Overall High Risk Of Bias Research Articles

Systematic review and pooled analysis of randomized controlled trials in countries of the Gulf Cooperation Council (GCC): Methods and quality assessment.

To describe variations in characteristics of randomized controlled trials conducted in the Gulf Cooperation Council (GCC) countries, and critically appraising the quality of design, conduct and analysis of the trials. We carried out a systematically comprehensive electronic search of articles published between 1990 and 2018 and indexed in several databases: i) MEDLINE/PubMed, ii) EMBASE, iii) Cochrane Central Register of Controlled Trials (CENTRAL), iv) ClinicalTrials.gov, and v) World Health Organization International Clinical Trials Registry Platform. We summarized the overall risk of bias present in all analyzed studies using the Cochrane Collaboration risk of bias tool (CCRBT). A remarkable shift in numbers of publications from 2006 onwards was found. The largest number of publications were from Saudi Arabia and consisted of hospitals/clinics based studies. Lack of randomization was found in the majority of reports, and nearly three-fourth of the studies involved the use of intention-to-treat (ITT) principle. However, the proportion of adequately generated random sequence methods has increased yearly, and this increase accounted for a relatively large proportion over the latter half of the studied period (p<0.001), in contrast to the proportion of allocation concealment and blinding. Journal impact factor was significantly correlated with the quality of random sequence generation (r=0.145; p=0.014). The randomization methods have gained more attention over the last 3 decades. Secondly, Journal impact factor can serve as an indicator of randomization quality. To mitigate the large rate of overall high risk of bias in GCC studies, high-quality trials must be considered by ensuring adequate allocation concealment and blinding methods. PROSPERO No. ID: CRD42022310331.

Home-Based Specialized Pediatric Palliative Care: A Systematic Review and Meta-Analysis.

Although specialized pediatric palliative care (SPPC) teams increasingly provide home-based care, the evidence of its impact has not yet been systematically evaluated. To examine the impact of home-based SPPC in children and adolescents with life-limiting conditions, regarding place of death, quality of life and symptom burden. We searched Medline, EMBASE, CINAHL, PsycINFO, the Cochrane Central Register of Controlled Trials, Web of Science and Scopus for studies comparing children and adolescents with life-limiting conditions receiving home-based SPPC with children and adolescents not receiving home-based SPPC, or studies reporting before-and-after measurements. We included studies that reported on place of death, quality of life and/or symptoms. Two authors independently screened the articles, extracted data, and assessed quality. Results were synthesized as a systematic narrative synthesis and meta-analysis, using a random-effects model. We included five studies, which reported on 392 children and adolescents. Meta-analysis showed that receiving home-based SPPC was associated with a more than fourfold increased likelihood of home death (risk ratio 4.64, 95% confidence interval 3.06-7.04; 3 studies; n=296). Most studies reported improved quality of life and reduced symptom burden. The included studies were of low to moderate quality with a high risk of bias. This systematic review suggests that home-based SPPC is associated with increased likelihood of home death, and might be associated with improved quality of life and reduced symptom burden. The small number of studies and an overall high risk of bias, however, makes the overall strength of evidence low.

Piperacillin/tazobactam versus carbapenems in patients with severe bacterial infections: A systematic review with meta-analysis.

Piperacillin/tazobactam or meropenem are often used to treat patients with severe bacterial infections. We aimed to compare the desirable and undesirable effects of empirical and/or definitive piperacillin/tazobactam versus carbapenems in patients with severe bacterial infections. We searched PubMed, Embase, CENTRAL, Epistemonikos, and trial registers for randomised clinical trials of empirical and/or definitive piperacillin/tazobactam versus carbapenems in adult patients with severe bacterial infection (i.e., any bacterial infection requiring hospitalisation). The primary outcome was all-cause short-term mortality within 90 days. Secondary outcomes were all-cause long-term mortality, adverse events, quality of life, days alive without or duration of life support, secondary infections, selection of fungi or resistant bacteria, and days alive and out of hospital or hospital length of stay. We calculated relative risks (RRs) using random effects and fixed effect meta-analyses along with trial sequential analyses. We included 31 trials (n=8790 patients) with overall high risk of bias. The RR for all-cause short-term mortality was 1.16 (95% confidence interval [CI]: 0.94-1.43, low certainty evidence), for adverse events 1.00 (98% CI: 0.96-1.04, moderate certainty evidence), for secondary infections 1.13 (98% CI: 0.76-1.68, very low certainty evidence), and for selection of fungi or resistant bacteria 1.61 (98% CI: 0.89-2.89, very low certainty evidence). There were no or limited data for the remaining outcomes. Based on very low or low certainty evidence, piperacillin/tazobactam may be associated with less favourable outcomes in patients with severe bacterial infections as compared with carbapenems, but the information size for a robust conclusion has not been reached.

Increased inhaled corticosteroids for treating acute asthma exacerbations

Increased inhaled corticosteroids for treating acute asthma exacerbations

Planned hospital birth compared with planned home birth for pregnant women at low risk of complications.

Observational studies of increasingly better quality and in different settings suggest that planned hospitalbirth in many places does not reduce mortality and morbidity but increases the frequency ofinterventions and complications. Euro-Peristat (part of the European Union's Health Monitoring Programme) has raised concerns about iatrogenic effects of obstetric interventions, and the World Health Organization (WHO) has raised concern thatthe increasing medicalisation of childbirth tends to undermine women's own capability to give birth and negatively impacts their childbirth experience. This is an update of a Cochrane Review first published in 1998, and previously updated in 2012. To compare the effects of planned hospital birth with planned home birth attended by a midwife or others with midwifery skills and backed up by a modern hospital system in case a transfer to hospital should turn out to be necessary. The primary focus is on women with an uncomplicated pregnancy and low risk of medical intervention during birth. SEARCH METHODS: For this update, we searched Cochrane Pregnancy and Childbirth's Trials Register (which includes trials from CENTRAL, MEDLINE, Embase, CINAHL, WHO ICTRP, and conference proceedings), ClinicalTrials.gov (16 July 2021), and reference lists of retrieved studies. Randomised controlled trials (RCTs) comparing planned hospital birth with planned home birth in low-risk women as described in the objectives. Cluster-randomised trials, quasi-randomised trials, and trials published only as an abstract were also eligible. Two review authors independently assessed trials for inclusion and risk of bias, extracted data, and checked the data for accuracy. We contacted study authors for additional information. We assessed the certainty of the evidence using the GRADE approach. MAIN RESULTS: We included one trial involving 11 participants. This was a small feasibility study to show that well-informed women - contrary to common beliefs - were prepared to be randomised. This update did not identify any additional studies for inclusion, but excluded one study that had been awaiting assessment. The included study was at high risk of bias for three out of seven risk of bias domains. The trial did not report on five of the seven primary outcomes, and reported zero events for one primary outcome (caesarean section), and non-zero events for the remaining primary outcome (baby not breastfed). Maternal mortality, perinatal mortality (non-malformed), Apgar < 7 at 5 minutes, transfer to neonatal intensive care unit, and maternal satisfaction were not reported. The overall certainty of the evidence for the two reported primary outcomes was very low according to our GRADE assessment (downgraded two levels for high overall risk of bias (due to high risk of bias arising from lack of blinding, high risk of selective reporting and lack of ability to check for publication bias) and two levels for very serious imprecision (single study with few events)). AUTHORS' CONCLUSIONS: This review shows that for selected, low-risk pregnant women, the evidence from randomised trials to support that planned hospital birth reduces maternal or perinatal mortality, morbidity, or any other critical outcome is uncertain. As the quality of evidence in favour of home birth from observational studies seems to be steadily increasing, it might be just as important to prepare a regularly updated systematic review including observational studies as described in the Cochrane Handbook for Systematic Reviews of Interventions as to attempt to set up new RCTs. As women and healthcare practitioners may be aware of evidence from observational studies, and as the International Federation of Gynecology and Obstetrics and the International Confederation of Midwives collaboratively conclude that there is strong evidence that out-of-hospital birth supported by a registered midwife is safe, equipoise may no longer exist, and randomised trials may now thus be considered unethical or hardly feasible.

Artificial intelligence as a diagnostic aid in cross-sectional radiological imaging of surgical pathology in the abdominopelvic cavity: a systematic review

ObjectivesThere is emerging use of artificial intelligence (AI) models to aid diagnostic imaging. This review examined and critically appraised the application of AI models to identify surgical pathology from radiological...

Risk Prediction Models for Cardiotoxicity of Chemotherapy Among Patients With Breast Cancer

Cardiotoxicity is a serious adverse effect that can occur in women undergoing treatment for breast cancer. Identifying patients who will develop cardiotoxicity remains challenging. To identify, describe, and evaluate all prognostic models developed to predict cardiotoxicity following treatment in women with breast cancer. This systematic review searched the Medline, Embase, and Cochrane databases up to September 22, 2021, to include studies developing or validating a prediction model for cardiotoxicity in women with breast cancer. The Prediction Model Risk of Bias Assessment Tool (PROBAST) was used to assess both the risk of bias and the applicability of the prediction modeling studies. Transparency reporting was assessed with the Transparent Reporting of a Multivariable Prediction Model for Individual Prognosis or Diagnosis (TRIPOD) tool. After screening 590 publications, we identified 7 prognostic model studies for this review. Six were model development studies and 1 was an external validation study. Outcomes included occurrence of cardiac dysfunction (echocardiographic parameters), heart failure, and composite clinical outcomes. Model discrimination, measured by the area under receiver operating curves or C statistic, ranged from 0.70 (95% IC, 0.62-0.77) to 0.87 (95% IC, 0.77-0.96). The most common predictors identified in final prediction models included age, baseline left ventricular ejection fraction, hypertension, and diabetes. Four of the developed models were deemed to be at high risk of bias due to analysis concerns, particularly for sample size, handling of missing data, and not presenting appropriate performance statistics. None of the included studies examined the clinical utility of the developed model. All studies met more than 80% of the items in TRIPOD checklist. In this systematic review of the 6 predictive models identified, only 1 had undergone external validation. Most of the studies were assessed as being at high overall risk of bias. Application of the reporting guidelines may help future research and improve the reproducibility and applicability of prediction models for cardiotoxicity following breast cancer treatment.

Menstrual Cycle, Glucose Control and Insulin Sensitivity in Type 1 Diabetes: A Systematic Review

The correlation between the menstrual cycle and glucose control in type 1 diabetes has been the focus of several studies since the 1920s, but a few critical aspects made it particularly challenging to reach conclusive evidence. The aim of this systematic review is to reveal more solid information about the impact of the menstrual cycle on glycaemic outcomes and insulin sensitivity in type 1 diabetes and highlight the less researched areas. The literature was searched by two authors independently using PubMed/MEDLINE, Embase and Scopus (last search on 2 November 2022). The retrieved data did not allow us to perform a meta-analysis. We included 14 studies published between 1990 and 2022, with sample sizes from 4 to 124 patients. We found a wide heterogeneity in the definition of the menstrual cycle phases, glucose metrics, techniques for determining insulin sensitivity, hormonal assessment and other interfering factors considered, with an overall high risk of bias. There is no conclusive evidence, and published data do not allow us to achieve quantitative results. In a subset of patients, a possible worsening of insulin sensitivity and hyperglycaemia in the luteal phase could be observed. From the clinical standpoint, a cautious strategy based on patient-specific patterns can be considered until new, solid evidence is obtained.

Predictive Modeling for Readmission to Intensive Care: A Systematic Review.

PubMed, Web of Science, Cochrane, and Embase. Primary literature that reported the development or validation of ICU readmission prediction models within from 2010 to 2021. Relevant study information was extracted independently by two authors using the Critical Appraisal and Data Extraction for Systematic Reviews of Prediction Modelling Studies checklist. Bias was evaluated using the Prediction model Risk Of Bias ASsessment Tool. Data sources, modeling methodology, definition of outcomes, performance, and risk of bias were critically evaluated to elucidate relevant relationships. Thirty-three articles describing models were included. Six studies had a high overall risk of bias due to improper inclusion criteria or omission of critical analysis details. Four other studies had an unclear overall risk of bias due to lack of detail describing the analysis. Overall, the most common (50% of studies) source of bias was the filtering of candidate predictors via univariate analysis. The poorest performing models used existing clinical risk or acuity scores such as Acute Physiologic Assessment and Chronic Health Evaluation II, Sequential Organ Failure Assessment, or Stability and Workload Index for Transfer as the sole predictor. The higher-performing ICU readmission prediction models used homogenous patient populations, specifically defined outcomes, and routinely collected predictors that were analyzed over time. Models predicting ICU readmission can achieve performance advantages by using longitudinal time series modeling, homogenous patient populations, and predictor variables tailored to those populations.

Effectiveness of Thromboprophylaxis Agents Following Hip Fracture: A Systematic Review and Network Meta-Analysis.

Multiple studies have compared different pharmacologic thromboprophylaxis agents after hip fracture surgery, including aspirin, unfractionated heparin (UFH), low-molecular-weight heparin (LMWH), direct oral anticoagulants (DOAC), and warfarin, resulting in variability in clinical practice. To guide clinical management, a systematic review and network meta-analysis (NMA), which enables the simultaneous assessment of the effects of multiple interventions for the same patient population, was performed. This study aimed to determine the comparative effectiveness of thromboprophylaxis in reducing venous thromboembolism (VTE) in patients with surgically treated hip fractures. The primary outcome was the effect of the treatment on the VTE rate, and the secondary outcome was the treatment effect on the bleeding rate. Relevant studies were identified by a systematic search of Embase, MEDLINE, and the Cochrane Central Register of Controlled Trials (CENTRAL) from January 2000 to February 2022. Title, abstract, and full-text screening; data extraction; and risk-of-bias assessment were performed. All studies examining thromboprophylaxis interventions (DOAC, LMWH, UFH, aspirin, and warfarin) in patients with a surgically treated hip fracture were included. Bayesian NMA was performed, and dichotomous outcome data were pooled using the odds ratio. Interventions were ranked using the surface under the cumulative ranking curve (SUCRA) for each outcome. A total of 19 studies were included after the screening of 466 citations and 77 full-text articles. Of the included studies, 15 studies had a high overall risk of bias. The NMA of the VTE outcome included 19 studies, 49,409 participants, and 6 thromboprophylaxis interventions. The NMA of the bleeding outcome included 3 studies, 18,163 participants, and 3 interventions. The mean age ranged from 43.5 to 86.2 years among the included studies. No thromboprophylaxis intervention was statistically different from any other intervention in its effect on the VTE or bleeding rate in hip fracture patients. This NMA demonstrated that there was no difference between the thromboprophylaxis interventions in reducing VTE or bleeding rates in hip fracture patients. More robust randomized controlled trials are needed to determine the most effective thromboprophylaxis interventions for patients with hip fractures. Therapeutic Level II. See Instructions for Authors for a complete description of levels of evidence.

The Influence of n-3PUFA Supplementation on Muscle Strength, Mass, and Function: A Systematic Review and Meta-Analysis.

The effects of omega 3 polyunsaturated fatty acids (n-3PUFA) supplementation on skeletal muscle are currently unclear. The purpose of this systematic review was to synthesize all available evidence regarding the influence of n-3PUFA supplementation on muscle mass, strength, and function in healthy young and older adults. Four databases were searched (Medline, Embase, Cochrane CENTRAL, and SportDiscus). Predefined eligibility criteria were determined according to Population, Intervention, Comparator, Outcomes, and Study Design. Only peer-reviewed studies were included. The Cochrane RoB2 Tool and the NutriGrade approach were used to access risk of bias and certainty in evidence. Effect sizes were calculated using pre-post scores and analyzed using a three-level, random-effects meta-analysis. When sufficient studies were available, subanalyses were performed in the muscle mass, strength, and function outcomes according to participant's age (<60 or ≥60 years), supplementation dosage (<2 or ≥2 g/day), and training intervention ("resistance training" vs. "none or other"). Overall, 14 individual studies were included, total 1443 participants (913 females; 520 males) and 52 outcomes measures. Studies had high overall risk of bias and consideration of all NutriGrade elements resulted in a certainty assessment of moderate meta-evidence for all outcomes. n-3PUFA supplementation had no significant effect on muscle mass (standard mean difference [SMD] = 0.07 [95% CI: -0.02, 0.17], P = 0.11) and muscle function (SMD = 0.03 [95% CI: -0.09, 0.15], P = 0.58), but it showed a very small albeit significant positive effect on muscle strength (SMD = 0.12 [95% CI: 0.006, 0.24], P = 0.04) in participants when compared with placebo. Subgroup analyses showed that age, supplementation dose, or cosupplementation alongside resistance training did not influence these responses. In conclusion, our analyses indicated that n-3PUFA supplementation may lead to very small increases in muscle strength but did not impact muscle mass and function in healthy young and older adults. To our knowledge, this is the first review and meta-analysis investigating whether n-3PUFA supplementation can lead to increases in muscle strength, mass, and function in healthy adults. Registered protocol: doi.org/10.17605/OSF.IO/2FWQT.

Vaccines for the common cold.

The common cold is a spontaneously remitting infection of the upper respiratory tract, characterised by a runny nose, nasal congestion, sneezing, cough, malaise, sore throat, and fever (usually < 37.8 ºC). Whilst the common cold is generally not harmful, it is a cause of economic burden due to school and work absenteeism. In the United States, economic loss due to the common cold is estimated at more than USD 40 billion per year, including an estimate of 70 million workdays missed by employees, 189 million school days missed by children, and 126 million workdays missed by parents caring for children with a cold. Additionally, data from Europe show that the total cost per episode may be up to EUR 1102. There is also a large expenditure due to inappropriate antimicrobial prescription. Vaccine development for the common cold has been difficult due to antigenic variability of the common cold viruses; even bacteria can act as infective agents. Uncertainty remains regarding the efficacy and safety of interventions for preventing the common cold in healthy people, thus we performed an update of this Cochrane Review, which was first published in 2011 and updated in 2013 and 2017. To assess the clinical effectiveness and safety of vaccines for preventing the common cold in healthy people. We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (April 2022), MEDLINE (1948 to April 2022), Embase (1974 to April 2022), CINAHL (1981 to April 2022), and LILACS (1982 to April 2022). We also searched three trials registers for ongoing studies, and four websites for additional trials (April 2022). We did not impose any language or date restrictions. Randomised controlled trials (RCTs) of any virus vaccine compared with placebo to prevent the common cold in healthy people. We used Cochrane's Screen4Me workflow to assess the initial search results. Four review authors independently performed title and abstract screening to identify potentially relevant studies. We retrieved the full-text articles for those studies deemed potentially relevant, and the review authors independently screened the full-text reports for inclusion in the review, recording reasons for exclusion of the excluded studies. Any disagreements were resolved by discussion or by consulting a third review author when needed. Two review authors independently collected data on a data extraction form, resolving any disagreements by consensus or by involving a third review author. We double-checked data transferred into Review Manager 5 software. Three review authors independently assessed risk of bias using RoB 1 tool as outlined in the Cochrane Handbook for Systematic Reviews of Interventions. We carried out statistical analysis using Review Manager 5. We did not conduct a meta-analysis, and we did not assess publication bias. We used GRADEpro GDT software to assess the certainty of the evidence and to create a summary of findings table. MAIN RESULTS: We did not identify any new RCTs for inclusion in this update. This review includes one RCT conducted in 1965 with an overall high risk of bias. The RCT included 2307 healthy young men in a military facility, all of whom were included in the analyses, and compared the effect of three adenovirus vaccines (live, inactivated type 4, and inactivated type 4 and 7) against a placebo (injection of physiological saline or gelatin capsule). There were 13 (1.14%) events in 1139 participants in the vaccine group, and 14 (1.19%) events in 1168 participants in the placebo group. Overall, we do not know if there is a difference between the adenovirus vaccine and placebo in reducing the incidence of the common cold (risk ratio 0.95, 95% confidence interval 0.45 to 2.02; very low-certainty evidence). Furthermore, no difference in adverse events when comparing live vaccine preparation with placebo was reported. We downgraded the certainty of the evidence to very low due to unclear risk of bias, indirectness because the population of this study was only young men, and imprecision because confidence intervals were wide and the number of events was low. The included study did not assess vaccine-related or all-cause mortality. AUTHORS' CONCLUSIONS: This Cochrane Review was based on one study with very low-certainty evidence, which showed that there may be no difference between the adenovirus vaccine and placebo in reducing the incidence of the common cold. We identified a need for well-designed, adequately powered RCTs to investigate vaccines for the common cold in healthy people. Future trials on interventions for preventing the common cold should assess a variety of virus vaccines for this condition, and should measure such outcomes as common cold incidence, vaccine safety, and mortality (all-cause and related to the vaccine).

The effects of outdoor versus indoor exercise on psychological health, physical health, and exercise behaviour: a systematic review of longitudinal trials

AbstractBackgroundA growing body of research is exploring the potential added health benefits of exercise when it is performed outdoors in nature, as compared with indoors. We systematically reviewed longitudinal trials comparing the effects of exercise in outdoor versus indoor environments on psychological and physical health, and exercise behaviour.MethodsWe searched the following nine databases from inception to March 2021 for English‐language, peer‐reviewed articles: MEDLINE, Embase, PubMed, Scopus, Web of Science, CINAHL, SportsDiscus, GreenFile, CENTRAL. We included randomized and non‐randomized trials that compared multiple bouts of exercise in outdoor versus indoor environments, and that assessed at least one of the following main outcomes of interest: physical health, psychological health, or exercise behaviour. We assessed risk of bias using the Revised Cochrane risk‐of‐bias tool for randomized trials. At least two authors screened articles for eligibility, extracted data, and evaluated risk of bias, with discrepancies resolved by discussion with at least one other author. Due to outcome heterogeneity and a paucity of studies, we performed a narrative synthesis.ResultsWe identified 10 eligible trials from 12 papers, including seven randomized controlled trials. Participants’ (n = 496 total) demographics varied widely (mean age ranging from 11‐80 years). Most exercise protocols involved 30‐60 minutes of aerobic training (walking or running) at moderate to high intensity. Other forms of training included mixed aerobic and resistance training, agility, balance, and strength training, and dual‐task training. Exercise sessions took place one to 5 times per week for one to 18 weeks. Outcomes overlapped minimally between trials, with psychological outcomes assessed in seven trials, physical outcomes assessed in eight trials, and behavioural outcomes assessed in three trials. In total, 123 comparisons were made between outdoor and indoor exercise, including 33 significant comparisons, all of which favoured outdoor exercise. Interpretation of findings was hindered by an overall high risk of bias, unclear reporting, and high heterogeneity in reported outcomes.ConclusionThere is limited evidence for added health or behaviour benefits of chronic exercise in outdoor environments, as compared with indoors, and a need for future, high‐quality longitudinal trials with adequate power and clear reporting.

PP120 Fluorescent In Situ Hybridization (FISH) Vs Conventional Cytogenetic (CC) For Detecting High-Risk Genetic Mutations In Multiple Myeloma

IntroductionThe Revised International Staging System (R-ISS) International Myeloma Working Group (IMWG) recommends a minimal panel to detect high-risk cytogenetics (del17p, t[4;14], t[14;16]) for patients with multiple myeloma (MM). In the Brazilian Public Health System, the use of FISH is currently authorized for rare diseases only, not including MM. In 2021, the Brazilian National Committee for Health Technology Incorporation, with the purpose of broadening the use of FISH to MM patients, requested a review to be undertaken by the Health Technology Assessment Center of University of Campinas’ Teaching Hospital. This study presents the results of a meta-analysis comparing FISH vs CC to the detection of the above-mentioned aberrations in MM patients.MethodsOn 25 June 2021, a pre-structured search on four databases (Embase, MEDLINE, Cochrane and LILACS) was performed to identify studies comparing FISH and CC results in MM patients for the detection of high-risk cytogenetics (del17p, t[4;14], and t[14;16]) in MM patients’ bone marrow samples. Study selection, risk of bias assessment, data extraction (frequency of positive tests) and quality of evidence assessment were performed by two independent researchers. Conflicts were solved in agreement meetings with a third researcher. Meta-analysis was performed using frequency of positives to obtain Risk Difference (RD), a surrogate measure of the surplus positive tests between FISH and CC.ResultsFrom a total of 1346 rendered entries, 11 studies were selected. Only observational studies were available. These studies presented an overall high risk of bias (QUADAS-2). A total of 781 patients were assessed (653 evaluated by FISH and 719 by CC). Meta-analysis results showed that, for t(4;14) FISH detected 12 percent more samples (RD:0.12 [95% confidence interval (CI):0.06-0.19]). For t(14;16), FISH detected 0.42 percent more samples (RD:0.00 [95%CI:-0.01-0.02]). And for del17p, FISH detected 1.6 percent more samples (RD:0.12 [95%CI:0.04-0.20]).ConclusionsFISH appears to be more effective than CC on the detection of t(4;414) and del17p aberrations, and can be a useful tool in hematology practice. The results of t(14;16) presented non-superiority, probably due to the low frequency of this aberration.

The efficacy of physical activity interventions in reducing antisocial behavior: a meta-analytic review

ObjectivesThis systematic review and meta-analysis examines the efficacy of physical activity interventions in the reduction of antisocial behavior in children and adults. Several possible moderators, including study design, sample characteristics (age, proportion male, and sample type), control group, and outcome characteristics (type of activity, duration, frequency), were also investigated.MethodsA literature search was performed in the following databases: PubMed, Ebsco/SportDiscus, Ebsco/APA PsycINFO, Ebsco/ERIC, Ebsco/Criminal Justice s, Embase.com, and Clarivate Analytics/Web of Science Core Collection from inception to June 2021. Studies were eligible if they reviewed the effect of chronic physical activity interventions on antisocial behavior compared to wait-list, no-exercise, or attention control samples. The following studies were excluded: animal studies, studies reporting on acute exercise, studies including yoga or mindfulness as the sole measure of physical activity, and studies including substance (ab)use and/or smoking as the only outcome measure. A random effects model was used to calculate pooled effect sizes. The risk of bias was assessed using the Cochrane risk-of-bias tool (version 2).ResultsThe search yielded 29 studies, of which 20 were included in the meta-analysis. Results indicate a significant small-to-medium effect (g = − 0.26) with a 95% confidence interval ranging from − 0.48 to − 0.04 in favor of physical activity interventions. Significant moderators included type of control group, type of physical activity, and type of antisocial behavior, with larger effect sizes for comparisons with inactive control groups (g = − 0.31), interventions containing walking, jogging, or running as the main type of physical activity (g = − 0.87), and anger/hostility as an antisocial outcome measure (g = − 0.42).ConclusionsPhysical activity interventions may be a promising way to reduce antisocial behavior in children and adults. However, due to the overall high risk of bias in the included studies, more sound evaluation research is needed to better understand the functioning and to improve the possible implementation of physical activity interventions.

Clinical First-Trimester Prediction Models for Gestational Diabetes Mellitus: A Systematic Review and Meta-Analysis.

Gestational diabetes mellitus (GDM) is a common pregnancy complication that negatively impacts the health of both the mother and child. Early prediction of the risk of GDM may permit prompt and effective interventions. This systematic review and meta-analysis aimed to summarize the study characteristics, methodological quality, and model performance of first-trimester prediction model studies for GDM. Five electronic databases, one clinical trial register, and gray literature were searched from the inception date to March 19, 2022. Studies developing or validating a first-trimester prediction model for GDM were included. Two reviewers independently extracted data according to an established checklist and assessed the risk of bias by the Prediction Model Risk of Bias Assessment Tool (PROBAST). We used a random-effects model to perform a quantitative meta-analysis of the predictive power of models that were externally validated at least three times. We identified 43 model development studies, six model development and external validation studies, and five external validation-only studies. Body mass index, maternal age, and fasting plasma glucose were the most commonly included predictors across all models. Multiple estimates of performance measures were available for eight of the models. Summary estimates range from 0.68 to 0.78 (I2 ranged from 0% to 97%). Most studies were assessed as having a high overall risk of bias. Only eight prediction models for GDM have been externally validated at least three times. Future research needs to focus on updating and externally validating existing models.

Comparing the Effect of Miniscrew-Supported and Conventional Maxillary Incisor Intrusion on the Inclination of Maxillary Incisors and Molars - A Systematic Review and Meta-Analysis.

The objective of this study was to compare the effect of miniscrew-supported maxillary incisor intrusion and conventional intrusion mechanics on maxillary incisors and molar inclination. Search databases (PubMed, Scopus, Web of Science, Embase, EBSCOhost, and the Cochrane Library) were searched for randomized trials on intrusion of maxillary incisors via miniscrew-supported and conventional mechanics. The revised Cochrane risk-of-bias tool for randomized trials (RoB 2.0) was used. Five outcomes ([i] inclination change of upper incisors, [ii] inclination change of upper molars, [iii] intrusion of incisors, [iv] vertical change in upper first molars, and [v] overbite correction achieved) were statistically pooled using Review Manager 5.3. Subgroup analysis was conducted to receive sturdiness in meta-analysis. The quality of evidence was assessed using the Grading of Recommendations Assessment, Development and Evaluation. Out of 1777 studies, 7 were finally subjected to quality assessment, and 6 were included in the meta-analysis. The incisor inclination following maxillary incisor intrusion increased in miniscrew-supported intrusion in comparison to Connecticut intrusion arch (CTA) subgroup with standard mean difference of 0.66 mm (95% confidence interval = 0.16, 1.03, I2 = 0%). All the included studies showed an increase in molar inclination (distal tipping) in the CTA subgroup compared to the micro-implant group. Of all the seven included studies, only one study was identified with some concerns for the risk of bias, and the other six were judged to have an overall high risk of bias. The incisal proclination during deep-bite correction by miniscrew-supported incisal intrusion is more than that in the CTA subgroup; however, the difference may not be clinically very relevant. There is a very low quality of evidence in favor of miniscrew-supported intrusion as compared to conventional intrusion, necessitating the need for good-quality trials.

Increased versus stable doses of inhaled corticosteroids for exacerbations of chronic asthma in adults and children.

Increased versus stable doses of inhaled corticosteroids for exacerbations of chronic asthma in adults and children.

Does ultrasonic activation of irrigation during endodontic therapy improve the clinical and microbiological effects?

Data sources A comprehensive collection of databases were searched from inception to August 2020, such as Cochrane, MEDLINE, Scopus and Web of science. Also, references and citations of retrieved records, conference proceedings and leading journals were searched.Study selection All randomised clinical trials on root-canal-treated adult permanent teeth that compared the outcomes of ultrasonically activated irrigation (UAI) to syringe irrigation (SI) were eligible. The outcomes considered were post-operative pain, pain intensity, periapical healing after 12 months, the incidence of microbial presence, microbial quantification, lipopolysaccharides (LPS) quantification and lipoteichoic acid quantification. Studies with insufficient data for risk of bias assessment or other outcomes were excluded.Data extraction and synthesis The two independent reviewers did the screening process in title, abstract and full-text assessment steps. Also, the data extraction process and risk of bias assessment were done by two independent reviewers. Any disagreement was resolved by consensus or the opinion of a third reviewer. Any missing information was filled in by contacting the authors. The Cochrane risk-of-bias tool for randomised trials was used to assess the risk of bias. The following domains were evaluated for risk of bias: randomisation process, deviation from the intended interventions, missing outcome data, outcome measurement and the selection of the reported results. If all domains were rated as 'low risk', judgements would be rated as 'low risk', otherwise, 'high risk'. The risk ratios and mean risk difference with 95% confidence interval (CI) were used as measure effect. The random effects model was used to combine the effects. The heterogeneity is measured by I2 test (I2 test >50% and p <0.1 considered as substantial heterogeneity). The level of certainty of evidence for clinically important outcomes was determined using the guidelines of Grading of Recommendations Assessment, Development and Evaluation working group.Results Four studies entered the meta-analysis stage based on pain outcomes. The overall risk of bias for three of them was assessed as high. All of them had examined pain incidence before 24 hours but only two studies have examined the occurrence of pain in the period of 24-72 hours and after 72 hours to 7 days. Considerable heterogeny was among the incidence of pain <24 hours between studies (I2= 83%). Therefore, the incidence of pain in two sub-groups of vital and non-vital pulp has been investigated. In the non-vital pulps, the incidence of pain by UAI was half of the incidence of SI pain (relative risk= 0.50; 95% CI 0.35-0.71; I2 = 0%; 308 teeth). But no significant difference was seen in vital pulps. Also, there was no significant difference in the occurrence of pain after 72 hours between the two methods. Two studies assessed the intensity of pain in three periods: <24 hours, 72-24 hours, more than 72 hours and less than 7 days. The combined results based on vital and non-vital groups resulted in no significant difference in any period. Pooled data of pain outcomes were assessed with very low or low confidence of evidence.Five studies with microbiology-related outcomes entered the final analysis stage. The overall risk of bias for two of them was high. Three studies evaluated the effect of the irrigation method on microbial presence as an outcome. High heterogeneity was among the results of the studies (I2= 72%). However, with and without subgroup analysis, meta-analysis results showed no significant difference between these two methods. A lower microbial count was found with UAI than SI in a meta-analysis of four studies (standardised mean difference-pooled - 0.40; 95% CI [-0.78, -0.02]; I2 = 0%; 126 teeth). Two studies measured LPs. The meta-analysis showed lower values of LPS with UAI compared to SI (34, 37) (mean difference pooled - 0.06; 95% CI [-0.11, -0.01]; 61 root canals; I2 = 29%). One study measured lipoteichoic acid and found no significant difference between the irrigation methods.Three studies with treatment-success-related outcomes entered the meta-analysis stage with an overall high risk of bias. Two studies' pooled data revealed no significant difference between the irrigation methods regarding treatment failure. One study assessed periapical-lesion volume after treatment and found no significant difference between the irrigation methods.Conclusions According to limited data, UAI may reduce the risk of post-operative pain during the first 24 hours and reduce microbial counts, particularly cultivable germs in cases of apical periodontitis. However, most meta-analyses are conducted on a small number of studies and have an overall 'very low' to 'low' certainty of evidence; as a result, the evidence is deemed insufficient to either support or disprove UAI efficacy when compared to SI.

Fluvoxamine for the treatment of COVID-19.

Fluvoxamine is a selective serotonin reuptake inhibitor (SSRI) that has been approved for the treatment of depression, obsessive-compulsive disorder, and a variety of anxiety disorders; it is available as an oral preparation. Fluvoxamine has not been approved for the treatment of infections, but has been used in the early treatment of people with mild to moderate COVID-19. As there are only a few effective therapies for people with COVID-19 in the community, a thorough understanding of the current evidence regarding the efficacy and safety of fluvoxamine as an anti-inflammatory and possible anti-viral treatment for COVID-19, based on randomised controlled trials (RCTs), is needed. To assess the efficacy and safety of fluvoxamine in addition to standard care, compared to standard care (alone or with placebo), or any other active pharmacological comparator with proven efficacy for the treatment of COVID-19 outpatients and inpatients. We searched the Cochrane COVID-19 Study Register (including Cochrane Central Register of Controlled Trials, MEDLINE, Embase, ClinicalTrials.gov, WHO ICTRP, medRxiv), Web of Science and WHO COVID-19 Global literature on COVID-19 to identify completed and ongoing studies up to 1 February 2022. We included RCTs that compared fluvoxamine in addition to standard care (also including no intervention), with standard care (alone or with placebo), or any other active pharmacological comparator with proven efficacy in clinical trials for the treatment of people with confirmed COVID-19, irrespective of disease severity, in both inpatients and outpatients. Co-interventions needed to be the same in both study arms. We excluded studies comparing fluvoxamine to other pharmacological interventions with unproven efficacy. We assessed risk of bias of primary outcomes using the Cochrane Risk of Bias 2 tool for RCTs. We used GRADE to rate the certainty of evidence to treat people with asymptomatic to severe COVID-19 for the primary outcomes including mortality, clinical deterioration, clinical improvement, quality of life, serious adverse events, adverse events of any grade, and suicide or suicide attempt. We identified two completed studies with a total of 1649 symptomatic participants. One study was conducted in the USA (study with 152 participants, 80 and 72 participants per study arm) and the other study in Brazil (study with 1497 high-risk participants for progression to severe disease, 741 and 756 participants per study arm) among outpatients with mild COVID-19. Both studies were double-blind, placebo-controlled trials in which participants were prescribed 100 mg fluvoxamine two or three times daily for a maximum of 15 days. We identified five ongoing studies and two studies awaiting classification (due to translation issues, and due to missing published data). We found no published studies comparing fluvoxamine to other pharmacological interventions of proven efficacy. We assessed both included studies to have an overall high risk of bias. Fluvoxamine for the treatment of COVID-19 in inpatients We did not identify any completed studies of inpatients. Fluvoxamine for the treatment of COVID-19 in outpatients Fluvoxamine in addition to standard care may slightly reduce all-cause mortality at day 28 (RR 0.69, 95% CI 0.38 to 1.27; risk difference (RD) 9 per 1000; 2 studies, 1649 participants; low-certainty evidence), and may reduce clinical deterioration defined as all-cause hospital admission or death before hospital admission (RR 0.55, 95% CI 0.16 to 1.89; RD 57 per 1000; 2 studies, 1649 participants; low-certainty evidence). We are very uncertain regarding the effect of fluvoxamine on serious adverse events (RR 0.56, 95% CI 0.15 to 2.03; RD 54 per 1000; 2 studies, 1649 participants; very low-certainty evidence) or adverse events of any grade (RR 1.06, 95% CI 0.82 to 1.37; RD 7 per 1000; 2 studies, 1649 participants; very low-certainty evidence). Neither of the studies reported on symptom resolution (clinical improvement), quality of life or suicide/suicide attempt. Based on a low-certainty evidence, fluvoxamine may slightly reduce all-cause mortality at day 28, and may reduce the risk of admission to hospital or death in outpatients with mild COVID-19. However, we are very uncertain regarding the effect of fluvoxamine on serious adverse events, or any adverse events. In accordance with the living approach of this review, we will continually update our search and include eligible trials as they arise, to complete any gaps in the evidence.