OBJECTIVE: We conducted a systematic review and meta-analysis to examine the relationship between stillbirth and various perinatal outcomes in subsequent pregnancy. DATA SOURCES: PubMed, the Cochrane Library, Embase, Web of Science, and CNKI databases were searched up to July 2023. STUDY ELIGIBILITY CRITERIA: Cohort studies that reported the association between stillbirth and perinatal outcomes in subsequent pregnancies were included. METHODS: We conducted this systematic review and meta-analysis in accordance with the PRISMA guidelines. Statistical analysis was performed using Rand Stata software. We used random-effects models to pool each outcome of interest. We performed a meta-regression analysis to explore the potential heterogeneity. The certainty (quality) of evidence assessment was performed using the GRADE approach. RESULTS: Nineteen cohort studies were included, involving 4,855,153 participants. From these studies, we identified 28,322 individuals with previous stillbirths who met the eligibility criteria. After adjusting for confounders, evidence of low to moderate certainty indicated that compared with women with previous live births, women with previous stillbirths had higher risks of recurrent stillbirth (odds ratio, 2.68; 95% confidence interval, 2.01-3.56), preterm birth (odds ratio, 3.15; 95% confidence interval, 2.07-4.80), neonatal death (odds ratio, 4.24; 95% confidence interval, 2.65-6.79), small for gestational age/intrauterine growth restriction (odds ratio, 1.3; 95% confidence interval, 1.0-1.8), low birthweight (odds ratio, 3.32; 95% confidence interval, 1.46-7.52), placental abruption (odds ratio, 3.01; 95% confidence interval, 1.01-8.98), instrumental delivery (odds ratio, 2.29; 95% confidence interval, 1.68-3.11), labor induction (odds ratio, 4.09; 95% confidence interval, 1.88-8.88), cesarean delivery (odds ratio, 2.38; 95% confidence interval, 1.20-4.73), elective cesarean delivery (odds ratio, 2.42; 95% confidence interval, 1.82-3.23), and emergency cesarean delivery (odds ratio, 2.35; 95% confidence interval, 1.81-3.06) in subsequent pregnancies, but had a lower rate of spontaneous labor (odds ratio, 0.22; 95% confidence interval, 0.13-0.36). However, there was no association between previous stillbirth and preeclampsia (odds ratio, 1.72; 95% confidence interval, 0.63-4.70) in subsequent pregnancies. CONCLUSION: Our systematic review and meta-analysis provide a more comprehensive understanding of adverse pregnancy outcomes associated with previous stillbirth. These findings could be used to inform counseling for couples who are considering pregnancy after a previous stillbirth.

Importance Large language models (LLMs) may facilitate the labor-intensive process of systematic reviews. However, the exact methods and reliability remain uncertain. Objective To explore the feasibility and reliability of using LLMs to assess risk of bias (ROB) in randomized clinical trials (RCTs). Design, Setting, and Participants A survey study was conducted between August 10, 2023, and October 30, 2023. Thirty RCTs were selected from published systematic reviews. Main Outcomes and Measures A structured prompt was developed to guide ChatGPT (LLM 1) and Claude (LLM 2) in assessing the ROB in these RCTs using a modified version of the Cochrane ROB tool developed by the CLARITY group at McMaster University. Each RCT was assessed twice by both models, and the results were documented. The results were compared with an assessment by 3 experts, which was considered a criterion standard. Correct assessment rates, sensitivity, specificity, and F1 scores were calculated to reflect accuracy, both overall and for each domain of the Cochrane ROB tool; consistent assessment rates and Cohen kappa were calculated to gauge consistency; and assessment time was calculated to measure efficiency. Performance between the 2 models was compared using risk differences. Results Both models demonstrated high correct assessment rates. LLM 1 reached a mean correct assessment rate of 84.5% (95% CI, 81.5%-87.3%), and LLM 2 reached a significantly higher rate of 89.5% (95% CI, 87.0%-91.8%). The risk difference between the 2 models was 0.05 (95% CI, 0.01-0.09). In most domains, domain-specific correct rates were around 80% to 90%; however, sensitivity below 0.80 was observed in domains 1 (random sequence generation), 2 (allocation concealment), and 6 (other concerns). Domains 4 (missing outcome data), 5 (selective outcome reporting), and 6 had F1 scores below 0.50. The consistent rates between the 2 assessments were 84.0% for LLM 1 and 87.3% for LLM 2. LLM 1's kappa exceeded 0.80 in 7 and LLM 2's in 8 domains. The mean (SD) time needed for assessment was 77 (16) seconds for LLM 1 and 53 (12) seconds for LLM 2. Conclusions In this survey study of applying LLMs for ROB assessment, LLM 1 and LLM 2 demonstrated substantial accuracy and consistency in evaluating RCTs, suggesting their potential as supportive tools in systematic review processes.

COVID-19 is not only associated with substantial acute liver and kidney injuries, but also with an elevated risk of post-acute sequelae involving the kidney and liver system. We aimed to investigate whether COVID-19 exposure increases the long-term risk of kidney and liver disease, and what are the magnitudes of these associations. We searched PubMed, Embase, Web of Science, , and the Living Overview of the Evidence COVID-19 Repository for cohort studies estimating the association between COVID-19 and kidney and liver outcomes. Random-effects meta-analyses were performed to combine the results of the included studies. We assessed the certainty of the evidence using the Grading of Recommendations Assessment, Development and Evaluation approach. Fifteen cohort studies with more than 32 million participants were included in the systematic review COVID-19 was associated with a 35% greater risk of kidney diseases (10 more per 1000 persons; low certainty evidence) and 54% greater risk of liver disease (3 more per 1000 persons; low certainty evidence). The absolute increases due to COVID-19 for acute kidney injury, chronic kidney disease, and liver test abnormality were 3, 8, and 3 per 1000 persons, respectively. Subgroup analyses found no differences between different type of kidney and liver diseases. The findings provide further evidence for the association between COVID-19 and incident kidney and liver conditions. The absolute magnitude of the effect of COVID-19 on kidney and liver outcomes was, however, relatively small.

Background: To refine the methods of developing clinical practice guidelines (CPGs) for integrative ChineseWestern medicine (ICWM), promoting the formation of trustworthy, implementable recommendations that integrate the strengths of Chinese and Western medicine. Methods: Using a nominal group technique (NGT) approach, a multidisciplinary expert panel was established. The panel identified key methodological issues in ICWM-CPG development through literature review and iterative discussions, and formulated methodological proposals to address these issues. The final set of proposals was achieved through consensus among the panel members. Results: The collaborative effort resulted in the identification of five pivotal methodological issues and the subsequent establishment of 22 specific recommendations. These encompass strict adherence to renowned standards, such as those proposed by the Institute of Medicine (IOM) and Guidelines International Network (G -I -N), the employment of methodologies like the GRADE approach and RIGHT statement, the strategic constitution of a balanced development group, the adept identification of ICWM-focused clinical inquiries, the nuanced integration of diverse evidence sources, and the detailed crafting of transparent, implementable recommendations. Conclusions: This study concentrates on the most crucial and prevalent methodological issues in ICWM-CPG development, proposing a series of recommendations. These suggestions result from a multidisciplinary expert consensus, aiming to provide methodological guidance for ICWM-CPG developers, building upon the current foundational methodologies.

Background: The clinical efficacy and safety of intravenous immunoglobulin (IVIg) treatment for COVID-19 remain controversial. This study aimed to map the current status and gaps of available evidence, and conduct a meta-analysis to further investigate the benefit of IVIg in COVID-19 patients. Methods: Electronic databases were searched for systematic reviews/meta-analyses (SR/MAs), primary studies with control groups, reporting on the use of IVIg in patients with COVID-19. A random-effects meta-analysis with subgroup analyses regarding study design and patient disease severity was performed. Our outcomes of interest determined by the evidence mapping, were mortality, length of hospitalization (days), length of intensive care unit (ICU) stay (days), number of patients requiring mechanical ventilation, and adverse events. Results: We included 34 studies (12 SR/MAs, 8 prospective and 14 retrospective studies). A total of 5571 hospitalized patients were involved in 22 primary studies. Random-effects meta-analyses of very low to moderate evidence showed that there was little or no difference between IVIg and standard care or placebo in reducing mortality (relative risk [RR] 0.91; 95% CI 0.78-1.06; risk difference [RD] 3.3% fewer), length of hospital (mean difference [MD] 0.37; 95% CI - 2.56, 3.31) and ICU (MD 0.36; 95% CI - 0.81, 1.53) stays, mechanical ventilation use (RR 0.92; 95% CI 0.68-1.24; RD 2.8% fewer), and adverse events (RR 0.98; 95% CI 0.84-1.14; RD 0.5% fewer) of patients with COVID-19. Sensitivity analysis using a fixed-effects model indicated that IVIg may reduce mortality (RR 0.76; 95% CI 0.60-0.97), and increase length of hospital stay (MD 0.68; 95% CI 0.09-1.28). Conclusion: Very low to moderate certainty of evidence indicated IVIg may not improve the clinical outcomes of hospitalized patients with COVID-19. Given the discrepancy between the random- and fixed-effects model results, further large-scale and well-designed RCTs are warranted

Gut microbiota has been identified as a unique endocrine organ linked to the development of cardiovascular disease and other illnesses, especially deteriorated in overweight and obese postmenopausal women. The object of this systematic review and meta-analysis aimed to assess the effects of oral supplementation with probiotics for overweight and obese postmenopausal women. We performed a systematic search for randomized controlled trials (RCTs) from inception to April 2022 in MEDLINE, Embase, Cochrane Library, Web of Science, and ClinicalTrials.gov. We also performed a hand search by reviewing reference lists to identify trials. The risk of bias in individual studies was assessed with the Cochrane risk of bias tool for randomized trials (RoB). Two reviewers independently selected studies and collected data. There were 6 studies from 5 RCTs with 281 participants in this systematic review. Compared with the placebo, the probiotics supplementation group had reductions in insulin (MD - 4.20 IU/L (95% CI - 8.11 to - 0.30 IU/L), I-2 = 54%), HOMA-IR (MD - 1.25 (95% CI - 2.49 to - 0.01), I-2 = 50%), and TNF-alpha (MD - 0.12 pg/mL (95% CI - 0.22 to - 0.01 pg/mL), I-2 = 44%). Improvements were also shown in body adiposity and lipid profile, but these effects were nonsignificant. In addition to body adiposity and cardiovascular risk markers, one trial showed the administration of probiotics also had an effect on iron metabolism. In conclusion, probiotics have a potential benefit on glucose metabolism and inflammatory process in overweight and obese postmenopausal women, but this effect is mild. It demonstrates that oral probiotics supplementation can be a complementary treatment for improving the fitness of postmenopausal women with overweight and obesity.

BackgroundPharmacological treatment is common in practice and widely used for the management of insomnia. However, evidence comparing the relative effectiveness, safety, and certainty of evidence among drug classes and individual drugs for insomnia are still lacking. This study aimed to determine the relative effectiveness, safety, and tolerability of drugs for insomnia.MethodsIn this systematic review and network meta-analysis we systematically searched PubMed, Embase, Cochrane Central Register of Controlled Trials, PsycINFO, and ClinicalTrials.gov, from inception to January 10, 2022 to identify randomized controlled trials that compared insomnia drugs with placebo or an active comparator in adults with insomnia. We conducted random-effects frequentist network meta-analyses to summarize the evidence, and used the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach to assess the certainty, categorize interventionsand present the findings.ResultsA total of 148 articles met our eligibility criteria; these included 153 trials which enrolled 46,412 participants and assessed 36 individual drugs from eight drug classes. Compared with placebo, both subjectively and objectively measured total sleep time were significantly improved with non-benzodiazepine (subjective: mean difference [MD] 25.07, 95% confidence interval [CI] 15.49-34.64, low certainty; objective: MD 22.34, 95% CI 7.64-37.05, high certainty), antidepressants (subjective: MD 54.40, 95% CI 34.96-75.83, low certainty; objective: MD 35.64, 95% CI 13.05-58.24, high certainty), and orexin receptor antagonists (subjective: MD 21.62, 95% CI 0.84-42.40, high certainty; objective: MD 31.81, 95% CI 2.66-60.95, high certainty); of which doxepin, almorexant, suvorexant, and lemborexant were among the relatively effective drugs with relatively good tolerability and lower risks of any adverse events (AEs). Both subjectively and objectively measured sleep onset latency were significantly shortened with non-benzodiazepines (subjective: MD - 10.12, 95% CI - 13.84 to - 6.40, moderate certainty; objective: MD - 12.11, 95% CI - 19.31 to - 4.90, moderate certainty) and melatonin receptor agonists (subjective: MD - 7.73, 95% CI - 15.21 to - 0.26, high certainty; objective: MD - 7.04, 95% CI - 12.12 to - 1.95, moderate certainty); in particular, zopiclone was among the most effective drugs with a lower risk of any AEs but worse tolerability. Non-benzodiazepines could significantly decrease both subjective and objective measured wake time after sleep onset (subjective: MD - 16.67, 95% CI - 21.79 to - 11.56, moderate certainty; objective: MD - 13.92, 95% CI - 22.71 to - 5.14, moderate certainty).ConclusionsNon-benzodiazepines probably improve total sleep time, sleep onset latency, and wake time after sleep onset. Other insomnia drug classes and individual drugs also showed potential benefits in improving insomnia symptoms. However, the choice of insomnia drugs should be based on the phenotype of insomnia presented, as well as each drug's safety and tolerability.Protocol registration PROSPERO (CRD42019138790).

This is the protocol for a Campbell systematic review. The objectives are as follows. This study has three main objectives: (1) To examine the time duration from title registration to publication of the protocol for a Campbell systematic review and publication of the completed Campbell systematic review; (2) To describe publication times in accordance with the characteristics of the reviews, which include year of publication, type of review, number of authors, number of collaborative institutions, the time gap between the date the search was conducted and review publication, and the length and complexity of the included review (including the number of pages, the number of tables and figures, the number of studies included in the review, the number and type of analyses undertaken, and the number of references); (3) To describe the differences in publication times between Campbell Review Groups.

Background: COVID-19 might be a risk factor for various chronic diseases. However, the association between COVID-19 and the risk of incident diabetes remains unclear. We aimed to meta-analyze evidence on the relative risk of incident diabetes in patients with COVID-19. Methods: In this systematic review and meta-analysis, the Embase, PubMed, CENTRAL, and Web of Science databases were searched from December 2019 to June 8, 2022. We included cohort studies that provided data on the number, proportion, or relative risk of diabetes after confirming the COVID-19 diagnosis. Two reviewers independently screened studies for eligibility, extracted data, and assessed risk of bias. We used a random-effects meta-analysis to pool the relative risk with corresponding 95 % confidence intervals. Prespecified subgroup and meta-regression analyses were conducted to explore the potential influencing factors. We converted the relative risk to the absolute risk difference to present the evidence. This study was registered in advance (PROSPERO CRD42022337841). Main findings: Ten articles involving 11 retrospective cohorts with a total of 47.1 million participants proved eligible. We found a 64 % greater risk (RR = 1.64, 95%CI: 1.51 to 1.79) of diabetes in patients with COVID-19 compared with non-COVID-19 controls, which could increase the number of diabetes events by 701 (558 more to 865 more) per 10,000 persons. We detected significant subgroup effects for type of diabetes and sex. Type 2 diabetes has a higher relative risk than type 1. Moreover, men may be at a higher risk of overall diabetes than women. Sensitivity analysis confirmed the robustness of the results. No evidence was found for publication bias. Conclusions: COVID-19 is strongly associated with the risk of incident diabetes, including both type 1 and type 2 diabetes. We should be aware of the risk of developing diabetes after COVID-19 and prepare for the associated health problems, given the large and growing number of people infected with COVID-19. However, the body of evidence still needs to be strengthened.

AimsWe aimed to determine the effects of different exercise modalities in patients with type 2 diabetes mellitus (T2DM). MethodsWe searched PubMed, Embase, and the Cochrane Library from their inception until July 2020 to identify randomised controlled trials (RCTs) on exercise in adults with T2DM. Paired reviewers independently performed study selection, data extraction, and risk of bias assessment. The certainty of the evidence was assessed using the Confidence in Network Meta-Analysis (CINeMA) framework. ResultsA total of 106 RCTs that enroled eight exercise modalities with 7438 patients were included. Six exercise modalities, except unsupervised aerobic/resistance exercise, significantly reduced glycosylated haemoglobin (HbA1c), with mean differences (MDs) ranging from 0.71 (95% confidence interval [CI]: 0.34-1.08) to 0.34 (95% CI: 0.17-0.52), low to high certainty, in comparison with no exercise. The evidence of low to moderate certainty showed that supervised aerobic/resistance exercise improved glycaemic control, body weight, blood pressure, and blood lipid profiles compared with no exercise. Flexibility exercise may be associated with glycaemic control (HbA1c: MD = 0.71, 95% CI: 0.34-1.08); fasting plasma glucose (MD = 1.48, 95% CI: 0.78-2.17), and weight loss (MD = 1.80, 95% CI: 0.85-2.75) compared with controls, but not blood pressure and lipid profiles. Balance exercise showed the largest benefit in improving total cholesterol (MD = 52.81, 95% CI: 28.47-77.16) and low certainty. We found no significant differences between exercises and the triacylglycerol (TG) level. ConclusionsOverall, our network meta-analyses support the recommendation for exercise in patients with T2DM, especially supervised exercises. Limited evidence supports the benefits of flexibility and balance exercises. The effectiveness of exercise modalities for TG reduction remains unclear.

Objective: Clinical Practice Guidelines (CPGs) have an indispensable role in guiding the selection of various treatments for insomnia, however, little is known about the quality of released insomnia CPGs. This study aims to critically appraise the quality of existing insomnia CPGs and identify quality limitations. Methods: PubMed, Web of Science, Embase, China National Knowledge Infrastructure, Wanfang, China Biology Medicine disc, and 6 databases of international guideline developing institutions were systematically searched. CPGs on the diagnosis or treatment of insomnia were included. Reviewers independently extracted basic information and development methods, and assessed methodological quality and reporting quality using the Appraisal of Guidelines for Research and Evaluation (AGREE) II tool and Reporting Items for practice Guidelines in Healthcare (RIGHT) checklist respectively. Intraclass correlation coefficients (ICCs) were used to measure the agreement among reviewers and assess inter-rater reliability. Results: Twenty-six CPGs were identified that focused on adults, children, or children with autistic spectrum disorder, patients in the intensive care unit, patients with cancer and pregnant, lactating or menopausal women. Twenty-two CPGs used nine grading systems to rate the level of evidence and strength of recommendation. 53.85% CPGs were classified as "recommended with modification" according to the AGREE II scores (ICC from 0.64 to 0.90), and 2 CPGs were "recommended". The "clarity of presentation" domain achieved the highest mean score (67.9% +/- 11.04%) but the "applicability" domain (37.1% +/- 12.67%) achieved the lowest. The average reporting rate of RIGHT items in all guidelines was 67.87%. Conclusions: The quality of guidelines varied substantially. Guideline developers should realize the importance of guideline applicability, patients' preferences and values. (c) 2022 Elsevier B.V. All rights reserved.

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White rice is the food more than half of the world's population depends on. White rice intake can significantly increase the glycemic load of consumers and bring some adverse health effects. However, the quality of evidence implicating white rice in adverse health outcomes remains unclear. To evaluate the association between white rice consumption and the risk of cardiometabolic and cancer outcomes, a systematic review and dose-response meta-analysis of the relevant publications were performed. Twenty-three articles including 28 unique prospective cohorts with 1,527,198 participants proved eligible after a comprehensive search in four databases. For the risk of type 2 diabetes mellitus (T2DM), the pooled RR was 1.18 (16 more per 1000 persons) for comparing the highest with the lowest category of white rice intake, with moderate certainty evidence. Females presented a higher risk (23 more per 1000 persons) in subgroup analysis. And every additional 150 grams of white rice intake per day was associated with a 6% greater risk of T2DM (5 more per 1000 persons) with a linear positive trend. We found no significant associations between white rice intake and risk of cardiovascular diseases (CVD), CVD mortality, cancer, and metabolic syndrome. In conclusion, moderate certainty evidence demonstrated that white rice intake was associated with T2DM risk, with a linear positive trend. However, low to very low certainty of evidence suggested that no substantial associations were found between white rice intake and other cardiometabolic and cancer outcomes. More cohorts are needed to strength the evidence body.

Sugar-sweetened beverages (SSBs), artificially sweetened beverages (ASBs), and 100% fruit juices are frequently consumed and have been documented that they could lead to serious disease burden. However, inconsistent evidence on the association between SSBs, ASBs, and 100% fruit juices consumption and mortality have been presented. PubMed, Embase, Web of Science, Cochrane Central Register of Controlled Trials, and PsycINFO were systematically searched. We conducted a random-effects meta-analysis and dose-response meta-analysis to assess the association and calculated the pooled hazard ratio with 95% confidence interval. And we evaluated the certainty of evidence using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach. Thirteen studies with 1,539,127 participants proved eligible. An SSB-consumption increase per 250 mL/day was associated with a 4% greater risk of all-cause mortality (5 more per 1000 persons; low certainty) and 8% greater risk of cardiovascular disease mortality (3 more per 1000 persons; low certainty). ASB-consumption increase per 250 mL/day demonstrated a 4% greater risk of all-cause mortality (5 more per 1000 persons; low certainty) and 4% greater risk of cardiovascular disease mortality (2 more per 1000 persons; low certainty). The association of SSBs and ASBs with cancer mortality was not significant, with a very low certainty of evidence. There was evidence of a linear dose-response association between SSB intake and cancer mortality, as well as between ASB intake and all-cause mortality and cancer mortality. We observed a non-linear dose-response association between ASB intake and CVD mortality and SSB intake and all-cause and CVD mortality. Low certainty of evidence demonstrated that per 250 mL/day consumption increase in SSBs and ASBs had a small impact on all-cause and cardiovascular disease mortality but not on cancer mortality. The association of 100% fruit juice consumption with all-cause and cardiovascular disease mortality was uncertain.

Background: The coronavirus disease 2019 (COVID-19) pandemic continues to grow worldwide, and systematic reviews (SRs)/meta-analyses (MAs) on COVID-19 can efficiently guide evidence-based clinical practice. However, SRs/MAs with weaknesses can mislead clinical practice and pose harm to patients, and too many useless SRs/MAs could pose confusion and waste sources. A "living" overview of SRs/MAs aims to provide an open, accessible and frequently updated resource summarizing the highest-level evidence of COVID-19, that can help evidence-users to quickly identify trusted evidence to guide the practice. This study aims to systematically give an overview SRs/MAs of COVID-19, assess their quality, and identify the best synthesis of evidence. Methods: Databases including Medline, EMBASE, Web of Science, China National Knowledge Infrastructure (CNKI), China Biology Medicine (CBM) and WanFang were systematically searched on May 1, 2020 using relevant terms for identify SRs/MAs related to COVID-19. The study selection, data extraction and quality assessment will be performed by independent reviewers, and results will be crosschecked. The authoritative tools (AMSTAR-2, PRISMA and its extensions) will be used to assess the methodological quality and reporting quality of included SRs/MAs, and potential influence factors will be explored. The consistency of conclusions will be compared among reviews and the best evidence will be summarized. In addition, we will conduct exploratory meta-analyses (MAs) of individual studies when applicable. Data will be reported as number with (or) percentage, risk ratio (RR) or odds ratio (OR), mean difference (MD) or standardized mean difference (SMD) with 95% confidence interval (CI) according to the specific results. R3.6.1 and Microsoft Excel 2016 will be used to analyze and manage data. Results: The results of this overview will be submitted to a peer-reviewed journal for publication. Conclusions: In this study, we will present for the first time, an overview of SRs/MAs, which provides a comprehensive, dynamic evidence landscape on prevalence, prevention, diagnosis, treatment, and prognosis of COVID-19.

To assess and compare the QoL of the older people dwelling in traditional family versus nursing home/institution. A comprehensive literature search was performed on 10 January 2018 to identify studies that investigated the QoL of older adults dwelling in family versus nursing home settings. Analyses were run using random-effects meta-analyses. A total of six cross-sectional studies with 1623 people were included. The quality of included studies was moderate. Meta-analysis showed that compared with nursing home support, the family support could significantly improve the physical health (6 studies, SMD = 0.50, 95%CI: 0.32-0.68, p < 0.05), mental status (6 studies, SMD = 0.45, 95%CI: 0.26-0.65, p < 0.05), and social relationship (5 studies, SMD = 0.51, 95%CI: 0.19-0.83, p < 0.05). Traditional family support model demonstrated a significant improvement in the physical health, psychological status and social relationships among older adults. The conclusions were driven by cross-sectional studies, Larger, adequately powered RCTs are required to confirm our finding.

Background Several clinical trials investigated the effects of enteral lactoferrin supplementation on the prevention of sepsis and necrotizing enterocolitis (NEC) in preterm infants, but the efficacy and safety remain disputed. Therefore, we systematically evaluated the effect of enteral lactoferrin supplementation in preterm infants through a meta-analysis with trial sequential analysis (TSA). Methods We searched six databases to identify randomized controlled trials (RCTs) that evaluated the effects of lactoferrin supplementation compared with placebo or no intervention in preterm infants. RevMan version 5.3 software was used to estimate pooled relative risks (RRs) with the random-effects model. TSA, subgroup analyses, and meta-regression analyses were also performed. Results Nine RCTs with 3515 samples were included. With low to moderate quality of evidence, compared with placebo, enteral lactoferrin supplementation did not significantly decrease the incidences of late-onset sepsis (RR = 0.63, 95% CI: 0.38 to 1.02,P= 0.06), NEC stage II or III (RR = 0.68, 95% CI: 0.30 to 1.52,P= 0.35), all-cause mortality (RR = 0.89, 95% CI: 0.51 to 1.57,P= 0.69), bronchopulmonary dysplasia (RR = 1.01, 95% CI: 0.90 to 1.13,P= 0.92), retinopathy of prematurity (RR = 0.80, 95% CI: 0.49 to 1.32,P= 0.38), invasive fungal infection (RR = 0.27, 95% CI: 0.02 to 3.94,P= 0.34), intraventricular hemorrhage (RR = 1.40, 95% CI: 0.39 to 5.08,P= 0.61), and urinary tract infection (RR = 0.35, 95% CI: 0.11 to 1.06,P= 0.06). Subgroup analysis revealed that lactoferrin significantly reduced the incidence of sepsis in infants with a birth weight below 1500 g (RR = 0.43, 95% CI: 0.22 to 0.84,P= 0.01). TSAs of the primary outcomes showed that the evidence is insufficient and further data is required. Conclusions Limited evidence suggested that enteral lactoferrin supplementation was associated with a reduction of late-onset sepsis in infants with a birth weight below 1500g, however, did not decrease the incidence of NEC stage II or III, all-cause mortality, and other adverse events in preterm infants. The present evidence was insufficient to inform clinical practice.

Objective: The study aimed to evaluate the effectiveness of health education intervention for the control of blood pressure (BP) in older adults with hypertension. Methods: Five databases were searched in March 2018 for randomized controlled trials to manage hypertension in older adults by health education. The primary outcomes were changes in systolic and diastolic BP. RevMan5 was used for meta-analysis. Results: Seven articles with 1,105 participants were included. In them, 393 (35.56%) older adults participated in health education interventions in the form of courses, and 226 (20.45%), in health education sessions. The meta-analysis suggested an overall reduction in systolic BP after health education courses (SMD, standardized mean difference = 4.80, 95% CI: 7.01-2.59, p < .05). Similar results were observed after health education sessions (SMD = 11.73, 95% CI: 17.63-5.82, p < .05). The diastolic BP reduction showed no difference after the health education course (p = .09). The random effects meta-analysis suggested an overall reduction in diastolic BP after health education sessions (SMD = 5.39, 95% CI: 7.98-2.79, p < .05). Conclusion: Although different health education methods had different effects on hypertension control, overall, educational interventions can potentially lead to improved BP control.

Objective: To assess the effectiveness of non-pharmacological interventions for seniors with depressive symptoms. Methods: A comprehensive literature search was performed. We conducted network meta-analysis in two ways, intervention classes (psychosocial, psychotherapy, physical activity, combined, treatment as usual) and individual intervention (11 categories). Whenever included studies used different scales, the different instruments were converted to the units of the scale most frequently used (the Geriatric Depression Scale), such that the effect size was reported as a mean difference (MD) with 95% confidence interval (CI). The risk of bias of RCTs included in this review was assessed according to the Cochrane Handbook. Bayesian NMA was conducted using R-3.4.0 software. Results: A total of 35 RCTs with 3,797 enrolled patients were included. Compared to conventional treatment, physical activity and psychotherapy resulted in significant improvements in depressive symptoms (MD: 2.25, 95%CrI: 0.99-3.56; SUCRA = 86.07%; MD: 1.75, 95% CrI: 0.90-2.64; SUCRA = 66.44%, respectively). Similar results were obtained for music (MD: 2.6; 95% CrI: 0.84-4.35;SUCRA = 80.53%), life review (MD:1.92; 95% CrI:0.71-3.14; SUCRA = 65.62%), cognitive behavioral therapy (MD: 1.27; 95% CrI: 0.23-2.38; SUCRA = 45.4%), aerobic (MD: 1.84; 95% CrI: 0.39-3.36; SUCRA = 63%) and resistance training (MD: 1.72; 95% CrI: 0.06-3.42; SUCRA = 59.24%). Network meta-regression showed that there were no statistically significant subgroup effects. Conclusions: Physical activity and psychotherapy demonstrated statistically significant superiority over conventional treatment. Music and life review therapy proved the most promising individual interventions. However, conclusions are limited by the lack of sufficient sample size and consensus regarding intervention categories and so an adequately powered study is necessary to consolidate these findings.

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.