tear formulations. PMID:26905373

Development and Implementation of a Registry of Patients Attending Multidisciplinary Pain Treatment Clinics: The Quebec Pain Registry

PubMed Central

Lanctôt, H.; Beaudet, N.; Boulanger, A.; Bourgault, P.; Cloutier, C.; De Koninck, Y.; Dion, D.; Dolbec, P.; Germain, L.; Sarret, P.; Shir, Y.; Taillefer, M.-C.; Trépanier, A.; Truchon, R.

2017-01-01

The Quebec Pain Registry (QPR) is a large research database of patients suffering from various chronic pain (CP) syndromes who were referred to one of five tertiary care centres in the province of Quebec (Canada). Patients were monitored using common demographics, identical clinical descriptors, and uniform validated outcomes. This paper describes the development, implementation, and research potential of the QPR. Between 2008 and 2013, 6902 patients were enrolled in the QPR, and data were collected prior to their first visit at the pain clinic and six months later. More than 90% of them (mean age ± SD: 52.76 ± 4.60, females: 59.1%) consented that their QPR data be used for research purposes. The results suggest that, compared to patients with serious chronic medical disorders, CP patients referred to tertiary care clinics are more severely impaired in multiple domains including emotional and physical functioning. The QPR is also a powerful and comprehensive tool for conducting research in a “real-world” context with 27 observational studies and satellite research projects which have been completed or are underway. It contains data on the clinical evolution of thousands of patients and provides the opportunity of answering important research questions on various aspects of CP (or specific pain syndromes) and its management. PMID:28280406

Prognosis and management of myocardial infarction: Comparisons between the French FAST-MI 2010 registry and the French public health database.

PubMed

Massoullié, Grégoire; Wintzer-Wehekind, Jérome; Chenaf, Chouki; Mulliez, Aurélien; Pereira, Bruno; Authier, Nicolas; Eschalier, Alain; Clerfond, Guillaume; Souteyrand, Géraud; Tabassome, Simon; Danchin, Nicolas; Citron, Bernard; Lusson, Jean-René; Puymirat, Étienne; Motreff, Pascal; Eschalier, Romain

2016-05-01

Multicentre registries of myocardial infarction management show a steady improvement in prognosis and greater access to myocardial revascularization in a more timely manner. While French registries are the standard references, the question arises: are data stemming solely from the activity of French cardiac intensive care units (ICUs) a true reflection of the entire French population with ST-segment elevation myocardial infarction (STEMI)? To compare data on patients hospitalized for STEMI from two French registries: the French registry of acute ST-elevation or non-ST-elevation myocardial infarction (FAST-MI) and the Échantillon généraliste des bénéficiaires (EGB) database. We compared patients treated for STEMI listed in the FAST-MI 2010 registry (n=1716) with those listed in the EGB database, which comprises a sample of 1/97th of the French population, also from 2010 (n=403). Compared with the FAST-MI 2010 registry, the EGB database population were older (67.2±15.3 vs 63.3±14.5 years; P<0.001), had a higher percentage of women (36.0% vs 24.7%; P<0.001), were less likely to undergo emergency coronary angiography (75.2% vs 96.3%; P<0.001) and were less often treated in university hospitals (27.1% vs 37.0%; P=0.001). There were no significant differences between the two registries in terms of cardiovascular risk factors, comorbidities and drug treatment at admission. Thirty-day mortality was higher in the EGB database (10.2% vs 4.4%; P<0.001). Registries such as FAST-MI are indispensable, not only for assessing epidemiological changes over time, but also for evaluating the prognostic effect of modern STEMI management. Meanwhile, exploitation of data from general databases, such as EGB, provides additional relevant information, as they include a broader population not routinely admitted to cardiac ICUs. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

Beyond PubMed: Searching the "Grey Literature" for Clinical Trial Results.

PubMed

Citrome, Leslie

2014-07-01

Clinical trial results have been traditionally communicated through the publication of scholarly reports and reviews in biomedical journals. However, this dissemination of information can be delayed or incomplete, making it difficult to appraise new treatments, or in the case of missing data, evaluate older interventions. Going beyond the routine search of PubMed, it is possible to discover additional information in the "grey literature." Examples of the grey literature include clinical trial registries, patent databases, company and industrywide repositories, regulatory agency digital archives, abstracts of paper and poster presentations on meeting/congress websites, industry investor reports and press releases, and institutional and personal websites.

The RD-Connect Registry & Biobank Finder: a tool for sharing aggregated data and metadata among rare disease researchers.

PubMed

Gainotti, Sabina; Torreri, Paola; Wang, Chiuhui Mary; Reihs, Robert; Mueller, Heimo; Heslop, Emma; Roos, Marco; Badowska, Dorota Mazena; de Paulis, Federico; Kodra, Yllka; Carta, Claudio; Martìn, Estrella Lopez; Miller, Vanessa Rangel; Filocamo, Mirella; Mora, Marina; Thompson, Mark; Rubinstein, Yaffa; Posada de la Paz, Manuel; Monaco, Lucia; Lochmüller, Hanns; Taruscio, Domenica

2018-05-01

In rare disease (RD) research, there is a huge need to systematically collect biomaterials, phenotypic, and genomic data in a standardized way and to make them findable, accessible, interoperable and reusable (FAIR). RD-Connect is a 6 years global infrastructure project initiated in November 2012 that links genomic data with patient registries, biobanks, and clinical bioinformatics tools to create a central research resource for RDs. Here, we present RD-Connect Registry & Biobank Finder, a tool that helps RD researchers to find RD biobanks and registries and provide information on the availability and accessibility of content in each database. The finder concentrates information that is currently sparse on different repositories (inventories, websites, scientific journals, technical reports, etc.), including aggregated data and metadata from participating databases. Aggregated data provided by the finder, if appropriately checked, can be used by researchers who are trying to estimate the prevalence of a RD, to organize a clinical trial on a RD, or to estimate the volume of patients seen by different clinical centers. The finder is also a portal to other RD-Connect tools, providing a link to the RD-Connect Sample Catalogue, a large inventory of RD biological samples available in participating biobanks for RD research. There are several kinds of users and potential uses for the RD-Connect Registry & Biobank Finder, including researchers collaborating with academia and the industry, dealing with the questions of basic, translational, and/or clinical research. As of November 2017, the finder is populated with aggregated data for 222 registries and 21 biobanks.

Developing the Safety of Atrial Fibrillation Ablation Registry Initiative (SAFARI) as a collaborative pan-stakeholder critical path registry model: a Cardiac Safety Research Consortium "Incubator" Think Tank.

PubMed

Al-Khatib, Sana M; Calkins, Hugh; Eloff, Benjamin C; Kowey, Peter; Hammill, Stephen C; Ellenbogen, Kenneth A; Marinac-Dabic, Danica; Waldo, Albert L; Brindis, Ralph G; Wilbur, David J; Jackman, Warren M; Yaross, Marcia S; Russo, Andrea M; Prystowsky, Eric; Varosy, Paul D; Gross, Thomas; Pinnow, Ellen; Turakhia, Mintu P; Krucoff, Mitchell W

2010-10-01

Although several randomized clinical trials have demonstrated the safety and efficacy of catheter ablation of atrial fibrillation (AF) in experienced centers, the outcomes of this procedure in routine clinical practice and in patients with persistent and long-standing persistent AF remain uncertain. Brisk adoption of this therapy by physicians with diverse training and experience highlights potential concerns regarding the safety and effectiveness of this procedure. Some of these concerns could be addressed by a national registry of AF ablation procedures such as the Safety of Atrial Fibrillation Ablation Registry Initiative that was initially proposed at a Cardiac Safety Research Consortium Think Tank meeting in April 2009. In January 2010, the Cardiac Safety Research Consortium, in collaboration with the Duke Clinical Research Institute, the US Food and Drug Administration, the American College of Cardiology, and the Heart Rhythm Society, held a follow-up meeting of experts in the field to review the construct and progress to date. Other participants included the National Heart, Lung, and Blood Institute; the Centers for Medicare and Medicaid Services; the Agency for Healthcare Research and Quality; the AdvaMed AF working group; and additional industry representatives. This article summarizes the discussions that occurred at the meeting of the state of the Safety of Atrial Fibrillation Ablation Registry Initiative, the identification of a clear pathway for its implementation, and the exploration of solutions to potential issues in the execution of this registry. Copyright © 2010 Mosby, Inc. All rights reserved.

Standard and reference materials for marine science. Third edition. Technical memo

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

Cantillo, A.Y.

1992-08-01

The third edition of the catalog of reference materials suited for use in marine science, originally compiled in 1986 for NOAA, IOC, and UNEP. The catalog lists close to 2,000 reference materials from sixteen producers and contains information about their proper use, sources, availability, and analyte concentrations. Indices are included for elements, isotopes, and organic compounds, as are cross references to CAS registry numbers, alternate names, and chemical structures of selected organic compounds. The catalog is being published independently by both NOAA and IOC/UNEP and is available from NOAA/NOS/ORCA in electronic form.

Automatic HTS force measurement instrument

DOEpatents

Sanders, S.T.; Niemann, R.C.

1999-03-30

A device is disclosed for measuring the levitation force of a high temperature superconductor sample with respect to a reference magnet includes a receptacle for holding several high temperature superconductor samples each cooled to superconducting temperature. A rotatable carousel successively locates a selected one of the high temperature superconductor samples in registry with the reference magnet. Mechanism varies the distance between one of the high temperature superconductor samples and the reference magnet, and a sensor measures levitation force of the sample as a function of the distance between the reference magnet and the sample. A method is also disclosed. 3 figs.

Efficient design of clinical trials and epidemiological research: is it possible?

PubMed

Lauer, Michael S; Gordon, David; Wei, Gina; Pearson, Gail

2017-08-01

Randomized clinical trials and large-scale, cohort studies continue to have a critical role in generating evidence in cardiovascular medicine; however, the increasing concern is that ballooning costs threaten the clinical trial enterprise. In this Perspectives article, we discuss the changing landscape of clinical research, and clinical trials in particular, focusing on reasons for the increasing costs and inefficiencies. These reasons include excessively complex design, overly restrictive inclusion and exclusion criteria, burdensome regulations, excessive source-data verification, and concerns about the effect of clinical research conduct on workflow. Thought leaders have called on the clinical research community to consider alternative, transformative business models, including those models that focus on simplicity and leveraging of digital resources. We present some examples of innovative approaches by which some investigators have successfully conducted large-scale, clinical trials at relatively low cost. These examples include randomized registry trials, cluster-randomized trials, adaptive trials, and trials that are fully embedded within digital clinical care or administrative platforms.

Non-pharmacological interventions for sleep promotion in the intensive care unit.

PubMed

Hu, Rong-Fang; Jiang, Xiao-Ying; Chen, Junmin; Zeng, Zhiyong; Chen, Xiao Y; Li, Yueping; Huining, Xin; Evans, David J W

2015-10-06

Adults in intensive care units (ICUs) often suffer from a lack of sleep or frequent sleep disruptions. Non-pharmacological interventions can improve the duration and quality of sleep and decrease the risk of sleep disturbance, delirium, post-traumatic stress disorder (PTSD), and the length of stay in the ICU. However, there is no clear evidence of the effectiveness and harms of different non-pharmacological interventions for sleep promotion in adults admitted to the ICU. To assess the efficacy of non-pharmacological interventions for sleep promotion in critically ill adults in the ICU.To establish whether non-pharmacological interventions are safe and clinically effective in improving sleep quality and reducing length of ICU stay in critically ill adults.To establish whether non-pharmacological interventions are cost effective. We searched the Cochrane Central Register of Controlled Trials (CENTRAL, 2014, Issue 6), MEDLINE (OVID, 1950 to June 2014), EMBASE (1966 to June 2014), CINAHL (Cumulative Index to Nursing and Allied Health Literature, 1982 to June 2014), Institute for Scientific Information (ISI) Web of Science (1956 to June 2014), CAM on PubMed (1966 to June 2014), Alt HealthWatch (1997 to June 2014), PsycINFO (1967 to June 2014), the China Biological Medicine Database (CBM-disc, 1979 to June 2014), and China National Knowledge Infrastructure (CNKI Database, 1999 to June 2014). We also searched the following repositories and registries to June 2014: ProQuest Dissertations & Theses Global, the US National Institutes of Health Ongoing Trials Register (www.clinicaltrials.gov), the metaRegister of Controlled Trials (ISRCTN Register) (www.controlled-trials.com), the Chinese Clinical Trial Registry (www.chictr.org.cn), the Clinical Trials Registry-India (www.ctri.nic.in), the Grey Literature Report from the New York Academy of Medicine Library (www.greylit.org), OpenGrey (www.opengrey.eu), and the World Health Organization International Clinical Trials Registry platform (www.who.int/trialsearch). We handsearched critical care journals and reference lists and contacted relevant experts to identify relevant unpublished data. We included all randomized controlled trials (RCT) and quasi-RCTs that evaluated the effects of non-pharmacological interventions for sleep promotion in critically ill adults (aged 18 years and older) during admission to critical care units or ICUs. Two authors independently screened the search results and assessed the risk of bias in selected trials. One author extracted the data and a second checked the data for accuracy and completeness. Where possible, we combined results in meta-analyses using mean differences and standardized mean differences for continuous outcomes and risk ratios for dichotomous outcomes. We used post-test scores in this review. We included 30 trials, with a total of 1569 participants, in this review. We included trials of ventilator mode or type, earplugs or eye masks or both, massage, relaxation interventions, foot baths, music interventions, nursing interventions, valerian acupressure, aromatherapy, and sound masking. Outcomes included objective sleep outcomes, subjective sleep quality and quantity, risk of delirium, participant satisfaction, length of ICU stay, and adverse events. Clinical heterogeneity (e.g., participant population, outcomes measured) and research design limited quantitative synthesis, and only a small number of studies were available for most interventions. The quality of the evidence for an effect of non-pharmacological interventions on any of the outcomes examined was generally low or very low. Only three trials, all of earplugs or eye masks or both, provided data suitable for two separate meta-analyses. These meta-analyses, each of two studies, showed a lower incidence of delirium during ICU stay (risk ratio 0.55, 95% confidence interval (CI) 0.38 to 0.80, P value = 0.002, two studies, 177 participants) and a positive effect of earplugs or eye masks or both on total sleep time (mean difference 2.19 hours, 95% CI 0.41 to 3.96, P value = 0.02, two studies, 116 participants); we rated the quality of the evidence for both of these results as low.There was also some low quality evidence that music (350 participants; four studies) may improve subjective sleep quality and quantity, but we could not pool the data. Similarly, there was some evidence that relaxation techniques, foot massage, acupressure, nursing or social intervention, and sound masking can provide small improvements in various subjective measures of sleep quality and quantity, but the quality of the evidence was low. The effects of non-pharmacological interventions on objective sleep outcomes were inconsistent across 16 studies (we rated the quality of the evidence as very low): the majority of studies relating to the use of earplugs and eye masks found no benefit; results from six trials of ventilator modes suggested that certain ventilator settings might offer benefits over others, although the results of the individual trials did not always agree with each other. Only one study measured length of stay in the ICU and found no significant effect of earplugs plus eye masks. No studies examined the effect of any non-pharmacological intervention on mortality, risk of post-traumatic stress disorder, or cost-effectiveness; the included studies did not clearly report adverse effects, although there was very low quality evidence that ventilator mode influenced the incidence of central apnoeas and patient-ventilator asynchronies. The quality of existing evidence relating to the use of non-pharmacological interventions for promoting sleep in adults in the ICU was low or very low. We found some evidence that the use of earplugs or eye masks or both may have beneficial effects on sleep and the incidence of delirium in this population, although the quality of the evidence was low. Further high-quality research is needed to strengthen the evidence base.

[Obstacles and facilitators of conducting studies - the perspective of colorectal cancer centers' coordinators].

PubMed

Kowalski, C; Ferencz, J; Benz, S; Post, S; Seufferlein, T; Stinner, B; Penzes, O; Wesselmann, S

2016-05-01

Clinical trials and health services research are crucial pillars for improving patient care. This paper examines factors inhibiting and promoting the study activity and the knowledge and use of trial registries (e. g. DRKS, StudyBox) as an opportunity to learn about existing studies. The coordinators of 274 cancer center sites certified according to the requirements of the German Cancer Society were surveyed using a standardized online questionnaire. Data were analyzed using descriptive and bivariate statistics to identify associations with characteristics of the sites (e. g. patient volume, ownership, teaching status). 176 sites participated in the survey (64.2 %). The central obstacle to study participa-tion from the centers' view is the low number of existing studies. General knowledge of the population about studies was considered low. Trial registries are known to almost all respondents, but are rarely used. The results of the survey suggest that comprehensive measures are needed to sustainably increase the study activity. These include, for example, better information about studies, for example through appropriate databases, and (industry-independent) research funding. One possible way to sensitize patients for studies could be the comprehensive education of the population about the purpose of studies. © Georg Thieme Verlag KG Stuttgart · New York.

Clinical trials for vaccine development in registry of Korea Food and Drug Administration.

PubMed

Kang, Seog-Youn

2013-01-01

Based on the action plan "Ensuring a stable supply of National Immunization Program vaccines and sovereignty of biopharmaceutical products," Korea Food and Drug Administration (KFDA) has made efforts to develop vaccines in the context of self reliance and to protect public health. Along with the recognized infrastructures for clinical trials, clinical trials for vaccines have also gradually been conducted at multinational sites as well as at local sites. KFDA will support to expand six to eleven kinds of vaccines by 2017. In accordance with integrated regulatory system, KFDA has promoted clinical trials, established national lot release procedure, and strengthened good manufacturing practices inspection and post marketing surveillance. Against this backdrop, KFDA will support the vaccine development and promote excellent public health protection.

Embedding clinical interventions into observational studies.

PubMed

Newman, Anne B; Avilés-Santa, M Larissa; Anderson, Garnet; Heiss, Gerardo; Howard, Wm James; Krucoff, Mitchell; Kuller, Lewis H; Lewis, Cora E; Robinson, Jennifer G; Taylor, Herman; Treviño, Roberto P; Weintraub, William

2016-01-01

Novel approaches to observational studies and clinical trials could improve the cost-effectiveness and speed of translation of research. Hybrid designs that combine elements of clinical trials with observational registries or cohort studies should be considered as part of a long-term strategy to transform clinical trials and epidemiology, adapting to the opportunities of big data and the challenges of constrained budgets. Important considerations include study aims, timing, breadth and depth of the existing infrastructure that can be leveraged, participant burden, likely participation rate and available sample size in the cohort, required sample size for the trial, and investigator expertise. Community engagement and stakeholder (including study participants) support are essential for these efforts to succeed. Copyright © 2015. Published by Elsevier Inc.

Long-Term Outcomes After Percutaneous Lower Extremity Arterial Interventions With Atherectomy vs. Balloon Angioplasty　- Propensity Score-Matched Registry.

PubMed

Janas, Adam; Buszman, Piotr P; Milewski, Krzysztof P; Wiernek, Szymon; Janas, Ksenia; Pruski, Maciej; Wojakowski, Wojciech; Błachut, Aleksandra; Picheta, Wojciech; Buszman, Pawel; Kiesz, Stefan

2017-02-24

The impact of endovascular revascularization of the lower extremity arteries with atherectomy (AT) compared with percutaneous transluminal angioplasty (PTA) is still unclear. Therefore, the aim of the study was to compare long-term outcomes after percutaneous PTA and AT in patients requiring endovascular revascularization.Methods and Results:This was a single-center, retrospective registry of obstructive and symptomatic PAD patients who underwent endovascular revascularization. PTA was performed in 215 patients, and AT in 204 (Silver Hawk, EV3, n=125; CSI 360°, n=66; Pathway Medical Technologies, n=13). There were no significant between-group differences in baseline characteristics except for increased CAD, dialysis and CLI prevalence in the PTA group. Following propensity score analysis 131 well-matched pairs were included in analysis. Bail-out stenting was more frequent in the reference group (PTA, 6.1% vs. AT, 0%; P=0.004). At 6- and 12-month follow-up there were no differences in TLR between the groups (PTA, 8.3% vs. AT, 5.3%; P=0.47; and PTA, 16.7% vs. AT, 13.7%; P=0.73, respectively). The difference was in favor of AT at 24-month follow-up (PTA, 29.0% vs. AT, 16.7%; P=0.05). No difference was observed in amputation rate (PTA, 0.7% vs AT, 1.5%; P=0.62). On Kaplan-Meier analysis there were no significant differences between groups in time to TLR, amputation or death. AT was associated with lower risk of TLR, and this should be confirmed in randomized controlled trials.

Rationale, development and implementation of the Resuscitation Outcomes Consortium Epistry-Cardiac Arrest.

PubMed

Morrison, Laurie J; Nichol, Graham; Rea, Thomas D; Christenson, Jim; Callaway, Clifton W; Stephens, Shannon; Pirrallo, Ronald G; Atkins, Dianne L; Davis, Daniel P; Idris, Ahamed H; Newgard, Craig

2008-08-01

To describe the development, design and consequent scientific implications of the Resuscitation Outcomes Consortium (ROC) population-based registry; ROC Epistry-Cardiac Arrest. The ROC Epistry--Cardiac Arrest is designed as a prospective population-based registry of all Emergency Medical Services (EMSs)-attended 9-1-1 calls for patients with out-of-hospital cardiac arrest occurring in the geographical area described by the eight US and three Canadian regions. The dataset was derived by an North American interdisciplinary steering committee. Enrolled cases include individuals of all ages who experience cardiac arrest outside the hospital, with evaluation by organized EMS personnel and: (a) attempts at external defibrillation (by lay responders or emergency personnel), or chest compressions by organized EMS personnel; (b) were pulseless but did not receive attempts to defibrillate or CPR by EMS personnel. Selected data items are categorized as mandatory or optional and undergo revisions approximately every 12 months. Where possible all definitions are referenced to existing literature. Where a common definition did not exist one was developed. Optional items include standardized CPR process data elements. It is anticipated the ROC Epistry--Cardiac Arrest will enroll between approximately 9000 and 13,500 treated all rhythm arrests and 4000 and 5000 ventricular fibrillation arrests annually and approximately 8000 EMS-attended but untreated arrests. We describe the rationale, development, design and future implications of the ROC Epistry--Cardiac Arrest. This paper will serve as the reference for subsequent ROC manuscripts and for the common data elements captured in both ROC Epistry--Cardiac Arrest and the ROC trials.

Methodological challenges to control for immortal time bias in addressing drug effects in type 2 diabetes

PubMed Central

Yang, Xi-Lin; Huo, Xiao-Xu; Chan, Juliana CN

2015-01-01

There are multiple biases in using observational studies to examine treatment effects such as those from prevalent drug users, immortal time and drug indications. We used renin angiotensin system (RAS) inhibitors and statins as reference drugs with proven efficacies in randomized clinical trials (RCTs) and examined their effectiveness in the prospective Hong Kong Diabetes Registry using adjustment methods proposed in the literature. Using time-dependent exposures to drug treatments yielded greatly inflated hazard ratios (HR) regarding the treatment effects of these drugs for cardiovascular disease (CVD) in type 2 diabetes. These errors were probably due to changing indications to use these drugs during follow up periods, especially at the time of drug commencement making time-dependent analysis extremely problematic. Using time-fixed analysis with exclusion of immortal time and adjustment for confounders at baseline and/or during follow-up periods, the HR of RAS inhibitors for CVD was comparable to that in RCT. The result supported the use of the Registry for performing pharmacoepidemiological analysis which revealed an attenuated low low-density lipoprotein cholesterol related cancer risk with RAS inhibitors. On the other hand, time-fixed analysis with including immortal time and adjustment for confounders at baseline and/or during follow-up periods, the HR of statins for CVD was similar to that in the RCT. Our results highlight the complexity and difficulty in removing these biases. We call for validations of the methods to cope with immortal time and drug use indications before applying them to particular research questions, so to avoid making erroneous conclusions. PMID:26413484

Methodological challenges to control for immortal time bias in addressing drug effects in type 2 diabetes.

PubMed

Yang, Xi-Lin; Huo, Xiao-Xu; Chan, Juliana Cn

2015-09-26

There are multiple biases in using observational studies to examine treatment effects such as those from prevalent drug users, immortal time and drug indications. We used renin angiotensin system (RAS) inhibitors and statins as reference drugs with proven efficacies in randomized clinical trials (RCTs) and examined their effectiveness in the prospective Hong Kong Diabetes Registry using adjustment methods proposed in the literature. Using time-dependent exposures to drug treatments yielded greatly inflated hazard ratios (HR) regarding the treatment effects of these drugs for cardiovascular disease (CVD) in type 2 diabetes. These errors were probably due to changing indications to use these drugs during follow up periods, especially at the time of drug commencement making time-dependent analysis extremely problematic. Using time-fixed analysis with exclusion of immortal time and adjustment for confounders at baseline and/or during follow-up periods, the HR of RAS inhibitors for CVD was comparable to that in RCT. The result supported the use of the Registry for performing pharmacoepidemiological analysis which revealed an attenuated low low-density lipoprotein cholesterol related cancer risk with RAS inhibitors. On the other hand, time-fixed analysis with including immortal time and adjustment for confounders at baseline and/or during follow-up periods, the HR of statins for CVD was similar to that in the RCT. Our results highlight the complexity and difficulty in removing these biases. We call for validations of the methods to cope with immortal time and drug use indications before applying them to particular research questions, so to avoid making erroneous conclusions.

Effectiveness of new antiplatelets in the prevention of recurrent myocardial infarction.

PubMed

Grimaldi-Bensouda, Lamiae; Danchin, Nicolas; Dallongeville, Jean; Falissard, Bruno; Furber, Alain; Cottin, Yves; Bonello, Laurent; Morel, Olivier; Leclercq, Florence; Puymirat, Etienne; Ghanem, Fahmi; Delarche, Nicolas; Benichou, Jacques; Abenhaim, Lucien

2018-03-13

To compare ticagrelor and prasugrel with clopidogrel for recurrent fatal and non-fatal myocardial infarction (reMI) in real-life conditions. Case-referent study using the Pharmacoepidemiological General Research eXtension (PGRx)-acute coronary syndrome (ACS) registry. Cases were patients with reMI from a cohort with index ACS or external to the cohort (same sites). Referents from the cohort, without recurrent event, were matched on index ACS type and date, age and sex with reMI cases. Multivariate conditional logistic regression assessed the OR (95% CI) for reMI associated with ticagrelor and prasugrel vs clopidogrel, adjusted for aspirin use and cardiovascular risk factors. 1047 cases and 2234 matched referents were included. Compared with clopidogrel, ticagrelor and prasugrel were associated with respective ORs of 0.65 (95% CI 0.52 to 0.81) and 0.71 (95% CI 0.53 to 0.96) for reMI occurrence. ORs for ticagrelor and prasugrel vs clopidogrel were: 0.50 (95% CI 0.38 to 0.67) and 0.66 (95% CI 0.45 to 0.95), 0.39 (95% CI 0.24 to 0.62) and 0.44 (95% CI 0.26 to 0.75), 0.63 (95% CI 0.43 to 0.92) and 1.20 (95% CI 0.69 to 2.07), 1.11 (95% CI 0.72 to 1.72) and 0.82 (95% CI 0.44 to 1.54) when index ACS was a first MI, a first ST-elevated MI (STEMI), a first non-STEMI and a recurrent ACS, respectively, and 0.63 (95% CI 0.45 to 0.87) and 0.77 (95% CI 0.41 to 1.45) forpatients aged ≥70 years. This real-world study showed a significant reduction of reMI with new antiplatelets compared with clopidogrel, ticagrelor being associated with a greater decrease of risk notably for first, either STEMI or non-STEMI. The larger magnitude of effect may be attributed to potential residual confounding or higher effectiveness compared with efficacy reported in trials (EMA Post Authorisation Study Registry Number EUPAS5905). © 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.

Development of Korean Rare Disease Knowledge Base

PubMed Central

Seo, Heewon; Kim, Dokyoon; Chae, Jong-Hee; Kang, Hee Gyung; Lim, Byung Chan; Cheong, Hae Il

2012-01-01

Objectives Rare disease research requires a broad range of disease-related information for the discovery of causes of genetic disorders that are maladies caused by abnormalities in genes or chromosomes. A rarity in cases makes it difficult for researchers to elucidate definite inception. This knowledge base will be a major resource not only for clinicians, but also for the general public, who are unable to find consistent information on rare diseases in a single location. Methods We design a compact database schema for faster querying; its structure is optimized to store heterogeneous data sources. Then, clinicians at Seoul National University Hospital (SNUH) review and revise those resources. Additionally, we integrated other sources to capture genomic resources and clinical trials in detail on the Korean Rare Disease Knowledge base (KRDK). Results As a result, we have developed a Web-based knowledge base, KRDK, suitable for study of Mendelian diseases that commonly occur among Koreans. This knowledge base is comprised of disease summary and review, causal gene list, laboratory and clinic directory, patient registry, and so on. Furthermore, database for analyzing and giving access to human biological information and the clinical trial management system are integrated on KRDK. Conclusions We expect that KRDK, the first rare disease knowledge base in Korea, may contribute to collaborative research and be a reliable reference for application to clinical trials. Additionally, this knowledge base is ready for querying of drug information so that visitors can search a list of rare diseases that is relative to specific drugs. Visitors can have access to KRDK via http://www.snubi.org/software/raredisease/. PMID:23346478

Preoperative intra-aortic balloon pump in patients undergoing coronary bypass surgery: a systematic review and meta-analysis.

PubMed

Dyub, Adel M; Whitlock, Richard P; Abouzahr, Labib L; Cinà, Claudio S

2008-01-01

To assess the effectiveness of preoperative intra-aortic balloon pump (IABP) placement in high-risk patients undergoing coronary bypass surgery (CABG). The primary outcome was hospital mortality and secondary outcomes were IABP-related complications (bleeding, leg ischemia, aortic dissection). MEDLINE, EMBASE, Cochrane registry of Controlled Trials, and reference lists of relevant articles were searched. We included randomized controlled trials (RCTs), and cohort studies that fulfilled our a priori inclusion criteria. Eligibility decisions, relevance, study validity, and data extraction were performed in duplicate using pre-specified criteria. Meta-analysis was conducted using a random effects model. Ten publications fulfilled our eligibility criteria, of which four were RCTs and six were cohort studies with controls. There were statistical as well as clinical heterogeneity among included studies. A total of 1034 patients received preoperative IABP and 1329 did not receive preoperative IABP. The pooled odds ratio (OR) for hospital mortality in patients treated with preoperative IABP was 0.41 (95% CI, 0.21-0.82, p = 0.01). The number needed to treat was 17. The pooled OR for hospital mortality from randomized trials was 0.18 (95% CI, 0.06-0.57, p = 0.003) and from cohort studies was 0.54 (95% CI, 0.24-1.2, p = 0.13). Overall, 3.7% (13 of 349) of patients who received preoperative IABP developed either limb ischemia or haematoma at the IABP insertion site, and most of these complications improved after discontinuation of IABP. Evidence from this meta-analysis support the use of preoperative IABP in high-risk patients to reduce hospital mortality.

Efficacy and Safety of the Absorb Everolimus-Eluting Bioresorbable Scaffold for Treatment of Patients With Diabetes Mellitus: Results of the Absorb Diabetic Substudy.

PubMed

Kereiakes, Dean J; Ellis, Stephen G; Kimura, Takeshi; Abizaid, Alexandre; Zhao, Weiying; Veldhof, Susan; Vu, Minh-Thien; Zhang, Zhen; Onuma, Yoshinobu; Chevalier, Bernard; Serruys, Patrick W; Stone, Gregg W

2017-01-09

The study sought to evaluate the efficacy and safety of the Absorb everolimus-eluting bioresorbable vascular scaffold (BVS) (Abbott Vascular, Abbott Park, Illinois) in patients with diabetes mellitus. Randomized, controlled trials have demonstrated comparable clinical outcomes following percutaneous coronary intervention with either Absorb BVS or metallic Xience everolimus-eluting stent. However, these trials lack power required to provide reliable treatment effect estimates in this high-risk population. In a pre-specified, powered analysis, patients with diabetes who received ≥1 Absorb were pooled from the ABSORB II, III, and JAPAN randomized trials and from the single arm ABSORB EXTEND registry. The study composite primary endpoint was target lesion failure (TLF) at 1 year following Absorb BVS compared with a performance goal of 12.7%. Among 754 diabetic patients included in analysis (27.3% insulin treated), the 1-year TLF rate was 8.3% (upper 1-sided 95% confidence limit: 10.1%; p = 0.0001 vs. performance goal). Scaffold thrombosis (definite or probable) was observed in 2.3% of patients. Multivariable regression identified older age, insulin treatment, and smaller pre-procedure reference vessel diameter as significant independent predictors of 1-year TLF. The Absorb diabetic substudy suggests efficacy and safety of the Absorb BVS for treatment of patients with diabetes mellitus. Copyright © 2017 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

Azilsartan medoxomil/chlorthalidone: a new fixed-dose combination antihypertensive.

PubMed

Pierini, Danielle; Anderson, Katherine Vogel

2013-05-01

To evaluate the efficacy, safety, and clinical utility of the combination product azilsartan medoxomil/chlorthalidone for the treatment of hypertension. Articles indexed in PubMed through December 2012 were identified using the MeSH terms azilsartan and chlorthalidone, Edarbyclor, TAK-490, and Edarbi. Additional information was gathered from references cited in the identified publications, the package insert, and from a review of the ClinicalTrials.gov registry. English-language articles, including clinical trials and reviews involving azilsartan medoxomil/chlorthalidone or each component individually for the treatment of hypertension were reviewed. The antihypertensive combination tablet azilsartan medoxomil/chlorthalidone is the first to combine an inhibitor of the renin-angiotensin-aldosterone system with chlorthalidone, a thiazide-type diuretic. In 4 randomized controlled trials (3 published to date), azilsartan medoxomil/chlorthalidone 40 mg/12.5 mg and 40 mg/25 mg reduced blood pressure (BP) significantly more than comparators did, including an approximately 5-mm Hg greater BP reduction than olmesartan medoxomil/hydrochlorothiazide 40 mg/25 mg and azilsartan medoxomil/hydrochlorothiazide. Reductions in 24-hour ambulatory BP and clinic BP were observed, and a greater proportion of patients achieved BP targets while receiving azilsartan medoxomil/chlorthalidone. Azilsartan medoxomil/chlorthalidone was generally well tolerated, with minor, transient increases in serum creatinine and without a significant effect on potassium homeostasis. No studies have directly examined cardiovascular morbidity and mortality benefits associated with this combination. The combination of azilsartan medoxomil/chlorthalidone has demonstrated safety and efficacy in lowering BP in hypertensive patients to a greater degree than olmesartan medoxomil/hydrochlorothiazide and azilsartan medoxomil/hydrochlorothiazide. As a fixed-dose combination tablet, it offers several clinical advantages.

A study of sertraline in dialysis (ASSertID): a protocol for a pilot randomised controlled trial of drug treatment for depression in patients undergoing haemodialysis.

PubMed

Friedli, Karin; Almond, Michael; Day, Clara; Chilcot, Joseph; Gane, Maria da Silva; Davenport, Andrew; Guirguis, Ayman; Fineberg, Naomi; Spencer, Benjamin; Wellsted, David; Farrington, Ken

2015-10-26

The prevalence of depression in people receiving haemodialysis is high with estimates varying between 20 and 40 %. There is little research on the effectiveness of antidepressants in dialysis patients with the few clinical trials suffering significant methodological issues. We plan to carry out a study to evaluate the feasibility of conducting a randomised controlled trial in patients on haemodialysis who have diagnosed Major Depressive Disorder. The study has two phases, a screening phase and the randomised controlled trial. Patients will be screened initially with the Beck Depression Inventory to estimate the number of patients who score 16 or above. These patients will be invited to an interview with a psychiatrist who will invite those with a diagnosis of Major Depressive Disorder to take part in the trial. Consenting patients will be randomised to either Sertraline or placebo. Patients will be followed-up for 6 months. Demographic and clinical data will be collected at screening interview, baseline interview and 2 weeks, and every month (up to 6 months) after baseline. The primary outcome is to evaluate the feasibility of conducting a randomised, double blind, placebo pilot trial in haemodialysis patients with depression. Secondary outcomes include estimation of the variability in the outcome measures for the treatment and placebo arms, which will allow for a future adequately powered definitive trial. Analysis will primarily be descriptive, including the number of patients eligible for the trial, drug exposure of Sertraline in haemodialysis patients and the patient experience of participating in this trial. There is an urgent need for this research in the dialysis population because of the dearth of good quality and adequately powered studies. Research with renal patients is particularly difficult as they often have complex medical needs. This research will therefore not only assess the outcome of anti-depressants in haemodialysis patients with depression but also the process of running a randomised controlled trial in this population. Hence, the outputs of this feasibility study will be used to inform the design and methodology of a definitive study, adequately powered to determine the efficacy of anti-depressants in patient on haemodialysis with depression. ISRCTN registry ISRCTN06146268 and EudraCT reference: 2012-000547-27.

Glycerin laxatives for prevention or treatment of feeding intolerance in very low birth weight infants.

PubMed

Anabrees, Jasim; Shah, Vibhuti S; AlOsaimi, Ahlam; AlFaleh, Khalid

2015-09-30

Feeding intolerance is a common clinical problem among preterm infants. It may be an early sign of necrotising enterocolitis, sepsis or other serious gastrointestinal conditions, or it may result from gut immaturity with delayed passage of meconium. Glycerin laxatives stimulate passage of meconium by acting as an osmotic dehydrating agent and increasing osmotic pressure in the gut; they stimulate rectal contraction, potentially reducing the incidence of feeding intolerance. To assess the effectiveness and safety of glycerin laxatives (enemas/suppositories) for prevention or treatment of feeding intolerance in very low birth weight (VLBW) infants. We searched the Cochrane Central Register of Controlled Trials (CENTRAL; 2015, Issue 4), MEDLINE, EMBASE and the Cumulative Index to Nursing and Allied Health Literature (CINAHL). We restricted our search to all randomised controlled trials and applied no language restrictions. We searched the references of identified studies and reviews on this topic and handsearched for additional articles. We searched the database maintained by the US National Institutes of Health (www.clinicaltrials.gov) and European trial registries to identify ongoing trials. We considered only randomised or quasi-randomised controlled trials that enrolled preterm infants < 32 weeks' gestational age (GA) and/or < 1500 g birth weight. We included trials if they administered glycerin laxatives and measured at least one prespecified clinical outcome. We used standard methods of The Cochrane Collaboration and its Neonatal Group to assess methodological quality of trials, to collect data and to perform analyses. We identified three trials that evaluated use of prophylactic glycerin laxatives in preterm infants. We identified no trials that evaluated therapeutic use of glycerin laxatives for feeding intolerance. Our review showed that prophylactic administration of glycerin laxatives did not reduce the time required to achieve full enteral feeds and did not influence secondary outcomes, including duration of hospital stay, mortality and weight at discharge. Prophylactic administration of glycerin laxatives resulted in failure of fewer infants to pass stool over the first 48 hours. Included trials reported no adverse events. Our review of available evidence for glycerin laxatives does not support the routine use of prophylactic glycerin laxatives in clinical practice. Additional studies are needed to confirm or refute the effectiveness and safety of glycerin laxatives for prevention or treatment of feeding intolerance in VLBW infants.

Huperzine A for vascular dementia

PubMed Central

Hao, Zilong; Liu, Ming; Liu, Zhiqin; Lu, DongHao

2014-01-01

Background Huperzine A, a form of herbal medicine, has been considered as an alternative treatment for vascular dementia (VaD) in China. Objectives To assess the efficacy and safety of Huperzine A in patients with vascular dementia. Search methods We searched ALOIS: the Cochrane Dementia and Cognitive Improvement Group’s Specialized Register on 10 February 2011 using the terms: chinese, plants, huperzine, HUP, ayapin, scoparon. ALOIS contains records of clinical trials identified from monthly searches of a number of major healthcare databases (The Cochrane Library, MEDLINE, EMBASE, PsycINFO, CINAHL, LILACS), numerous trial registries and grey literature sources. We also searched the following databases in March 2011 using the terms ‘Huperzine A’, ‘Shishanjianjia’, ‘Haboyin’ and ‘Shuangyiping’: The Chinese Biomedical Database (CBM) (1977 to March 2011); Chinese Science and Technique Journals Database (VIP) (1989 to March 2011); China National Knowledge Infrastructure (CNKI) (1979 to March 2011); Google (March 2011). In addition, we searched relevant reference lists. We also contacted researchers to request additional information where necessary. Selection criteria We considered randomized controlled trials comparing Huperzine A with placebo in people with vascular dementia eligible for inclusion. Data collection and analysis Two review authors independently applied the inclusion criteria, assessed trial quality and extracted the data. We resolved any disagreement by discussion. Main results We included only one small trial, involving 14 participants with vascular dementia. No significant effect of Huperzine A on cognitive function measured by MMSE (WMD 2.40; 95% CI −4.78 to 9.58) was observed. There was a significant beneficial effect of Huperzine A on performance of activities of daily living (WMD −13.00; 95% CI −23.24 to −2.76) after six months of treatment. No deaths from any cause at the end of treatment were reported. Behaviour, quality of life and caregiver burden were not assessed in the included trial. Authors’ conclusions There is currently no high quality evidence to support the use of Huperzine A for the treatment of vascular dementia. Further randomized placebo controlled trials are needed to determine whether there is worthwhile benefit. PMID:19370686

Substantial underreporting of anastomotic leakage after anterior resection for rectal cancer in the Swedish Colorectal Cancer Registry.

PubMed

Rutegård, Martin; Kverneng Hultberg, Daniel; Angenete, Eva; Lydrup, Marie-Louise

2017-12-01

The causes and effects of anastomotic leakage after anterior resection are difficult to study in small samples and have thus been evaluated using large population-based national registries. To assess the accuracy of such research, registries should be validated continuously. Patients who underwent anterior resection for rectal cancer during 2007-2013 in 15 different hospitals in three healthcare regions in Sweden were included in the study. Registry data and information from patient records were retrieved. Registered anastomotic leakage within 30 postoperative days was evaluated, using all available registry data and using only the main variable anastomotic insufficiency. With the consensus definition of anastomotic leakage developed by the International Study Group on Rectal Cancer as reference, validity measures were calculated. Some 1507 patients were included in the study. The negative and positive predictive values for registered anastomotic leakage were 96 and 88%, respectively, while the κ-value amounted to 0.76. The false-negative rate was 29%, whereas the false-positive rate reached 1.3% (the vast majority consisting of actual leaks, but occurring after postoperative day 30). Using the main variable anastomotic insufficiency only, the false-negative rate rose to 41%. There is considerable underreporting of anastomotic leakage after anterior resection for rectal cancer in the Swedish Colorectal Cancer Registry. It is probable that this causes an underestimation of the true effects of leakage on patient outcomes, and further quality control is needed.

Feasibility of evaluating quality cancer care using registry data and electronic health records: a population-based study.

PubMed

Caldarella, Adele; Amunni, Gianni; Angiolini, Catia; Crocetti, Emanuele; Di Costanzo, Francesco; Di Leo, Angelo; Giusti, Francesco; Pegna, Andrea Lopes; Mantellini, Paola; Luzzatto, Lucio; Paci, Eugenio

2012-08-01

To evaluate the quality of patients care, a set of indicators of the standards of cancer care were defined. We developed a set of indicators to assess the implementation in daily practice of recommendation produced by a regional network (Istituto Toscano Tumori). This set was tested in a retrospective study in the resident population of the Tuscany Region; the regional health system is organized on 12 local health authorities which refer to three macro areas (Area Vasta). The study included incident colorectal, lung and breast cancer cases listed in 2004 for the Tuscan Cancer Registry, a population-based registry which collected tumor cases diagnosed in all residents in Tuscany. Electronic data from registry database were used to determine the compliance with each indicator for patients in 2004. To validate the results, an ad hoc clinical survey including the same geographical area for the year 2006 was performed. None. The proportion of patients who fulfilled each of the indicators. Our study showed the feasibility of the evaluation of the quality of cancer care using cancer registry population-based data and major computerized information systems. The estimation of the selected indicators confirmed a good homogeneity among areas, and globally revealed a good intraregional performance. Further work is needed to develop specific quality measures, particularly about structural data and to continually revise indicators of quality of care. Data from a cancer registry, however, can be useful to evaluate quality of cancer care.

Estimating canine cancer incidence: findings from a population-based tumour registry in northwestern Italy.

PubMed

Baioni, Elisa; Scanziani, Eugenio; Vincenti, Maria Claudia; Leschiera, Mauro; Bozzetta, Elena; Pezzolato, Marzia; Desiato, Rosanna; Bertolini, Silvia; Maurella, Cristiana; Ru, Giuseppe

2017-06-28

Canine cancer registry data can be put to good use in epidemiological studies. Quantitative comparison of tumour types may reveal unusual cancer frequencies, providing directions for research and generation of hypotheses of cancer causation in a specific area, and suggest leads for identifying risk factors. Here we report canine cancer incidence rates calculated from a population-based registry in an area without any known specific environmental hazard. In its 90 months of operation from 2001 to 2008 (the observation period in this study), the population-based Piedmont Canine Cancer Registry collected data on 1175 tumours confirmed by histopathological diagnosis. The incidence rate was 804 per 100,000 dog-years for malignant tumours and 897 per 100,000 dog-years for benign tumours. Higher rates for all cancers were observed in purebred dogs, particularly in Yorkshire terrier and Boxer. The most prevalent malignant neoplasms were cutaneous mastocytoma and hemangiopericytoma, and mammary gland complex carcinoma and simplex carcinoma. The Piedmont canine cancer registry is one of few of its kind whose operations have been consistently supported by long-term public funding. The registry-based cancer incidence rates were estimated with particular attention to the validity of data collection, thus minimizing the potential for bias. The findings on cancer incidence rates may provide a reliable reference for comparison studies. Researches conducted on dogs, used as sentinels for community exposure to environmental carcinogens, can be useful to detect excess risks in the incidence of malignant tumours in the human population.

EARLY Treatment with azilsartan compared to ACE-inhibitors in anti-hypertensive therapy – rationale and design of the EARLY hypertension registry

PubMed Central

2013-01-01

Background Arterial hypertension is highly prevalent but poorly controlled. Blood pressure (BP) reduction substantially reduces cardiovascular morbidity and mortality. Recent randomized, double-blind clinical trials demonstrated that azilsartan medoxomil (AZM) is more effective in reducing BP than the ubiquitary ACE inhibitor ramipril. Therefore, we aimed to test whether these can be verified under clinical practice conditions. Methods/Design The “Treatment with Azilsartan Compared to ACE-Inhibitors in Anti-Hypertensive Therapy” (EARLY) registry is a prospective, observational, national, multicenter registry with a follow-up of up to 12 months. It will include up to 5000 patients on AZM or ACE-inhibitor monotherapy in a ratio of 7 to 3. A subgroup of patients will undergo 24-hour BP monitoring. EARLY has two co-primary objectives: 1) Description of the safety profile of azilsartan and 2) achievement of BP targets based on recent national and international guidelines for patients treated with azilsartan in comparison to those treated with ACE-inhibitors. The most important secondary endpoints are the determination of persistence with treatment and the documentation of cardiovascular and renal events. Recruitment commenced in January 2012 and will be completed by February 2013. Conclusions The data obtained will supplement previous results from randomized controlled trials to document the potential value of utilizing azilsartan medoxomil in comparison to ACE-inhibitor treatment for target BP achievement in clinical practice. PMID:23819631

Aromatherapy for pain management in labour.

PubMed

Smith, Caroline A; Collins, Carmel T; Crowther, Caroline A

2011-07-06

Many women would like to avoid pharmacological or invasive methods of pain management in labour and this may contribute towards the popularity of complementary methods of pain management. This review examined currently available evidence supporting the use of aromatherapy for pain management in labour. To examine the effects of aromatherapy for pain management in labour on maternal and perinatal morbidity. We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (31 October 2010), The Cochrane Complementary Medicine Field's Trials Register (October 2010), the Cochrane Central Register of Controlled Trials (The Cochrane Library 2010, Issue 4), MEDLINE (1966 to 31 October 2010), CINAHL (1980 to 31 October 2010), the Australian and New Zealand Trials Registry (31 October 2010), Chinese Clinical Trial Register (31 October 2010), Current Controlled Trials (31 October 2010), ClinicalTrials.gov (31 October 2010), ISRCTN Register (31 October 2010), National Center for Complementary and Alternative Medicine (NCCAM) (31 October 2010) and the WHO International Clinical Trials Registry Platform (31 October 2010). Randomised controlled trials comparing aromatherapy with placebo, no treatment or other non-pharmacological forms of pain management in labour. Two authors independently assessed trial quality and extracted data. We contacted study authors for additional information. We included two trials (535 women) in the review. The trials found no difference between groups for the primary outcomes of pain intensity, assisted vaginal birth (risk ratio (RR) 1.04, 95% confidence interval (CI) 0.48 to 2.28, one trial, 513 women; RR 0.83, 95% CI 0.06 to 11.70, one trial, 22 women), and caesarean section (RR 0.98, 95% CI 0.49 to 1.94, one trial, 513 women; RR 2.54, 95% CI 0.11 to 56.25, one trial, 22 women); there were more babies admitted to neonatal intensive care in the control group of one trial (RR 0.08, 95% CI 0.00 to 1.42, one trial, 513 women) but this difference did not reach statistical significance. The trials found no differences between groups for the secondary outcomes of use of pharmacological pain relief (RR 0.35, 95% CI 0.04 to 3.32, one trial, 513 women; RR 2.50, 95% CI 0.31 to 20.45, one trial, 22 women), spontaneous vaginal delivery (RR 1.00, 95% CI 0.94 to 1.06, one trial, 513 women; RR 0.93, 95% CI 0.67 to 1.28, one trial, 22 women) or length of labour and augmentation (RR 1.14, 95% CI 0.90 to 1.45, one trial, 513 women). The risk of bias was low in the trials. There is a lack of studies evaluating the role of aromatherapy for pain management in labour. Further research is needed before recommendations can be made for clinical practice.

ResearchMatch: A National Registry to Recruit Volunteers for Clinical Research

PubMed Central

Harris, Paul A.; Scott, Kirstin W; Lebo, Laurie; Hassan, NikNik; Lighter, Chad; Pulley, Jill

2013-01-01

The authors designed ResearchMatch, a disease-neutral, web-based recruitment registry to help match individuals who wish to participate in clinical research studies with researchers actively searching for volunteers throughout the United States. In this article, they describe ResearchMatch’s stakeholders, workflow model, technical infrastructure, and, for the registry’s first 19 months of operation, utilization metrics. Having launched volunteer registration tools in November 2009 and researcher registration tools in March 2010, ResearchMatch had, as of June 2011, registered 15,871 volunteer participants from all 50 states. The registry was created as a collaborative project for institutions in the Clinical and Translational Science Awards (CTSA) consortium. Also as of June 2011, a total of 751 researchers from 61 participating CTSA institutions had registered to use the tool to recruit participants into 540 active studies and trials. ResearchMatch has proven successful in connecting volunteers with researchers, and the authors are currently evaluating regulatory and workflow options to open access to researchers at non-CTSA institutions. PMID:22104055

A missing ancestry - Genetic Testing | NIH MedlinePlus the Magazine

MedlinePlus

... Testing - From Genetics Home Reference: the benefits, costs, risks, and limitations of genetic testing Genetic Testing Registry -A publicly funded medical genetics information resource developed for physicians, other health care providers, and researchers MedlinePlus — Genetic Testing CLINSEQ®: ...

Strategies for successful trauma registry implementation in low- and middle-income countries-protocol for a systematic review.

PubMed

Paradis, Tiffany; St-Louis, Etienne; Landry, Tara; Poenaru, Dan

2018-02-21

The benefits of trauma registries have been well described. The crucial data they provide may guide injury prevention strategies, inform resource allocation, and support advocacy and policy. This has been shown to reduce trauma-related mortality in various settings. Trauma remains a leading cause of mortality in low- and middle-income countries (LMICs). However, the implementation of trauma registries in LMICs can be challenging due to lack of funding, specialized personnel, and infrastructure. This study explores strategies for successful trauma registry implementation in LMICs. The protocol was registered a priori (CRD42017058586). A peer-reviewed search strategy of multiple databases will be developed with a senior librarian. As per PRISMA guidelines, first screen of references based on abstract and title and subsequent full-text review will be conducted by two independent reviewers. Disagreements that cannot be resolved by discussion between reviewers shall be arbitrated by the principal investigator. Data extraction will be performed using a pre-defined data extraction sheet. Finally, bibliographies of included articles will be hand-searched. Studies of any design will be included if they describe or review development and implementation of a trauma registry in LMICs. No language or period restrictions will be applied. Summary statistics and qualitative meta-narrative analyses will be performed. The significant burden of trauma in LMIC environments presents unique challenges and limitations. Adapted strategies for deployment and maintenance of sustainable trauma registries are needed. Our methodology will systematically identify recommendations and strategies for successful trauma registry implementation in LMICs and describe threats and barriers to this endeavor. The protocol was registered on the PROSPERO international prospective register of systematic reviews ( CRD42017058586 ).

Evidence regarding lingual fixed orthodontic appliances' therapeutic and adverse effects is insufficient.

PubMed

Afrashtehfar, Kelvin I

2016-06-01

Data sourcesMedline, Cochrane Database of Systematic Reviews, Database of Abstracts of Reviews of Effects, Cochrane Central Register of Controlled Trials, Virtual Health Library and Web of Science were systematically searched up to July 2015 without limitations. Scopus, Google Scholar, ClinicalTrials.gov, the ISRCTN registry as well as reference lists of the trials included and relevant reviews were manually searched.Study selectionRandomised (RCTs) and prospective non-randomised clinical trials (non-RCTs) on human patients that compared therapeutic and adverse effects of lingual and labial appliances were considered. One reviewer initially screened titles and subsequently two reviewers independently screened the selected abstracts and full texts.Data extraction and synthesisThe data were extracted independently by the reviewers. Missing or unclear information, ongoing trials and raw data from split-mouth trials were requested from the authors of the trials. The quality of the included trials and potential bias across studies were assessed using Cochrane's risk of bias tool and the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach. For parallel trials, mean difference (MD) and the relative risk (RR) were used for continuous (objective speech performance, subjective speech performance, intercanine width, intermolar width and sagittal anchorage loss) and binary outcomes (eating difficulty), respectively. The standardised mean difference (SMD) was chosen to pool, after conversion, the outcome (oral discomfort) that assessed both binary and continuous. Random-effects meta-analyses were conducted, followed by subgroup and sensitivity analyses.ResultsThirteen papers pertaining to 11 clinical trials (three parallel RCTs, one split-mouth RCT and seven parallel prospective non-RCTs) were included with a total of 407 (34% male/66% female) patients. All trials had at least one bias domain at high risk of bias. Compared with labial appliances, lingual appliances were associated with increased overall oral discomfort, increased speech impediment (measured using auditory analysis), worse speech performance assessed by laypersons, increased eating difficulty and decreased intermolar width. On the other hand, lingual appliances were associated with increased intercanine width and significantly decreased anchorage loss of the maxillary first molar during space closure. However, the quality of all analyses included was judged as very low because of the high risk of bias of the included trials, inconsistency and imprecision.ConclusionsBased on existing trials there is insufficient evidence to make robust recommendations for lingual fixed orthodontic appliances regarding their therapeutic or adverse effects, as the quality of evidence was low.

Obesity in Youth with Type 1 Diabetes in Germany, Austria, and the United States.

PubMed

DuBose, Stephanie N; Hermann, Julia M; Tamborlane, William V; Beck, Roy W; Dost, Axel; DiMeglio, Linda A; Schwab, Karl Otfried; Holl, Reinhard W; Hofer, Sabine E; Maahs, David M

2015-09-01

To examine the current extent of the obesity problem in 2 large pediatric clinical registries in the US and Europe and to examine the hypotheses that increased body mass index (BMI) z-scores (BMIz) are associated with greater hemoglobin A1c (HbA1c) and increased frequency of severe hypoglycemia in youth with type 1 diabetes (T1D). International (World Health Organization) and national (Centers for Disease Control and Prevention/German Health Interview and Examination Survey for Children and Adolescents) BMI references were used to calculate BMIz in participants (age 2-<18 years and ≥ 1 year duration of T1D) enrolled in the T1D Exchange (n = 11,435) and the Diabetes Prospective Follow-up (n = 21,501). Associations between BMIz and HbA1c and severe hypoglycemia were assessed. Participants in both registries had median BMI values that were greater than international and their respective national reference values. BMIz was significantly greater in the T1D Exchange vs the Diabetes Prospective Follow-up (P < .001). After stratification by age-group, no differences in BMI between registries existed for children 2-5 years, but differences were confirmed for 6- to 9-, 10- to 13-, and 14- to 17-year age groups (all P < .001). Greater BMIz were significantly related to greater HbA1c levels and more frequent occurrence of severe hypoglycemia across the registries, although these associations may not be clinically relevant. Excessive weight is a common problem in children with T1D in Germany and Austria and, especially, in the US. Our data suggest that obesity contributes to the challenges in achieving optimal glycemic control in children and adolescents with T1D. Copyright © 2015 Elsevier Inc. All rights reserved.

Management and outcomes in chronic thromboembolic pulmonary hypertension: From expert centers to a nationwide perspective.

PubMed

Escribano-Subías, P; Del Pozo, R; Román-Broto, A; Domingo Morera, J A; Lara-Padrón, A; Elías Hernández, T; Molina-Ferragut, L; Blanco, I; Cortina, J; Barberà, J A

2016-01-15

The Spanish "Registry of Pulmonary Arterial Hypertension" (REHAP), started in 2007, includes chronic thromboembolic hypertension (CTEPH) patients. Based on data provided by this registry and retrospective data from patients diagnosed during 2006 (≤ 12 months since the registry was created), clinical management and long-term outcomes of CTEPH patients are analyzed nationwide for the first time in a scenario of a decentralized organization model of CTEPH management. A total of 391 patients (median [Q1:Q3] age 63.7 [48.0;73.3] years, 58% females) with CTEPH included during the period January 1, 2006-December 31, 2013 in the REHAP registry were analyzed. Rate of pulmonary endarterectomy (PEA) was 31.2%, and highly asymmetric among centers: rate was 47.9% at two centers designated as CTEPH expert centers, while it was 4.6% in other centers. Among patients not undergoing PEA, 82% were treated with therapies licensed for pulmonary arterial hypertension (PAH). Five-year survival rate was 86.3% for PEA patients, and 64.9% for non-PEA patients. Among non-PEA patients, presenting proximal lesions (42% of non-referred patients) was associated with a 3-fold increase in mortality. PEA patients achieved significantly better hemodynamic and clinical outcomes at one-year follow-up compared to non-PEA patients. Patients not being referred for PEA assessment were older and had a worse functional capacity. Older age was the most deterrent factor for non-operability. Despite the increase in diagnosis and expertise in PEA-specialized centers, an important percentage of patients do not benefit of PEA in a decentralized organization model of CTEPH management. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Massage, reflexology and other manual methods for pain management in labour.

PubMed

Smith, Caroline A; Levett, Kate M; Collins, Carmel T; Dahlen, Hannah G; Ee, Carolyn C; Suganuma, Machiko

2018-03-28

Many women would like to avoid pharmacological or invasive methods of pain management in labour, and this may contribute towards the popularity of complementary methods of pain management. This review examined the evidence currently available on manual methods, including massage and reflexology, for pain management in labour. This review is an update of the review first published in 2012. To assess the effect, safety and acceptability of massage, reflexology and other manual methods to manage pain in labour. For this update, we searched Cochrane Pregnancy and Childbirth's Trials Register (30 June 2017), the Cochrane Central Register of Controlled Trials (CENTRAL; 2017, Issue 6), MEDLINE (1966 to 30 June 2017, CINAHL (1980 to 30 June 2017), the Australian New Zealand Clinical Trials Registry (4 August 2017), Chinese Clinical Trial Registry (4 August 2017), ClinicalTrials.gov, (4 August 2017), the National Center for Complementary and Integrative Health (4 August 2017), the WHO International Clinical Trials Registry Platform (ICTRP) (4 August 2017) and reference lists of retrieved trials. We included randomised controlled trials comparing manual methods with standard care, other non-pharmacological forms of pain management in labour, no treatment or placebo. We searched for trials of the following modalities: massage, warm packs, thermal manual methods, reflexology, chiropractic, osteopathy, musculo-skeletal manipulation, deep tissue massage, neuro-muscular therapy, shiatsu, tuina, trigger point therapy, myotherapy and zero balancing. We excluded trials for pain management relating to hypnosis, aromatherapy, acupuncture and acupressure; these are included in other Cochrane reviews. Two review authors independently assessed trial quality, extracted data and checked data for accuracy. We contacted trial authors for additional information. We assessed the quality of the evidence using the GRADE approach. We included a total of 14 trials; 10 of these (1055 women) contributed data to meta-analysis. Four trials, involving 274 women, met our inclusion criteria but did not contribute data to the review. Over half the trials had a low risk of bias for random sequence generation and attrition bias. The majority of trials had a high risk of performance bias and detection bias, and an unclear risk of reporting bias. We found no trials examining the effectiveness of reflexology.MassageWe found low-quality evidence that massage provided a greater reduction in pain intensity (measured using self-reported pain scales) than usual care during the first stage of labour (standardised mean difference (SMD) -0.81, 95% confidence interval (CI) -1.06 to -0.56, six trials, 362 women). Two trials reported on pain intensity during the second and third stages of labour, and there was evidence of a reduction in pain scores in favour of massage (SMD -0.98, 95% CI -2.23 to 0.26, 124 women; and SMD -1.03, 95% CI -2.17 to 0.11, 122 women). There was very low-quality evidence showing no clear benefit of massage over usual care for the length of labour (in minutes) (mean difference (MD) 20.64, 95% CI -58.24 to 99.52, six trials, 514 women), and pharmacological pain relief (average risk ratio (RR) 0.81, 95% CI 0.37 to 1.74, four trials, 105 women). There was very low-quality evidence showing no clear benefit of massage for assisted vaginal birth (average RR 0.71, 95% CI 0.44 to 1.13, four trials, 368 women) and caesarean section (RR 0.75, 95% CI 0.51 to 1.09, six trials, 514 women). One trial reported less anxiety during the first stage of labour for women receiving massage (MD -16.27, 95% CI -27.03 to -5.51, 60 women). One trial found an increased sense of control from massage (MD 14.05, 95% CI 3.77 to 24.33, 124 women, low-quality evidence). Two trials examining satisfaction with the childbirth experience reported data on different scales; both found more satisfaction with massage, although the evidence was low quality in one study and very low in the other.Warm packsWe found very low-quality evidence for reduced pain (Visual Analogue Scale/VAS) in the first stage of labour (SMD -0.59, 95% CI -1.18 to -0.00, three trials, 191 women), and the second stage of labour (SMD -1.49, 95% CI -2.85 to -0.13, two trials, 128 women). Very low-quality evidence showed reduced length of labour (minutes) in the warm-pack group (MD -66.15, 95% CI -91.83 to -40.47; two trials; 128 women).Thermal manual methodsOne trial evaluated thermal manual methods versus usual care and found very low-quality evidence of reduced pain intensity during the first phase of labour for women receiving thermal methods (MD -1.44, 95% CI -2.24 to -0.65, one trial, 96 women). There was a reduction in the length of labour (minutes) (MD -78.24, 95% CI -118.75 to -37.73, one trial, 96 women, very low-quality evidence). There was no clear difference for assisted vaginal birth (very low-quality evidence). Results were similar for cold packs versus usual care, and intermittent hot and cold packs versus usual care, for pain intensity, length of labour and assisted vaginal birth.Music One trial that compared manual methods with music found very low-quality evidence of reduced pain intensity during labour in the massage group (RR 0.40, 95% CI 0.18 to 0.89, 101 women). There was no evidence of benefit for reduced use of pharmacological pain relief (RR 0.41, 95% CI 0.16 to 1.08, very low-quality evidence).Of the seven outcomes we assessed using GRADE, only pain intensity was reported in all comparisons. Satisfaction with the childbirth experience, sense of control, and caesarean section were rarely reported in any of the comparisons. Massage, warm pack and thermal manual methods may have a role in reducing pain, reducing length of labour and improving women's sense of control and emotional experience of labour, although the quality of evidence varies from low to very low and few trials reported on the key GRADE outcomes. Few trials reported on safety as an outcome. There is a need for further research to address these outcomes and to examine the effectiveness and efficacy of these manual methods for pain management.

Value and usability of unpublished data sources for systematic reviews and network meta-analyses.

PubMed

Halfpenny, Nicholas James Anthony; Quigley, Joan Mary; Thompson, Juliette Catherine; Scott, David Alexander

2016-12-01

Peer-reviewed publications and conference proceedings are the mainstay of data sources for systematic reviews and network meta-analyses (NMA), but access to informative unpublished data is now becoming commonplace. To explore the usefulness of three types of 'grey' literature-clinical trials registries, clinical study reports and data from regulatory authorities-we conducted four case studies. The reporting of outcome data in peer-reviewed publications, the clinical trials registries and the clinical study reports for two clinical trials-one in melanoma, one in juvenile idiopathic arthritis (JIA)-was examined. In addition, we assessed the value of including unpublished data from the European Medicines Agency (EMA) and US Food and Drug Administration (FDA) in evidence syntheses of hepatitis C virus (HCV) and chronic obstructive pulmonary disease (COPD), respectively. For the clinical trials in melanoma and JIA, we identified outcome parameters on ClinicalTrials.gov additional to those reported in the peer-reviewed publications: subgroup data and additional efficacy end points/extended follow-up, respectively. The clinical study report also provided results for several subgroups unavailable elsewhere. For HCV and COPD, additional outcome data were obtained from the EMA European Public Assessment Report (EPAR) and the FDA, respectively, including data on subgroups and mortality. We conclude that data from these grey literature sources have the potential to influence results of systematic reviews and NMAs, and may thus have implications for healthcare decisions. However, it is important to consider carefully the availability, reliability and consequent usability of these data sources in systematic reviews and NMAs. 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/.

Rationale, Design, and Methodology of the APOLLON trial: A comPrehensive, ObservationaL registry of heart faiLure with midrange and preserved ejectiON fraction.

PubMed

Özlek, Bülent; Özlek, Eda; Çelik, Oğuzhan; Çil, Cem; Doğan, Volkan; Tekinalp, Mehmet; Zencirkıran Ağuş, Hicaz; Kahraman, Serkan; Ösken, Altuğ; Rencüzoğulları, İbrahim; Tanık, Veysel Ozan; Bekar, Lütfü; Çakır, Mustafa Ozan; Kaya, Bedri Caner; Tibilli, Hakan; Çelik, Yunus; Başaran, Özcan; Mert, Kadir Uğur; Sevinç, Samet; Demirci, Erkan; Dondurmacı, Engin; Biteker, Murat

2018-05-01

Although almost half of chronic heart failure (HF) patients have mid-range (HFmrEF) and preserved left-ventricular ejection fraction (HFpEF), no studies have been carried out with these patients in our country. This study aims to determine the demographic characteristics and current status of the clinical background of HFmrEF and HFpEF patients in a multicenter trial. A comPrehensive, ObservationaL registry of heart faiLure with mid range and preserved ejectiON fraction (APOLLON) trial will be an observational, multicenter, and noninterventional study conducted in Turkey. The study population will include 1065 patients from 12 sites in Turkey. All data will be collected at one point in time and the current clinical practice will be evaluated (ClinicalTrials.gov number NCT03026114). We will enroll all consecutive patients admitted to the cardiology clinics who were at least 18 years of age and had New York Heart Association class II, III, or IV HF, elevated brain natriuretic peptide levels within the last 30 days, and an left ventricular ejection fraction (LVEF) of at least 40%. Patients fulfilling the exclusion criteria will not be included in the study. Patients will be stratified into two categories according to LVEF: mid-range EF (HFmrEF, LVEF 40%-49%) and preserved EF (HFpEF, LVEF ≥50%). Regional quota sampling will be performed to ensure that the sample was representative of the Turkish population. Demographic, lifestyle, medical, and therapeutic data will be collected by this specific survey. The APOLLON trial will be the largest and most comprehensive study in Turkey evaluating HF patients with a LVEF ≥40% and will also be the first study to specifically analyze the recently designated HFmrEF category.

Intravenous immunoglobulin treatment of the complex regional pain syndrome: a randomized trial.

PubMed

Goebel, Andreas; Baranowski, Andrew; Maurer, Konrad; Ghiai, Artemis; McCabe, Candy; Ambler, Gareth

2010-02-02

Treatment of long-standing complex regional pain syndrome (CRPS) is empirical and often of limited efficacy. Preliminary data suggest that the immune system is involved in sustaining this condition and that treatment with low-dose intravenous immunoglobulin (IVIG) may substantially reduce pain in some patients. To evaluate the efficacy of IVIG in patients with longstanding CRPS under randomized, controlled conditions. A randomized, double-blind, placebo-controlled crossover trial. (National Research Registry number: N0263177713; International Standard Randomised Controlled Trial Number Registry: 63918259) University College London Hospitals Pain Management Centre. Persons who had pain intensity greater than 4 on an 11-point (0 to 10) numerical rating scale and had CRPS for 6 to 30 months that was refractory to standard treatment. IVIG, 0.5 g/kg, and normal saline in separate treatments, divided by a washout period of at least 28 days. The primary outcome was pain intensity 6 to 19 days after the initial treatment and the crossover treatment. 13 eligible participants were randomly assigned between November 2005 and May 2008; 12 completed the trial. The average pain intensity was 1.55 units lower after IVIG treatment than after saline (95% CI, 1.29 to 1.82; P < 0.001). In 3 patients, pain intensity after IVIG was less than after saline by 50% or more. No serious adverse reactions were reported. The trial was small, and recruitment bias and chance variation could have influenced results and their interpretation. IVIG, 0.5 g/kg, can reduce pain in refractory CRPS. Studies are required to determine the best immunoglobulin dose, the duration of effect, and when repeated treatments are needed. Association of Anaesthetists of Great Britain and Ireland, University College London Hospitals Charity, and CSL-Behring.

Economic Evaluations of Pharmaceuticals Granted a Marketing Authorisation Without the Results of Randomised Trials: A Systematic Review and Taxonomy.

PubMed

Hatswell, Anthony J; Freemantle, Nick; Baio, Gianluca

2017-02-01

Pharmaceuticals are usually granted a marketing authorisation on the basis of randomised controlled trials (RCTs). Occasionally the efficacy of a treatment is assessed without a randomised comparator group (either active or placebo). To identify and develop a taxonomic account of economic modelling approaches for pharmaceuticals licensed without RCT data. We searched PubMed, the websites of UK health technology assessment bodies and the International Society for Pharmacoeconomics and Outcomes Research Scientific Presentations Database for assessments of treatments granted a marketing authorisation by the US Food and Drug Administration or European Medicines Agency from January 1999 to May 2014 without RCT data (74 indications). The outcome of interest was the approach to modelling efficacy data. Fifty-one unique models were identified in 29 peer-reviewed articles, 30 health technology appraisals, and 15 International Society for Pharmacoeconomics and Outcomes Research abstracts concerning 30 indications (44 indications had not been modelled). We noted the high rate of non-submission to health technology assessment agencies (28/98). The majority of models (43/51) were based on 'historical controls'-comparisons to previous meta-analysis or pooling of trials (5), individual trials (16), registries/case series (15), or expert opinion (7). Other approaches used the patient as their own control, performed threshold analysis, assumed time on treatment was added to overall survival, or performed cost-minimisation analysis. There is considerable variation in the quality and approach of models constructed for drugs granted a marketing authorisation without a RCT. The most common approach is of a naive comparison to historical data (using other trials/registry data as a control group), which has considerable scope for bias.

Dietary Sodium Modifies Serum Uric Acid Concentrations in Humans.

PubMed

Todd, Alwyn S; Walker, Robert J; MacGinley, Robert J; Kelly, Jaimon; Merriman, Tony R; Major, Tanya J; Johnson, Richard J

2017-11-06

Subjects with hypertension are frequently obese or insulin resistant, both conditions in which hyperuricemia is common. Obese and insulin-resistant subjects are also known to have blood pressure that is more sensitive to changes in dietary sodium intake. Whether hyperuricemia is a resulting consequence, moderating or contributing factor to the development of hypertension has not been fully evaluated and very few studies have reported interactions between sodium intake and serum uric acid. We performed further analysis of our randomized controlled clinical trials (Australian New Zealand Clinical Trials Registry #12609000161224 and #12609000292279) designed to assess the effects of modifying sodium intake on concentrations of serum markers, including uric acid. Uric acid and other variables (including blood pressure, renin, and aldosterone) were measured at baseline and 4 weeks following the commencement of low (60 mmol/day), moderate (150 mmol/day), and high (200-250 mmol/day) dietary sodium intake. The median aldosterone-to-renin ratio was 1.90 [pg/ml]/[pg/ml] (range 0.10-11.04). Serum uric acid fell significantly in both the moderate and high interventions compared to the low sodium intervention. This pattern of response occurred when all subjects were analyzed, and when normotensive or hypertensive subjects were analyzed alone. Although previously reported in hypertensive subjects, these data provide evidence in normotensive subjects of an interaction between dietary sodium intake and serum uric acid. As this interaction is present in the absence of hypertension, it is possible it could play a role in hypertension development, and will need to be considered in future trials of dietary sodium intake. The trials were registered with the Australian and New Zealand Clinical Trials Registry as ACTRN12609000161224 and ACTRN1260. © American Journal of Hypertension, Ltd 2017. All rights reserved. For Permissions, please email: journals.permissions@oup.com

Implementation of a children's hospital-wide central venous catheter insertion and maintenance bundle.

PubMed

Helder, Onno; Kornelisse, René; van der Starre, Cynthia; Tibboel, Dick; Looman, Caspar; Wijnen, René; Poley, Marten; Ista, Erwin

2013-10-14

Central venous catheter-associated bloodstream infections in children are an increasingly recognized serious safety problem worldwide, but are often preventable. Central venous catheter bundles have proved effective to prevent such infections. Successful implementation requires changes in the hospital system as well as in healthcare professionals' behaviour. The aim of the study is to evaluate process and outcome of implementation of a state-of-the-art central venous catheter insertion and maintenance bundle in a large university children's hospital. An interrupted time series design will be used; the study will encompass all children who need a central venous catheter. New state-of-the-art central venous catheter bundles will be developed. The Pronovost-model will guide the implementation process. We developed a tailored multifaceted implementation strategy consisting of reminders, feedback, management support, local opinion leaders, and education. Primary outcome measure is the number of catheter-associated infections per 1000 line-days. The process outcome is degree of adherence to use of these central venous catheter bundles is the secondary outcome. A cost-effectiveness analysis is part of the study. Outcomes will be monitored during three periods: baseline, pre-intervention, and post-intervention for over 48 months. This model-based implementation strategy will reveal the challenges of implementing a hospital-wide safety program. This work will add to the body of knowledge in the field of implementation. We postulate that healthcare workers' willingness to shift from providing habitual care to state-of-the-art care may reflect the need for consistent care improvement. Trial registration: Dutch trials registry, trial # 3635. Dutch trials registry (http://www.trialregister.nl), trial # 3635.

Effectiveness of an intervention to facilitate the implementation of healthy eating and physical activity policies and practices in childcare services: a randomised controlled trial.

PubMed

Jones, Jannah; Wyse, Rebecca; Finch, Meghan; Lecathelinais, Christophe; Wiggers, John; Marshall, Josephine; Falkiner, Maryann; Pond, Nicole; Yoong, Sze Lin; Hollis, Jenna; Fielding, Alison; Dodds, Pennie; Clinton-McHarg, Tara; Freund, Megan; McElduff, Patrick; Gillham, Karen; Wolfenden, Luke

2015-10-25

The primary aim of this study was to evaluate the effectiveness of an intervention to increase the implementation of healthy eating and physical activity policies and practices by centre-based childcare services. The study also sought to determine if the intervention was effective in improving child dietary intake and increasing child physical activity levels while attending childcare. A parallel group, randomised controlled trial was conducted in a sample of 128 childcare services. Intervention strategies included provision of implementation support staff, securing executive support, staff training, consensus processes, academic detailing visits, tools and resources, performance monitoring and feedback and a communications strategy. The primary outcome of the trial was the proportion of services implementing all seven healthy eating and physical activity policies and practices targeted by the intervention. Outcome data were collected via telephone surveys with nominated supervisors and room leaders at baseline and immediately post-intervention. Secondary trial outcomes included the differences between groups in the number of serves consumed by children for each food group within the Australian Guide to Healthy Eating and in the proportion of children engaged in sedentary, walking or very active physical activity assessed via observation in a random subsample of 36 services at follow-up. There was no significant difference between groups for the primary trial outcome (p = 0.44). Relative to the control group, a significantly larger proportion of intervention group services reported having a written nutrition and physical activity policy (p = 0.05) and providing adult-guided activities to develop fundamental movement skills (p = 0.01). There were no significant differences between groups at follow-up on measures of child dietary intake or physical activity. The findings of the trial were equivocal. While there was no significant difference between groups for the primary trial outcome, the intervention did significantly increase the proportion of intervention group services implementing two of the seven healthy eating and physical activity policies and practices. High levels of implementation of a number of policies and practices at baseline, significant obesity prevention activity in the study region and higher than previously reported intra-class correlation of child behaviours may, in part, explain the trial findings. Australian Clinical Trials Registry (reference ACTRN12612000927820 ).

Web-based Therapy Plus Support by a Coach in Depressed Patients Referred to Secondary Mental Health Care: Randomized Controlled Trial.

PubMed

Hatcher, Simon; Whittaker, Robyn; Patton, Murray; Miles, Wayne Sylvester; Ralph, Nicola; Kercher, Katharina; Sharon, Cynthia

2018-01-23

The evidence for the effectiveness of Web-based therapies comes mainly from nonclinical populations, with a few studies in primary care. There is little evidence from patients referred to secondary mental health care with depression. Adherence to Web-based therapies is often poor. One way to increase this is to create a new health service role of a coach to guide people through the therapy. This study aimed to test in people referred to secondary care with depression if a Web-based therapy (The Journal) supported by a coach plus usual care would be more effective in reducing depression compared with usual care plus an information leaflet about Web-based resources after 12 weeks. We conducted a randomized controlled trial with two parallel arms and a process evaluation that included structured qualitative interviews analyzed using thematic analysis. The coach had a background in occupational therapy. Participants were recruited face-to-face at community mental health centers. We recruited 63 people into the trial (intervention 35, control 28). There were no statistically significant differences in the change from baseline in Patient Health Questionnaire-9 (PHQ-9) scores at 12 weeks comparing The Journal with usual care (mean change in PHQ-9 score 9.4 in the intervention group and 7.1 in the control group, t 41 =1.05, P=.30; mean difference=2.3, 95% CI -2.1 to 6.7). People who were offered The Journal attended on average about one less outpatient appointment compared with usual care, although this difference was not statistically significant (intervention mean number of visits 2.8 (SD 5.5) compared with 4.1 (SD 6.7) in the control group, t 45 =-0.80, P=.43; mean difference=1.3, 95% CI -4.5 to 2.0). The process evaluation found that the mean number of lessons completed in the intervention group was 2.5 (SD=1.9; range=0-6) and the number of contacts with the coach was a mean of 8.1 (SD=4.4; range=0-17). The qualitative interviews highlighted the problem of engaging clinicians in research and their resistance to recruitment: technical difficulties with The Journal, which prevented people logging in easily; difficulty accessing The Journal as it was not available on mobile devices; participants finding some lessons difficult; and participants saying they were too busy to complete the sessions. The study demonstrated that it is feasible to use a coach in this setting, that people found it helpful, and that it did not conflict with other care that participants were receiving. Future trials need to engage clinicians at an early stage to articulate where Web-based therapies fit into existing clinical pathways; Web-based therapies should be available on mobile devices, and logging in should be easy. The role of the coach should be explored in larger trials. Australian New Zealand Clinical Trials Registry (ACTRN): 12613000015741; https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=363351&isReview=true (Archived by WebCite at http://www.webcitation.org/6wEyCc6Ss). ©Simon Hatcher, Robyn Whittaker, Murray Patton, Wayne Sylvester Miles, Nicola Ralph, Katharina Kercher, Cynthia Sharon. Originally published in JMIR Mental Health (http://mental.jmir.org), 23.01.2018.

One-year clinical outcome of biodegradable polymer sirolimus-eluting stent in all-comers population. Insight from the ULISSE registry (ULtimaster Italian multicenter all comerS Stent rEgistry).

PubMed

Godino, Cosmo; Beneduce, Alessandro; Ferrante, Giuseppe; Ielasi, Alfonso; Pivato, Andrea Carlo; Chiarito, Mauro; Cappelletti, Alberto; Perfetti, Giulia; Magni, Valeria; Prati, Eugenio; Falcone, Stefania; Pierri, Adele; De Martini, Stefano; Montorfano, Matteo; Parisi, Rosario; Rutigliano, David; Locuratolo, Nicola; Anzuini, Angelo; Tespilli, Maurizio; Margonato, Alberto; Benassi, Alberto; Briguori, Carlo; Fabbiocchi, Franco; Reimers, Bernhard; Bartorelli, Antonio; Colombo, Antonio

2018-06-01

This study was designed to confirm in a large population of unselected patients the promising results of Ultimaster® biodegradable polymer sirolimus-eluting stent (BP-SES) already shown in previous trial. ULISSE is an observational, multicenter, national registry evaluating all patients undergoing PCI with the Ultimaster® BP-SES. Incidence of 1-year TLF (cardiac death or target vessel MI or clinically indicated TLR) was the primary endpoint. Pre-specified subgroup analysis was performed for diabetic patients and for those with lesion longer than 25 mm, bifurcation and CTO lesions. 1660 patients were enrolled in 9 Italian cardiology centers, 82% were males, mean age of 68 ± 10 years, and 29% were diabetics. Overall 2422 lesions were treated, 65% type B2/C lesions, 7% CTOs, 17% bifurcations and 38% long lesions. The incidence of 1-year TLF was 5%, with 3.2% of clinically indicated TLR. TLF occurred in 8% of the patients with diabetes mellitus, and 7% in bifurcation, 6.7% in CTO and 6.2% in long lesions. Definite overall ST was 0.9%, and 1.2% in patients treated for type B2/C lesions. Multivariate logistic regression analysis identified stenting on unprotected LMT (OR = 4.80), stenting on ISR lesion (OR = 3.19) and need for rotational atherectomy (OR = 6.24) as the strongest independent predictors of TLF. The results of this national all-comers registry show that the Ultimaster® BP-SES real-world performance was comparable with that observed in the clinical trial, with low rate of primary endpoint and TLR. Long term follow-up will be necessary to prove the theoretical advantage of the BP-SES over time. Copyright © 2017. Published by Elsevier B.V.

Integrated image data and medical record management for rare disease registries. A general framework and its instantiation to theGerman Calciphylaxis Registry.

PubMed

Deserno, Thomas M; Haak, Daniel; Brandenburg, Vincent; Deserno, Verena; Classen, Christoph; Specht, Paula

2014-12-01

Especially for investigator-initiated research at universities and academic institutions, Internet-based rare disease registries (RDR) are required that integrate electronic data capture (EDC) with automatic image analysis or manual image annotation. We propose a modular framework merging alpha-numerical and binary data capture. In concordance with the Office of Rare Diseases Research recommendations, a requirement analysis was performed based on several RDR databases currently hosted at Uniklinik RWTH Aachen, Germany. With respect to the study management tool that is already successfully operating at the Clinical Trial Center Aachen, the Google Web Toolkit was chosen with Hibernate and Gilead connecting a MySQL database management system. Image and signal data integration and processing is supported by Apache Commons FileUpload-Library and ImageJ-based Java code, respectively. As a proof of concept, the framework is instantiated to the German Calciphylaxis Registry. The framework is composed of five mandatory core modules: (1) Data Core, (2) EDC, (3) Access Control, (4) Audit Trail, and (5) Terminology as well as six optional modules: (6) Binary Large Object (BLOB), (7) BLOB Analysis, (8) Standard Operation Procedure, (9) Communication, (10) Pseudonymization, and (11) Biorepository. Modules 1-7 are implemented in the German Calciphylaxis Registry. The proposed RDR framework is easily instantiated and directly integrates image management and analysis. As open source software, it may assist improved data collection and analysis of rare diseases in near future.

A Diagnosis of Lynch Syndrome - Genetic Testing | NIH MedlinePlus the Magazine

MedlinePlus

... Testing - From Genetics Home Reference: the benefits, costs, risks, and limitations of genetic testing Genetic Testing Registry -A publicly funded medical genetics information resource developed for physicians, other health care providers, and researchers MedlinePlus — Genetic Testing CLINSEQ®: ...

Clinical trials for vaccine development in registry of Korea Food and Drug Administration

PubMed Central

2013-01-01

Based on the action plan "Ensuring a stable supply of National Immunization Program vaccines and sovereignty of biopharmaceutical products," Korea Food and Drug Administration (KFDA) has made efforts to develop vaccines in the context of self reliance and to protect public health. Along with the recognized infrastructures for clinical trials, clinical trials for vaccines have also gradually been conducted at multinational sites as well as at local sites. KFDA will support to expand six to eleven kinds of vaccines by 2017. In accordance with integrated regulatory system, KFDA has promoted clinical trials, established national lot release procedure, and strengthened good manufacturing practices inspection and post marketing surveillance. Against this backdrop, KFDA will support the vaccine development and promote excellent public health protection. PMID:23596594

A population-based registry as a source of health indicators for rare diseases: the ten-year experience of the Veneto Region’s rare diseases registry

PubMed Central

2014-01-01

Background Although rare diseases have become a major public health issue, there is a paucity of population-based data on rare diseases. The aim of this epidemiological study was to provide descriptive figures referring to a sizable group of unrelated rare diseases. Methods Data from the rare diseases registry established in the Veneto Region of north-east Italy (population 4,900,000), referring to the years from 2002 to 2012, were analyzed. The registry is based on a web-based system accessed by different users. Cases are enrolled by two different sources: clinicians working at Centers of expertise officially designated to diagnose and care patients with rare diseases and health professionals working in the local health districts. Deaths of patients are monitored by Death Registry. Results So far, 19,547 patients with rare diseases have been registered, and 23% of them are pediatric cases. The overall raw prevalence of the rare diseases monitored in the population under study is 33.09 per 10,000 inhabitants (95% CI 32.56-33.62), whilst the overall incidence is 3.85 per 10,000 inhabitants (95% CI 3.67-4.03). The most commonly-recorded diagnoses belong to the following nosological groups: congenital malformations (Prevalence: 5.45/10,000), hematological diseases (4.83/10,000), ocular disorders (4.47/10,000), diseases of the nervous system (3.51/10,000), and metabolic disorders (2,95/10,000). Most of the deaths in the study population occur among pediatric patients with congenital malformations, and among adult cases with neurological diseases. Rare diseases of the central nervous system carry the highest fatality rate (71.36/1,000). Rare diseases explain 4.2% of general population Years of Life Lost (YLLs), comparing to 1.2% attributable to infectious diseases and 2.6% to diabetes mellitus. Conclusions Our estimates of the burden of rare diseases at population level confirm that these conditions are a relevant public health issue. Our snapshot of their epidemiology is important for public health planning purposes, going to show that population-based registries are useful tools for generating health indicators relating to a considerable number of rare diseases, rather than to specific conditions. PMID:24646171

Antibiotics for treating gonorrhoea in pregnancy.

PubMed

Comunián-Carrasco, Gabriella; Peña-Martí, Guiomar E; Martí-Carvajal, Arturo J

2018-02-21

Gonorrhoea is a sexually transmitted infection that is caused by Neisseria gonorrhoeae, and is a major public health challenge today. N gonorrhoeae can be transmitted from the mother's genital tract to the newborn during birth, and can cause gonococcal ophthalmia neonatorum as well as systemic neonatal infections. It can also cause endometritis and pelvic sepsis in the mother. This review updates and replaces an earlier Cochrane Review on antibiotics for treating this infectious condition. To assess the clinical effectiveness and harms of antibiotics for treating gonorrhoea in pregnant women. We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (31 May 2017), LILACS database (1982 to April 5, 2017), the WHO International Clinical Trials Registry Platform (ICTRP; April 5, 2017), ClinicalTrials.gov (April 5, 2017), the ISRCTN Registry (April 5, 2017), and Epistemonikos (April 5, 2017). We also searched reference lists of all retrieved articles. We included randomised controlled trials (RCTs) comparing the use of antibiotics for treating gonorrhoea in pregnancy. The antibiotics could have been used alone or in combination, were administered parenterally, orally, or both, and were compared with another antibiotic.We included RCTs regardless of their publication status (published, unpublished, published as an article, an abstract, or a letter), language, or country. We applied no limits on the length of follow-up.We excluded RCTs using a cluster- or cross-over design, or quasi-RCTs. Three review authors independently assessed trials for inclusion and risk of bias, extracted data, and checked them for accuracy. We included two RCTs, that randomised 514 pregnant women (347 women analysed) at a mean gestational age of 22 weeks. Both trials were conducted in the outpatient department of the same two hospitals in the USA between 1993 and 2001, and had a follow-up of 14 days. One of the trials was sponsored by a drug company. We considered both trials to be at a high risk of bias.One trial compared ceftriaxone (125 mg, intramuscular) with cefixime (400 mg, oral); the other trial had three arms, and assessed ceftriaxone (250 mg, intramuscular) versus either amoxicillin (3 g, oral) plus probenecid (1 g, oral) or spectinomycin (2 g, intramuscular). We did not include the spectinomycin data because this medication is no longer produced. We were unable to conduct meta-analysis because the trials compared different medications.We found inconclusive evidence that there were clear differences in the cure of gonococcal infections (genital, extragenital, or both) between intramuscular ceftriaxone versus oral amoxicillin plus oral probenecid (risk ratio (RR) 1.07, 95% confidence interval (CI) 0.98 to 1.16; one RCT; 168 women; very low-quality evidence) or intramuscular ceftriaxone versus oral cefixime (RR 0.99, 95% CI 0.91 to 1.08; one RCT; 95 women; very low-quality evidence).Neither of the trials reported on two of this review's primary maternal outcomes: incidence of obstetric complications (miscarriage, premature rupture of membranes, preterm delivery, or fetal death), or disseminated gonococcal infection, or on the incidence of neonatorum ophthalmia in the neonates.One trial reported one case of vomiting in the oral amoxacillin plus probenecid group. Trials reported pain at the injection sites, but did not quantify it. Hyperberbilurrubinemia was more frequent in neonates whose mothers were exposed to ceftriaxone. There were no clear differences between groups for neonatal malformation. This Cochrane Review found high levels of cure of gonococcal infections in pregnancy with the given antibiotic regimens. However, the evidence in this review is inconclusive as it does not support one particular regimen over another. This conclusion was based on very low-quality evidence (downgraded for poor trial design, imprecision) from two trials (involving 514 women), which we assessed to be at a high risk of bias for a number of domains. The harm profiles of the antibiotic regimes featured in this review remain unknown.High-quality RCTs are needed, with sufficient power to assess the clinical effectiveness and potential harms of antibiotics in pregnant women with gonorrhoea. These should be planned according to Standard Protocol Items: Recommendations for Interventional Trials (SPIRIT),conducted following CONSORT recommendations, and based on Patient-Centered Outcomes Research Institute (PCORI) outcomes.

Beyond PubMed: Searching the “Grey Literature” for Clinical Trial Results

PubMed Central

2014-01-01

Clinical trial results have been traditionally communicated through the publication of scholarly reports and reviews in biomedical journals. However, this dissemination of information can be delayed or incomplete, making it difficult to appraise new treatments, or in the case of missing data, evaluate older interventions. Going beyond the routine search of PubMed, it is possible to discover additional information in the “grey literature.” Examples of the grey literature include clinical trial registries, patent databases, company and industrywide repositories, regulatory agency digital archives, abstracts of paper and poster presentations on meeting/congress websites, industry investor reports and press releases, and institutional and personal websites. PMID:25337445

Target organ damage and incident type 2 diabetes mellitus: the Strong Heart Study.

PubMed

de Simone, Giovanni; Wang, Wenyu; Best, Lyle G; Yeh, Fawn; Izzo, Raffaele; Mancusi, Costantino; Roman, Mary J; Lee, Elisa T; Howard, Barbara V; Devereux, Richard B

2017-05-12

Recent analyses in a registry of hypertensive patients suggested that preceding left ventricular (LV) hypertrophy (LVH) and/or carotid atherosclerosis are associated with incident type 2 diabetes, independent of confounders. We assess the relation between prevalent cardio-renal target organ damage (TOD) and subsequent incident type 2 diabetes in a population-based study with high prevalence of obesity. We selected 2887 non-diabetic participants from two cohorts of the Strong Heart Study (SHS). Clinical exam, laboratory tests and echocardiograms were performed. Adjudicated TODs were LVH, left atrium (LA) dilatation, and high urine albumin/creatinine ratio (UACR). Multivariable logistic regression models were used to identify variables responsible for the association between initial TODs and incident diabetes at 4-year follow-up (FU). After 4 years, 297 new cases of diabetes (10%) were identified, 216 of whom exhibited baseline impaired fasting glucose (IFG, 73%, p < 0.0001). Participants developing type 2 diabetes exhibited higher inflammatory markers, fat-free mass and adipose mass and higher prevalence of initial LVH and LA dilatation than those without (both p < 0.04). In multivariable logistic regression, controlling for age, sex, family relatedness, presence of arterial hypertension and IFG, all three indicators of TOD predicted incident diabetes (all p < 0.01). However, the effects of TOD was offset when body fat and inflammatory markers were introduced into the model. In this population-based study with high prevalence of obesity, TOD precedes clinical appearance of type 2 diabetes and is related to the preceding metabolic status, body composition and inflammatory status. Trial registration Trial registration number: NCT00005134, Name of registry: Strong Heart Study, URL of registry: https://clinicaltrials.gov/ct2/show/NCT00005134, Date of registration: May 25, 2000, Date of enrolment of the first participant to the trial: September 1988.

Fundus autofluorescence imaging: systematic review of test accuracy for the diagnosis and monitoring of retinal conditions.

PubMed

Frampton, G K; Kalita, N; Payne, L; Colquitt, J L; Loveman, E; Downes, S M; Lotery, A J

2017-07-01

We conducted a systematic review of the accuracy of fundus autofluorescence (FAF) imaging for diagnosing and monitoring retinal conditions. Searches in November 2014 identified English language references. Sources included MEDLINE, EMBASE, the Cochrane Library, Web of Science, and MEDION databases; reference lists of retrieved studies; and internet pages of relevant organisations, meetings, and trial registries. For inclusion, studies had to report FAF imaging accuracy quantitatively. Studies were critically appraised using QUADAS risk of bias criteria. Two reviewers conducted all review steps. From 2240 unique references identified, eight primary research studies met the inclusion criteria. These investigated diagnostic accuracy of FAF imaging for choroidal neovascularisation (one study), reticular pseudodrusen (three studies), cystoid macular oedema (two studies), and diabetic macular oedema (two studies). Diagnostic sensitivity of FAF imaging ranged from 32 to 100% and specificity from 34 to 100%. However, owing to methodological limitations, including high and/or unclear risks of bias, none of these studies provides conclusive evidence of the diagnostic accuracy of FAF imaging. Study heterogeneity precluded meta-analysis. In most studies, the patient spectrum was not reflective of those who would present in clinical practice and no studies adequately reported whether FAF images were interpreted consistently. No studies of monitoring accuracy were identified. An update in October 2016, based on MEDLINE and internet searches, identified four new studies but did not alter our conclusions. Robust quantitative evidence on the accuracy of FAF imaging and how FAF images are interpreted is lacking. We provide recommendations to address this.

Drug-resistant tuberculosis clinical trials: proposed core research definitions in adults.

PubMed

Furin, J; Alirol, E; Allen, E; Fielding, K; Merle, C; Abubakar, I; Andersen, J; Davies, G; Dheda, K; Diacon, A; Dooley, K E; Dravnice, G; Eisenach, K; Everitt, D; Ferstenberg, D; Goolam-Mahomed, A; Grobusch, M P; Gupta, R; Harausz, E; Harrington, M; Horsburgh, C R; Lienhardt, C; McNeeley, D; Mitnick, C D; Nachman, S; Nahid, P; Nunn, A J; Phillips, P; Rodriguez, C; Shah, S; Wells, C; Thomas-Nyang'wa, B; du Cros, P

2016-03-01

Drug-resistant tuberculosis (DR-TB) is a growing public health problem, and for the first time in decades, new drugs for the treatment of this disease have been developed. These new drugs have prompted strengthened efforts in DR-TB clinical trials research, and there are now multiple ongoing and planned DR-TB clinical trials. To facilitate comparability and maximise policy impact, a common set of core research definitions is needed, and this paper presents a core set of efficacy and safety definitions as well as other important considerations in DR-TB clinical trials work. To elaborate these definitions, a search of clinical trials registries, published manuscripts and conference proceedings was undertaken to identify groups conducting trials of new regimens for the treatment of DR-TB. Individuals from these groups developed the core set of definitions presented here. Further work is needed to validate and assess the utility of these definitions but they represent an important first step to ensure there is comparability in clinical trials on multidrug-resistant TB.

New approaches to trials in glomerulonephritis.

PubMed

Craig, Jonathan C; Tong, Allison; Strippoli, Giovanni F M

2017-01-01

Randomized controlled trials are required to reliably identify interventions to improve the outcomes for people with glomerulonephritis (GN). Unfortunately, although easier, observational studies are inherently unreliable even though the findings of both study designs agree most of the time. Currently there are ∼790 trials in GN, but suboptimal design and reporting, together with small sample sizes, mean that they may not be reliable for decision making. If the history is somewhat bleak, the future looks bright, with recent initiatives to improve the quality, size and relevance of clinical trials in nephrology, including greater patient engagement, trial networks, core outcome sets, registry-based trials and adaptive designs. Given the current state of the evidence informing the care of people with GN, disruptive technologies and pervasive culture change is required to ensure that the potential of trials to improve the health of people with this complex condition is to be realized. © The Author 2017. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved.

Protocol for a randomised controlled trial of 90% kanuka honey versus 5% aciclovir for the treatment of herpes simplex labialis in the community setting.

PubMed

Semprini, Alex; Singer, Joseph; Shortt, Nicholas; Braithwaite, Irene; Beasley, Richard

2017-08-03

Worldwide, about 90% of people are infected with the herpes simplex virus, 30% of whom will experience recurrent herpes simplex labialis, commonly referred to as 'cold sores', which can last up to 10 days. The most common treatment is aciclovir cream which reduces healing time by just half a day compared with no specific treatment. This is a protocol for a randomised controlled trial (RCT) to determine the efficacy of medical grade kanuka honey-based topical treatment (Honevo) in reducing the healing time and pain of cold sores, compared with topical aciclovir treatment (Viraban). This open-label, parallel-group, active comparator superiority RCT will compare the efficacy of medical grade kanuka honey with 5% aciclovir cream in the treatment of cold sores in the setting of a pharmacy research network of 60 sites throughout New Zealand. Adults presenting with a cold sore (N=950) will be randomised by pharmacy-based investigators. The pharmacy-based investigators will dispense the investigational product to randomised participants and both study groups apply the treatment five times daily until their skin returns to normal or for 14 days, whichever occurs first. In response to a daily SMS message, participants complete an assessment of their cold sore healing, with reference to a visual guide, and transmit it to the investigators by a smartphone eDiary in real time. The primary outcome variable is time (in days) from randomisation to return to normal skin. Secondary endpoints include total healing time stratified by stage of the lesion at onset of treatment, highest pain severity and time to pain resolution. New Zealand Ethics Registration 15/NTB/93. Results will be published in a peer-reviewed medical journal, presented at academic meetings and reported to participants. Australia New Zealand Clinical Trials Registry: ACTRN12615000648527, pre-results.SCOTT Registration: 15/SCOTT/14 PROTOCOL VERSION: 4.0 (12 June 2017). © 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.

Design of a randomized, non-inferiority trial to evaluate the reliability of videoconferencing for remote consultation of diabetes

PubMed Central

2014-01-01

Background An estimated 366 million people are living with diabetes worldwide and it is predicted that its prevalence will increase to 552 million by 2030. Management of this disease and its complications is a challenge for many countries. Optimal glycaemic control is necessary to minimize complications, but less than 70% of diabetic patients achieve target levels of blood glucose, partly due to poor access to qualified health care providers. Telemedicine has the potential to improve access to health care, especially for rural and remote residents. Video teleconsultation, a real-time (or synchronous) mode of telemedicine, is gaining more popularity around the world through recent improvements in digital telecommunications. If video consultation is to be offered as an alternative to face-to-face consultation in diabetes assessment and management, then it is important to demonstrate that this can be achieved without loss of clinical fidelity. This paper describes the protocol of a randomised controlled trail for assessing the reliability of remote video consultation for people with diabetes. Methods/Design A total of 160 people with diabetes will be randomised into either a Telemedicine or a Reference group. Participants in the Reference group will receive two sequential face-to-face consultations whereas in the Telemedicine group one consultation will be conducted face-to-face and the other via videoconference. The primary outcome measure will be a change in the patient’s medication. Secondary outcome measures will be findings in physical examination, detecting complications, and patient satisfaction. A difference of less than 20% in the aggregated level of agreement between the two study groups will be used to identify if videoconference is non-inferior to traditional mode of clinical care (face-to-face). Discussion Despite rapid growth in application of telemedicine in a variety of medical specialities, little is known about the reliability of videoconferencing for remote consultation of people with diabetes. Results of this proposed study will provide evidence of the reliability of specialist consultation offered by videoconference for people with diabetes. Trial registration number Australian New Zealand Clinical Trials Registry ACTRN12612000315819. PMID:24528569

An innovative and collaborative partnership between patients with rare disease and industry-supported registries: the Global aHUS Registry.

PubMed

Woodward, Len; Johnson, Sally; Walle, Johan Vande; Beck, Joran; Gasteyger, Christoph; Licht, Christoph; Ariceta, Gema

2016-11-21

Patients are becoming increasingly involved in research which can promote innovation through novel ideas, support patient-centred actions, and facilitate drug development. For rare diseases, registries that collect data from patients can increase knowledge of the disease's natural history, evaluate clinical therapies, monitor drug safety, and measure quality of care. The active participation of patients is expected to optimise rare-disease management and improve patient outcomes. However, few reports address the type and frequency of interactions involving patients, and what research input patient groups have. Here, we describe a collaboration between an international group of patient organisations advocating for patients with atypical haemolytic uraemic syndrome (aHUS), the aHUS Alliance, and an international aHUS patient registry (ClinicalTrials.gov NCT01522183). The aHUS Registry Scientific Advisory Board (SAB) invited the aHUS Alliance to submit research ideas important to patients with aHUS. This resulted in 24 research suggestions from patients and patient organisations being presented to the SAB. The proposals were classified under seven categories, the most popular of which were understanding factors that cause disease manifestations and learning more about the clinical and psychological/social impact of living with the disease. Subsequently, aHUS Alliance members voted for up to five research priorities. The top priority was: "What are the outcomes of a transplant without eculizumab and what non-kidney damage is likely in patients with aHUS?". This led directly to the initiation of an ongoing analysis of the data collected in the Registry on patients with kidney transplants. This collaboration resulted in several topics proposed by the aHUS Alliance being selected as priority activities for the aHUS Registry, with one new analysis already underway. A clear pathway was established for engagement between a patient advocacy group and an international research network. This should ensure the development of a long-term partnership which clearly benefits both groups.

TREatment of ATopic eczema (TREAT) Registry Taskforce: An international Delphi exercise to identify a core set of domains and domain items for national atopic eczema photo- and systemic therapy registries.

PubMed

Gerbens, L A A; Apfelbacher, C J; Irvine, A D; Barbarot, S; de Booij, R J; Boyce, A E; Deleuran, M; Eichenfield, L F; Hof, M H; Middelkamp-Hup, M A; Roberts, A; Schmitt, J; Vestergaard, C; Wall, D; Weidinger, S; Williamson, P R; Flohr, C; Spuls, P I

2018-05-15

Evidence of immunomodulatory therapies to guide clinical management for atopic eczema (AE) is scarce, despite frequent and often off-label use. Patient registries provide valuable evidence for the effects of treatments under real world conditions which can inform treatment guidelines, give the opportunity for health economic evaluation and the evaluation of quality of care, as well as pharmacogenetic and -dynamic research which cannot be adequately addressed in clinical trials. The TREatment of ATopic eczema (TREAT) Registry Taskforce aims to seek international consensus on a core set of domains and items ('what to measure') for AE research registries, using a Delphi approach. Participants from six stakeholder groups were included: doctors, nurses, non-clinical researchers, patients, industry and regulatory body representatives. The eDelphi comprised 3 sequential online rounds, requesting participants to rate the importance of each proposed domain item. Participants could add domain items to the proposed list in round 1. A final consensus meeting was held to ratify the core set. 479 participants from 36 countries accessed the eDelphi platform, of whom 86%, 79% and 74% completed rounds 1, 2, and 3 respectively. At the face-to-face consensus meeting attended by 42 participants the final core set was established containing 19 domains with 69 domain items (49 baseline and 20 follow-up items). This core set of domains and items to be captured by national AE systemic therapy registries will standardise data collection and thereby allow direct comparability across registries and facilitate data pooling between countries. Ultimately, it will provide greater insight into the effectiveness, safety and cost-effectiveness of photo- and systemic immunomodulatory therapies. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

Safety of percutaneous left atrial appendage closure: results from the Watchman Left Atrial Appendage System for Embolic Protection in Patients with AF (PROTECT AF) clinical trial and the Continued Access Registry.

PubMed

Reddy, Vivek Y; Holmes, David; Doshi, Shephal K; Neuzil, Petr; Kar, Saibal

2011-02-01

The Watchman Left Atrial Appendage System for Embolic Protection in Patients With AF (PROTECT AF) randomized trial compared left atrial appendage closure against warfarin in atrial fibrillation (AF) patients with CHADS₂ ≥1. Although the study met the primary efficacy end point of being noninferior to warfarin therapy for the prevention of stroke/systemic embolism/cardiovascular death, there was a significantly higher risk of complications, predominantly pericardial effusion and procedural stroke related to air embolism. Here, we report the influence of experience on the safety of percutaneous left atrial appendage closure. The study cohort for this analysis included patients in the PROTECT AF trial who underwent attempted device left atrial appendage closure (n=542 patients) and those from a subsequent nonrandomized registry of patients undergoing Watchman implantation (Continued Access Protocol [CAP] Registry; n=460 patients). The safety end point included bleeding- and procedure-related events (pericardial effusion, stroke, device embolization). There was a significant decline in the rate of procedure- or device-related safety events within 7 days of the procedure across the 2 studies, with 7.7% and 3.7% of patients, respectively, experiencing events (P=0.007), and between the first and second halves of PROTECT AF and CAP, with 10.0%, 5.5%, and 3.7% of patients, respectively, experiencing events (P=0.006). The rate of serious pericardial effusion within 7 days of implantation, which had made up >50% of the safety events in PROTECT AF, was lower in the CAP Registry (5.0% versus 2.2%, respectively; P=0.019). There was a similar experience-related improvement in procedure-related stroke (0.9% versus 0%, respectively; P=0.039). Finally, the functional impact of these safety events, as defined by significant disability or death, was statistically superior in the Watchman group compared with the warfarin group in PROTECT AF. This remained true whether significance was defined as a change in the modified Rankin score of ≥1, ≥2, or ≥3 (1.8 versus 4.3 events per 100 patient-years; relative risk, 0.43; 95% confidence interval, 0.24 to 0.82; 1.5 versus 3.7 events per 100 patient-years; relative risk, 0.41; 95% confidence interval, 0.22 to 0.82; and 1.4 versus 3.3 events per 100 patient-years; relative risk, 0.43; 95% confidence interval, 0.22 to 0.88, respectively). As with all interventional procedures, there is a significant improvement in the safety of Watchman left atrial appendage closure with increased operator experience. Clinical Trial Registration- URL: http://clinicaltrials.gov. Unique identifier: NCT00129545.

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

PubMed Central

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

2016-01-01

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

Pregnancy outcomes decline in recipients over age 44: an analysis of 27,959 fresh donor oocyte in vitro fertilization cycles from the Society for Assisted Reproductive Technology.

PubMed

Yeh, Jason S; Steward, Ryan G; Dude, Annie M; Shah, Anish A; Goldfarb, James M; Muasher, Suheil J

2014-05-01

To use a large and recent national registry to provide an updated report on the effect of recipient age on the outcome of donor oocyte in vitro fertilization (IVF) cycles. Retrospective cohort study. United States national registry for assisted reproductive technology. Recipients of donor oocyte treatment cycles between 2008 and 2010, with cycles segregated into five age cohorts: ≤34, 35 to 39, 40 to 44, 45 to 49, and ≥50 years. None. Implantation, clinical pregnancy, live-birth, and miscarriage rates. In donor oocyte IVF cycles, all age cohorts ≤39 years had similar rates of implantation, clinical pregnancy, and live birth when compared with the 40- to 44-year-old reference group. Patients in the two oldest age groups (45 to 49, ≥50 years) experienced statistically significantly lower rates of implantation, clinical pregnancy, and live birth compared with the reference group. Additionally, all outcomes in the ≥50-year-old group were statistically significantly worse than the 45- to 49-year-old group, demonstrating progressive decline with advancing age. Recent national registry data suggest that donor oocyte recipients have stable rates of pregnancy outcomes before age 45, after which there is a small but steady and significant decline. Copyright © 2014 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

Insufficient evidence for the role of school dental screening in improving oral health.

PubMed

Holmes, Richard D

2018-03-23

Data sourcesThe Cochrane Oral Health's Trials Register, the Cochrane Central Register of Controlled Trials (CENTRAL), Medline, Embase, the US National Institutes of Health Trials Registry (ClinicalTrials.gov) and the World Health Organization International Clinical Trials Registry Platform databases.Study selectionRandomised controlled trials (cluster or parallel) evaluating school dental screening compared with no intervention or with one type of screening compared with another were included.Data extraction and synthesisTwo reviewers independently abstracted data and assessed risk of bias. Risk ratios were calculated for dichotomous outcomes, with data being pooled where appropriate. The GRADE approach was used to interpret findings.ResultsSix trials involving 19,498 children were included. Two were considered to be at low risk of bias, three at unclear risk and one at high risk. No conclusions could be made from four studies comparing traditional screening versus no screening because the evidence was inconsistent. Two trials evaluating criteria-based screening versus no screening suggested a possible benefit; RR = 1.07 (95% CI; 0.99-1.16). No difference was found when comparing criteria-based screening with traditional screening, RR = 1.01, (95% CI; 0.94-1.08). No trials reported on long-term follow-up or cost-effectiveness and adverse events.ConclusionsThe trials included in this review evaluated short-term effects of screening, assessing follow-up periods of three to eight months. We found very low certainty evidence that was insufficient to allow us to draw conclusions about whether there is a role for traditional school dental screening in improving dental attendance. For criteria-based screening, we found low-certainty evidence that it may improve dental attendance when compared to no screening. However, when compared to traditional screening there was no evidence of a difference in dental attendance (very low-certainty evidence).We found low-certainty evidence to conclude that personalised or specific referral letters improve dental attendance when compared to non-specific counterparts. We also found low-certainty evidence that screening supplemented with motivation (oral health education and offer of free treatment) improves dental attendance in comparison to screening alone.We did not find any trials addressing cost-effectiveness and adverse effects of school dental screening.

Evaluation of the sensitivity of the 'Wiley registry of tandem mass spectral data, MSforID' with MS/MS data of the 'NIST/NIH/EPA mass spectral library'.

PubMed

Oberacher, Herbert; Whitley, Graeme; Berger, Bernd

2013-04-01

Tandem mass spectral libraries are versatile tools for small molecular identification finding application in forensic science, doping control, drug monitoring, food and environmental analysis, as well as metabolomics. Two important libraries are the 'Wiley Registry of Tandem Mass Spectral Data, MSforID' (Wiley Registry MSMS) and the collection of MS/MS spectra part of the 2011 edition of the 'NIST/NIH/EPA Mass Spectral Library' (NIST 11 MSMS). Herein, the sensitivity and robustness of the Wiley Registry MSMS were evaluated using spectra extracted from the NIST 11 MSMS library. The sample set was found to be heterogeneous in terms of mass spectral resolution, type of CID, as well as applied collision energies. Nevertheless, sensitive compound identification with a true positive identification rate ≥95% was possible using either the MSforID Search program or the NIST MS Search program 2.0g for matching. To rate the performance of the Wiley Registry MSMS, cross-validation experiments were repeated using subcollections of NIST 11 MSMS as reference library and spectra extracted from the Wiley Registry MSMS as positive controls. Unexpectedly, with both search algorithms tested, correct results were obtained in less than 88% of cases. We examined possible causes for the results of the cross validation study. The large number of precursor ions represented by a single tandem mass spectrum only was identified as the basic cause for the comparably lower sensitivity of the NIST library. Copyright © 2013 John Wiley & Sons, Ltd.

Permanent Pacemaker Implantation after TAVR – Predictors and Impact on Outcomes

PubMed Central

Sinning, Jan-Malte; Hammerstingl, Christoph; Werner, Nikos; Grube, Eberhard; Nickenig, Georg

2015-01-01

The number of patients undergoing transcatheter aortic valve replacement (TAVR) worldwide is increasing steadily. Atrioventricular conduction disturbances, with or without the need for permanent pacemaker (PPM) implantation, are one of the most common adverse events after TAVR. Among transcatheter heart valves (THV), rates of conduction abnormalities vary from less than 10 % to more than 50 %. Depending on the reported data referred to, historical data showed that up to one-third of the patients required implantation of a PPM following TAVR. Although generally considered as a minor complication, PPM may have a profound impact on prognosis and quality of life after TAVR. Current data support the hypothesis that conduction abnormalities leading to pacemaker dependency result from mechanical compression of the conduction system by the prosthesis stent frame and individual predisposing conduction defects such as right bundle-branch block (RBBB). With several large randomised trials and registry studies having been published recently and second generation THV having been introduced, the debate about predictors for pacemaker implantation and their impact on outcome after TAVR is still ongoing. PMID:29588683

Diffusion, outcomes and implementation of minimally invasive liver surgery: a snapshot from the I Go MILS (Italian Group of Minimally Invasive Liver Surgery) Registry.

PubMed

Aldrighetti, Luca; Ratti, Francesca; Cillo, Umberto; Ferrero, Alessandro; Ettorre, Giuseppe Maria; Guglielmi, Alfredo; Giuliante, Felice; Calise, Fulvio

2017-09-01

The Italian Group of MILS (I Go MILS) prospective registry was established in 2014 with the goals to create a hub for data and projects on a national basis and to promote the diffusion and implementation of MILS programs on a national scale. The primary endpoint of the present study is to give a snapshot of the real diffusion and outcomes of MILS in Italy, while analyzing the role of the registry in the implementation of MILS programs nationwide. The I Go MILS Registry is a prospective and intention-to-treat registry opened to any Italian center performing MILS, without restriction criteria based on number of procedures. The Registry is developed through the eClinical, an electronic platform for the management of clinical trials and is based on 34 clinical variables, regarding indication, intra- and postoperative course. Clinical outcomes and data regarding implementation of MILS activity have been analyzed for the aim of the study. Between November 2014 and June 2017, data from 1678 MILS performed in 48 centers have been collected (mean number of procedures per center 35, range 1-302). 22% of procedures were performed for benign and 78% for malignant disease (HCC constituted the 49.1% and CRLM the 31.2% of malignant tumors). Major liver resections (>3 liver segments), including right and left hepatectomies, trisectionectomies and ALPPS procedures were 10% of the series. Mean blood loss was 200 ± 230 mL Morbidity rate was 20.5% and mortality was 0.3%. 10.4% of cases were converted to open approach. Median length of stay was 5 days. MILS/total resections ratio in 13 experienced centers increased from 14 to 30% after Registry establishment. MILS programs are well established in Italy, with progressive increase both in the number of cases and in the numerosity of centers. The I Go MILS Registry is playing a crucial role in monitoring the development of MILS in the real world on a national basis while giving a significant contribution to the implementation of MILS programs.

Uses of available record systems in epidemiologic studies of reproductive toxicology

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

Polednak, A.P.; Janerich, D.T.

The uses of available record systems in epidemiologic studies of reproductive toxicology are described with reference to New York State. The available record systems (and relevant reproductive end points) described include: a newborn screening program for metabolic diseases and hemoglobinopathies (relevant to point mutations); chromosome registries and prenatal cytogenetics (for chromosome anomalies); live birth certificates (for birth defects, birthweight, sex ratio, etc); fetal death certificates (for spontaneous fetal deaths); and a statewide cancer registry (for childhood cancers and transplacental carcinogenesis). The uses and limitations of these record systems are discussed, along with examples of their use in descriptive and analyticmore » epidemiologic studies. Descriptive studies outlined include investigations of temporal and geographic trends in birth defects, birth weight, and fetal deaths, with reference to environmental questions (eg, Love Canal, nuclear power plants). Analytic studies described concern parental occupation in relation to specific birth defects (neural tube defects and Down syndrome) and maternal use of contraceptive drugs.« less

A new data management system for the French National Registry of human alveolar echinococcosis cases.

PubMed

Charbonnier, Amandine; Knapp, Jenny; Demonmerot, Florent; Bresson-Hadni, Solange; Raoul, Francis; Grenouillet, Frédéric; Millon, Laurence; Vuitton, Dominique Angèle; Damy, Sylvie

2014-01-01

Alveolar echinococcosis (AE) is an endemic zoonosis in France due to the cestode Echinococcus multilocularis. The French National Reference Centre for Alveolar Echinococcosis (CNR-EA), connected to the FrancEchino network, is responsible for recording all AE cases diagnosed in France. Administrative, epidemiological and medical information on the French AE cases may currently be considered exhaustive only on the diagnosis time. To constitute a reference data set, an information system (IS) was developed thanks to a relational database management system (MySQL language). The current data set will evolve towards a dynamic surveillance system, including follow-up data (e.g. imaging, serology) and will be connected to environmental and parasitological data relative to E. multilocularis to better understand the pathogen transmission pathway. A particularly important goal is the possible interoperability of the IS with similar European and other databases abroad; this new IS could play a supporting role in the creation of new AE registries. © A. Charbonnier et al., published by EDP Sciences, 2014.

A new data management system for the French National Registry of human alveolar echinococcosis cases

PubMed Central

Charbonnier, Amandine; Knapp, Jenny; Demonmerot, Florent; Bresson-Hadni, Solange; Raoul, Francis; Grenouillet, Frédéric; Millon, Laurence; Vuitton, Dominique Angèle; Damy, Sylvie

2014-01-01

Alveolar echinococcosis (AE) is an endemic zoonosis in France due to the cestode Echinococcus multilocularis. The French National Reference Centre for Alveolar Echinococcosis (CNR-EA), connected to the FrancEchino network, is responsible for recording all AE cases diagnosed in France. Administrative, epidemiological and medical information on the French AE cases may currently be considered exhaustive only on the diagnosis time. To constitute a reference data set, an information system (IS) was developed thanks to a relational database management system (MySQL language). The current data set will evolve towards a dynamic surveillance system, including follow-up data (e.g. imaging, serology) and will be connected to environmental and parasitological data relative to E. multilocularis to better understand the pathogen transmission pathway. A particularly important goal is the possible interoperability of the IS with similar European and other databases abroad; this new IS could play a supporting role in the creation of new AE registries. PMID:25526544

Effects of Anma massage therapy (Japanese massage) for gynecological cancer survivors: study protocol for a randomized controlled trial

PubMed Central

2013-01-01

Background Cancer patients and survivors regularly feel anxious about cancer recurrence or death, even after the conclusion of medical treatment, and they are often highly physiologically and psychologically stressed. Massage therapy is one of the most widely used complementary and alternative therapies used in the hope of alleviating such stress and physical and psychological complaints and to improve health-related quality of life. This randomized phase III, two-armed, parallel group, clinical trial was designed after obtaining positive findings in a preliminary study. The primary objective is to verify the effects of continuous Japanese massage therapy, referred to as Anma therapy, for cancer survivors. The secondary objective is to confirm the immediate effects of a single Anma massage session for cancer survivors. Methods/Design Sixty cancer survivors older than 20 years of age who have had histologically confirmed uterine cervical, endometrial, ovarian, fallopian tube or peritoneal cancer in the past, but with no recurrence for more than 3 years since receiving standard medical treatment, are being recruited by gynecologists in medical facilities. In the coordinating office, they are randomly allocated to two groups (n = 30 each): an Anma massage group receiving a 40-min Anma massage session once weekly over a 2-month intervention period (total of eight Anma massage sessions) and a control group being followed by medical doctors and receiving no Anma massage sessions. The primary end point is the severity of physical subjective symptoms that cancer survivors report in daily life, assessed using a Visual Analogue Scale. Secondary end points are urine and saliva analyses, psychological condition and health-related quality-of-life scores as determined on the basis of a self-report questionnaire. Discussion Using the evidence-based findings of this trial, medical professionals should be able to explain the benefits conferred by Anma massage to cancer survivors and provide higher-quality information to better inform patients regarding their decisions about whether to receive such therapy. Trial registration This trial is registered with the UMIN Clinical Trials Registry as UMIN000009097. PMID:23883162

External versus internal fixation for bicondylar tibial plateau fractures: systematic review and meta-analysis.

PubMed

Metcalfe, David; Hickson, Craig J; McKee, Lesley; Griffin, Xavier L

2015-12-01

It is uncertain whether external fixation or open reduction internal fixation (ORIF) is optimal for patients with bicondylar tibial plateau fractures. A systematic review using Ovid MEDLINE, Embase Classic, Embase, AMED, the Cochrane Library, Open Grey, Orthopaedic Proceedings, WHO International Clinical Trials Registry Platform, Current Controlled Trials, US National Institute for Health Trials Registry, and the Cochrane Central Register of Controlled Trials. The search was conducted on 3rd October 2014 and no language limits were applied. Inclusion criteria were all clinical study designs comparing external fixation with open reduction internal fixation of bicondylar tibial plateau fractures. Studies of only one treatment modality were excluded, as were those that included unicondylar tibial plateau fractures. Treatment effects from studies reporting dichotomous outcomes were summarised using odds ratios. Continuous outcomes were converted to standardized mean differences to assess the treatment effect, and inverse variance methods used to combine data. A fixed effect model was used for meta-analyses. Patients undergoing external fixation were more likely to have returned to preinjury activities by six and twelve months (P = 0.030) but not at 24 months follow-up. However, external fixation was complicated by a greater number of infections (OR 2.59, 95 % CI 1.25-5.36, P = 0.01). There were no statistically significant differences in the rates of deep infection, venous thromboembolism, compartment syndrome, or need for re-operation between the two groups. Although external fixation and ORIF are associated with different complication profiles, both are acceptable strategies for managing bicondylar tibial plateau fractures.

Procedural and short-term safety of bronchial thermoplasty in clinical practice: evidence from a national registry and Hospital Episode Statistics.

PubMed

Burn, Julie; Sims, Andrew J; Keltie, Kim; Patrick, Hannah; Welham, Sally A; Heaney, Liam G; Niven, Robert M

2017-10-01

Bronchial thermoplasty (BT) is a novel treatment for severe asthma. Its mode of action and ideal target patient group remain poorly defined, though clinical trials provided some evidence on efficacy and safety. This study presents procedural and short-term safety evidence from routine UK clinical practice. Patient characteristics and safety outcomes (procedural complications, 30-day readmission and accident and emergency (A&E) attendance, length of stay) were assessed using two independent data sources, the British Thoracic Society UK Difficult Asthma Registry (DAR) and Hospital Episodes Statistics (HES) database. A matched cohort (with records in both) was used to estimate safety outcome event rates and compare them with clinical trials. Between June 2011 and January 2015, 215 procedure records (83 patients; 68 treated in England) were available from DAR and 203 (85 patients) from HES. 152 procedures matched (59 patients; 6 centres), and of these, 11.2% reported a procedural complication, 11.8% resulted in emergency respiratory readmission, 0.7% in respiratory A&E attendance within 30 days (20.4% had at least one event) and 46.1% involved a post-procedure stay. Compared with published clinical trials which found lower hospitalisation rates, BT patients in routine clinical practice were, on average, older, had worse baseline lung function and asthma quality of life. A higher proportion of patients experienced adverse events compared with clinical trials. The greater severity of disease amongst patients treated in clinical practice may explain the observed rate of post-procedural stay and readmission. Study of long-term safety and efficacy requires continuing data collection.

Responding to a significant recruitment challenge within three nationwide psychoeducational trials for cancer patients.

PubMed

Stanton, Annette L; Morra, Marion E; Diefenbach, Michael A; Miller, Suzanne M; Slevin Perocchia, Rosemarie; Raich, Peter C; Fleisher, Linda; Wen, Kuang-Yi; Tran, Zung Vu; Mohamed, Nihal E; George, Roshini; Bright, Mary Anne; Marcus, Alfred C

2013-09-01

When faced with a significant recruitment challenge for three nationwide psychoeducational trials targeting prostate and breast cancer patients, the Cancer Information Service Research Consortium initiated outreach efforts to increase accrual. Recruitment is reported by major outreach strategy to inform the use of similar campaigns, either as primary recruitment efforts or to supplement "in-reach" recruitment within oncology settings. During a 33-month period, recruitment was tracked from the National Cancer Institute's Cancer Information Service (CIS), the American Cancer Society (ACS), Dr. Susan Love Research Foundation's Love/Avon Army of Women (AOW), Internet advertising, press releases, radio/television interviews, recruitment materials in community venues, and outreach to churches and cancer support organizations. Across projects, the majority (89 %) of recruited participants (N = 2,134) was obtained from the CIS (n = 901, 19 months of recruitment), AOW (n = 869, 18 months), and ACS (n = 123, 12 months). Other efforts showed minimal gain in recruitment. Cancer information programs (e.g., CIS and ACS) and registries of individuals willing to participate in cancer-related research (e.g., AOW) can represent exceptional resources for outreach recruitment of cancer patients, especially when the eligibility criteria are highly restrictive. However, these resources do not yield samples representative of the larger population of adults diagnosed with cancer, and conclusions from such trials must be tempered accordingly. Inadequate recruitment to randomized controlled trials limits the creation of useful interventions for cancer survivors. By enrolling in cancer registries and taking part in research, cancer survivors can contribute to the development of effective resources for the survivor population.

Establishing a Core Outcome Measure for Graft Health: a Standardized Outcomes in Nephrology - Kidney Transplantation (SONG-Tx) Consensus Workshop Report.

PubMed

Tong, Allison; Sautenet, Benedicte; Poggio, Emilio D; Lentine, Krista L; Oberbauer, Rainer; Mannon, Roslyn; Murphy, Barbara; Padilla, Benita; Chow, Kai Ming; Marson, Lorna; Chadban, Steve; Craig, Jonathan C; Ju, Angela; Manera, Karine E; Hanson, Camilla S; Josephson, Michelle A; Knoll, Greg

2018-02-22

Graft loss, a critically important outcome for transplant recipients, is variably defined and measured, and incompletely reported in trials. We convened a consensus workshop on establishing a core outcome measure for graft loss for all trials in kidney transplantation. Twenty-five kidney transplant recipients/caregivers and 33 health professionals from eight countries participated. Transcripts were analyzed thematically. Five themes were identified. "Graft loss as a continuum" conceptualizes graft loss as a process, but requiring an endpoint defined as a discrete event. In "defining an event with precision and accuracy," loss of graft function requiring chronic dialysis (minimum 90 days) provided an objective and practical definition; re-transplant would capture preemptive transplantation; relisting was readily measured but would overestimate graft loss; and allograft nephrectomy was redundant in being preceded by dialysis. However, the thresholds for renal replacement therapy varied. Conservative management was regarded as too ambiguous and complex to use routinely. "Distinguishing death-censored graft loss" would ensure clarity and meaningfulness in interpreting results. "Consistent reporting for decision-making" by specifying time points and metrics (ie time to event) was suggested. "Ease of ascertainment and data collection" of the outcome from registries could support use of registry data to efficiently extend follow-up of trial participants. A practical and meaningful core outcome measure for graft loss may be defined as chronic dialysis or re-transplant, and distinguished from loss due to death. Consistent reporting of graft loss using standardized metrics and time points may improve the contribution of trials to decision-making in kidney transplantation.

Incorporating Dynamic Assessment of Fluid Responsiveness Into Goal-Directed Therapy: A Systematic Review and Meta-Analysis

PubMed Central

Fridfinnson, Jason A.; Kumar, Anand; Blanchard, Laurie; Rabbani, Rasheda; Bell, Dean; Funk, Duane; Turgeon, Alexis F.; Abou-Setta, Ahmed M.; Zarychanski, Ryan

2017-01-01

Objective: Dynamic tests of fluid responsiveness have been developed and investigated in clinical trials of goal-directed therapy. The impact of this approach on clinically relevant outcomes is unknown. We performed a systematic review and meta-analysis to evaluate whether fluid therapy guided by dynamic assessment of fluid responsiveness compared with standard care improves clinically relevant outcomes in adults admitted to the ICU. Data Sources: Randomized controlled trials from MEDLINE, EMBASE, CENTRAL, clinicaltrials.gov, and the International Clinical Trials Registry Platform from inception to December 2016, conference proceedings, and reference lists of relevant articles. Study Selection: Two reviewers independently identified randomized controlled trials comparing dynamic assessment of fluid responsiveness with standard care for acute volume resuscitation in adults admitted to the ICU. Data Extraction: Two reviewers independently abstracted trial-level data including population characteristics, interventions, clinical outcomes, and source of funding. Our primary outcome was mortality at longest duration of follow-up. Our secondary outcomes were ICU and hospital length of stay, duration of mechanical ventilation, and frequency of renal complications. The internal validity of trials was assessed in duplicate using the Cochrane Collaboration’s Risk of Bias tool. Data Synthesis: We included 13 trials enrolling 1,652 patients. Methods used to assess fluid responsiveness included stroke volume variation (nine trials), pulse pressure variation (one trial), and stroke volume change with passive leg raise/fluid challenge (three trials). In 12 trials reporting mortality, the risk ratio for death associated with dynamic assessment of fluid responsiveness was 0.59 (95% CI, 0.42–0.83; I2 = 0%; n = 1,586). The absolute risk reduction in mortality associated with dynamic assessment of fluid responsiveness was –2.9% (95% CI, –5.6% to –0.2%). Dynamic assessment of fluid responsiveness was associated with reduced duration of ICU length of stay (weighted mean difference, –1.16 d [95% CI, –1.97 to –0.36]; I2 = 74%; n = 394, six trials) and mechanical ventilation (weighted mean difference, –2.98 hr [95% CI, –5.08 to –0.89]; I2 = 34%; n = 334, five trials). Three trials were adjudicated at unclear risk of bias; the remaining trials were at high risk of bias. Conclusions: In adult patients admitted to intensive care who required acute volume resuscitation, goal-directed therapy guided by assessment of fluid responsiveness appears to be associated with reduced mortality, ICU length of stay, and duration of mechanical ventilation. High-quality clinical trials in both medical and surgical ICU populations are warranted to inform routine care. PMID:28817481

Methodology Series Module 4: Clinical Trials.

PubMed

Setia, Maninder Singh

2016-01-01

In a clinical trial, study participants are (usually) divided into two groups. One group is then given the intervention and the other group is not given the intervention (or may be given some existing standard of care). We compare the outcomes in these groups and assess the role of intervention. Some of the trial designs are (1) parallel study design, (2) cross-over design, (3) factorial design, and (4) withdrawal group design. The trials can also be classified according to the stage of the trial (Phase I, II, III, and IV) or the nature of the trial (efficacy vs. effectiveness trials, superiority vs. equivalence trials). Randomization is one of the procedures by which we allocate different interventions to the groups. It ensures that all the included participants have a specified probability of being allocated to either of the groups in the intervention study. If participants and the investigator know about the allocation of the intervention, then it is called an "open trial." However, many of the trials are not open - they are blinded. Blinding is useful to minimize bias in clinical trials. The researcher should familiarize themselves with the CONSORT statement and the appropriate Clinical Trials Registry of India.

Methodology Series Module 4: Clinical Trials

PubMed Central

Setia, Maninder Singh

2016-01-01

In a clinical trial, study participants are (usually) divided into two groups. One group is then given the intervention and the other group is not given the intervention (or may be given some existing standard of care). We compare the outcomes in these groups and assess the role of intervention. Some of the trial designs are (1) parallel study design, (2) cross-over design, (3) factorial design, and (4) withdrawal group design. The trials can also be classified according to the stage of the trial (Phase I, II, III, and IV) or the nature of the trial (efficacy vs. effectiveness trials, superiority vs. equivalence trials). Randomization is one of the procedures by which we allocate different interventions to the groups. It ensures that all the included participants have a specified probability of being allocated to either of the groups in the intervention study. If participants and the investigator know about the allocation of the intervention, then it is called an “open trial.” However, many of the trials are not open – they are blinded. Blinding is useful to minimize bias in clinical trials. The researcher should familiarize themselves with the CONSORT statement and the appropriate Clinical Trials Registry of India. PMID:27512184

Clinical trial network for the promotion of clinical research for rare diseases in Japan: muscular dystrophy clinical trial network.

PubMed

Shimizu, Reiko; Ogata, Katsuhisa; Tamaura, Akemi; Kimura, En; Ohata, Maki; Takeshita, Eri; Nakamura, Harumasa; Takeda, Shin'ichi; Komaki, Hirofumi

2016-07-11

Duchenne muscular dystrophy (DMD) is the most commonly inherited neuromuscular disease. Therapeutic agents for the treatment of rare disease, namely "orphan drugs", have recently drawn the attention of researchers and pharmaceutical companies. To ensure the successful conduction of clinical trials to evaluate novel treatments for patients with rare diseases, an appropriate infrastructure is needed. One of the effective solutions for the lack of infrastructure is to establish a network of rare diseases. To accomplish the conduction of clinical trials in Japan, the Muscular dystrophy clinical trial network (MDCTN) was established by the clinical research group for muscular dystrophy, including the National Center of Neurology and Psychiatry, as well as national and university hospitals, all which have a long-standing history of research cooperation. Thirty-one medical institutions (17 national hospital organizations, 10 university hospitals, 1 national center, 2 public hospitals, and 1 private hospital) belong to this network and collaborate to facilitate clinical trials. The Care and Treatment Site Registry (CTSR) calculates and reports the proportion of patients with neuromuscular diseases in the cooperating sites. In total, there are 5,589 patients with neuromuscular diseases in Japan and the proportion of patients with each disease is as follows: DMD, 29 %; myotonic dystrophy type 1, 23 %; limb girdle muscular dystrophy, 11 %; Becker muscular dystrophy, 10 %. We work jointly to share updated health care information and standardized evaluations of clinical outcomes as well. The collaboration with the patient registry (CTSR), allows the MDCTN to recruit DMD participants with specific mutations and conditions, in a remarkably short period of time. Counting with a network that operates at a national level is important to address the corresponding national issues. Thus, our network will be able to contribute with international research activity, which can lead to an improvement of neuromuscular disease treatment in Japan.

Comparison of outcome measures and complication rates following three different approaches for primary total hip arthroplasty: a pragmatic randomised controlled trial.

PubMed

Talia, Adrian J; Coetzee, Cassandra; Tirosh, Oren; Tran, Phong

2018-01-08

Total hip arthroplasty is one of the most commonly performed surgical procedures worldwide. There are a number of surgical approaches for total hip arthroplasty and no high-level evidence supporting one approach over the other. Each approach has its unique benefits and drawbacks. This trial aims to directly compare the three most common surgical approaches for total hip arthroplasty. This is a single-centre study conducted at Western Health, Melbourne, Australia; a large metropolitan centre. It is a pragmatic, parallel three-arm, randomised controlled trial. Sample size will be 243 participants (81 in each group). Randomisation will be secure, web-based and managed by an independent statistician. Patients and research team will be blinded pre-operatively, but not post-operatively. Intervention will be either direct anterior, lateral or posterior approach for total hip arthroplasty, and the three arms will be directly compared. Participants will be aged over 18 years, able to provide informed consent and recruited from our outpatients. Patients who are having revision surgery or have indications for hip replacement other than osteoarthritis (i.e., fracture, malignancy, development dysplasia) will be excluded from the trial. The Oxford Hip Score will be determined for patients pre-operatively and 6 weeks, 6, 12 and 24 months post-operatively. The Oxford Hip Score at 24 months will be the primary outcome measure. Secondary outcome measures will be dislocation, infection, intraoperative and peri-prosthetic fracture rate, length of hospital stay and pain level, reported using a visual analogue scale. Many studies have evaluated approaches for total hip arthroplasty and arthroplasty registries worldwide are now collecting this data. However no study to date has compared these three common approaches directly in a randomised fashion. No trial has used patient-reported outcome measures to evaluate success. This pragmatic study aims to identify differences in patient perception of total hip arthroplasty depending on surgical approach. Australian New Zealand Clinical Trials Registry, ACTRN12617000272392 . Registered on 22 February 2017.

Correction to: A national cohort study on pediatric Behçet's disease: cross-sectional data from an Italian registry.

PubMed

Gallizzi, Romina; Pidone, Caterina; Cantarini, Luca; Finetti, Martina; Cattalini, Marco; Filocamo, Giovanni; Insalaco, Antonella; Rigante, Donato; Consolini, Rita; Maggio, Maria Cristina; Civino, Adele; Martino, Silvana; Olivieri, Alma Nunzia; Fabio, Giovanna; Pastore, Serena; Mauro, Angela; Sutera, Diana; Trimarchi, Giuseppe; Ruperto, Nicolino; Gattorno, Marco; Cimaz, Rolando

2018-04-23

Following publication of the original article [1], the authors reported that the names of two institutional authors - EUROFEVER and the Paediatric Rheumatology International Trials Organisation (PRINTO) - had been unintentionally omitted in the final online version of the manuscript. The corrected author list is shown in this Correction..

Physiotherapy intervention in Parkinson’s disease: systematic review and meta-analysis

PubMed Central

Patel, Smitaa; Meek, Charmaine; Herd, Clare P; Clarke, Carl E; Stowe, Rebecca; Shah, Laila; Sackley, Catherine; Deane, Katherine H O; Wheatley, Keith; Ives, Natalie

2012-01-01

Objective To assess the effectiveness of physiotherapy compared with no intervention in patients with Parkinson’s disease. Design Systematic review and meta-analysis of randomised controlled trials. Data sources Literature databases, trial registries, journals, abstract books, and conference proceedings, and reference lists, searched up to the end of January 2012. Review methods Randomised controlled trials comparing physiotherapy with no intervention in patients with Parkinson’s disease were eligible. Two authors independently abstracted data from each trial. Standard meta-analysis methods were used to assess the effectiveness of physiotherapy compared with no intervention. Tests for heterogeneity were used to assess for differences in treatment effect across different physiotherapy interventions used. Outcome measures were gait, functional mobility and balance, falls, clinician rated impairment and disability measures, patient rated quality of life, adverse events, compliance, and economic analysis outcomes. Results 39 trials of 1827 participants met the inclusion criteria, of which 29 trials provided data for the meta-analyses. Significant benefit from physiotherapy was reported for nine of 18 outcomes assessed. Outcomes which may be clinically significant were speed (0.04 m/s, 95% confidence interval 0.02 to 0.06, P<0.001), Berg balance scale (3.71 points, 2.30 to 5.11, P<0.001), and scores on the unified Parkinson’s disease rating scale (total score −6.15 points, −8.57 to −3.73, P<0.001; activities of daily living subscore −1.36, −2.41 to −0.30, P=0.01; motor subscore −5.01, −6.30 to −3.72, P<0.001). Indirect comparisons of the different physiotherapy interventions found no evidence that the treatment effect differed across the interventions for any outcomes assessed, apart from motor subscores on the unified Parkinson’s disease rating scale (in which one trial was found to be the cause of the heterogeneity). Conclusions Physiotherapy has short term benefits in Parkinson’s disease. A wide range of physiotherapy techniques are currently used to treat Parkinson’s disease, with little difference in treatment effects. Large, well designed, randomised controlled trials with improved methodology and reporting are needed to assess the efficacy and cost effectiveness of physiotherapy for treating Parkinson’s disease in the longer term. PMID:22867913

Complement inhibitors for age-related macular degeneration.

PubMed

Williams, Michael A; McKay, Gareth J; Chakravarthy, Usha

2014-01-15

Given the relatively high prevalence of age-related macular degeneration (AMD) and the increased incidence of AMD as populations age, the results of trials of novel treatments are awaited with much anticipation. The complement cascade describes a series of proteolytic reactions occurring throughout the body that generate proteins with a variety of roles including the initiation and promotion of immune reactions against foreign materials or micro-organisms. The complement cascade is normally tightly regulated, but much evidence implicates complement overactivity in AMD and so it is a logical therapeutic target in the treatment of AMD. To assess the effects and safety of complement inhibitors in the prevention or treatment of advanced AMD. We searched CENTRAL (which contains the Cochrane Eyes and Vision Group Trials Register) (The Cochrane Library 2013, Issue 11), Ovid MEDLINE, Ovid MEDLINE In-Process and Other Non-Indexed Citations, Ovid MEDLINE Daily, Ovid OLDMEDLINE (January 1946 to November 2013), EMBASE (January 1980 to November 2013), Allied and Complementary Medicine Database (AMED) (January 1985 to November 2013), Latin American and Caribbean Literature on Health Sciences (LILACS) (January 1982 to November 2013), OpenGrey (System for Information on Grey Literature in Europe) (www.opengrey.eu/), Web of Science Conference Proceedings Citation Index - Science (CPCI-S) (January 1990 to November 2013), the metaRegister of Controlled Trials (mRCT) (www.controlled-trials.com), ClinicalTrials.gov (www.clinicaltrials.gov) and the WHO International Clinical Trials Registry Platform (ICTRP) (www.who.int/ictrp/search/en). We did not use any date or language restrictions in the electronic searches for trials. We last searched the electronic databases on 21 November 2013. We also performed handsearching of proceedings, from 2012 onwards, of meetings and conferences of specific professional organisations. We planned to include randomised controlled trials (RCTs) with parallel treatment groups which investigated either the prevention or treatment of advanced AMD by inhibition of the complement cascade. Two authors (MW and GMcK) independently evaluated all the titles and abstracts resulting from the searches. We contacted companies running clinical trials which had not yet reported results to request information. Since no trials met our inclusion criteria, we undertook no assessment of quality or meta-analysis. We identified and screened 317 references but there were no published RCTs that met the inclusion criteria. We identified two ongoing studies: one phase I study and one phase II study. There is insufficient information at present to generate evidence-based recommendations on the potential safety and efficacy of complement inhibitors for prevention or treatment of AMD. However we anticipate the results of ongoing trials.

The Practice Pattern of Percutaneous Coronary Intervention in Korea: Based on Year 2014 Cohort of Korean Percutaneous Coronary Intervention (K-PCI) Registry.

PubMed

Gwon, Hyeon-Cheol; Jeon, Dong Woon; Kang, Hyun-Jae; Jang, Jae-Sik; Park, Duk-Woo; Shin, Dong-Ho; Moon, Keon-Woong; Kim, Jung-Sun; Kim, Juhan; Bae, Jang-Whan; Hur, Seung-Ho; Kim, Byung Ok; Choi, Donghoon; Han, Kyoo-Rok; Kim, Hyo-Soo

2017-05-01

Appropriate use criteria (AUC) was developed to improve the quality of percutaneous coronary intervention (PCI). However, these criteria should consider the current practice pattern in the country where they are being applied. The algorithm for the Korean PCI practice pattern (KP3) was developed by modifying the United States-derived AUC in expert consensus meetings. KP3 class A was defined as any strategy with evidence from randomized trials that was more conservative for PCI than medical therapy or coronary artery bypass graft (CABG). Class C was defined as any strategy with less evidence from randomized trials and more aggressive for PCI than medical therapy or CABG. Class B was defined as a strategy that was partly class A and partly class C. We applied the KP3 classification system to the Korean PCI registry. The KP3 class A was noted in 67.7% of patients, class B in 28.8%, and class C in 3.5%. The median proportion of class C cases per center was 2.0%. The distribution of KP3 classes varied significantly depending on clinical and angiographic characteristics. The proportion of KP3 class C cases per center was not significantly dependent on PCI volume, but rather on the percentage of ACS cases in each center. We report the current PCI practice pattern by applying the new KP3 classification in a nationwide PCI registry. The results should be interpreted carefully with due regard for the complex relationships between the determining variables and the healthcare system in Korea.

THC:CBD spray and MS spasticity symptoms: data from latest studies.

PubMed

Rekand, Tiina

2014-01-01

New clinical experience with 9-delta-tetrahydocannabinol (THC) and cannabidiol (CBD) oromucosal spray (Sativex®) involving more than an additional 1,000 patients with MS spasticity (approximately 150 in clinical studies and 900 in post-marketing surveillance studies) have become available in 2013 and are reviewed. A randomized, placebo controlled long-term follow-up clinical trial with THC:CBD spray versus placebo demonstrated that it was not associated with cognitive decline, depression or significant mood changes after 12 months of treatment. Furthermore, in a prospective observational pilot study involving 33 patients (60% female) aged 33-68 years and a mean disease duration of 6.6 years, THC:CBD oromucosal spray did not adversely influence standard driving ability in patients with moderate to severe MS spasticity. Other new long term observational data about the use of THC:CBD oromucosal spray in clinical practice are available from patient registries in the UK, Germany and Spain. Findings to date reinforce the efficacy and safety observed in Phase III clinical trials. It is of interest that in practice average dosages used by patients tended to be lower than those reported in clinical studies (5-6.4 vs. >8 sprays/day), and effectiveness was maintained in the majority of patients. Importantly, no additional safety concerns were identified in the registry studies which included findings from patients who have been treated for prolonged periods (in the German/UK registry 45% of patients had >2 years exposure). Thus, these new data support a positive benefit-risk relationship for THC:CBD oromucosal spray during longer-term use. © 2014 S. Karger AG, Basel.

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

Vitamin D supplementation during pregnancy: state of the evidence from a systematic review of randomised trials.

PubMed

Roth, Daniel E; Leung, Michael; Mesfin, Elnathan; Qamar, Huma; Watterworth, Jessica; Papp, Eszter

2017-11-29

Objectives  To estimate the effects of vitamin D supplementation during pregnancy on 11 maternal and 27 neonatal/infant outcomes; to determine frequencies at which trial outcome data were missing, unreported, or inconsistently reported; and to project the potential contributions of registered ongoing or planned trials. Design  Systematic review and meta-analysis of randomised controlled trials; systematic review of registered but unpublished trials. Data sources  Medline, Embase, PubMed, Cochrane Database of Systematic Reviews, and Cochrane Central Register of Controlled Trials from inception to September 2017; manual searches of reference lists of systematic reviews identified in the electronic search; and online trial registries for unpublished, ongoing, or planned trials. Eligibility criteria for study selection  Trials of prenatal vitamin D supplementation with randomised allocation and control groups administered placebo, no vitamin D, or vitamin D ≤600 IU/day (or its equivalent), and published in a peer reviewed journal. Results  43 trials (8406 participants) were eligible for meta-analyses. Median sample size was 133 participants. Vitamin D increased maternal/cord serum concentration of 25-hydroxyvitamin D, but the dose-response effect was weak. Maternal clinical outcomes were rarely ascertained or reported, but available data did not provide evidence of benefits. Overall, vitamin D increased mean birth weight of 58.33 g (95% confidence interval 18.88 g to 97.78 g; 37 comparisons) and reduced the risk of small for gestational age births (risk ratio 0.60, 95% confidence interval 0.40 to 0.90; seven comparisons), but findings were not robust in sensitivity and subgroup analyses. There was no effect on preterm birth (1.0, 0.77 to 1.30; 15 comparisons). There was strong evidence that prenatal vitamin D reduced the risk of offspring wheeze by age 3 years (0.81, 0.67 to 0.98; two comparisons). For most outcomes, meta-analyses included data from a minority of trials. Only eight of 43 trials (19%) had an overall low risk of bias. Thirty five planned/ongoing randomised controlled trials could contribute 12 530 additional participants to future reviews. Conclusions  Most trials on prenatal vitamin D published by September 2017 were small and of low quality. The evidence to date seems insufficient to guide clinical or policy recommendations. Future trials should be designed and powered to examine clinical endpoints, including maternal conditions related to pregnancy (such as pre-eclampsia), infant growth, and respiratory outcomes. Systematic review registration  PROSPERO CRD42016051292. 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.

Corticosteroids as adjuvant therapy for ocular toxoplasmosis.

PubMed

Jasper, Smitha; Vedula, Satyanarayana S; John, Sheeja S; Horo, Saban; Sepah, Yasir J; Nguyen, Quan Dong

2017-01-26

Ocular infection caused by Toxoplasma gondii, a parasite, may result in inflammation in the retina, choroid, and uvea, and consequently lead to complications such as glaucoma, cataract, and posterior synechiae. The objective of this systematic review was to assess the effects of adjunctive use of corticosteroids to anti-parasitic therapy versus anti-parasitic therapy alone for ocular toxoplasmosis. We searched CENTRAL (which contains the Cochrane Eyes and Vision Trials Register (2016; Issue 11)), MEDLINE Ovid, Epub Ahead of Print, In-Process & Other Non-Indexed Citations, MEDLINE Ovid Daily (January 1946 to December 2016), Embase (January 1980 to December 2016), Latin American and Caribbean Literature on Health Sciences (LILACS (January 1982 to December 2016)), the ISRCTN registry (www.isrctn.com/editAdvancedSearch), ClinicalTrials.gov (www.clinicaltrials.gov), and the World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP; www.who.int/ictrp/search/en). We used no date or language restrictions in the electronic searches for trials. We last searched the electronic databases on 7 December 2016. We had planned to include randomized and quasi-randomized controlled trials. Eligible trials would have enrolled participants of any age who were immunocompetent and were diagnosed with acute ocular toxoplasmosis. Included trials would have compared anti-parasitic therapy plus corticosteroids versus anti-parasitic therapy alone, different doses or times of initiation of corticosteroids. Two authors independently screened titles and abstracts retrieved through the electronic searches. We retrieved full-text reports of studies categorized as 'unsure' or 'include' after we reviewed the abstracts. Two authors independently reviewed each full-text report for eligibility. Discrepancies were resolved through discussion. We identified no completed or ongoing trial that was eligible for this Cochrane review. Although research has identified a wide variation in practice regarding the use of corticosteroids, our review did not identify any evidence from randomized controlled trials for or against the role of corticosteroids in the management of ocular toxoplasmosis. Several questions remain unanswered by well-conducted randomized trials in this context, including whether the use of corticosteroids as an adjunctive agent is more effective than the use of anti-parasitic therapy alone; if so, when corticosteroids should be initiated in the treatment regimen (early versus late course of treatment), and what would be the best dose and duration of steroid use.

Corticosteroids as adjuvant therapy for ocular toxoplasmosis

PubMed Central

Jasper, Smitha; Vedula, Satyanarayana S; John, Sheeja S; Horo, Saban; Sepah, Yasir J; Nguyen, Quan Dong

2017-01-01

Background Ocular infection caused by Toxoplasma gondii, a parasite, may result in inflammation in the retina, choroid, and uvea, and consequently lead to complications such as glaucoma, cataract, and posterior synechiae. Objectives The objective of this systematic review was to assess the effects of adjunctive use of corticosteroids to anti-parasitic therapy versus anti-parasitic therapy alone for ocular toxoplasmosis. Search methods We searched CENTRAL (which contains the Cochrane Eyes and Vision Trials Register (2016; Issue 11)), MEDLINE Ovid, Epub Ahead of Print, In-Process & Other Non-Indexed Citations, MEDLINE Ovid Daily (January 1946 to December 2016), Embase (January 1980 to December 2016), Latin American and Caribbean Literature on Health Sciences (LILACS (January 1982 to December 2016)), the ISRCTN registry (www.isrctn.com/editAdvancedSearch), ClinicalTrials.gov (www.clinicaltrials.gov), and the World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP; www.who.int/ictrp/search/en). We used no date or language restrictions in the electronic searches for trials. We last searched the electronic databases on 7 December 2016. Selection criteria We had planned to include randomized and quasi-randomized controlled trials. Eligible trials would have enrolled participants of any age who were immunocompetent and were diagnosed with acute ocular toxoplasmosis. Included trials would have compared anti-parasitic therapy plus corticosteroids versus anti-parasitic therapy alone, different doses or times of initiation of corticosteroids. Data collection and analysis Two authors independently screened titles and abstracts retrieved through the electronic searches. We retrieved full-text reports of studies categorized as ’unsure’ or ’include’ after we reviewed the abstracts. Two authors independently reviewed each full-text report for eligibility. Discrepancies were resolved through discussion. Main results We identified no completed or ongoing trial that was eligible for this Cochrane review. Authors’ conclusions Although research has identified a wide variation in practice regarding the use of corticosteroids, our review did not identify any evidence from randomized controlled trials for or against the role of corticosteroids in the management of ocular toxoplasmosis. Several questions remain unanswered by well-conducted randomized trials in this context, including whether the use of corticosteroids as an adjunctive agent is more effective than the use of anti-parasitic therapy alone; if so, when corticosteroids should be initiated in the treatment regimen (early versus late course of treatment), and what would be the best dose and duration of steroid use. PMID:28125765

Increasing adherence to obstructive sleep apnea treatment with a group social cognitive therapy treatment intervention: a randomized trial.

PubMed

Bartlett, Delwyn; Wong, Keith; Richards, Dianne; Moy, Emma; Espie, Colin A; Cistulli, Peter A; Grunstein, Ronald

2013-11-01

To examine whether a social cognitive therapy (SCT) intervention increases continuous positive airway pressure (CPAP) use compared to equivalent social interaction (SI) time. Individuals with obstructive sleep apnea (OSA) referred for CPAP therapy. Participants received a 30-min group education session regarding OSA and CPAP. Groups of three to four participants were then randomly assigned to an SCT session or social interaction. CPAP usage was assessed at 7 nights, then 1, 3, and 6 months. The two primary outcomes were adherence, usage ≥ 4 h per night at 6 months, and uptake of CPAP. Questionnaires were given pretreatment and posttreatment. Two hundred six individuals were randomized to SI (n = 97) or SCT (n = 109). CPAP uptake was not different between groups (82% in SI, 88% in SCT groups, P = 0.35). There were no differences between groups in adherence: 63-66% at 1 week, and at 6 months 55-47% (P = 0.36). Higher pretreatment apnea-hypopnea index, higher baseline self-efficacy, and use of CPAP (≥ 4 h) at 1 week were independent predictors of CPAP adherence at 6 months. CPAP adherence increased by a factor of 1.8 (odds ratio = 1.8, 95% confidence interval 1.1-3.0) for every one-unit increase in self-efficacy. There was no difference between groups postintervention in self-efficacy scores, sleepiness, mood, or sleep quality. In this randomized trial, a single SCT application did not increase adherence when compared with SI time. Although self-efficacy scores prior to CPAP predicted adherence, self-efficacy was not increased by the interventions. Increasing intensity and understanding of SCT interventions may be needed to improve CPAP adherence. Australian New Zealand Clinical Trials Registry, ACTRN12607000424404.

Effect of patient education in the management of coronary heart disease: a systematic review and meta-analysis of randomized controlled trials.

PubMed

Brown, James P R; Clark, Alexander M; Dalal, Hasnain; Welch, Karen; Taylor, Rod S

2013-08-01

To assess the effects of patient education on mortality, morbidity, health-related quality of life (HRQoL), and healthcare costs in people with coronary heart disease (CHD). Systematic review and meta-analysis. Data sources were Cochrane Library, Medline, Embase, PsycINFO, CINAHL, and ongoing trial registries until August 2010. We also checked study references. The study selection was based on design (randomized controlled trials with follow up of at least 6 months, published from 1990 onwards), population (adults with CHD), intervention (patient education stated to be the primary intervention), and comparators (usual care or no educational intervention). Thirteen studies (68,556 people with CHD) were included. Educational interventions ranged from two visits to a 4-week residential stay with 11 months of reinforcement sessions. Compared to no educational intervention, there was weak evidence that education reduced all-cause mortality (pooled relative risk (RR) 0.79, 95% CI 0.55 to 1.13) and cardiac morbidity outcomes: myocardial infarction (pooled RR 0.63, 95% CI 0.26 to 1.48), revascularization (pooled RR 0.58, 95% CI 0.19 to 1.71), and hospitalization (pooled RR 0.83, 95% CI 0.65 to 1.07) at median 18-months follow up. There was evidence to suggest that education can improve HRQoL and decrease healthcare costs by reductions in downstream healthcare utilization. Our review had insufficient power to exclude clinically important effects of education on mortality and morbidity. Nevertheless it supports the practice of CHD secondary prevention and rehabilitation programmes including education as an intervention. Further research is needed to determine the most effective and cost-effective format, duration, timing, and methods of education delivery.

Inferior or double joint spaces injection versus superior joint space injection for temporomandibular disorders: a systematic review and meta-analysis.

PubMed

Li, Chunjie; Zhang, Yifan; Lv, Jun; Shi, Zongdao

2012-01-01

To compare the effect and safety of inferior or double temporomandibular joint spaces drug injection versus superior temporomandibular joint space injection in the treatment of temporomandibular disorders. MEDLINE (via Ovid, 1948 to March 2011), CENTRAL (Issue 1, 2011), Embase (1984 to March 2011), CBM (1978 to March 2011), and World Health Organization International Clinical Trials Registry Platform were searched electronically; relevant journals as well as references of included studies were hand-searched for randomized controlled trials comparing effect or safety of inferior or double joint spaces drug injection technique with those of superior space injection technique. Risk of bias assessment with the tool recommended by Cochrane Collaboration, reporting quality assessment with CONSORT and data extraction, were carried out independently by 2 reviewers. Meta-analysis was delivered with RevMan 5.0.23. Four trials with 349 participants were included. All the included studies had moderate risk of bias. Meta-analysis showed that inferior or double spaces injection technique could significantly increase 2.88 mm more maximal mouth opening (P = .0001) and alleviate pain intensity in the temporomandibular area on average by 9.01 mm visual analog scale scores (P = .0001) compared with superior space injection technique, but could not markedly change synthesized clinical index (P = .05) in the short term; nevertheless, they showed more beneficial maximal mouth opening (P = .002), pain relief (P < .0001), and synthesized clinical variable (P < .0001) in the long term than superior space injection. No serious adverse events were reported. Inferior or double temporomandibular joint spaces drug injection technique shows better effect than superior space injection technique, and their safety is affirmative. However, more high-quality studies are still needed to test and verify the evidence. Crown Copyright © 2012. Published by Elsevier Inc. All rights reserved.

SOGC clinical practice guidelines: Substance use in pregnancy: no. 256, April 2011.

PubMed

Wong, Suzanne; Ordean, Alice; Kahan, Meldon

2011-08-01

To improve awareness and knowledge of problematic substance use in pregnancy and to provide evidence-based recommendations for the management of this challenging clinical issue for all health care providers. This guideline reviews the use of screening tools, general approach to care, and recommendations for clinical management of problematic substance use in pregnancy. Evidence-based recommendations for screening and management of problematic substance use during pregnancy and lactation. Medline, PubMed, CINAHL, and The Cochrane Library were searched for articles published from 1950 using the following key words: substance-related disorders, mass screening, pregnancy complications, pregnancy, prenatal care, cocaine, cannabis, methadone, opioid, tobacco, nicotine, solvents, hallucinogens, and amphetamines. Results were initially restricted to systematic reviews and randomized control trials/controlled clinical trials. A subsequent search for observational studies was also conducted because there are few RCTs in this field of study. Articles were restricted to human studies published in English. Additional articles were located by hand searching through article reference lists. Searches were updated on a regular basis and incorporated in the guideline up to December 2009. Grey (unpublished) literature was also identified through searching the websites of health technology assessment and health technology assessment-related agencies, clinical practice guideline collections, clinical trial registries, and national and international medical specialty societies. The quality of evidence was rated using the criteria described in the Report of the Canadian Task Force on the Preventive Health Care. Recommendations for practice were ranked according to the method described in that report (Table 1). This guideline is intended to increase the knowledge and comfort level of health care providers caring for pregnant women who have substance use disorders. Improved access to health care and assistance with appropriate addiction care leads to reduced health care costs and decreased maternal and neonatal morbidity and mortality.

Statistical analysis plan for the family-led rehabilitation after stroke in India (ATTEND) trial: A multicenter randomized controlled trial of a new model of stroke rehabilitation compared to usual care.

PubMed

Billot, Laurent; Lindley, Richard I; Harvey, Lisa A; Maulik, Pallab K; Hackett, Maree L; Murthy, Gudlavalleti Vs; Anderson, Craig S; Shamanna, Bindiganavale R; Jan, Stephen; Walker, Marion; Forster, Anne; Langhorne, Peter; Verma, Shweta J; Felix, Cynthia; Alim, Mohammed; Gandhi, Dorcas Bc; Pandian, Jeyaraj Durai

2017-02-01

Background In low- and middle-income countries, few patients receive organized rehabilitation after stroke, yet the burden of chronic diseases such as stroke is increasing in these countries. Affordable models of effective rehabilitation could have a major impact. The ATTEND trial is evaluating a family-led caregiver delivered rehabilitation program after stroke. Objective To publish the detailed statistical analysis plan for the ATTEND trial prior to trial unblinding. Methods Based upon the published registration and protocol, the blinded steering committee and management team, led by the trial statistician, have developed a statistical analysis plan. The plan has been informed by the chosen outcome measures, the data collection forms and knowledge of key baseline data. Results The resulting statistical analysis plan is consistent with best practice and will allow open and transparent reporting. Conclusions Publication of the trial statistical analysis plan reduces potential bias in trial reporting, and clearly outlines pre-specified analyses. Clinical Trial Registrations India CTRI/2013/04/003557; Australian New Zealand Clinical Trials Registry ACTRN1261000078752; Universal Trial Number U1111-1138-6707.

School dental screening programmes for oral health.

PubMed

Arora, Ankita; Khattri, Shivi; Ismail, Noorliza Mastura; Kumbargere Nagraj, Sumanth; Prashanti, Eachempati

2017-12-21

School dental screening refers to visual inspection of children's oral cavity in a school setting followed by making parents aware of their child's current oral health status and treatment needs. Screening at school intends to identify children at an earlier stage than symptomatic disease presentation, hence prompting preventive and therapeutic oral health care for the children. This review evaluates the effectiveness of school dental screening in improving oral health status. To assess the effectiveness of school dental screening programmes on overall oral health status and use of dental services. Cochrane Oral Health's Information Specialist searched the following databases: Cochrane Oral Health's Trials Register (to 15 March 2017), the Cochrane Central Register of Controlled Trials (CENTRAL, the Cochrane Register of Studies, to 15 March 2017), MEDLINE Ovid (1946 to 15 March 2017), and Embase Ovid (15 September 2016 to 15 March 2017). The US National Institutes of Health Trials Registry (ClinicalTrials.gov) and the World Health Organization International Clinical Trials Registry Platform were searched for ongoing trials. No restrictions were placed on language or publication status when searching the electronic databases; however, the search of Embase was restricted to the last six months due to the Cochrane Centralised Search Project to identify all clinical trials and add them to CENTRAL. We included randomised controlled trials (RCTs) (cluster or parallel) that evaluated school dental screening compared with no intervention or with one type of screening compared with another. We used standard methodological procedures expected by Cochrane. We included six trials (four were cluster-RCTs) with 19,498 children who were 4 to 15 years of age. Four trials were conducted in the UK and two were based in India. We assessed two trials to be at low risk of bias, one trial to be at high risk of bias and three trials to be at unclear risk of bias.None of the six trials reported the proportion of children with untreated caries or other oral diseases.Four trials evaluated traditional screening versus no screening. We performed a meta-analysis for the outcome 'dental attendance' and found an inconclusive result with high heterogeneity. The heterogeneity was found it to be, in part, due to study design (three cluster-RCTs and one individual-level RCT). Due to the inconsistency, we downgraded the evidence to 'very low certainty' and are unable to draw conclusions about this comparison.Two cluster-RCTs (both four-arm trials) evaluated criteria-based screening versus no screening and showed a pooled effect estimate of RR 1.07 (95% CI 0.99 to 1.16), suggesting a possible benefit for screening (low-certainty evidence). There was no evidence of a difference when criteria-based screening was compared to traditional screening (RR 1.01, 95% CI 0.94 to 1.08) (very low-certainty evidence).In one trial, a specific (personalised) referral letter was compared to a non-specific one. Results favoured the specific referral letter with an effect estimate of RR 1.39 (95% CI 1.09 to 1.77) for attendance at general dentist services and effect estimate of RR 1.90 (95% CI 1.18 to 3.06) for attendance at specialist orthodontist services (low-certainty evidence).One trial compared screening supplemented with motivation to screening alone. Dental attendance was more likely after screening supplemented with motivation, with an effect estimate of RR 3.08 (95% CI 2.57 to 3.71) (low-certainty evidence).None of the trials had long-term follow-up to ascertain the lasting effects of school dental screening.None of the trials reported cost-effectiveness and adverse events. The trials included in this review evaluated short-term effects of screening, assessing follow-up periods of three to eight months. We found very low certainty evidence that was insufficient to allow us to draw conclusions about whether there is a role for traditional school dental screening in improving dental attendance. For criteria-based screening, we found low-certainty evidence that it may improve dental attendance when compared to no screening. However, when compared to traditional screening there was no evidence of a difference in dental attendance (very low-certainty evidence).We found low-certainty evidence to conclude that personalised or specific referral letters improve dental attendance when compared to non-specific counterparts. We also found low-certainty evidence that screening supplemented with motivation (oral health education and offer of free treatment) improves dental attendance in comparison to screening alone.We did not find any trials addressing cost-effectiveness and adverse effects of school dental screening.

Anticonvulsants for preventing seizures in patients with chronic subdural haematoma.

PubMed

Ratilal, Bernardo O; Pappamikail, Lia; Costa, João; Sampaio, Cristina

2013-06-06

Anticonvulsant therapy is sometimes used prophylactically in patients with chronic subdural haematoma, although the benefit is unclear. To assess the effects of prophylactic anticonvulsants in patients with chronic subdural haematoma, in both the pre- and post-operative periods. We searched the Cochrane Injuries Group's Specialised Register, CENTRAL (The Cochrane Library), MEDLINE (OvidSP), EMBASE (OvidSP), PubMed, LILACS, and the databases clinicaltrials.gov, the WHO International Clinical Trials Registry Platform, and Current Controlled Trials. The search was through 27th March 2013. Randomised controlled trials comparing any anticonvulsant versus placebo or no intervention. Three authors screened the search results to identify relevant studies. No studies met the inclusion criteria for the review. No randomised controlled trials were identified. No formal recommendations can be made about the use of prophylactic anticonvulsants in patients with chronic subdural haematoma based on the literature currently available. There are no randomised controlled trials on this topic, and non-controlled studies have conflicting results. There is an urgent need for well-designed randomised controlled trials.

Aggregator: a machine learning approach to identifying MEDLINE articles that derive from the same underlying clinical trial.

PubMed

Shao, Weixiang; Adams, Clive E; Cohen, Aaron M; Davis, John M; McDonagh, Marian S; Thakurta, Sujata; Yu, Philip S; Smalheiser, Neil R

2015-03-01

It is important to identify separate publications that report outcomes from the same underlying clinical trial, in order to avoid over-counting these as independent pieces of evidence. We created positive and negative training sets (comprised of pairs of articles reporting on the same condition and intervention) that were, or were not, linked to the same clinicaltrials.gov trial registry number. Features were extracted from MEDLINE and PubMed metadata; pairwise similarity scores were modeled using logistic regression. Article pairs from the same trial were identified with high accuracy (F1 score=0.843). We also created a clustering tool, Aggregator, that takes as input a PubMed user query for RCTs on a given topic, and returns article clusters predicted to arise from the same clinical trial. Although painstaking examination of full-text may be needed to be conclusive, metadata are surprisingly accurate in predicting when two articles derive from the same underlying clinical trial. Copyright © 2014 Elsevier Inc. All rights reserved.

Sample size of the reference sample in a case-augmented study.

PubMed

Ghosh, Palash; Dewanji, Anup

2017-05-01

The case-augmented study, in which a case sample is augmented with a reference (random) sample from the source population with only covariates information known, is becoming popular in different areas of applied science such as pharmacovigilance, ecology, and econometrics. In general, the case sample is available from some source (for example, hospital database, case registry, etc.); however, the reference sample is required to be drawn from the corresponding source population. The required minimum size of the reference sample is an important issue in this regard. In this work, we address the minimum sample size calculation and discuss related issues. Copyright © 2017 John Wiley & Sons, Ltd. Copyright © 2017 John Wiley & Sons, Ltd.

Maternity leave in normal pregnancy.

PubMed

Leduc, Dean

2011-08-01

To assist maternity care providers in recognizing and discussing health- and illness-related issues in pregnancy and their relationship to maternity benefits. Published literature was retrieved through searches of PubMed or Medline, CINAHL, and The Cochrane Library in 2009 using appropriate controlled vocabulary (e.g., maternity benefits) and key words (e.g., maternity, benefits, pregnancy). Results were restricted to systematic reviews, randomized controlled trials/controlled clinical trials, and observational studies. There were no date or language restrictions. Searches were updated on a regular basis and incorporated in the guideline to December 2009. Grey (unpublished) literature was identified through searching the web sites of health technology assessment and health technology assessment-related agencies, clinical practice guideline collections, clinical trial registries, and national and international medical specialty societies.

Comparison of interventional cardiology in two European countries: a nationwide Internet based registry study.

PubMed

Gudnason, T; Gudnadottir, G S; Lagerqvist, B; Eyjolfsson, K; Nilsson, T; Thorgeirsson, G; Thorgeirsson, G; Andersen, K; James, S

2013-09-30

The practice of interventional cardiology differs between countries and regions. In this study we report the results of the first nation-wide long-term comparison of interventional cardiology in two countries using a common web-based registry. The Swedish Coronary Angiography and Angioplasty Registry (SCAAR) was used to prospectively and continuously collect background-, quality-, and outcome parameters for all coronary angiographies (CA) and percutaneous coronary interventions (PCI) performed in Iceland and Sweden during one year. The rate of CA per million inhabitants was higher in Iceland than in Sweden. A higher proportion of patients had CA for stable angina in Iceland than in Sweden, while the opposite was true for ST elevation myocardial infarction. Left main stem stenosis was more commonly found in Iceland than in Sweden. The PCI rate was similar in the two countries as was the general success rate of PCI, achievement of complete revascularisation and the overall stent use. Drug eluting stents were more commonly used in Iceland (23% vs. 19%). The use of fractional flow reserve (0.2% vs. 10%) and the radial approach (0.6% vs. 33%) was more frequent in Sweden than in Iceland. Serious complications and death were very rare in both countries. By prospectively comparing interventional cardiology in two countries, using a common web based registry online, we have discovered important differences in technique and indications. A discovery such as this can lead to a change in clinical practice and inspire prospective multinational randomised registry trials in unselected, real world populations. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

Patients with advanced and metastatic renal cell carcinoma treated with targeted therapy in the Czech Republic: twenty cancer centres, six agents, one database.

PubMed

Poprach, Alexandr; Bortlíček, Zbyněk; Büchler, Tomáš; Melichar, Bohuslav; Lakomý, Radek; Vyzula, Rostislav; Brabec, Petr; Svoboda, Marek; Dušek, Ladislav; Gregor, Jakub

2012-12-01

The incidence and mortality of renal cell carcinoma (RCC) in the Czech Republic are among the highest in the world. Several targeted agents have been recently approved for the treatment of advanced/metastatic RCC. Presentation of a national clinical database for monitoring and assessment of patients with advanced/metastatic RCC treated with targeted therapy. The RenIS (RENal Information System, http://renis.registry.cz ) registry is a non-interventional post-registration database of epidemiological and clinical data of patients with RCC treated with targeted therapies in the Czech Republic. Twenty cancer centres eligible for targeted therapy administration participate in the project. As of November 2011, six agents were approved and reimbursed from public health insurance, including bevacizumab, everolimus, pazopanib, sorafenib, sunitinib, and temsirolimus. As of 10 October 2011, 1,541 patients with valid records were entered into the database. Comparison with population-based data from the Czech National Cancer Registry revealed that RCC patients treated with targeted therapy are significantly younger (median age at diagnosis 59 vs. 66 years). Most RenIS registry patients were treated with sorafenib and sunitinib, many patients sequentially with both agents. Over 10 % of patients were also treated with everolimus in the second or third line. Progression-free survival times achieved were comparable to phase III clinical trials. The RenIS registry has become an important tool and source of information for the management of cancer care and clinical practice, providing comprehensive data on monitoring and assessment of RCC targeted therapy on a national level.

Ginkgo biloba extract for age-related macular degeneration.

PubMed

Evans, Jennifer R

2013-01-31

Ginkgo is used in the treatment of peripheral vascular disease and 'cerebral insufficiency'. It is thought to have several potential mechanisms of action including increased blood flow, platelet activating factor antagonism, and prevention of membrane damage caused by free radicals. Vascular factors and oxidative damage are thought to be two potential mechanisms in the pathology of age-related macular degeneration (AMD). The objective of this review was to determine the effect of Ginkgo biloba extract on the progression of AMD. We searched CENTRAL (which contains the Cochrane Eyes and Vision Group Trials Register) (The Cochrane Library 2012, Issue 10), Ovid MEDLINE, Ovid MEDLINE In-Process and Other Non-Indexed Citations, Ovid MEDLINE Daily, Ovid OLDMEDLINE (January 1946 to October 2012), EMBASE (January 1980 to October 2012), Allied and Complementary Medicine Database (AMED) (January 1985 to October 2012), OpenGrey (System for Information on Grey Literature in Europe) (www.opengrey.eu/), the metaRegister of Controlled Trials (mRCT) (www.controlled-trials.com), ClinicalTrials.gov (www.clinicaltrials.gov) and the WHO International Clinical Trials Registry Platform (ICTRP) (www.who.int/ictrp/search/en). We did not use any date or language restrictions in the electronic searches for trials. We last searched the electronic databases on 5 October 2012. We searched the reference lists of identified reports and the Science Citation Index. We also contacted investigators of included studies for additional information. All randomised trials in people with AMD where Ginkgo biloba extract had been compared to control were included. The review author extracted data using a standardised form. The data were verified with the trial investigators. Trial quality was assessed. Two published trials were identified that randomised a total of 119 people. In one study conducted in France, 20 people were randomly allocated to Gingko biloba extract EGb 761 80 mg twice daily or placebo. In the other study conducted in Germany, 99 people were randomly allocated to two different doses of Ginkgo biloba extract EGb 761 (240 mg per day and 60 mg per day). Treatment duration in both studies was six months. Both trials reported some positive effects of Ginkgo biloba on vision however their results could not be pooled. Adverse effects and quality of life for people with AMD were not reported. The question as to whether people with AMD should take Ginkgo biloba extract to prevent progression of the disease has not been answered by research to date. Two small trials have suggested possible benefit of Gingko biloba on vision and further trials are warranted. Ginkgo biloba is widely used in China, Germany, and France. Future trials should be larger, and last longer, in order to provide a more robust measure of the effect of Gingko biloba extract on AMD.

REACH: study protocol of a randomised trial of rehabilitation very early in congenital hemiplegia

PubMed Central

Boyd, Roslyn N; Ziviani, Jenny; Sakzewski, Leanne; Novak, Iona; Badawi, Nadia; Pannek, Kerstin; Elliott, Catherine; Greaves, Susan; Guzzetta, Andrea; Whittingham, Koa; Valentine, Jane; Morgan, Cathy; Wallen, Margaret; Eliasson, Ann-Christin; Findlay, Lisa; Ware, Robert; Fiori, Simona; Rose, Stephen

2017-01-01

Objectives Congenital hemiplegia is the most common form of cerebral palsy (CP). Children with unilateral CP show signs of upper limb asymmetry by 8 months corrected age (ca) but are frequently not referred to therapy until after 12 months ca. This study compares the efficacy of infant-friendly modified constraint-induced movement therapy (Baby mCIMT) to infant friendly bimanual therapy (Baby BIM) on upper limb, cognitive and neuroplasticity outcomes in a multisite randomised comparison trial. Methods and analysis 150 infants (75 in each group), aged between 3 and 6 months ca, with asymmetric brain injury and clinical signs of upper extremity asymmetry will be recruited. Children will be randomised centrally to receive equal doses of either Baby mCIMT or Baby BIM. Baby mCIMT comprises restraint of the unimpaired hand using a simple restraint (eg, glove, sock), combined with intensive parent implemented practice focusing on active use of the impaired hand in a play-based context. In contrast, Baby BIM promotes active play requiring both hands in a play-based context. Both interventions will be delivered by parents at home with monthly home visits and interim telecommunication support by study therapists. Assessments will be conducted at study entry; at 6, 12 months ca immediately postintervention (primary outcome) and 24 months ca (retention). The primary outcome will be the Mini-Assisting Hand Assessment. Secondary outcomes include the Bayley Scale for Infant and Toddler Development (cognitive and motor domains) and the Hand Assessment of Infants. A subset of children will undertake MRI scans at 24 months ca to evaluate brain lesion severity and brain (re)organisation after intervention. Ethics and dissemination Full ethical approvals for this study have been obtained from the relevant sites. The findings will be disseminated in peer-reviewed publications. Trial registration number Australian and New Zealand Clinical Trials Registry: ACTRN12615000180516, Pre results. PMID:28928195

Antiviral efficacy and safety of abacavir-containing combination antiretroviral therapy as first-line treatment of HIV-infected children and adolescents: a systematic review protocol

PubMed Central

2014-01-01

Background Abacavir is one of the recommended nucleoside reverse transcriptase inhibitors (NRTIs) for the treatment of HIV infections among children and adolescents. However, there are concerns that the antiviral efficacy of abacavir might be low when compared to other NRTIs especially among children. There are also concerns that abacavir use may lead to serious adverse events such as hypersensitivity reactions and has potential predisposition to developing cardiovascular diseases. Methods We plan to do a systematic review to evaluate the antiviral efficacy and safety of abacavir-containing combination antiretroviral therapy as first-line treatment of HIV-infected children aged between 3 months and 18 years, compared with other NRTIs. We will search Scopus, Cochrane Central Register of Controlled Trials, MEDLINE, and Web of Science databases for eligible studies regardless of language or publication status. We will check the reference lists of included studies, search relevant conference proceedings, email the authors of included studies and also look for unpublished and ongoing trials in prospective clinical trial registries. Two authors will independently screen search outputs, select studies, extract data and assess the risk of bias in included studies. All disagreements will be resolved by discussion and consensus. Where data allow, we will conduct meta-analysis for similar types of participants, study designs, interventions, and outcome measures. If the results are statistically homogeneous, we will use the fixed-effect model; otherwise, we will use the random-effects model and explore the reasons for heterogeneity using subgroup analyses. Heterogeneity will be assessed with the Chi-squared test and quantified with the I-squared statistic. Discussion The findings will be useful to policy makers and programme managers to inform treatment and management of HIV in children and adolescents and to point out research gaps for future research. Trial registration This review is registered with PROSPERO, registration number CRD42014009157. PMID:25115243

Care delivery and self-management strategies for children with epilepsy.

PubMed

Fleeman, Nigel; Bradley, Peter M

2018-03-01

In response to criticism that epilepsy care for children has little impact, healthcare professionals and administrators have developed various service models and strategies to address perceived inadequacies. To assess the effects of any specialised or dedicated intervention for epilepsy versus usual care in children with epilepsy and in their families. We searched the Cochrane Epilepsy Group Specialized Register (27 September 2016), the Cochrane Central Register of Controlled Trials (CENTRAL; 2016, Issue 9) in the Cochrane Library, MEDLINE (1946 to 27 September 2016), Embase (1974 to 27 September 2016), PsycINFO (1887 to 27 September 2016) and CINAHL Plus (1937 to 27 September 2016). In addition, we also searched clinical trials registries for ongoing or recently completed trials, contacted experts in the field to seek information on unpublished and ongoing studies, checked the websites of epilepsy organisations and checked the reference lists of included studies. We included randomised controlled trials (RCTs), cohort studies or other prospective studies with a (matched or unmatched) control group (controlled before-and-after studies), or time series studies. We used standard methodological procedures expected by Cochrane. Our review included six interventions reported through seven studies (of which five studies were designed as RCTs). They reported on different education and counselling programmes for children and parents; teenagers and parents; or children, adolescents and their parents. Each programme showed some benefits for the well-being of children with epilepsy, but all had methodological flaws (e.g. in one of the studies designed as an RCT, randomisation failed), no single programme was independently evaluated with different study samples and no interventions were sufficiently homogeneous enough to be included in a meta-analysis,. While each of the programmes in this review showed some benefit to children with epilepsy, their impacts were extremely variable. No programme showed benefits across the full range of outcomes, and all studies had major methodological problems. At present there is insufficient evidence in favour of any single programme.

EPA Facility Registry Service (FRS): OIL

EPA Pesticide Factsheets

This dataset contains location and facility identification information from EPA's Facility Registry Service (FRS) for the subset of facilities that link to the Oil database. The Oil database contains information on Spill Prevention, Control, and Countermeasure (SPCC) and Facility Response Plan (FRP) subject facilities to prevent and respond to oil spills. FRP facilities are referred to as substantial harm facilities due to the quantities of oil stored and facility characteristics. FRS identifies and geospatially locates facilities, sites or places subject to environmental regulations or of environmental interest. Using vigorous verification and data management procedures, FRS integrates facility data from EPA's national program systems, other federal agencies, and State and tribal master facility records and provides EPA with a centrally managed, single source of comprehensive and authoritative information on facilities. This data set contains the subset of FRS integrated facilities that link to Oil facilities once the Oil data has been integrated into the FRS database. Additional information on FRS is available at the EPA website https://www.epa.gov/enviro/facility-registry-service-frs.

Phase I of roadmap towards incorporating intelligent structure technology for refining bridge inspection in Mississippi.

DOT National Transportation Integrated Search

2011-02-25

"Bridge scour refers to the removal of sediments from the bridge foundation by flood. It is the most detrimental cause for the majority of : bridge failures in the United States. In the National Bridge Registry, there are 484,546 highway bridges over...

Measurement guidelines for the sequestration of forest carbon

Treesearch

Timothy R.H. Pearson; Sandra L. Brown; Richard A. Birdsey

2007-01-01

Measurement guidelines for forest carbon sequestration were developed to support reporting by public and private entities to greenhouse gas registries. These guidelines are intended to be a reference for designing a forest carbon inventory and monitoring system by professionals with a knowledge of sampling, statistical estimation, and forest measurements. This report...

A New Ethical Challenge for Institutional Review Boards (IRBs)/Ethics Committees (ECs) in the Assessment of Pediatric Clinical Trials.

PubMed

Rose, Klaus; Kummer, Hans

2015-05-28

Both the US and EU have introduced pediatric pharmaceutical legislation to facilitate clinical trials in children and development of better medicines for children. The first concerns were published in 2014 that the European Medicines Agency (EMA)'s Pediatric Committee (PDCO) may be over-enthusiastic and has compelled questionable pediatric clinical trials from pharmaceutical companies. Numerous clinical trials are mandated in rare conditions for which not enough patients exist for even one trial. Furthermore, where these trials are mandated in adolescent patients, the legal age limit of the 18th birthday is confused with a medical age limit and can result in separate clinical trials in adolescent patients that neither make medical nor scientific sense nor will ever recruit enough patients for a meaningful outcome. To confirm our concerns we searched the registry clinicaltrials.gov and found examples for PDCO-triggered unethical trials. We conclude that such trials should not be accepted by institutional review boards (IRBs)/ethics committees (ECs) and that clinical trials resulting from negotiations with EMA's PDCO need extra careful scrutiny by IRBs/ECs in order to prevent unethical studies and damage to pediatric research and unnecessary risks to pediatric patients.

Re-Engineering Alzheimer Clinical Trials: Global Alzheimer's Platform Network.

PubMed

Cummings, J; Aisen, P; Barton, R; Bork, J; Doody, R; Dwyer, J; Egan, J C; Feldman, H; Lappin, D; Truyen, L; Salloway, S; Sperling, R; Vradenburg, G

2016-06-01

Alzheimer's disease (AD) drug development is costly, time-consuming, and inefficient. Trial site functions, trial design, and patient recruitment for trials all require improvement. The Global Alzheimer Platform (GAP) was initiated in response to these challenges. Four GAP work streams evolved in the US to address different trial challenges: 1) registry-to-cohort web-based recruitment; 2) clinical trial site activation and site network construction (GAP-NET); 3) adaptive proof-of-concept clinical trial design; and 4) finance and fund raising. GAP-NET proposes to establish a standardized network of continuously funded trial sites that are highly qualified to perform trials (with established clinical, biomarker, imaging capability; certified raters; sophisticated management system. GAP-NET will conduct trials for academic and biopharma industry partners using standardized instrument versions and administration. Collaboration with the Innovative Medicines Initiative (IMI) European Prevention of Alzheimer's Disease (EPAD) program, the Canadian Consortium on Neurodegeneration in Aging (CCNA) and other similar international initiatives will allow conduct of global trials. GAP-NET aims to increase trial efficiency and quality, decrease trial redundancy, accelerate cohort development and trial recruitment, and decrease trial costs. The value proposition for sites includes stable funding and uniform training and trial execution; the value to trial sponsors is decreased trial costs, reduced time to execute trials, and enhanced data quality. The value for patients and society is the more rapid availability of new treatments for AD.

Childhood cancer registration in New Zealand: A registry collaboration to assess and improve data quality.

PubMed

Ballantine, Kirsten R; Hanna, Susan; Macfarlane, Scott; Bradbeer, Peter; Teague, Lochie; Hunter, Sarah; Cross, Siobhan; Skeen, Jane

2018-06-11

To evaluate the completeness and accuracy of child cancer registration in New Zealand. Registrations for children aged 0-14 diagnosed between 1/1/2010 and 31/12/2014 were obtained from the New Zealand Cancer Registry (NZCR) and the New Zealand Children's Cancer Registry (NZCCR). Six key data fields were matched using National Health Index numbers in order to identify and resolve registration discrepancies. Capture-recapture methods were used to assess the completeness of cancer registration. 794 unique cases were reported; 718 from the NZCR, 721 from the NZCCR and 643 from both registries. 27 invalid cancer registrations were identified, including 19 residents of the Pacific Islands who had travelled to New Zealand for treatment. The NZCCR provided 55 non-malignant central nervous system tumour and 16 Langerhans cell histiocytosis cases which were not registered by the NZCR. The NZCR alerted the NZCCR to 18 cases missed due to human error and 23 cases that had not been referred to the specialist paediatric oncology centres. 762 cases were verified as true incident cases, an incidence rate of 166.8 per million. Registration accuracy for six key data fields was 98.6%. According to their respective inclusion criteria case completeness was 99.3% for the NZCR and 94.4% for the NZCCR. For childhood malignancies covered by both registries, capture-recapture methods estimated case ascertainment at greater than 99.9%. With two national registries covering childhood cancers, New Zealand is uniquely positioned to undertake regular cooperative activities to ensure high quality data is available for research and patient care. Copyright © 2018 Elsevier Ltd. All rights reserved.

Use of large healthcare databases for rheumatology clinical research.

PubMed

Desai, Rishi J; Solomon, Daniel H

2017-03-01

Large healthcare databases, which contain data collected during routinely delivered healthcare to patients, can serve as a valuable resource for generating actionable evidence to assist medical and healthcare policy decision-making. In this review, we summarize use of large healthcare databases in rheumatology clinical research. Large healthcare data are critical to evaluate medication safety and effectiveness in patients with rheumatologic conditions. Three major sources of large healthcare data are: first, electronic medical records, second, health insurance claims, and third, patient registries. Each of these sources offers unique advantages, but also has some inherent limitations. To address some of these limitations and maximize the utility of these data sources for evidence generation, recent efforts have focused on linking different data sources. Innovations such as randomized registry trials, which aim to facilitate design of low-cost randomized controlled trials built on existing infrastructure provided by large healthcare databases, are likely to make clinical research more efficient in coming years. Harnessing the power of information contained in large healthcare databases, while paying close attention to their inherent limitations, is critical to generate a rigorous evidence-base for medical decision-making and ultimately enhancing patient care.

Memory systems in the rat: effects of reward probability, context, and congruency between working and reference memory.

PubMed

Roberts, William A; Guitar, Nicole A; Marsh, Heidi L; MacDonald, Hayden

2016-05-01

The interaction of working and reference memory was studied in rats on an eight-arm radial maze. In two experiments, rats were trained to perform working memory and reference memory tasks. On working memory trials, they were allowed to enter four randomly chosen arms for reward in a study phase and then had to choose the unentered arms for reward in a test phase. On reference memory trials, they had to learn to visit the same four arms on the maze on every trial for reward. Retention was tested on working memory trials in which the interval between the study and test phase was 15 s, 15 min, or 30 min. At each retention interval, tests were performed in which the correct WM arms were either congruent or incongruent with the correct RM arms. Both experiments showed that congruency interacted with retention interval, yielding more forgetting at 30 min on incongruent trials than on congruent trials. The effect of reference memory strength on the congruency effect was examined in Experiment 1, and the effect of associating different contexts with working and reference memory on the congruency effect was studied in Experiment 2.

Comparison of self-report influenza vaccination coverage with data from a population based computerized vaccination registry and factors associated with discordance.

PubMed

Jiménez-García, Rodrigo; Hernandez-Barrera, Valentín; Rodríguez-Rieiro, Cristina; Carrasco Garrido, Pilar; López de Andres, Ana; Jimenez-Trujillo, Isabel; Esteban-Vasallo, María D; Domínguez-Berjón, Maria Felicitas; de Miguel-Diez, Javier; Astray-Mochales, Jenaro

2014-07-31

We aim to compare influenza vaccination coverages obtained using two different methods; a population based computerized vaccination registry and self-reported influenza vaccination status as captured by a population survey. The study was conducted in the Autonomous Community of Madrid (ACM), Spain, and refers to the 2011/12 influenza vaccination campaign. Information on influenza vaccination status according to a computerized registry was extracted from the SISPAL database and crossed with the electronic clinical records in primary care (ECRPC). Self-reported vaccine uptake was obtained from subjects living in the ACM included in the 2011-12 Spanish National Health Survey (SNHS). Independent study variables included: age, sex, immigrant status and the presence of high risk chronic conditions. Vaccination coverages were calculated according to study variables. Crude and adjusted prevalence ratios were computed to assess concordance. The study population included 5,245,238 adults living in the ACM in year 2011 with an individual ECRPC and 1449 adult living the ACM and interviewed in the SNHS from October 2011 to June 2012. The weighted vaccination coverage for the study population according to self-reported data was 19.77% and 15.04% from computerized registries resulting in a crude prevalence ratio (cPR) of 1.31 (95% CI 1.20-1.44) so self-reported data significantly overestimated 31% the registry coverage. Self-reported coverages are always higher than registry based coverages when the study population is stratified by the study variables. Self-reported overestimation was higher among men than women, younger age groups, immigrants and those without chronic conditions. Both methods provide the most concordant estimations for the target population of the influenza vaccine. Self-report influenza vaccination uptake overestimates vaccination registries coverages. The validity of self-report seems to be negatively affected by socio-demographic variables and the absence of chronic conditions. Possible strategies must be considered and implemented to improve both coverage estimation methods. Copyright © 2014 Elsevier Ltd. All rights reserved.

Sodium Bicarbonate for Control of ICP: A Systematic Review.

PubMed

Zeiler, Frederick A; Sader, Nicholas; West, Michael; Gillman, Lawrence M

2018-01-01

Our goal was to perform a systematic review of the literature on the use of intravenous sodium bicarbonate for intracranial pressure (ICP) reduction in patients with neurologic illness. Data sources: articles from MEDLINE, BIOSIS, EMBASE, Global Health, Scopus, Cochrane Library, the International Clinical Trials Registry Platform (inception to April 2015), reference lists of relevant articles, and gray literature were searched. 2 reviewers independently extracted data including population characteristics and treatment characteristics. The strength of evidence was adjudicated using both the Oxford and Grading of Recommendation Assessment Development and Education methodology. Our search strategy produced a total 559 citations. Three original articles were included in the review. There were 2 prospective studies, 1 randomized control trial and 1 single arm, and 1 retrospective case report.Across all studies there were a total of 19 patients studied, with 31 episodes of elevated ICP being treated. Twenty-one of those episodes were treated with sodium bicarbonate infusion, with the remaining 10 treated with hypertonic saline in a control model. All elevated ICP episodes treated with sodium bicarbonate solution demonstrated a significant drop in ICP, without an elevation of serum partial pressure of carbon dioxide. No significant complications were described. There currently exists Oxford level 4, Grading of Recommendation Assessment Development and Education D evidence to support an ICP reduction effect with intravenous sodium bicarbonate in TBI. No comments on its impact in other neuropathologic states, or on patient outcomes, can be made at this time.

Protocol and baseline data from The Inala Chronic Disease Management Service evaluation study: a health services intervention study for diabetes care

PubMed Central

2010-01-01

Background Type 2 Diabetes Mellitus is one of the most disabling chronic conditions worldwide, resulting in significant human, social and economic costs and placing huge demands on health care systems. The Inala Chronic Disease Management Service aims to improve the efficiency and effectiveness of care for patients with type 2 diabetes who have been referred by their general practitioner to a specialist diabetes outpatient clinic. Care is provided by a multidisciplinary, integrated team consisting of an endocrinologist, diabetes nurse educators, General Practitioner Clinical Fellows (general practitioners who have undertaken focussed post-graduate training in complex diabetes care), and allied health personnel (a dietitian, podiatrist and psychologist). Methods/Design Using a geographical control, this evaluation study tests the impact of this model of diabetes care provided by the service on patient outcomes compared to usual care provided at the specialist diabetes outpatient clinic. Data collection at baseline, 6 and 12-months will compare the primary outcome (glycaemic control) and secondary outcomes (serum lipid profile, blood pressure, physical activity, smoking status, quality of life, diabetes self-efficacy and cost-effectiveness). Discussion This model of diabetes care combines the patient focus and holistic care valued by the primary care sector with the specialised knowledge and skills of hospital diabetes care. Our study will provide empirical evidence about the clinical effectiveness of this model of care. Trial registration Australian New Zealand Clinical Trials Registry ACTRN12608000010392. PMID:20492731

[Does impact factor influence the ethics of the instructions provided to journal authors?].

PubMed

Teixeira, Renan Kleber Costa; Yamaki, Vitor Nagai; Gonçalves, Thiago Barbosa; Botelho, Nara Macedo; Silva, José Antonio Cordero da

2013-01-01

Verify whether a journal's impact factor is a mechanism that modifies the ethical requirements described in the instructions provided to authors of articles published in Brazilian medical journals. 48 selected journals were divided into two groups: impact-factor (n=24), and no-impact-factor (n=24). The number of ethical requirements was compared between both groups based on a specific research protocol, ranging from zero to six points, analyzing the presence of an approval by a research ethics committee; reference to the fact that the research follows the precepts of the Declaration of Helsinki and the rules of Resolution 196/96; use of an informed consent; information about the authors' conflicts of interest; and a request for registration of clinical trials in the Brazilian Clinical Trials Registry. The average score of the impact-factor group was significantly higher than that of the no-impact-factor group (3.12 ± 1.03 vs. 2.08 ± 1.64, p=0.0121). When each ethical requirement was compared between the groups, there was significant difference only between the requirement of an informed consent and the disclosure of conflicts of interest (p < 0.05). The impact factor is a determinant factor on the ethics included in the instructions to authors of articles in scientific journals, showing that higher-quality journals seek better-designed articles that are conscientious at the beginning of the research. Copyright © 2013 Elsevier Editora Ltda. All rights reserved.

Do emergency medicine journals promote trial registration and adherence to reporting guidelines? A survey of "Instructions for Authors".

PubMed

Sims, Matthew T; Henning, Nolan M; Wayant, C Cole; Vassar, Matt

2016-11-24

The aim of this study was to evaluate the current state of two publication practices, reporting guidelines requirements and clinical trial registration requirements, by analyzing the "Instructions for Authors" of emergency medicine journals. We performed a web-based data abstraction from the "Instructions for Authors" of the 27 Emergency Medicine journals catalogued in the Expanded Science Citation Index of the 2014 Journal Citation Reports and Google Scholar Metrics h5-index to identify whether each journal required, recommended, or made no mention of the following reporting guidelines: EQUATOR Network, ICMJE, ARRIVE, CARE, CONSORT, STARD, TRIPOD, CHEERS, MOOSE, STROBE, COREQ, SRQR, SQUIRE, PRISMA-P, SPIRIT, PRISMA, and QUOROM. We also extracted whether journals required or recommended trial registration. Authors were blinded to one another's ratings until completion of the data validation. Cross-tabulations and descriptive statistics were calculated using IBM SPSS 22. Of the 27 emergency medicine journals, 11 (11/27, 40.7%) did not mention a single guideline within their "Instructions for Authors," while the remaining 16 (16/27, 59.3%) mentioned one or more guidelines. The QUOROM statement and SRQR were not mentioned by any journals whereas the ICMJE guidelines (18/27, 66.7%) and CONSORT statement (15/27, 55.6%) were mentioned most often. Of the 27 emergency medicine journals, 15 (15/27, 55.6%) did not mention trial or review registration, while the remaining 12 (12/27, 44.4%) at least mentioned one of the two. Trial registration through ClinicalTrials.gov was mentioned by seven (7/27, 25.9%) journals while the WHO registry was mentioned by four (4/27, 14.8%). Twelve (12/27, 44.4%) journals mentioned trial registration through any registry platform. The aim of this study was to evaluate the current state of two publication practices, reporting guidelines requirements and clinical trial registration requirements, by analyzing the "Instructions for Authors" of emergency medicine journals. In this study, there was not a single reporting guideline mentioned in more than half of the journals. This undermines efforts of other journals to improve the completeness and transparency of research reporting. Reporting guidelines are infrequently required or recommended by emergency medicine journals. Furthermore, few require clinical trial registration. These two mechanisms may limit bias and should be considered for adoption by journal editors in emergency medicine. UMIN000022486.

Design and rationale of dabigatran's stroke prevention in real life in Turkey (D-SPIRIT).

PubMed

Türk, Uğur Önsel; Alioğlu, Emin; Tunçer, Eşref; Özpelit, Mehmet Emre; Pekel, Nihat; Tengiz, İstemihan; Çetin, Nurullah; Dalgıç, Onur; Topaloğlu, Caner; Bilgin, Nazile; Altın, Cihan; Özdemirkıran, Tolga; Tülüce, Kamil; Türkoğlu, Ebru İpek; Özpelit, Ebru

2016-04-01

The D-SPIRIT registry is designed to investigate the safety and efficacy of dabigatran etexilate in patients with nonvalvular atrial fibrillation (NVAF) and to collect data on outcomes in clinical practice. The D-SPIRIT is a national, prospective, observational, post-marketing registry involving patients with NVAF who have been taking dabigatran etexilate therapy for stroke prevention for a minimum of 6 months prior to enrollment. The registry will collect and analyze data from routine care, enrolling up to 600 patients in 9 centers. Patients will be followed up for 2 years to evaluate effectiveness and safety. A sample size of 600 subjects is proposed based on the following assumptions; Two-sided significance level of 0.05 (1-sided significance level of 0.025), ischemic stroke incidence rate of 0.768%-1.111%, hemorrhagic stroke incidence rate of 0.109%-0.130%, transient ischemic attack incidence rate of 0.722%-0.623%, therapy discontinuation incidence rate of 40% at day 730, and duration of enrollment period of 12 months with non-uniformed enrollment rate. Ethics approval was given by Dokuz Eylül University Ethics Committee of Clinical Research (2014/54) and approved by the Turkish Ministry of Health. Potential results of D-SPIRIT registry will add data from clinical practice to those from the RE-LY trial to expand knowledge of dabigatran etexilate treatment in patients with NVAF.

Protocol for a multi-centre randomised controlled trial comparing arthroscopic hip surgery to physiotherapy-led care for femoroacetabular impingement (FAI): the Australian FASHIoN trial.

PubMed

Murphy, Nicholas J; Eyles, Jillian; Bennell, Kim L; Bohensky, Megan; Burns, Alexander; Callaghan, Fraser M; Dickenson, Edward; Fary, Camdon; Grieve, Stuart M; Griffin, Damian R; Hall, Michelle; Hobson, Rachel; Kim, Young Jo; Linklater, James M; Lloyd, David G; Molnar, Robert; O'Connell, Rachel L; O'Donnell, John; O'Sullivan, Michael; Randhawa, Sunny; Reichenbach, Stephan; Saxby, David J; Singh, Parminder; Spiers, Libby; Tran, Phong; Wrigley, Tim V; Hunter, David J

2017-09-26

Femoroacetabular impingement syndrome (FAI), a hip disorder affecting active young adults, is believed to be a leading cause of hip osteoarthritis (OA). Current management approaches for FAI include arthroscopic hip surgery and physiotherapy-led non-surgical care; however, there is a paucity of clinical trial evidence comparing these approaches. In particular, it is unknown whether these management approaches modify the future risk of developing hip OA. The primary objective of this randomised controlled trial is to determine if participants with FAI who undergo hip arthroscopy have greater improvements in hip cartilage health, as demonstrated by changes in delayed gadolinium-enhanced magnetic resonance imaging (MRI) of cartilage (dGEMRIC) index between baseline and 12 months, compared to those who undergo physiotherapy-led non-surgical management. This is a pragmatic, multi-centre, two-arm superiority randomised controlled trial comparing hip arthroscopy to physiotherapy-led management for FAI. A total of 140 participants with FAI will be recruited from the clinics of participating orthopaedic surgeons, and randomly allocated to receive either surgery or physiotherapy-led non-surgical care. The surgical intervention involves arthroscopic FAI surgery from one of eight orthopaedic surgeons specialising in this field, located in three different Australian cities. The physiotherapy-led non-surgical management is an individualised physiotherapy program, named Personalised Hip Therapy (PHT), developed by a panel to represent the best non-operative care for FAI. It entails at least six individual physiotherapy sessions over 12 weeks, and up to ten sessions over six months, provided by experienced musculoskeletal physiotherapists trained to deliver the PHT program. The primary outcome measure is the change in dGEMRIC score of a ROI containing both acetabular and femoral head cartilages at the chondrolabral transitional zone of the mid-sagittal plane between baseline and 12 months. Secondary outcomes include patient-reported outcomes and several structural and biomechanical measures relevant to the pathogenesis of FAI and development of hip OA. Interventions will be compared by intention-to-treat analysis. The findings will help determine whether hip arthroscopy or an individualised physiotherapy program is superior for the management of FAI, including for the prevention of hip OA. Australia New Zealand Clinical Trials Registry reference: ACTRN12615001177549 . Trial registered 2/11/2015 (retrospectively registered).

Enabling Interoperability - Supporting a Diversity of Search Paradigms Using Shared Ontologies and Federated Registries

NASA Astrophysics Data System (ADS)

Hughes, J. S.; Crichton, D. J.; Hardman, S. H.; Mattman, C. A.; Ramirez, P. M.

2009-12-01

Experience suggests that no single search paradigm will meet all of a community’s search requirements. Traditional forms based search is still considered critical by a significant percentage of most science communities. However text base and facet based search are improving the community’s perception that search can be easy and that the data is available and can be located. Finally semantic search promises ways to find data that were not conceived when the metadata was first captured and organized. This situation suggests that successful science information systems must be able to deploy new search applications quickly, efficiently, and often for ad-hoc purposes. Federated registries allow data to be packaged or associated with their metadata and managed as simple registry objects. Standard reference models for federated registries now exist that ensure registry objects are uniquely identified at registration and that versioning, classification, and cataloging are addressed automatically. Distributed but locally governed, federated registries also provide notification of registry events and federated query, linking, and replication of registry objects. Key principles for shared ontology development in the space sciences are that the ontology remains independent of its implementation and be extensible, flexible and scalable. The dichotomy between digital things and physical/conceptual things in the domain need to be unified under a standard model, such as the Open Archive Information System (OAIS) Information Object. Finally the fact must be accepted that ontology development is a difficult task that requires time, patience and experts in both the science domain and information modeling. The Planetary Data System (PDS) has adopted this architecture for it next generation information system, PDS 2010. The authors will report on progress, briefly describe key elements, and illustrate how the new system will be phased into operations to handle both legacy and new science data. In particular the shared ontology is being used to drive system implementation through the generation of standards documents and software configuration files. The resulting information system will help meet the expectations of modern scientists by providing more of the information interconnectedness, correlative science, and system interoperability that they desire. Fig.1 - Data Driven Architecture

Is the large simple trial design used for comparative, post-approval safety research? A review of a clinical trials registry and the published literature.

PubMed

Reynolds, Robert F; Lem, Joanna A; Gatto, Nicolle M; Eng, Sybil M

2011-10-01

Post-approval, observational drug safety studies face well known difficulties in controlling for confounding, particularly confounding by indication for drug use. A study design that addresses confounding by indication is the large simple trial (LST). LSTs are characterized by large sample sizes, often in the thousands; broad entry criteria consistent with the approved medication label; randomization based on equipoise, i.e. neither physician nor patient believes that one treatment option is superior; minimal, streamlined data collection requirements; objectively-measured endpoints (e.g. death, hospitalization); and follow-up that minimizes interventions or interference with normal clinical practice. In theory then, the LST is a preferred study design for drug and vaccine safety research because it controls for biases inherent to observational research while still providing results that are generalizable to 'real-world' use. To evaluate whether LSTs are used for comparative safety evaluation and if the design is, in fact, advantageous compared with other designs, we conducted a review of the published literature (1949 through 31 December 2010) and the ClinicalTrials.gov registry (2000 through 31 December 2010). Thirteen ongoing or completed safety LSTs were identified. The design has rarely been used in comparative drug safety research, which is due to the operational, financial and scientific hurdles of implementing the design. The studies that have been completed addressed important clinical questions and, in some cases, led to re-evaluation of medical practice. We conclude the design has demonstrated utility for comparative safety research of medicines and vaccines if the necessary scientific and operational conditions for its use are met.

The effectiveness of proprioceptive-based exercise for osteoarthritis of the knee: a systematic review and meta-analysis.

PubMed

Smith, Toby O; King, Jonathan J; Hing, Caroline B

2012-11-01

Osteoarthritis (OA) is a leading cause of functional impairment and pain. Proprioceptive defects may be associated with the onset and progression of OA of the knee. The purpose of this study was to determine the effectiveness of proprioceptive exercises for knee OA using meta-analysis. A systematic review was conducted on 12th December 2011 using published (Cochrane Library, MEDLINE, EMBASE, CINAHL, AMED, PubMed, PEDro) and unpublished/trial registry (OpenGrey, the WHO International Clinical Trials Registry Platform, Current Controlled Trials and the UK National Research Register Archive) databases. Studies were included if they were full publications of randomized or non-randomised controlled trials (RCT) comparing a proprioceptive exercise regime, against a non-proprioceptive exercise programme or non-treatment control for adults with knee OA. Methodological appraisal was performed using the PEDro checklist. Seven RCTs including 560 participants (203 males and 357 females) with a mean age of 63 years were eligible. The methodological quality of the evidence base was moderate. Compared to a non-treatment control, proprioceptive exercises significantly improved functional outcomes in people with knee OA during the first 8 weeks following commencement of their exercises (p < 0.02). When compared against a general non-proprioceptive exercise programme, proprioceptive exercises demonstrated similar outcomes, only providing superior results with respect to joint position sense-related measurements such as timed walk over uneven ground (p = 0.03) and joint position angulation error (p < 0.01). Proprioceptive exercises are efficacious in the treatment of knee OA. There is some evidence to indicate the effectiveness of proprioceptive exercises compared to general strengthening exercises in functional outcomes.

Predictors of physical and mental health-related quality of life outcomes among myocardial infarction patients

PubMed Central

2013-01-01

Background Health-related quality of life (HRQoL) is an important outcome for patients diagnosed with coronary heart disease. This report describes predictors of physical and mental HRQoL at six months post-hospitalisation for myocardial infarction. Methods Participants were myocardial infarction patients (n=430) admitted to two tertiary referral centres in Brisbane, Australia who completed a six month coronary heart disease secondary prevention trial (ProActive Heart). Outcome variables were HRQoL (Short Form-36) at six months, including a physical and mental summary score. Baseline predictors included demographics and clinical variables, health behaviours, and psychosocial variables. Stepwise forward multiple linear regression analyses were used to identify significant independent predictors of six month HRQoL. Results Physical HRQoL was lower in participants who: were older (p<0.001); were unemployed (p=0.03); had lower baseline physical and mental HRQoL scores (p<0.001); had lower confidence levels in meeting sufficient physical activity recommendations (p<0.001); had no intention to be physically active in the next six months (p<0.001); and were more sedentary (p=0.001). Mental HRQoL was lower in participants who: were younger (p=0.01); had lower baseline mental HRQoL (p<0.001); were more sedentary (p=0.01) were depressed (p<0.001); and had lower social support (p=0.001). Conclusions This study has clinical implications as identification of indicators of lower physical and mental HRQoL outcomes for myocardial infarction patients allows for targeted counselling or coronary heart disease secondary prevention efforts. Trial registration Australian Clinical Trials Registry, Australian New Zealand Clinical Trials Registry, CTRN12607000595415. PMID:24020831