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European Journal of Epidemiology Apr 2022Physical inactivity in individuals with spinal cord injury (SCI) has been suggested to be an important determinant of increased cardiometabolic disease (CMD) risk.... (Meta-Analysis)
Meta-Analysis Review
Physical inactivity in individuals with spinal cord injury (SCI) has been suggested to be an important determinant of increased cardiometabolic disease (CMD) risk. However, it remains unclear whether physically active SCI individuals as compared to inactive or less active individuals have truly better cardiometabolic risk profile. We aimed to systematically review and quantify the association between engagement in regular physical activity and/or exercise interventions and CMD risk factors in individuals with SCI. Four medical databases were searched and studies were included if they were clinical trials or observational studies conducted in adult individuals with SCI and provided information of interest. The Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach was applied to rate the certainty of evidence. Of 5816 unique citations, 11 randomized clinical trials, 3 non-randomized trial and 32 cross-sectional studies comprising more than 5500 SCI individuals were included in the systematic review. In meta-analysis of RCTs and based on evidence of moderate certainty, physical activity in comparison to control intervention was associated with: (i) better glucose homeostasis profile [WMD of glucose, insulin and Assessment of Insulin Resistance (HOMA-IR) were - 3.26 mg/dl (95% CI - 5.12 to - 1.39), - 3.19 μU/ml (95% CI - 3.96 to - 2.43)] and - 0.47 (95% CI - 0.60 to - 0.35), respectively], and (ii) improved cardiorespiratory fitness [WMD of relative and absolute oxygen uptake relative (VO) were 4.53 ml/kg/min (95% CI 3.11, 5.96) and 0.26 L/min (95% CI 0.21, 0.32) respectively]. No differences were observed in blood pressure, heart rate and lipids (based on evidence of low/moderate certainty). In meta-analysis of cross-sectional studies and based on the evidence of very low to low certainty, glucose [WMD - 3.25 mg/dl (95% CI - 5.36, - 1.14)], insulin [- 2.12 μU/ml (95% CI - 4.21 to - 0.03)] and total cholesterol [WMD - 6.72 mg/dl (95% CI - 13.09, - 0.34)] were lower and HDL [WMD 3.86 mg/dl (95% CI 0.66, 7.05)] and catalase [0.07 UgHb-1 (95% CI 0.03, 0.11)] were higher in physically active SCI individuals in comparison to reference groups. Based on limited number of cross-sectional studies, better parameters of systolic and diastolic cardiac function and lower carotid intima media thickness were found in physically active groups. Methodologically sound clinical trials and prospective observational studies are required to further elaborate the impact of different physical activity prescriptions alone or in combination with other life-style interventions on CMD risk factors in SCI individuals.
Topics: Adult; Humans; Cardiometabolic Risk Factors; Carotid Intima-Media Thickness; Cross-Sectional Studies; Exercise; Glucose; Insulins; Observational Studies as Topic; Spinal Cord Injuries; Clinical Trials as Topic
PubMed: 35391647
DOI: 10.1007/s10654-022-00859-4 -
Neurocritical Care Apr 2022One of the challenges in bringing new therapeutic agents (since nimodipine) in for the treatment of cerebral ischemia associated with aneurysmal subarachnoid hemorrhage... (Review)
Review
One of the challenges in bringing new therapeutic agents (since nimodipine) in for the treatment of cerebral ischemia associated with aneurysmal subarachnoid hemorrhage (aSAH) is the incongruence in therapeutic benefit observed between phase II and subsequent phase III clinical trials. Therefore, identifying areas for improvement in the methodology and interpretation of results is necessary to increase the value of phase II trials. We performed a systematic review of phase II trials that continued into phase III trials, evaluating a therapeutic agent for the treatment of cerebral ischemia associated with aSAH. We followed the Preferred Reporting Items for Systematic reviews and Meta-Analyses guidelines for systematic reviews, and review was based on a peer-reviewed protocol (International Prospective Register of Systematic Reviews no. 222965). A total of nine phase III trials involving 7,088 patients were performed based on eight phase II trials involving 1558 patients. The following therapeutic agents were evaluated in the selected phase II and phase III trials: intravenous tirilazad, intravenous nicardipine, intravenous clazosentan, intravenous magnesium, oral statins, and intraventricular nimodipine. Shortcomings in several design elements of the phase II aSAH trials were identified that may explain the incongruence between phase II and phase III trial results. We suggest the consideration of the following strategies to improve phase II design: increased focus on the selection of surrogate markers of efficacy, selection of the optimal dose and timing of intervention, adjustment for exaggerated estimate of treatment effect in sample size calculations, use of prespecified go/no-go criteria using futility design, use of multicenter design, enrichment of the study population, use of concurrent control or placebo group, and use of innovative trial designs such as seamless phase II to III design. Modifying the design of phase II trials on the basis of lessons learned from previous phase II and phase III trial combinations is necessary to plan more effective phase III trials.
Topics: Brain Ischemia; Cerebral Infarction; Clinical Trials, Phase II as Topic; Clinical Trials, Phase III as Topic; Humans; Multicenter Studies as Topic; Nicardipine; Nimodipine; Subarachnoid Hemorrhage; Treatment Outcome; Vasospasm, Intracranial
PubMed: 34940927
DOI: 10.1007/s12028-021-01372-4 -
Dermatology (Basel, Switzerland) 2023Hidradenitis suppurativa (HS) is a chronic inflammatory disease that disproportionally affects women, as well as Black and biracial individuals. While adalimumab remains...
BACKGROUND
Hidradenitis suppurativa (HS) is a chronic inflammatory disease that disproportionally affects women, as well as Black and biracial individuals. While adalimumab remains the only therapy approved by the Food and Drug Administration for HS, many HS clinical trials for novel and re-tasked therapies are ongoing or upcoming. To optimize treatment equity, reflect the patient population, and facilitate trial participation, it is important to elucidate aspects of clinical trial protocols that may systematically exclude specific patient groups or impose hardships.
OBJECTIVE
The study aimed to systematically review inclusion and exclusion criteria as well as participant demographics in HS clinical trials.
METHODS
A literature search of PubMed, Embase, Cochrane Central, and Web of Science databases was conducted. Peer-reviewed publications of randomized controlled trials that were written in English and had at least 10 participants were included. Title and abstract screening and data extraction were completed by two independent reviewers, with disagreements resolved by a third.
RESULTS
Twenty-three studies totaling 1,496 adult participants met the inclusion criteria. Race and ethnicity were not reported in 473/1,496 (31.6%) and 1,420/1,496 (94.9%) trial participants, respectively. Trial participants were predominantly white (811/1,023, 79.3%) and female (1,057/1,457, 72.5%). The median of each study's average age was 35.7 years (IQR 33.5-38.0), and 17/23 (73.9%) trials excluded pediatric patients. Nearly all participants had Hurley Stage II (499/958, 52.0%) or Hurley Stage III (385/958, 40.2%) disease. Many trials excluded patients who were pregnant (19/23, 82.6%) and breastfeeding (13/23, 56.5%), or who had HS that was "too severe" (8/23, 34.8%) or "too mild" (16/23, 70.0%). Frequently, trial protocols required prolonged washout periods from HS therapies, relatively long duration in the study's placebo arm, and prohibited concurrent analgesic use.
CONCLUSIONS
This systematic review of 23 HS clinical trials totaling 1,496 participants identified substantial hardships imposed by trial participation, high rates of missing race and ethnicity data, and low representation of key patient groups, including those who identify as Black. Future trials with pragmatic study designs, broader inclusion criteria, and study sites in diverse communities may alleviate burdens of trial participation and improve enrollment of diverse patient groups.
Topics: Adult; Humans; Female; Hidradenitis Suppurativa; Clinical Trials as Topic; Adalimumab; Demography; Randomized Controlled Trials as Topic
PubMed: 36108592
DOI: 10.1159/000526069 -
The Cochrane Database of Systematic... Feb 2020Acute pulmonary embolism (PE) is a common cause of death, accounting for 50,000 to 200,000 deaths annually. It is the third most common cause of mortality among the... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Acute pulmonary embolism (PE) is a common cause of death, accounting for 50,000 to 200,000 deaths annually. It is the third most common cause of mortality among the cardiovascular diseases, after coronary artery disease and stroke. The advent of multi-detector computed tomographic pulmonary angiography (CTPA) has allowed better assessment of PE regarding visualisation of the peripheral pulmonary arteries, increasing its rate of diagnosis. More cases of peripheral PEs, such as isolated subsegmental PE (SSPE) and incidental PE, have thereby been identified. These two conditions are usually found in patients with few or none of the classic PE symptoms such as haemoptysis or pleuritic pain, acute dyspnoea or circulatory collapse. However, in patients with reduced cardiopulmonary reserve, classic PE symptoms can be found with isolated SSPEs. Incidental SSPE is found casually in asymptomatic patients, usually by diagnostic imaging performed for other reasons (for example routine CT for cancer staging in oncology patients). Traditionally, all PEs are anticoagulated in a similar manner independent of their location, or number and size of the thrombi. It has been suggested that many patients with SSPE may be treated without benefit, increasing adverse events by a possible unnecessary use of anticoagulants. Patients with isolated SSPE, or incidental PE, may have a more benign clinical presentation compared to those with proximal PEs. However, the clinical significance in patients, and their prognosis, needs to be studied to evaluate whether anticoagulation therapy is required. This is the second update of the Cochrane systematic review published in 2014.
OBJECTIVES
To assess the effectiveness and safety of anticoagulation therapy versus control in patients with isolated subsegmental pulmonary embolism (SSPE) or incidental SSPE.
SEARCH METHODS
The Cochrane Vascular Information Specialist searched the Cochrane Vascular Specialised Register, CENTRAL, MEDLINE, Embase, CINAHL and AMED databases and World Health Organization International Clinical Trials Registry Platform and ClinicalTrials.gov trials registers to 26 November 2019. We also undertook reference checking to identify additional studies.
SELECTION CRITERIA
We included randomised controlled trials of anticoagulation therapy versus control in patients with SSPE or incidental SSPE.
DATA COLLECTION AND ANALYSIS
Two review authors inspected all citations identified to ensure reliable assessment. If relevant studies were identified, we planned for two review authors to independently extract data and to assess the methodological quality of identified trials using the criteria recommended in the Cochrane Handbook for Systematic Reviews of Interventions.
MAIN RESULTS
We did not identify any studies that met the inclusion criteria.
AUTHORS' CONCLUSIONS
There is no evidence from randomised controlled trials to assess the effectiveness and safety of anticoagulation therapy versus control in patients with isolated subsegmental pulmonary embolism (SSPE) or incidental SSPE. Well-conducted research is required before informed practice decisions can be made.
Topics: Acute Disease; Anticoagulants; Dyspnea; Humans; Prognosis; Pulmonary Embolism; Randomized Controlled Trials as Topic; Treatment Outcome; Watchful Waiting
PubMed: 32030721
DOI: 10.1002/14651858.CD010222.pub4 -
Journal of Addictive Diseases 2022Auriculotherapy has been used to reduce withdrawal symptoms during drug detoxication. The purpose of this study was to review the results of the randomized controlled...
Auriculotherapy has been used to reduce withdrawal symptoms during drug detoxication. The purpose of this study was to review the results of the randomized controlled trials (RCTs) that examined the impact of auriculotherapy on addiction. This study aimed to find an effective protocol involving auricular acupuncture points, intervention duration and frequency, and stimulating methods. We searched PubMed, Cumulative Index to Nursing and Allied Health Literature (CINAHL), and Medline for articles published between January 1, 1994, and March 31, 2021. The keywords used were auricular, acupuncture, addiction, substance misuse, smoking, randomized controlled trial, clinical trial, and human. Each RCT was evaluated for quality applying the risk of bias tool by the Cochrane group. Effect size (Hedges's g) was calculated using the mean values and standard deviation of the experimental and control groups. The risk for bias of these studies was moderate to high and only four studies (11.1%) earned scores of 6, indicating the lowest risk of bias and highest quality RCT. Out of 36 studies, 23 (64%) reported that auriculotherapy was effective for treating addiction such as opioids, cocaine, alcohol, heroin, nicotine, and gambling. The most commonly used combination of acupuncture points (four of 36 studies) was shenmen, sympathetic, liver, lung, and kidney, which are called NADA protocol. The following most frequently used combination of acupressure points (four out of 36 studies) was shenmen, subcortex, heart, lung, and liver. Acupressure could be considered to be used for the treatment of addiction.
Topics: Auriculotherapy; Behavior, Addictive; Humans; Randomized Controlled Trials as Topic; Smoking; Substance Withdrawal Syndrome; Treatment Outcome
PubMed: 35179436
DOI: 10.1080/10550887.2021.2016011 -
Eye & Contact Lens Sep 2023To conduct a systematic review and meta-analysis of randomized controlled trials (RCTs) on the effects of orthokeratology for slowing myopia progression in children. (Meta-Analysis)
Meta-Analysis
OBJECTIVE
To conduct a systematic review and meta-analysis of randomized controlled trials (RCTs) on the effects of orthokeratology for slowing myopia progression in children.
METHODS
We performed a specific search on PubMed, Embase, Cochrane Library, Clinical Trials, CNKI, SinoMed, and Wanfang Data for RCTs conducted up to October 1, 2022. We pooled the weighted mean difference (WMD) between the orthokeratology and control groups for axial length (AL) elongation and the odds ratio (OR) for rates of adverse events and dropout.
RESULTS
Seven RCTs involving 655 eyes were included. There were significant differences in the effects of orthokeratology versus control in slowing AL elongation with WMD of -0.11 mm (95% confidence interval (CI), -0.13 to -0.08; P <0.01) at 6 months, -0.16 mm (95% CI, -0.18 to -0.13; P <0.01) at 12 months, -0.23 mm (95% CI, -0.29 to -0.18; P <0.01) at 18 months, and -0.28 mm (95% CI, -0.38 to -0.19; P <0.01) at 24 months, respectively. Myopia control rate declined, with 64%, 53%, 50%, and 47% recorded for 6, 12, 18, and 24 months, respectively. There was no statistical significance for adverse events between orthokeratology and control groups (OR=2.63, 95% CI, 0.72-9.61; P =0.11).
CONCLUSION
Orthokeratology can effectively slow myopia progression in children, and the efficacy of myopia control decreases with time.
Topics: Child; Humans; Randomized Controlled Trials as Topic; Myopia; Axial Length, Eye; Odds Ratio; Orthokeratologic Procedures; Refraction, Ocular
PubMed: 37284749
DOI: 10.1097/ICL.0000000000001006 -
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 -
PloS One 2024Cardiovascular diseases (CVD) are the leading causes of morbidity and mortality. Heart rate variability (HRV) represents the modulatory capacity of the autonomous... (Clinical Trial)
Clinical Trial Meta-Analysis
BACKGROUND
Cardiovascular diseases (CVD) are the leading causes of morbidity and mortality. Heart rate variability (HRV) represents the modulatory capacity of the autonomous nervous system and influences mortality. By surveying this meta-analysis, we investigated the impact of physical activity on HRV.
METHODS
Databases, online journal libraries and clinical trial registries were searched for publications of randomized controlled and non-randomized controlled trials concerning adults with coronary artery disease (CAD)/ischemic heart disease (IHD), congestive heart failure (CHF), peripheral arterial disease (PAD) or after acute coronary syndrome (ACS) joining an intervention group with physical activity or a control group with usual care or no intervention. Extracted time-domain and frequency-domain parameter of HRV were analyzed in a meta-analysis using a random effect model. Subgroup analyses concerning intervention type, study design and type of heart disease and sensitivity analysis were performed.
RESULTS
Significant results were obtained for RR-Interval (p = 0.05) and standard deviation of Normal-to-Normal intervals (SDNN) (p = 0.01) for short-term assessment and for the ratio of low-frequency power (LF) to high-frequency power (HF) (p = 0.05) for 24-hour assessment. Subgroup analyses also resulted significant: root-mean-square difference of successive normal R-R intervals (RMSSD) (p = 0.01), SDNN (p = 0.02) and HF (p < 0.01) concerning CHF.
CONCLUSION
We were able to demonstrate the positive impact of physical activity on HRV, especially in patients with CHF. Cardiac rehabilitation exercise programs need to be individualized to identify the most beneficial method of training for improving the prognosis of patients with CVD.
Topics: Adult; Humans; Heart Rate; Coronary Artery Disease; Myocardial Ischemia; Heart Failure; Randomized Controlled Trials as Topic
PubMed: 38578755
DOI: 10.1371/journal.pone.0299793 -
Biomolecules Sep 2023Cyclin-dependent kinase 4 and 6 inhibitors (CDK4/6is) have transformed the treatment of hormone receptor-positive (HR+) and human epidermal growth factor receptor... (Review)
Review
Cyclin-dependent kinase 4 and 6 inhibitors (CDK4/6is) have transformed the treatment of hormone receptor-positive (HR+) and human epidermal growth factor receptor 2-negative (HER2-) breast cancer over the last decade. These inhibitors are currently established as first- and second-line systemic treatment choices for both endocrine-sensitive and -resistant breast cancer populations alongside endocrine therapy (ET) or monotherapy. Data on targeted therapy continue to mature, and the number of publications has been constantly rising. Although these drugs have been demonstrated to prolong overall survival (as well as progression-free survival (PFS) in breast cancer patients), changing the paradigm of all current knowledge, they also cause important adverse events (AEs). This review provides the latest summary and update on the safety profile of the three CDK4/6 inhibitors, as it appears from all major phase II and III randomized clinical trials regarding palbociclib, ribociclib, and abemaciclib, including the most relevant 15 clinical trials.
Topics: Humans; Female; Breast Neoplasms; Progression-Free Survival; Cyclin-Dependent Kinase 4; Clinical Trials, Phase II as Topic
PubMed: 37759823
DOI: 10.3390/biom13091422 -
Clinical and Experimental Allergy :... Mar 2022To determine whether treatment effectiveness can be established for a range of vocal cord dysfunction (VCD) interventions in adolescents and adults. (Review)
Review
OBJECTIVE
To determine whether treatment effectiveness can be established for a range of vocal cord dysfunction (VCD) interventions in adolescents and adults.
DESIGN
A systematic review of the literature and risk of bias appraisal was completed using the Joanna Briggs Institute Critical Appraisal Tools. Data were qualitatively synthesized in the broad intervention groups of glottic airway and respiratory retraining, pharmacological therapies, airway device therapies and psychological therapies.
DATA SOURCES
Nine electronic databases, two clinical trial registries and the grey literature were searched from inception to September 2021 for articles on VCD interventions or equivalent terms.
ELIGIBILITY CRITERIA
Studies were included if they were randomized controlled trials, non-randomized controlled trials, quasi-experimental pre- and post-test studies and within-subject repeated measure designs, participants were 13 years or older, VCD was diagnosed using laryngoscopy or CT larynx, VCD intervention was provided and outcome measures reported on VCD symptoms.
RESULTS
The search yielded no randomized controlled trials. There were 17 quasi-experimental studies that met the eligibility criteria, and these studies reported on glottic airway and respiratory retraining, botulinum toxin injections, inspiratory muscle strength training and amitriptyline; all were associated with VCD symptom reduction. In addition, 2 within-subject repeated measure studies reported inspiratory muscle strength training and respiratory retraining to be effective in reducing symptoms in participants with exertional VCD. The included studies were reported in full-text publications (11) and conference proceedings (8). There was a high risk of bias and low quality of evidence across all intervention areas.
CONCLUSION
Glottic airway and respiratory retraining, botulinum toxin injections, low-dose amitriptyline and inspiratory muscle strength training devices have been associated with symptom reduction in adults and adolescents with vocal cord dysfunction. Limited objective data exist to support the effectiveness of these interventions, and robust controlled trials are needed in this area. Systematic Review Registration: CRD42018092274 (PROSPERO).
Topics: Adolescent; Adult; Humans; Randomized Controlled Trials as Topic; Treatment Outcome; Vocal Cord Dysfunction
PubMed: 34699093
DOI: 10.1111/cea.14036