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Purpose Targeted temperature management (TTM) may improve survival and functional outcome in comatose survivors of out-of-hospital cardiac arrest (OHCA), though the optimal target temperature remains unknown. We conducted a systematic review and network meta-analysis to investigate the efficacy and safety of deep hypothermia (31–32 °C), moderate hypothermia (33–34 °C), mild hypothermia (35–36 °C), and normothermia (37–37.8 °C) during TTM. Methods We searched six databases from inception to June 2021 for randomized controlled trials (RCTs) evaluating TTM in comatose OHCA survivors. Two reviewers performed screening, full text review, and extraction independently. The primary outcome of interest was survival with good functional outcome. We used GRADE to rate our certainty in estimates. Results We included 10 RCTs (4218 patients). Compared with normothermia, deep hypothermia (odds ratio [OR] 1.30, 95% confidence interval [CI] 0.73–2.30), moderate hypothermia (OR 1.34, 95% CI 0.92–1.94) and mild hypothermia (OR 1.44, 95% CI 0.74–2.80) may have no effect on survival with good functional outcome (all low certainty). Deep hypothermia may not improve survival with good functional outcome, as compared to moderate hypothermia (OR 0.97, 95% CI 0.61–1.54, low certainty). Moderate hypothermia (OR 1.23, 95% CI 0.86–1.77) and deep hypothermia (OR 1.27, 95% CI 0.70–2.32) may have no effect on survival, as compared to normothermia. Finally, incidence of arrhythmia was higher with moderate hypothermia (OR 1.45, 95% CI 1.08–1.94) and deep hypothermia (OR 3.58, 95% CI 1.77–7.26), compared to normothermia (both high certainty). Conclusions Mild, moderate, or deep hypothermia may not improve survival or functional outcome after OHCA, as compared to normothermia. Moderate and deep hypothermia were associated with higher incidence of arrhythmia. Routine use of moderate or deep hypothermia in comatose survivors of OHCA may potentially be associated with more harm than benefit.

Childhood obesity is an important predisposing factor for most non-communicable diseases. The aim of this review was to provide evidence on the prevalence and trends of childhood obesity and overweight in Iran. Multiple international and Iranian scientific databases were searched for relevant literatures. Two independent reviewers identified relevant papers in several steps. Separate meta-analyses (using fixed- or random-effect models) were performed to estimate the overall, age, sex, and age–sex specific prevalence of obesity and overweight. Stratified analysis based on Centers for Disease Control and Prevention, International Obesity Task Force, and World Health Organization definition criteria and study year also were performed. We included 107 studies in the meta-analysis (49 English and 58 Persian). Based on Centers for Disease Control and Prevention definition criteria, the overall prevalence of obesity and overweight remained relatively constant in the 2000s and are estimated to be about 5.1% (95% confidence interval [CI], 4.4–5.8) and 10.8% (95% CI, 10.2–11.4), respectively. The meta-regression analysis showed that the prevalence of obesity and overweight did not vary significantly with respect to sex and age of study participants. Girls had a lower prevalence of obesity and higher prevalence of overweight than boys. This review, which is the first of its kind in the Middle East and North Africa, suggests that although the trend in the prevalence of childhood obesity in Iranian children is not considerably high, but the escalating trend of excess weight among young children is alarming and should be considered by providers of interventional preventive programs at national and regional levels.

ObjectivesNo consensus exists on digital breast tomosynthesis (DBT) utilization for breast cancer detection. We performed a diagnostic test accuracy systematic review and meta-analysis comparing DBT, combined DBT and digital mammography (DM), and DM alone for breast cancer detection in average-risk women.MethodsMEDLINE and EMBASE were searched until September 2018. Comparative design studies reporting on the diagnostic accuracy of DBT and/or DM for breast cancer detection were included. Demographic, methodologic, and diagnostic accuracy data were extracted. Risk of bias was assessed using the Quality Assessment of Diagnostic Accuracy Studies (QUADAS)-2 tool. Accuracy metrics were pooled using bivariate random-effects meta-analysis. The impact of multiple covariates was assessed using meta-regression. PROSPERO ID: CRD 42018111287.ResultsThirty-eight studies reporting on 488,099 patients (13,923 with breast cancer) were included. Eleven studies were at low risk of bias. DBT alone, combined DBT and DM, and DM alone demonstrated sensitivities of 88% (95% confidence interval [CI] 83–92), 88% (CI 83–92), and 79% (CI 75–82), as well as specificities of 84% (CI 76–89), 81% (CI 73–88), and 79% (CI 71–85), respectively. The greater sensitivities of DBT alone and combined DBT and DM compared to DM alone were preserved in the combined meta-regression models accounting for other covariates (p = 0.003–0.006). No significant difference in diagnostic accuracy between DBT alone and combined DBT and DM was identified (p = 0.175–0.581).ConclusionsDBT is more sensitive than DM, while the addition of DM to DBT provides no additional diagnostic benefit. Consideration of these findings in breast cancer imaging guidelines is recommended.Key Points• Digital breast tomosynthesis with or without additional digital mammography is more sensitive in detecting breast cancer than digital mammography alone in women at average risk for breast cancer.• The addition of digital mammography to digital breast tomosynthesis provides no additional diagnostic benefit in detecting breast cancer compared to digital breast tomosynthesis alone.• The specificity of digital breast tomosynthesis with or without additional digital mammography is no different than digital mammography alone in the detection of breast cancer.

PurposeSystematic review and network meta-analysis to investigate the efficacy of noninvasive respiratory strategies, including noninvasive positive pressure ventilation (NIPPV) and high-flow nasal cannula (HFNC), in reducing extubation failure among critically ill adults.MethodsWe searched databases from inception through October 2021 for randomized controlled trials (RCTs) evaluating noninvasive respiratory support therapies (NIPPV, HFNC, conventional oxygen therapy, or a combination of these) following extubation in critically ill adults. Two reviewers performed screening, full text review, and extraction independently. The primary outcome of interest was reintubation. We used GRADE to rate the certainty of our findings.ResultsWe included 36 RCTs (6806 patients). Compared to conventional oxygen therapy, NIPPV (OR 0.65 [95% CI 0.52–0.82]) and HFNC (OR 0.63 [95% CI 0.45–0.87]) reduced reintubation (both moderate certainty). Sensitivity analyses showed that the magnitude of the effect was highest in patients with increased baseline risk of reintubation. As compared to HFNC, no difference in incidence of reintubation was seen with NIPPV (OR 1.04 [95% CI 0.78–1.38], low certainty). Compared to conventional oxygen therapy, neither NIPPV (OR 0.8 [95% CI 0.61–1.04], moderate certainty) or HFNC (OR 0.9 [95% CI 0.66–1.24], low certainty) reduced short-term mortality. Consistent findings were demonstrated across multiple subgroups, including high- and low-risk patients. These results were replicated when evaluating noninvasive strategies for prevention (prophylaxis), but not in rescue (application only after evidence of deterioration) situations.ConclusionsOur findings suggest that both NIPPV and HFNC reduced reintubation in critically ill adults, compared to conventional oxygen therapy. NIPPV did not reduce incidence of reintubation when compared to HFNC. These findings support the preventative application of noninvasive respiratory support strategies to mitigate extubation failure in critically ill adults, but not in rescue conditions.

Network meta-analysis (NMA) is an increasingly popular statistical method of synthesising evidence to assess the comparative benefits and harms of multiple treatments in a single analysis. Several automated software packages facilitate conducting NMA using either of two alternative approaches, Bayesian or frequentist frameworks. Researchers must choose a framework for conducting NMA (Bayesian or frequentist) and select appropriate model(s), and those conducting NMA need to understand the assumptions and limitations of different approaches. Bayesian models are more frequently used and can be more flexible but require checking additional assumptions and greater statistical expertise that are often ignored. The present paper describes the important theoretical aspects of Bayesian and frequentist models for NMA and the applications and considerations of contrast-synthesis and arm-synthesis NMAs. In addition, we present evidence from a limited number of simulation and empirical studies that compared different frequentist and Bayesian models and provide an overview of available automated software packages to perform NMA. We will conclude that when analysts choose appropriate models, there are seldom important differences in the results of Bayesian and frequentist approaches and that network meta-analysts should therefore focus on model features rather than the statistical framework.

Cognitive behavioural therapy (CBT) has been shown to be effective for several psychiatric and somatic conditions; however, most randomized controlled trials (RCTs) have administered treatment in person and whether remote delivery is similarly effective remains uncertain. We sought to compare the effectiveness of therapist-guided remote CBT and in-person CBT. We systematically searched MEDLINE, Embase, PsycINFO, CINAHL, and the Cochrane Central Register of Controlled Trials from inception to July 4, 2023, for RCTs that enrolled adults (aged ≥ 18 yr) presenting with any clinical condition and that randomized participants to either therapist-guided remote CBT (e.g., teleconference, videoconference) or in-person CBT. Paired reviewers assessed risk of bias and extracted data independently and in duplicate. We performed random-effects model meta-analyses to pool patient-important primary outcomes across eligible RCTs as standardized mean differences (SMDs). We used Grading of Recommendations Assessment, Development and Evaluation (GRADE) guidance to assess the certainty of evidence and used the Instrument to Assess the Credibility of Effect Modification Analyses (ICEMAN) to rate the credibility of subgroup effects. We included 54 RCTs that enrolled a total of 5463 patients. Seventeen studies focused on treatment of anxiety and related disorders, 14 on depressive symptoms, 7 on insomnia, 6 on chronic pain or fatigue syndromes, 5 on body image or eating disorders, 3 on tinnitus, 1 on alcohol use disorder, and 1 on mood and anxiety disorders. Moderate-certainty evidence showed little to no difference in the effectiveness of therapist-guided remote and in-person CBT on primary outcomes (SMD −0.02, 95% confidence interval −0.12 to 0.07). Moderate-certainty evidence showed little to no difference in the effectiveness of in-person and therapist-guided remote CBT across a range of mental health and somatic disorders, suggesting potential for the use of therapist-guided remote CBT to facilitate greater access to evidence-based care. Systematic review registration: Open Science Framework (https://osf.io/7asrc)

ObjectiveThe objective of this study is to evaluate the comparative benefits and harms of opioids and cannabis for medical use for chronic non-cancer pain.DesignSystematic review and network meta-analysis.Data sourcesEMBASE, MEDLINE, CINAHL, AMED, PsycINFO, PubMed, Web of Science, Cannabis-Med, Epistemonikos and the Cochrane Library (CENTRAL) from inception to March 2021.Study selectionRandomised trials comparing any type of cannabis for medical use or opioids, against each other or placebo, with patient follow-up ≥4 weeks.Data extraction and synthesisPaired reviewers independently extracted data. We used Bayesian random-effects network meta-analyses to summarise the evidence and the Grading of Recommendations, Assessment, Development and Evaluations (GRADE) approach to evaluate the certainty of evidence and communicate our findings.ResultsNinety trials involving 22 028 patients were eligible for review, among which the length of follow-up ranged from 28 to 180 days. Moderate certainty evidence showed that opioids provide small improvements in pain, physical functioning and sleep quality versus placebo; low to moderate certainty evidence supported similar effects for cannabis versus placebo. Neither was more effective than placebo for role, social or emotional functioning (all high to moderate certainty evidence). Moderate certainty evidence showed there is probably little to no difference between cannabis for medical use and opioids for physical functioning (weighted mean difference (WMD) 0.47 on the 100-point 36-item Short Form Survey physical component summary score, 95% credible interval (CrI) −1.97 to 2.99), and cannabis resulted in fewer discontinuations due to adverse events versus opioids (OR 0.55, 95% CrI 0.36 to 0.83). Low certainty evidence suggested little to no difference between cannabis and opioids for pain relief (WMD 0.23 cm on a 10 cm Visual Analogue Scale (VAS), 95% CrI −0.06 to 0.53) or sleep quality (WMD 0.49 mm on a 100 mm VAS, 95% CrI −4.72 to 5.59).ConclusionsCannabis for medical use may be similarly effective and result in fewer discontinuations than opioids for chronic non-cancer pain.PROSPERO registration numberCRD42020185184.

Background Mother-to-child transmission is the primary cause of HIV cases among children. Antiretroviral therapy (ART) plays a critical role in preventing mother-to-child transmission and reducing HIV progression, morbidity, and mortality among mothers. However, after more than two decades of ART during pregnancy, the comparative effectiveness and safety of ART medications during pregnancy are unclear, and existing evidence is contradictory. This study aimed to assess the effectiveness and safety of different ART regimens among pregnant women living with HIV at preconception or during pregnancy. Methods We searched MEDLINE, Embase, Cochrane Central Register of Controlled Trials, and Web of Science. We included randomized trials that enrolled pregnant women living with HIV and randomized them to receive ART for at least four weeks. Pairs of reviewers independently completed screening for eligible studies, extracted data, and assessed the risk of bias using the Cochrane risk of bias tool. Our outcomes of interest included low birth weight, stillbirth, preterm birth, mother-to-child transmission of HIV, neonatal death, and congenital anomalies. Network meta-analysis was performed using a random-effects frequentist model, and the certainty of evidence was evaluated using the GRADE approach. Results We found 14 eligible randomized trials enrolling 9,561 pregnant women. The median duration of ART uptake ranged from 6.0 to 17.4 weeks. No treatment was statistically better than a placebo in reducing the rate of neonatal mortality, stillbirth, congenital defects, preterm birth, or low birth weight deliveries. Compared to placebo, zidovudine (ZDV)/lamivudine (3TC) and ZDV monotherapy likely reduce mother-to-child transmission (odds ratio (OR): 0.13; 95% CI: 0.05 to 0.31, high-certainty; and OR: 0.50; 95% CI: 0.33 to 0.74, moderate-certainty). Moderate-certainty evidence suggested that ZDV/3TC was associated with decreased odds of stillbirth (OR: 0.47; 95% CI: 0.09 to 2.60). Conclusions Our analysis provides high- to moderate-certainty evidence that ZDV/3TC and ZDV are more effective in reducing the odds of mother-to-child transmission, with ZDV/3TC also demonstrating decreased odds of stillbirth. Notably, our findings suggest an elevated odds of stillbirth and preterm birth associated with all other ART regimens.

Background and Aims Despite the availability of HIV preventive measures, new HIV infections are still on the rise. The Dapivirine Vaginal Ring (DVR) is a silicone circular ring that continuously distributes 25 mg of Dapivirine into a woman's vagina for 28 days to prevent HIV infection; however, the effectiveness of DVR is largely dependent on adherence. To date, adherence to DVR has not been aggregated and summarized. The objective of this systematic review is to summarize the evidence on adherence to DVR for HIV‐1 prevention among African women and to aggregate findings into a quantitative estimate. Methods We will conduct a systematic review of studies in which DVR has been used to prevent HIV‐1 in African women. We will search MEDLINE, Global Health, CINAHL, and EMBASE from database inception to December 2024. We will include observational studies and randomized trials of women between 15 and 49 years of age, resident in Africa, who have used the DVR. Our primary outcome will be adherence to DVR. Pairs of reviewers will independently screen for eligible studies and will extract relevant data. We will perform a random‐effects meta‐analysis for DVR adherence. Certainty of the evidence will be assessed using the GRADE approach. Discussion This systematic review and meta‐analysis will contribute to a better understanding of how DVR adherence aids in preventing HIV‐1 infection in women, as well as the factors that influence observed adherence. Its findings can provide important foundational knowledge for future research and innovation in DVR and other PrEP tools. Findings from this protocol article will be disseminated as peer‐reviewed publications, at conferences, and as part of a master's thesis.

To determine the effectiveness and safety of amino acids in preventing the mortality and morbidity among preterm infants. We conducted a systematic review and network meta-analysis. We searched MEDLINE, EMBASE, Web of Science, CINAHL, Scopus, Cochrane, and Google Scholar, and grey literature, from databases inception to January 2021. We included randomized trials that evaluated any amino acids on preterm or low-birth weight infants. We performed frequentist pairwise and network meta-analyses and used the GRADE methodology to assess the certainty of the evidence and provide a summary of the results.We included 18 trials (3702 infants). Low certainty evidence showed that there seems to be no benefit for arginine, glutamine, or N-acetylcysteine in reducing all-cause mortality. Oral arginine likely results in reduction of necrotizin enterocolitis (NEC) stage ≥ II (OR 0.48; 95% CI 0.26–0.90; moderate certainty). Oral glutamine may reduce the likelihood of developing late-onset sepsis (LOS) compared to placebo (OR 0.62; 95% CI 0.47–0.82; low certainty); and likely reduces time to reach full enteral feeding (MD = − 2.63 days; 95% CI − 4.99 to − 0.27; moderate certainty). Amino acids may have no effect on mortality. Oral arginine may reduce severe NEC, and oral glutamine may reduce LOS and the time to reach full feeding. Systematic review registration : PROSPERO registration number: CRD4201603873.