Cost-effectiveness of population-based screening for chronic obstructive pulmonary disease in China: a simulation modeling study.

Background: China has the highest disease burden of chronic obstructive pulmonary disease (COPD) in the world; however, the diagnosis rate remains low. Screening for COPD in the population may improve early diagnosis and long-term health outcomes for patients with COPD. In this study, we aimed to evaluate the cost-effectiveness of population-based COPD screening policies in China. Methods: We developed a microsimulation model that simulated incidence, natural history, and clinical management of COPD over a lifetime horizon among the general population aged 35-80 years in China. We evaluated population-based screening policies with different screening methods (one-step with COPD Screening Questionnaire or two-step with additional portable spirometer test) and frequencies (one-time or every 1-10 years). We calculated the incremental cost-effectiveness ratio (ICER) of the screening policies compared with the status quo (without screening) and identified the most cost-effective screening policy. Scenario and sensitivity analyses were performed to assess the impact of key parameters and the robustness of model results. Findings: Compared with the status quo, all population-based COPD screening policies were cost-effective with estimated ICERs ranging between $8034 and $13,209 per quality-adjusted-life-year (QALY), all under the willingness-to-pay value of $38,441/QALY (three times China's gross domestic product per capita). A total of 0.39%-8.10% of COPD-related deaths and 0.58%-2.70% of COPD exacerbations were projected to be averted by COPD screening. Among all screening policies, annual two-step screening was the most cost-effective. Improving the linkage from screening to diagnosis and treatment could further increase population health benefits and the cost-effectiveness of COPD screening. Interpretation: Population-based screening for COPD could be cost-effective in China. Offering public programs for COPD screening similar to existing preventive health services for other chronic diseases could be a promising strategy to improve population health outcomes and mitigate the disease burden of COPD in China. Funding: Alexander von Humboldt Foundation, National Natural Science Foundation of China, CAMS Innovation Fund for Medical Science, Chinese Academy of Engineering project, and Horizon Europe.

Decentralized stochastic sharpness-aware minimization algorithm.

In recent years, distributed stochastic algorithms have become increasingly useful in the field of machine learning. However, similar to traditional stochastic algorithms, they face a challenge where achieving high fitness on the training set does not necessarily result in good performance on the test set. To address this issue, we propose to use of a distributed network topology to improve the generalization ability of the algorithms. We specifically focus on the Sharpness-Aware Minimization (SAM) algorithm, which relies on perturbation weights to find the maximum point with better generalization ability. In this paper, we present the decentralized stochastic sharpness-aware minimization (D-SSAM) algorithm, which incorporates the distributed network topology. We also provide sublinear convergence results for non-convex targets, which is comparable to consequence of Decentralized Stochastic Gradient Descent (DSGD). Finally, we empirically demonstrate the effectiveness of these results in deep networks and discuss their relationship to the generalization behavior of SAM.

Knowledge and trust of mothers regarding childhood vaccination in Rwanda.

INTRODUCTION: Knowledge and trust are some of the contributing factors to vaccine acceptance(VA) and Vaccine hesitancy (VH) is one of the top threats to global health. A significant drop in childhood vaccination has been observed in recent years. One important reason that influences mothers' choice to either postpone or avoid children's vaccinations is knowledge and trust in childhood vaccines. This study aimed to assess mothers' knowledge and trust on vaccination of their children, and to examine the association between vaccination knowledge and selected socio-demographic factors. METHODS: A cross-sectional survey was conducted from January 2022 to March 2022 to assess the knowledge and trust of mothers regarding childhood vaccination. Data was collected with self-administered questionnaires. Multivariable logistic regression analysis was employed to assess factors associated with childhood vaccine knowledge and trust. RESULTS: Of the 2,126 Rwandan parents who participated in the study, the proportions with good knowledge of - and good trust in childhood vaccination were 95.5% and 91.4%, respectively. The popular sources of information about childhood vaccination were health care professionals (91.8%) and mass media (28.9%). Multinomial logistic regression analysis showed that good knowledge of - and trust in childhood vaccination were associated with the relationship with child(ren), education, occupation, and monthly income. The Multinomial logistic regression also revealed that the determinants of good knowledge of - and trust in childhood vaccination were; caregiver (p = 4.0 × 10-4, adjusted Odds Ratio (aOR); 1.7, 95%C.I; 1.3 - 2.3), no formal educational status (p = 3.3 × 10-2, aOR; 1.7, 95%C.I; 1.0 - 3.0), the unemployed occupational status (p = 2.4 × 10-2, aOR; 1.2, 95%C.I; 1.0 - 1.4), and persons on more than $401 per month (p = 2.0 × 10-4, aOR; 3.5, 95%C.I; 1.8 - 6.8). CONCLUSION: The majority of parents in Rwanda had both good knowledge of-and good trust regarding childhood vaccination. Public health strategies to promote vaccination, education programmes as well as improved communication tools between health care professionals/traditional leaders/religious leaders and parents need to be considered to achieve favourable vaccination attitudes and practices for all parents in Rwanda.

Epidemiological and genetic characteristics of norovirus in Hangzhou, China, in the postepidemic era.

OBJECTIVE: Norovirus (NoV) is an important human pathogen that can cause severe gastroenteritis in vulnerable populations. This study aimed to analyze the epidemiological and genetic characteristics of 2021-2023 NoV in Hangzhou, China. METHODS: This study enrolled patients aged 0-18 years who underwent NoV RNA detection in the hospital between January 2021 and October 2023 and analyzed the epidemiological characteristics of NoV. Polymerase chain reaction (PCR) was used to detect NoV RNA. Subtype classification and whole-genome sequencing were performed. RESULTS: There was a high prevalence of NoV infection in 2023, with NoV-positive samples accounting for 63.10 % of the total number of positive samples collected during the three-year period. The prevalence was abnormally high in summer, and the number of positive samples accounted for 48.20 % of the total positive samples for the whole year, which was much greater than the level in the same period in previous years (2023, 48.20% vs 2021, 13.66% vs 2022, 15.21 %). The GⅡ.4 subtype played a leading role, followed by increased mixed infection with GⅠ.5 and GⅡ.4. Whole-genome sequencing results suggested that GII.P16-GⅡ.4 had R297H and D372N key locus mutations. The evolutionary rate was 4.29 × 10-3 for the RdRp gene and 4.84 × 10-3 for the VP1 gene. The RdRp gene and VP1 gene of NoV GII.P16-GⅡ.4 have undergone rapid population evolution during the COVID-19 epidemic. CONCLUSION: In the summer of 2023, an abnormally high incidence of NoV appeared in Hangzhou, China. The major epidemic strain GII.P16-GⅡ.4 showed a certain range of gene mutations and a fast evolutionary rate.

Chronic sleep fragmentation impairs brain interstitial clearance in young wildtype mice.

Accumulating evidence shows that most chronic neurological diseases have a link with sleep disturbances, and that patients with chronically poor sleep undergo an accelerated cognitive decline. Indeed, a single-night of sleep deprivation may increase metabolic waste levels in cerebrospinal fluid. However, it remains unknown how chronic sleep disturbances in isolation from an underlying neurological disease may affect the glymphatic system. Clearance of brain interstitial waste by the glymphatic system occurs primarily during sleep, driven by multiple oscillators including arterial pulsatility, and vasomotion. Herein, we induced sleep fragmentation in young wildtype mice and assessed the effects on glymphatic activity and cognitive functions. Chronic sleep fragmentation reduced glymphatic function and impaired cognitive functions in healthy mice. A mechanistic analysis showed that the chronic sleep fragmentation suppressed slow vasomotion, without altering cardiac-driven pulsations. Taken together, results of this study document that chronic sleep fragmentation suppresses brain metabolite clearance and impairs cognition, even in the absence of disease.

Cost-Effectiveness of a Workplace-Based Hypertension Management Program in Real-World Practice in the Kailuan Study.

BACKGROUND: In 2009, a workplace-based hypertension management program was launched among men with hypertension in the Kailuan study. This program involved monitoring blood pressure semimonthly, providing free antihypertensive medications, and offering personalized health consultations. However, the cost-effectiveness of this program remains unclear. METHODS AND RESULTS: This analysis included 12 240 participants, with 6120 in each of the management and control groups. Using a microsimulation model derived from 10-year follow-up data, we estimated costs, quality-adjusted life years (QALYs), life-years, and incremental cost-effectiveness ratios (ICERs) for workplace-based management compared with routine care in both the study period and over a lifetime. Analyses are conducted from the societal perspective. Over the 10-year follow-up, patients in the management group experienced an average gain of 0.06 QALYs with associated incremental costs of $633.17 (4366.85 RMB). Projecting over a lifetime, the management group was estimated to increase by 0.88 QALYs or 0.92 life-years compared with the control group, with an incremental cost of $1638.64 (11 301.37 RMB). This results in an incremental cost-effectiveness ratio of $1855.47 per QALY gained and $1780.27 per life-year gained, respectively, when comparing workplace-based management with routine care. In probabilistic sensitivity analyses, with a threshold willingness-to-pay of $30 765 per QALY (3 times 2019 gross domestic product per capita), the management group showed a 100% likelihood of being cost-effective in 10 000 samples. CONCLUSIONS: Workplace-based management, compared with routine care for Chinese men with hypertension, could be cost-effective both during the study period and over a lifetime, and might be considered in working populations in China and elsewhere.

Neuroprotection of rhubarb extract against cerebral ischaemia-reperfusion injury via the gut-brain axis pathway.

BACKGROUND: The gut-brain axis (GBA) plays a central role in cerebral ischaemia-reperfusion injury (CIRI). Rhubarb, known for its purgative properties, has demonstrated protective effects against CIRI. However, it remains unclear whether this protective effect is achieved through the regulation of the GBA. AIM: This study aims to investigate the mechanism by which rhubarb extract improves CIRI by modulating the GBA pathway. METHODS: We identified the active components of rhubarb extract using LC-MS/MS. The model of middle cerebral artery occlusion (MCAO) was established to evaluate the effect of rhubarb extract. We conducted 16S rDNA sequencing and untargeted metabolomics to analyze intestinal contents. Additionally, we employed HE staining, TUNEL staining, western blot, and ELISA to assess intestinal barrier integrity. We measured the levels of inflammatory cytokines in serum via ELISA. We also examined blood-brain barrier (BBB) integrity using Evans blue (EB) penetration, transmission electron microscopy (TEM), western blot, and ELISA. Neurological function scores and TTC staining were utilized to evaluate neurological outcomes. RESULTS: We identified twenty-six active components in rhubarb. Rhubarb extract enhanced α-diversity, reduced the abundance of Enterobacteriaceae, and partially rectified metabolic disorders in CIRI rats. It also ameliorated pathological changes, increased the expressions of ZO-1, Occludin, and Claudin 1 in the colon, and reduced levels of LPS and d-lac in serum. Furthermore, it lowered the levels of IL-1ß, IL-6, IL-10, IL-17, and TNF-α in serum. Rhubarb extract mitigated BBB dysfunction, as evidenced by reduced EB penetration and improved hippocampal microstructure. It upregulated the expressions of ZO-1, Occludin, Claudin 1, while downregulating the expressions of TLR4, MyD88, and NF-κB. Similarly, rhubarb extract decreased the levels of IL-1ß, IL-6, and TNF-α in the hippocampus. Ultimately, it reduced neurological function scores and cerebral infarct volume. CONCLUSION: Rhubarb effectively treats CIRI, potentially by inhibiting harmful bacteria, correcting metabolic disorders, repairing intestinal barrier function, alleviating BBB dysfunction, and ultimately improving neurological outcomes.

Cost of care for Alzheimer's disease and related dementias in the United States: 2016 to 2060.

Medical and long-term care for Alzheimer's disease and related dementias (ADRDs) can impose a large economic burden on individuals and societies. We estimated the per capita cost of ADRDs care in the in the United States in 2016 and projected future aggregate care costs during 2020-2060. Based on a previously published methodology, we used U.S. Health and Retirement Survey (2010-2016) longitudinal data to estimate formal and informal care costs. In 2016, the estimated per patient cost of formal care was $28,078 (95% confidence interval [CI]: $25,893-$30,433), and informal care cost valued in terms of replacement cost and forgone wages was $36,667 ($34,025-$39,473) and $15,792 ($12,980-$18,713), respectively. Aggregate formal care cost and formal plus informal care cost using replacement cost and forgone wage methods were $196 billion (95% uncertainty range [UR]: $179-$213 billion), $450 billion ($424-$478 billion), and $305 billion ($278-$333 billion), respectively, in 2020. These were projected to increase to $1.4 trillion ($837 billion-$2.2 trillion), $3.3 trillion ($1.9-$5.1 trillion), and $2.2 trillion ($1.3-$3.5 trillion), respectively, in 2060.

The effect of nonpharmaceutical interventions on influenza virus transmission.

Background: The use of nonpharmaceutical interventions (NPIs) during severe acute respiratory syndrome 2019 (COVID-19) outbreaks may influence the spread of influenza viruses. This study aimed to evaluate the impact of NPIs against SARS-CoV-2 on the epidemiological features of the influenza season in China. Methods: We conducted a retrospective observational study analyzing influenza monitoring data obtained from the China National Influenza Center between 2011 and 2023. We compared the changes in influenza-positive patients in the pre-COVID-19 epidemic, during the COVID-19 epidemic, and post-COVID-19 epidemic phases to evaluate the effect of NPIs on influenza virus transmission. Results: NPIs targeting COVID-19 significantly suppressed influenza activity in China from 2019 to 2022. In the seventh week after the implementation of the NPIs, the number of influenza-positive patients decreased by 97.46% in southern regions of China and 90.31% in northern regions of China. However, the lifting of these policies in December 2022 led to an unprecedented surge in influenza-positive cases in autumn and winter from 2022 to 2023. The percentage of positive influenza cases increased by 206.41% (p < 0.001), with high positivity rates reported in both the northern and southern regions of China. Conclusion: Our findings suggest that NPIs against SARS-CoV-2 are effective at controlling influenza epidemics but may compromise individuals' immunity to the virus.

Transforming growth factor-ß1 protects against white matter injury and reactive astrogliosis via the p38 MAPK pathway in rodent demyelinating model.

In central nervous system (CNS), demyelination is a pathological process featured with a loss of myelin sheaths around axons, which is responsible for the diseases of multiple sclerosis, neuromyelitis optica, and so on. Transforming growth factor-beta1 (TGF-ß1) is a multifunctional cytokine participating in abundant physiological and pathological processes in CNS. However, the effects of TGF-ß1 on CNS demyelinating disease and its underlying mechanisms are controversial and not well understood. Herein, we evaluated the protective potential of TGF-ß1 in a rodent demyelinating model established by lysophosphatidylcholine (LPC) injection. It was identified that supplement of TGF-ß1 evidently rescued the cognitive deficit and motor dysfunction in LPC modeling mice assessed by novel object recognition and balance beam behavioral tests. Besides, quantified by luxol fast blue staining, immunofluorescence, and western blot, administration of TGF-ß1 was found to significantly ameliorate the demyelinating lesion and reactive astrogliosis by suppressing p38 MAPK pathway. Mechanistically, the results of in vitro experiments indicated that treatment of TGF-ß1 could directly promote the differentiation and migration of cultured oligodendrocytes. Our study revealed that modulating TGF-ß1 activity might serve as a promising and innovative therapeutic strategy in CNS demyelinating diseases.

MiR-9 promotes G-MDSC recruitment and tumor proliferation by targeting SOCS3 in breast cancer.

Myeloid-derived suppressor cells (MDSCs) are a heterogeneous group of cells that differentiate from myeloid cells, proliferate in cancer and inflammatory reactions, and mainly exert immunosuppressive functions. Nonetheless, the precise mechanisms that dictate both the accumulation and function of MDSCs remain only partially elucidated. In the course of our investigation, we observed a positive correlation between the content of MDSCs especially G-MDSCs and miR-9 level in the tumor tissues derived from miR-9 knockout MMTV-PyMT mice and 4T1 tumor-bearing mice with miR-9 overexpression. Combined with RNA-seq analysis, we identified SOCS2 and SOCS3 as direct targets of miR-9. Additionally, our research unveiled the pivotal role of the CCL5/CCR5 axis in orchestrating the chemotactic recruitment of G-MDSCs within the tumor microenvironment, a process that is enhanced by miR-9. These findings provide fresh insights into the molecular mechanisms governing the accumulation of MDSCs within the framework of breast cancer development.

The effects of parental retirement on adult children's health: Evidence from China.

Using representative data from China, we examine the causal effects of parental retirement on the health of adult children. To do so, we adopt a fuzzy regression discontinuity design and exploit the mandatory retirement ages in China as cut-off points. We find no evidence that parental retirement has significant effects on the mental health, healthcare utilization, or risky health behaviors of adult children. However, paternal retirement and maternal retirement have different effects on adult children's Self-reported health (SRH). Paternal retirement has a significantly negative effect only on the SRH of sons, while maternal retirement does not induce such effects. Potential mechanisms of intergenerational transfer through which parental retirement might affect adult children's health are also explored.

Escherichia coli Infection Sepsis: An Analysis of Specifically Expressed Genes and Clinical Indicators.

Since E. coli is the most prevalent sepsis bacterium, studying its pathogenic molecular pathways may help with its early diagnosis and individualized treatment. However, few studies have investigated the molecular characterization of E. coli infection only. We extracted E. coli infection-specific genes and indicators from published data and clinical laboratory results in this study. GSE65088 showed 277, 377, and 408 DEGs for E. coli and other bacteria, E. coli and healthy groups, and other bacteria and healthy groups, respectively. DEGs, the MEgreen module with the highest relevance in WGCNA, and the first three MCODE subnetworks were used to find E. coli infection-specific hub genes. HSPA1B and TNF were verified in GSE6269 with ROC-AUCs of 0.7038 and 0.7116, respectively. CIBERSORT showed increased B-cell naive and T-cell CD4 naive infiltration in E. coli infectious sepsis. Patients infected with E. coli were younger than those infected with other pathogens. Compared to the other bacterially infectious sepsis patients, the E. coli patients had low globulin, prealbumin, creatine kinase, and high bilirubin levels. The clinically significant difference indicator IL-2, in combination with hub genes, better differentiated the healthy and E. coli groups, with an ROC-AUC of 0.8793. The study suggested that HSPA1B and TNF may be E.-coli-infection-specific genes, which may help explain the molecular mechanism of infectious sepsis.

In Vitro/In Vivo Preparation and Evaluation of cRGDyK Peptide-Modified Polydopamine-Bridged Paclitaxel-Loaded Nanoparticles.

Cancer remains a disease with one of the highest mortality rates worldwide. The poor water solubility and tissue selectivity of commonly used chemotherapeutic agents contribute to their poor efficacy and serious adverse effects. This study proposes an alternative to the traditional physicochemically combined modifications used to develop targeted drug delivery systems, involving a simpler surface modification strategy. cRGDyK peptide (RGD)-modified PLGA nanoparticles (NPs) loaded with paclitaxel were constructed by coating the NP surfaces with polydopamine (PD). The average particle size of the produced NPs was 137.6 ± 2.9 nm, with an encapsulation rate of over 80%. In vitro release tests showed that the NPs had pH-responsive drug release properties. Cellular uptake experiments showed that the uptake of modified NPs by tumor cells was significantly better than that of unmodified NPs. A tumor cytotoxicity assay demonstrated that the modified NPs had a lower IC50 and greater cytotoxicity than those of unmodified NPs and commercially available paclitaxel formulations. An in vitro cytotoxicity study indicated good biosafety. A tumor model in female BALB/c rats was established using murine-derived breast cancer 4T1 cells. RGD-modified NPs had the highest tumor-weight suppression rate, which was higher than that of the commercially available formulation. PTX-PD-RGD-NPs can overcome the limitations of antitumor drugs, reduce drug toxicity, and increase efficacy, showing promising potential in cancer therapy.

The macroeconomic burden of noncommunicable diseases and mental health conditions in South America.

Noncommunicable diseases and mental health conditions (referred to collectively as NMHs) are the greatest cause of preventable death, illness, and disability in South America and negatively affect countries' economic performance through their detrimental impacts on labor supply and capital investments. Sound, evidence-based policy-making requires a deep understanding of the macroeconomic costs of NMHs and of their distribution across countries and diseases. The paper estimates and projects the macroeconomic burden of NMHs over the period 2020-2050 in 10 South American countries. We estimate the impact of NMHs on gross domestic product (GDP) through a human capital-augmented production function approach, accounting for mortality and morbidity effects of NMHs on labor supply, for the impact of treatment costs on physical capital accumulation, and for variations in human capital by age. Our central estimates suggest that the overall burden of NMHs in these countries amounts to $7.3 trillion (2022 international $, 3% discount rate, 95% confidence interval: $6.8-$7.8 trillion). Overall, the macroeconomic burden of NMHs is around 4% of total GDP over 2020-2050, with little variation across countries (from 3.2% in Peru to 4.5% in Brazil). In other words, without NMHs, annual GDP over 2020-2050 would be about 4% larger. In most countries, the largest macroeconomic burden is associated with cancers. Results from the paper point to a significant macroeconomic burden of NMHs in South America and provide a strong justification for investment in NMH prevention, early detection, treatment, and formal and informal care.

Association of triglyceride-glucose index trajectory and frailty in urban older residents: evidence from the 10-year follow-up in a cohort study.

BACKGROUND: Frailty is an age-related geriatric syndrome that leads to a series of clinically negative events. A better understanding of the factors associated with frailty assists in preventing its progression. The triglyceride-glucose (TyG) index, a simple alternative index of insulin resistance, has not yet been proven to be associated with frailty. The present study aimed to investigate the association between the TyG index and its trajectory with frailty from a cross-sectional, retrospective and prospective level based on an ongoing cohort. METHODS: This longitudinal study included 1,866 older residents from the "Fujian prospective aging cohort" (ChiCTR 2,000,032,949). The TyG index was calculated as ln [fasting triglyceride (mg/dL) ╳ fasting plasma glucose (mg/dL)/2] and group-based trajectory model (GBTM) was applied to identify the trajectory of TyG index. The association between different trajectory groups of TyG index with frailty risk were estimated using multinomial logistic regression analysis. RESULTS: In the cross-sectional analysis, the highest quartile of the TyG index was associated with an increased risk of frailty (TyG index Q4 vs. Q1, OR = 1.50, 95% CI 1.00-2.25, P = 0.048). Restricted cubic splines demonstrated an increasing trend for TyG index and frailty risk. During a follow-up of ten years, three distinct trajectories of the TyG index were identified: low-stable (n = 697, 38.3%), moderate-stable (n = 910, 50.0%) and high-stable (n = 214, 11.7%). Compared with those in the stable-low group of TyG index trajectory, the ORs (95% CI) of prefrailty and frailty risk were 1.79 (95% CI 1.11-2.88) and 2.17 (95% CI 1.01-3.88) for the high-stable group, respectively (P = 0.017 and P = 0.038). In the subgroup analysis, the association of the high-stable trajectory of TyG and frailty status were only observed in subjects with BMI ≥ 24 kg/m2. Prospectively, the highest quartile of the TyG index was associated with a 2.09-fold significantly increased risk of one-year ADL/IADL decline (P = 0.045). CONCLUSIONS: The present study suggests a potential role for a high and sustainable level of TyG index in the risk of frailty. The trajectories of the TyG index can help to identify older individuals at a higher risk of frailty who deserve primitive preventive and therapeutic approaches.

Machine learning approaches reveal highly heterogeneous air quality co-benefits of the energy transition.

Estimating health benefits of reducing fossil fuel use from improved air quality provides important rationales for carbon emissions abatement. Simulating pollution concentration is a crucial step of the estimation, but traditional approaches often rely on complicated chemical transport models that require extensive expertise and computational resources. In this study, we develop a machine learning framework that is able to provide precise and robust annual average fine particle (PM2.5) concentration estimations directly from a high-resolution fossil energy use dataset. Applications of the framework with Chinese data reveal highly heterogeneous health benefits of avoiding premature mortality by reducing fossil fuel use in different sectors and regions in China with a mean of $19/tCO2 and a standard deviation of $38/tCO2. Reducing rural and residential coal use offers the highest co-benefits with a mean of $151/tCO2. Our findings prompt careful policy designs to maximize cost-effectiveness in the transition toward a carbon-neutral energy system.