BMJ medicine最新文献

Objective: To examine the association between maternal mRNA covid-19 vaccination during the first trimester of pregnancy and the prevalence of major congenital anomalies in offspring.

Design: Population based cohort study with sibling matched analysis.

Setting: Multiple health administrative databases, linked and analysed at ICES, an independent, non-profit research institute that collects and analyses healthcare and demographic data, Ontario, Canada, from 16 October 2021 to 1 May 2023.

Population: 174 296 singleton live births >20 weeks' gestation with an expected birth date between 16 October 2021 and 1 May 2023: 34 181 (20%) born to mothers who received one or two doses of an mRNA covid-19 vaccine in the first trimester and 34 951 (20%) born to mothers who did not receive a vaccine before or during pregnancy. The sibling matched analysis included 13 312 infants exposed to a covid-19 vaccine in the first trimester and 15 089 matched older siblings with the same mother, with an expected birth date after 16 October 2016 and no reported in utero exposure to a covid-19 vaccine.

Main outcome measures: Major congenital anomalies, overall and grouped by specific organ systems, diagnosed within 28 days of birth.

Results: Major congenital anomalies were present in 832 (24.3 per 1000 live births) infants exposed to an mRNA covid-19 vaccine in the first trimester compared with 927 (26.5 per 1000 live births) infants not exposed to a vaccine, resulting in an adjusted prevalence ratio of 0.89 (95% confidence interval (CI) 0.79 to 1.01). Major congenital anomalies were present in 283 (21.3 per 1000 live births) and 343 (22.7 per 1000 live births) infants exposed to an mRNA covid-19 vaccine in the first trimester and their older siblings not exposed to a vaccine, respectively (adjusted prevalence ratio 0.91, 95% CI 0.77 to 1.07). First trimester vaccination was not associated with an increase in major congenital anomalies grouped by specific organ system in the primary or sibling matched analyses. Results were similar across a range of subgroup and sensitivity analyses.

Conclusions: In this large population based cohort study and sibling matched analysis, mRNA covid-19 vaccination during the first trimester of pregnancy was not associated with an increase in major congenital anomalies in offspring, overall or grouped by organ system.

Objective: To assess the benefits and harms of deep brain stimulation for Parkinson's disease.

Design: Systematic review with meta-analysis and trial sequential analysis.

Data sources: Cochrane Central Register of Controlled Trials (CENTRAL), Medline, Embase, Latin American and Caribbean Health Sciences Literature (LILACS), and other sources, from inception to 9 May 2023.

Eligibility criteria for selecting studies: Randomised clinical trials of deep brain stimulation with antiparkinsonian drug treatment use versus antiparkinsonian drugs only (primary comparison, seven trials) for Parkinson's disease. Other comparisons were deep brain stimulation versus surgery with sham stimulation (three trials) and versus resective surgery (two trials).

Results: Primary outcomes were all cause mortality, serious adverse events, and disease specific symptoms. In seven trials, 1125 participants were randomised to receive deep brain stimulation with antiparkinsonian drugs versus antiparkinsonian drugs only. All results had a high risk of bias and the certainty of the evidence was very low for all primary outcomes. Information size was insufficient for assessing all cause mortality (risk ratio 2.69, 95% confidence interval (CI) 0.79 to 9.24; I²=0.0%; τ²=0.00; P=0.12; four trials). Meta-analysis showed that deep brain stimulation increased the risk of serious adverse events (risk ratio 2.36, 95% CI 1.37 to 4.09; I²=73.7%; τ²=0.24; P<0.01; six trials) mainly because of an increased risk of perioperative complications, such as cerebral haemorrhages and postoperative confusion, and hardware related events, such as infection at the stimulator site, dislocation of the device, or reoperations. Meta-analyses indicated that deep brain stimulation might reduce some symptoms specific to Parkinson's disease, but assessment of disease specific symptoms in these trials had methodological limitations, including not reporting overall symptom scores.

Conclusions: The certainty of evidence was very low for all primary outcomes, and based on the included evidence, the beneficial effects were questionable because of methodological limitations. Compared with only antiparkinsonian drug treatment, deep brain stimulation with antiparkinsonian drugs seemed to increase the risk of serious adverse events, mainly because of perioperative complications and hardware related events. Conducting randomised clinical trials of adequate methodological quality to effectively evaluate the effects of deep brain stimulation is crucial.

Systematic review registration: PROSPERO CRD42022306556.

Abstract:

Objectives: To describe the effect of multimorbidity on adverse patient centred outcomes in people attending emergency department.

Design: Population based cohort study.

Setting: Emergency departments in NHS Lothian in Scotland, from 1 January 2012 to 31 December 2019.

Participants: Adults (≥18 years) attending emergency departments.

Data sources: Linked data from emergency departments, hospital discharges, and cancer registries, and national mortality data.

Main outcome measures: Multimorbidity was defined as at least two conditions from the Elixhauser comorbidity index. Multivariable logistic or linear regression was used to assess associations of multimorbidity with 30 day mortality (primary outcome), hospital admission, reattendance at the emergency department within seven days, and time spent in emergency department (secondary outcomes). Primary analysis was stratified by age (<65 v ≥65 years).

Results: 451 291 people had 1 273 937 attendances to emergency departments during the study period. 43 504 (9.6%) had multimorbidity, and people with multimorbidity were older (median 73 v 43 years), more likely to arrive by emergency ambulance (57.8% v 23.7%), and more likely to be triaged as very urgent (23.5% v 9.2%) than people who do not have multimorbidity. After adjusting for other prognostic covariates, multimorbidity, compared with no multimorbidity, was associated with higher 30 day mortality (8.2% v 1.2%, adjusted odds ratio 1.81 (95% confidence interval (CI) 1.72 to 1.91)), higher rate of hospital admission (60.1% v 20.5%, 1.81 (1.76 to 1.86)), higher reattendance to an emergency department within seven days (7.8% v 3.5%, 1.41 (1.32 to 1.50)), and longer time spent in the department (adjusted coefficient 0.27 h (95% CI 0.26 to 0.27)). The size of associations between multimorbidity and all outcomes were larger in younger patients: for example, the adjusted odds ratio of 30 day mortality was 3.03 (95% CI 2.68 to 3.42) in people younger than 65 years versus 1.61 (95% CI 1.53 to 1.71) in those 65 years or older.

Conclusions: Almost one in ten patients presenting to emergency department had multimorbidity using Elixhauser index conditions. Multimorbidity was strongly associated with adverse outcomes and these associations were stronger in younger people. The increasing prevalence of multimorbidity in the population is likely to exacerbate strain on emergency departments unless practice and policy evolve to meet the growing demand.

Objective: To assess inequalities in all cause and cause specific mortality in young people and if there are differences across gender and age groups.

Design: Nationwide cohort study of socioeconomic predictors.

Setting: Denmark, 1 January 2010 to 31 December 2022.

Participants: All Danes of ages 15 to 24 years during the study period summing to a total of 9 314 807 person years and 2297 deaths. Participant and parental information were linked to obtain information on socioeconomic background to investigate differences in parents' educational level, employment status, and family's disposable income, using annually updated nationwide registers.

Main outcome measures: All cause and cause specific mortality including natural deaths (ie, medical conditions and diseases) and unnatural deaths (accidents, suicides, and homicides). Poisson regression was used to calculate incidence rate ratios and 95% confidence intervals (CI).

Results: Overall mortality rate was 24.7 (95% CI 23.7 to 25.7) and higher for men (33.2 (31.5 to 34.8)) compared with women (15.8 (14.6 to 16.9)). All cause and cause specific mortality were higher in financially disadvantaged groups compared with more affluent groups, and consistently so for all three measures of socioeconomic position. Results generally reflected a dose dependent association showing a higher mortality with lower levels of socioeconomic position. For instance, incidence rate ratios of all cause mortality related to parents' education was 2.3 (95% CI 2.0 to 2.7) for elementary level, 1.5 (1.3 to 1.6) for low, and 1.3 (1.1 to 1.4) for medium level as compared with high level. For deaths, incidence rate ratios of elementary education level compared with the most well educated group were 2.2 (1.5 to 3.2) for natural causes, 3.3 (2.5 to 4.4) for accidents, 1.6 (1.2 to 2.2) for suicides, and 3.1 (0.8 to 12) for homicides. Associations were similar in strata of men and women and by age group (15-17 v 18-24 years). Mortality in young men was considerably higher than in young women for all of the causes.

Conclusion: Young people from disadvantaged backgrounds have a markedly higher mortality from all causes than those from more affluent families. The socioeconomic position of their parents was associated with premature mortality in a dose dependent manner meaning that this effect is not only a concern for marginalised groups. Public health attention should be directed to respond to these inequities by strengthening advocacy for adolescent health, ensuring focus on adolescents in health policies and strategies, using the response to adolescent health as an indicator of equity, and prioritising research into the underlying mechanisms linking socioeconomic position in adolescence and mortality.