BMC Medicine最新文献

Background: Sleep quality during pregnancy and the postpartum period is increasingly acknowledged as a critical influencing factor of postpartum. However, the complexities of this relationship, particularly the core depressive symptoms across varying sleep quality trajectories, remain poorly understood.

Methods: This study included 372 participants from the "Be Resilient to Postpartum Depression" cohort, with data collected at four intervals spanning early pregnancy to 42 days after childbirth. Validated instruments were used to evaluate both sleep quality and postpartum depression. Data analysis employed group-based trajectory modeling and computer-simulated network analysis.

Results: Two distinct trajectories of sleep quality were identified: "increasingly poor" trajectory (41.4%), which exhibited a markedly higher rate of postpartum depression (OR = 2.75, P < 0.001), and "stably good" trajectory (58.6%). Within the "increasingly poor" trajectory, the symptom "Things have been getting on top of me" emerged as both the core and aggravating symptom. In the "stably good" group, the core and aggravating symptom was "I have felt scared or panicky for no very good reason." Additionally, "I have been anxious or worried for no good reason" and "I have been so unhappy that I have had difficulty sleeping" were identified as key symptoms associated with alleviating depressive symptoms in the "increasingly poor" and the "stably good" groups, respectively.

Conclusions: The study underscores the heterogeneous nature of sleep quality trajectories and their distinct associations with postpartum depressive symptoms, highlighting the necessity for tailored mental health interventions.

Background: Although obesity is a well-established risk factor for endometrial cancer, its relationship with genetic susceptibility in determining cancer risk remains unexplored. Current endometrial cancer risk prediction relies primarily on epidemiological factors, with limited consideration of genetic risk. We hypothesized that integrating polygenic risk score (PRS) information with established epidemiological factors could improve risk stratification and reveal whether genetic and lifestyle factors operate independently or jointly.

Methods: We generated a polygenic risk score for endometrial cancer in 129,829 unrelated female participants of European genetic ancestry (including 956 incident cases with endometrial cancer) in the UK Biobank cohort. We evaluated the prediction model performance using area under the receiver operating characteristic curves (AUCs) and assessed individual and joint associations of body mass index (BMI) and PRS with endometrial cancer using Cox proportional hazards models.

Results: The integrated model incorporating PRS and epidemiological risk factors achieved statistically significant improvement in predicting endometrial cancer compared with epidemiologic factors alone (AUC = 0.739 versus 0.728; P = 3.98 × 10^-5). Participants in the top 1% PRS distribution had a 3.06-fold increased risk (95% CI 1.97-4.76), with a number needed to screen of 58 individuals. BMI and PRS demonstrated independent effects on endometrial cancer risk, with participants with a BMI ≥ 30 kg/m² in the top PRS tertile showing the highest endometrial cancer risk (HR = 4.94; 95% CI 3.65-6.68). Even participants with a BMI < 25 kg/m² in the top PRS tertile had a significantly increased risk (HR = 2.01; 95% CI 1.45-2.78).

Conclusions: Integrating PRS with epidemiological risk factors provides potential for enhanced endometrial cancer risk stratification. PRS effects persist independently of BMI, suggesting genetic risk assessment could complement current screening approaches focused on Lynch Syndrome and identify additional high-risk individuals for targeted prevention strategies.

Background: Smoking poses health risks to women across the lifespan. This study aimed to examine age-related differences in smoking, quit attempts, and cessation outcomes among women in Great Britain, overall and by socioeconomic position.

Methods: We analysed cross-sectional data from 30,519 women (≥ 16 years) in Great Britain participating in a nationally representative survey between 2023 and 2025. We used logistic regression with restricted cubic splines to obtain age-specific estimates of smoking prevalence, the quit attempt rate, the success rate of quit attempts, and the overall quit rate, among all women and by socioeconomic position (indexed by occupational social grade; ABC1 = more advantaged, C2DE = less advantaged). We calculated prevalence ratios (PR; C2DE/ABC1) to illustrate the extent of socioeconomic disparities.

Results: Overall, smoking prevalence was highest among women in their 20s and 30s and declined with age. However, there were notable differences by socioeconomic position. While it declined steadily with age among more advantaged women, smoking prevalence peaked in the early 40s among less advantaged women and was more than twice that of more advantaged women in mid-life (PR range = 2.02-2.47 between ages 35 and 60). Quit attempts decreased linearly with age, with similar prevalence and trends across socioeconomic groups. The success rate of quit attempts was highest among women in their 20s and 30s, but dropped in mid-life and further in older age. Women from less advantaged backgrounds had lower success rates, particularly between ages 45 and 60 (PR range = 0.70-0.73). The overall quit rate among past-year smokers was highest at age 31 for more advantaged women (23.3%) and at age 25 for less advantaged women (22.9%). Quit rates were substantially lower between ages 40 and 60 among less advantaged women (PR range = 0.65-0.69).

Conclusions: Smoking behaviours and cessation outcomes among women in Great Britain vary by both age and socioeconomic position, with particularly high smoking prevalence and low quit rates among less advantaged women in mid-life, corresponding with perimenopause and the menopausal transition. These disparities highlight the need for tailored smoking cessation strategies to improve quit success and reduce smoking prevalence across the lifespan.

Background: Evidence suggests we must change both the type of food we consume and the way we produce it, at a transformational scale, to protect population and planetary health and avoid exacerbating existing diet-related health inequalities.

Discussion: We summarise key findings from behaviour change theory and literature, highlighting the need for means, motive and opportunity to enact behaviour change. We evaluate and contrast the implications for interventions aimed at individuals vs. businesses, arguing that policy must shift focus from individual responsibility to systemic change.

Conclusion: Past public health interventions have tended to focus on individuals' motivation, with limited impact, while interventions that target the motivation of businesses, if enacted, would likely garner substantially greater impact. Governments implementing mandatory reporting could provide the foundation to realign the incentives that shape business practices. This would subsequently enable mandatory targets to be introduced on foods sold, providing in turn the necessary conditions - the means and opportunity - for individuals to enact dietary change.

Background: Tinnitus affects 10-15% of adults globally, yet there are still no effective treatments for this major health condition. Repetitive transcranial magnetic stimulation (rTMS), a noninvasive neuromodulation technique, allows modulation of pathologically altered functional activities to promote symptom remission. However, its efficacy critically depends on the selection of stimulation targets, and substantial interindividual variability has been observed in clinical trials. Here, we aimed to identify potential target regions that are causally involved in alleviating distinct functional abnormalities using the digital twin brain (DTB).

Methods: A cohort of 89 participants was used to characterize whole-brain neural activity patterns. Multimodal neuroimaging data were used to develop the tinnitus-specific DTB and to generate causal response maps based on more than 1.64 million virtual stimulations. Whole-brain gene expression data were further integrated to examine the neurobiological plausibility of the DTB-derived causal response maps. Finally, we validated the predictive capacity of such response maps using an independent rTMS dataset.

Results: We identified two aberrant brain states that emerged sequentially with disease progression, predominantly overlapping with the somatomotor and default mode networks, respectively. DTB-derived causal response maps revealed that the modulation of sensory and cognitive states requires stimulation of distinct, functionally specialized regions. Specifically, parieto-occipital regions play a crucial role in sensory modulation, while the dorsolateral prefrontal cortex exerts a causal influence on cognitive modulation. Moreover, these causal response maps correlate with the expression of tinnitus risk genes. By incorporating individual connectivity profiles of target regions, DTB-derived causal response maps accurately predicted rTMS effects on both sensory state (r > 0.85, P_permutation < 0.01) and cognitive state (r > 0.78, P_permutation < 0.05). Particularly, the predictive capacity exhibited a state-specific nature.

Conclusions: This work suggests that brain functional alterations in tinnitus evolve with disease progression, and DTB has the potential to predict rTMS effects on distinct brain states, thereby informing more precise and targeted noninvasive brain stimulation interventions for tinnitus.

Trial registration: Trial registered with https://www.chictr.org.cn/indexEN.html, Explore the mechanism of repetitive transcranial magnetic stimulation intervention in tinnitus based on multi-modal functional magnetic resonance imaging (ChiCTR2100047989), Submitted June 2021, First Patient Enrolled July 2021.

Background: Hypertensive heart disease (HHD) and hypertrophic cardiomyopathy (HCM) are characterized by left ventricular hypertrophy and diastolic dysfunction. Despite overlapping remodeling features, their distinct mechanisms and therapeutic responses remain unclear. This study integrated genetic, imaging, and proteomic data to identify key mediators underlying β1-adrenergic receptor blockers (β1-blockers)-related therapeutic heterogeneity between HHD and HCM.

Methods: Genetic instruments for β1-blockers were derived from two genome-wide association studies and integrated with cardiac magnetic resonance radiomic traits and plasma proteomic data from the UK Biobank, along with disease outcomes from FinnGen. A refined two-stage network Mendelian randomization framework with pleiotropy-robust estimators identified mediators of treatment response. To further elucidate their biological and clinical significance, additional analyses were performed, including drug-target profiling, molecular docking, adverse events (AEs) assessment, and drug prediction.

Results: We identified three types of imaging features and ten mediator proteins that contributed to therapeutic responses in HHD and HCM. These mediators were categorized as either mediating (aligned with therapeutic outcomes) or suppressing (opposing therapeutic outcomes). Left ventricular regional radial strain acted as a suppressing factor in HHD but a mediating factor in HCM, whereas end-diastolic and end-systolic volumes consistently showed suppressing effects in both. Regional myocardial wall thickness also exerted a suppressing role in HCM. Among protein mediators, APOE, CGREF1, ITGA5, LSP1, NOS3, and NPPB were linked to HHD, whereas DUSP13, ITGA11, NID1, and SERPINA4 were related to HCM. Specifically, APOE, ITGA5, NOS3, NPPB, DUSP13, and ITGA11 acted as mediating factors, while CGREF1, LSP1, NID1, and SERPINA4 served as suppressing ones. These findings remained robust after pleiotropy adjustment and other genetic analyses. Molecular docking revealed interactions between ADRB1, the β1-blockers target, and downstream proteins, while drug prediction identified eight potential compounds linked to these mediators. Additionally, AE analyses indicated that some targets, such as DUSP13, could both mitigate and aggravate common AEs while contributing to cardiac therapy.

Conclusions: This integrative multi-omics analysis revealed distinct imaging and proteomic mechanisms of genetically proxied β1-blockers in HHD and HCM, providing genetic evidence for differential therapeutic responses and highlighting molecular targets for precision cardiovascular therapy.

Background: This phase II clinical trial evaluated the R2-GemOx-PD1i regimen, a combination of penpulimab (a modified PD1 inhibitor) with lenalidomide and rituximab, gemcitabine, and oxaliplatin, in treating refractory or relapsed (R/R) diffuse large B-cell lymphoma (DLBCL).

Methods: Patients received an induction treatment of up to six cycles of R2-GemOx-PD-1i at standard doses every 2 weeks, followed by pembrolizumab and lenalidomide as maintenance or autologous stem cell transplantation (ASCT) as consolidation. The primary objective was to evaluate the complete response rate (CRR) after the induction phase.

Results: Fifty-four patients were included, including subgroups treated without intent for consolidation with ASCT (N = 38) and those utilizing R2-GemOx-PD1i as a bridge to ASCT (N = 16). The overall response rate (ORR) for all patients was 66.7%, with a CRR of 57.4%. The median progression-free survival (PFS) was 30.4 months, and the median overall survival (OS) was not reached for all patients. Patients receiving R2-GemOx-PD1i without intent for ASCT had ORR and CRR of 63.2% and 52.6%, respectively, with median PFS and OS of 21.2 months and not reached, respectively. Patients receiving R2-GemOx-PD1i as a bridge to ASCT had ORR and CRR of 75.0% and 68.8%, respectively, with median PFS and OS of both not reached, respectively. The most frequent treatment-related adverse events were neutropenia (36, 66.6%) and anemia (32, 59.2%). Hypothyroidism was the most common immune-related adverse event (20 [37.0%]).

Conclusion: The R2-GemOx-PD1i regimen demonstrated encouraging antitumor activity with manageable toxicity in R/R DLBCL, providing some reassurance about its safety and tolerability.

Trial registration: ClinicalTrials.gov, NCT05186558 (Dec 23, 2021).

Background: Timely detection of drug-resistant tuberculosis (DR-TB) is essential for effective treatment and preventing poor outcomes. Rapid molecular diagnostics are promising alternatives to conventional phenotypic drug susceptibility testing (pDST), offering faster and more accessible detection of resistance. This study evaluated the cost-effectiveness of rapid molecular assays, alone or combined with pDST, for detecting resistance to isoniazid, rifampicin, and fluoroquinolones from a South African healthcare provider perspective.

Methods: A decision-analytic model was developed to simulate TB-related outcomes for a hypothetical cohort of microbiologically confirmed TB patients. Nine diagnostic strategies were evaluated: pDST alone; four rapid molecular tests (line probe assays [LPAs], Xpert MTB/RIF [Xpert] followed by Xpert MTB/XDR [Xpert XDR], Xpert MTB/RIF Ultra [Xpert Ultra] followed by Xpert XDR, and targeted next-generation sequencing [tNGS]); and combinations pairing each molecular test with pDST. Outcomes included early treatment rates, mortality, direct medical costs, disability-adjusted life-years (DALYs), and incremental cost-effectiveness ratios (ICERs). Base-case, sensitivity, and scenario analyses were performed.

Results: In the base-case analysis, 'Xpert followed by Xpert XDR + pDST' was the preferred cost-effective strategy, with an ICER of USD 6,554/DALY averted-below South Africa's GDP per capita threshold. While 'tNGS + pDST' yielded the greatest health benefits-lowest DALYs (1.9877), highest early treatment rate (995.54/1,000 tested), and lowest mortality (90.22/1000 tested)-its ICER (USD 25,918/DALY averted) exceeded three times the GDP per capita, rendering it not cost-effective. Sensitivity analyses highlighted the impact of diagnostic accuracy and treatment timing on cost-effectiveness outcomes. Probabilistic sensitivity analysis showed 'tNGS + pDST' had the highest probability of being cost-effective when the willingness-to-pay threshold exceeded USD 10,500/DALY averted. Diagnostic replacement scenario analysis revealed that tNGS alone could be a cost-effective alternative (ICER = USD 1712 per DALY averted) when pDST was unavailable. An extended two-year time horizon analysis confirmed base-case robustness.

Conclusions: Combining rapid molecular diagnostics with pDST offers a cost-effective and clinically beneficial approach for DR-TB detection in high-burden settings. The Xpert-based strategy provides an optimal balance of diagnostic yield, early treatment, and economic efficiency in South Africa. tNGS represents a feasible alternative in settings where pDST is inaccessible, warranting further evaluation for broader implementation.

Background: To evaluate the safety and efficacy of a newly developed catheter coated with antimicrobial poly-L-lysine (PLL) in reducing the risk of catheter-associated bacteriuria.

Methods: A prospective, multicenter, randomized controlled noninferiority trial was conducted among patients who required indwelling catheterization between February 23, 2023, and January 30, 2024. The experimental group used antimicrobial PLL catheters, and the control group used noble metal alloys (NMA) coated catheters. The primary outcome was the incidence of catheter-associated bacteriuria. The secondary outcome was the total bacterial count per unit surface area of the catheter body in the urethra after catheterization. The safety evaluation included complications related to catheterization. The noninferiority threshold was set at 10%.

Results: Three hundred patients were enrolled, while the full analysis set (FAS) included 150 patients who received PLL catheters and 150 patients who received NMA catheters. There were 10 cases (6.9%) of bacteriuria in the experimental group and 15 cases (10.1%) in the control group. The difference in the incidence of bacteriuria between the experimental and control groups was - 3.1% (95% CI [- 7.2%, 6.6%], p = 0.3195). Four patients experienced symptoms compared to 6 in the control group during catheterization (p = 0.750). The proportion of patients experiencing abnormal urine white blood cells in the experimental group was lower (6.2% vs. 12.8%, p = 0.0194). The incidence of catheter-related adverse events was 3 cases (2.0%) in the experimental group and 6 cases (4.0%) in the control group (p = 0.5011).

Conclusions: The short-term use of PLL catheters demonstrated noninferior efficacy in preventing bacteriuria compared with NMA catheters. The PLL catheters have good safety profile and low toxicity. Further trials involving more patients and long duration period are imperative to demonstrate the generalizability of the findings.

Trial registration: This study was registered at https://www.chictr.org.cn/showproj.html?proj=188879 on February 3, 2023, and ID is ChiCTR2200059331.

Background: While diabetes-related complications have been widely investigated, the burden of infectious diseases across the diabetes spectrum remains relatively understudied.

Methods: We developed a Bayesian approach to compare infection risk across 9,476 patients with type 1 diabetes (T1D), 74,270 with type 2 diabetes (T2D), and 32,095 with prediabetes.

Results: Patients with T1D, T2D, and prediabetes had multifold increased risk for all organ system- and pathogen-based composite infection outcomes. We also quantified risk for 1,401 individual infection outcomes, finding increased risk for most infections among patients with either T1D, T2D, or prediabetes. Patients had increased risk for well-established diabetes-associated infections (e.g., mucormycosis) and less commonly associated infections (e.g., West Nile Virus encephalitis). Finally, we found disparities in risk across sociodemographic subgroups (i.e., age, sex, ethnicity, ancestry, and insurance status).

Conclusions: Our comprehensive findings advance previous research by quantifying risk for wide-ranging infection outcomes across diverse patients with T1D, T2D, and prediabetes through an innovative Bayesian approach.