The long-term genetic stability and individual specificity of the human gut microbiome.

By following up the gut microbiome, 51 human phenotypes and plasma levels of 1,183 metabolites in 338 individuals after 4 years, we characterize microbial stability and variation in relation to host physiology. Using these individual-specific and temporally stable microbial profiles, including bacterial SNPs and structural variations, we develop a microbial fingerprinting method that shows up to 85% accuracy in classifying metagenomic samples taken 4 years apart. Application of our fingerprinting method to the independent HMP cohort results in 95% accuracy for samples taken 1 year apart. We further observe temporal changes in the abundance of multiple bacterial species, metabolic pathways, and structural variation, as well as strain replacement. We report 190 longitudinal microbial associations with host phenotypes and 519 associations with plasma metabolites. These associations are enriched for cardiometabolic traits, vitamin B, and uremic toxins. Finally, mediation analysis suggests that the gut microbiome may influence cardiometabolic health through its metabolites.

Population-Based Evaluation of Vaccine Effectiveness against SARS-CoV-2 Infection, Severe Illness, and Death, Taiwan.

Taiwan provided several COVID-19 vaccine platforms: mRNA (BNT162b2, mRNA-1273), adenoviral vector-based (AZD1222), and protein subunit (MVC-COV1901). After Taiwan shifted from its zero-COVID strategy in April 2022, population-based evaluation of vaccine effectiveness (VE) became possible. We conducted an observational cohort study of 21,416,151 persons to examine VE against SARS-CoV-2 infection, moderate and severe illness, and death during March 22, 2021-September 30, 2022. After adjusting for age and sex, we found that persons who completed 3 vaccine doses (2 primary, 1 booster) or received MVC-COV1901 as the primary series had the lowest hospitalization incidence (0.04-0.20 cases/100,000 person-days). We also found 95.8% VE against hospitalization for 3 doses of BNT162b2, 91.0% for MVC-COV1901, 81.8% for mRNA-1273, and 65.7% for AZD1222, which had the lowest overall VE. Our findings indicated that protein subunit vaccines provide similar protection against SARS-CoV-2---associated hospitalization as mRNA vaccines and can inform mix-and-match vaccine selection in other countries.

Exposure to polycyclic aromatic hydrocarbons promotes the progression of low-grade cervical intraepithelial neoplasia: A population-based cohort study in China.

Low-grade cervical intraepithelial neoplasia (CIN1) is an early stage of cervical cancer development. Previously, we reported that exposure to polycyclic aromatic hydrocarbons (PAHs) increases the risk of cervical precancerous lesions, especially in females with a high-risk human papillomavirus (HR-HPV) infection. However, the effects of PAHs on CIN1 progression remain unclear. A community-based prospective cohort study was conducted to evaluate the role of exposure to PAHs in the progression of CIN1. A total of 564 patients diagnosed with CIN1 were followed-up at 6, 12, and 24 months, post-diagnosis, to determine CIN1 reversion, persistence, and progression. Exposure to PAHs was determined by the urine 1-hydroxipayrene (1-OHP) level. Our results showed that the 1-OHP level was significantly higher in patients with CIN1 persistence/progression than in those with reversion (P < .05). High exposure to PAHs increased the risk of CIN1 persistence/progression, with hazard ratios (HR), 95% confidence intervals (CI) of (1.62, 1.24-2.67), (1.98, 1.42-2.75), and (2.37, 1.61-3.49) at 6, 12, and 24 months, post-diagnosis, respectively. The effect was enhanced with HR-HPV positivity, as determined at 6 (1.82, 1.24-2.67), 12 (3.02, 1.74-5.23), and 24 (2.51, 1.48-4.26) months, post-diagnosis. Moreover, the predictive value of exposure to PAHs for CIN1 persistence/progression was higher in HR-HPV-positive patients than in HR-HPV-negative patients. The results revealed that exposure to PAHs facilitated the malignant progression of CIN1 and hindered its reversal, particularly in patients with HR-HPV infection. Our findings provide novel insights into early prevention and intervention targeting the initiation and progression of cervical neoplasia.

Current use of estrogen-containing oral contraceptives or hormone therapy and risk of COVID-19 infection and hospitalization: a population-based cohort study.

The association between current use of oral contraceptives (OCs) among women younger than 50 years (n = 306 541), and hormone therapy (HT) among women aged 50 years or older (n = 323 203), and coronavirus 2019 (COVID-19) infection and hospitalization was evaluated in this population-based cohort. Current OC/HT use was recorded monthly using prescription dispensing data. COVID-19 infections were identified from March 2020 through February 2021. COVID-19 infections and hospitalizations were identified through diagnosis codes and laboratory tests. We used weighted generalized estimating equations models to estimate multivariable adjusted odds ratios (aORs) for COVID-19 infection associated with time-varying OC/HT use. Among women with COVID-19, logistic regression models were used to evaluate OC/HT use and COVID-19 hospitalization. Over 12 months, 11 727 (3.8%) women younger than 50 years and 8661 (2.7%) women aged 50 years or older experienced COVID-19 infections. There was no evidence of an association between OC use and infection (aOR = 1.05; 95% CI, 0.97-1.12). There was a modest association between HT use and infection (aOR = 1.19; 95% CI, 1.03-1.38). Women using OCs had a 39% lower risk of hospitalization (aOR = 0.61; 95% CI, 0.38-1.00), but there was no association of HT use with hospitalization (aOR = 0.89; 95% CI, 0.51-1.53). These findings do not suggest a meaningfully greater risk of COVID-19 infection associated with OC or HT use. OC use may be associated with lower COVID-19 hospitalization risk.

Polycystic ovary syndrome and risk of breast cancer in premenopausal and postmenopausal women: a nationwide population-based cohort study.

PURPOSE: Although some reproductive and metabolic characteristics of polycystic ovary syndrome (PCOS) are known risk factors for breast cancer, the evidence regarding a potential association between PCOS and breast cancer is scarce. In this population-based cohort study including all 1,719,452 women born in Denmark between 1940 and 1993, we investigated the association between PCOS and breast cancer. METHODS: PCOS diagnoses, cancer diagnoses, covariates, migrations, and vital status were all obtained from national population and health registers. Hazard ratios (HR) and 95% confidence intervals (CI) for breast cancer overall and for histological subtypes separately were calculated based on adjusted cox proportional hazards models. RESULTS: During a median follow-up of 26 years, 63,078 women were diagnosed with breast cancer. We found an increased risk of breast cancer overall among women with PCOS compared with women without PCOS (HR: 1.21, 95% CI 1.02-1.44). In analyses stratified for menopausal status, the increased risk was restricted to postmenopausal women (HR: 1.63, 95% CI 1.23-2.15). The results for ductal and lobular histological subtypes analyses separately resembled those observed for breast cancer overall. CONCLUSION: This is the first study to report an increased risk of breast cancer among women with a history of PCOS. The increased risk was seemingly confined to postmenopausal women. Our results therefore contribute to an increased knowledge of the etiology of breast cancer, but our findings should be further confirmed in other large cohort studies with an appropriately long follow-up period.

The effects of contemporary treatment of DCIS on the risk of developing an ipsilateral invasive Breast cancer (iIBC) in the Dutch population.

PURPOSE: To assess the effects of contemporary treatment of ductal carcinoma in situ (DCIS) on the risk of developing an ipsilateral invasive breast cancer (iIBC) in the Dutch female population. METHODS: Clinical data was obtained from the Netherlands Cancer Registry (NCR), a nationwide registry of all primary malignancies in the Netherlands integrated with the data from PALGA, the Dutch nationwide network and registry of histo- and cytopathology in the Netherlands, on all women in the Netherlands treated for primary DCIS from 2005 to 2015, resulting in a population-based cohort of 14.419 women. Cumulative iIBC incidence was assessed and associations of DCIS treatment type with subsequent iIBC risk were evaluated by multivariable Cox regression analyses. RESULTS: Ten years after DCIS diagnosis, the cumulative incidence of iIBC was 3.1% (95% CI: 2.6-3.5%) in patients treated by breast conserving surgery (BCS) plus radiotherapy (RT), 7.1% (95% CI: 5.5-9.1) in patients treated by BCS alone, and 1.6% (95% CI: 1.3-2.1) in patients treated by mastectomy. BCS was associated with a significantly higher risk for iIBC compared to BCS + RT during the first 5 years after treatment (HR 2.80, 95% CI: 1.91-4.10%). After 5 years of follow-up, the iIBC risk declined in the BCS alone group but remained higher than the iIBC risk in the BCS + RT group (HR 1.73, 95% CI: 1.15-2.61). CONCLUSIONS: Although absolute risks of iIBC were low in patients treated for DCIS with either BCS or BCS + RT, risks remained higher in the BCS alone group compared to patients treated with BCS + RT for at least 10 years after DCIS diagnosis.

Risk of borderline ovarian tumors after fertility treatment - Results from a Danish cohort of infertile women.

OBJECTIVE: Results from previous studies examining the association between fertility treatment and borderline ovarian tumors are inconsistent. The aim of this study was to investigate the association between fertility treatment and borderline ovarian tumors in a cohort of infertile women. METHODS: This cohort study was based on the Danish Infertility Cohort and included all infertile women aged 20-45 years living in Denmark between 1 January 1995 and 31 December 2017 (n = 146,891). Information on use of fertility drugs, borderline ovarian tumors and cancer diagnoses, covariates, emigration, and vital status was obtained by linkage to national registers. Cox proportional hazard models were used to estimate hazard ratios (HR) and 95% confidence intervals (CI) with adjustment for potential confounders for overall borderline ovarian tumors and for serous- and mucinous borderline ovarian tumors separately. RESULTS: During a median 11.3 years of follow-up, 144 women developed a borderline ovarian tumor. No marked associations between ever use of clomiphene citrate, gonadotropins, gonadotropin-releasing hormone receptor modulators, human chorionic gonadotropin or progesterone and borderline ovarian tumors were observed, neither overall nor for serous and mucinous borderline ovarian tumors analysed separately. Further, no clear associations with borderline ovarian tumors were found according to cumulative dose, time since first use or parity status for any fertility drugs. CONCLUSIONS: No marked associations between use of fertility drugs and borderline ovarian tumors were observed. However, the cohort's relatively young age at end of follow-up emphasizes the importance of extending the follow-up period for women who have used fertility drugs.

Predictors of lung function in early adulthood: A population-based cohort study.

BACKGROUND AND OBJECTIVE: Lung function reaches a peak/plateau in early adulthood before declining with age. Lower early adult lung function may increase the risk for chronic obstructive pulmonary disease (COPD) in mid-late adult life. Understanding the effects of multiple childhood/adolescent exposures and their potential interactions on plateau lung function would provide insights into the natural history of COPD. METHODS: Longitudinal spirometry data from 688 participants with complete data from a population-based birth cohort (original n = 1037) were used to investigate associations between a wide range of childhood/adolescent exposures and repeated measures of FEV1, FVC and FEV1/FVC during the early-adult plateau phase. Generalized estimating equations were used to accommodate the multiple timepoints per participant. RESULTS: FEV1 reached a peak/plateau between ages 18 and 26 and FVC from 21 to 32 years, whereas FEV1/FVC declined throughout early adulthood. Childhood asthma and airway hyperresponsiveness were associated with lower early adult FEV1 and FEV1/FVC. Smoking by age 18 was associated with lower FEV1/FVC. Higher BMI during early adulthood was associated with lower FEV1 and FVC and lower FEV1/FVC. Physical activity during adolescence was positively associated with FEV1 and FEV1/FVC but this was only statistically significant in men. There was no convincing evidence of interactions between exposures. CONCLUSION: Childhood asthma and airway hyperresponsiveness are associated with lower lung function in early adulthood. Interventions targeting these may reduce the risk of COPD in mid-late adult life. Promotion of physical activity during adolescence, prevention of cigarette smoking and maintenance of a healthy body weight in early adulthood are also priorities.

Preterm children born below 33-35 weeks of gestation have an increased risk of mathematical difficulties.

AIM: To investigate the association between gestational age (GA) and grade point averages by domains of language and mathematics at the end of lower secondary education. METHODS: A nationwide register-based study including all Danish children born in 1992-1997 who completed lower secondary education. Grades were evaluated by GA. Domain-specific differences in grades were investigated, and academic profiles were made. RESULTS: The study population comprised 319 796 children. For language, only minor differences in grades were observed. The grades in mathematics ranged from 7.02 (95% confidence interval [CI]: 7.00-7.04) at GA = 40 weeks to 5.86 (95% CI: 5.61-6.11) at GA <28 weeks. Grade differences showed lower grades in mathematics, compared to language, below GA 33-35 weeks. The academic profile of mathematical difficulties was more prevalent among GA <32 weeks. Average/high grades within both domains represented the predominant academic profile, constituting 68.8% at GA 39-41 weeks and 56.6% at GA <28 weeks. CONCLUSION: Only in mathematics decreasing GA was associated with lower grades. Increased mathematical difficulties were found below GA 33-35 weeks. The academic profile of mathematical difficulties was more prevalent among GA <32 weeks. However, the absolute differences in grades were small, and the predominant academic profile was average/high grades within both domains across all GA.

Risk factors of epistaxis in rural Denmark: a cross-sectional population-based survey of data from the Lolland-Falster health study.

PURPOSE: Epistaxis is a common condition that affects about 60% of the population in their lifetime, with 6% needing medical attention. Little is known about the epidemiology and risk factors of epistaxis outside the health care system. This study aimed to investigate the prevalence and risk factors of epistaxis in a rural Danish population using data from the Lolland-Falster Health Study (LOFUS). METHODS: We conducted a cross-sectional survey based on data from LOFUS, a household-based, prospective cohort study in the rural provincial area of Lolland-Falster, Denmark. We enrolled 10,065 participants (≥ 50 years) and collected data on demographics, comorbidities, medication, lifestyle factors, and laboratory parameters. Logistic regressions were used to test for correlations between epistaxis and different risk factors. RESULTS: In total 5.3% of the participants had experienced epistaxis within the past 30 days, and 7.9% had sought medical attention for epistaxis at some point in their lives. We identified several factors that were significantly correlated with increased odds of epistaxis, such as male gender, age group 50-59 years, high BMI (> 25), allergy, diabetes, hypertension, atherosclerosis, angina, and anticoagulant treatment. Excellent or good self-reported health was correlated to significantly lower odds of epistaxis. CONCLUSION: This study provides a comprehensive overview of the prevalence and risk factors of epistaxis outside the health care system. Our study suggests that preventive measures targeting these risk factors may reduce the incidence and severity of epistaxis in this population.

Association between Cesarean section delivery and increased risk of childhood Kawasaki disease.

AIM: Cesarean section delivery is associated with microbiota disruption and immuno-dysregulation during childhood, but the association with Kawasaki disease remains uncertain. We aimed to evaluate the association between Cesarean section and Kawasaki disease. METHODS: We examined the association between Kawasaki disease between six and eighteen months and Cesarean section within a birth cohort of 15,796 mother-infant pairs in Taiwan. The associations were assessed with Poisson regression in the study population, in the 1:2 propensity score-matched subpopulation, and compared with febrile convulsion, trauma and accidents during the same interval as negative control outcomes. RESULTS: Cesarean section was found to increase the risk of Kawasaki disease among overall population (adjusted relative risk [aRR]: 2.22, 95 % confidence interval (CI): 1.14-4.34) and the matched subpopulation (aRR: 2.29, 95 % CI: 1.14-4.68 in PS-matched subpopulation). Meanwhile, there was no association between Cesarean section and the clinic visits for febrile convulsion, trauma and accidents. CONCLUSION: In conclusion, this study identified a potential association between Cesarean section delivery and a higher risk of Kawasaki disease during six-to eighteen months of the prospective birth cohort in Taiwan.

Multiparametric Prediction Models for Coronavirus Disease 2019 Vaccine Selection: Results of a Comparative Population-Based Cohort Study.

BACKGROUND: An understanding vaccine-dependent effects on protective and sustained humoral immune response is crucial to planning future vaccination strategies against coronavirus disease 2019 (COVID-19). METHODS: In this multicenter, population-based, cohort study including 4601 individuals after primary vaccination against COVID-19 ≥ 4 months earlier we compared factors associated with residual antibody levels against severe acute respiratory syndrome coronavirus-2 receptor-binding domain (RBD) across different vaccination strategies (BNT162b2, mRNA-1273, or ChAdOx1). RESULTS: Our main model including 3787 individuals (2 × BNT162b2, n = 2271; 2 × mRNA-1273, n = 251; 2 × ChAdOx1, n = 1265), predicted significantly lower levels of anti-RBD antibodies after 6 months in individuals vaccinated with ChAdOx1 (392.7 binding antibody units per milliliter [BAU/mL]) compared with those vaccinated with BNT162b2 (1179.5 BAU/mL) or mRNA-1273 (2098.2 BAU/mL). Vaccine-dependent association of antibody levels was found for age with a significant predicted difference in BAU/ml per year for BNT162b2 (-21.5; 95% confidence interval [CI], -24.7 to -18.3) and no significant association for mRNA-1273 (-4.0; 95% CI, -20.0 to 12.1) or ChAdOx1 (1.7; 95% CI, .2 to 3.1). The predicted decrease over time since full immunization was highest in mRNA-1273 (-23.4; 95% CI, -31.4 to -15.4) compared with BNT162b2 (-5.9; 95% CI, -7 to -4.8). CONCLUSIONS: Our study revealed population-based evidence of vaccine-dependent effects of age and time since full immunization on humoral immune response. Findings underline the importance of individualized vaccine selection, especially in elderly individuals.

Postvaccination immune responses and risk of primary total hip arthroplasty-A population-based cohort study.

OBJECTIVE: To investigate the relationship between individual postvaccination immune responses and subsequent risk of total hip arthroplasty (THA) due to idiopathic osteoarthritis (OA) or rheumatoid arthritis (RA). METHOD: Results of tuberculin skin tests (TSTs) following the Bacille Calmette-Guerin (BCG) vaccination were used as a marker of individual immune responses. TST results from the mandatory mass tuberculosis screening program 1948-1975 (n = 236 770) were linked with information on subsequent THA during 1987-2020 from the Norwegian Arthroplasty Register. The multivariable Cox proportional hazard regression was performed. RESULTS: A total of 10 698 individuals received a THA during follow-up. In men, there was no association between TST and risk of THA due to OA (Hazard ratio [HR] 1.01, 95% confidence interval [CI] 0.92-1.12 for positive versus negative TST and HR 1.06, 95% CI 0.95-1.18 for strong positive vs negative TST), while the risk estimates increased with increasingly restrictive sensitivity analyses. In women, there was no association with THA due to OA for positive versus negative TST (HR 0.98, 95% CI 0.92-1.05), while a strong positive TST was associated with reduced risk of THA (HR 0.90, 95% CI 0.84-0.97). No significant associations were observed in the sensitivity analysis for women or for THA due to RA. CONCLUSION: Our results suggest that an increased postvaccination immune response is associated with a nonsignificant trend of increased risk of THA among men and a decreased risk among women, although risk estimates were small.

The representative COVID-19 cohort Munich (KoCo19): from the beginning of the pandemic to the Delta virus variant.

BACKGROUND: Population-based serological studies allow to estimate prevalence of SARS-CoV-2 infections despite a substantial number of mild or asymptomatic disease courses. This became even more relevant for decision making after vaccination started. The KoCo19 cohort tracks the pandemic progress in the Munich general population for over two years, setting it apart in Europe. METHODS: Recruitment occurred during the initial pandemic wave, including 5313 participants above 13 years from private households in Munich. Four follow-ups were held at crucial times of the pandemic, with response rates of at least 70%. Participants filled questionnaires on socio-demographics and potential risk factors of infection. From Follow-up 2, information on SARS-CoV-2 vaccination was added. SARS-CoV-2 antibody status was measured using the Roche Elecsys® Anti-SARS-CoV-2 anti-N assay (indicating previous infection) and the Roche Elecsys® Anti-SARS-CoV-2 anti-S assay (indicating previous infection and/or vaccination). This allowed us to distinguish between sources of acquired antibodies. RESULTS: The SARS-CoV-2 estimated cumulative sero-prevalence increased from 1.6% (1.1-2.1%) in May 2020 to 14.5% (12.7-16.2%) in November 2021. Underreporting with respect to official numbers fluctuated with testing policies and capacities, becoming a factor of more than two during the second half of 2021. Simultaneously, the vaccination campaign against the SARS-CoV-2 virus increased the percentage of the Munich population having antibodies, with 86.8% (85.5-87.9%) having developed anti-S and/or anti-N in November 2021. Incidence rates for infections after (BTI) and without previous vaccination (INS) differed (ratio INS/BTI of 2.1, 0.7-3.6). However, the prevalence of infections was higher in the non-vaccinated population than in the vaccinated one. Considering the whole follow-up time, being born outside Germany, working in a high-risk job and living area per inhabitant were identified as risk factors for infection, while other socio-demographic and health-related variables were not. Although we obtained significant within-household clustering of SARS-CoV-2 cases, no further geospatial clustering was found. CONCLUSIONS: Vaccination increased the coverage of the Munich population presenting SARS-CoV-2 antibodies, but breakthrough infections contribute to community spread. As underreporting stays relevant over time, infections can go undetected, so non-pharmaceutical measures are crucial, particularly for highly contagious strains like Omicron.

The association between smoking, changes in smoking behavior, and acute pancreatitis: A population-based cohort study in Korea.

BACKGROUND AND AIMS: In the Asian population, existing studies regarding the association between smoking and acute pancreatitis are few in number. The aim of this study was to investigate the incidence of acute pancreatitis according to smoking habits and smoking habit changes of the Korean population. METHODS: We used clinical data from individuals (aged 20 years or older) who received health examinations arranged by the Korean National Health Insurance Service in 2009 (n = 4 238 822) or in 2009 and 2011 (n = 2 617 306). The incidence of acute pancreatitis was analyzed according to smoking status or smoking habit change reported by individuals during their health examination. Newly diagnosed acute pancreatitis was identified using claims data from baseline to the date of diagnosis or until December 31, 2018. RESULTS: The risk of acute pancreatitis was significantly higher in current smokers compared with never-smokers regardless of age or sex. The adjusted hazard ratio (HR) of acute pancreatitis in current smokers increased according to the amount of smoking (HR 1.28; 95% confidence interval [CI], 1.12-1.45 in <10 cigarettes/day, HR 1.4; CI, 1.3-1.52 in 10-19 cigarettes/day, HR 1.66; CI, 1.55-1.78 in ≥20 cigarettes/day). The adjusted HR of acute pancreatitis in continuous smokers was 1.66 (CI, 1.53-1.8) compared with never-smokers and was higher than smokers who quit smoking (HR 1.34; CI, 1.17-1.54). CONCLUSIONS: In this Korean population-based cohort study, smoking increased the incidence of acute pancreatitis in a dose-dependent manner, and smoking cessation helped decrease the incidence of acute pancreatitis.

Increased risk of glaucoma development in patients with central serous chorioretinopathy: results of a 11-year population-based cohort study.

PURPOSE: To investigate whether patients with central serous chorioretinopathy (CSC) have increased risk of developing glaucoma. METHODS: Patients diagnosed with CSC between 1 January 2008 and 31 December 2018 were included in this study using data from the Taiwanese National Health Insurance Research Database (NHIRD). The CSC cohort was matched with a non-CSC cohort using the propensity score matching method, based on sex, age (in 10-year intervals), index date year, comorbidities, and steroid use, resulting in equal numbers of patients in both cohorts. Patients were followed up until 31 December 2019 or until they were withdrawn from the NHIRD. The incidence of glaucoma was compared between the two cohorts using the Cox regression model, and the risk of developing glaucoma was estimated using the Kaplan-Meier method. RESULTS: After adjusting for sex, age, comorbidities, and steroid use, the CSC cohort showed a significantly higher risk of developing glaucoma compared to those without CSC (adjusted HR = 3.99; 95% CI = 3.44-4.62). The cumulative incidence of glaucoma in the CSC cohort was also significantly higher than in the non-CSC cohort (log-rank test, p < 0.001). Among the glaucoma subtypes, normal tension glaucoma had the highest risk (adjusted HR = 5.79; 95% CI = 3.41-9.85), followed by primary open-angle glaucoma (adjusted HR = 2.77; 95% CI = 2.12-3.62). CONCLUSIONS: In conclusion, our study shows that CSC patients are at a higher risk of developing glaucoma, especially NTG. Awareness and regular glaucoma screenings are essential for patients with CSC.

Association between BMI trajectories in late-middle age and subsequent dementia risk in older age: a 26-year population-based cohort study.

BACKGROUND: The association between body mass index (BMI) and dementia risk differs depending on follow-up time and age at BMI measurement. The relationship between BMI trajectories in late-middle age (50-65 years old) and the risk of dementia in older age (> 65 years old) has not been revealed. METHODS: In the present study, participants from the Health and Retirement Study were included. BMI trajectories were constructed by combining BMI trend and variation information. The association between BMI trajectories at the age of 50-65 years and dementia risk after the age of 65 years was investigated. Participants with European ancestry and information on polygenic scores for cognitive performance were pooled to examine whether genetic predisposition could modify the association. RESULTS: A total of 10,847 participants were included in the main analyses. A declining BMI trend and high variation in late-middle age were associated with the highest subsequent dementia risk in older age compared with an ascending BMI trend and low variation (RR = 1.76, 95% CI = 1.45-2.13). Specifically, in stratified analyses on BMI trajectories and dementia risk based on each individual's mean BMI, the strongest association between a declining BMI trend with high variation and elevated dementia risk was observed in normal BMI group (RR = 2.66, 95% CI = 1.72-4.1). Similar associations were found when participants were stratified by their genetic performance for cognition function without interaction. CONCLUSIONS: A declining BMI trend and high variation in late-middle age were associated with a higher risk of dementia. Early monitoring of these individuals is needed to prevent dementia in older individuals.

Comparison of clinical characteristics and disease burden between early- and late-onset type 2 diabetes patients: a population-based cohort study.

BACKGROUND: The clinical characteristics of early-onset type 2 diabetes (T2D) patients are not fully understood. To address this gap, we conducted a cohort study to evaluate clinical characteristics and disease burden in the new-onset T2D population, especially regarding the progression of diseases. METHODS: This cohort study was conducted using a population-based database. Patients who were diagnosed with T2D were identified from the database and were classified into early- (age < 40) and late-onset (age ≥ 40) groups. A descriptive analysis was performed to compare clinical characteristics and disease burden between early- and late-onset T2D patients. The progression of disease was compared using Kaplan‒Meier analysis. RESULTS: A total of 652,290 type 2 diabetic patients were included. Of those, 21,347 were early-onset patients, and 300,676 were late-onset patients. Early-onset T2D patients had poorer glycemic control than late-onset T2D patients, especially at the onset of T2D (HbA1c: 9.3 [7.5, 10.9] for early-onset vs. 7.7 [6.8, 9.2] for late-onset, P < 0.001; random blood glucose: 10.9 [8.0, 14.3] for early-onset vs. 8.8 [6.9, 11.8] for late-onset, P < 0.001). Insulin was more often prescribed for early-onset patients (15.2%) than for late-onset patients (14.8%). Hypertension (163.0 [28.0, 611.0] days) and hyperlipidemia (114.0 [19.0, 537.0] days) progressed more rapidly among early-onset patients, while more late-onset patients developed hypertension (72.7% vs. 60.1%, P < 0.001), hyperlipidemia (65.4% vs. 51.0%, P < 0.001), cardiovascular diseases (66.0% vs. 26.7%, P < 0.001) and chronic kidney diseases (5.5% vs. 2.1%, P < 0.001) than early-onset patients. CONCLUSIONS: Our study results indicate that patients with newly diagnosed early-onset T2D had earlier comorbidities of hypertension and hyperlipidemia. Both clinical characteristics and treatment patterns suggest that the degree of metabolic disturbance is more severe in patients with early-onset type 2 diabetes. This highlights the importance of promoting healthy diets or lifestyles to prevent T2D onset in young adults.

Effects of chiropractic use on medical healthcare utilization and costs in adults with back pain in Ontario, Canada from 2003 to 2018: a population-based cohort study.

BACKGROUND: Adults with back pain commonly consult chiropractors, but the impact of chiropractic use on medical utilization and costs within the Canadian health system is unclear. We assessed the association between chiropractic utilization and subsequent medical healthcare utilization and costs in a population-based cohort of Ontario adults with back pain. METHODS: We conducted a population-based cohort study that included Ontario adult respondents of the Canadian Community Health Survey (CCHS) with back pain from 2003 to 2010 (n = 29,475), followed up to 2018. The CCHS data were individually-linked to individual-level health administrative data up to 2018. Chiropractic utilization was self-reported consultation with a chiropractor in the past 12 months. We propensity score-matched adults with and without chiropractic utilization, accounting for confounders. We evaluated back pain-specific and all-cause medical utilization and costs at 1- and 5-year follow-up using negative binomial and linear (log-transformed) regression, respectively. We assessed whether sex and prior specialist consultation in the past 12 months were effect modifiers of the association. RESULTS: There were 6972 matched pairs of CCHS respondents with and without chiropractic utilization. Women with chiropractic utilization had 0.8 times lower rate of cause-specific medical visits at follow-up than those without chiropractic utilization (RR5years = 0.82, 95% CI 0.68-1.00); this association was not found in men (RR5years = 0.96, 95% CI 0.73-1.24). There were no associations between chiropractic utilization and all-cause physician visits, all-cause emergency department visits, all-cause hospitalizations, or costs. Effect modification of the association between chiropractic utilization and cause-specific utilization by prior specialist consultation was found at 1-year but not 5-year follow-up; cause-specific utilization at 1 year was lower in adults without prior specialist consultation only (RR1year = 0.74, 95% CI 0.57-0.97). CONCLUSIONS: Among adults with back pain, chiropractic use is associated with lower rates of back pain-specific utilization in women but not men over a 5-year follow-up period. Findings have implications for guiding allied healthcare delivery in the Ontario health system.

Patients with obstructive sleep apnea are at great risk of flavor disorders: a 15-year population-based cohort study.

OBJECTIVE: Obstructive sleep apnea (OSA) results from upper airway remodeling, which has been suggested to alter sensory and motor neuron function due to hypoxia or snore vibration. This study investigated whether OSA was associated with the risk of flavor disorder (FD). MATERIALS AND METHODS: Seven thousand and eight hundred sixty-five patients with OSA and 7865 propensity score-matched controls without OSA were enrolled between 1999 and 2013 through a nationwide cohort study. The propensity score matching was based on age, sex, comorbidities including hypertension, hyperlipidemia, chronic obstructive pulmonary disease (COPD), asthma, ankylosing spondylitis, and Charlson comorbidity index, and co-medications during the study period, including statins and angiotensin-converting enzyme (ACE) inhibitors. The adjusted hazard ratio (aHR) of incident FD following OSA was derived using a Cox proportional hazard model. A log-rank test was used to evaluate the time-dependent effect of OSA on FD. Age, sex, comorbidities, and co-medications were stratified to identify subgroups susceptible to OSA-associated FD. RESULTS: Patients with OSA were at a significantly great risk of FD (aHR = 1.91, 95% CI = 1.08-3.38), which was time-dependent (log-rank test p = 0.013). Likewise, patients with hyperlipidemia were at a significant great risk of FD (aHR = 2.99, 95% CI = 1.33-6.69). Subgroup analysis revealed that female patients with OSA were at higher risks of FD (aHR = 2.39, 95%CI = 1.05-5.47). CONCLUSIONS: Patients with OSA were at significantly great risk of incident FD during the 15-year follow-up period, especially in female patients with OSA. CLINICAL RELEVANCE: Timely interventions for OSA may prevent OSA-associated FD.