BMC Medicine最新文献

Background: In Australia, diabetes is the fastest growing chronic condition, with prevalence trebling over the past three decades. Despite reported sex differences in diabetes outcomes, disparities in management and health targets remain unclear. This population-based retrospective study used MedicineInsight primary healthcare data to investigate sex differences in diabetes prevalence, incidence, management, and achievement of health targets.

Methods: Adults (aged ≥ 18 years) attending 39 general practices in Western Australia were included. Diabetes incidence and prevalence were estimated by age category. Health targets assessed included body mass index (BMI), blood pressure, blood lipids, and glycated haemoglobin (HbA_1c) levels. Medical management of diabetes-associated conditions was also investigated. Time-to-incident diabetes was modelled using a Weibull regression. A multilevel mixed-effects logistic regression model investigated risk-adjusted sex differences in achieving the HbA_1c health target (HbA_1c ≤ 7.0% (≤ 53 mmol/mol)).

Results: Records of 668,891 individuals (53.4% women) were analysed. Diabetes prevalence ranged from 1.3% (95% confidence interval (CI) 1.2%-1.3%) in those aged < 50 years to 7.2% (95% CI 7.1%-7.3%) in those aged ≥ 50 years and was overall higher in men. In patients younger than 30 years, incidence was higher in women, with this reversing after the age of 50. Among patients with diabetes, BMI ≥ 35 kg/m² was more prevalent in women, whereas current and past smoking were more common in men. Women were less likely than men to achieve lipid health targets and less likely to receive prescriptions for lipid, blood pressure, or glucose-lowering agents. Men with incident diabetes were 21% less likely than women to meet the HbA1_c target. Similarly, ever recorded retinopathy, nephropathy, neuropathy, hypertension, dyslipidaemia, coronary heart disease, heart failure, peripheral vascular disease and peripheral artery disease were higher in men than women.

Conclusions: This research underscores variations in diabetes epidemiology and management based on sex. Tailoring diabetes management should consider the patient's sex.

Background: Drug target Mendelian randomization describes the use of genetic variants as instrumental variables for studying the effects of pharmacological agents. The paradigm can be used to inform on all aspects of drug development and has become increasingly popular over the last decade, particularly given the time- and cost-efficiency with which it can be performed even before commencing clinical studies.

Main body: In this review, we describe the recent emergence of drug target Mendelian randomization, its common pitfalls, how best to address them, as well as potential future directions. Throughout, we offer advice based on our experiences on how to approach these types of studies, which we hope will be useful for both practitioners and those translating the findings from such work.

Conclusions: Drug target Mendelian randomization is nuanced and requires a combination of biological, statistical, genetic, epidemiological, clinical, and pharmaceutical expertise to be utilized to its full potential. Unfortunately, these skillsets are relatively infrequently combined in any given study.

Background: The Netherlands is one of few countries worldwide which has used the bivalent HPV vaccine for girls-only for over a decade. This allows assessment of vaccine effectiveness (VE) against female genital HPV DNA-positivity of this vaccine in an observational post-licencing real-world setting. Additionally, it is unclear whether catch-up vaccination campaigns result in similar VE as routine vaccination. Therefore, type-specific and grouped VE were assessed and compared for women who had been eligible for catch-up vaccination at 13-16 years with those who had been eligible for routine vaccination at 12 years.

Methods: PASSYON is a Dutch biennial repeated cross-sectional (2011-2021) study among sexual health clinic clients aged 16-24 years old. Women provided self-collected vaginal samples, questionnaires on demographics and sexual behaviour were administered, and women self-reported HPV vaccination status. Samples were analysed using a PCR-based assay (SPF₁₀-LiPA₂₅). Type-specific and grouped VE estimates, adjusted with propensity score stratification, were assessed against genital positivity for 14 HPV types. VE for targeted and non-targeted genotypes were compared between women who had been eligible for the catch-up and those who had been eligible for routine vaccination.

Results: The study included 4488 female participants who had been eligible for HPV vaccination and provided genital swabs (1561 eligible for catch-up, 2927 for routine vaccination). Very high VE against genital HPV-16 and HPV-18 was observed (resp. 93.5% and 89.5%) and significant cross-protection against six other genotypes (HPV-31/33/35/45/52/58), varying from 18.0% (HPV-52) to 79.6% (HPV-45). VE estimates were comparable between women who had been eligible for the catch-up campaign and those eligible for routine vaccination: VE HPV-16/HPV-18: 92.2% (95%CI: 87.9-94.9) vs. 91.8% (95%CI: 86.0-95.2).

Conclusions: In real-world settings, the VE of bivalent vaccine is high against targeted genotypes, with cross-protection against 6 other genotypes. Catch-up campaigns up to age 16 years can be as effective as routine vaccination at age 12, although it is recommendable to provide HPV vaccination at an age at which most are likely not sexually active yet. This may inform countries considering catch-up campaigns when introducing or extending the use of HPV vaccination within their national immunisation programmes.

Background: Understanding the frequency of violence experienced by female sex workers (FSWs) and how violence contributes to HIV transmission can help improve HIV programs.

Methods: Using recent recommendations for modelling structural factors and associated causal pathways, we developed a HIV transmission dynamic model for FSWs and their clients in Mombasa, Kenya, mechanistically representing three types of violence (sexual violence, SV; physical violence, PV; police assault and arrest, PAA). Each type of violence affects HIV transmission through key mediators (condom non-use, HIV testing). We parameterized the model using data from a cross-sectional study of FSWs aged 15-24 recruited from a systematic geographical mapping sampling frame in Mombasa, Kenya (Cheuk E et al., Frontiers in Reproductive Health 2(7), 2020). Using this model, calibrated (and cross-validated) to HIV epidemiological and violence outcomes, we estimated the incidence of violence episodes, the contribution of violence to the HIV epidemic measured by the transmission population-attributable fraction, and the potential impact of possible violence interventions.

Results: The median estimated incidence of PAA in 2023 among FSWs who had not previously experienced that type of violence was 0.20 (95% credible interval: 0.17-0.22) per person-year (ppy), about double the incidence of SV and PV (0.10 (0.09-0.11), 0.11 (0.09-0.12), respectively). The incidence of violence was higher among FSWs who had previously experienced violence: the incidence of recurrent PV was 2.65 (1.82-3.37) ppy, while the incidence of recurrent SV and PAA were 1.26 (0.80-1.67) and 1.37 (0.94-1.74 ppy, respectively. In this setting, we estimated that a median of 35.3% (3.4-55.8%) infections in FSWs and clients combined over the next 10 years may be due to all types of violence (and mediators), mainly through reduced condom use in FSWs who have ever experienced SV (34.6% (2.4-55.5%)). Interventions that prevent future violence without mitigating the effects of past violence may only prevent 8.8% (0.8-14.0%) infections over 10 years.

Conclusions: FSWs in Mombasa experience violence frequently. In this population, we find that addressing sexual violence, including mitigating the effects of past violence, is potentially important in reducing HIV transmission in this population. However, the wide uncertainty range shows longitudinal studies are needed to strengthen the evidence of the influence of violence on HIV risk behavior. We find that the recommendations for modelling structural factors provide a useful framework for describing the model.

Background: Computerised cognitive training (CCT) can improve the cognitive abilities of people with mild cognitive impairment (MCI), especially when the CCT contains a learning system, which is a type of machine learning (ML) that automatically selects exercises at a difficulty that corresponds to the person's peak performance and thus enables individualised training.

Methods: We developed one individualised CCT (iCCT) with ML and one basic CCT (bCCT) for an active control group (CG). The study aimed to determine whether iCCT in the intervention group (IG) resulted in significantly greater enhancements in overall cognitive functioning for individuals with MCI (age 60+) compared with bCCT in the CG across a 6-month period. This double-blind randomised controlled study was conducted entirely virtually. The 89 participants were community-dwelling people with a psychometric diagnosis of MCI living in Germany. The iCCT stimulates various cognitive functions, especially working memory, visuo-constructional reasoning, and decision-making. The bCCT includes fewer and simpler tasks. Both CCTs were used at home. At baseline and after 6 months, we assessed cognitive functioning with the Montreal Cognitive Assessment (MoCA). A mixed-model ANCOVA was conducted as the main analysis.

Results: Both CCTs led to significant increases in average global cognition. The estimated marginal means of the MoCA score increased significantly in the CG by an average of 0.9 points (95% CI [0.2, 1.7]) from 22.3 (SE = 0.25) to 23.2 (SE = 0.41) points (p = 0.018); in the IG, the MoCA score increased by an average of 2.2 points (95% CI [1.4, 2.9]) from 21.9 (SE = 0.26) to 24.1 (SE = 0.42) points (p < 0.001). In a confound-adjusted multiple regression model, the interaction between time and group was statistically significant (F = 4.92; p = 0.029). The effect size was small to medium (partial η² = 0.057). On average, the participants used the CCTs three times per week with an average duration of 34.9 min per application. The iCCT was evaluated as more attractive and more stimulating than the bCCT.

Conclusions: By using a multi-tasking CCT three times a week for 30 min, people with MCI living at home can significantly improve their cognitive abilities within 6 months. The use of ML significantly increases the effectiveness of cognitive training and improves user satisfaction.

Trial registration: ISRCTN14437015; registered February 27, 2020.

Background: Published data on whether post-stroke delirium (PSD) is an independent predictor of outcomes in patients with acute stroke are inconsistent and have not yet been synthesized and quantified via meta-analyses.

Methods: This systematic review and meta-analysis followed the Meta-analysis of Observational Studies in Epidemiology (MOOSE) and Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines. The study protocol involved a search of the PubMed, Embase, PsycINFO, and Medline databases from 1946 to November 1, 2023, of which prospective observational and case-control studies were included. The quality of the included studies was rated using the Newcastle Ottawa Scale. Pooled effect estimates calculated using a random-effects model were expressed as the odds ratios (ORs), hazard ratios (HRs), and standardized mean differences (SMDs) with 95% confidence intervals (CIs). The protocol was registered in PROSPERO (CRD42023472551).

Results: The search yielded 39 eligible articles comprising 3295 and 9643 patients with and without PSD, respectively. Thirty studies were high quality, while 9 had moderate quality. The primary analyses, adequately adjusting for predefined confounders, showed that PSD was significantly associated with mortality risk (average follow-up of 19.50 months; OR, 3.47; 95% CI, 2.35-5.12; I², 26.0%) and poor neurological function (average follow-up of 21.75 months; OR, 3.62; 95% CI, 2.15-6.09; I², 0). Secondary analyses, with or without inadequate adjustment, showed that PSD was significantly associated with prolonged hospital length of stay, increased risk of institutionalization, poor cognitive outcomes, and quality of life after discharge.

Conclusions: This systematic review and meta-analysis provides evidence that PSD was independently associated with mortality and poor neurological function after controlling for pre-specified confounders. The prevention of PSD remains a high clinical and research priority.