Bias In Individual Studies Research Articles

Contrast-enhanced CT scan (CECT) for the detection of hollow viscus and mesenteric injuries in blunt trauma - an updated systematic review of the literature and meta-analysis of diagnostic test accuracy.

Despite improved awareness of blunt traumatic hollow viscus and mesenteric injuries (THVMI), the accuracy of contrast-enhanced CT (CECT) varies considerably among studies. This systematic review and meta-analysis of test accuracy aims to explore the diagnostic performance of CECT in detecting THVMI in blunt trauma. The study was conducted according to the Cochrane recommendations searching the PubMed, Scopus, and Cochrane Library datasets from 2000 to 8 September 2023 (PROSPERO ID: CRD42023473041). Surgical exploration, autopsy, and discharge from the hospital after monitoring were set as reference standard. To explore the diagnostic accuracy of CECT in detecting THVMI hierarchical models were developed. The risk of bias in individual studies was assessed with the QUADAS-2 tool. Sensitivity analysis was conducted to detect sources of heterogeneity. Twelve studies, for a total of 4537 patients, were deemed eligible. After identification of outliers and sensitivity analysis, the pooled sensitivity, specificity, positive and negative likelihood ratios, and diagnostic odds ratio were 0.85 (95% CI: 0.69-0.93), 0.94 (95% CI: 0.8-0.98), 14.65 (95% CI: 4.22-50.85), 0.16 (95% CI: 0.07-0.34), 92.3 (95% CI: 29.75-286.34), respectively. The Area under the HSROC curve was 0.95 (95% CI: 0.92-0.96). Meta-regression analysis identified the year of publication as a covariate significantly associated with heterogeneity. A high risk of bias was detected in the "patient selection" domains. CECT has a fundamental role in identifying THVMI with high specificity but suboptimal sensitivity. Clinical criteria are still of paramount importance, especially in cases of ambiguous initial CECT images.

Histopathological risk assessment in multisite epithelial dysplasia: A meta‐analysis

AbstractObjectiveHistopathological grading of oral epithelial dysplasia (OED) is the current standard for stratifying cancer progression risk but is associated with subjectivity and variability. This problem is not commonly seen regarding the grading of epithelial dysplasia in other sites. This systematic review aims to compare grading systems for oral, anal, penile, and cervical epithelial dysplasia to determine their predictive accuracy for recurrence and malignant transformation (MT) outcomes.MethodsThe review protocol was registered in PROSPERO (CRD42023403035) and was reported according to the PRISMA checklist. A comprehensive search was performed in the main databases and gray literature. The risk of bias in individual studies was analyzed using the Joanna Briggs Institute checklist for each study design.ResultsForty‐six studies were deemed eligible and included in this systematic review, of which 45 were included in the quantitative analysis. Meta‐analysis revealed that the binary system demonstrated a higher predictive ability for MT/recurrence of OED compared to multilevel systems. Higher predictive accuracy of MT was also observed for binary grading systems in anal intraepithelial neoplasia.ConclusionsNo significant difference was found between the current grading systems of epithelial dysplasia in different body parts. However, binary grading systems have shown better clinical outcomes.

The efficacy and safety of hydroxychloroquine for COVID-19 prophylaxis and clinical assessment: an updated meta-analysis of randomized trials.

Coronavirus disease 2019 (COVID-19), a disease that affected tens of millions of people, upended the lives of countless individuals around the globe. The chloroquine (CQ) and its analogue hydroxychloroquine (HCQ) were the most frequently cited as potential treatments and preventatives against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The primary aim of this investigation was to scrutinize the effectiveness and safety of HCQ for COVID-19 prevention and to present powerful evidence and reference for clinical practice. PubMed, Ovid and the Cochrane COVID-19 Register of Controlled Trials (CENTRAL) were systematically searched from inception to January 31, 2022. Randomized controlled trials (RCTs) trials that included participants who were SARS-CoV-2 negative at the time of registration were enrolled in this meta-analysis. The intervention group took HCQ or CQ orally. The control group was not blinded by quinine or placebo. Pooled relative risk (RR) of SARS-CoV-2 infection, mortality, hospitalization, adverse events, and compliance were calculated. The software tools utilized for statistical analyses were Stata 14 and Review Manager 5.3. A total of 9 studies including 7,825 participants were enrolled. Bias of individual studies were assessed as low risk. The pooled RR for SARS-CoV-2 infection was 0.75 [95% confidence interval (CI): 0.68-0.83] (z=-4.01, P<0.0001; I2=11%). The pooled RR for hospitalization was 0.72 (95% CI: 0.35-1.50) (z=0.87, P=0.39; I2=0.0%). The pooled RR for mortality and adverse events were 3.26 (95% CI: 0.13-79.74) (z=0.72, P=0.47; I2=0.0%) and 1.90 (95% CI: 1.20-3.02) (z=2.73, P=0.0063; I2=94%). Results of this meta-analysis indicated significant impact of HCQ on SARS-CoV-2 infection with higher risk of adverse events. These findings must be considered with caution, and further research is necessary to delineate the specific circumstances where HCQ may be effective for COVID-19 prevention.

Changes in medical student attendance and its impact on student educational outcomes: a systematic review protocol

IntroductionThe COVID-19 pandemic has had a significant impact on medical education, with many institutions shifting to online learning to ensure the safety of students and staff. However, there has been...

A systematic review of simulation studies which compare existing statistical methods to account for non-compliance in randomised controlled trials

IntroductionNon-compliance is a common challenge for researchers and may reduce the power of an intention-to-treat analysis. Whilst a per protocol approach attempts to deal with this issue, it can result in biased estimates. Several methods to resolve this issue have been identified in previous reviews, but there is limited evidence supporting their use. This review aimed to identify simulation studies which compare such methods, assess the extent to which certain methods have been investigated and determine their performance under various scenarios.MethodsA systematic search of several electronic databases including MEDLINE and Scopus was carried out from conception to 30th November 2022. Included papers were published in a peer-reviewed journal, readily available in the English language and focused on comparing relevant methods in a superiority randomised controlled trial under a simulation study. Articles were screened using these criteria and a predetermined extraction form used to identify relevant information. A quality assessment appraised the risk of bias in individual studies. Extracted data was synthesised using tables, figures and a narrative summary. Both screening and data extraction were performed by two independent reviewers with disagreements resolved by consensus.ResultsOf 2325 papers identified, 267 full texts were screened and 17 studies finally included. Twelve methods were identified across papers. Instrumental variable methods were commonly considered, but many authors found them to be biased in some settings. Non-compliance was generally assumed to be all-or-nothing and only occurring in the intervention group, although some methods considered it as time-varying. Simulation studies commonly varied the level and type of non-compliance and factors such as effect size and strength of confounding. The quality of papers was generally good, although some lacked detail and justification. Therefore, their conclusions were deemed to be less reliable.ConclusionsIt is common for papers to consider instrumental variable methods but more studies are needed that consider G-methods and compare a wide range of methods in realistic scenarios. It is difficult to make conclusions about the best method to deal with non-compliance due to a limited body of evidence and the difficulty in combining results from independent simulation studies.PROSPERO registration numberCRD42022370910.

The short-, medium-, and long-term prevalence of physical health comorbidities in first-episode psychosis: a systematic review protocol

Background Individuals with first-episode psychosis (FEP) face an increased risk of physical comorbidities, notably cardiovascular diseases, metabolic disorders, respiratory disorders, and certain types of cancer. Previous reviews report pooled physical health prevalence from chronic psychosis and FEP groups. By contrast, this review will focus on antipsychotic-naïve FEP cohorts and incorporate data from observational longitudinal studies and antipsychotic intervention studies to understand the progression of physical health comorbidities from the onset to later stages of psychosis. This review aims to systematically examine the short-, medium-, and long-term period prevalence of these comorbidities in FEP and variations related to demographic factors. Methods A systematic review will be conducted using the PRISMA and MOOSE guidelines. Medline, Embase, PsycINFO, and CINAHL+, as well as Clinical Trials gov.uk, OpenGrey, WHO International Clinical Trials Registry Platform, Current Controlled Trials, United States National Institute of Health Trials Registry, and the Irish Health Repository, will be searched from inception. Longitudinal studies exploring physical health outcomes in FEP cohorts and antipsychotic intervention studies monitoring health outcomes in antipsychotic naïve FEP individuals will be eligible for inclusion. Two reviewers will independently screen titles, abstracts, and full-text articles. Bias in individual studies will be assessed using the JBI Critical Appraisal Checklist. A meta-analysis of the short-, medium-, and long-term prevalence of cardiovascular, metabolic, cancer, and respiratory outcomes and a narrative synthesis will be conducted. If possible, a meta-regression on the impact of demographic variables will be conducted. Conclusions This systematic review will clarify the progression of physical health comorbidities in FEP, informing early intervention strategies and policies for this population. Subsequent findings will be submitted to a leading journal, supplemented by a recovery education module for patient groups and a lay summary for wider dissemination. Registration The study was registered in PROSPERO, the International Prospective Register of Systematic Reviews (CRD42023431072; 17/06/2023).

Identifying factors controlling cellular uptake of gold nanoparticles by machine learning

There is strong interest to improve the therapeutic potential of gold nanoparticles (GNPs) while ensuring their safe development. The utility of GNPs in medicine requires a molecular-level understanding of how GNPs interact with biological systems. Despite considerable research efforts devoted to monitoring the internalisation of GNPs, there is still insufficient understanding of the factors responsible for the variability in GNP uptake in different cell types. Data-driven models are useful for identifying the sources of this variability. Here, we trained multiple machine learning models on 2077 data points for 193 individual nanoparticles from 59 independent studies to predict cellular uptake level of GNPs and compared different algorithms for their efficacies of prediction. The five ensemble learners (Xgboost, random forest, bootstrap aggregation, gradient boosting, light gradient boosting machine) made the best predictions of GNP uptake, accounting for 80–90% of the variance in the test data. The models identified particle size, zeta potential, GNP concentration and exposure duration as the most important drivers of cellular uptake. We expect this proof-of-concept study will foster the more effective use of accumulated cellular uptake data for GNPs and minimise any methodological bias in individual studies that may lead to under- or over-estimation of cellular internalisation rates.

Quality of systematic reviews with meta-analyses of resveratrol: A methodological systematic review.

Recently, several meta-analyses (MAs) have focused on the health effects of resveratrol. However, the methodological and reporting quality of these MAs has not yet been fully evaluated so far. Therefore, the present study evaluated the quality of these MAs through a methodological systematic review. Systematic searches were conducted in PubMed, Embase, Web of Science, and Cochrane Library from inception until May 20, 2022, and PubMed was used to update the search until September 6, 2023. The methodological and reporting quality of the selected MAs was evaluated using AMSTAR-2 and PRISMA 2009. Fifty-one MAs published during 2013-2023 were included. In each review, the number of primary studies ranged from 3 to 37, and the number of participants ranged from 50 to 2114. Among the first-listed primary outcomes, only 23 (45.10%) were "positive." As for the methodological quality, most MAs (44, 86.27%) on resveratrol were rated critically low. Inadequate reporting of the included MAs mainly involved items 2 ("Structured summary"), 5 ("Protocol and registration"), 8 ("Search"), 9 ("Study selection"), 10 ("Data collection process"), 12 ("Risk of bias in individual studies"), and 24 ("Summary of evidence") based on the PRISMA 2009. Additionally, journal's impact factor, number of authors, and funding support were positively associated with the overall methodological quality but were not statistically significant (p > 0.05). Future MAs on resveratrol require better design, implementation, and reporting by following the Cochrane Handbook, AMSTAR-2, and PRISMA.

New Onset Seizures in Hospitalized COVID-19 Patients; A Systematic Review and Meta-Analysis.

Seizures in COVID-19 patients continue to be a common reason for consulting the neurology service in the inpatient setting. This paper assesses the frequency of new onset seizures in adult hospitalized COVID-19 patients. PubMed and EMBASE were searched, with fifteen cohort studies identified to calculate the primary outcome, which was the frequency of new onset seizures in hospitalized COVID-19 patients. An inverse variance meta-analysis of single proportions with a random effects model was applied to these cohort studies to calculate the primary outcome. Risk of bias in individual studies was assessed using the 10-item risk of bias tool for prevalence studies. The meta-analysis revealed a frequency of .71% (95% confidential interval: .32-1.25, I2 = 89%, 147/28242 patients) for acute symptomatic seizures in patients with COVID-19. For secondary outcomes, the risk of seizures in patients who had EEG completed was 8.49% (95% confidential interval: .62-24.07, I2 = 14%, 44/535 patients). Slightly less than half of patients with COVID-19 and seizures were reported to have acute imaging abnormalities (45.7%) with acute vascular insults being commonly reported. Only a small percentage of COVID-19 patients with seizures (2.8%) met the criteria for COVID-19 encephalitis as determined by the international encephalitis consortium. The frequency of seizures in COVID-19 was .71% (95% confidential interval: .32-1.25). Slightly less than half of COVID-19 patients had head imaging abnormalities as a complication of COVID-19 infection. Only a small percentage of patients with seizures and COVID-19 met the criteria for COVID-19 encephalitis.

Clinical efficacy of transcrestal sinus floor augmentation, in comparison with lateral approach, in sites with residual bone height ≤6 mm: A systematic review and meta-analysis.

This paper addressed two focused questions: Focused question 1 (Q1) "what is the clinical efficacy of transcrestal sinus floor augmentation (TSFA), as compared to lateral sinus floor augmentation (LSFA) in sites with residual bone height (RBH) ≤6 mm, in randomized clinical trials (RCTs) and controlled clinical trials (CCTs)?"; Focused question 2 (Q2) "what is the estimated effectiveness of TSFA for outcomes in Q1, in RCTs, CCTs or cohort studies?" An electronic search (PubMed, EMBASE, The Cochrane Central Register of Controlled Trials) and hand search were conducted from January 1986 until December 2022. All eligible clinical studies expressly reporting TSFA in sites with RBH ≤6 mm were included. The data were extracted, and the risk of bias in individual studies was evaluated. Meta-analysis was performed whenever possible. Seven RCTs were included for Q1 and 25 studies (9 RCTs, 2 CCTs, 14 single arm cohort studies) for Q2. Q1: Meta-analysis did not show significant difference in the implant survival, sinus membrane perforation and marginal bone loss between TSFA and LSFA groups. Q2: Meta-analysis showed TSFA had a high implant survival rate (96.5%, 95% CI: 93.2%-98.9%) at least 1 year after surgery, and limited sinus membrane perforation (5.4%, 95% CI: 2.7%-8.8%). The results also presented higher patient satisfaction for TSFA. With the limitations of the present study (high risk of bias in individual studies), it can be concluded that there was no significant difference in implant survival, Schneiderian membrane perforation and MBL between two approaches in sites with RBH ≤6 mm.

Methods for Evaluating the Efficacy of Medical Castration: A Systematic Review.

Measuring serum testosterone determination during medical castration is recommended by prostate cancer (PCa) guidelines to assess its efficacy and define castration resistance. It has been suggested that other biochemical compounds, such as free testosterone or luteinising hormone (LH), could also assess castration efficacy. We aimed to analyse the current evidence for serum biochemical compounds that could be appropriate candidates for evaluating medical castration efficacy. A systematic review was conducted after two investigators independently searched the literature in the PubMed, Cochrane Library, and EMBASE databases published between January 1980 and February 2023. Their searches used the medical subject headings 'prostatic neoplasms', 'testosterone and androgen antagonists', 'gonadotropin-releasing hormone/analogues and derivatives', 'free testosterone', and 'luteinising hormone'. Studies were selected according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses criteria, and their eligibility was based on the Participants, Intervention, Comparator, and Outcome strategy. The search was limited to original articles published in English. Among the 6599 initially identified titles, 15 original studies analysing the clinical impact of serum testosterone levels in PCa patients undergoing androgen deprivation therapy (ADT) were selected for evidence acquisition. The risk of bias in individual studies was assessed using the Quality Assessment of Diagnostic Accuracy Studies 2 tool. All selected studies used immunoassays to measure serum testosterone, although only methods based on liquid or gas chromatography and mass spectrometry are recommended to measure low testosterone concentrations. The reported series were not uniform in clinical stage, ADT types, and the time or number of serum testosterone measurements. Only some studies found low serum testosterone levels (<20 or <32 ng/dL) associated with greater survival free of biochemical progression and castration resistance. We conclude that little current evidence justifies the measurement of serum testosterone during ADT using no appropriate methods. No reported longitudinal studies have examined the clinical impact of serum testosterone measured using liquid chromatography with tandem mass spectrometry (LC-MSMS), free testosterone, or LH in PCa patients undergoing medical castration. We conclude that well-designed longitudinal studies examining the clinical impact of serum testosterone measured with LC-MSMS, serum-free testosterone, and LH on biochemical progression and castration resistance in PCa patients undergoing neo-adjuvant castration in radiation therapy or continuous castration are needed.

Effect of e-health interventions on HIV prevention: a protocol of systematic review and meta-analysis

BackgroundGlobal epidemiological data indicates that despite implementation of multiple interventions and significant financial investment, the HIV/AIDS epidemic remained inadequately controlled as of 2020. E-health presents a novel approach in delivering health information and health care and has gained popularity in HIV prevention worldwide. However, evidence on the effectiveness of e-health interventions on HIV prevention among diverse populations remains inadequate. Our study aims to systematically evaluate the effectiveness of varying e-health interventions on HIV prevention, with the objective of providing data support and guidance for the development of future e-health HIV intervention strategies.MethodsA systematic search of electronic English databases, including MEDLINE through PubMed, Embase, Scopus, and Web of Science, along with three Chinese databases, including National Knowledge Infrastructure (CNKI), Chinese Wanfang Digital Periodicals (WANFANG), and Chinese Science and Technology Periodicals (VIP) database, will be conducted for the period of 1 January 1980 to 31 December 2022. Additionally, gray literature and unpublished trials in trial registers will be searched. Studies aimed at HIV prevention through e-health interventions, with full-text publications available in either English or Chinese, will be included. Study types will be limited to RCT, cluster RCT, and quasi-experiment study. The risk of bias in individual studies will be assessed following the guideline highlighted by the Cochrane Handbook for Systematic Reviews of Interventions. The outcomes will cover cognitive, behavioral, psychological, management, and biological measures of individuals involved in e-health interventions. The quality of evidence will be assessed by the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) approach. Ultimately, a systematic review with meta-analysis will be conducted to compare the effectiveness of e-health interventions among diverse populations.DiscussionThis systematic review seeks to establish novel insights into the effectiveness of e-health interventions in diverse populations worldwide. It will inform the design and use of e-health interventions to optimize HIV-related strategies.Systematic review registrationPROSPERO CRD42022295909.

Effects of Tai Chi and Qigong on cognitive and physical functions in older adults: systematic review, meta-analysis, and meta-regression of randomized clinical trials

BackgroundOlder adults experience age-related declines in physical and cognitive functions due to interactions between aging and chronic diseases. Tai Chi and Qigong (TCQ) might be beneficial in improving the physical function and delaying the cognitive decline of this population. The potential underlying mechanism was explored to determine the effects of TCQ on cognitive function via direct or indirect pathways.PurposeThe objective of this systematic review was to determine the effects of TCQ on cognitive and physical functions in older adults using meta-analysis, and to determine the impact of TCQ on cognitive function while controlling for physical function using a meta-regression approach.MethodsA systematic search of 13 electronic databases (in English, Korean, and Chinese languages) identified 10,292 potentially eligible studies published between inception and May 2022. The bias in individual studies was assessed using the Cochrane Risk of Bias (version 2.0) tool. The heterogeneity of the studies was evaluated using a 95% prediction interval, and the meta-analysis and meta-regression were implemented using the Comprehensive Meta-Analysis (version 3) software.ResultsOur search identified 17 randomized studies (n = 2,365, mean age = 70.3 years). The results of the meta-analysis that used a random-effects model indicated that TCQ had significant effects on both cognitive (Hedges' g = 0.29, 95% confidence interval [CI] = 0.17 to 0.42) and physical (Hedges' g = 0.32, 95% CI = 0.19 to 0.44) functions. We used meta-regression to explore the effect size of TCQ in association with physical function level. The regression model was significant (Q = 25.01, p = .070), and 55% of the heterogeneity was explained by physical function as a moderator variable. The effects of TCQ on cognitive function remained significant in this model when controlling for the effect of physical function (β = 0.46, p = .011).ConclusionThis meta-regression of 17 randomized studies strongly suggests that TCQ has beneficial effects on physical and cognitive functions in older adults. The effect of TCQ on cognitive function remained significant after taking into account the significant effects of physical function as a moderator. The findings imply the potential health benefits of TCQ by promoting cognitive function in older adults directly and indirectly through enhancing physical function.PROSPERO registration number*PROSPERO international prospective register of systematic reviews, registration ID CRD42023394358.

Effect of plant milk consumption on childhood growth: protocol for a systematic review

IntroductionThere has been considerable debate about whether plant milks can support the nutritional requirements of growing children. The proposed systematic review aims to assess the evidence on the relationship between...

Home-Based Exercise Therapy in the Management of Intermittent Claudication: A Systematic Review and Meta-Analysis.

The current literature strongly supports the use of supervised exercise therapy (SET) as the first-line treatment for symptomatic peripheral arterial disease (PAD) such as intermittent claudication (IC). However, this form of treatment remains underutilised in clinical practice. The home-based exercise therapy (HBET), in which patients must conduct themselves unsupervised is generally less effective than SET in terms of improving functional walking capacity. Nevertheless, it may be a useful alternative where SET is unavailable. The objective of this systematic review is to determine the effectiveness of HBET in reducing symptoms of IC in patients with PAD. Studies eligible for inclusion in this systematic review were parallel-group randomised controlled trials (RCTs) published in the English language that compared the effect of HBET to a comparator arm (SET or no exercise/attention control) in adults with PAD and IC. Studies were eligible if outcome measures were available at baseline and at 12 weeks of follow-up or more. The electronic databases PubMed, Google Scholar, and the Cochrane Library were searched from the earliest records up to January 2021. The Cochrane Collaboration risk of bias tool for RCTs (RoB 2)was used to assess the risk of bias in individual studies, and the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) classification system was used to appraise the quality of evidence for each outcome across all studies. The primary investigator independently collected, pooled, and analysed the data. The data was then entered into the ReviewManager 5 (RevMan 5) software, and a meta-analysis was performed by using a fixed or random effects model depending on the presence or absence of statistical heterogeneity. The review author identified seven RCTs involving a total of 754 patients which were included in this study. Overall, the risk of bias in the included studies was moderate. Even though the results were variable, this analysis supported the ability of HBET to improve functional walking capacity and self-reported quality of life (QoL) to an extent. This review shows that a home-based exercise intervention with regular professional support and encouragement is beneficial in improving functional walking capacity as well as some aspects of QoL in patients with PAD and IC when compared to no exercise. However, when HBET is compared to hospital-based supervised exercise intervention, SET yields greater benefits.

Effects of citrulline on endurance performance in young healthy adults: a systematic review and meta-analysis.

Citrulline is a popular dietary supplement, primarily thought to exert ergogenic effects on exercise performance through the enhancement of nitric oxide (NO) synthesis and ammonia buffering. However, recent findings surrounding citrulline's effect on endurance performance have been inconsistent. A systematic review and meta-analysis of the relevant literature have yet to be undertaken. To determine if acute ingestion of citrulline has an ergogenic effect on endurance performance in young healthy adults. A systematic search of three databases was undertaken to find peer-reviewed randomized controlled trials (RCTs) published in English investigating the effects of citrulline supplementation on endurance performance in young healthy adults. Two independent investigators completed a three-phased screening procedure against pre-determined eligibility criteria. Included studies evaluated loading or bolus dosage regimes of citrulline in participants aged 18 or over that were at least recreationally active. Outcome measures focused on time-to-completion (TTC) or time-to-exhaustion (TTE) in continuous submaximal intensity exercise. Cochrane's Risk of Bias 2 (RoB 2) tool was used to assess the risk of bias in individual studies. Meta-analysis was conducted using a fixed-effects model to pool the weighted estimate of standardized mean differences (SMD) across studies. A chi-squared test assessed heterogeneity between studies. This review was conducted and reported in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Nine studies (n = 158 participants) met the eligibility criteria; five reported TTE outcomes (I2 = 0%, χ2 = 0.37, df = 4, P = 0.99) and four reported TTC outcomes (I2 = 0%, χ2 = 0.46, df = 3, P = 0.93), both with a low between-study heterogeneity. The results of the meta-analyses showed no significant difference in the endurance performance measures, TTE (pooled SMD = 0.03 [-0.27, 0.33]) and TTC (pooled SMD = -0.07 [-0.50, 0.15]), after acute ingestion of citrulline supplementation or a control in young healthy adults. The current evidence suggests no significant benefit of citrulline supplementation for endurance performance. However, the small evidence base requires further research to fully evaluate this topic. Recommendations include a focus on female populations; higher continuous doses of citrulline over seven days; and TTC outcome measures over longer distances to simulate competition.

Effects of almond intake on oxidative stress parameters: A systematic review and meta-analysis of clinical trials.

Several randomized controlled trials (RCTs) have shown that almonds can improve oxidative stress indices, but the results are controversial. Therefore, the goal of this research was to carry out a systematic review and meta-analysis of all RCTs that evaluated the effect of almonds on selected oxidative stress indices. A systematic search was conducted up to April 2022 on PubMed, Scopus, Web of Science, and Google Scholar. We have selected the studies that investigated the effects of almonds on malondialdehyde (MDA), and oxidized low-density lipoprotein (Ox-LDL) levels in adults. Data were pooled by using the random-effects model. The risk of bias in individual studies was assessed using the Cochrane Collaboration risk of bias tool. Seven RCTs involving 424 participants were analyzed. The results indicated that almond intake led to a significant decrease in MDA levels (WMD: -6.63nmol/ml; 95% CI: -8.72 to -4.54; P<0.001). However, no significant effect was observed on Ox-LDL (Hedges' g: -0.12; 95% CI: -0.34 to 0.10; P=0.28). Sensitivity analysis showed that overall estimates were not affected by the elimination of any study. We did not observe any evidence regarding publication bias. The present meta-analysis suggests that almond intake can improve MDA levels and might play a beneficial role in the reinforcement of the antioxidant defense system and amelioration of oxidative stress in adults. There is a need for more studies with larger groups to better estimate this effect.

Effectiveness of handwashing with soap for preventing acute respiratory infections in low-income and middle-income countries: a systematic review and meta-analysis

Acute respiratory infection (ARI) is a leading cause of morbidity and mortality globally, with 83% of ARI mortality occurring in low-income and middle-income countries (LMICs) before the COVID-19 pandemic. We aimed to estimate the effect of interventions promoting handwashing with soap on ARI in LMICs. In our systematic review and meta-analysis, we searched MEDLINE, Embase, Web of Science, Scopus, Cochrane Library, Global Health, and Global Index Medicus for studies of handwashing with soap interventions in LMICs from inception to May 25, 2021. We included randomised and non-randomised controlled studies of interventions conducted in domestic, school, or childcare settings. Interventions promoting hand hygiene methods other than handwashing with soap were excluded, as were interventions in health-care facilities or the workplace. The primary outcome was ARI morbidity arising from any pathogen for participants of any age. Secondary outcomes were lower respiratory infection, upper respiratory infection, influenza confirmed by diagnostic test, COVID-19 confirmed by diagnostic test, and all-cause mortality. We extracted relative risks (RRs), using random-effects meta-analysis to analyse study results, and metaregression to evaluate heterogeneity. We assessed risk of bias in individual studies using an adapted Newcastle-Ottawa scale, and assessed the overall body of evidence using a Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) approach. The study is registered with PROSPERO, CRD42021231414. 26 studies with 161 659 participants met inclusion criteria, providing 27 comparisons (21 randomised). Interventions promoting handwashing with soap reduced any ARI compared with no handwashing intervention (RR 0·83 [95% CI 0·76-0·90], I2 88%; 27 comparisons). Interventions also reduced lower respiratory infections (0·78 [0·64-0·94], I2 64%; 12 comparisons) and upper respiratory infections (0·74 [0·59-0·93], I2 91%; seven comparisons), but not test-confirmed influenza (0·94 [0·42-2·11], I2 90%; three comparisons), test-confirmed COVID-19 (no comparisons), or all-cause mortality (prevalence ratio 0·95 [95% CI 0·71-1·27]; one comparison). For ARI, no heterogeneity covariates were significant at p<0·1 and the GRADE rating was moderate certainty evidence. Interventions promoting handwashing with soap can reduce ARI in LMICs, and could help to prevent the large burden of respiratory disease. Bill & Melinda Gates Foundation, Reckitt Global Hygiene Institute, and UK FCDO.

Thiazide diuretics alone or combined with potassium-sparing diuretics to treat hypertension: a systematic review and network meta-analysis of randomized controlled trials.

The magnitude of blood pressure (BP)-lowering effects and decrease of the adverse effects of thiazide diuretics provided by potassium-sparing diuretics remain uncertain. The aim of this study was to compare the BP-lowering efficacy and the incidence of adverse effects of high (T+) and low-dose (T-) thiazide diuretics, alone or combined with high (PS+) or low-dose (PS-) potassium-sparing diuretics in patients with primary hypertension. A systematic literature search was performed in PubMed/MEDLINE, the Cochrane Central Register of Controlled Trials, Embase, Web of Science, Scopus and LILACS. Randomized double-blind placebo or active-controlled trials (RCT) with 3 weeks to 1 year of follow-up were included. Sample size, mean and standard deviation from baseline, follow-up and change from baseline values were extracted by two independent reviewers. Pairwise random effect models and Bayesian network meta-analysis models were used to compare the effects of treatments. The risk of bias in individual studies was assessed using the Rob 1.0 tool. The primary outcome was the mean difference in office SBP. Secondary outcomes were the mean difference in biochemical parameters and the incidence of nonmelanoma skin cancer. Two hundred and seventy-six double-blind RCTs involving 58 807 participants (mean age: 55 years; 45% women) were included. All treatment groups were more effective than placebo in lowering BP, with mean differences (MDs) of change from baseline ranging from -7.66 mmHg [95% credible interval (95% CrI), -8.53 to -6.79] for T- to -12.77 mmHg (95% CrI, -15.22 to -10.31) for T+PS-. T+ alone or combined with potassium-sparing was more effective in reducing BP than T-. The surface under the cumulative ranking curve (SUCRA) estimated ranking showed that the best effectiveness in lowering SBP was found for T+PS- (0.69), T+PS+ (0.65) and T+ (0.54). Compared with placebo, all treatments (except T-PS-) were associated with more potassium reduction and T+ compared with all other treatments and T- when compared with T-PS-. Compared with placebo, all active treatments (except T+PS+) showed higher elevations of uric acid. The increase of plasma glucose promoted by thiazides alone was reduced by potassium-sparing agents. Thiazides with potassium-sparing diuretics are associated with increased BP-lowering efficacy compared with thiazides alone while minimizing hypokalaemia and hyperglycaemia. These findings demonstrate that thiazide and potassium-sparing diuretic combination is preferable to thiazide alone in treating hypertension.

Congenital Adrenal Hyperplasia and Human Leukocyte Antigen B: A Meta-Analysis.

The link between specific human leukocyte antigen (HLA)-B genes and congenital adrenal hyperplasia (CAH) has been a subject of interest. This study investigates the association between specific HLA-B haplotypes and CAH through a meta-analysis. Google Scholar was used as a database. Articles were included if the research was conducted between 1970 and 2022, was not a meta-analysis, and had odds ratios or enough data points to calculate an odds ratio. The National Institutes of Health (NIH) quality assessment tool of case-control studies was used to evaluate the risk of bias in individual studies, and MetaXL was used to generate data and create a forest plot for analysis. Twelve studies met the selection criteria and were included in the study (641 patients and 3,614 controls). Two HLA-B haplotypes showed increased odds of CAH compared to controls: B14 (OR=3.81; 95%CI=2.88, 5.05; I2=3%) and B35 (OR=1.88; 95%CI=1.22, 2.90; I2=25%). All other HLAs either showed no significant effect or had high heterogeneity. The results suggest that specific HLA-B haplotypes have increased odds of developing CAH, specifically B14 and B35. These findings may prove helpful in the pre- and post-natal diagnosis of CAHas well as the identification of carriers and prediction of patient prognosis.