BMC Medicine最新文献

Background: Sleep problems are common among older adults and are associated with a wide range of adverse health outcomes. Concerns about pharmacological treatments have increased interest in non-pharmacological interventions; however, evidence comparing their relative effectiveness remains limited.

Methods: A systematic search was conducted in PubMed, Scopus, Embase, Web of Science, Cochrane Library, and CINAHL. Randomized controlled trials (RCTs) evaluating non-pharmacological interventions in adults aged ≥ 60 years published between 2000 and 2024 were included. Network meta-analyses were conducted using random-effects models to estimate standardized mean differences (SMDs) with 95% confidence intervals (CIs). P-scores were used to rank the efficacy of interventions. The protocol was registered in PROSPERO (CRD42024521492).

Results: Thirty-four RCTs involving 3078 participants and 21 interventions were included. Eleven interventions significantly improved sleep quality. Cognitive behavioral therapy for insomnia plus positive mood strategies (CBT-I+) showed the largest effect (P-score = 0.99, SMD = - 3.32, 95% CI - 4.59 to - 2.06), followed by cognitive behavioral therapy for insomnia (CBT-I) (P-score = 0.92, SMD = - 2.18, 95% CI - 3.04 to - 1.31). Subgroup analyses indicated that music therapy (MUS) was more effective among participants with PSQI < 10 (SMD = - 1.25, 95% CI - 1.85 to - 0.65), whereas CBT-I+ showed greater effects for those with PSQI ≥ 10 (SMD = - 5.48, 95% CI - 6.80 to - 4.16). By intervention setting, traditional Chinese health-promotion exercise (TCHPE) was more effective in home-based settings (SMD = - 1.55, 95% CI - 2.60 to - 0.50), whereas CBT-I+ showed greater effects in non-home settings (SMD = - 3.31, 95% CI - 4.57 to - 2.06).

Conclusions: CBT-I+ was associated with the greatest improvements in sleep quality among older adults, particularly those with baseline PSQI ≥ 10 and in non-home settings. MUS showed greater benefits among older adults with baseline PSQI < 10, and TCHPE showed greater benefits in home-based settings. These findings support stratified, context-specific intervention selection. Given the low GRADE certainty, these results should be interpreted with caution.

The development of techniques to culture and differentiate adult and pluripotent stem cells into diverse cell types over the past decades has sparked an increasing interest in the use of cells for organ regeneration. Such therapies aim to replace lost or damaged cells with functional ones. This can be achieved either through tissue engraftment of therapeutic cells or via their paracrine effects on resident cells, thereby offering a potential cure for debilitating degenerative diseases. The development of regenerative cell therapies, however, is ultimately complex. Effective cell therapy requires the delivery and successful engraftment of therapeutic cells to the correct location or sufficient paracrine activity, while ensuring safety is key to gaining support from funders, caregivers, and patients. A wide variety of cell sources has been used for the development of regenerative cell therapies, ranging from mesenchymal stromal cells (MSC) that act to stimulate local progenitor cells through their secretome to tissue-specific cell types differentiated from adult or pluripotent stem cells and organoids that engraft in tissues. While cell administration to patients is challenging based on both practical and ethical perspectives, the development of techniques to preserve transplant organs ex situ on machine perfusion devices offers a unique opportunity for studying regenerative cell therapy for organ repair in a safe and controllable environment. The present review addresses the current progress of cell therapy for organ regeneration of the intestine, kidney, liver, lung, and heart and discusses the challenges and opportunities of this potentially curing therapeutic approach.

Background: The survival benefit of adjuvant chemotherapy after chemoradiotherapy in locally advanced rectal cancer (LARC) remains unproven, whereas total neoadjuvant therapy (TNT) incorporating preoperative chemotherapy has demonstrated improved outcomes. However, the total chemotherapy duration delivered across neoadjuvant and adjuvant phases varies substantially in clinical practice. We investigated the impact of total chemotherapy duration in the STELLAR trial.

Methods: This post hoc analysis was based on the phase III randomized trial, comparing short-course radiotherapy followed by four cycles of chemotherapy (TNT) with long-course chemoradiotherapy (CRT) in LARC patients. Five hundred thirty-nine patients with available chemotherapy duration data were included, with a median follow-up of 68.1 months. Patients were categorized: group 1 (no chemotherapy, n = 121), group 2 (3 to 12 weeks, n = 113), group 3 (15 weeks, n = 30), and group 4 (≥ 18 weeks, n = 275). Disease-free survival (DFS), overall survival (OS), distant metastasis (DM), and locoregional recurrence (LRR) were assessed using time-dependent Cox regression.

Results: Group 4 achieved the highest 5-year OS (82.1%) and DFS (66.0%) rates. Compared with groups 1 and 2, group 4 demonstrated significantly improved OS (adj. P ≤ 0.001) and improved DFS versus group 1 (HR 0.621, 95% CI 0.443-0.870, adj. P = 0.017). In the TNT cohort, group 4 was associated with significantly improved OS and DFS compared with group 2 (adj. P < 0.01), but not with group 3. Additionally, group 4 showed a significantly lower risk of LRR than group 3. In the CRT cohort, group 4 was associated with improved OS compared with group 1 (adj. P = 0.005); however, this association was not retained in surgical patients. No significant differences in DFS, DM, or LRR were observed across groups in the CRT cohort.

Conclusions: In TNT cohort, minimum 18 weeks of chemotherapy was associated with improved OS and DFS compared to 3 to 12 weeks. The observed OS benefit of minimum 18 weeks versus no chemotherapy in the CRT cohort was not retained among surgical patients. These findings suggest caution in shortening chemotherapy duration, particularly in high-risk patients treated with TNT, and warrant confirmation in prospective TNT-specific trials.

Trial registration: The STELLAR trial was registered at ClinicalTrials.gov (identifier: NCT02533271); however, this post hoc analysis was retrospectively conducted.

Background: Patients undergoing percutaneous coronary intervention (PCI) remain at substantial residual inflammatory risk, potentially driven by clonal hematopoiesis of indeterminate potential (CHIP), a novel pro-inflammatory contributor to atherogenesis. However, the clinical implications of CHIP-inflammation interplay in secondary prevention remain insufficiently understood. We aimed to investigate the joint impact of CHIP and systemic inflammation on prognosis among PCI patients.

Methods: This cohort included PCI patients receiving guideline-directed lipid-lowering and dual antiplatelet therapies. CHIP mutations were identified by targeted sequencing with a mean sequencing depth of 985 × . Systemic inflammation was assessed using 12 routine inflammatory indices. Cox proportional hazards models were used to assess the impact of CHIP and inflammatory indices on 5-year all-cause mortality, the primary outcome. Major adverse cardiac and cerebrovascular events (MACCE) comprised all-cause mortality, nonfatal myocardial infarction, ischemic stroke, stent thrombosis, and unplanned revascularization.

Results: Among 3640 PCI patients, 799 (21.95%) carried CHIP mutations. During a median follow-up of 5.06 years, CHIP was independently associated with increased risks of all-cause (hazard ratio (HR), 1.76; 95% confidence interval (CI), 1.20-2.57) and cardiac mortality (HR, 2.19; 95% CI, 1.31-3.65). Notably, this association was significantly modified by systemic inflammatory burden, as reflected by aggregate index of systemic inflammation (AISI), monocyte-lymphocyte ratio (MLR), systemic immune-inflammatory index (SII), and systemic inflammatory response index (SIRI) (adjusted P_interaction < 0.05). Specifically, CHIP conferred no excess mortality risk in low-inflammatory states, as reflected by SII (HR, 0.92; 95% CI, 0.52-1.66), whereas elevated inflammation significantly amplified CHIP-related mortality risk (HR, 3.36; 95% CI, 1.94-5.82), even among small-clone carriers (variant allele fraction 0.5-2%). Although no overall association was observed between CHIP and 5-year MACCE, significant associations emerged under elevated levels of SII (HR, 1.31; 95% CI, 1.05-1.64) and SIRI (HR, 1.38; 95% CI, 1.10-1.72). Moreover, incorporating CHIP into the GRACE score, a traditional risk assessment tool, yielded a modest yet significant improvement in long-term mortality prediction after PCI (ΔC-index, 3%; 95% CI, 0.9-6.6%).

Conclusions: Hematopoiesis-related genetic alterations conferred excess prognostic risk, primarily in the presence of elevated hematological inflammation, underscoring the potential benefit of inflammatory burden management in PCI patients harboring CHIP.

Background: Birthweight readily measurable marker of fetal growth that may influence health across the lifespan. We aimed to investigate the potential causal association between birthweight and healthy aging and to identify the mediating roles of subsequent socioeconomic, behavioral, functional, and disease-related factors to inform life-course strategies to promote healthy aging and reduce health inequities.

Methods: We performed two-sample Mendelian randomization analyses in European-ancestry participants to estimate the effect of birthweight (n = 298,142-423,683) on two robust, composite healthy aging phenotypes (genetically independent phenotype of aging (aging-GIP) and multivariate aging-related genetic factor (mvAge)) and six individual aging phenotypes, including healthspan, resilience, parental lifespan, self-rated health, phenotypic age deceleration, and 90^th percentile self-longevity (n = 34,710-1,958,774), and screened for 100 candidate mediators (n = 14,267-1,812,017) using a two-step mediation analysis.

Results: Genetically determined each 1-SD higher birthweight was associated with higher aging-GIP (β [95% CI] in different models ranging from 0.131 [0.066-0.196] to 0.162 [0.089-0.235] SDs) and mvAge (0.036 [0.010-0.063] to 0.045 [0.024-0.067]), independent of later-life obesity indicators; also with more interpretable benefits, including 12%-16% higher odds of longer healthspan, a 0.079-0.089 SD improvement in resilience, and a 1.22-1.74 year increase in parental lifespan. Of 100 candidates, 26 and 25 mediated the effect of birthweight on aging-GIP and mvAge, respectively, including socioeconomic indicators (education, household income, occupational attainment; individual mediation proportion: 12.72%-27.79%); behaviors (e.g., cheese intake, age at first sex; 10.38%-29.56%); physical functions (e.g., blood pressure, grip strength; 7.57%-42.65%); and cardiometabolic diseases (e.g., type 2 diabetes, cardiovascular diseases; 25.02%-70.11%).

Conclusions: Higher birthweight within the normal range directly promotes healthy aging, mediated by multifaceted modifiable factors. Our findings advocate adopting a life-course approach to foster healthy aging, starting with optimal birthweight and extending to interventions that enhance socioeconomic status, promote healthy behaviors, strengthen physical functions, and prevent cardiometabolic diseases.

Background: Previous research has indicated an association between hypermobility and autism. This study examined whether being autistic affects diagnosis, symptoms, and health experiences of people with hypermobility, including hypermobile Ehlers-Danlos syndrome (hEDS) and hypermobility spectrum disorders (HSD). We compare three groups: autistic adults, non-autistic adults, and adults who are not autistic but have a high level of autistic traits. Additionally, we examined which health and social factors predicted self-reported physical and mental health outcomes for autistic and non-autistic people with hEDS/HSD.

Method: A total of 1754 participants completed an online questionnaire about their diagnostic experience, hypermobile symptoms, co-occurring health conditions, self-rated physical and mental health, engagement with health services, and employment and benefits status. Around 25% of respondents were autistic; a further 25% had high levels of autistic traits.

Results: Autistic participants had more symptoms of hEDS/HSD and were more likely to have co-occurring physical and mental health conditions, compared with non-autistic and high autistic trait respondents. Autistic and high autistic trait participants self-reported poorer physical and mental health compared with non-autistic participants. Autistic participants' mental health was impacted by limitations to everyday activities, whereas non-autistic participants were more impacted by difficulties with self-care.

Conclusions: Autistic and non-autistic people may experience hEDS/HSD differently, which may impact the type of supports that are most beneficial to them.

Background: Good quality postnatal care is of key importance for maternal and infant health. During the pandemic, healthcare services were reconfigured with increased virtual delivery, reducing infection transmission risk for pregnant women, new mothers, newborn babies, and healthcare workers. Post-pandemic, this shift of maternity care from face-to-face towards virtual care provision has persisted. Whilst some have extolled this trend, the evidence is mixed, both for clinical outcomes and for patient perceptions and experiences. We sought to explore the experiences and perceptions of women affected by these changes, to inform ongoing maternity services development.

Methods: This study reports responses of women participating in the COVID Symptom Study Biobank, drawn from the King's College London/ZOE COVID Symptom Study, representing a convenience sample of UK women of reproductive age (18-50 years). Participants were invited to complete an online questionnaire, from 7 September to 1 December 2021. Demographic analyses are presented for all respondents. Content analysis was used to analyse all free-text responses.

Results: Overall, 1036 respondents delivered at least one live baby during the pandemic, of whom 821 respondents provided a total of 1466 qualitative responses about their care in-person (n = 550 responses), by video (n = 125), or by telephone (n = 791). Mothers liked the convenience and promptness of virtual care, and generally felt it was a good way to meet their healthcare needs, with two caveats: First, they appreciated the option to escalate care quickly (i.e. a tiered process), which seemed to occur with little difficulty in most cases; second, they perceived physical examination as very important in certain circumstances, particularly when a baby was unwell.

Conclusions: Our findings show women are pragmatic and reasonable about the benefits and risks of differing modes of postpartum care delivery, including virtual care. Our study supports a tiered approach to the provision of postnatal care, which balances perceived efficiencies, preferences of the individual seeking care, and level of clinical concern.

Background: Ovarian cancer (OC) is frequently diagnosed at an advanced stage, where tumor heterogeneity and rapid development of chemoresistance contribute to a poor prognosis. The lack of reliable predictive biomarkers further hinders the development of effective treatment strategies. Patient-derived organoids (PDOs) have recently emerged as promising preclinical models with the potential to predict therapeutic responses.

Methods: OC PDOs were generated from ascites samples representing diverse histological subtypes. Histological and genomic fidelity to parental tumors was confirmed through histopathological analysis and whole-exome sequencing. Drug sensitivity to cisplatin and poly (ADP-ribose) polymerase (PARP) inhibitors was evaluated and correlated with 1-year clinical outcomes. We also investigated the therapeutic efficacy of oncolytic herpes simplex virus 2 (OH2) both as a single agent and in combination with cisplatin. The expression of cancer stem cell (CSC) markers CD44 and ALDH1A1 under treatment conditions was analyzed using immunohistochemistry and flow cytometry.

Results: PDOs were successfully established with an 86.2% success rate. These PDOs faithfully recapitulated the histopathological and genomic features of their corresponding tumors, maintaining intratumoral heterogeneity, and were amenable to xenotransplantation. Drug sensitivity assays demonstrated that PDOs accurately predicted patient-specific responses to cisplatin and PARP inhibitors. OH2 exhibited direct cytotoxicity in both cisplatin-sensitive and cisplatin-resistant PDOs, reducing cell viability by 20-60%. Notably, the combination treatment with OH2 and cisplatin enhanced antitumor efficacy, resulting in a significant reduction of the CD44⁺CSC subpopulation.

Conclusions: Ascites-derived OC PDOs represent a robust platform for individualized drug testing. The combination of OH2 and cisplatin offers a novel and effective strategy for circumventing chemoresistance in OC.

Background: Depression is the most common mental health disorder among the older populations, leading to a higher reduction in quality of life and an increased financial burden on the health care system. One promising non-pharmacological approach for improving mental health in older adults is the use of art-based interventions.

Methods: This systematic review and meta-analysis followed PRISMA guidelines. Eligible randomized controlled trials (RCTs) examined any form of art intervention (including music, dance, and visual arts) targeting depression in adults aged > 55 years. Databases searched included PubMed, Scopus, Web of Science, PsycINFO, and the Cochrane Library through July 2025. Two reviewers independently extracted data, assessed risk of bias using the Cochrane RoB 2 tool, and determined study eligibility. Standardized mean differences (SMDs) were calculated using random-effects meta-analysis, followed by subgroup analyses, meta-regression, and publication bias assessment (Egger's test and funnel plot).

Results: Out of the 41 RCTs reviewed, 37 report results from 23 of these studies and were eligible for meta-analysis, including a total of 3791 participants. In the pooled analysis, it was revealed that art-based interventions had a greater impact in lowering levels of depression as compared to their respective controls (SMD =  - 0.93, 95% CI: - 1.19 to - 0.68, p < 0.001) and had a high degree of heterogeneity (I² = 91.7%). Subgroup analyses suggested receptive interventions had a stronger effect (SMD =  - 1.97, 95% CI: - 1.43 to - 2.50, p < 0.001) than active interventions (SMD =  - 0.67, 95% CI: - 0.42 to - 0.91, p < 0.001) and interventions provided in the hospital or care home settings. Also, meta-regressions showed no significant association of effect size with the independent variables of age of subjects, number of sessions, or duration of intervention. Most of the studies had moderate to high risk of bias. Egger's test indicated no significant publication bias (p = 0.133).

Conclusions: Art-based interventions effectively reduce depression in older adults and can serve as valuable complements to mental health strategies for aging populations. However, due to heterogeneous study designs and variable quality, additional high-quality trials are needed to confirm these benefits and optimize intervention delivery.

Background: Sex and gender influence medical decision making, yet little is known about how the sex of a consultant shapes the prescribing behaviour of female primary care physicians (PCPs). This study examined whether consultant sex affects female PCPs' likelihood of following recommendations that conflict with clinical guidelines and explored the factors underlying trust in consultants.

Methods: We conducted a web-based experimental study using case vignettes on sleeping medication and antibiotics. A total of 482 female PCPs in England were randomly assigned to conditions with no recommendation or with recommendations from male or female consultants. The outcomes included prescribing decisions, confidence, perceived difficulty, and effort.

Results: In the absence of recommendations, female PCPs rarely prescribe non-guideline medications, reflecting cautious baseline behaviour. Consultant recommendations increased prescribing across both vignettes, with higher rates in both consultant conditions than in the control condition (sleeping medication: 43.3% male vs. 33.6% female vs. 30.4% control, χ²(2, N = 482) = 6.61, p = 0.037; antibiotics: 14.9% male vs. 14.5% female vs. 5.3% control, χ²(2, N = 482) = 9.55, p = 0.008). Regression analyses confirmed that both male and female consultant recommendations significantly increased the odds of prescribing antibiotics compared with the control condition (male: OR = 3.33, 95% CI [1.43-7.76]; female: OR = 3.29, 95% CI [1.39-7.79]). Only the male consultant's recommendation significantly increased the prescribing of sleeping medication (OR = 1.89, 95% CI [1.13-3.15]), whereas the female consultant's recommendation had no significant effect (OR = 1.22, 95% CI [0.71-2.10]). However, direct comparisons between male and female consultants were not statistically significant. Across conditions, participants generally reported high confidence in their decisions and perceived low difficulty and effort. Consultant recommendations in the antibiotic vignette were associated with lower confidence and higher perceived difficulty and effort.

Conclusions: Consultant recommendations, independent from consultant's sex, increased the likelihood of non-guideline prescribing among female PCPs. The absence of statistically significant differences between male and female consultants suggests that the presence of a recommendation itself may be more influential than consultant sex. Strengthening physicians' confidence and supporting guideline-based decision-making may help reduce susceptibility to social influence.