BMC Medicine最新文献

Background: Cancer survivors face elevated risks of heart failure (HF) and death, with cardiac dysfunction being a significant concern. Current evaluations often emphasize systolic function while insufficiently addressing diastolic function. This study aims to investigate the prevalence of diastolic dysfunction and assess its prognostic implications in long-term cancer survivors.

Methods: We analyzed participants from the Atherosclerosis Risk in Communities (ARIC) Study with complete echocardiographic assessments and documented cancer histories. Diastolic function was classified by guideline criteria: normal (≤ 1 abnormal parameter), indeterminate (2 abnormal parameters), and dysfunction (≥ 3 abnormal parameters). The primary outcomes were incident HF and all-cause death. Diastolic dysfunction prevalence was compared between cancer survivors and non-cancer participants after propensity score matching. Cox regression, Kaplan-Meier, and restricted cubic spline (RCS) analyses were used to assess associated risks.

Results: A total of 5322 participants were included, with 18.4% (N = 979) being cancer survivors. The mean age of cancer survivors at echocardiography was 76.3 (5.10) years, with a median of 12.17 years since diagnosis. There were no significant differences in diastolic dysfunction prevalence (12.26% vs 10.73%, P = 0.29) after matching. Cox regression revealed a graded association between diastolic dysfunction and risks of HF and death. Fully adjusted hazard ratios were 2.59 (95% CI: 1.59-4.20, P < 0.001) for indeterminate diastolic function and 4.41 (95% CI: 2.40-8.12, P < 0.001) for diastolic dysfunction in HF; and 1.68 (95% CI: 1.26-2.25, P < 0.001) for indeterminate and 2.21 (95% CI: 1.51-3.22, P < 0.001) for diastolic dysfunction in all-cause death. These results were consistent across subgroup and sensitivity analyses and supported by Kaplan-Meier curves. RCS analyses demonstrated dose-response relationships between individual diastolic parameters and outcomes.

Conclusions: Diastolic dysfunction is prevalent among long-term cancer survivors and is stepwise associated with adverse outcomes. These findings underscore the essential need for ongoing monitoring of diastolic function in this population.

Background: In England, the number of takeaway food outlets ('takeaways') has been increasing for over two decades. Takeaway management zones around schools are an effective way to restrict the growth of new takeaways but their impacts on population health have not been estimated.

Methods: To model the impact of takeaway management zones on health, we used estimates of change in and exposure to takeaways (across home, work, and commuting buffers) based on a previous evaluation suggesting that 50% of new outlets were prevented from opening because of management zones. Based on previous cross-sectional findings, we estimated changes in body mass index (BMI) from changes in takeaway exposure, from 2018 to 2040. We used PRIMEtime, a proportional multistate lifetable model, and BMI change to estimate the impact of the intervention, in a closed-cohort of adults (25-64 years), on incidence of 12 non-communicable diseases, obesity prevalence, quality-adjusted life years (QALYs), and healthcare costs saved by 2040 in six local authorities (LAs) across the rural-urban spectrum in England (Wandsworth, Manchester, Blackburn with Darwen, Sheffield, North Somerset, and Fenland).

Results: By 2031, compared to no intervention, reductions in outlet exposure ranged from 3 outlets/person in Fenland to 28 outlets/person in Manchester. This corresponded to mean per person reductions in BMI of 0.08 and 0.68 kg/m², respectively. Relative to no intervention, obesity prevalence was estimated to be reduced in both sexes in all LAs, including by 2.3 percentage points (PP) (95% uncertainty interval:2.9PP, 1.7PP) to 1.5PP (95%UI:1.9PP, 1.1PP) in males living in Manchester and Wandsworth by 2040, respectively. Model estimates showed reductions in incidence of disease, including type II diabetes (e.g. 964 (95% UI: 1565, 870) fewer cases/100,000 population for males in Manchester)), cardiovascular diseases, asthma, certain cancers, and low back pain. Savings in healthcare costs (millions) ranged from £1.65 (95% UI: £1.17, £2.25)/100,000 population in North Somerset to £2.02 (95% UI: £1.39, £2.83)/100,000 population in Wandsworth. Gains in QALYs/100,000 person were broadly similar across LAs.

Conclusions: Takeaway management zones in England have the potential to meaningfully contribute towards reducing obesity prevalence and associated healthcare burden in the adult population, at the local level and across the rural-urban spectrum.

Background: Clinical management of patients with chronic cardiometabolic disease is complicated by polypharmacy. Consequently, when patients clinically deteriorate, physicians are challenged to distinguish both medication nonadherence and drug-drug interactions (DDI) from chronic disease progression.

Methods: In this randomized controlled trial, we enrolled U.S. board-certified Primary Care Physicians (PCPs) serving patients with cardiometabolic disease. PCPs were randomized and managed their patients with (intervention), or without (control), a novel chronic disease management test (CDMT) that can detect medication nonadherence and DDIs. Patients' medical records were abstracted at baseline and 3-month follow-up. Primary outcomes were the CDMT's impact on both the PCPs' detection of medication nonadherence and DDI, and the frequency of performing medication nonadherence- and DDI-related clinical actions. Secondary outcomes examined the types of clinical actions performed. Primary and secondary outcomes were analyzed by logistic regression using single variable and clustered multivariable modeling to adjust for similarities in patient characteristics, by PCP practice.

Results: Sixteen intervention and 20 control PCPs shared de-identified records for 126 and 207 patients, respectively. There were no significant demographic differences between the two study arms, among PCPs or patients. At baseline, there was no significant difference between the intervention and control PCPs in the percentage of clinical actions performed for medication nonadherence (P = 0.98) and DDI (P = 0.41). At 3-month follow-up (after CDMT), 69.1% of intervention compared to 20.3% of control patients with medication nonadherence had a related clinical action performed (P < 0.001). Regarding DDI, 37.3% of intervention compared to 0.5% of control patients had a relevant clinical action performed in follow-up (P < 0.001). Across the range of medication nonadherence- and DDI-related actions, the intervention compared to the control PCPs were more likely to adjust the medication regimen (24.1% vs. 9.5%) and document medication nonadherence in the patient chart (31.0% vs. 14.3%) at follow-up (P = 0.04).

Conclusions: Although intervention and control PCPs similarly detected and acted upon medication nonadherence and DDI at baseline, intervention PCPs' detection increased significantly after using the CDMT. Also, the clinical actions performed with CDMT support were more clinically rigorous. These outcomes support the clinical utility of CDMT in the management of symptomatic patients with cardiometabolic disease and polypharmacy.

Trial registration: https://clinicaltrials.gov/study/NCT05910684 .

Background: Bipolar disorder is a complex polygenic disorder that is characterized by recurrent episodes of depression and mania, the heterogeneity of which is likely complicated by epigenetic modifications that remain to be elucidated.

Methods: We performed transcriptomic analysis of peripheral blood RNA from monozygotic (MZ) twins discordant for bipolar disorder to identify disease-associated differentially expressed long noncoding RNAs (DE-lncRNAs), which were further validated in the PsychENCODE brain RNA-seq dataset. We then performed behavioral tests, electrophysiological assays, chromatin immunoprecipitation, and PCR to investigate the function of DE-lncRNAs in the mouse and cell models. Statistical analyses were performed using GraphPad Prism 9.0 or SPSS.

Results: We identified a bipolar disorder-associated upregulated long non-coding RNA (lncRNA), AP1AR-DT. We observed that overexpression of AP1AR-DT in the mouse medial prefrontal cortex (mPFC) resulted in a reduction of both the total spine density and the spontaneous excitatory postsynaptic current (sEPSC) frequency of mPFC neurons as well as depressive and anxiety-like behaviors. A combination of the results of brain transcriptome analysis of AP1AR-DT overexpressing mice brains with the known genes associated with bipolar disorder revealed that NEGR1, which encodes neuronal growth regulator 1, is one of the AP1AR-DT targets and is reduced in vivo upon gain of AP1AR-DT in mice. We further demonstrated that overexpression of recombinant Negr1 in the mPFC neurons of AP1AR-DT_OE mice ameliorates depressive and anxiety-like behaviors and normalizes the reduced excitatory synaptic transmission induced by the gain of AP1AR-DT. We finally identified that AP1AR-DT reduces NEGR1 expression by competing for the transcriptional activator NRF1 in the overlapping binding site of the NEGR1 promoter region.

Conclusions: The epigenetic and pathophysiological mechanism linking AP1AR-DT to the modulation of depressive and anxiety-like behaviors and excitatory synaptic function provides etiological implications for bipolar disorder.

Background: Online food delivery (OFD) platforms offer easy access to an abundance of energy-dense and nutrient-poor takeaway foods and may exacerbate existing unhealthy food environments. Efforts to improve population diets include a range of policy recommendations focused on improving the healthiness of food environments; however, the way in which such policies may apply to OFD platforms is not clear. This paper aimed to synthesise the existing evidence to inform nutrition-related policies applicable to OFD platforms for population health and well-being. A secondary aim was to scan existing nutrition-related policies in Australia and internationally, which have the potential to be applicable to OFD platforms.

Methods: Seven electronic databases including Medline, Embase, CINAHL, Business Source Ultimate, Scopus, Web of Science, and Proquest were searched from January 2010 to October 2023. Evidence from studies was mapped to five existing policy domains outlined by the Healthy Food Environment Policy Index (Food-EPI) including (i) food labelling; (ii) food promotion; (iii) food composition and nutritional quality; (iv) food retail; and (v) food pricing. Relevant data sources were searched for currently implemented nutrition-related government policies that may have relevance to OFD platforms.

Results: A total of 2012 records were screened, and 43 studies were included. There were 70 relevant study outcomes across the included studies, which addressed one or more of the 5 domains. Of these, 21 were relevant to 'Food Promotion' (30%), 18 to 'Food Retail' (26%), 15 to 'Food Composition (21%), 11 to 'Food Prices' (16%), and six to 'Food Labelling' (9%). Three existing policies from international jurisdictions (England, Singapore, EU) included OFD platforms, of which one was a voluntary measure. Several existing policies under food labelling have the potential to be amended to include OFD platforms under regulatory definitions.

Conclusion: OFD platforms have emerged as a disruptor to how people acquire their food and have yet to be widely included in existing nutrition-related policies. Advancing the evidence base to support the design of effective policy actions and mitigate the potential negative health impacts of OFD platforms will support efforts to improve population diets.

Background: Front-of-pack (FOP) warning labels have demonstrated effectiveness for reducing sugar-sweetened beverage (SSB) consumption and switching to water. However, an unintended consequence is that they may also increase switching to non-sugar-sweetened beverages (NSSBs). A non-hypothetical experimental study examined the effectiveness of combining sugar and sweetener FOP warning labels to reduce sugary drink consumption and prevent NSSB substitution. The study also examined potential integration with Australia and New Zealand's existing Health Star Rating (HSR) system to determine suitability for local context and other jurisdictions with interpretive labelling schemes already in place.

Methods: Participants (N = 414) accessed an online convenience store app via an on-campus laptop to select one drink from an array of 10 beverages, on three occasions. Drink options included a variety of SSBs, 100% fruit juice, NSSBs, and water. Following an escalating exposure procedure, drinks were presented (1) without any additional labelling, (2) with warning labels added to sugary drinks or to both sugary drinks and NSSBs (according to allocated condition), then (3) with HSR icons added to all drinks. Participants were informed they would receive a complementary drink, based on their selections, following the completion of a brief questionnaire.

Results: Baseline results indicated that SSBs and water were the most and least popular drink choices, respectively. Placing FOP warning labels on sugary drinks decreased selection of SSBs and increased NSSB and water choices. Water became the most popular individual drink choice in response to warnings on sugary drinks. Placing FOP warning labels on both sugary drinks and NSSBs successfully avoided an increase in NSSB choices, whilst also increasing water selections, but did not significantly decrease selection of SSBs until HSR ratings were added. The incorporation of HSR icons consolidated warning label effects on NSSB and water selection across both conditions.

Conclusions: Results demonstrate the potential of FOP sugar warning labels for addressing beverage consumption behaviours. The incorporation of sweetener warning labels may successfully avoid substitution towards NSSBs, whilst still promoting water choices, but may also dilute the impact of the sugary drinks warning labels. Warning labels were complementary to existing interpretive FOP labels.

Background: Chronic insomnia increases the risk of various health problems and mental illness. Existing research suggests promise for both transcranial direct current stimulation (tDCS) and repetitive transcranial magnetic stimulation (rTMS) in treating chronic insomnia individually. However, the combined effects of tDCS and rTMS on this condition remain unclear. This study aimed to verify the efficacy and safety of tDCS combined with rTMS for the treatment of adult patients with chronic insomnia.

Methods: This was a randomised double-blind parallel-group controlled study. Overall, 157 participants with chronic insomnia were randomly assigned to one of three neurotherapy regimens: tDCS + rTMS, sham tDCS + rTMS, or tDCS + sham rTMS. All groups received 20 treatment sessions over 4 consecutive weeks. The primary outcome was the change in patients' sleep as assessed by the Pittsburgh Sleep Quality Index (PSQI) at 2 weeks, 4 weeks, and 3 months of follow-up. The secondary outcome was the assessment of different dimensions of depression and anxiety in patients through the Hamilton Depression Scale (HAMD) and Hamilton Anxiety Scale (HAMA), as well as the occurrence of adverse events.

Results: Throughout the intervention and after the 3-month follow-up, the tDCS + rTMS group had significantly reduced total PSQI scores compared with the other two groups [tDCS + rTMS, 9.21 vs. sham tDCS + rTMS, 10.03; difference - 1.10; 95% confidence interval (CI), - 1.82 to - 0.38; p = 0.003; tDCS + rTMS, 9.21 vs. tDCS + sham rTMS, 10.76; difference - 2.14; 95% CI, - 2.90 to - 1.38; p < 0.001; sham tDCS + rTMS, 10.03 vs. tDCS + sham rTMS, 10.76; difference - 1.04; 95% CI, - 1.82 to - 0.26; p = 0.010), indicating improved overall sleep quality. Total HAMD and insomnia factor scores were significantly lower in the tDCS + rTMS group than in the other two groups after treatment (p < 0.05). Notably, no adverse events or serious adverse reactions were observed during the study period.

Conclusions: Combining tDCS with rTMS effectively relieved insomnia symptoms, achieving a significant therapeutic effect after 2-week of intervention, and demonstrating the persistence of treatment effects in later follow-up, emphasising the advantages of combination therapy in improving treatment stability and long-term benefits, reflecting the rapid and effective augmentation of combination therapy. This combined therapy may serve as a safe and effective treatment for adults with chronic insomnia.

Trial registration: This study was registered as a clinical trial with the China Clinical Trial Registration Center (ChiCTR2100052681).

Background: In the contemporary management of heart failure with reduced ejection fraction (HFrEF), the recommended quadruple guideline-directed medical therapy (GDMT) consists of angiotensin receptor-neprilysin inhibitor (ARNI), evidence-based beta-blockers (BB), mineralocorticoid receptor antagonists (MRA), and sodium-glucose cotransporter-2 inhibitors (SGLT-2i). This study explored the impact of adding implantable cardioverter-defibrillator (ICD) therapy to this comprehensive regimen in HFrEF patients.

Methods: Utilizing deidentified data from the National Electronic Database of the Turkish Ministry of Health, we conducted a nationwide retrospective cohort study on 5450 HFrEF patients receiving quadruple GDMT, including ARNI. Among them, 709 patients underwent additional ICD or cardiac resynchronization therapy defibrillator (CRT-D) implantation. Propensity score matching ensured balanced baseline characteristics between groups. Primary endpoint was determined as all-cause mortality.

Results: In the matched cohort, all-cause mortality occurred in 108 out of 619 patients (17.4%) in the GDMT group and 101 out of 619 patients (16.3%) in the ICD group, with a hazard ratio (HR) of 0.74 and a 95% confidence interval (CI) ranging from 0.57 to 0.98. The median follow-up time was 1365 days in the matched cohort, 1283 days in the GDMT group. Subgroup analyses consistently demonstrated benefits, particularly among individuals aged 61 years and older (HR: 0.60, 95% CI: 0.42-0.87, p = 0.006), those with sinus rhythm (HR: 0.55, 95% CI: 0.34-0.89, p = 0.013), individuals not using amiodarone (HR: 0.61, 95% CI: 0.42-0.89, p = 0.011), and those with an estimated glomerular filtration rate lower than 61.9 (HR: 0.66, 95% CI: 0.48-0.91, p = 0.011).

Conclusions: This study may offer a glimmer of hope that even after achieving the best current optimal medical therapy, the addition of device therapy could still yield positive outcomes in the management of patients with HFrEF.

Background: This study explored the influence of type 2 diabetes and impaired glucose tolerance (IGT) on the risk of the multimorbidity cluster of cardiovascular disease (CVD) and cancer.

Methods: A total of 1629 participants in the Da Qing Diabetes Prevention Outcome Study were recruited in the present analysis, including normal glucose tolerance (NGT, N = 492), IGT (N = 540), and newly diagnosed type 2 diabetes (N = 597) groups. Cox proportional hazards analyses were performed to assess the relationship between NGT, IGT, and newly diagnosed type 2 diabetes and the risk of the multimorbidity cluster of CVD and cancer.

Results: The incidence rates for multimorbidity cluster CVD and cancer were 1.25, 3.17, and 3.23 per 1000 person-years in people with NGT, IGT, and the newly diagnosed type 2 diabetes groups, respectively, over 34-year follow-up. Cox analysis revealed that diabetes status (as time-dependent variable) was significantly associated with the subsequent increased risk of multimorbidity cluster of CVD and cancer compared with non-diabetes (hazard ratios [HR] = 2.55, 95% confidence interval [CI] 1.51-4.31) after adjustment of potential confounders. Similar analysis showed that this risk was significantly higher in the IGT and newly diagnosed type 2 diabetes groups compared with NGT, with HR of 3.28 (95% CI 1.83-5.87) and HR of 3.90 (95% CI 2.14-7.09), respectively. Whereas compared diabetes with IGT group, this risk was not significantly different.

Conclusions: Similar to newly diagnosed type 2 diabetes, IGT is significantly associated with an increased risk of the multimorbidity cluster of CVD and cancer compared with NGT. This finding highlights the urgent need for an active detection of IGT and effective prevention and management of diabetes.

Background: We are now in the fifth year of an ongoing pandemic, and Canada continues to experience significant surges of COVID-19 infections. In addition to the acute impacts of deaths and hospitalizations, there is growing awareness of an accumulation of organ damage and disability which is building a "health debt" that will affect Canadians for decades to come. Calls in 2023 for an inquiry into the handling of the COVID-19 pandemic went unheeded, despite relevant precedent. Canada urgently needs a comprehensive review of its successes and failures to chart a better response in the near- and long-term.

Main body: While Canada fared better than many comparators in the early years of the COVID-19 pandemic, it is clearly still in a public health crisis. Infections are not only affecting Canadians' daily lives but also eroding healthcare capacity. Post-COVID condition is having accumulating and profound individual, social, and economic consequences. An inquiry is needed to understand the current evidence underlying policy choices, identify a better course of action on various fronts, and build resilience. More must be done to reduce transmission, including a serious public education campaign to better inform Canadians about COVID and effective mitigations, especially the benefits of respirator masks. We need a national standard for indoor air quality to make indoor public spaces safer, particularly schools. Data collection must be more robust, especially to understand and mitigate the disproportionate impacts on under-served communities and high-risk populations. General confidence in public health must be rebuilt, with a focus on communication and transparency. In particular, the wide variation in provincial policies has sown mistrust: evidence-based policy should be consistent. Finally, Canada's early success in vaccination has collapsed, and this development needs a careful post-mortem.

Conclusions: A complete investigation of Canada's response to the pandemic is not yet possible because that response is still ongoing and, while we have learned much, there remain areas of dispute and uncertainty. However, an inquiry is needed to conduct a rapid assessment of the current evidence and policies and provide recommendations on how to improve in 2025 and beyond as well as guidance for future pandemics.