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Trials Oct 2023In this commentary, we discuss a recent article in Trials that raised concerns about the number of poorly performed randomised trials in the medical literature and...
In this commentary, we discuss a recent article in Trials that raised concerns about the number of poorly performed randomised trials in the medical literature and discuss the trials literature more widely. Although we all aim for higher methodological standards in trials, we argue that (i) the idea that 'most randomised trials are bad', which the recent article concludes is an overly simplistic representation of the situation, and (ii) the suggestion that an increased focus on methodological review during trial development (e.g. ethical boards performing some assessment of the methodologists on a trial), while well meaning, may have negative unintended consequences. We therefore propose that (a) trials should be assessed on their merits and weaknesses, including an assessment of risk of bias but placing that in a wider context; (b) we should recognise that although the methodological conduct of trials is of utmost importance, interventions that aim to improve this could have unintended consequences-such as bureaucracy-that have an overall negative effect; and (c) we should therefore generate an evidence base for policy interventions to improve conduct of trials rather than applying arbitrary rules.
Topics: Humans; Bias; Randomized Controlled Trials as Topic; Research Design
PubMed: 37864198
DOI: 10.1186/s13063-023-07706-1 -
Systematic Reviews Oct 2023Since 1997, several meta-analyses (MAs) of placebo-controlled randomised efficacy trials of homoeopathy for any indication (PRETHAIs) have been published with different...
BACKGROUND AND OBJECTIVE
Since 1997, several meta-analyses (MAs) of placebo-controlled randomised efficacy trials of homoeopathy for any indication (PRETHAIs) have been published with different methods, results and conclusions. To date, a formal assessment of these MAs has not been performed. The main objective of this systematic review of MAs of PRETHAIs was to evaluate the efficacy of homoeopathic treatment.
METHODS
The inclusion criteria were as follows: MAs of PRETHAIs in humans; all ages, countries, settings, publication languages; and MAs published from 1 Jan. 1990 to 30 Apr. 2023. The exclusion criteria were as follows: systematic reviews without MAs; MAs restricted to age or gender groups, specific indications, or specific homoeopathic treatments; and MAs that did not assess efficacy. We searched 8 electronic databases up to 14 Dec. 2020, with an update search in 6 databases up to 30 April 2023. The primary outcome was the effect estimate for all included trials in each MA and after restricting the sample to trials with high methodological quality, according to predefined criteria. The risk of bias for each MA was assessed by the ROBIS (Risk Of Bias In Systematic reviews) tool. The quality of evidence was assessed by the GRADE framework. Statistical analyses were performed to determine the proportion of MAs showing a significant positive effect of homoeopathy vs. no significant difference.
RESULTS
Six MAs were included, covering individualised homoeopathy (I-HOM, n = 2), nonindividualised homoeopathy (NI-HOM, n = 1) and all homoeopathy types (ALL-HOM = I-HOM + NI-HOM, n = 3). The MAs comprised between 16 and 110 trials, and the included trials were published from 1943-2014. The median trial sample size ranged from 45 to 97 patients. The risk of bias (low/unclear/high) was rated as low for three MAs and high for three MAs. Effect estimates for all trials in each MA showed a significant positive effect of homoeopathy compared to placebo (5 of 5 MAs, no data in 1 MA). Sensitivity analyses with sample restriction to high-quality trials were available from 4 MAs; the effect remained significant in 3 of the MAs (2 MAs assessed ALL-HOM, 1 MA assessed I-HOM) and was no longer significant in 1 MA (which assessed NI-HOM).
DISCUSSION
The quality of evidence for positive effects of homoeopathy beyond placebo (high/moderate/low/very low) was high for I-HOM and moderate for ALL-HOM and NI-HOM. There was no support for the alternative hypothesis of no outcome difference between homoeopathy and placebo. The available MAs of PRETHAIs reveal significant positive effects of homoeopathy beyond placebo. This is in accordance with laboratory experiments showing partially replicable effects of homoeopathically potentised preparations in physico-chemical, in vitro, plant-based and animal-based test systems.
SYSTEMATIC REVIEW REGISTRATION
PROSPERO CRD42020209661. The protocol for this SR was finalised and submitted on 25 Nov. 2020 and registered on 26 Dec. 2020.
Topics: Humans; Bias; Homeopathy; Research Design; Meta-Analysis as Topic; Randomized Controlled Trials as Topic
PubMed: 37805577
DOI: 10.1186/s13643-023-02313-2 -
Journal of the International Society of... Dec 2023Citrulline may amplify the effects of L-arginine and nitric oxide concentration, which may augment vasodilation and blood flow, thereby enhancing aerobic exercise... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
Citrulline may amplify the effects of L-arginine and nitric oxide concentration, which may augment vasodilation and blood flow, thereby enhancing aerobic exercise performance. The purpose of this randomized, double-blind, placebo-controlled crossover study was to investigate effects of L-citrulline + Glutathione on aerobic exercise performance and blood flow in well-trained men.
METHODS
Twenty-five males (Mean ± SD; Age: 22.2 ± 2.4 yrs; Height: 177.0 ± 4.8 cm; Weight: 75.3 ± 6.9 kg) were randomly assigned to the L-citrulline + Glutathione (Setria Performance Blend: SPB; L-citrulline [2 g] + glutathione [200 mg], 6 capsules) or placebo (PL; 3.1 g cellulose, 6 capsules) group. Participants performed a maximal oxygen consumption treadmill test to determine peak velocity (PV) and returned after eight days of ingesting either PL or SPB. Three timed treadmill runs to exhaustion (TTE) were performed at 90%, 100%, and 110% PV. Brachial artery blood flow and vessel diameter were assessed using ultrasound at 1-hr prior to exercise (1hrPrEX), after each exercise bout, immediately post-exercise (immediate PEX), and 30 minutes post exercise (30minPEX) at visits 2 and 4. Blood analytes were assessed via venous blood draws at visit 1, visit 3, and 1hrPEX, immediate PEX, and 30minPEX at visits 2 and 4. After a 14-day washout, participants repeated the same procedures, ingesting the opposite treatment. Separate repeated measures ANOVAs were performed for TTE, vessel diameter, blood flow, and blood analytes.
RESULTS
Blood flow was significantly augmented 30minPEX ( = 0.04) with SPB in comparison with PL. L-citrulline and L-arginine plasma concentrations were significantly elevated immediately PEX ( = 0.001) and 30-minPEX ( = 0.001) following SPB in comparison to PL.
CONCLUSION
Acute ingestion of SPB after eight days may enhance blood flow, L-citrulline, and L-arginine plasma concentrations after high-intensity exercise, which may enhance performance.
CLINICAL TRIAL REGISTRATION
[https://clinicaltrials.gov/ct2/show/nct04090138], identifier [NCT04090138].
Topics: Male; Humans; Young Adult; Adult; Dietary Supplements; Citrulline; Cross-Over Studies; Capsules; Glutathione; Double-Blind Method; Arginine
PubMed: 37125500
DOI: 10.1080/15502783.2023.2206386 -
European Journal of Nutrition Oct 2023The aim of this study was to explore the isolated and combined effects of caffeine and citrulline malate (CitMal) on jumping performance, muscular strength, muscular... (Randomized Controlled Trial)
Randomized Controlled Trial
Effect of isolated and combined ingestion of caffeine and citrulline malate on resistance exercise and jumping performance: a randomized double-blind placebo-controlled crossover study.
PURPOSE
The aim of this study was to explore the isolated and combined effects of caffeine and citrulline malate (CitMal) on jumping performance, muscular strength, muscular endurance, and pain perception in resistance-trained participants.
METHODS
Using a randomized and double-blind study design, 35 resistance-trained males (n = 18) and females (n = 17) completed four testing sessions following the ingestion of isolated caffeine (5 mg/kg), isolated CitMal (12 g), combined doses of caffeine and CitMal, and placebo. Supplements were ingested 60 min before performing a countermovement jump (CMJ) test (outcomes included jump height, rate of force development, peak force, and peak power), one-repetition maximum (1RM) squat and bench press, and repetitions to muscular failure in the squat and bench press with 60% of 1RM. Pain perception was evaluated following the repetitions to failure tests. The study was registered at ISRCTN (registration number: ISRCTN11694009).
RESULTS
Compared to the placebo condition, isolated caffeine ingestion and co-ingestion of caffeine and CitMal significantly enhanced strength in 1RM bench press (Cohen's d: 0.05-0.06; 2.5-2.7%), muscular endurance in the squat (d: 0.46-0.58; 18.6-18.7%) and bench press (d: 0.48-0.64; 9.3-9.5%). However, there was no significant difference between isolated caffeine ingestion and caffeine co-ingested with CitMal, and isolated CitMal supplementation did not have an ergogenic effect in any outcome. No main effect of condition was found in the analysis for CMJ-derived variables, 1RM squat and pain perception.
CONCLUSION
Caffeine ingestion appears to be ergogenic for muscular strength and muscular endurance, while adding CitMal does not seem to further enhance these effects.
Topics: Male; Female; Humans; Caffeine; Cross-Over Studies; Physical Endurance; Resistance Training; Double-Blind Method; Muscle Strength; Performance-Enhancing Substances; Eating
PubMed: 37450275
DOI: 10.1007/s00394-023-03212-x -
PloS One 2023Testing whether data are from a normal distribution is a traditional problem and is of great concern for data analyses. The normality is the premise of many statistical...
Testing whether data are from a normal distribution is a traditional problem and is of great concern for data analyses. The normality is the premise of many statistical methods, such as t-test, Hotelling T2 test and ANOVA. There are numerous tests in the literature and the commonly used ones are Anderson-Darling test, Shapiro-Wilk test and Jarque-Bera test. Each test has its own advantageous points since they are developed for specific patterns and there is no method that consistently performs optimally in all situations. Since the data distribution of practical problems can be complex and diverse, we propose a Cauchy Combination Omnibus Test (CCOT) that is robust and valid in most data cases. We also give some theoretical results to analyze the good properties of CCOT. Two obvious advantages of CCOT are that not only does CCOT have a display expression for calculating statistical significance, but extensive simulation results show its robustness regardless of the shape of distribution the data comes from. Applications to South African Heart Disease and Neonatal Hearing Impairment data further illustrate its practicability.
Topics: Computer Simulation; Normal Distribution; Sample Size; Data Analysis
PubMed: 37535617
DOI: 10.1371/journal.pone.0289498 -
American Journal of Transplantation :... Jan 2024Face transplantation is a viable reconstructive approach for severe craniofacial defects. Despite the evolution witnessed in the field, ethical aspects, clinical and...
Face transplantation is a viable reconstructive approach for severe craniofacial defects. Despite the evolution witnessed in the field, ethical aspects, clinical and psychosocial implications, public perception, and economic sustainability remain the subject of debate and unanswered questions. Furthermore, poor data reporting and sharing, the absence of standardized metrics for outcome evaluation, and the lack of consensus definitions of success and failure have hampered the development of a "transplantation culture" on a global scale. We completed a 2-round online modified Delphi process with 35 international face transplant stakeholders, including surgeons, clinicians, psychologists, psychiatrists, ethicists, policymakers, and researchers, with a representation of 10 of the 19 face transplant teams that had already performed the procedure and 73% of face transplants. Themes addressed included patient assessment and selection, indications, social support networks, clinical framework, surgical considerations, data on patient progress and outcomes, definitions of success and failure, public image and perception, and financial sustainability. The presented recommendations are the product of a shared commitment of face transplant teams to foster the development of face transplantation and are aimed at providing a gold standard of practice and policy.
Topics: Humans; Facial Transplantation; Consensus; Delphi Technique; Vascularized Composite Allotransplantation; Research Design
PubMed: 37666457
DOI: 10.1016/j.ajt.2023.08.023 -
PharmacoEconomics Nov 2023The aim of this valuation study was to produce a value set to support the use of EQ-5D-5L data in decision making in Slovenia.
OBJECTIVES
The aim of this valuation study was to produce a value set to support the use of EQ-5D-5L data in decision making in Slovenia.
METHODS
The study design followed the published EuroQol research protocol, and a quota sample was defined according to age, sex, and region. Overall, 1012 adult respondents completed 10 time trade-off and seven discrete choice experiment tasks in face-to-face interviews. The Tobit model was used to analyse the composite time trade-off (cTTO) data in order to generate values for the 3125 EQ-5D-5L health states.
RESULTS
The data showed logical consistency, with more severe states being given lower values. The greatest disutility was shown in the pain/discomfort and anxiety/depression dimensions. In the EQ-5D-5L value set, the values range from -1.09 to 1. With the exception of UA5 (unable to perform usual activities), all other levels on all health dimensions were statistically different from 0 and from each other. Compared with the existing EQ-5D-3L value set, there is a slightly lower share of 'worse than dead' states (32.1% compared with 33.7%) and the minimum value is lower.
CONCLUSIONS
Results have important implications for users of the EQ-5D-5L in Slovenia and regions. It is a robust and up-to-date value set and should be the preferred value set used in adults in Slovenia and in neighbouring countries without their own value set.
Topics: Adult; Humans; Health Status; Quality of Life; Slovenia; Surveys and Questionnaires; Research Design
PubMed: 37341959
DOI: 10.1007/s40273-023-01280-9 -
Journal of the International Society of... Dec 2023Because betaine (BET) supplementation may improve muscular strength and endurance, it seems plausible that BET will also influence CrossFit performance (CF). (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
Because betaine (BET) supplementation may improve muscular strength and endurance, it seems plausible that BET will also influence CrossFit performance (CF).
PURPOSE
The aim of this study was to evaluate the effects of three weeks of BET supplementation on body composition, CF performance, muscle power in the Wingate anaerobic test (WAnT), and the concentrations of selected hormones. The secondary aims were to analyze the effectiveness of two different BET doses (2.5 and 5.0 g/d) and their interaction with the methylenetetrahydrofolate reductase (MTHFR) genotype.
METHODS
The study was designed in a double-blinded randomized cross-over fashion. Forty-three CF practitioners completed the entire study. CF performance was measured using the Fight Gone Bad (FGB) workout and muscle power was evaluated in a 30-second WAnT. Body composition was determined by air-displacement plethysmography. Blood was drawn to assess hormone concentrations. The C677T single nucleotide polymorphism (rs180113) in the gene was analyzed.
RESULTS
FGB total improved with BET by 8.7 ± 13.6% ( < 0.001), but no significant changes were observed with placebo (- 0.4 ± 10.0%, = 0.128). No changes were also observed in WAnT and body composition. After BET supplementation testosterone concentration increased by 7.0 ± 15.4% with BET ( = 0.046) (no change with placebo: 1.5 ± 19.6%, = 0.884) but had no effect on concentrations of insulin-like growth factor or cortisol. Finally, there were no significant interactions between genotype and BET dose in any outcome.
CONCLUSIONS
BET supplementation may improve CF performance and increase testosterone concentration. However, there was no evidence of a difference between dosages (2.5 and 5.0 g/d) and genotypes. The trial was registered on clinicaltrials.gov (NCT03702205) on 10 October 2018.
Topics: Humans; Betaine; Cross-Over Studies; Double-Blind Method; Testosterone; Dietary Supplements
PubMed: 37409757
DOI: 10.1080/15502783.2023.2231411