Sex Subgroup Analyses Research Articles

Sex-specific association of comorbid heart failure on mortality after Alzheimer's disease diagnosis in older adults aged 75 years and above: A health insurance claims data analysis in Japan.

Research on the influence of heart failure on mortality after Alzheimer's disease diagnosis is limited. To evaluate the association between comorbid heart failure and mortality following Alzheimer's disease diagnosis, particularly considering sex differences. We analyzed administrative claims data from Japan, involving 32,363 individuals (11,064 men and 21,299 women) aged 75 or older newly diagnosed with Alzheimer's disease, with 7% having comorbid heart failure. Cox proportional hazard models and population attributable fractions (PAFs) were used to evaluate the association between comorbid heart failure and mortality within one year following Alzheimer's disease diagnosis. Individuals with Alzheimer's disease and heart failure had a multivariate-adjusted hazard ratio of 1.51 (95% confidence interval [CI], 1.32-1.73) for mortality during the one-year follow-up period compared to those with Alzheimer's disease and without heart failure. Subgroup analysis by sex revealed a higher mortality hazard ratio in women of 1.63 (95% CI, 1.36-1.95) than that in men of 1.39 (95% CI, 1.13-1.71). Further age and sex subgroup analysis indicated that women across all age brackets-75-79, 80-84, and ≥ 85 years-had higher mortality hazard ratios. The PAF for heart failure increased with age in both sexes, with women having higher PAFs than men, and the sex difference in PAF being most pronounced in the 75-79 age category (men: 1.4%, women: 4.0%). Hazard ratios and PAFs for mortality associated with comorbid heart failure in newly diagnosed Alzheimer's disease are higher in women than in men, which persists across all age subgroups.

Post-marketing safety of panitumumab: a real-world pharmacovigilance study

ABSTRACT Background Panitumumab has been extensively applied in antitumor therapy, and the regulation of its adverse drug reactions (ADRs) has become extremely important. This study utilized the U.S. Food and Drug Administration Adverse Event Reporting System (FAERS) database to extract real-world panitumumab ADR signals and provide relevant information for drug safety. Research design and methods ROR, PRR, BCPNN, and MGPS were used to identify real-world ADR signals associated with panitumumab. Results Analysis of 9,033 patients identified 263 ADR signals across 20 MedDRA System Organ Classifications. New signals including peripheral sensory neuropathy, gene mutation, decreased neutrophil count, polyneuropathy, ileus, neutropenia, and febrile neutropenia. Age and sex subgroup analyses revealed specific risks, such as polyneuropathy and gene mutation in those under 65 years of age, decreased neutrophil count and peripheral sensory neuropathy in those over 65 years of age, and febrile neutropenia in men. Ileus was highlighted as a novel ADR in gastrointestinal disorders, with no significant age or sex differences. Conclusion This study identified new signals of ADR associated with panitumumab, providing valuable information for the clinical use of panitumumab.

Psoriasis and risk of new-onset degenerative valvular heart disease: a prospective cohort study.

Recent evidence indicates that degenerative valvular heart disease (VHD) and psoriasis share overlapping risk factors and simultaneous presence of inflammation, yet this relationship has not been thoroughly explored. Drawing on the prospective cohort data from the UK Biobank, baseline information on psoriasis and the incidence of eight specific types of degenerative VHD-aortic stenosis (AS), aortic regurgitation, mitral stenosis, mitral regurgitation, tricuspid stenosis, tricuspid regurgitation, pulmonary stenosis, and pulmonary regurgitation-during the follow-up period were recorded. Cox proportional hazards models were conducted to estimate the association between psoriasis and the risk of degenerative VHD, adjusted for demographic indicators, lifestyle factors, comorbidities, and medication. A total of 494 510 participants were included in the study. Among the participants without psoriasis, 13 672 events of degenerative VHD were observed during a median follow-up of 13.78 years, yielding an incidence rate of 2.14 per 1 000 person-years. In contrast, In the psoriasis group (n=10 917), 422 events of degenerative VHD were reported during a median follow-up of 13.70 years, corresponding to an incidence rate of 2.93 per 1 000 person-years. After fully adjusting, participants with psoriasis had a significantly increased risk of AS (HR, 1.24; 95% CI, 1.07-1.43), yet no significant associations were observed between psoriasis and the risk of other degenerative valve diseases. In sex subgroup analyses, there was an interaction between sex and psoriasis in the occurrence of AS (p-interaction=0.039), suggesting a high risk in women. Psoriasis was significantly associated with the risk of new-onset AS and may be more distinct in females, while no significant associations were observed between psoriasis and the risk of developing other degenerative valve diseases.

Early onset and increasing disparities in neurodevelopmental delays from birth to age 6 in children from low socioeconomic backgrounds.

To analyze the complex relationship between socioeconomic status (SES) and neurodevelopmental achievements by investigating the temporal dynamics of these associations from birth to age 6. This retrospective cohort study was conducted over 6 years using population-based data from the National Health Insurance Service and integrated data from the National Health Screening Program for Infants and Children. Participants were children born between 2009 and 2011 in Korea without neurodevelopmental delays with potential developmental implications. We analyzed results from the Korean Developmental Screening Test, administered at age 6, which covered overall assessment and six domains of gross and fine motor function, cognition, language, sociality, and self-care. The secondary outcome was to determine when neurodevelopmental outcomes began after birth and how these differences changed over time. Of 276,167 individuals (49.2% males), 66,325, 138,980, and 60,862 had low, intermediate, and high SES, respectively. Neurodevelopmental delays observed across all developmental domains were more prevalent in the low-SES group than in the high-SES group. Disparities in neurodevelopment according to these statuses were apparent as early as age 2 and tended to increase over time (interaction, P < 0.001). The cognition and language domains exhibited the most substantial disparities between SES levels. These disparities persisted in subgroup analyses of sex, birthweight, head circumference, birth data, and breastfeeding variables. Low SES was significantly associated with an increased risk of adverse neurodevelopmental outcomes in preschool children, particularly those affecting cognitive and language domains. These differences manifested in early childhood and widened over time.

Association of allostatic load with depression, anxiety, and suicide: a prospective cohort study

BackgroundAllostatic load (AL) is an objective measure of the biological components of chronic stress within clinical practice, potentially influencing depression, anxiety, and suicide. This study investigates the association between AL and these mental disorders. MethodsIn this cohort study of 333,017 adults, participants without prior diagnoses of depression, anxiety, or suicide were observed from March 13, 2006, to October 31, 2022. AL was estimated using 10 biomarkers reflecting metabolic, cardiovascular, and inflammatory dysregulation. Diagnoses were based on the International Classification of Diseases 10th Revision (ICD-10). We performed Cox proportional hazards models to assess the relationship between AL and these mental disorders. Additionally, we conducted subgroup analyses for sex, age, and Townsend Deprivation Index (TDI), along with sensitivity analyses. ResultsThe median follow-up period was 12.99 years. Over the follow-up period, 13,441 (4.04%) participants developed depression, 13,903 (4.17%) developed anxiety and 796 (0.24%) committed suicide. In fully adjusted model, individuals with high AL had an increased risk of depression (HR = 1.389, P = 8.38 ×10-27), anxiety (HR = 1.304, P = 5.82 ×10-19) and suicide (HR = 1.433, P = 4.46 ×10-3). Women and younger individuals with high AL were vulnerable to depression and anxiety, while moderate AL levels were significantly associated with suicide in men and younger participants. Moreover, individuals with middle and high AL had an elevated risk of comorbid depression and anxiety. ConclusionsHigh AL is positively associated with increased risks of depression, anxiety, and suicide, highlighting its potential as a predictive tool in mental health.

Association of sodium-glucose cotransporter 2 inhibitors with risk of incident dementia and all-cause mortality in older patients with type 2 diabetes: A retrospective cohort study using the TriNetX US collaborative networks.

Limited evidence exists to support any specific medication over others to prevent dementia in older patients with type 2 diabetes (T2D). We investigated whether treatment with sodium-glucose cotransporter 2 (SGLT-2) inhibitors is associated with a lower risk of incident dementia and all-cause mortality, relative to dipeptidyl peptidase-4 (DPP-4) inhibitors and glucagon-like peptide-1 receptor agonists (GLP-1 RA). In this retrospective, active-comparator cohort study, we used data from the TriNetX electronic health records network. Our primary cohort comprised patients with T2D aged ≥50 years, registered between January 2012 and December 2022. Patients with a history of dementia were excluded. We used Kaplan-Meier survival analysis to estimate the incidence of dementia and all-cause mortality in our cohort after they had used glucose-lowering drugs for at least 12 months. Propensity score matching was performed to balance the SGLT-2 inhibitor, DPP-4 inhibitor and GLP-1 RA cohorts. Subgroup analyses for sex and age were also conducted. Our first cohort comprised 193 948 patients treated with metformin and SGLT-2 inhibitors and an equal number of patients treated with metformin and DPP-4 inhibitors. In this cohort, the risk of dementia and all-cause mortality was lower in patients treated with SGLT-2 inhibitors than in those treated with DPP-4 inhibitors (hazard ratio [HR]: 0.62, 95% confidence interval [CI]: 0.59-0.65, for dementia; HR: 0.54, 95% CI: 0.52-0.56, for all-cause mortality). Our second cohort comprised 165 566 patients treated with metformin and SGLT-2 inhibitors and an equal number of patients treated with metformin and GLP-1 RAs. In this cohort, the risk of dementia and all-cause mortality was lower in those treated with SGLT-2 inhibitors than in those treated with GLP-1 RAs (HR: 0.92, 95% CI: 0.87-0.98, for dementia; HR: 0.88, 95% CI: 0.85-0.91, for all-cause mortality). The use of SGLT-2 inhibitor was associated with a lower risk of incident dementia and all-cause mortality in older adults with T2D compared to DPP-4 inhibitor and GLP-1 RA.

Effects of Lacticaseibacillus rhamnosus HN001 on Happiness and Mental Well-Being: Findings from a Randomized Controlled Trial.

Lacticaseibacillus rhamnosus HN001 (HN001) is a probiotic strain widely studied for its potential to improve human health. Previous studies have demonstrated promising results for HN001 in the improvement of mental well-being, particularly in terms of increased happiness and support for stress management in healthy adults. To further explore these findings, a double-blind, placebo-controlled trial was conducted with 120 participants aged ≥ 18 years with mild to high stress measured by the Perceived Stress Scale (PSS). The participants were randomly assigned to receive either HN001 or placebo for 28 days. Psychological assessments, including the Oxford Happiness Questionnaire (OHQ), were completed at baseline, day 14, and day 28. Secondary outcomes included changes in PSS scores, as well as depression, anxiety, stress, and total score levels measured by the DASS-21 questionnaire. While not statistically significant, participants who received HN001 showed an improvement in OHQ (mean change, 13.3) and PSS total scores (mean change, -8.1) over time compared with the placebo group (mean change, 10.2 and -6.6, respectively). Furthermore, 39% of the participants moved from not happy to happy, compared with only 29% in the placebo group. Post-hoc analysis showed a statistically significant interaction between intervention and study day for OHQ and PSS total scores, with p-values of 0.014 and 0.043, respectively. No adverse effects were observed. HN001 showed improvements in both happiness and PSS scores. Furthermore, sex subgroup analysis revealed statistically significant differences in both outcomes, emphasizing the need for larger and longer intervention studies.

The risk of geriatric syndromes in older COVID-19 survivors among the nonvaccinated population: a real world retrospective cohort study.

We aimed to analyse the differences in the risk of geriatric syndromes between older adults with and without coronavirus disease 2019 (COVID-19). We conducted a retrospective cohort study of patients from the US Collaborative Network in the TriNetX between January 1, 2020, and December 31, 2022. We included individuals aged older than 65years with at least 2 health care visits who underwent severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) polymerase chain reaction (PCR) tests during the study period. We excluded those with SARS-CoV-2 vaccination, diagnosis with neoplasm and geriatric syndromes before the index date, and death within 30days after the index date. The index date was defined as the first date of the PCR test for SARS-CoV-2 during the study period. Hazard ratios (HRs) and 95% confidence intervals (CIs) for eight geriatric syndromes were estimated for propensity score-matched older adults with and without COVID-19. Subgroup analyses of sex and age were also performed. After propensity score matching, 315826 patients were included (mean [standard deviation] age, 73.5 [6.4] years; 46.7% males and 51.7% females). The three greatest relative increases in the risk of geriatric syndromes in the COVID-19 cohort were cognitive impairment (HR: 3.13; 95% CI: 2.96-3.31), depressive disorder (HR: 2.72; 95% CI: 2.62-2.82) and pressure injury (HR: 2.52; 95% CI: 2.34-2.71). The risk of developing geriatric syndromes is much higher in the COVID-19 cohort. It is imperative that clinicians endeavour to prevent or minimise the development of these syndromes in the post-COVID-19 era.

Artificial Intelligence for Early Detection of Pediatric Eye Diseases Using Mobile Photos

Identifying pediatric eye diseases at an early stage is a worldwide issue. Traditional screening procedures depend on hospitals and ophthalmologists, which are expensive and time-consuming. Using artificial intelligence (AI) to assess children's eye conditions from mobile photographs could facilitate convenient and early identification of eye disorders in a home setting. To develop an AI model to identify myopia, strabismus, and ptosis using mobile photographs. This cross-sectional study was conducted at the Department of Ophthalmology of Shanghai Ninth People's Hospital from October 1, 2022, to September 30, 2023, and included children who were diagnosed with myopia, strabismus, or ptosis. A deep learning-based model was developed to identify myopia, strabismus, and ptosis. The performance of the model was assessed using sensitivity, specificity, accuracy, the area under the curve (AUC), positive predictive values (PPV), negative predictive values (NPV), positive likelihood ratios (P-LR), negative likelihood ratios (N-LR), and the F1-score. GradCAM++ was utilized to visually and analytically assess the impact of each region on the model. A sex subgroup analysis and an age subgroup analysis were performed to validate the model's generalizability. A total of 1419 images obtained from 476 patients (225 female [47.27%]; 299 [62.82%] aged between 6 and 12 years) were used to build the model. Among them, 946 monocular images were used to identify myopia and ptosis, and 473 binocular images were used to identify strabismus. The model demonstrated good sensitivity in detecting myopia (0.84 [95% CI, 0.82-0.87]), strabismus (0.73 [95% CI, 0.70-0.77]), and ptosis (0.85 [95% CI, 0.82-0.87]). The model showed comparable performance in identifying eye disorders in both female and male children during sex subgroup analysis. There were differences in identifying eye disorders among different age subgroups. In this cross-sectional study, the AI model demonstrated strong performance in accurately identifying myopia, strabismus, and ptosis using only smartphone images. These results suggest that such a model could facilitate the early detection of pediatric eye diseases in a convenient manner at home.

Combined immunogenicity evaluation for a new single-dose live-attenuated chikungunya vaccine.

Chikungunya is a serious and debilitating viral infection with a significant disease burden. VLA1553 (IXCHIQ®) is a live-attenuated vaccine licensed for active immunization for prevention of disease caused by chikungunya virus (CHIKV). Immunogenicity following a single dose of VLA1553 was evaluated in healthy adults aged ≥18years in two Phase 3 trials [N = 656 participants (per protocol analysis set)]. Immunogenicity data to 180days post-vaccination [geometric mean titres (GMTs), seroresponse rate, seroconversion rate] were pooled for the two trials. A comparison of subgroups based on age, sex, body mass index (BMI), race and baseline seropositivity was included. All analyses were descriptive. Most participants were aged 18-64years (N = 569/656 [86.7%]), there were slightly more females (N = 372/656 [56.7%]), most were not Hispanic/Latino (N = 579/656 [88.3%]), and most were White (N = 517/656 [78.8%]). In baseline seronegative participants, GMT peaked at Day 29 post-vaccination, and subsequently declined slightly but remained elevated until Day 180. At Days 29, 85 and 180, seroresponse rate was 98.3, 97.7 and 96.4% and seroconversion rate was 98.5, 98.4 and 98.2%. There were no differences in seroresponse rate in participants aged 18-64years or ≥65years at Day 29 (98.1 vs 100%), Day 85 (97.4 vs 100%) and Day 180 (96.3 vs 96.5%) nor based on sex, BMI, ethnicity or race. An immune response was shown in a small heterogenous population of baseline seropositive participants, with GMTs showing the same trend as baseline seronegative participants. A single dose of VLA1553 elicited a very strong immune response by Day 29 that remained elevated at Day 180 in both baseline seronegative and seropositive participants in a combined evaluation of two Phase 3 trials. The vaccine was similarly immunogenic in participants aged ≥65years and 18-64years, and there were no differences based on subgroup analyses for sex, BMI, ethnicity or race.

Bisphenol AF exposure synergistically increases the risk for suicidality among early adolescents with child maltreatment: A prospective cohort study

BackgroundChild maltreatment (CM) is correlated with suicidality risk among adolescents. Additionally, exposure to bisphenol AF (BPAF) may increase this risk. However, the combined effect of CM and BPAF exposure remains unknown and should be further investigated. MethodsIn this study, 1,475 early adolescents (mean age = 12.48 years) from the Chinese Early Adolescents Cohort were enrolled. Data were collected at three time points with an interval of 12 months between 2019 and 2021. Participants’ history of CM and suicidality (including suicidal ideation and suicidal attempts) were evaluated using a self-report questionnaire. Blood samples were obtained from participants to measure serum BPAF concentrations at baseline. Group-based trajectory modeling was employed to identify different developmental trajectories of suicidality across the three waves. After adjusting for potential confounders, the association between CM and BPAF exposure on suicidal ideation and suicidal attempts was assessed using logistic regression and Poisson regression analyses. ResultsParticipants with CM were associated with a risk of one- and two-year incident suicidality (all ps < 0.05), and BPAF levels were positively associated with two-year incident suicidal ideation (adjusted OR = 1.68, 95% CI: 1.13–2.50). Additionally, middle and high levels of BPAF exposure synergistically increase the risk for one- and two-year incident suicidal ideation among participants with CM (adjusted ORs = 2.00–3.83). Similarly, participants exposed to high-level BPAF as well as CM were at a greater risk of one- and two-year incident suicidal attempts than those with low-level BPAF exposure and no CM (adjusted incidence rate ratio [IRRs] = 2.82–4.34). Moreover, compared with participants with a low developmental trajectory of suicidality across the three waves, high BPAF exposure exhibited a significant synergistic effect on participants with CM in the persistently high suicidal ideation trajectory and the increasing suicidal attempts trajectory (all ps < 0.05). Sex subgroup analysis revealed that females were more susceptible to the synergistic effect of BPAF and CM exposure on suicidality than males. ConclusionsEnvironmental factors and the psychological status of individuals may synergistically increase their susceptibility to suicidality. These results offer novel insights into enhancing our understanding of suicidality among adolescents.

Trends and disparities in colorectal cancer hospitalizations and outcomes: a 10-year joinpoint trend study

Background Colorectal cancer (CRC) poses a significant burden on healthcare systems globally. Sociodemographic factors intricately influence CRC epidemiology, yet their impact on inpatient care remains underexplored. This study aimed to assess trends in CRC hospitalization and the effect of sociodemographic factors on outcomes of CRC patients. Methods A retrospective longitudinal analysis was conducted using data from the Healthcare Cost and Utilization Project National Inpatient Sample. Trends in CRC admissions were assessed, stratified by sociodemographic variables. Disparities in hospital-associated outcomes were examined. Statistical methods included multivariable regression and joinpoint regression analysis. Results The prevalence of CRC hospitalizations uptrended from 760 per 100,000 hospitalizations in 2010 to 841 per 100,000 hospitalizations in 2019 (P trend < 0.001). The mean age decreased from 67 to 66 years (P < 0.001). Male gender and White race were predominant across the study period. Inpatient mortality decreased from 4.5% in 2010 to 4.16% in 2019 (P trend = 0.033). On sex subgroup analysis, men had a significantly higher mortality rate (P = 0.034). Racially, Blacks had the highest mortality rate (P = 0.550) and only Whites showed a significant decline in mortality over the study period (P = 0.003). Hospitalization length decreased while total hospital charges increased. Conclusion Our study highlights sociodemographic disparities in CRC outcomes, emphasizing the need for targeted interventions to address inequity in screening, diagnosis, and treatment. Continued research is needed to inform effective healthcare practices in mitigating these disparities and improving survival outcomes.

Mendelian randomization study of the relationship between blood and urine biomarkers and schizophrenia in the UK Biobank cohort

BackgroundThe identification of suitable biomarkers is of crucial clinical importance for the early diagnosis of treatment-resistant schizophrenia (TRS). This study aims to comprehensively analyze the association between TRS and blood and urine biomarkers.MethodsCandidate TRS-related single nucleotide polymorphisms (SNPs) were obtained from a recent genome-wide association study. The UK Biobank cohort, comprising 376,807 subjects with blood and urine biomarker testing data, was used to calculate the polygenic risk score (PRS) for TRS. Pearson correlation analyses were performed to evaluate the correlation between TRS PRS and each of the biomarkers, using calculated TRS PRS as the instrumental variables. Bidirectional two-sample Mendelian randomization (MR) was used to assess potential causal associations between candidate biomarkers with TRS.ResultsHere we identify a significant association between TRS PRS and phosphate (r = 0.007, P = 1.96 × 10−4). Sex subgroup analyses identify seven and three candidate biomarkers associated with TRS PRS in male and female participants, respectively. For example, total protein and phosphate for males, creatinine and phosphate for females. Bidirectional two-sample MR analyses indicate that TRS is negatively associated with cholesterol (estimate = −0.363, P = 0.008). Conversely, TRS is positively associated with total protein (estimate = 0.137, P = 0.027), mean corpuscular volume (estimate = 0.032, P = 2.25 × 10−5), and mean corpuscular hemoglobin (estimate = 0.018, P = 0.007).ConclusionsOur findings provide insights into the roles of blood and urine biomarkers in the early detection and treatment of TRS.

A Comparison of the Periprosthetic Fracture Rate of Cemented and Cementless Total Knee Arthroplasties: An Analysis of Data From the National Joint Registry

BackgroundPeriprosthetic fractures are serious complications of knee arthroplasty often requiring complex surgery. There is concern of increased periprosthetic fracture risk with cementless components given the reliance on interference fit for primary stability. It is unknown how the periprosthetic fracture risk compares between cemented and cementless total knee arthroplasties (TKAs). MethodsA total of 22,477 cemented and 22,477 cementless TKAs from the National Joint Registry and Hospital Episodes Statistics database were propensity score matched on patient and surgical factors. Cumulative periprosthetic fracture rates were calculated using Kaplan-Meier analyses and compared with Cox regressions. Subgroup analyses were performed in different age, body mass index, and sex groups. ResultsThe 3-month fracture rate in the cemented and cementless TKA groups were 0.02% and 0.04%, respectively. At 10 years, the cumulative fracture rate after cemented TKA was 1.2%, and after cementless was 1.4%. During the study period, there were no significant differences in fracture rates between cemented and cementless TKAs with a hazards ratio 1.14 (confidence interval 0.94 to 1.37, P = .20) at 10 years postoperatively. There were no significant differences in fracture rates between fixation types on subgroup analyses of sex, body mass index, and age groups. Female sex was a risk factor for fracture in both cemented (odds ratio 2.35, P < .001) and cementless TKAs (odds ratio 2.97, P < .001). ConclusionsThe periprosthetic fracture rates following cemented and cementless TKA surgery are low being approximately 1.2% and 1.4%, respectively at 10 years. There were no significant differences in periprosthetic fracture rates requiring readmission between cemented and cementless TKAs. Level of evidenceIII.

Epidemiology of adult hand injuries presenting to a tertiary hand surgery unit: a review of 4216 cases.

This study investigates the pattern of hand injuries presenting to a UK regional tertiary centre. All referrals to our Hand Surgery Unit in 2019 were reviewed. Subgroup analyses of sex, deprivation, occupational injuries and assault cases were carried out. Over the study period, 4216 cases were referred. Most were male (70%), with a median age of 36 years and from a deprived area (75.2%). Soft tissue injury was documented in 53.6% and bone injury (fracture/dislocation) in 52.4%. Surgical management was required in 2214 (52.5%) cases. Work-related injuries accounted for 16.7% of cases and were more likely to require surgery. Assault-related injuries accounted for 8% of cases, with a male preponderance. Our findings can help facilitate service provision and guide regional and national prevention policies.Level of evidence: III.

Externally validated deep learning model to identify prodromal Parkinson’s disease from electrocardiogram

Little is known about electrocardiogram (ECG) markers of Parkinson’s disease (PD) during the prodromal stage. The aim of the study was to build a generalizable ECG-based fully automatic artificial intelligence (AI) model to predict PD risk during the prodromal stage, up to 5 years before disease diagnosis. This case–control study included samples from Loyola University Chicago (LUC) and University of Tennessee-Methodist Le Bonheur Healthcare (MLH). Cases and controls were matched according to specific characteristics (date, age, sex and race). Clinical data were available from May, 2014 onward at LUC and from January, 2015 onward at MLH, while the ECG data were available as early as 1990 in both institutes. PD was denoted by at least two primary diagnostic codes (ICD9 332.0; ICD10 G20) at least 30 days apart. PD incidence date was defined as the earliest of first PD diagnostic code or PD-related medication prescription. ECGs obtained at least 6 months before PD incidence date were modeled to predict a subsequent diagnosis of PD within three time windows: 6 months–1 year, 6 months–3 years, and 6 months–5 years. We applied a novel deep neural network using standard 10-s 12-lead ECGs to predict PD risk at the prodromal phase. This model was compared to multiple feature engineering-based models. Subgroup analyses for sex, race and age were also performed. Our primary prediction model was a one-dimensional convolutional neural network (1D-CNN) that was built using 131 cases and 1058 controls from MLH, and externally validated on 29 cases and 165 controls from LUC. The model was trained on 90% of the MLH data, internally validated on the remaining 10% and externally validated on LUC data. The best performing model resulted in an external validation AUC of 0.67 when predicting future PD at any time between 6 months and 5 years after the ECG. Accuracy increased when restricted to ECGs obtained within 6 months to 3 years before PD diagnosis (AUC 0.69) and was highest when predicting future PD within 6 months to 1 year (AUC 0.74). The 1D-CNN model based on raw ECG data outperformed multiple models built using more standard ECG feature engineering approaches. These results demonstrate that a predictive model developed in one cohort using only raw 10-s ECGs can effectively classify individuals with prodromal PD in an independent cohort, particularly closer to disease diagnosis. Standard ECGs may help identify individuals with prodromal PD for cost-effective population-level early detection and inclusion in disease-modifying therapeutic trials.

The association between cholecystectomy and the risk of colorectal cancer: an updated systematic review and meta-analysis of cohort studies.

The effect of cholecystectomy on the development of colorectal cancer (CRC) has prompted a large number of population-based studies. However, the results of these studies are debatable and inconclusive. Our aim in the present study was to conduct an updated systematic review and meta-analysis to explore the causality between cholecystectomy and CRC. Cohort studies published in the PubMed, Web of Science, Embase, Medline, and Cochrane databases up to May 2022 were retrieved. Pooled relative risks (RRs) and 95% confidence intervals (CIs) were analyzed using a random effects model. Eighteen studies, involving 1,469,880 cholecystectomy and 2,356,238 non-cholecystectomy cases, were eligible for the final analysis. Cholecystectomy was not associated with the development of CRC (P=0.109), colon cancer (P=0.112), or rectal cancer (P=0.184). Subgroup analysis of sex, lag period, geographic region, and study quality revealed no significant differences in the relationship between cholecystectomy and CRC. Interestingly, cholecystectomy was significantly associated with right-sided colon cancer (RR =1.20, 95% CI: 1.04-1.38; P=0.010), especially in the cecum, the ascending colon and/or the hepatic flexure (RR =1.21, 95% CI: 1.05-1.40; P=0.007) but not in the transverse, descending, or sigmoid colon. Cholecystectomy has no effect on the risk of CRC overall, but a harmful effect on the risk of right-sided colon cancer proximally.

Risk factors for incident falls in Singaporean community-dwelling adult men and women: a prospective cohort study

ObjectivesOur study aimed to identify the risk factors of incident falls between men and women.DesignProspective cohort study.SettingThe study recruited participants from the Central region of Singapore. Baseline and follow-up data...

Participation in Household Physical Activity Lowers Mortality Risk in Chinese Women and Men.

The health benefits of sport and physical exercise (SPE) have been well documented, while the influence of household physical activity (HPA) on health has received much less research attention. This study aims to provide epidemiologic insight into the role HPA plays in the development of all-cause, cardiovascular disease (CVD), respiratory disease (RESP), and cancer mortality in a nationwide cohort of Chinese adults. We conceived a prospective cohort comprising 30,791 participants aged ≥16 years from 25 provinces of China using data derived from baseline (2010) and 4 waves of follow-up (2012-2018) investigations of the China Family Panel Studies. Self-reported times of HPA and SPE were collected by interviewing participants with a standard questionnaire. Cox proportional hazard models were used to assess the associations of HPA and SPE with all-cause, CVD, RESP, and cancer mortality, adjusting for demographic and socioeconomic factors, lifestyle behaviors, and health status. A restricted cubic spline smoother was used to investigate the dose-response relationships of HPA and SPE with mortality outcomes. Sex subgroup analyses were conducted to examine the potential effect disparity between men and women. To investigate the interactive effects of HPA and SPE, we calculated the relative excess risk due to the interaction and attributable proportion of additive effects to the total observed effects. During a median follow-up of 7.2 years, a total of 1,649 deaths occurred, with 209 cases from CVD, 123 from RESP, and 323 from cancer. HPA was identified to be associated with reduced mortality outcomes, suggesting remarkably reduced risks of 43-60% in all-cause mortality, 42-50% in CVD mortality, 36-71% in RESP mortality, and 38-46% in cancer mortality. In general, higher levels of HPA tended to be associated with lower risks. An approximately inverted J-shape association was identified between HPA and all-cause and cause-specific mortality, suggesting strong evidence for potential nonlinearity. Women performing HPA had a lower risk of all-cause, CVD, and cancer mortality. We did not identify significant evidence for additive interaction between HPA and SPE. HPA is independently associated with a reduced risk of mortality in Chinese women and men. More biological studies are needed to validate our findings and clarify the mechanisms underlying the association.

Short-Term Effects of Air Pollution on the Risk of Influenza in Jinan, China during 2020–2021: A Time-Series Analysis

Background: Air pollution leads to many adverse diseases, especially respiratory diseases and cardiac symptoms. However, it has not been studied the association between air pollution and influenza cases in Jinan City, especially during the outbreak of COVID-19; Methods: The data were obtained from China’s Disease Information System, and influenza cases during 2020–2021 in Jinan City were collected from it. We used the generalized additive Poisson model to measure the association between air pollutants and the daily influenza cases after adjusting for possible influence variables; Results: There were 4767 influenza cases. PM2.5 and PM10 on lag 0, lag 3, and lag 4 were significantly associated with an increased risk of influenza; gaseous pollutants (NO2 and SO2) led to higher risk than particulate matter pollutants (PM2.5 and PM10). There were no significant differences for sex subgroup analyses. Except for O3, the incidence risk of males and females was highest on lag 3 and lag 4. For the study of different age groups, influenza cases aged over 59 years had a slightly larger relative risk when exposed to all air pollutants (except O3) than the younger group; Conclusions: The overall number of influenza cases decreased in 2020–2021. PM2.5, SO2, CO, and NO2 were significantly associated with the risk of influenza during 2020–2021. Countermeasures should be developed according to the characteristics of influenza risk to prevent and control it.