Objective We explored the comparative effectiveness of available therapies for chronic pain associated with temporomandibular disorders (TMD). DESIGN Systematic review and network meta-analysis of randomised clinical trials (RCTs).DATA SOURcES MEDLINE, EMBASE, CINAHL, CENTRAL, and SCOPUS were searched to May 2021, and again in January 2023.STUDY SELEcTION Interventional RCTs that enrolled patients presenting with chronic pain associated with TMD.DATA EXTRAcTION AND SYNTHESIS Pairs of reviewers independently identified eligible studies, extracted data, and assessed risk of bias. We captured all reported patient-important outcomes, including pain relief, physical functioning, emotional functioning, role functioning, social functioning, sleep quality, and adverse events. We conducted frequentist network meta-analyses to summarise the evidence and used the GRADE approach to rate the certainty of evidence and categorise interventions from most to least beneficial.RESULTS 233 trials proved eligible for review, of which 153-enrolling 8713 participants and exploring 59 interventions or combinations of interventions-were included in network meta-analyses. All subsequent effects refer to comparisons with placebo or sham procedures. Effects on pain for eight interventions were supported by high to moderate certainty evidence. The three therapies probably most effective for pain relief were cognitive behavioural therapy (CBT) augmented with biofeedback or relaxation therapy (risk difference (RD) for achieving the minimally important difference (MID) in pain relief of 1 cm on a 10 cm visual analogue scale: 36% (95% CI 33 to 39)), therapist-assisted jaw mobilisation (RD 36% (95% CI 31 to 40)), and manual trigger point therapy (RD 32% (29 to 34)). Five interventions were less effective, yet more effective than placebo, showing RDs ranging between 23% and 30%: CBT, supervised postural exercise, supervised jaw exercise and stretching, supervised jaw exercise and stretching with manual trigger point therapy, and usual care (such as home exercises, self stretching, reassurance). Moderate certainty evidence showed four interventions probably improved physical functioning: supervised jaw exercise and stretching (RD for achieving the MID of 5 points on the short form-36 physical component summary score: 43% (95% CI 33 to 51)), manipulation (RD 43% (25 to 56)), acupuncture (RD 42% (33 to 50)), and supervised jaw exercise and mobilisation (RD 36% (19 to 51)). The evidence for pain relief or physical functioning among other interventions, and all evidence for adverse events, was low or very low certainty.cONcLUSION When restricted to moderate or high certainty evidence, interventions that promote coping and encourage movement and activity were found to be most effective for reducing chronic TMD pain.REGISTRATION PROSPERO (CRD42021258567)

Objective:To determine the relative efficacy of structured named diet and health behaviour programmes (dietary programmes) for prevention of mortality and major cardiovascular events in patients at increased risk of cardiovascular disease. Design:Systematic review and network meta-analysis of randomised controlled trials. Data sources:AMED (Allied and Complementary Medicine Database), CENTRAL (Cochrane Central Register of Controlled Trials), Embase, Medline, CINAHL (Cumulative Index to Nursing and Allied Health Literature), and ClinicalTrials.gov were searched up to September 2021. Study selection:Randomised trials of patients at increased risk of cardiovascular disease that compared dietary programmes with minimal intervention (eg, healthy diet brochure) or alternative programmes with at least nine months of follow-up and reporting on mortality or major cardiovascular events (such as stroke or non-fatal myocardial infarction). In addition to dietary intervention, dietary programmes could also include exercise, behavioural support, and other secondary interventions such as drug treatment. Outcomes and measures:All cause mortality, cardiovascular mortality, and individual cardiovascular events (stroke, non-fatal myocardial infarction, and unplanned cardiovascular interventions). Review methods:Pairs of reviewers independently extracted data and assessed risk of bias. A random effects network meta-analysis was performed using a frequentist approach and grading of recommendations assessment, development and evaluation (GRADE) methods to determine the certainty of evidence for each outcome. Results:40 eligible trials were identified with 35 548 participants across seven named dietary programmes (low fat, 18 studies; Mediterranean, 12; very low fat, 6; modified fat, 4; combined low fat and low sodium, 3; Ornish, 3; Pritikin, 1). At last reported follow-up, based on moderate certainty evidence, Mediterranean dietary programmes proved superior to minimal intervention for the prevention of all cause mortality (odds ratio 0.72, 95% confidence interval 0.56 to 0.92; patients at intermediate risk: risk difference 17 fewer per 1000 followed over five years), cardiovascular mortality (0.55, 0.39 to 0.78; 13 fewer per 1000), stroke (0.65, 0.46 to 0.93; 7 fewer per 1000), and non-fatal myocardial infarction (0.48, 0.36 to 0.65; 17 fewer per 1000). Based on moderate certainty evidence, low fat programmes proved superior to minimal intervention for prevention of all cause mortality (0.84, 0.74 to 0.95; 9 fewer per 1000) and non-fatal myocardial infarction (0.77, 0.61 to 0.96; 7 fewer per 1000). The absolute effects for both dietary programmes were more pronounced for patients at high risk. There were no convincing differences between Mediterranean and low fat programmes for mortality or non-fatal myocardial infarction. The five remaining dietary programmes generally had little or no benefit compared with minimal intervention typically based on low to moderate certainty evidence. Conclusions:Moderate certainty evidence shows that programmes promoting Mediterranean and low fat diets, with or without physical activity or other interventions, reduce all cause mortality and non-fatal myocardial infarction in patients with increased cardiovascular risk. Mediterranean programmes are also likely to reduce stroke risk. Generally, other named dietary programmes were not superior to minimal intervention.

Objectives: To compare different modalities of renal replacement therapy in critically ill adults with acute kidney injury. Data sources: We searched Medline, PubMed, Embase, Cochrane Central Register of Controlled Trials, and ClinicalTrials.gov from inception to 25 May, 2020. We included randomized controlled trials comparing the efficacy and safety of different renal replacement therapy modalities in critically ill patients with acute kidney injury. Study selection: Ten reviewers (working in pairs) independently screened studies for eligibility, extracted data, and assessed risk of bias. Data extraction: We performed random-effects frequentist network meta-analyses and used the Grading of Recommendations, Assessment, Development, and Evaluation approach to assess certainty of evidence. The primary analysis was a four-node analysis: continuous renal replacement therapy, intermittent hemodialysis, slow efficiency extended dialysis, and peritoneal dialysis. The secondary analysis subdivided these four nodes into nine nodes including continuous veno-venous hemofiltration, continuous veno-venous hemodialysis, continuous veno-venous hemodiafiltration, continuous arterio-venous hemodiafiltration, intermittent hemodialysis, intermittent hemodialysis with hemofiltration, slow efficiency extended dialysis, slow efficiency extended dialysis with hemofiltration, and peritoneal dialysis. We set the minimal important difference threshold for mortality as 2.5% (relative difference, 0.04). Data synthesis: Thirty randomized controlled trials (n = 3,774 patients) proved eligible. There may be no difference in mortality between continuous renal replacement therapy and intermittent hemodialysis (relative risk, 1.04; 95% CI, 0.93-1.18; low certainty), whereas continuous renal replacement therapy demonstrated a possible increase in mortality compared with slow efficiency extended dialysis (relative risk, 1.06; 95% CI, 0.85-1.33; low certainty) and peritoneal dialysis (relative risk, 1.16; 95% CI, 0.92-1.49; low certainty). Continuous renal replacement therapy may increase renal recovery compared with intermittent hemodialysis (relative risk, 1.15; 95% CI, 0.91-1.45; low certainty), whereas both continuous renal replacement therapy and intermittent hemodialysis may be worse for renal recovery compared with slow efficiency extended dialysis and peritoneal dialysis (low certainty). Peritoneal dialysis was probably associated with the shortest duration of renal support and length of ICU stay compared with other interventions (low certainty for most comparisons). Slow efficiency extended dialysis may be associated with shortest length of hospital stay (low or moderate certainty for all comparisons) and days of mechanical ventilation (low certainty for all comparisons) compared with other interventions. There was no difference between continuous renal replacement therapy and intermittent hemodialysis in terms of hypotension (relative risk, 0.92; 95% CI, 0.72-1.16; moderate certainty) or other complications of therapy, but an increased risk of hypotension and bleeding was seen with both modalities compared with peritoneal dialysis (low or moderate certainty). Complications of slow efficiency extended dialysis were not sufficiently reported to inform comparisons. Conclusions: The results of this network meta-analysis suggest there is no difference in mortality between continuous renal replacement therapy and intermittent hemodialysis although continuous renal replacement therapy may increases renal recovery compared with intermittent hemodialysis. Slow efficiency extended dialysis with hemofiltration may be the most effective intervention at reducing mortality. Peritoneal dialysis is associated with good efficacy, and the least number of complications however may not be practical in all settings. Importantly, all conclusions are based on very low to moderate certainty evidence, limited by imprecision. At the very least, ICU clinicians should feel comfortable that the differences between continuous renal replacement therapy, intermittent hemodialysis, slow efficiency extended dialysis, and, where clinically appropriate, peritoneal dialysis are likely small, and any of these modalities is a reasonable option to employ in critically ill patients.

OBJECTIVE To compare the effects of treatments for coronavirus disease 2019 (covid-19). DESIGN Living systematic review and network meta-analysis. DATA SOURCES US Centers for Disease Control and Prevention COVID-19 Research Articles Downloadable Database, which includes 25 electronic databases and six additional Chinese databases to 20 July 2020. STUDY SELECTION Randomised clinical trials in which people with suspected, probable, or confirmed covid-19 were randomised to drug treatment or to standard care or placebo. Pairs of reviewers independently screened potentially eligible articles. METHODS After duplicate data abstraction, a bayesian random effects network meta-analysis was conducted. Risk of bias of the included studies was assessed using a modification of the Cochrane risk of bias 2.0 tool, and the certainty of the evidence using the grading of recommendations assessment, development and evaluation (GRADE) approach. For each outcome, interventions were classified in groups from the most to the least beneficial or harmful following GRADE guidance. RESULTS 23 randomised controlled trials were included in the analysis performed on 26 June 2020. The certainty of the evidence for most comparisons was very low because of risk of bias (lack of blinding) and serious imprecision. Glucocorticoids were the only intervention with evidence for a reduction in death compared with standard care (risk difference 37 fewer per 1000 patients, 95% credible interval 63 fewer to 11 fewer, moderate certainty) and mechanical ventilation (31 fewer per 1000 patients, 47 fewer to 9 fewer, moderate certainty). These estimates are based on direct evidence; network estimates for glucocorticoids compared with standard care were less precise because of network heterogeneity. Three drugs might reduce symptom duration compared with standard care: hydroxychloroquine (mean difference -4.5 days, low certainty), remdesivir (-2.6 days, moderate certainty), and lopinavir-ritonavir (-1.2 days, low certainty). Hydroxychloroquine might increase the risk of adverse events compared with the other interventions, and remdesivir probably does not substantially increase the risk of adverse effects leading to drug discontinuation. No other interventions included enough patients to meaningfully interpret adverse effects leading to drug discontinuation. CONCLUSION Glucocorticoids probably reduce mortality and mechanical ventilation in patients with covid-19 compared with standard care. The effectiveness of most interventions is uncertain because most of the randomised controlled trials so far have been small and have important study limitations.