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Pain Dec 2013The National Institutes of Health released the trial registry ClinicalTrials.gov in 2000 to increase public reporting and clinical trial transparency. This systematic... (Review)
Review
The National Institutes of Health released the trial registry ClinicalTrials.gov in 2000 to increase public reporting and clinical trial transparency. This systematic review examined whether registered primary outcome specifications (POS; ie, definitions, timing, and analytic plans) in analgesic treatment trials correspond with published POS. Trials with accompanying publications (n = 87) were selected from the Repository of Registered Analgesic Clinical Trials (RReACT) database of all postherpetic neuralgia, diabetic peripheral neuropathy, and fibromyalgia clinical trials registered at ClinicalTrials.gov as of December 1, 2011. POS never matched precisely; discrepancies occurred in 79% of the registry-publication pairs (21% failed to register or publish primary outcomes [PO]). These percentages did not differ significantly between industry and non-industry-sponsored trials. Thirty percent of the trials contained unambiguous POS discrepancies (eg, omitting a registered PO from the publication, "demoting" a registered PO to a published secondary outcome), with a statistically significantly higher percentage of non-industry-sponsored than industry-sponsored trials containing unambiguous POS discrepancies. POS discrepancies due to ambiguous reporting included vaguely worded PO registration; or failing to report the timing of PO assessment, statistical analysis used for the PO, or method to address missing PO data. At best, POS discrepancies may be attributable to insufficient registry requirements, carelessness (eg, failing to report PO assessment timing), or difficulty uploading registry information. At worst, discrepancies could indicate investigator impropriety (eg, registering imprecise PO ["pain"], then publishing whichever pain assessment produced statistically significant results). Improvements in PO registration, as well as journal policies requiring consistency between registered and published PO descriptions, are needed.
Topics: Analgesics; Clinical Trials as Topic; Humans; Practice Guidelines as Topic; Publication Bias; Registries; Treatment Outcome
PubMed: 23962590
DOI: 10.1016/j.pain.2013.08.011 -
Clinical Neuropharmacology 2017The aim of this study was to review the safety and efficacy of aripiprazole as monotherapy and adjunct therapy for the treatment of post-traumatic stress disorder (PTSD). (Review)
Review
OBJECTIVE
The aim of this study was to review the safety and efficacy of aripiprazole as monotherapy and adjunct therapy for the treatment of post-traumatic stress disorder (PTSD).
METHODS
A search of both MEDLINE (1956 to May 2017) and EMBASE (1957 to May 2017) was conducted using the terms "aripiprazole" and "post-traumatic stress disorder," "posttraumatic stress disorder," or "PTSD." Studies evaluating the primary endpoint of PTSD in patients taking aripiprazole as monotherapy or adjunct therapy were analyzed for relevance. Those that met the objective of this study were included for evaluation: 1 placebo-controlled trial; 4 open-label trials; and 1 retrospective chart review.
RESULTS
In patients with a history of PTSD, aripiprazole resulted in significant improvements in the primary outcome, including Clinician-Administered PTSD Symptom Scale or PTSD Checklist-Military scores, in all but 1 study analyzed. Study durations ranged from 10 to 16 weeks. Initial doses of aripiprazole ranged from 2 to 15 mg daily that could be titrated up or down in the range of 2 to 30 mg daily based on efficacy and tolerability. Overall, aripiprazole was well tolerated with the most common treatment-related study discontinuations attributed to the adverse events of anxiety, insomnia, akathisia, asthenia, restlessness, and somnolence.
CONCLUSIONS
Based on the reviewed literature, aripiprazole is a reasonable therapy option as monotherapy or adjunct therapy in patients with PTSD. Larger randomized controlled trials are needed to better understand the role of this atypical antipsychotic in patients with PTSD.
Topics: Antipsychotic Agents; Aripiprazole; Clinical Trials as Topic; Humans; Stress Disorders, Post-Traumatic
PubMed: 29059134
DOI: 10.1097/WNF.0000000000000251 -
Journal of Clinical Pharmacology Sep 2017A systematic review of the Bristol-Myers Squibb normal healthy volunteers (NHVs) database identified phase 1 trials that included NHVs administered placebo with the aim... (Review)
Review
A systematic review of the Bristol-Myers Squibb normal healthy volunteers (NHVs) database identified phase 1 trials that included NHVs administered placebo with the aim of characterizing normal inter- and intraindividual safety parameter variability. Twenty-five single and multiple ascending dose studies, median duration 28 (2 to 63) days, were included in the pooled analysis (355 NHVs). Laboratory evaluations, vital signs, electrocardiograms, and adverse events were assessed. The most commonly occurring adverse event was headache (28 [7.9%] NHVs; 519.5 events/100 person-years). During the dosing period (on placebo), evaluations showed 5.1 events/100 measures of alanine aminotransferase and 7.3 events/100 measures of creatine kinase 1× above the upper limit of normal. Alanine aminotransferase and creatine kinase elevations occurred in 28 (7.9%) and 39 (11.0%) NHVs, respectively; 105 (30.3%) NHVs had low and 46 (13.3%) had high diastolic blood pressure. This analysis may inform future study designs and provide a context for interpretation of safety signals in early phase clinical trials.
Topics: Clinical Trials, Phase I as Topic; Electrocardiography; Healthy Volunteers; Humans; Placebos; Randomized Controlled Trials as Topic; Vital Signs
PubMed: 28510323
DOI: 10.1002/jcph.913 -
The Angle Orthodontist Mar 2009To assess, by systematically reviewing the literature, the functional changes of the masticatory muscles associated with posterior crossbite in the primary and mixed... (Review)
Review
OBJECTIVE
To assess, by systematically reviewing the literature, the functional changes of the masticatory muscles associated with posterior crossbite in the primary and mixed dentition.
MATERIALS AND METHODS
A literature survey from the Medline database covering the period from January 1965 to February 2008 was performed. Randomized controlled trials, controlled clinical trials, and clinical trials that evaluated bite force, surface electromyography, and signs and symptoms of temporomandibular disorders (TMD) were included. Two reviewers extracted the data independently and assessed the quality of the studies.
RESULTS
The search strategy resulted in 494 articles, of which 8 met the inclusion criteria. Children with posterior crossbite can have reduced bite force and asymmetrical muscle function during chewing or clenching, in which the anterior temporalis is more active and the masseter less active on the crossbite side than the noncrossbite side. Moreover, there is a significant association between posterior crossbite and TMD symptomatology.
CONCLUSION
The consequences of the functional changes for the growth and development of the stomatognathic system deserves further investigation.
Topics: Bite Force; Clinical Trials as Topic; Controlled Clinical Trials as Topic; Dentition, Mixed; Electromyography; Humans; Malocclusion; Mastication; Masticatory Muscles; Randomized Controlled Trials as Topic; Temporomandibular Joint Disorders; Tooth, Deciduous
PubMed: 19216602
DOI: 10.2319/030708-137.1 -
Acta Reumatologica Portuguesa 2014Ankylosing spondylitis is a systemic rheumatic disease that affects the axial skeleton, causing inflammatory back pain, structural and functional changes which decrease... (Meta-Analysis)
Meta-Analysis Review
Ankylosing spondylitis is a systemic rheumatic disease that affects the axial skeleton, causing inflammatory back pain, structural and functional changes which decrease quality of life. Several treatments for ankylosing spondylitis have been proposed and among them the use of exercise. The present study aims to synthesize information from the literature and identify the results of controlled clinical trials on exercise in patients with ankylosing spondylitis with the New York modified diagnostic criteria and to assess whether exercise is more effective than physical activity to reduce functional impairment. The sources of studies used were: LILACS, Pubmed, EBSCOhost, B-on, personal communication, manual research and lists of references. The criteria used for the studies selection was controlled clinical trials, participants with New York modified diagnostic criteria for ankylosing spondylitis, and with interventions through exercise. The variables studied were related to primary outcomes such as BASFI (Bath Ankylosing Spondylitis Functional Index) as a functional index, BASDAI (Bath Ankylosing Spondylitis Disease Activity Index) as an index of intensity of disease activity and BASMI (Bath Ankylosing Spondylitis Metrology Index) as a metrological index assessing patient's limitation on movement. From the 603 studies identified after screening only 37 articles were selected for eligibility, from which 18 studies were included. The methodological quality was assessed to select those with an high methodological expressiveness using the PEDro scale. A cumulative meta-analysis was subsequently performed to compare exercise versus usual level of physical activity. Exercise shows significant statistical outcomes for the BASFI, BASDAI and BASMI, higher than those found for usual level of physical activity.
Topics: Controlled Clinical Trials as Topic; Exercise Therapy; Humans; Spondylitis, Ankylosing; Treatment Outcome
PubMed: 25351868
DOI: No ID Found -
World Neurosurgery May 2017Cement leakage is the most common complication of vertebroplasty and kyphoplasty. So far, the reported risk factors remain conflicting because of limited data and lack... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Cement leakage is the most common complication of vertebroplasty and kyphoplasty. So far, the reported risk factors remain conflicting because of limited data and lack of uniform measurement and evaluation. Here, we performed a systematic review and meta-analysis of potential risk factors for cement leakage after vertebroplasty or kyphoplasty.
METHODS
Relevant literature was retrieved using PubMed, EMBASE, Cochrane Controlled Trial Register, and MEDLINE with no language restriction, supplemented by a hand search of the reference lists of selected articles. A fixed-effects model was used if homogeneity existed among included studies; otherwise, a random-effects model was used. The results were presented with weighted mean difference for continuous outcomes and odds ratio (OR) for dichotomous outcomes with a 95% confidence interval (CI).
RESULTS
Twenty-two studies consisting of 2872 patients with 4187 vertebrae were included in the meta-analysis. The incidences of cement leakage for percutaneous vertebroplasty and percutaneous balloon kyphoplasty were 54.7% and 18.4%, respectively. The significant risk factors for new vertebral compression fractures were intravertebral cleft (OR, 1.40; 95% CI, 1.09-1.78; P < 0.01), cortical disruption (OR, 5.56; 95% CI, 1.84-16.81; P < 0.01), cement viscosity (OR, 3.32; 95% CI, 1.36-8.07; P < 0.01) and injected cement volume (weighted mean difference, 0.59; 95% CI, 0.02-1.17; P < 0.05). Age, sex and fracture type, operation level, and surgical approach were not significant risk factors.
CONCLUSIONS
The results of this meta-analysis suggest that patients with intravertebral cleft, cortical disruption, low cement viscosity, and high volume of injected cement may be at high risk for cement leakage after vertebroplasty or kyphoplasty. Rigorous patient selection and individual therapeutic strategy irrespective of age, sex and fracture type, operation level, and surgical approach may reduce the occurrence of cement leakage. Given the inherent limitation of the meta-analysis, more large sample-sized randomized controlled trials are needed to further validate the present findings.
Topics: Bone Cements; Clinical Trials as Topic; Extravasation of Diagnostic and Therapeutic Materials; Fractures, Compression; Humans; Kyphoplasty; Risk Factors; Treatment Outcome; Vertebroplasty
PubMed: 28192270
DOI: 10.1016/j.wneu.2017.01.124 -
Neurology Nov 2013Neurofibromatosis (NF) is a genetic disease with multiple clinical manifestations that can significantly impact quality of life (QOL). Clinical trials should include... (Review)
Review
OBJECTIVES
Neurofibromatosis (NF) is a genetic disease with multiple clinical manifestations that can significantly impact quality of life (QOL). Clinical trials should include patient-reported outcomes (PROs) as endpoints to assess treatment effects on various aspects of QOL, but there is no consensus on the selection and use of such measures in NF. This article describes the PRO Working Group of the Response Evaluation in Neurofibromatosis and Schwannomatosis (REiNS) Collaboration, its main goals, methods for identifying appropriate PRO measures for NF clinical trials, and recommendations for assessing pain intensity.
METHODS
The REiNS PRO group selected core endpoint domains important to assess in NF. The members developed criteria to rate PRO measures, including patient characteristics, psychometric properties, and feasibility, and utilized a systematic process to evaluate PROs for NF clinical trials. Within the subdomain of pain intensity, the group reviewed the Numerical Rating Scale-11 (NRS-11), the Visual Analogue Scale, and the Faces Pain Scale-Revised using this process.
RESULTS
Based on the review criteria, each of these pain intensity scales is brief, reliable, valid, and widely used. However, the NRS-11 was given the highest rating for use in NF clinical trials due to recommendations from pain experts and other consensus groups, its extensive use in research, strong psychometric data including sensitivity to change, and excellent feasibility in ages ≥ 8 years.
CONCLUSIONS
The systematic review criteria and process are effective for identifying appropriate PRO measures and provide information utilized by the REiNS Collaboration to achieve consensus regarding PROs in NF clinical trials.
Topics: Clinical Trials as Topic; Consensus; Humans; Neurilemmoma; Neurofibromatoses; Pain Measurement; Patient Outcome Assessment; Skin Neoplasms
PubMed: 24249806
DOI: 10.1212/01.wnl.0000435747.02780.bf -
Journal of Hospital Medicine Nov 2007A rapid response system (RRS) consists of providers who immediately assess and treat unstable hospitalized patients. Examples include medical emergency teams and rapid... (Comparative Study)
Comparative Study Meta-Analysis Review
BACKGROUND
A rapid response system (RRS) consists of providers who immediately assess and treat unstable hospitalized patients. Examples include medical emergency teams and rapid response teams. Early reports of major improvements in patient outcomes led to widespread utilization of RRSs, despite the negative results of a subsequent cluster-randomized trial.
PURPOSE
To evaluate the effects of RRSs on clinical outcomes through a systematic literature review.
DATA SOURCES
MEDLINE, BIOSIS, and CINAHL searches through August 2006, review of conference proceedings and article bibliographies.
STUDY SELECTION
Randomized and nonrandomized controlled trials, interrupted time series, and before-after studies reporting effects of an RRS on inpatient mortality, cardiopulmonary arrests, or unscheduled ICU admissions.
DATA EXTRACTION
Two authors independently determined study eligibility, abstracted data, and classified study quality.
DATA SYNTHESIS
Thirteen studies met inclusion criteria: 1 cluster-randomized controlled trial (RCT), 1 interrupted time series, and 11 before-after studies. The RCT showed no effects on any clinical outcome. Before-after studies showed reductions in inpatient mortality (RR = 0.82, 95% CI: 0.74-0.91) and cardiac arrest (RR = 0.73, 95% CI: 0.65-0.83). However, these studies were of poor methodological quality, and control hospitals in the RCT reported reductions in mortality and cardiac arrest rates comparable to those in the before-after studies.
CONCLUSIONS
Published studies of RRSs have not found consistent improvement in clinical outcomes and have been of poor methodological quality. The positive results of before-after trials likely reflects secular trends and biased outcome ascertainment, as the improved outcomes they reported were of similar magnitude to those of the control group in the RCT. The effectiveness of the RRS concept remains unproven.
Topics: Emergency Medical Services; Humans; Randomized Controlled Trials as Topic; Treatment Outcome
PubMed: 18081187
DOI: 10.1002/jhm.238 -
Sleep & Breathing = Schlaf & Atmung Sep 2015Snoring is the sound produced by the vibration of the soft tissues caused by the air passing through a narrow upper airway during sleep. It is usually associated with... (Comparative Study)
Comparative Study Review
BACKGROUND
Snoring is the sound produced by the vibration of the soft tissues caused by the air passing through a narrow upper airway during sleep. It is usually associated with the conditions that increase upper airway resistance, but can occur in their absence too (primary snoring). Considering its sheer prevalence, the associated comorbidities, like carotid atherosclerosis and the social disorder that it can represent, treatment for snoring must be considered even in the absence of any other medical condition. Treatment options include conservative approaches like weight reduction, smoking and alcohol cessation, sleep positioning, mechanical nasal dilators, and continuous positive airway pressure (CPAP) to more radical approaches like surgery. Till date, we have no drugs for treating the primary pathology of snoring.
METHODS
A systematic literature search was carried out in PUBMED and EMBASE, and we found only nine randomized control trial's and one interventional study focusing on the pharmacotherapy of snoring per se, even as the literature is replete with studies evaluating drug therapy for obstructive sleep apnea.
RESULT
Drugs evaluated include protriptyline, pseudoephedrine and domperidone, mometasone, nasal surfactant, Botulinum toxin type A, and some homeopathic and oil-based nasal sprays. The selected studies showed no strength in data and had a great methodological heterogeneity, so it is impossible to compare the analyzed studies.
DISCUSSION
Even though there are no consistent data to support pharmacologic treatment for primary snoring, through the critical analysis of these studies, we have discussed about the future directions for clinical trials in this area to arrive at a clinically meaningful decision.
Topics: Humans; Randomized Controlled Trials as Topic; Sleep Apnea, Obstructive; Snoring; Treatment Outcome
PubMed: 25680547
DOI: 10.1007/s11325-015-1123-0 -
Leukemia & Lymphoma 2016A decreasing number of new therapeutic drugs reaching the clinic has led to the publication of regulatory guidelines on human microdosing trials by the European... (Meta-Analysis)
Meta-Analysis Review
A decreasing number of new therapeutic drugs reaching the clinic has led to the publication of regulatory guidelines on human microdosing trials by the European Medicines Agency in 2004 and the US Food and Drug Administration in 2006. Microdosing trials are defined by the administration of 1/100th of the therapeutic dose and designed to investigate basic drug properties. This review investigates the current application of phase 0 trials in medical research. Thirty-three studies found in PubMed and EMBASE were systematically reviewed for aim and analytical method. Pharmacokinetic studies have been a major focus of phase 0 trials, but drug distribution, drug-drug interactions, imaging and pharmacogenomics have also been investigated. Common analytical methods were tandem mass liquid chromatography, accelerator mass spectrometry and positron emission tomography. New ongoing trials are investigating the pharmacodynamics and chemoresistance of marketed drugs, suggesting that the application of phase 0 trials is still evolving.
Topics: Biological Availability; Chromatography, Liquid; Clinical Trials as Topic; Drug Interactions; Drug Monitoring; Europe; Humans; Metabolomics; Pharmaceutical Preparations; Pharmacogenetics; Tandem Mass Spectrometry; Tissue Distribution; United States
PubMed: 26428262
DOI: 10.3109/10428194.2015.1101097