Background: Specific treatments targeting Ebola virus are crucial in managing Ebola virus disease. To support the development of clinical practice guidelines on medications for Ebola virus disease, we aimed to evaluate the efficacy and safety of therapies for patients with Ebola virus disease. Methods: In this systematic review and network meta-analysis, we searched MEDLINE, Embase, the Cochrane Central Register of Controlled Trials, Scopus, Global Health, African Index Medicus, World Health Organization Global Index Medicus, the Cumulative Index to Nursing and Allied Health Literature, ClinicalTrials.gov, Epistemonikos, bioRxiv, medRxiv, and SSRN without language restrictions for randomised controlled trials (RCTs) published between database inception and Jan 1, 2022, comparing at least one therapeutic agent for Ebola virus disease against standard care or another therapeutic agent for Ebola virus disease. Two reviewers assessed study eligibility and extracted summary data independently using a standardised form. Our outcomes of interest were mortality, adverse maternal outcomes, risk of onward transmission, duration of admission to a health-care facility, functional status after Ebola virus disease, serious adverse events from medication, adverse perinatal outcomes, time to symptom resolution, and time to viral clearance. We did frequentist network meta-analyses to estimate the effect of all interventions and applied the Grading of Recommendations Assessment, Development and Evaluation approach to rate the certainty of the evidence. We registered the protocol with PROSPERO, CRD42022296539. Findings: We identified 7840 records through database searches, of which two RCTs with a total of 753 patients proved eligible. Only data on mortality, the duration of admission, serious adverse events, and time to viral clearance were available for meta-analysis. Compared with standard care, REGN-EB3 (relative risk [RR] 0·40, 95% CI 0·18 to 0·89; moderate certainty) and mAb114 (0·42, 0·19 to 0·93; moderate certainty) probably reduce mortality. Whether ZMapp (0·60, 0·28 to 1·26; very low certainty) and remdesivir (0·64, 0·29 to 1·39; very low certainty) reduce mortality compared with standard care is uncertain. With high certainty, REGN-EB3 reduces mortality compared with ZMapp (0·67, 0·52 to 0·88) and remdesivir (0·63, 0·49 to 0·82). With high certainty, mAb114 also reduces mortality compared with ZMapp (0·71, 0·55 to 0·91) and remdesivir (0·66, 0·52 to 0·84). Compared with standard care, REGN-EB3, mAb114, ZMapp, and remdesivir might have little or no effect on the time to viral clearance (mean difference ranged from -0·25 days to -1·14 days; low certainty). ZMapp might reduce the duration of admission compared with standard care (mean difference -2·02 days, 95% CI -4·05 to 0·01; low certainty). Findings for all comparisons suggested that there might be little or no difference in the prevalence of serious adverse events, but certainty was low or very low in all comparisons but one. Interpretation: REGN-EB3 and mAb114 separately reduce mortality compared with ZMapp, remdesivir, or standard care in patients with Ebola virus disease. These findings suggest that health-care workers should prioritise the use of REGN-EB3 and mAb114 for patients with Ebola virus disease during future outbreaks.

The complications and symptoms of hypoparathyroidism remain incompletely defined. Measuring serum parathyroid hormone (PTH) and calcium levels early after total thyroidectomy may predict the development of chronic hypoparathyroidism. The study aimed (i) to identify symptoms and complications associated with chronic hypoparathyroidism and determine the prevalence of those symptoms and complications (Part I), and (ii) to examine the utility of early postoperative measurements of PTH and calcium in predicting chronic hypoparathyroidism (Part II). We searched Medline, Medline In-Process, EMBASE, and Cochrane CENTRAL to identify complications and symptoms associated with chronic hypoparathyroidism. We used two predefined criteria (at least three studies reported the complication and symptom and had statistically significantly greater pooled relative estimates). To estimate prevalence, we used the median and interquartile range (IQR) of the studies reporting complications and symptoms. For testing the predictive values of early postoperative measurements of PTH and calcium, we used a bivariate model to perform diagnostic test meta-analysis. In Part I, the 93 eligible studies enrolled a total of 18,973 patients and reported on 170 complications and symptoms. We identified nine most common complications or symptoms probably associated with chronic hypoparathyroidism. The complications or symptoms and the prevalence are as follows: nephrocalcinosis/nephrolithiasis (median prevalence among all studies 15%), renal insufficiency (12%), cataract (17%), seizures (11%), arrhythmia (7%), ischemic heart disease (7%), depression (9%), infection (11%), and all-cause mortality (6%). In Part II, 18 studies with 4325 patients proved eligible. For PTH measurement, regarding the posttest probability, PTH values above 10 pg/mL 12-24 hours postsurgery virtually exclude chronic hypoparathyroidism irrespective of pretest probability (100%). When PTH values are below 10 pg/mL, posttest probabilities range from 3% to 64%. Nine complications and symptoms are probably associated with chronic hypoparathyroidism. A PTH value above a threshold of 10 pg/mL 12-24 hours after total thyroidectomy is a strong predictor that the patients will not develop chronic hypoparathyroidism. Patients with PTH values below the threshold need careful monitoring as some will develop chronic hypoparathyroidism. (c) 2022 American Society for Bone and Mineral Research (ASBMR).

The efficacy and safety of parathyroid hormone (PTH) therapy for managing long-term hypoparathyroidism is being evaluated in ongoing clinical trials. We undertook a systematic review and meta-analysis of currently available randomized controlled trials to investigate the benefits and harms of PTH therapy and conventional therapy in the management of patients with chronic hypoparathyroidism. To identify eligible studies, published in English, we searched Embase, PubMed, and Cochrane CENTRAL from inception to May 2022. Two reviewers independently extracted data and assessed the risk of bias. We defined patients' important outcomes and used grading of recommendations, assessment, development, and evaluation (GRADE) to provide the structure for quantifying absolute effects and rating the quality of evidence. Seven randomized trials of 12 publications that enrolled a total of 386 patients proved eligible. The follow-up duration ranged from 1 to 36 months. Compared with conventional therapy, PTH therapy probably achieves a small improvement in physical health-related quality of life (mean difference [MD] 3.4, 95% confidence interval [CI] 1.5-5.3, minimally important difference 3.0, moderate certainty). PTH therapy results in more patients reaching 50% or greater reduction in the dose of active vitamin D and calcium (relative risk [RR] = 6.5, 95% CI 2.5-16.4, 385 more per 1000 patients, high certainty). PTH therapy may increase hypercalcemia (RR =2.4, 95% CI 1.2-5.04, low certainty). The findings may support the use of PTH therapy in patients with chronic hypoparathyroidism. Because of limitations of short duration and small sample size, evidence from randomized trials is limited regarding important benefits of PTH therapy compared with conventional therapy. Establishing such benefits will require further studies. © 2022 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR).

Growing evidence indicates that insomnia may be associated with mortality. However, these findings have been inconsistent. We systematically searched MEDLINE and EMBASE to identify prospective cohort studies that assessed the association between insomnia disorder/individual insomnia symptoms and the risk of mortality among adults aged ≥18 yrs. We addressed this association using summary hazard ratios (HRs) and 95% confidence intervals (CIs) calculated using random-effects meta-analysis, and the GRADE approach to rate the certainty of evidence. Twenty-nine cohorts including 1,598,628 individuals (55.3% men; mean age 63.7 yrs old) with a median follow-up duration of 10.5 yrs proved eligible. Difficulty falling asleep (DFA) and non-restorative sleep (NRS) were associated with an increased risk of all-cause mortality (DFA: HR = 1.13, 95%CI 1.03 to 1.23, p = 0.009, moderate certainty; NRS: HR = 1.23, 95%CI 1.07 to 1.42, p = 0.003, high certainty) and cardiovascular disease mortality (DFA: 1.20, 95%CI: 1.01, 1.43; p = 0.04, moderate certainty; NRS: HR = 1.48, 95%CI 1.06 to 2.06, p = 0.02, moderate certainty). Convincing associations between DFA and all-cause mortality were restricted to the mid to older-aged population (moderate credibility). Insomnia disorder, difficulty maintaining sleep, and early morning awakening proved to be unassociated with all-cause and cardiovascular disease mortality. No insomnia symptoms proved to be associated with cancer-related mortality.