Age at diagnosis modifies associations of type 2 diabetes with cancer incidence and mortality: a retrospective matched-cohort study.

AIMS/HYPOTHESIS: The age-specific associations between type 2 diabetes and cancer risk are not fully understood. The aim of this study was to assess how age at diagnosis modifies the associations between type 2 diabetes and cancer risk. METHODS: We used data from the Yinzhou Health Information System, and included 42,279 individuals who were newly diagnosed with type 2 diabetes between 2010 and 2014, as well as 166,010 age- and sex-matched control individuals without diabetes who were selected randomly from the electronic health records of the entire population. Patients were divided into four age groups according to age at diagnosis: <50, 50-59, 60-69 and ≥70 years. Stratified Cox proportional hazards regression models, with age as the time scale, were used to estimate the HRs and 95% CIs for the associations of type 2 diabetes with the risks of overall and site-specific cancers. Population-attributable fractions were also calculated for outcomes associated with type 2 diabetes. RESULTS: During median follow-up periods of 9.20 and 9.32 years, we identified 15,729 incident cancer cases and 5383 cancer deaths, respectively. Patients diagnosed with type 2 diabetes before 50 years of age had the highest relative risks of cancer incidence and mortality, with HRs (95% CI) of 1.35 (1.20, 1.52) for overall cancer incidence, 1.39 (1.11, 1.73) for gastrointestinal cancer incidence, 2.02 (1.50, 2.71) for overall cancer mortality, and 2.82 (1.91, 4.18) for gastrointestinal cancer mortality. Risk estimates decreased gradually with each decade increase in diagnostic age. The population-attributable fractions for overall cancer and gastrointestinal cancer mortality also decreased with increasing age. CONCLUSIONS/INTERPRETATION: The associations of type 2 diabetes with cancer incidence and mortality varied by age at diagnosis, with a higher relative risk among patients who were diagnosed at a younger age.

Incidence of Inflammatory Bowel Disease in Urban China: A Nationwide Population-based Study.

BACKGROUND & AIMS: Limited studies have evaluated the burden of inflammatory bowel disease (IBD) in China. We aimed to estimate the incidence of IBD including ulcerative colitis (UC) and Crohn's disease (CD) in urban China. METHODS: The national urban incidence in 2016 was calculated based on urban basic medical insurance from 2012 to 2016 in China by using a 4-year washout period. The incidence in Yinzhou District estimated from the Yinzhou electronic health care record database was used to test the accuracy of the results from insurance data. RESULTS: A total of 95,555 patients with IBD were identified. The incidence in 2016 was 10.04 (95% confidence interval, 6.95-13.71) per 100,000 person-years. The incidence rates of both UC and CD were higher among males than among females. There was a sharp increase in UC incidence before the age of 30 years and stabilization in later years (50-79 years old), whereas CD incidence peaked at 30 to 34 years old and experienced decline subsequently. The incidence of UC was much greater than that of CD, with a UC-to-CD incidence ratio of 12.61. The results from the Yinzhou database confirmed these results. CONCLUSIONS: This study is the first to draw a portrait of the distribution of IBD in urban China. The difference in IBD incidence between urban China and other countries suggests an association between the IBD burden and industrialization process. The accelerating urbanization and industrialization process in China, a country with a population of 1.4 billion people, will likely increase the burden of IBD.

Impact of HPV vaccination on HPV infection and cervical related disease burden in real-world settings (HPV-RWS): protocol of a prospective cohort.

BACKGROUND: Cervical cancer is one of the most common cancers in women and could be prevented by human papilloma virus (HPV) vaccination. Cervarix, the first available HPV vaccine, has been widely administrated to Chinese women, while little was known about its effect on the prevention and control for HPV related diseases in China. The study aims to assess the impact of Cervarix on HPV infection and cervical related diseases in real world. METHODS: This is a prospective, multi-age birth cohort study to investigate the incidence and continuous status of HPV infection, and relevant cervical diseases by exposure status (with Cervarix vaccination history or without any HPV vaccination history). It is planned to recruit 12,118 eligible women at age of 9 to 45 years from vaccination clinics or hospital outpatient clinics, and then follow up them for three years. The standard questionnaire will be used to collect information such as demographic characteristics, menstruation and obstetrical histories, history of sexual behavior, personal behavior history, history of disease and pathogen infection, medication history, and family history at baseline. After three years, the changes of these behaviors will be investigated again, and other related health status information will be retrieved from the electronic health records during the follow-up period. If available physically and legally, the cervical cancer screening will be performed, including type-specific HPV deoxyribonucleic acid (DNA) polymerase chain reaction (PCR) testing and contingent thinprep cytologic test (TCT) and colposcopy. The free cervical cancer screening will be captured and uploaded timely to the Yinzhou Regional Health Information Platform (YRHIP); therefore, the long-term outcomes of participants will be monitored. DISCUSSION: This prospective cohort study will assess the impact of HPV vaccine on HPV infection and related cervical diseases in women aged 9-45 years, which makes up for the lack of evidence in Chinese women. The results of this study will provide support for understanding the impact of HPV vaccination in China, and make a contribution to increasing HPV vaccination and cervical cancer screening coverage in China. TRIAL REGISTRATION: This study has been retrospectively registered on clinicaltrials.gov (NCT05341284) on April 22, 2022.

Association of outpatient fluoroquinolone prescribing with the National Medical Products Administration announcements of label changes in China.

BACKGROUND: In 2017 and 2021, the National Medical Products Administration (NMPA) announced to revise the drug label of fluoroquinolones. We aimed to evaluate the association of fluoroquinolone prescribing with the NMPA announcements of label changes. RESEARCH DESIGN AND METHODS: Monthly prevalence of fluoroquinolone prescriptions for uncomplicated urinary tract infections (uUTI), acute exacerbation of chronic bronchitis (AECB), and acute sinusitis (AS) between 2016 and 2022 was calculated, and interrupted time series analysis was applied to assess the impacts of NMPA label changes on fluoroquinolone use. RESULTS: Prevalence of fluoroquinolone prescriptions decreased by 2.39% (95% CI, -4.72% to -0.07%) for uUTI but increased by 3.02% (95% CI, 1.71% to 4.34%) for AS immediately after the 2017 label change. Moreover, after the 2021 label change, fluoroquinolone use decreased shortly in all the three indications. However, a significant increasing trend was observed in fluoroquinolone use for AECB episodes, and fluoroquinolons were used for 61.4% of treated uUTI, 31.6% of treated AECB, and 5.42% of treated AS at the end of 2022, respectively. CONCLUSIONS: The label changes issued by the NMPA had no substantial impacts on fluoroquinolone prescribing in the study region in China. Fluoroquinolone prescribing was still highly prevalent for uUTI and AECB and thus requiring further antimicrobial stewardship.

The impact of the COVID-19 pandemic and the free vaccination policy on seasonal influenza vaccination uptake among older adults in Ningbo, Eastern China.

In 2020-21, during the COVID-19 pandemic, a free influenza vaccination program was initiated among the elderly residents in Ningbo, China. The impact of the COVID-19 pandemic and free vaccination policy on influenza vaccine uptake needs to be evaluated. The influenza vaccine uptake among individuals born before 31 December, 1962 from 2017-18 to 2022-23 season in Ningbo was analyzed. Multivariate logistic regressions were used to estimate the impact of the COVID-19 pandemic and free vaccination policy. Our analysis included an average of 1,856,565 individuals each year. Influenza vaccination coverage increased from 1.14% in 2017-18 to 33.41% in 2022-23. The vaccination coverage among the free policy target population was 50.03% in 2022-23. Multivariate analysis showed that free vaccination policy increased influenza vaccine uptake most (OR = 11.99, 95%CI: 11.87-12.11). The initial phase of the pandemic was associated with a positive effect on influenza vaccination (OR = 2.09, 95%CI: 2.07-2.12), but followed by a negative effect in the subsequent two seasons(2021-22: OR = 0.75, 95%CI: 0.73-0.76; 2022-23: OR = 0.40, 95%CI: 0.39-0.40). COVID-19 vaccination in the current season was a positive predictor of influenza vaccine uptake while not completing booster COVID-19 vaccination before was negative predictor in 2022-23. Having influenza vaccine history and having ILI medical history during the last season were also positive predictors of influenza vaccine uptake. Free vaccination policies have enhanced influenza vaccination coverage among elderly population. The COVID-19 pandemic plays different roles in different seasons. Our study highlights the need for how to implement free vaccination policies targeting vulnerable groups with low vaccination coverage.

Associations Between Thiazolidinediones Use and Incidence of Rheumatoid Arthritis: A Retrospective Population-Based Cohort Study.

OBJECTIVE: Preclinical studies suggest that thiazolidinediones (TZDs) may have a protective effect on rheumatoid arthritis (RA), but evidence from population-based studies is scarce. This study aimed to assess the association between use of TZDs and incidence of RA in a retrospective cohort of patients with type 2 diabetes mellitus (T2DM). METHODS: A retrospective cohort of patients with T2DM who were new users of TZDs or alpha glucosidase inhibitors (AGIs) was assembled. We applied the inverse probability of treatment weighted Cox model to estimate the hazard ratio (HR) of RA incidence associated with the use of TZDs compared with AGIs. RESULTS: The final analysis included 56,796 new users of AGIs and 14,892 new users of TZDs. The incidence of RA was 187.4 and 135.2 per 100,000 person-years in AGI users and TZD users, respectively. Compared with use of AGIs, TZD use was associated with a reduction in RA incidence, with an HR of 0.72 (95% confidence interval [95% CI] 0.59-0.89). HRs for cumulative use of TZDs for 0.51 to 4.0 years and more than 4 years with incidence of RA were 0.55 (95% CI 0.35-0.88) and 0.74 (95% CI 0.57-0.98), respectively. Various subgroup analyses and sensitivity analyses were consistent with the primary analysis. CONCLUSION: Use of TZDs is associated with a decreased risk of incident RA in patients with T2DM.

Influence of early use of sodium-glucose transport protein 2 inhibitors, glucagon-like peptide-1 receptor agonists and dipeptidyl peptidase-4 inhibitors on the legacy effect of hyperglycemia.

Background: A phenomenon known as legacy effect was observed that poor glycemic control at early stage of patients with newly-diagnosed type 2 diabetes (T2D) increases the risk of subsequent cardiovascular diseases (CVD). Early use of some novel anti-hyperglycemic agents, such as sodium-glucose transport protein 2 inhibitors (SGLT-2i), may attenuate this effect, but the evidence is limited. Methods: Two retrospective cohorts of newly diagnosed T2D patients from 2010-2023 were assembled using the Yinzhou Regional Health Care Database (YRHCD) with different definitions of the early exposure period - the 1-year exposure cohort and 2-year exposure cohort, which were comprised of subjects who had HbA1c measurement data within 1 year and 2 years after their T2D diagnosis, respectively. Using Cox proportional hazards models, we examined the association between high HbA1c level (HbA1c>7%) during the early exposure period and the risk of subsequent CVD. This analysis was performed in the overall cohort and three subpopulations with different treatments during the early exposure period, including patients initiating SGLT-2i or glucagon-like peptide-1 receptor agonists (GLP-1RA), patients using dipeptidyl peptidase-4 inhibitors (DPP-4i), and patients without using SGLT-2i, GLP-1RA, and DPP-4i. Besides, subgroup analyses were performed by stratifying patients into age <55 and ≥55 years. Results: A total of 21,477 and 22,493 patients with newly diagnosed T2D were included in the two final cohorts. Compared with patients with mean HbA1c ≤ 7% during the early exposure period, those with HbA1c>7% had higher risks of incident CVD, with a HR of 1.165 (95%CI, 1.056-1.285) and 1.143 (95%CI, 1.044-1.252) in 1-year and 2-year exposure period cohort. Compared to non-users, in patients initiating SGLT-2i/GLP-1RA within 1 or 2 years after T2D diagnosis, higher HbA1c level at baseline was not associated with CVD in both two cohorts. In subgroup analyses, results were generally consistent with the main analysis. Conclusions: Poor glycemic control in the early stage of T2D increased later CVD risk in Chinese adults with newly diagnosed T2D. Compared to non-users, this association was smaller and non-significant in patients receiving SGLT-2i/GLP-1RA during the early stage of T2D, indicating early use of these drugs may have the potential to mitigate legacy effects of hyperglycemia.

Population-Based Influenza Vaccine Effectiveness Against Laboratory-Confirmed Influenza Infection in Southern China, 2023-2024 Season.

Background: In China, the 2022-2023 influenza season began earlier and was characterized by higher levels of influenza activity and co-circulation of various respiratory pathogens compared with seasons before the coronavirus disease 2019 (COVID-19) pandemic. Timely and precise estimates of influenza vaccine effectiveness (IVE) against infections can be used to guide public health measures. Methods: A test-negative study was conducted to estimate IVE against laboratory-confirmed influenza using data from the CHinese Electronic health Records Research in Yinzhou (CHERRY) study that prospectively integrated laboratory, vaccination, and health administrative data in Yinzhou, southern China. We included patients who presented influenza-like illness and received nucleic acid tests and/or antigen tests between October 2023 and March 2024. Estimates of IVE were adjusted for age, gender, month of specimen submitted, chronic comorbidities, and hospitalization status. Results: A total of 205 028 participants, including 96 298 influenza cases (7.6% vaccinated) and 108 730 influenza-negative controls (13.4% vaccinated), were eligible for this analysis. The estimates of IVE were 49.4% (95% CI, 47.8%-50.9%), 41.9% (95% CI, 39.8%-44.0%), and 59.9% (95% CI, 57.9%-61.9%) against overall influenza, influenza A, and influenza B, respectively. A lower IVE was observed for individuals aged 7-17 years (38.6%), vs 45.8% for 6 months-6 years, 46.7% for 18-64 years, and 46.1% for ≥65 years. Vaccination reduced the risk of infection by 44.4% among patients with chronic comorbidities. IVEs varied by epidemic weeks with the changes in influenza activity levels and the switch of dominant influenza strains. Conclusions: Influenza vaccination in the 2023-2024 season was protective against infection for the entire population.

External Validation of the Kidney Failure Risk Equation Among Urban Community-Based Chinese Patients With CKD.

Rationale & Objective: The Kidney Failure Risk Equations have been proven to perform well in multinational databases, whereas validation in Asian populations is lacking. This study sought to externally validate the equations in a community-based chronic kidney disease cohort in China. Study Design: A retrospective cohort study. Setting & Participants: Patients with and estimated glomerular filtration rate (eGFR) < 60 mL/min/1.73 m2 dwelling in an industrialized coastal city of China. Exposure: Age, sex, eGFR, and albuminuria were included in the 4-variable model, whereas serum calcium, phosphate, bicarbonate, and albumin levels were added to the previously noted variables in the 8-variable model. Outcome: Initiation of long-term dialysis treatment. Analytical Approach: Model discrimination, calibration, and clinical utility were evaluated by Harrell's C statistic, calibration plots, and decision curve analysis, respectively. Results: A total of 4,587 participants were enrolled for validation of the 4-variable model, whereas 1,414 were enrolled for the 8-variable model. The median times of follow-up were 4.0 (interquartile range: 2.6-6.3) years for the 4-variable model and 3.4 (2.2-5.6) years for the 8-variable model. For the 4-variable model, the C statistics were 0.750 (95% CI: 0.615-0.885) for the 2-year model and 0.766 (0.625-0.907) for the 5-year model, whereas the values were 0.756 (0.629-0.883) and 0.774 (0.641-0.907), respectively, for the 8-variable model. Calibration was acceptable for both the 4-variable and 8-variable models. Decision curve analysis for the models at the 5-year scale performed better throughout different net benefit thresholds than the eGFR-based (<30 mL/min/1.73 m2) strategy. Limitations: A large proportion of patients lack albuminuria measurements, and only a subset of population could provide complete data for the 8-variable equation. Conclusions: The kidney failure risk equations showed acceptable discrimination and calibration and better clinical utility than the eGFR-based strategy for incidence of kidney failure among community-based urban Chinese patients with chronic kidney disease.

Accurate and reliable risk evaluation of chronic kidney disease (CKD) prognosis can be helpful for physicians to make decisions concerning treatment opportunity and therapeutic strategy. The kidney failure risk equation is an outstanding model for predicting risk of kidney failure among patients with CKD. However, the equation is lacking validation among Chinese populations. In the current study, we demonstrated that the equation had good discrimination among an urban community-based cohort of patients with CKD in China. The calibration was also acceptable. Decision curve analysis also showed that the equation performed better than a traditional kidney function-based strategy. The results provide the basis for using predictions derived from the kidney failure risk equation to improve the management of patients with CKD in community settings in China.

Improving cardiovascular risk prediction through machine learning modelling of irregularly repeated electronic health records.

Aims: Existing electronic health records (EHRs) often consist of abundant but irregular longitudinal measurements of risk factors. In this study, we aim to leverage such data to improve the risk prediction of atherosclerotic cardiovascular disease (ASCVD) by applying machine learning (ML) algorithms, which can allow automatic screening of the population. Methods and results: A total of 215 744 Chinese adults aged between 40 and 79 without a history of cardiovascular disease were included (6081 cases) from an EHR-based longitudinal cohort study. To allow interpretability of the model, the predictors of demographic characteristics, medication treatment, and repeatedly measured records of lipids, glycaemia, obesity, blood pressure, and renal function were used. The primary outcome was ASCVD, defined as non-fatal acute myocardial infarction, coronary heart disease death, or fatal and non-fatal stroke. The eXtreme Gradient boosting (XGBoost) algorithm and Least Absolute Shrinkage and Selection Operator (LASSO) regression models were derived to predict the 5-year ASCVD risk. In the validation set, compared with the refitted Chinese guideline-recommended Cox model (i.e. the China-PAR), the XGBoost model had a significantly higher C-statistic of 0.792, (the differences in the C-statistics: 0.011, 0.006-0.017, P < 0.001), with similar results reported for LASSO regression (the differences in the C-statistics: 0.008, 0.005-0.011, P < 0.001). The XGBoost model demonstrated the best calibration performance (men: Dx = 0.598, P = 0.75; women: Dx = 1.867, P = 0.08). Moreover, the risk distribution of the ML algorithms differed from that of the conventional model. The net reclassification improvement rates of XGBoost and LASSO over the Cox model were 3.9% (1.4-6.4%) and 2.8% (0.7-4.9%), respectively. Conclusion: Machine learning algorithms with irregular, repeated real-world data could improve cardiovascular risk prediction. They demonstrated significantly better performance for reclassification to identify the high-risk population correctly.

Using big data to analyze the vaccination status of children with congenital heart disease in Yinzhou District, China.

Congenital heart disease (CHD) represents a significant population warranting particular attention concerning vaccination coverage. To comprehend the vaccination status of CHD within Yinzhou District, Ningbo City, China, and to facilitate the formulation of preventive, control, and immunization strategies against vaccine-preventable diseases in children with congenital heart conditions. Using the China Yinzhou Electronic Health Record Study (CHERRY) database, we analyzed the vaccination coverage of children with CHD born between January 1, 2016 and September 20, 2021, and analyzed the influencing factors associated with the level of vaccination coverage. This study involved 762 children diagnosed with CHD at the age of 12 months, revealing that 86.74% of these children had received at least one dose of the National Immunization Program (NIP) vaccines. The coverage for non-NIP vaccines, such as the rotavirus vaccine, influenza vaccine, Influenza Haemophilus influenzae Type b (Hib) Conjugate Vaccine, 13-valent pneumococcal conjugate vaccine (PCV13), and inactivated enterovirus type 71 vaccine (EV71), stood at 27.30%, 7.74%, 63.25%, 33.76%, and 34.51%, respectively. The completion coverage for the entire vaccination schedule were 27.30%, 5.51%, 55.77%, 34.25%, and 25.59%, respectively. There was a statistically significant correlation between vaccination coverage in classification of diagnostic medical institutions and the types of diagnosed diseases. Compared to their typically developing counterparts, 12-month-old children afflicted with CHD exhibit a slightly diminished vaccination coverage, alongside a discernible inclination toward delayed vaccination. Notably, the determination to undergo vaccinations seems predominantly influenced by the classification of diagnostic medical institutions. In practical terms, proactive measures involving early diagnosis, comprehensive health assessments, and timely interventions ought to be implemented to enhance vaccination rates while prioritizing safety.

Association between visit-to-visit lipid variability and risk of ischemic heart disease: a cohort study in China.

AIMS: To explore the associations between visit-to-visit lipid variability and risk of ischemic heart disease (IHD) in a population-based cohort in China. METHODS: We evaluated lipid variability in 30,217 individuals from the Yinzhou Health Information System who had ≥3 recorded lipid measurements during 2010-2014. We used various indicators including standard deviation (SD), coefficient of variation (CV), variability independent of the mean (VIM), and average real variability (ARV) to quantify the variability in triglycerides, total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), and low-density lipoprotein cholesterol (LDL-C). We used Cox proportional hazards models to estimate hazard ratios (HRs) and 95% confidence intervals (CIs). RESULTS: Overall, a total of 1305 participants with IHD were identified during the follow-up of 194,421 person-years. Subjects in Q4 had a 21% elevated risk of IHD (HR = 1.21, 95% CI: 1.03-1.41) for LDL-C variability (CV) compared with the reference (Q1). The HRs for Q4 vs Q1 were 1.21 (95% CI: 1.04-1.42) for HDL-C variability, and 1.28 (95% CI: 1.10-1.50) for TC variability. However, no association was observed between triglycerides variability and risk of IHD. CONCLUSIONS: Higher variability in LDL-C, HDL-C, and TC levels was associated with an elevated risk of IHD, suggesting that lipid variability could be considered as an independent risk factor of IHD.

Effect of 200 mEq/L Na+ hypertonic saline resuscitation on systemic inflammatory response and oxidative stress in severely burned rats.

BACKGROUND: Excessive release of inflammatory mediators and oxidative stress play important roles in the increased vascular permeability and systemic edema during the early stage of severe burn. This study investigates the effect of 200 mEq/L Na(+) hypertonic saline (HS) on systemic inflammatory response and oxidative stress in severely burned rats. MATERIALS AND METHODS: Sprague-Dawley rats were divided into three groups: sham group, burn plus lactated Ringer's group, and burn plus HS group. Lung edema was assessed in terms of wet-weight-to-dry-weight ratio. Tumor necrosis factor α and interleukin 6 concentrations in serum were examined by enzyme-linked immunosorbent assay. Peripheral blood mononuclear cells were isolated and the expression of p38 mitogen-activated protein kinase was determined by Western blot analysis. The lung and intestinal concentrations of malondialdehyde, an indicator of oxidative stress, were also measured. RESULTS: Resuscitation with 200 mEq/L Na(+) HS significantly decreased the lung wet-weight-to-dry-weight ratio and abolished hyponatremia induced by burn injury. HS treatment also prevented the increases of myeloperoxidase activity and malondialdehyde content in the lung and intestine of severely burned rats. However, there were no significant differences, either in serum tumor necrosis factor α and interleukin 6 concentrations or with respect to the p38 mitogen-activated protein kinase expression in peripheral blood mononuclear cells, between the burn plus lactated Ringer's group and burn plus HS group (P > 0.05). CONCLUSIONS: Initial resuscitation with 200 mEq/L Na(+) HS after severe burn injury decreases pulmonary edema, prevents hyponatremia, and attenuates oxidative stress, but is not capable of inhibiting the systemic inflammatory response.

Thiazolidinedione use is associated with reduced risk of dementia in patients with type 2 diabetes mellitus: A retrospective cohort study.

BACKGROUND: Type 2 diabetes mellitus (T2DM) and dementia cause heavy health burden in mainland China, where few studies have investigated the association between glucose-lowering agents and dementia risk. We aimed to assess the association between use of thiazolidinediones (TZDs) and dementia incidence in a mainland Chinese population with T2DM. METHODS: A retrospective cohort of T2DM patients who were new users of TZDs or alpha glucosidase inhibitors (AGIs) was assembled using the Yinzhou Regional Health Care Database. A Cox model with inverse probability of treatment weighting (IPTW) for controlling potential founding was applied to estimate the hazard ratio (HR) of the association between use of TZDs and dementia risk. RESULTS: A total of 49 823 new users of AGIs and 12 752 new users of TZDs were included in the final cohort. In the primary analysis, the incidence of dementia was 195.7 and 78.2 per 100 000 person-years in users of AGIs and TZDs respectively. TZD use was associated with a reduced risk of incident dementia after adjusting for potential confounding using IPTW, with a HR of 0.51 (95% CI, 0.38-0.67). The results in various subgroup analyses and sensitivity analyses were consistent with the findings of the primary analysis. CONCLUSIONS: Use of TZDs is associated with a decreased risk of dementia incidence in a mainland Chinese population with T2DM.

Validation and comparison of cardiovascular risk prediction equations in Chinese patients with Type 2 diabetes.

AIMS: For patients with diabetes, the European guidelines updated the cardiovascular disease (CVD) risk prediction recommendations using diabetes-specific models with age-specific cut-offs, whereas American guidelines still advise models derived from the general population. We aimed to compare the performance of four cardiovascular risk models in diabetes populations. METHODS AND RESULTS: Patients with diabetes from the CHERRY study, an electronic health records-based cohort study in China, were identified. Five-year CVD risk was calculated using original and recalibrated diabetes-specific models [Action in Diabetes and Vascular disease: PreterAx and diamicroN-MR Controlled Evaluation (ADVANCE) and the Hong Kong cardiovascular risk model (HK)] and general population-based models [Pooled Cohort Equations (PCE) and Prediction for Atherosclerotic cardiovascular disease Risk in China (China-PAR)]. During a median 5.8-year follow-up, 46 558 patients had 2605 CVD events. C-statistics were 0.711 [95% confidence interval: 0.693-0.729] for ADVANCE and 0.701 (0.683-0.719) for HK in men, and 0.742 (0.725-0.759) and 0.732 (0.718-0.747) in women. C-statistics were worse in two general population-based models. Recalibrated ADVANCE underestimated risk by 1.2% and 16.8% in men and women, whereas PCE underestimated risk by 41.9% and 24.2% in men and women. With the age-specific cut-offs, the overlap of the high-risk patients selected by every model pair ranged from only 22.6% to 51.2%. When utilizing the fixed cut-off at 5%, the recalibrated ADVANCE selected similar high-risk patients in men (7400) as compared to the age-specific cut-offs (7102), whereas age-specific cut-offs exhibited a reduction in the selection of high-risk patients in women (2646 under age-specific cut-offs vs. 3647 under fixed cut-off). CONCLUSION: Diabetes-specific CVD risk prediction models showed better discrimination for patients with diabetes. High-risk patients selected by different models varied significantly. Age-specific cut-offs selected fewer patients at high CVD risk especially in women.

This large electronic health records-based real-world study indicated that the diabetes-specific cardiovascular risk models had better discriminative abilities than the models derived from the general population in Chinese patients with Type 2 diabetes.Current guidelines-recommended models, i.e. ADVANCE, PCE, and China-PAR, selected significantly different high-risk groups with various observed cardiovascular risks, indicating the potential considerable misclassification of risk stratification in clinical decision-making for preventive interventions.Compared with the fixed cut-off, the influence of the age-specific cut-offs for high risk of cardiovascular disease was different in men and women: age-specific cut-offs selected ∼27% fewer high-risk patients in women but similar in men.

Evaluating the effectiveness and cost-effectiveness of free influenza vaccination policy for older adults in Yinzhou, China: Study protocol of a real-world analyses.

BACKGROUND: Influenza causes excessive morbidity and mortality among older adults. While influenza vaccine provides protection against its infection, the vaccination coverage in China among older adults has been very low. Previous evidence on the cost-effectiveness of government-sponsored free influenza vaccination programs in China was primarily based on literature data, which might not always reflect real-world patient populations. The Yinzhou Health Information System (YHIS) is a regional database that captures electronic health records, insurance claims data, etc. for all residents in Yinzhou district, Zhejiang province, China. We will use YHIS to study the effectiveness, influenza-related direct medical cost and cost-effectiveness analysis (CEA) of the free influenza vaccination program for older adults. In this paper, we describe the study design and innovations in detail. METHODS: We will establish a retrospective cohort of permanent older residents aged 65 and over, using YHIS between 2016 and 2021. We will estimate the vaccine coverage rate, influenza incidence rate and influenza-related direct medical cost from 2016 to 2021. Regression discontinuity will be used to estimate vaccine effectiveness for the 2020/2021 season. We will build a decision tree model to compare the cost-effectiveness of three influenza vaccination options (free trivalent influenza vaccine, free quadrivalent influenza vaccine, and no policy) from both societal and health system perspectives. Parameter inputs will be gathered from both YHIS and published literature. We will calculate the incremental cost-effectiveness ratio with cost and quality-adjusted life years (QALYs) discounted at 5 % annually. DISCUSSION: Our CEA solidifies multiple sources including regional real-world data and literature for a rigorous evaluation of the government-sponsored free influenza vaccination program. The results will provide real-world evidence from real-world data on the cost-effectiveness of a real-world policy. Our findings are expected to support evidence-based policy making and to promote health for older adults.

Achievement of low-density lipoprotein cholesterol targets in Chinese patients with atherosclerotic cardiovascular disease after receiving statins and ezetimibe.

Background: The importance of low-density lipoprotein cholesterol (LDL-C) lowering to reduce atherosclerotic cardiovascular disease (ASCVD) risk is strongly emphasized. If the LDL-C goals are not achieved with statin therapy, combination with ezetimibe is recommended. Studies revealed a substantial gap between obtained LDL-C levels and LDL-C target in ASCVD patients. However, little is known about the achievement of LDL-lowering treatment targets in ASCVD patients receiving ezetimibe in addition to statins. Materials and methods: This was a retrospective cohort study based on EHR data from the regional health information system of Yinzhou, an eastern coastal area of China. ASCVD Patients stratified as very high risk, taking both statin and ezetimibe for lipid control, and had at least one lipid test after ezetimibe initiation were included between January 2013 and July 2020. Descriptive statistics were used to summarize the LDL-C values and target value (1.8 mmol/L according to the Chinese guideline, 1.4 mmol/L according to the European guideline) achievements. Multivariable logistic regression was used to explore the influencing factors of target achievement rate. Results: A total of 1,727 patients were included. The median follow-up time was 15.0 months. Taking 1.8 mmol/L as the target value, the achievement rates of LDL-C over the first 3 follow up years were 50.6, 31.3, and 30.3%, respectively. Taking 1.4 mmol/L as the target value, the achievement rates were 25.6, 15.5, and 16.5%, respectively. Multivariable analysis suggested that male patients (OR = 1.78, 95%CI: 1.27-2.49), combined use of atorvastatin or rosuvastatin with ezetimibe (vs other statins, OR = 4.64, 95% CI: 1.83-11.76), better medication adherence (OR = 1.03, 95% CI: 1.01-1.04) and smoking cessation (vs smoking, OR = 2.26, 95% CI: 1.27-4.02) were associated with a higher achievement rate, while baseline LDL-C level (OR = 0.48, 95% CI: 0.41-0.56) and treatment course of statin before ezetimibe (OR = 0.93, 95% CI: 0.89-0.98) were negatively associated with achievement rate. Conclusion: Long-term follow-up data based on a Chinese regional database shows that in very high-risk ASCVD patients taking ezetimibe in addition to statins, achievement rate of LDL-lowering treatment targets is still low and far from satisfactory in real-world setting. More efforts are needed to achieve optimal LDL-C levels.

Thiazolidinedione use and risk of Parkinson's disease in patients with type 2 diabetes mellitus.

The health burden of Parkinson's disease (PD) and diabetes increases rapidly in China. However, no population-based study of the association between glucose lowering agents and PD incidence has been conducted in mainland Chinese population. Preclinical studies indicate that thiazolidinediones (TZDs) have neuroprotective effects against PD through stimulating peroxisome proliferator-activated receptor gamma. Nevertheless, debate remains in human studies. We assembled a retrospective cohort of type 2 diabetes mellitus (T2DM) patients who were new users of TZDs or alpha glucosidase inhibitors (AGIs) using the Yinzhou Regional Health Care Database. A Cox model with inverse probability of treatment weighting (IPTW) was applied to estimate the hazard ratio (HR) of PD incidence associated with the use of TZDs compared with AGIs. The final cohort included 12,704 new users of TZDs and 49,696 new users of AGIs. The incidence of PD was 135 per 100,000 person-years in TZD users and 203 per 100,000 person-years in the AGI group. An inverse association between use of TZDs and incidence of PD, with a HR of 0.74 (95% confidence interval, 0.59-0.92), was observed after adjusting for potential confounding using IPTW. The results of various subgroup analyses and sensitivity analyses were consistent with the findings of the primary analysis. Our results indicated that the use of TZD is associated with a decreased risk of PD incidence in a mainland Chinese population with T2DM. Given the heavy disease burden of PD and diabetes in China, these findings could provide some evidence for developing effective prevention and control measures to reduce the future incidence of PD in China.

The effectiveness of influenza vaccine among elderly Chinese: A regression discontinuity design based on Yinzhou regional health information platform.

In China, a free influenza vaccination policy is being implemented among individuals aged 70 years and over in Zhejiang province during the COVID-19 pandemic. The objective was to assess the effectiveness of influenza vaccine in reducing hospitalization and mortality in the elderly. We used data from the Regional Health Information Platform in Yinzhou located in Zhejiang province and applied a regression discontinuity design to estimate the intention-to-treat effect on admission and mortality rates by month of age in the population who was near the age of 70 years threshold. At age 70 years, the influenza vaccination rate increased by 29.1% (95% CI, 28.2% to 29.9%) compared to those under 70 in the study population. When turning age 70 years, the potential effectiveness of receiving influenza vaccine was 8.2% (95% CI, -36.8% to 51.3%) for total hospitalization and the evaluation of vaccine effectiveness was 13.1% (95% CI, -34.2 to 61.8) for the all-cause mortality. An increase in the influenza vaccination rate was associated with a weak decline in most outcomes, but no significance was found for all outcomes. Influenza vaccination had a limited effect on hospital admission and mortality for the free influenza vaccination program that can be related to the low vaccination rate among the Chinese elderly. Supplementation strategies and future studies may be needed to expand immunization coverage and validate this finding, and further provide a reference for other cities to promote the free influenza vaccination policy in China, especially under circumstances of the COVID-19 pandemic.

Sulfonylurea and Cancer Risk Among Patients With Type 2 Diabetes: A Population-Based Cohort Study.

Background: Current evidence of the association between the use of sulfonylurea and cancer risk is highly conflicting and little evidence of this association is from the mainland Chinese population. This study aimed to evaluate the potential effects of sulfonylurea use on cancer risk among patients with type 2 diabetes mellitus (T2DM). Methods: A retrospective cohort study of T2DM patients who were new users of sulfonylurea or metformin was conducted using the Yinzhou Regional Health Care Database. A marginal structural Cox model was used to estimate the hazard ratio (HR) of cancer associated with the use of sulfonylurea compared with metformin, with time-varying confounders controlled by inverse probability weighting. Secondary analyses using different glucose-lowering drugs (GLDs) as comparator and sensitivity analyses for potential bias due to latency period, model misspecification, missing data, analyses strategy (intention-to-treat and per-protocol), and diagnosis validation were performed to examine the robustness of the results. Results: After fully controlling for time-varying confounding, baseline confounding, and competing risk, the use of sulfonylurea was not associated with the risk of any cancer (HR 1.09; 95% CI, 0.93-1.27), compared with the use of metformin. In the secondary analyses, compared with α - glucosidase inhibitors, thiazolidinediones, glinides, other GLDs except sulfonylure and insulin, and T2DM patients not treated with sulfonylureas, the HRs of the association between sulfonylurea use and cancer risk were 0.92 (95% CI; 0.78-1.08), 0.89 (95% CI; 0.66-1.19), 0.85 (95% CI; 0.71-1.02), 1.04 (95% CI; 0.89-1.22), and 1.07 (95% CI; 0.99-1.16), respectively. The results of analyses for various subgroups, risk of site-specific cancers, cumulative duration, dose-response relationship, and sensitivity analyses of different latency periods and missing data were generally consistent with the findings of the primary analyses. Conclusion: No association between sulfonylurea use and cancer risk was found in this study after properly controlling biases due to time-varying confounders and other sources. Further studies on the association between sulfonylurea use and the risk of cancer by using data from a Chinese population with higher representativeness are needed.