BMJ medicine最新文献

Objective: To summarise the effects of metformin on covid-19 to inform a World Health Organization (WHO) clinical practice guideline.

Design: Systematic review and meta-analysis.

Data sources: As part of a living systematic review and network meta-analysis of drug treatments for covid-19 (covid-19 LNMA), a search was performed of the WHO covid-19 database, six Chinese databases, and the Epistemonikos Foundation's Living Overview of the Evidence covid-19 Repository (covid-19 L-OVE).

Eligibility criteria for selecting studies: Randomised controlled trials that compared metformin with placebo in patients with acute covid-19 infection.

Data synthesis: Frequentist pairwise meta-analyses were performed using the restricted maximum likelihood random effects model. The effects of interventions on selected outcomes were summarised using risk ratios, risk difference, and mean difference when appropriate, along with their corresponding 95% confidence intervals (CIs). To estimate absolute effects, the control arm event rate was used as the baseline risk. The 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 evidence using the GRADE (grading of recommendations assessment, development and evaluation) approach, with the minimally important difference in effect as the threshold.

Results: Three randomised controlled trials of 1869 patients were included; one study provided long term follow-up on long covid. Metformin might have little or no impact on mortality (risk ratio 0.76, 95% CI 0.30 to 1.90; risk difference 3 fewer per 1000, 95% CI 8 fewer to 11 more; low certainty). The effects of metformin on admission to hospital because of covid-19 remain uncertain (risk ratio 0.74, 95% CI 0.28 to 1.95; risk difference 15 fewer per 1000, 95% CI 42 fewer to 55 more; very low certainty). Metformin results in little or no difference in adverse effects leading to discontinuation (risk difference 0.2 more per 1000, 95% CI 2.7 fewer to 3.1 more; high certainty). Metformin might decrease the development of long covid (risk ratio 0.6, 95% CI 0.4 to 0.9; risk difference 41 fewer per 1000, 95% CI 62 fewer to 10 fewer; low certainty). However, the effect is based on a single trial of 1126 patients, which has a high risk of bias owing to missing data, and nearly half of the participants were unvaccinated.

Conclusions: Current evidence based on randomised trials suggests no significant effect of metformin on acute clinical outcomes in patients with non-severe covid-19. Metformin might reduce the incidence of long covid when used to treat patients with non-severe acute covid-19 infection, but this was suggested by low certainty evidence from a single trial.

Objective: To provide evidence for a reduced surveillance protocol to detect gestational trophoblastic neoplasia after normalisation of human chorionic gonadotrophin (hCG) levels following uterine evacuation of a complete hydatidiform mole.

Design: National retrospective population study.

Setting: Two UK Trophoblastic Disease Treatment Centres (Sheffield and London), 1 January 1980 to 30 November 2020.

Participants: 17 424 patients with hCG normalisation after evacuation of their complete hydatidiform mole were included. Complete hydatidiform moles were verified by centralised pathological review. Patients were excluded if lost to follow-up or required treatment before normalisation of hCG levels.

Main outcome measures: Incidence and clinical presentation of gestational trophoblastic neoplasia after normalisation of hCG levels following uterine evacuation of a complete hydatidiform mole.

Results: Of 17 424 patients whose hCG normalised after complete hydatidiform mole evacuation, 99.8% (n=17 393 of 17 424) did not subsequently develop gestational trophoblastic neoplasia. The overall risk of gestational trophoblastic neoplasia after previous normalisation of hCG levels was 0.2% (n=31 of 17 424 patients). The risk of developing gestational trophoblastic neoplasia after uterine evacuation was substantially lower if hCG levels returned to normal in <56 days rather than ≥56 days (posterior medians 0.06%, 95% credible interval 0.01% to 0.14% v 0.22%, 0.15% to 0.31%), with a posterior relative risk of 0.25 (0.06 to 0.72). Most patients who developed gestational trophoblastic neoplasia (71.0%, n=22 of 31) had received a diagnosis after the current six month surveillance protocol. The cumulative risk of developing gestational trophoblastic neoplasia in patients whose hCG levels normalised early increased minimally with time. If a patient had normal hCG levels in <56 days, a clinically relevant time point, the risk of developing gestational trophoblastic neoplasia was small (0.04%, about 1 in 2619 patients) at 39 months after normalisation. The equivalent risk for a patient who had normal hCG levels in ≥56 days was 0.16% (about 1 in 642 patients). All 31 women who developed gestational trophoblastic neoplasia achieved sustained remission after subsequent treatment.

Conclusions: The findings of the study indicate that surveillance protocols could safely change to one confirmatory normal hCG value for patients whose hCG levels return to normal in <56 days of evacuation of a complete hydatidiform mole. Patients whose hCG levels return to normal in ≥56 days should be counselled on the remaining risk of gestational trophoblastic neoplasia over time to help decide the length of subsequent follow-up.

Objective: To quantify the prognostic value of mid-trimester cervical length for spontaneous preterm birth in asymptomatic women with twin pregnancy and to assess whether other factors may modify any association.

Designs: A two stage meta-analysis of individual participant data in a Cox proportional hazard model was performed using cervical length as a continuous variable.

Data sources: Medline, Embase, Cochrane, and LILACS, among others, were searched to identify eligible studies; the search was from 1 January 2000 to 30 September 2020. Risk of bias was assessed with the QUIPS tool. Studies were from eight countries between 2001 and 2018.

Eligibility criteria: Individual participant data were sought for eligible studies that reported mid-trimester (defined between 16 and 26 weeks) transvaginal sonographic cervical length and also gestational age at birth in asymptomatic women with twin pregnancy. The primary outcome was spontaneous preterm birth before 37 weeks.

Results: Among 29 eligible studies, authors of 17 studies provided individual participant data for 6437 women with a twin pregnancy (69.1% of individual participant data). Mean cervical length measurement was 39 mm (SD=9, range 1-74 mm). 2889 women (44.9%) delivered before 37 weeks' gestation, and 934 (14.9%) delivered before 34 weeks. Each 1 mm increase in cervical length was associated with a 4.0% reduction in the rate of spontaneous preterm birth before 37 weeks (hazard ratio 0.96 (95% confidence interval 0.95 to 0.97)), and a 6.8% reduction in the rate of spontaneous preterm birth before 34 weeks' gestation (0.93 (0.92 to 0.95)). The prognostic value remained stable in models adjusting for different sets of variables.

Conclusion: The prognostic value of cervical length for spontaneous preterm birth in twin pregnancy is on a continuous scale. No specific cervical length has been identified that can reliably predict or exclude all spontaneous preterm births.

Study registration: CRD42020146987.

Objective: To evaluate the effectiveness and benefit-harm balance of various statins for the primary prevention of cardiovascular disease in people with HIV.

Design: Target trial and modelling study.

Setting: North American AIDS Cohort Collaboration on Research and Design (NA-ACCORD), 1995 to 2019. NA-ACCORD integrates individual level data from >20 HIV cohorts across the US and Canada from people with HIV who have successfully linked into care.

Participants: 157 699 people with HIV enrolled in one of the cohorts of NA-ACCORD. 54 165 eligible individuals, aged 40-75 years, were enrolled in the target trial.

Main outcome measures: The primary outcomes for the target trial were the 10 year effects of statins on cardiovascular disease events (fatal and non-fatal myocardial infarction, hospital admission for unstable angina, coronary or arterial revascularisation, fatal and non-fatal stroke, or transient ischaemic attack) and harm outcomes (type 2 diabetes, mild cognitive impairment, rhabdomyolysis, and myopathy). The secondary outcome was the 10 year risk threshold where the reduction in cardiovascular disease outweighed the increased risk of harm outcomes, showing an overall net benefit of statins.

Results: Participants who first started receiving treatment with statins (statin initiators) had a 21% reduction in cardiovascular disease events (hazard ratio 0.79, 95% confidence interval (CI) 0.72 to 0.87) and a 26% reduction in the combined risk of stroke and myocardial infarction (0.74, 0.56 to 0.98), but a 12% increase in the risk of type 2 diabetes (1.12, 1.01 to 1.25) compared with participants who developed the indication but did not take statins (non-initiators). The effects on cognitive impairment (hazard ratio 1.13, 95% CI 0.82 to 1.56), myopathy (1.10, 0.76 to 1.61), and rhabdomyolysis (1.09, 0.68 to 1.75) were not statistically significant. On average, the benefit of statins exceeded harms for individuals with a 10 year baseline risk of cardiovascular disease of ≥13.8%. Subgroup specific thresholds included men (14.2%), women (11.1%), ages 40-64 years (13.8%) versus 65-75 years (15.1%), and CD4 count >200 cells/mm³ (13.6%) versus <200 cells/mm³ (15.3%). Varying weights for cardiovascular disease yielded thresholds ranging from 11.6% to 54.0%, whereas weights for harm outcomes resulted in thresholds ranging from 5.0% to >30.0%.

Conclusions: In this study, statins benefitted individuals with HIV with a moderate or high risk of cardiovascular disease, but the threshold for net benefit varied by patient subgroup and preference, implying the need to customise statin treatment to individual risks, preferences, and treatment goals. Given the limitations of observational data, further controlled studies are needed to evaluate the efficacy and safety of statins in people with HIV receiving mode

[This corrects the article DOI: 10.1136/bmjmed-2023-000709.].

Abstract:

Objective: To assess whether relaxation and stress management techniques are useful in reducing blood pressure in individuals with hypertension and prehypertension.

Design: Systematic review and network meta-analysis.

Data sources: Medline, PsycInfo, and CENTRAL (Cochrane Central Register of Controlled Trials) from inception to 23 February 2024, and CINAHL (Cumulative Index to Nursing and Allied Health Literature) from inception to 27 February 2024.

Eligibility criteria for selecting studies: Studies published in English of adults with hypertension (blood pressure ≥140/90 mm Hg) or prehypertension (blood pressure ≥120/80 mm Hg but <140/90 mm Hg). Studies that compared non-pharmacological interventions used to promote relaxation or reduce stress with each other, or with a control group (eg, no intervention, waiting list, or standard care). Where possible, network meta-analysis was used to compare the efficacy of the different interventions. Studies were assessed with the risk of bias 2 tool (RoB2), and those at high risk of bias were excluded from the primary analysis. The certainty of the evidence was assessed with CINeMA (Confidence in Network Meta-Analysis) and GRADE (Grading of Recommendations Assessment, Development, and Evaluation).

Results: 182 studies were included (166 for hypertension and 16 for prehypertension). Results from a random effects network meta-analysis showed that, at short term follow-up (≤3 months), most relaxation interventions appeared to have a beneficial effect on systolic and diastolic blood pressure for individuals with hypertension. Between study heterogeneity was moderate (τ=2.62-4.73). Compared with a passive comparator (ie, no intervention, waiting list, or usual care), moderate reductions in systolic blood pressure were found for breathing control (mean difference -6.65 mm Hg, 95% credible interval -10.39 to -2.93), meditation (mean difference -7.71 mm Hg, -14.07 to -1.29), meditative movement (including tai chi and yoga, mean difference -9.58 mm Hg, -12.95 to -6.17), mindfulness (mean difference -9.90 mm Hg, -16.44 to -3.53), music (mean difference -6.61 mm Hg, -11.62 to -1.56), progressive muscle relaxation (mean difference -7.46 mm Hg, -12.15 to -2.96), psychotherapy (mean difference -9.83 mm Hg, -16.24 to -3.43), and multicomponent interventions (mean difference -6.78 mm Hg, -11.59 to -1.99). Reductions were also seen in diastolic blood pressure. Few studies conducted follow-up for more than three months, but effects on blood pressure seemed to lessen over time. Limited data were available for prehypertension; only two studies compared short term follow-up of relaxation therapies with a passive comparator, and the effects on systolic blood pressure were small (mean difference -3.84 mm Hg, 95% credible interval -6.25 to -1.43 for meditative movement; mean difference

Objective: To examine the causal effects of loneliness on mortality among Australian women aged 45 years and older.

Design: Causal inference analysis of longitudinal data.

Participants: A population based sample of Australian women aged 45 years and older (n=11 412).

Main outcome measures: Targeted maximum likelihood estimations were used to analyse the causal relationship between loneliness and all cause mortality over 18 years. The adjusted risk of death associated with the total number of loneliness waves (loneliness persistency) and the consecutive number of loneliness waves (loneliness chronicity) was presented using risk ratios and risk differences with 99.5% confidence intervals (CIs).

Results: The association between the number of waves of reported loneliness and mortality risk showed a dose-dependent pattern. Compared with women who did not report loneliness in any wave, people who reported loneliness at two, four, and six waves had an incrementally higher risk of dying during the follow-up period: risk ratio 1.49 (99.5% CI 1.26 to 1.75) at two waves, 2.18 (1.79 to 2.66) at four waves, and 3.15 (2.35 to 4.23) at six waves. The risk difference showed a similar trend to the risk ratios with higher excess mortality among women who reported experiencing loneliness for six waves compared with those who did not report loneliness at all (10.86% (99.5% CI 10.58% to 11.15%)). Similar trends were found when loneliness was experienced across consecutive waves.

Conclusions: Loneliness seems to be causally linked to mortality risk with a dose-dependent relationship. Acknowledging loneliness as an independent health risk underscores the importance of screening for loneliness and incorporating public health interventions into healthcare practices.