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BMC Complementary and Alternative... Feb 2018In 2010, the World Health Organization published benchmarks for training in osteopathy in which osteopathic visceral techniques are included. The purpose of this study... (Review)
Review
BACKGROUND
In 2010, the World Health Organization published benchmarks for training in osteopathy in which osteopathic visceral techniques are included. The purpose of this study was to identify and critically appraise the scientific literature concerning the reliability of diagnosis and the clinical efficacy of techniques used in visceral osteopathy.
METHODS
Databases MEDLINE, OSTMED.DR, the Cochrane Library, Osteopathic Research Web, Google Scholar, Journal of American Osteopathic Association (JAOA) website, International Journal of Osteopathic Medicine (IJOM) website, and the catalog of Académie d'ostéopathie de France website were searched through December 2017. Only inter-rater reliability studies including at least two raters or the intra-rater reliability studies including at least two assessments by the same rater were included. For efficacy studies, only randomized-controlled-trials (RCT) or crossover studies on unhealthy subjects (any condition, duration and outcome) were included. Risk of bias was determined using a modified version of the quality appraisal tool for studies of diagnostic reliability (QAREL) in reliability studies. For the efficacy studies, the Cochrane risk of bias tool was used to assess their methodological design. Two authors performed data extraction and analysis.
RESULTS
Eight reliability studies and six efficacy studies were included. The analysis of reliability studies shows that the diagnostic techniques used in visceral osteopathy are unreliable. Regarding efficacy studies, the least biased study shows no significant difference for the main outcome. The main risks of bias found in the included studies were due to the absence of blinding of the examiners, an unsuitable statistical method or an absence of primary study outcome.
CONCLUSIONS
The results of the systematic review lead us to conclude that well-conducted and sound evidence on the reliability and the efficacy of techniques in visceral osteopathy is absent.
TRIAL REGISTRATION
The review is registered PROSPERO 12th of December 2016. Registration number is CRD4201605286 .
Topics: Databases, Bibliographic; Humans; Musculoskeletal Diseases; Osteopathic Medicine; Randomized Controlled Trials as Topic; Treatment Outcome
PubMed: 29452579
DOI: 10.1186/s12906-018-2098-8 -
The Cochrane Database of Systematic... Oct 2014Paroxysmal nocturnal hemoglobinuria (PNH) is a chronic, not malignant, disease of the hematopoietic stem cells, associated with significant morbidity and mortality. It... (Review)
Review
BACKGROUND
Paroxysmal nocturnal hemoglobinuria (PNH) is a chronic, not malignant, disease of the hematopoietic stem cells, associated with significant morbidity and mortality. It is a rare disease with an estimated incidence of 1.3 new cases per one million individuals per year. The treatment of PNH has been largely empirical and symptomatic, with blood transfusions, anticoagulation, and supplementation with folic acid or iron. Eculizumab, a biological agent that inhibits complement cascade, was developed for preventing hemolytic anemia and severe thrombotic episodes.
OBJECTIVES
To assess the clinical benefits and harms of eculizumab for treating patients with paroxysmal nocturnal hemoglobinuria (PNH).
SEARCH METHODS
We conducted a comprehensive search strategy. We searched the Cochrane Central Register of Controlled Trials (CENTRAL, The Cochrane Library 2014, Issue 5), Ovid MEDLINE (from 1946 to 15 May 2014), EMBASE (from 1980 to 25 June 2014), and LILACS (from 1982 to 25 June 2014). We did not apply any language restrictions.
SELECTION CRITERIA
We included randomized controlled trials (RCTs) irrespective of their publication status or language. No limits were applied with respect to period of follow-up. We excluded quasi-RCTs. We included trials comparing eculizumab with placebo or best available therapy. We included any patient with a confirmed diagnosis of PNH. Primary outcome was overall survival.
DATA COLLECTION AND ANALYSIS
We independently performed a duplicate selection of eligible trials, risk of bias assessment, and data extraction. We estimated risk ratios (RRs) and 95% confidence interval (CIs) for dichotomous outcomes, and mean differences (MDs) and 95% CIs for continuous outcomes. We used a random-effects model for analysis.
MAIN RESULTS
We identified one multicenter (34 sites) phase III RCT involving 87 participants. The trial compared eculizumab versus placebo, and was conducted in the US, Canada, Europe, and Australia with 26 weeks of follow-up. This small trial had high risk of bias in many domains (attrition and selective reporting). It was sponsored by a pharmaceutical company. No patients died during the study. By using the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (scores can range from 0 to 100, with higher scores on the global health status and functioning scales indicating improvement), the trial showed improvement in health-related quality of life in patients treated with eculizumab (mean difference (MD) 19.4, 95% CI 8.25 to 30.55; P = 0.0007; low quality of evidence). By using the Functional Assessment of Chronic Illness Therapy Fatigue instrument (scores can range from 0 to 52, with higher scores indicating improvement in fatigue), the trial showed a reduction in fatigue (MD 10.4, 95% CI 9.97 to 10.83; P = 0.00001; moderate quality of evidence) in the eculizumab group compared with placebo. Eculizumab compared with placebo showed a greater proportion of patients with transfusion independence: 51% (22/43) versus 0% (0/44); risk ratio (RR) 46.02, 95% CI 2.88 to 735.53; P = 0.007; moderate quality of evidence; and withdrawal for any reason: 4.7% (2/43) versus 22.72% (10/44); RR 0.20, 95% CI 0.05 to 0.88; P = 0.03; moderate quality of evidence. Due to the low rate of events observed, the included trial did not show any difference between eculizumab and placebo in terms of serious adverse events: 9.3% (4/43) versus 20.4% (9/44); RR 0.15, 95% CI 0.15 to 1.37; P = 0.16; low quality of evidence. We did not observe any difference between intervention and placebo for the most frequent adverse events. One participant receiving placebo showed an episode of thrombosis. The trial did not assess overall survival, transformation to myelodysplastic syndrome and acute myelogenous leukemia, or development or recurrence of aplastic anemia on treatment.
AUTHORS' CONCLUSIONS
This review has detected an absence of evidence for eculizumab compared with placebo for treating paroxysmal nocturnal hemoglobinuria (PNH), in terms of overall survival, nonfatal thrombotic events, transformation to myelodysplastic syndrome and acute myelogenous leukemia, and development and recurrence of aplastic anemia on treatment. Current evidence indicates that compared with placebo, eculizumab increases health-related quality of life and increases transfusion independence. During the execution of the included trial, no patients died. Furthermore, the intervention seems to reduce fatigue and withdrawals for any reason. The safety profile of eculizumab is unclear. These conclusions are based on one small trial with risk of attrition and selective reporting bias.Therefore, prescription of eculizumab for treating patients with PNH can neither be supported nor rejected, unless new evidence from a large high quality trial alters this conclusion. Therefore, we urge the reader to interpret the trial results with much caution. Future trials on this issue should be conducted according to the SPIRIT statement and reported according to the CONSORT statement by independent investigators, and using the Foundation of Patient-Centered Outcomes Research recommendations.
Topics: Antibodies, Monoclonal, Humanized; Clinical Trials, Phase III as Topic; Hemoglobinuria, Paroxysmal; Humans; Multicenter Studies as Topic; Randomized Controlled Trials as Topic
PubMed: 25356860
DOI: 10.1002/14651858.CD010340.pub2 -
The Cochrane Database of Systematic... Oct 2015Currently, two separate Cochrane reviews, ‘’ and ‘’ describe the effect of antibiotics for acute rhinosinusitis. Although both Cochrane reviews study the same... (Meta-Analysis)
Meta-Analysis Review
Currently, two separate Cochrane reviews, ‘’ and ‘’ describe the effect of antibiotics for acute rhinosinusitis. Although both Cochrane reviews study the same condition, they look at different populations (patients in which the diagnosis was based on clinical signs and symptoms and patients in which the diagnosis was confirmed by imaging). Because of this, the conclusions are different in these Cochrane reviews. This was confusing for clinicians who needed to read both Cochrane reviews to know which conclusions are most applicable to their patients. This review is being withdrawn and will be incorporated into the updated publication of ‘’. This ‘merged’ review will still maintain the relevant distinction between the two populations. However, information on the effectiveness of antibiotics for rhinosinusitis will be published in the ‘merged’ Cochrane review. We will omit the comparison between antibiotics (as published in this Cochrane review) because the choice for certain antibiotics and/or doses differs according to the local antibiotic resistance patterns and therefore this comparison is less relevant. The editorial group responsible for this previously published document have withdrawn it from publication.
Topics: Acute Disease; Adult; Anti-Bacterial Agents; Clinical Trials as Topic; Humans; Maxillary Sinusitis; Randomized Controlled Trials as Topic
PubMed: 26471061
DOI: 10.1002/14651858.CD000243.pub4 -
Journal of the National Cancer Institute Apr 2020The US Food and Drug Administration's accelerated approval and later withdrawal of bevacizumab in patients with metastatic breast cancer (mBC) is a seminal case for... (Meta-Analysis)
Meta-Analysis
BACKGROUND
The US Food and Drug Administration's accelerated approval and later withdrawal of bevacizumab in patients with metastatic breast cancer (mBC) is a seminal case for ongoing debates about the validity of using progression-free survival (PFS) as a surrogate measure for overall survival (OS) in cancer drug approvals. We systematically reviewed and meta-analyzed the evidence around bevacizumab's regulatory approval and withdrawal in mBC.
METHODS
We searched for all published phase II or III clinical trials testing bevacizumab as a first-line therapy for patients with mBC. Data were extracted on trial demographics, interventions, and outcomes. Descriptive analysis was stratified by whether the trial was initiated before, during, or after the accelerated approval. We used a cumulative random-effects meta-analysis to assess the evolution of evidence of the effect of bevacizumab on PFS and OS. We estimated the association between the trial-level PFS and OS effect using a nonlinear mixed-regression model.
RESULTS
Fifty-two studies were included. Trial activity dramatically dropped after the accelerated approval was withdrawn. Eight clinical trials reported hazard ratios (hazard ratios) and were meta-analyzed. The cumulative hazard ratio for PFS was 0.72 (95% CI = 0.65 to 0.79), and the cumulative hazard ratio for OS was 0.90 (95% CI = 0.80 to 1.01). The regression model showed a statistically nonsignificant association between PFS benefit and OS benefit (β = 0.43, SE = 0.81).
CONCLUSION
The US Food and Drug Administration's decision-making in this case was consistent with the evolving state of evidence. However, the fact that seven clinical trials are insufficient to conclude validity (or lack thereof) for a trial-level surrogate suggests that it would be more efficient to conduct trials using the more clinically meaningful endpoints.
Topics: Antineoplastic Agents, Immunological; Bevacizumab; Breast Neoplasms; Clinical Trials, Phase II as Topic; Clinical Trials, Phase III as Topic; Decision Making; Drug Approval; Endpoint Determination; Female; Humans; Legislation, Drug; Neoplasm Metastasis; Nonlinear Dynamics; Progression-Free Survival; Randomized Controlled Trials as Topic; Regression Analysis; Survival Rate; United States; United States Food and Drug Administration
PubMed: 31651981
DOI: 10.1093/jnci/djz211 -
Contemporary Clinical Trials Nov 2014Underrepresentation of racial and ethnic minorities in clinical trials remains a reality while they have disproportionately higher rates of health disparities. (Review)
Review
BACKGROUND
Underrepresentation of racial and ethnic minorities in clinical trials remains a reality while they have disproportionately higher rates of health disparities.
OBJECTIVE
The purpose of this study was to identify successful community-engaged interventions that included health care providers as a key strategy in addressing barriers to clinical trial enrollment of underrepresented patients.
DESIGN
A systematic review of the literature on interventions addressing enrollment barriers to clinical trials for racial and ethnic minorities was performed in Ovid MEDLINE, EBSCO Megafile, and EBSCO CINAHL. The systematic review identified 360 studies, and 20 were selected using the inclusion criteria. An iterative process extracted information from the eligible studies.
RESULTS
The 20 selected studies were analyzed and then grouped by first author, nature of the clinical research initiative, priority populations, key strategies, and study outcomes. Nine of the studies addressed cancer clinical trials and 11 related to chronic medical conditions, including diabetes, hypertension management, and chronic kidney disease. The key strategies employed were categorized according to their presumed impact on barriers incurred at distinct steps in study recruitment: clinical trial awareness, opportunity to participate, and acceptance of enrollment. The strategies were further categorized by whether they would address barriers associated with minority perceptions of the research process and barriers related to how studies were designed and implemented.
CONCLUSION
Multiple and flexible strategies targeting providers and participants at provider sites and within communities might be needed to enroll underrepresented populations into clinical trials.
Topics: Awareness; Clinical Trials as Topic; Ethnicity; Humans; Minority Groups; Patient Selection; Racial Groups
PubMed: 25131812
DOI: 10.1016/j.cct.2014.08.004 -
Expert Opinion on Biological Therapy Jun 2016This meta-analysis evaluated the effect of single agent brentuximab vedotin (BV) in patients with relapsed/refractory Hodgkin lymphoma (HL). (Meta-Analysis)
Meta-Analysis Review
OBJECTIVES
This meta-analysis evaluated the effect of single agent brentuximab vedotin (BV) in patients with relapsed/refractory Hodgkin lymphoma (HL).
PATIENTS AND METHODS
A systematic literature search was performed and included studies published from 1(st) January 2012 to 1(st) July 2015 investigating BV in patients with relapsed/refractory HL. Data was extracted and reviewed by two investigators then analyzed using the comprehensive meta-analysis version 3 software.
RESULTS
22 out of 4048 screened records met the eligibility criteria. These records included 903 patients. The median age of the cohort was 31 years (range: 26-45). 86% received ≥ 3 previous lines of systemic therapy. 529 (58.7%) and 232 (25.7%) underwent high dose chemotherapy and autologous and/or allogeneic stem transplantation prior of BV respectively. The overall response rate to BV was 62.7% (range: 30-100%). The complete response, partial response, stable disease and progressive disease rates were 31.8%, 35.1%, 19.5% and 11.7% respectively. The one year progression free survival and estimated one year overall survival were 47.6% and 79.5% respectively.
CONCLUSION
In this largest published pooled cohort, BV produces high responses with encouraging progression free and overall survival in relapsed/refractory HL patients. Our results enhance the role of BV in heavily pretreated HL patients.
Topics: Adult; Brentuximab Vedotin; Clinical Trials as Topic; Disease Progression; Disease-Free Survival; Hodgkin Disease; Humans; Immunoconjugates; Middle Aged; Remission Induction; Retrospective Studies; Transplantation, Homologous
PubMed: 27096887
DOI: 10.1080/14712598.2016.1180362 -
Toxins Apr 2024Botulinum toxin type A (BONT-A) has shown promise in improving the mood-related symptoms of psychiatric disorders by targeting muscles linked to the expression of... (Review)
Review
Botulinum toxin type A (BONT-A) has shown promise in improving the mood-related symptoms of psychiatric disorders by targeting muscles linked to the expression of negative emotions. We conducted a systematic review of past and ongoing efficacy trials of BONT-A therapy for psychiatric disorders to identify relevant trends in the field and discuss the refinement of therapeutic techniques. A comprehensive search for published clinical trials using BONT-A injections for psychiatric disorders was performed on 4 May 2023 through OVID databases (MEDLINE, Embase, APA PsycINFO). Unpublished clinical trials were searched through the ClinicalTrials.gov and International Clinical Trial Registry Platform public registries. The risk of bias was assessed using the JBI Critical Appraisal tools for use in systematic reviews. We identified 21 studies (17 published, 4 unpublished clinical trials) involving 471 patients. The studies focused on evaluating the efficacy of BONT-A for major depressive, borderline personality, social anxiety, and bipolar disorders. BONT-A was most commonly injected into the glabellar area, with an average dose ranging between 37.75 U and 44.5 U in published studies and between 32.7 U and 41.3 U in unpublished trials. The results indicated significant symptom reductions across all the studied psychiatric conditions, with mild adverse effects. Thus, BONT-A appears to be safe and well-tolerated for psychiatric disorders of negative affectivity. However, despite the clinical focus, there was a noted shortage of biomarker-related assessments. Future studies should focus on pursuing mechanistic explorations of BONT-A effects at the neurobiological level.
Topics: Humans; Mental Disorders; Botulinum Toxins, Type A; Clinical Trials as Topic; Treatment Outcome
PubMed: 38668616
DOI: 10.3390/toxins16040191 -
CNS Drugs Oct 2019Roughly 80% of the symptom improvement experienced on antidepressants in clinical trials is also observed in the placebo comparison group. Understanding the correlates... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Roughly 80% of the symptom improvement experienced on antidepressants in clinical trials is also observed in the placebo comparison group. Understanding the correlates of placebo improvement and response is important to designing efficient and successful trials of future antidepressants.
OBJECTIVE
The objective of this meta-analysis was to investigate the magnitude of placebo symptom improvement and placebo response rates in second-generation antidepressant trials of depression, anxiety, and obsessive-compulsive disorder.
METHODS
We searched PubMed on 10 June, 2016, with no date or language limits, to identify randomized placebo-controlled trials of second-generation antidepressants in adults with depression, anxiety, or obsessive-compulsive disorder. We used a random-effects meta-analysis to examine the magnitude of placebo symptom improvement using standardized mean difference and placebo response rate. Stratified subgroup analysis and meta-regression were utilized to examine the effect of diagnostic indication and correlates of placebo symptom improvement.
RESULTS
The meta-analysis included 164 trials involving 19,591 participants. Magnitude of placebo improvement and placebo response rates varied significantly between diagnostic indications. The magnitude of placebo improvement was much lower in obsessive-compulsive disorder (standardized mean difference = 0.58, 95% confidence interval 0.36-0.79) than in depression (standardized mean difference = 1.22, 95% confidence interval 1.12-1.32) or anxiety (standardized mean difference = 1.01, 95% confidence interval 0.90-1.12) trials. There was a large amount of heterogeneity in placebo improvement between studies (Q = 899, df = 110, p < 0.001, I = 88%). A greater number of study sites and a later publication year were associated with a greater magnitude of placebo improvement and response rate. Presence of a placebo lead-in and absence of non-US sites were associated with a reduced magnitude of placebo improvement. Trial duration was positively associated with the magnitude of placebo improvement in depression trials but negatively associated with the magnitude of placebo improvement in anxiety and obsessive-compulsive disorder trials.
CONCLUSIONS
Magnitude of placebo symptom improvement differed significantly based on diagnostic indication with improvement being significantly less in obsessive-compulsive disorder than anxiety and depression. Some trial characteristics were associated with a greater magnitude of placebo improvement in trials across disorders but others were disorder specific.
Topics: Antidepressive Agents, Second-Generation; Anxiety; Clinical Trials as Topic; Depression; Humans; Obsessive-Compulsive Disorder; Randomized Controlled Trials as Topic
PubMed: 31573058
DOI: 10.1007/s40263-019-00662-y -
The Lancet. Psychiatry May 2016Around 30% of patients with schizophrenia show an inadequate response to antipsychotics-ie, treatment resistance. Neuroimaging studies can help to uncover the underlying... (Review)
Review
Around 30% of patients with schizophrenia show an inadequate response to antipsychotics-ie, treatment resistance. Neuroimaging studies can help to uncover the underlying neurobiological reasons for such resistance and identify these patients earlier. Additionally, studies examining the effect of clozapine on the brain can help to identify aspects of clozapine that make it uniquely effective in patients with treatment resistance. We did a systematic search of PubMed between Jan 1, 1980, and April 13, 2015, to identify all neuroimaging studies that examined treatment-resistant patients or longitudinally assessed the effects of clozapine treatment. We identified 330 articles, of which 61 met the inclusion criteria. Replicated differences between treatment-resistant and treatment-responsive patients include reductions in grey matter and perfusion of frontotemporal regions, and increases in white matter and basal ganglia perfusion, with effect sizes ranging from 0·4 to greater than 1. Clozapine treatment led to reductions in caudate nucleus volume in three separate studies. The available evidence supports the hypothesis that some of the neurobiological changes seen in treatment-resistant schizophrenia lie along a continuum with treatment-responsive schizophrenia, whereas other differences are categorical in nature and have potential to be used as biomarkers. However, further replication is needed, and for neuroimaging findings to be clinically translatable, future studies need to focus on a-priori hypotheses and be adequately powered.
Topics: Antipsychotic Agents; Brain; Clinical Trials as Topic; Drug Resistance; Humans; Schizophrenia; Treatment Outcome
PubMed: 26948188
DOI: 10.1016/S2215-0366(15)00540-4 -
International Journal For Equity in... Mar 2018Clinical trials for identification of efficient and effective new diagnostic and treatment modalities are needed to address disproportionately high burden of... (Review)
Review
BACKGROUND
Clinical trials for identification of efficient and effective new diagnostic and treatment modalities are needed to address disproportionately high burden of communicable (e.g., HIV/AIDS, tuberculosis, and malaria) and non-communicable diseases (e.g., diabetes) in developing countries. However, gross under-representation in global clinical trial platforms contributes to sustained health inequity in these countries. We reviewed the literature on barriers facing clinical researchers in developing countries for conducting clinical trials in their countries.
METHODS
Literature indexed in PubMed, Embase, CINAHL and Web of Science, WHO Global Health Library were searched. Grey literature was also searched. Search key words included barriers, challenges, clinical trials and developing countries. Articles within the scope of this review were appraised by two reviewers.
RESULTS
Ten studies, which are reported in 15 papers, were included in this review. Following critical review we identified five unifying themes for barriers. Barriers for conducting clinical trials included lack of financial and human capacity, ethical and regulatory system obstacles, lack of research environment, operational barriers and competing demands.
CONCLUSION AND RECOMMENDATION
There were substantial barriers at system, organization and individual level. We propose that to address this problem, instituting a system for wider implementation of local investigator-initiated trials is warranted. These trials are more applicable to local populations because they build on local healthcare knowledge. They are more demand-led, influence policy and responsive to a country's needs because they are driven by a local or national agenda.
Topics: Attitude to Health; Clinical Trials as Topic; Communication Barriers; Developing Countries; Humans; Research Support as Topic
PubMed: 29566721
DOI: 10.1186/s12939-018-0748-6