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Mycoses Aug 2021Onychomycosis is the most common nail disease seen in clinical practice. Inclusion of diverse groups in onychomycosis clinical trials subjects is necessary to generalise... (Review)
Review
BACKGROUND
Onychomycosis is the most common nail disease seen in clinical practice. Inclusion of diverse groups in onychomycosis clinical trials subjects is necessary to generalise efficacy data.
OBJECTIVES
We aimed to systematically review race and ethnicity reporting and representation, as well as, treatment outcomes in onychomycosis clinical trials.
METHODS
A PubMed search for onychomycosis clinical trials was performed in August 2020. Primary clinical trial data were included and post hoc analyses were excluded. Categorical variables were compared using chi-squared and Fisher's exact tests. Statistical significance was set at p < .05. Photos in articles were categorised by Fitzpatrick skin type.
RESULTS
Only 32/182 (17.5%) trials reported on race and/or ethnicity and only one trial compared treatment efficacy in different subgroups. Darker skin colours were infrequently depicted in articles. Topical treatment, location with ≥1 US-based site, industry funding type and publication date after 2000 were significantly associated with reporting of racial/ethnic data (p < .05 for all comparisons).
LIMITATIONS
Demographics on excluded subjects and methods of recruitment were not available. Assigning Fitzpatrick skin type is inherently subjective.
CONCLUSIONS
This study highlights a need for consistent reporting of races and ethnicities of onychomycosis clinical trial participants with subgroup analyses of treatment efficacies.
Topics: Administration, Topical; Antifungal Agents; Clinical Trials as Topic; Foot Dermatoses; Humans; Onychomycosis; Treatment Outcome
PubMed: 33655595
DOI: 10.1111/myc.13262 -
Trials Apr 2021Patient-reported outcomes (PROs) are used in clinical trials to assess the effectiveness and tolerability of interventions. Inclusion of participants from different... (Review)
Review
BACKGROUND
Patient-reported outcomes (PROs) are used in clinical trials to assess the effectiveness and tolerability of interventions. Inclusion of participants from different ethnic backgrounds is essential for generalisability of cancer trial results. PRO data collection should include appropriately translated patient-reported outcome measures (PROMs) to minimise missing data and sample attrition.
METHODS
Protocols and/or publications from cancer clinical trials using a PRO endpoint and registered on the National Institute for Health Research Portfolio were systematically reviewed for information on recruitment, inclusion of ethnicity data, and use of appropriately translated PROMs. Semi-structured interviews were conducted with key stakeholders to explore barriers and facilitators for optimal PRO trial design, diverse recruitment and reporting, and use of appropriately translated PROMs.
RESULTS
Eighty-four trials met the inclusion criteria, only 14 (17%) (n = 4754) reported ethnic group data, and ethnic group recruitment was low, 611 (13%). Although 8 (57%) studies were multi-centred and multi-national, none reported using translated PROMs, although available for 7 (88%) of the studies. Interviews with 44 international stakeholders identified a number of perceived barriers to ethnically diverse recruitment including diverse participant engagement, relevance of ethnicity to research question, prominence of PROs, and need to minimise investigator burden. Stakeholders had differing opinions on the use of translated PROMs, the impact of trial designs, and recruitment strategies on diverse recruitment. Facilitators of inclusive research were described and examples of good practice identified.
CONCLUSIONS
Greater transparency is required when PROs are used as primary or secondary outcomes in clinical trials. Protocols and publications should demonstrate that recruitment was accessible to diverse populations and facilitated by trial design, recruitment strategies, and appropriate PROM usage. The use of translated PROMs should be made explicit when used in cancer clinical trials.
Topics: Clinical Trials as Topic; Humans; Neoplasms; Patient Reported Outcome Measures; Research Personnel
PubMed: 33902699
DOI: 10.1186/s13063-021-05255-z -
Epilepsy & Behavior : E&B Feb 2021To perform a systematic review and meta-analysis to summarize and quantitatively evaluate the electroencephalogram (EEG) findings in patients with coronavirus disease... (Meta-Analysis)
Meta-Analysis
OBJECTIVE
To perform a systematic review and meta-analysis to summarize and quantitatively evaluate the electroencephalogram (EEG) findings in patients with coronavirus disease 2019 (COVID-19).
METHODS
The MEDLINE, CENTRAL, and ClinicalTrials.Gov databases were comprehensively assessed and searched for observational studies with EEG findings in patients with COVID-19. Pooled proportions of EEG findings with 95% confidence intervals (CIs) were assessed using a random effects model. The quality of assessment for each study, heterogeneity between the studies, and publication bias were also evaluated.
RESULTS
In total, 12 studies with 308 patients were included in the meta-analysis. Abnormal background activity and generalized slowing in the pooled proportions were common findings among the patients with COVID-19 (96.1% [95% CI: 89.4-99.9]; I = 60%; p < 0.01 and 92.3% [95% CI: 81.2-99.3]; I = 74%; p < 0.01, respectively). The proportion of patients with epileptiform discharges (EDs) was 20.3% ([95% CI: 9.85-32.9]; I = 78%; p < 0.01). The proportion of EDs varied between patients with a history of epilepsy or seizures (59.5% [95% CI: 33.9-83.2]; I = 0%; p = 0.49) and patients without them (22.4% [95% CI: 10.4-36.4]; I = 46%; p = 0.07). The findings of seizures and status epilepticus on EEG were observed in 2.05% ([95% CI: 0.02-6.04]; I = 39%; p = 0.08) and 0.80% ([95% CI: 0.00.-3.69]; I = 28%; p = 0.17) of the patients, respectively.
CONCLUSION
The proportion of abnormal background activity in patients with COVID-19 was high (96.1%). Epileptiform discharges were present in 20.3% of the cases and the proportion varied between people who had a history of epilepsy/seizure and those who did not. However, the proportion of seizures and status epilepticus on EEG was low (2.05% and 0. 80%, respectively).
Topics: COVID-19; Clinical Trials as Topic; Electroencephalography; Epilepsy; Humans
PubMed: 33342709
DOI: 10.1016/j.yebeh.2020.107682 -
Ageing Research Reviews Jul 2023To investigate the effects of the three kinds of anti-amyloid-β (Aβ) drugs on cognitive and other functions, fluid and neuroimaging biomarkers, and safety on patients... (Meta-Analysis)
Meta-Analysis
Effects of three kinds of anti-amyloid-β drugs on clinical, biomarker, neuroimaging outcomes and safety indexes: A systematic review and meta-analysis of phase II/III clinical trials in Alzheimer's disease.
OBJECTIVE
To investigate the effects of the three kinds of anti-amyloid-β (Aβ) drugs on cognitive and other functions, fluid and neuroimaging biomarkers, and safety on patients with Alzheimer's disease (AD), and rank the three kinds of anti-Aβ drugs.
METHODS
We searched Medline, Embase, Cochrane Central Register of Controlled Trials, ClinicalTrials.gov, and AlzForum from inception to January 21, 2023 to include randomized controlled clinical trials. Random effects meta-analyses were performed.
RESULTS
Forty-one clinical trials (20929 participants, 9167 male) were included. Anti-Aβ drugs had significant but relatively low efficacy in preventing cognitive decline (ADAS-Cog SMD -0.07, 95% CI: -0.10 to -0.03, p < 0.001; CDR-SOB -0.05, -0.09 to -0.01, p = 0.017). Instrumental variable meta-analysis and trial sequential analysis confirmed the reliability of the pooled estimation. Beneficial effects were also observed by assessing other cognitive and activity of daily living scales and biomarkers, with acceptable safety of anti-Aβ drugs. Meta-regression demonstrated significant association between higher baseline mini-mental statement examination scores (MMSE) and better cognitive protective effects on cognitive function (ADAS-Cog β: -0.02, -0.05 to 0.00, p = 0.017) and clearance of pathological productions of anti-Aβ drugs. Network meta-analysis ranked the passive immunotherapy drugs to have the best cognitive efficacy, followed by active immunotherapy and small molecule drugs.
CONCLUSION
Anti-Aβ drugs have relatively low efficacy in preventing cognitive decline, and they reduce pathological productions with acceptable safety. Patients with higher baseline MMSE scores benefit more from anti-Aβ drugs. Passive immunotherapy anti-Aβ drugs show relatively better efficacy than active immunotherapy and small molecule anti-Aβ drugs.
Topics: Humans; Male; Alzheimer Disease; Amyloid beta-Peptides; Biomarkers; Clinical Trials, Phase II as Topic; Neuroimaging; Reproducibility of Results
PubMed: 37217078
DOI: 10.1016/j.arr.2023.101959 -
The Annals of Pharmacotherapy Aug 2023This article reviews clinical trials to assess the efficacy, safety, and clinical application of once-daily roflumilast 0.3% cream for the treatment of plaque psoriasis. (Review)
Review
OBJECTIVE
This article reviews clinical trials to assess the efficacy, safety, and clinical application of once-daily roflumilast 0.3% cream for the treatment of plaque psoriasis.
DATA SOURCES
A systematic review of the literature was performed using the terms OR OR in MEDLINE (PubMed) and EMBASE databases between January 2012 and October 2022. Bibliographies and the ClinicalTrials.gov website were also searched to identify further studies.
STUDY SELECTION AND DATA EXTRACTION
Studies written in English and relevant to pharmacology, clinical trials, and safety were considered for inclusion.
DATA SYNTHESIS
In two 8-week phase III clinical trials, disease severity as assessed by a score of "clear" or "almost clear" and a 2-point improvement on Investigator Global Assessment (IGA) was 42.4% and 37.5% at week 8 in DERMIS-1 and DERMIS-2, respectively, compared to 6.1% and 6.9% in the control groups. In the 52-week phase III trial, treatment success rates for plaque psoriasis and intertriginous psoriasis were similar to the 8-week data with 45% of patients in the treatment group were evaluated as an IGA of "clear" or "almost clear" at week 52.
RELEVANCE TO PATIENT CARE AND CLINICAL PRACTICE IN COMPARISON TO EXISTING DRUGS
Roflumilast is a new US Food and Drug Administration (FDA)-approved topical phosphodiesterase inhibitor that shows promise for the treatment of mild-severe plaque psoriasis. It is an effective and safe topical nonsteroidal alternative to currently available topical corticosteroids, but there are currently no comparative studies with other psoriasis treatments.
CONCLUSION
Roflumilast is effective and safe for the treatment of plaque psoriasis and intertriginous psoriasis. Future trials should compare its efficacy and tolerability with that of the older, clinically established topical corticosteroids. Prohibitive factors may include limited patient adherence to topical treatments and cost.
Topics: Humans; Adrenal Cortex Hormones; Aminopyridines; Dermatologic Agents; Immunoglobulin A; Psoriasis; Severity of Illness Index; Treatment Outcome; Clinical Trials as Topic
PubMed: 36420929
DOI: 10.1177/10600280221137750 -
Medicine Aug 2023Tezepelumab is a human thymic stromal lymphopoietin (TSLP) antibody with effects in asthma. Therefore, our study aimed to evaluate the overall efficacy and safety of... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Tezepelumab is a human thymic stromal lymphopoietin (TSLP) antibody with effects in asthma. Therefore, our study aimed to evaluate the overall efficacy and safety of tezepelumab for the treatment of uncontrolled asthma.
METHODS
The databases Cochrane Library, PubMed, Embase, Web of Science, and Clinical Trials were searched from inception to April 1, 2022. Only randomized controlled trial (RCTs) that evaluated tezepelumab and a comparator for treating uncontrolled asthma were included. Additionally, articles were limited to English. The primary outcome was clinical efficacy, and the secondary outcome was adverse events. The risk of bias and quality were assessed by the Cochrane Collaboration bias assessment tool. The meta-analysis was performed using Review Manager Version 5.3.
RESULTS
Four RCTs with a total of 1600 patients were included in the study. Pooled analysis indicated that tezepelumab had significantly decreased annualized asthma exacerbations (odds ratio [OR] = 0.67, 95% confidence interval [CI] = [0.57, -0.80], P < .00001) and the asthma control questionnaire score of 6 (ACQ-6) among the patients (standard mean difference [SMD] = -0.29, 95% CI = [-0.39, -0.20], P < .00001) compared to placebo. Furthermore, tezepelumab treatment significantly improved forced expiratory volume in 1 second (FEV1, SMD = 0.28, 95% CI = [0.11, 0.45], P = .001). Regarding safety, the pooled analysis indicated that patients treated with tezepelumab showed no significant difference in adverse events that led to discontinuation of the treatment, but they experienced some other (non-serious) adverse events compared to the placebo group. However, there was a significant decrease in the incidence of serious adverse events and any adverse events in the tezepelumab group. Tezepelumab use was associated with adverse events, including nasopharyngitis, headache, and bronchitis, despite effectively treating asthma.
CONCLUSION
Tezepelumab effectively improved FEV1, reduced the disease symptom score, and decreased the risk of exacerbations in uncontrolled asthma patients. Tezepelumab was associated with some adverse events compared to placebo. This suggests that careful management of adverse events is required if tezepelumab is used to treat asthma patients.
Topics: Humans; Randomized Controlled Trials as Topic; Asthma; Antibodies, Monoclonal, Humanized; Treatment Outcome
PubMed: 37565847
DOI: 10.1097/MD.0000000000034746 -
Biomedica : Revista Del Instituto... Oct 2020Introduction: Recently, researchers from China and France reported on the effectiveness of chloroquine and hydroxychloroquine for the inhibition of SARS-CoV-2 viral...
Introduction: Recently, researchers from China and France reported on the effectiveness of chloroquine and hydroxychloroquine for the inhibition of SARS-CoV-2 viral replication in vitro. Timely dissemination of scientific information is key in times of pandemic. A systematic review of the effect and safety of these drugs on COVID-19 is urgently needed. Objective: To map published studies until March 25, 2020, on the use of chloroquine and its derivates in patients with COVID-19. Materials and methods: We searched on PubMed, Embase, Lilacs, and 15 registries from the World Health Organization’s International Clinical Trials Registry Platform for theoretical and empirical research in English, Spanish, Italian, French, or Portuguese until March 25, 2020, and made a narrative synthesis of the results. Results: We included 19 records and 24 trial registries (n=43) including 18,059 patients. China registered 66% (16/24) of the trials. Nine trials evaluate chloroquine exclusively and eight hydroxychloroquine. The records are comments (n=9), in vitro studies (n=3), narrative reviews (n=2), clinical guidelines (n=2), as well as a systematic review, an expert consensus, and a clinical trial. Conclusions: One small (n=26), non-randomized, and flawed clinical trial supports hydroxychloroquine use in patients with COVID-19. There is an urgent need for more clinical trial results to determine the effect and safety of chloroquine and hydroxychloroquine on COVID-19.
Topics: Antiviral Agents; Betacoronavirus; COVID-19; Chloroquine; Clinical Trials as Topic; Compassionate Use Trials; Coronavirus Infections; Cytokine Release Syndrome; Drug Repositioning; Humans; Hydroxychloroquine; Multicenter Studies as Topic; Pandemics; Pneumonia, Viral; Randomized Controlled Trials as Topic; Registries; SARS-CoV-2; Treatment Outcome; Virus Replication; COVID-19 Drug Treatment
PubMed: 33152192
DOI: 10.7705/biomedica.5478 -
Journal of Clinical Epidemiology Dec 2023To inform clinical practice guidelines, randomized controlled trials (RCTs) of the management of pneumonia need to address the outcomes that are most important to...
OBJECTIVES
To inform clinical practice guidelines, randomized controlled trials (RCTs) of the management of pneumonia need to address the outcomes that are most important to patients and health professionals using consistent instruments, to enable results to be compared, contrasted, and combined as appropriate. This systematic review describes the outcomes reported in clinical trials of pneumonia management and the instruments used to measure these outcomes.
STUDY DESIGN AND SETTING
Based on a prospective protocol, we searched MEDLINE/PubMed, Cochrane CENTRAL and clinical trial registries for ongoing or completed clinical trials evaluating pneumonia management in adults in any clinical setting. We grouped reported outcomes thematically and classified them following the COMET Initiative's taxonomy. We describe instruments used for assessing each outcome.
RESULTS
We found 280 eligible RCTs of which 115 (41.1%) enrolled critically ill patients and 165 (58.9%) predominantly noncritically ill patients. We identified 43 distinct outcomes and 108 measurement instruments, excluding nonvalidated scores and questionnaires. Almost all trials reported clinical/physiological outcomes (97.5%). Safety (63.2%), mortality (56.4%), resource use (48.6%) and life impact (11.8%) outcomes were less frequently addressed. The most frequently reported outcomes were treatment success (60.7%), mortality (56.4%) and adverse events (41.1%). There was significant variation in the selection of measurement instruments, with approximately two-thirds used in less than 10 of the 280 RCTs. None of the patient-reported outcomes were used in 10 or more RCTs.
CONCLUSION
This review reveals significant variation in outcomes and measurement instruments reported in clinical trials of pneumonia management. Outcomes that are important to patients and health professionals are often omitted. Our findings support the need for a rigorous core outcome set, such as that being developed by the European Respiratory Society.
Topics: Adult; Humans; Pneumonia; Treatment Outcome; Clinical Trials as Topic
PubMed: 37898460
DOI: 10.1016/j.jclinepi.2023.10.011 -
Annals of Palliative Medicine Nov 2021Vascular punctures are widely used in clinical applications; however, clinical trials have identified complications and poor prognosis for patients undergoing common... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Vascular punctures are widely used in clinical applications; however, clinical trials have identified complications and poor prognosis for patients undergoing common peripheral vein puncture as compared to ultrasound-guided peripheral venipuncture and catheterization. Ultrasound-guided peripheral venipuncture and catheterization is accurate, simple, has fewer associated complications, and will gradually take the place of common peripheral vein puncture.
METHODS
To study the safety of ultrasound-guided peripheral venous catheterization, a meta-analysis was conducted of relevant articles dating from establishment date of the database (such as PubMed, MEDLINE and EMBASE) to March 2021, with the search keywords being peripheral venipuncture, ultrasound guidance, vascular injury rate, and hematoma formation rate. A total of 8 trials were used to determine accuracy indicators, which included puncture failure rate, arterial injury rate, hematoma formation rate, pneumothorax incidence rate, and hemothorax incidence rate.
RESULTS
There were statistically significant differences between the two methods for peripheral venipuncture and catheterization in terms of puncture failure rate [odds ratio (OR) =0.08; 95% CI: 0.04-0.16; P<0.00001], incidence of vascular injury (OR =0.15; 95% CI: 0.07-0.32; P<0.00001), probability of hematoma formation during the puncture process (OR =0.24; 95% CI: 0.08-0.69; P=0.008), and probability of pneumothorax during puncture (OR =0.10; 95% CI: 0.02-0.55; P=0.008).
DISCUSSION
Eight articles were included for meta-analysis. Ultrasound-guided peripheral venipuncture and catheterization is a commonly used puncture method for patients needing rapid fluid infusion with pressure or a pressure pump, repeated transfusion of blood product, or multiple daily venous blood drawing test. The results were very clear, and the puncture failure rate and other complications of ultrasound-guided peripheral venipuncture catheterization were low.
Topics: Catheterization, Central Venous; Clinical Trials as Topic; Humans; Incidence; Phlebotomy; Ultrasonography; Ultrasonography, Interventional
PubMed: 34872297
DOI: 10.21037/apm-21-3163 -
Journal of Bone and Mineral Research :... Sep 2021The objective of this study was to investigate the effects of vitamin D supplementation versus placebo on muscle health. For this systematic review and trial-level... (Meta-Analysis)
Meta-Analysis
The objective of this study was to investigate the effects of vitamin D supplementation versus placebo on muscle health. For this systematic review and trial-level meta-analysis of placebo-controlled trials, a systematic search of randomized controlled trials published until October 2020 was performed in Medline, Embase, and Google Scholar. We included studies in humans (except athletes) on supplementation with vitamin D2 or D3 versus placebo, regardless of administration form (daily, bolus, and duration) with or without calcium co-supplementation. The predefined endpoints were physical performance reported as timed up and go test (TUG; seconds), chair rising test (seconds), 6-minute walking distance (m), and Short Physical Performance Battery (SPPB; points). Furthermore, endpoints were maximum muscle strength (Newton) measured at handgrip, elbow flexion, elbow extension, knee flexion, and knee extension, as well as muscle (lean tissue) mass (kg). Falls were not included in the analysis. Cochrane Review Manager (version 5.4.1.) calculating mean difference (MD) using a random effect model was used. In total, 54 randomized controlled trials involving 8747 individuals were included. Vitamin D versus placebo was associated with a significantly longer time spent performing the TUG (MD 0.15 [95% confidence interval (CI) 0.03 to 0.26] seconds, N = 19 studies, I = 0%, n = 5223 participants) and a significant lower maximum knee flexion strength (MD -3.3 [-6.63 to -0.03] Newton, N = 12 studies, I = 0%, n = 765 participants). Total score in the SPPB showed a tendency toward worsening in response to vitamin D compared with placebo (MD -0.18 [-0.37 to 0.01] points, N = 8 studies, I = 0%, n = 856 participants). Other measures of muscle health did not show between-group differences. In subgroup analyses, including studies with low vitamin D levels, effects of vitamin D supplementation did not differ from placebo. Available evidence does not support a beneficial effect of vitamin D supplementation on muscle health. Vitamin D may have adverse effects on muscle health, which needs to be considered when recommending vitamin D supplementation. © 2021 American Society for Bone and Mineral Research (ASBMR).
Topics: Cholecalciferol; Dietary Supplements; Hand Strength; Humans; Muscles; Postural Balance; Randomized Controlled Trials as Topic; Time and Motion Studies; Vitamin D
PubMed: 34405916
DOI: 10.1002/jbmr.4412