PEDro or Cochrane to Assess the Quality of Clinical Trials? A Meta-Epidemiological Study.

OBJECTIVE There is debate on how the methodological quality of clinical trials should be assessed. We compared trials of physical therapy (PT) judged to be of adequate quality based on summary scores from the Physiotherapy Evidence Database (PEDro) scale with trials judged to be of adequate quality by Cochrane Risk of Bias criteria. DESIGN Meta-epidemiological study within Cochrane Database of Systematic Reviews. METHODS Meta-analyses of PT trials were identified in the Cochrane Database of Systematic Reviews. For each trial PeDro and Cochrane assessments were extracted from the PeDro and Cochrane databases. Adequate quality was defined as adequate generation of random sequence, concealment of allocation, and blinding of outcome assessors (Cochrane criteria) or as trials with a PEDro summary score ≥5 or ≥6 points. We combined trials of adequate quality using random-effects meta-analysis. RESULTS Forty-one Cochrane reviews and 353 PT trials were included. All meta-analyses included trials with PEDro scores ≥5, 37 (90.2%) included trials with PEDro scores ≥6 and only 22 (53.7%) meta-analyses included trials of adequate quality according to the Cochrane criteria. Agreement between PeDro and Cochrane was poor for PeDro scores of ≥5 points (kappa = 0.12; 95% CI 0.07 to 0.16) and slight for ≥6 points (kappa 0.24; 95% CI 0.16-0.32). When combining effect sizes of trials deemed to be of adequate quality according to PEDro or Cochrane criteria, we found that a substantial difference in the combined effect size (≥0.15) was evident in 9 (22%) out of the 41 meta-analyses for PEDro cutoff ≥5 and 10 (24%) for cutoff ≥6. CONCLUSIONS The PeDro and Cochrane approaches lead to different sets of trials of adequate quality, and different combined treatment estimates from meta-analyses of these trials. A consistent approach to assessing RoB in trials of physical therapy should be adopted.

Hyperthermia-related clinical trials on cancer treatment within the ClinicalTrials.gov registry

PURPOSE Hyperthermia has been shown to improve the effectiveness of chemotherapy and radiotherapy in the treatment of cancer. This paper summarises all recent clinical trials registered in the ClinicalTrials.gov registry. MATERIALS AND METHODS The records of 175,538 clinical trials registered at ClinicalTrials.gov were downloaded on 29 September 2014 and a database was established. We searched this database for hyperthermia or equivalent words. RESULTS A total of 109 trials were identified in which hyperthermia was part of the treatment regimen. Of these, 49 trials (45%) had hyperthermic intraperitoneal chemotherapy after cytoreductive surgery (HIPEC) as the primary intervention, and 14 other trials (13%) were also testing some form of intraperitoneal hyperthermic chemoperfusion. Seven trials (6%) were testing perfusion attempts to other locations (thoracic/pleural n = 4, limb n = 2, hepatic n = 1). Sixteen trials (15%) were testing regional hyperthermia, 13 trials (12%) whole body hyperthermia, seven trials (6%) superficial hyperthermia and two trials (2%) interstitial hyperthermia. One remaining trial tested laser hyperthermia. CONCLUSIONS In contrast to the general opinion, this analysis shows continuous interest and ongoing clinical research in the field of hyperthermia. Interestingly, the majority of trials focused on some form of intraperitoneal hyperthermic chemoperfusion. Despite the high number of active clinical studies, HIPEC is a topic with limited attention at the annual meetings of the European Society for Hyperthermic Oncology and the Society of Thermal Medicine. The registration of on-going clinical trials is of paramount importance for the achievement of a comprehensive overview of available clinical research activities involving hyperthermia.

Impact of Clinical Presentation (Stable Angina Pectoris vs Unstable Angina Pectoris or Non-ST-Elevation Myocardial Infarction vs ST-Elevation Myocardial Infarction) on Long-Term Outcomes in Women Undergoing Percutaneous Coronary Intervention With Drug-Eluting Stents

The long-term risk associated with different coronary artery disease (CAD) presentations in women undergoing percutaneous coronary intervention (PCI) with drug-eluting stents (DES) is poorly characterized. We pooled patient-level data for women enrolled in 26 randomized clinical trials. Of 11,577 women included in the pooled database, 10,133 with known clinical presentation received a DES. Of them, 5,760 (57%) had stable angina pectoris (SAP), 3,594 (35%) had unstable angina pectoris (UAP) or non-ST-segment-elevation myocardial infarction (NSTEMI), and 779 (8%) had ST-segment-elevation myocardial infarction (STEMI) as clinical presentation. A stepwise increase in 3-year crude cumulative mortality was observed in the transition from SAP to STEMI (4.9% vs 6.1% vs 9.4%; p <0.01). Conversely, no differences in crude mortality rates were observed between 1 and 3 years across clinical presentations. After multivariable adjustment, STEMI was independently associated with greater risk of 3-year mortality (hazard ratio [HR] 3.45; 95% confidence interval [CI] 1.99 to 5.98; p <0.01), whereas no differences were observed between UAP or NSTEMI and SAP (HR 0.99; 95% CI 0.73 to 1.34; p = 0.94). In women with ACS, use of new-generation DES was associated with reduced risk of major adverse cardiac events (HR 0.58; 95% CI 0.34 to 0.98). The magnitude and direction of the effect with new-generation DES was uniform between women with or without ACS (pinteraction = 0.66). In conclusion, in women across the clinical spectrum of CAD, STEMI was associated with a greater risk of long-term mortality. Conversely, the adjusted risk of mortality between UAP or NSTEMI and SAP was similar. New-generation DESs provide improved long-term clinical outcomes irrespective of the clinical presentation in women.

The TREAT-NMD DMD Global Database: analysis of more than 7,000 Duchenne muscular dystrophy mutations.

Analyzing the type and frequency of patient-specific mutations that give rise to Duchenne muscular dystrophy (DMD) is an invaluable tool for diagnostics, basic scientific research, trial planning, and improved clinical care. Locus-specific databases allow for the collection, organization, storage, and analysis of genetic variants of disease. Here, we describe the development and analysis of the TREAT-NMD DMD Global database (http://umd.be/TREAT_DMD/). We analyzed genetic data for 7,149 DMD mutations held within the database. A total of 5,682 large mutations were observed (80% of total mutations), of which 4,894 (86%) were deletions (1 exon or larger) and 784 (14%) were duplications (1 exon or larger). There were 1,445 small mutations (smaller than 1 exon, 20% of all mutations), of which 358 (25%) were small deletions and 132 (9%) small insertions and 199 (14%) affected the splice sites. Point mutations totalled 756 (52% of small mutations) with 726 (50%) nonsense mutations and 30 (2%) missense mutations. Finally, 22 (0.3%) mid-intronic mutations were observed. In addition, mutations were identified within the database that would potentially benefit from novel genetic therapies for DMD including stop codon read-through therapies (10% of total mutations) and exon skipping therapy (80% of deletions and 55% of total mutations).

Incidence and predictors of cutaneous manifestations during the early course of systemic sclerosis: a 10-year longitudinal study from the EUSTAR database.

OBJECTIVES To longitudinally map the onset and identify risk factors for skin sclerosis and digital ulcers (DUs) in patients with systemic sclerosis (SSc) from an early time point after the onset of Raynaud's phenomenon (RP) in the European Scleroderma Trials and Research (EUSTAR) cohort. METHODS 695 patients with SSc with a baseline visit within 1 year after RP onset were followed in the prospective multinational EUSTAR database. During the 10-year observation period, cumulative probabilities of cutaneous lesions were assessed with the Kaplan-Meier method. Cox proportional hazards regression analysis was used to evaluate risk factors. RESULTS The median modified Rodnan skin score (mRSS) peaked 1 year after RP onset, and was 15 points. The 1-year probability to develop an mRSS ≥2 in at least one area of the arms and legs was 69% and 25%, respectively. Twenty-five per cent of patients developed diffuse cutaneous involvement in the first year after RP onset. This probability increased to 36% during the subsequent 2 years. Only 6% of patients developed diffuse cutaneous SSc thereafter. The probability to develop DUs increased to a maximum of 70% at the end of the 10-year observation. The main factors associated with diffuse cutaneous SSc were the presence of anti-RNA polymerase III autoantibodies, followed by antitopoisomerase autoantibodies and male sex. The main factor associated with incident DUs was the presence of antitopoisomerase autoantibodies. CONCLUSION Early after RP onset, cutaneous manifestations exhibit rapid kinetics in SSc. This should be accounted for in clinical trials aiming to prevent skin worsening.

An analysis of the effects of a peer mentor program and other factors on HIV patients' retention in care and clinical outcomes at Thomas Street Health Clinic, Houston Texas

Research examining programs designed to retain patients in health care focus on repeated interactions between outreach workers and patients (Bradford et al. 2007; Cheever 2007). The purpose of this study was to determine if patients who are peer-mentored at their intake exam remain in care longer and attend more physicians' visits than those who were not mentored. Using patients' medical records and a previously created mentor database, the study determined how many patients attended their intake visit but subsequently failed to establish regular care. The cohort study examined risk factors for establishing care, determined if patients lacking a peer mentor failed to establish care more than peer mentor assisted patients, and subsequently if peer mentored patients had better health outcomes. The sample consists of 1639 patients who were entered into the Thomas Street Patient Mentor Database between May 2005 and June 2007. The assignment to the mentored group was haphazardly conducted based on mentor availability. The data from the Mentor Database was then analyzed using descriptive statistical software (SPSS version 15; SPSS Inc., Chicago, Illinois, USA). Results indicated that patients who had a mentor at intake were more likely to return for primary care HIV visits at 90 and 180 days. Mentored patients also were more likely to be prescribed ART within 180 days from intake. Other risk factors that impacted remaining in care included gender, previous care status, time from diagnosis to intake visit, and intravenous drug use. Clinical health outcomes did not differ significantly between groups. This supports that mentoring did improve outcomes. Continuing to use peer-mentoring programs for HIV care may help in increasing retention of patients in care and improving patients' health in a cost effective manner. Future research on the effects of peer mentoring on mentors, and effects of concordance of mentor and patient demographics may help to further improve peer-mentoring programs. ^

The identification and prevalence of veterinary clinical events in U.S. military working dogs deployed to Iraq between March 20, 2003, and December 31, 2007

Objective. The purpose of this study was to identify the medical issues experienced by Military Working Dogs during their period of deployment in Iraq.^ Design. This study was a retrospective cross-sectional survey based on database and medical record abstraction.^ Population. Military Working Dogs (MWDs) that were deployed to Iraq at any time between 20 March 2003 and 31 December 2007 were the inclusive population of interest. Seven hundred ninety-five (795) MWDs were identified as having been deployed to Iraq during the inclusive dates. Four hundred ninety-six (496) MWDs were identified that had medical events during the deployment period. ^ Procedures. Eligible MWDs were identified through several sources, to include database query, medical record abstraction questionnaire, and medical record abstraction. Demographic information collected for each MWD included tattoo, name, age, gender, breed, Branch of Service, and duty certification. Information on each veterinary/medical clinical event (VCE) was collected. This information was coded, and data entered into a database for organization. Frequency and prevalence information were determined for each category of VCE.^ Results. The top four VCEs experienced by MWDs while deployed in Iraq were gastrohepatic, dermatologic, traumatic injury, and appendicular musculoskeletal issues.^ Conclusions. Training, equipment, and supplies for veterinary personnel who care for the deployed MWDs should be tailored accordingly to suit the identified medical needs of the MWDs. ^

Are pharmacological randomised controlled clinical trials relevant to real-life asthma populations? : A protocol for an UNLOCK study from the IPCRG

Funding The IPCRG provided funding for this research project as an UNLOCK Group study for which the funding was obtained through an unrestricted grant by Novartis AG, Basel, Switzerland. Novartis has no role in study design, data collection and analysis, decision to publish or preparation of the manuscript. This study will include data from the Optimum Patient Care Research Database and is undertaken in collaboration with Optimum Patient Care and the Respiratory Effectiveness Group.

IMGT/HLA Database—a sequence database for the human major histocompatibility complex

The IMGT/HLA Database (www.ebi.ac.uk/imgt/hla/) specialises in sequences of polymorphic genes of the HLA system, the human major histocompatibility complex (MHC). The HLA complex is located within the 6p21.3 region on the short arm of human chromosome 6 and contains more than 220 genes of diverse function. Many of the genes encode proteins of the immune system and these include the 21 highly polymorphic HLA genes, which influence the outcome of clinical transplantation and confer susceptibility to a wide range of non-infectious diseases. The database contains sequences for all HLA alleles officially recognised by the WHO Nomenclature Committee for Factors of the HLA System and provides users with online tools and facilities for their retrieval and analysis. These include allele reports, alignment tools and detailed descriptions of the source cells. The online IMGT/HLA submission tool allows both new and confirmatory sequences to be submitted directly to the WHO Nomenclature Committee. The latest version (release 1.7.0 July 2000) contains 1220 HLA alleles derived from over 2700 component sequences from the EMBL/GenBank/DDBJ databases. The HLA database provides a model which will be extended to provide specialist databases for polymorphic MHC genes of other species.

OrCGDB: a database of genes involved in oral cancer

The Oral Cancer Gene Database (OrCGDB; http://www.tumor-gene.org/Oral/oral.html) was developed to provide the biomedical community with easy access to the latest information on the genes involved in oral cancer. The information is stored in a relational database and accessed through a WWW interface. The OrCGDB is organized by gene name, which is linked to information describing properties of the gene. This information is stored as a collection of findings (‘facts’) that are entered by the database curator in a semi-structured format from information in primary publications using a WWW interface. These facts include causes of oncogenic activation, chromosomal localization of the gene, mutations associated with the gene, the biochemical identity and activity of the gene product, synonyms for the gene name and a variety of clinical information. Each fact is associated with a MEDLINE citation. The user can search the OrCGDB by gene name or by entering a textword. The OrCGDB is part of a larger WWW-based tumor gene database and represents a new approach to catalog and display the research literature.

Characterization of adverse drug reactions with neuropsychiatric clinical manifestations reported spontaneously to the portuguese pharmacovigilance system in the greater Lisbon area

Trabalho Final do Curso de Mestrado Integrado em Medicina, Faculdade de Medicina, Universidade de Lisboa, 2014

Systematic review of outcome domains and instruments used in clinical trials of tinnitus treatments in adults

BACKGROUND: There is no evidence-based guidance to facilitate design decisions for confirmatory trials or systematic reviews investigating treatment efficacy for adults with tinnitus. This systematic review therefore seeks to ascertain the current status of trial designs by identifying and evaluating the reporting of outcome domains and instruments in the treatment of adults with tinnitus. METHODS: Records were identified by searching PubMed, EMBASE CINAHL, EBSCO, and CENTRAL clinical trial registries (ClinicalTrials.gov, ISRCTN, ICTRP) and the Cochrane Database of Systematic Reviews. Eligible records were those published from 1 July 2006 to 12 March 2015. Included studies were those reporting adults aged 18 years or older who reported tinnitus as a primary complaint, and who were enrolled into a randomised controlled trial, a before and after study, a non-randomised controlled trial, a case-controlled study or a cohort study, and written in English. Studies with fewer than 20 participants were excluded. RESULTS: Two hundred and twenty-eight studies were included. Thirty-five different primary outcome domains were identified spanning seven categories (tinnitus percept, impact of tinnitus, co-occurring complaints, quality of life, body structures and function, treatment-related outcomes and unclear or not specified). Over half the studies (55 %) did not clearly define the complaint of interest. Tinnitus loudness was the domain most often reported (14 %), followed by tinnitus distress (7 %). Seventy-eight different primary outcome instruments were identified. Instruments assessing multiple attributes of the impact of tinnitus were most common (34 %). Overall, 24 different patient-reported tools were used, predominantly the Tinnitus Handicap Inventory (15 %). Loudness was measured in diverse ways including a numerical rating scale (8 %), loudness matching (4 %), minimum masking level (1 %) and loudness discomfort level (1 %). Ten percent of studies did not clearly report the instrument used. CONCLUSIONS: Our findings indicate poor appreciation of the basic principles of good trial design, particularly the importance of specifying what aspect of therapeutic benefit is the main outcome. No single outcome was reported in all studies and there was a broad diversity of outcome instruments. PROSPERO REGISTRATION: The systematic review protocol is registered on PROSPERO (International Prospective Register of Systematic Reviews): CRD42015017525 . Registered on 12 March 2015 revised on 15 March 2016.

The European Narcolepsy Network (EU-NN) database.

Narcolepsy with cataplexy is a rare disease with an estimated prevalence of 0.02% in European populations. Narcolepsy shares many features of rare disorders, in particular the lack of awareness of the disease with serious consequences for healthcare supply. Similar to other rare diseases, only a few European countries have registered narcolepsy cases in databases of the International Classification of Diseases or in registries of the European health authorities. A promising approach to identify disease-specific adverse health effects and needs in healthcare delivery in the field of rare diseases is to establish a distributed expert network. A first and important step is to create a database that allows collection, storage and dissemination of data on narcolepsy in a comprehensive and systematic way. Here, the first prospective web-based European narcolepsy database hosted by the European Narcolepsy Network is introduced. The database structure, standardization of data acquisition and quality control procedures are described, and an overview provided of the first 1079 patients from 18 European specialized centres. Due to its standardization this continuously increasing data pool is most promising to provide a better insight into many unsolved aspects of narcolepsy and related disorders, including clear phenotype characterization of subtypes of narcolepsy, more precise epidemiological data and knowledge on the natural history of narcolepsy, expectations about treatment effects, identification of post-marketing medication side-effects, and will contribute to improve clinical trial designs and provide facilities to further develop phase III trials.

Prevalence of mixed neuropathologies in autopsied older adults and associations with clinical disease progression

Thesis (Ph.D.)--University of Washington, 2016-06

OMERACT-OARSI Initiative: Osteoarthritis Research Society International set of responder criteria for osteoarthritis clinical trials revisited.

Background: The OARSI Standing Committee for Clinical Trials Response Criteria Initiative had developed two sets of responder criteria to present the results of changes after treatment in three symptomatic domains (pain, function, and patient's global assessment) as a single variable for clinical trials (1). For each domain, a response was defined by both a relative and an absolute change, with different cut-offs with regard to the drug, the route of administration and the OA localization. Objective: To propose a simplified set of responder criteria with a similar cut-off, whatever the drug, the route or the OA localization. Methods: Data driven approach: (1) Two databases were considered The 'elaboration' database with which the formal OARSI sets of responder criteria were elaborated and The 'revisit' database. (2) Six different scenarios were evaluated: The two formal OARSI sets of criteria Four proposed scenarios of simplified sets of criteria Data from clinical randomized blinded placebo controlled trials were used to evaluate the performances of the two formal scenarios with two different databases ('elaboration' versus 'revisit') and those of the four proposed simplified scenarios within the 'revisit' database. The placebo effect, active effect, treatment effect, and the required sample arm size to obtain the placebo effect and the active treatment effect observed were the performances evaluated for each of the six scenarios. Experts' opinion approach: Results were discussed among the participants of the OMERACT VI meeting, who voted to select the definite OMERACT-OARSI set of criteria (one of the six evaluated scenarios). Results: Data driven approach: Fourteen trials totaling 1886 CA patients and fifteen studies involving 8164 CA patients were evaluated in the 'elaboration' and the 'revisit' databases respectively. The variability of the performances observed in the 'revisit' database when using the different simplified scenarios was similar to that observed between the two databases ('elaboration' versus 'revisit') when using the formal scenarios. The treatment effect and the required sample arm size were similar for each set of criteria. Experts' opinion approach: According to the experts, these two previous performances were the most important of an optimal set of responder criteria. They chose the set of criteria considering both pain and function as evaluation domain and requiring an absolute change and a relative change from baseline to define a response, with similar cut-offs whatever the drug, the route of administration or the CA localization. Conclusion: This data driven and experts' opinion approach is the basis for proposing an optimal simplified set of responder criteria for CA clinical trials. Other studies, using other sets of CA patients, are required in order to further validate this proposed OMERACT - OARSI set of criteria. (C) 2004 OsteoArthritis Research Society International. Published by Elsevier Ltd. All rights reserved.