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This study is to estimate the lifetime risks of hip fracture in Chinese patients with type 2 diabetes. The lifetime risks of hip fracture have not been reported across the age spectrum in male adults and female adults with type 2 diabetes. A retrospective cohort study was conducted on 25275 men and 27953 women with type 2 diabetes aged 30–100 years old and participated in the National Diabetes Case Management Program in 2002–2004 in Taiwan. Sociodemographic factors, biomarkers, and comorbidity at the baseline and hip fracture events were analyzed with Cox proportional hazards regression models with age as the time scale. Significant differences in the lifetime risks of hip fracture were observed between men and women with type 2 diabetes. The cumulative lifetime incidences (%) of hip fracture at 50, 60, 65, 70, 75, 80, and 85 years old for men were 0.11, 0.40, 0.84, 1.84, 3.82, 8.53, and 16.72, respectively. The corresponding lifetime incidences (%) for women at 50, 60, 65, 70, 75, 80, and 85 years old were 0.05, 0.50, 1.36, 3.89, 9.56, 21.19, and 35.45, respectively. With competing risks, the significant multivariate-adjusted hazard ratio of developing hip fracture included smoking, alcohol drinking, duration of diabetes, type of oral hypoglycemic drugs use (no medication, sulfonylurea only, thiazolidinediones (TZD) only or TZD plus others, other single or multiple oral agents, insulin use, insulin plus oral hypoglycemic drug use), loop diuretics use, use of corticosteroids, normal weight or underweight, hyperlipidemia, and chronic obstructive pulmonary disease. The gender differences in lifetime hip fracture risk were significant. Thiazolidinediones and insulin use are factors with the greater magnitude of strength of association among those significantly associated with hip fracture.

Background This study determined (1) whether a change in frailty status after a 1 year follow up is associated with healthcare utilization and evaluated (2) whether a change in frailty status after a 1 year follow up and health care utilization are associated with all-cause mortality in a sample of Taiwan population. Methods This work is a population-based prospective cohort study involving residents aged ≥65 years in 2009. A total of 548 elderly patients who received follow-ups in the subsequent year were included in the current data analysis. Fried frailty phenotype was measured at baseline and 1 year. Information on the outpatient visits of each specialty doctor, emergency care utilization, and hospital admission during the 2 month period before the second interview was collected through standardized questionnaires administered by an interviewer. Deaths were verified by indexing to the national database of deaths. Results At the subsequent 1 year follow-up, 73 (13.3%), 356 (64.9%), and 119 (21.7%) elderly participants exhibited deterioration, no change in status, and improvement in frailty states, respectively. Multivariate logistic analysis showed the high risk of any type of outpatient use (odds ratios [OR] 1.94, 95% confidence interval [CI] 1.02–3.71) among older adults with worse frailty status compared with those who were robust at baseline and had unchanged frailty status after 1 year. After multivariate adjustment, participants with high outpatient clinic utilization had significantly higher mortality than those with low outpatient clinic visits among unchanged pre-frail or frail (hazard ratios [HR] 2.79, 95% CI: 1.46–5.33) and frail to pre-frail/robust group (HR 9.32, 95% CI: 3.82–22.73) if the unchanged robustness and low outpatient clinic visits group was used as the reference group. Conclusions The conditions associated with frailty status, either after 1 year or at baseline, significantly affected the outpatient visits and may have increased medical expenditures. Combined change in frailty status and number of outpatient visits is related to increased mortality.

Platinum diselenide (PtSe2) is a group-10 two-dimensional (2D) transition metal dichalcogenide that exhibits the most prominent atomic-layer-dependent electronic behavior of "semiconductor-to-semimetal" transition when going from monolayer to bulk form. This work demonstrates an efficient photoelectrochemical (PEC) conversion for direct solar-to-hydrogen (H2) production based on 2D layered PtSe2/Si heterojunction photocathodes. By systematically controlling the number of atomic layers of wafer-scale 2D PtSe2 films through chemical vapor deposition (CVD), the interfacial band alignments at the 2D layered PtSe2/Si heterojunctions can be appropriately engineered. The 2D PtSe2/p-Si heterojunction photocathode consisting of a PtSe2 thin film with a thickness of 2.2 nm (or 3 atomic layers) exhibits the optimized band alignment and delivers the best PEC performance for hydrogen production with a photocurrent density of -32.4 mA cm-2 at 0 V and an onset potential of 1 mA cm-2 at 0.29 V versus a reversible hydrogen electrode (RHE) after post-treatment. The wafer-scale atomic-layer controlled band engineering of 2D PtSe2 thin-film catalysts integrated with the Si light absorber provides an effective way in the renewable energy application for direct solar-to-hydrogen production.

Chronic neck pain may affect sensorimotor integration, which is critical for postural control. Accordingly, this study investigated whether individuals with chronic neck pain display altered muscle activation and postural control compared with those of healthy adults while performing functional reach tasks. Three-dimensional kinematic analyses and electromyographic analyses were performed. 20 individuals with chronic neck pain and twenty healthy adults were recruited. The reach distance, anterior displacements of the centers of mass and pressure, and activity of the cervical muscles were recorded during functional reach tasks. Compared with the healthy adults, the individuals with chronic neck pain showed significantly smaller anterior displacements of the centers of mass and pressure and reduced muscle activity of the upper trapezius muscle. However, no difference in the reach distance was observed between the two groups. It is speculated that a functional reach task may not be sensitive enough to detect changes in the postural control of individuals with chronic neck pain. For individuals with chronic neck pain, a combination of clinical measures and quantitative assessments of the centers of mass and pressure is suggested to facilitate the early detection of changes in postural control.

Extensive studies on lead halide perovskites have shown that these materials are excellent candidates as gain mediums. Recently, many efforts have been made to incorporate perovskite lasers in integrated optical circuits. Possible solutions would be to utilize standard lithography with an etching/lift-off process or a direct laser etching technique. However, due to the fragile nature of the lead halide perovskites which gives rise to significant material deterioration during the lithography and etching processes, realizing a small-size, low-roughness, and single-mode laser remains a challenge. Here, a lithographic in-mold patterning method realized by nanocrystal concentration control and a multi-step filling-drying process is proposed to demonstrate CsPbBr3 nanocrystals distributed-Bragg-reflector (DBR) waveguide lasers. This method realizes the patterning of the CsPbBr3 nanocrystal laser cavity and DBR grating without lift-off and etching processes, and the smallest fabricated structures are obtained in a few hundred nanometers. The single-mode lasing is demonstrated at room temperature with a threshold of 23.5 μJ cm-2. The smallest full width at half maximum FWHM of the laser output is 0.4 nm. Due to the fabrication process and the DBR laser geometry, the lasers can be fabricated in a compact array, which is important for incorporating perovskite-based lasers in complex optoelectronic circuits.

Aim The objective of this study was to explore the association between mitochondrial DNA (mtDNA) haplogroups and physical performances in Han older adults. Methods This study was an 8-year follow-up prospective cohort study. A total of 104 Han older adults completed the measurements of the 6-min walk test, grip strength and mitochondrial DNA sequencing. The mtDNA haplogroups were classified by using HaploGrep2 software. We used the mixed model to analyze the longitudinal effect of mtDNA haplogroups on physical performance tests among three waves of data. Results The mean age at wave 3 among men and women were 78.3 and 77.2 years, respectively. The overall proportions of mtDNA haplogroups in this study population was 26.9% F, 21.2% M, 15.4% R, 14.4% D, 8.7% B and others. After adjusted for age, sex, ethnicity, body mass index and exercise, the interaction of mtDNA haplogroup M and waves significantly affected the 6-min walk distance. Notably, the adjusted mean of the 6-min walk distance among the group of mtDNA haplogroup M was significantly lower than other haplogroups at wave 3. The adjusted mean of grip strength among the group of mtDNA haplogroup R was significantly higher than other haplogroups at wave 3. Conclusions This finding suggests that mtDNA haplogroups might have effects on the 6-min walk test and grip strength in Han older adults, although studies of the physical performance of older adults with larger sample sizes are necessary to further substantiate these findings. Geriatr Gerontol Int 2021; 21: 166-171.

Background. Traditional Chinese medicine (TCM) for the treatment of female infertility remains ambiguous. The aim of the present case-control study was to examine the association between TCM treatment and successful pregnancy among infertile women. Methods. This population-based case-control study included the data from 2,627 infertile women with successful pregnancy and 2,627 infertile women without successful pregnancy using datasets from the Longitudinal Health Insurance Database 2000 of the National Health Insurance Research Database during 2000–2010. The odds ratios (ORs) and 95% confidence intervals (CIs) for the relationship between TCM use and successful pregnancy in infertility women were estimated using logistic regression. Results. Patients who received TCM treatment significantly increased in successful pregnancy (OR = 1.48; 95% CI = 1.31–1.66), compared with patients without TCM. Si-Wu-Tang (OR = 4.25; 95% CI = 2.18, 8.30), Gui-Zhi-Fu-Ling-Wan (OR = 3.27; 95% CI = 2.13, 5.02), and Jia-Wei-Xiao-Yao-San (OR = 3.17; 95% CI = 2.35, 4.28) were the TCM agents that were most strongly associated with successful pregnancy among infertile women. Conclusions. Our study findings indicate that TCM is associated with higher likelihood of successful pregnancy in infertile women, which is worthy of further investigation by randomized control trial.

Background Angiotensin receptor blockers (ARBs) have been reported to ameliorate anxiety and mood disorders in animal models. Cohort links between ARB use and suicide risk in humans require clarification. Methods Data were obtained from the National Health Insurance Research Database. Patients diagnosed as having hypertension according to the criteria of the International Classification of Diseases, Ninth Revision, Clinical Modification (401-405) from January 1, 2000 to December 31, 2012 were enrolled as the target population. We defined enrollees who had received ARB prescriptions for at least 28 days as ARB users. Those who had never taken ARB prior or during the study period were defined as ARB nonusers and were propensity score–matched with ARB users. The end outcome was confirmation of a suicide attempt. Results After propensity score matching was conducted, 40,976 ARB users and 40,976 nonusers were selected as the matched cohorts. The overall incidence rate of suicide attempt was significantly lower in ARB users than in nonusers (0.51 vs. 1.07 per 10,000 person-years; adjusted hazard ratio = 0.48, 95% confidence interval = 0.26–0.87). A Kaplan–Meier survival analysis with a log-rank test revealed a lower cumulative incidence of suicide attempt in ARB users than in nonusers (p Conclusions ARB use was not associated with an increased risk for suicide compared with non-ARB use.

Background We hypothesized that renin–angiotensin system (RAS) blockers have systemic protective effects beyond the respiratory tract and could reduce the risk of viral infections. Methods We used the National Health Insurance Research Database and identified 2 study cohorts: the angiotensin receptor blocker (ARB) cohort and angiotensin-converting enzyme inhibitor (ACEI) cohort. Propensity score matching was applied at a 1:1 ratio by all associated variables to select 2 independent control cohorts for the ARB and ACEI cohorts. A Cox proportional hazards model was applied to assess the end outcome of viral infection. Results The number of ARB and ACEI users was 20 207 and 18 029, respectively. The median age of ARB users and nonusers was 53.7 and 53.8 years, respectively. The median follow-up duration of ARB users and nonusers was 7.96 and 7.08 years; the median follow-up duration of ACEI users and nonusers was 8.70 and 8.98 years, respectively. The incidence rates of viral infections in ARB users and nonusers were 4.95 and 8.59 per 1000 person-years, respectively, and ARB users had a lower risk of viral infection than nonusers (adjusted hazard ratio [aHR], 0.53 [95% confidence interval {CI}, .48–.58]). The incidence rates of viral infections in ACEI users and nonusers were 6.10 per 1000 person-years and 7.72 per 1000 person-years, respectively, and ACEI users had a lower risk of viral infection than nonusers (aHR, 0.81 [95% CI, .74–.88]). Conclusions Hypertensive patients using either ARBs or ACEIs exhibit a lower risk of viral infection than nonusers.

Objective The objective of the study was to evaluate the prevalences and trends of multimorbidity and polypharmacy in older adults in Taiwan. Methods An observational study was performed using the 2000-2013 database of the Taiwan National Health Insurance Program (analysis in 2018). Participants ≥65 years were included in the study. Multimorbidity was defined as participants having two or more chronic diseases annually. Polypharmacy was defined as the average daily number of prescribed medications ≥5. Results The prevalences of multimorbidity were 42.4% in 2000 and 56% in 2013. The prevalences of polypharmacy were 22.9% in 2000 and 32.1% in 2013. Conclusions From 2000 to 2013, multimorbidity and polypharmacy were prevalent among older adults in Taiwan. Public health efforts to intervene the primary prevention for chronic diseases should be considered in older adults.

The prolonged head forward and neck flexion posture associated with tablet computer use is a known risk factor for neck pain. Neck pain related dysfunction may cause proprioceptive errors and deficits in balance control. Thus, this study aimed to investigate the impact of prolonged tablet computer use with head forward and neck flexion posture on the pain intensity, cervical position sense and balance control in mechanical neck pain patients. The prolonged head forward and neck flexion posture associated with tablet computer use is a known risk factor for neck pain. Neck pain related dysfunction may cause proprioceptive errors and deficits in balance control. Thus, this study aimed to investigate the impact of prolonged tablet computer use with head forward and neck flexion posture on the pain intensity, cervical position sense and balance control in mechanical neck pain patients.The prolonged head forward and neck flexion posture associated with tablet computer use is a known risk factor for neck pain. Neck pain related dysfunction may cause proprioceptive errors and deficits in balance control. Thus, this study aimed to investigate the impact of prolonged tablet computer use with head forward and neck flexion posture on the pain intensity, cervical position sense and balance control in mechanical neck pain patients. Twenty subjects with mechanical neck pain (24.1 ± 3.4 years) and 20 healthy controls (23.7 ± 3.3 years) were recruited from a university environment. A neck pain inducing protocol simulating prolonged tablet computer usage with neck flexion posture was performed by the mechanical neck pain subjects until the point of moderate pain. The neck pain related scores, cervical range of motion and neck tissue hardness were evaluated in both the healthy controls and the neck pain subjects before the neck pain inducing protocol. Differences in the cervical joint position sense, neck tissue hardness and static standing balance performance of the healthy controls and mechanical neck pain subjects were investigated after the neck pain inducing protocol. The mechanical neck pain subjects demonstrated a lower cervical range of motion and a harder neck tissue status than the control subjects. The pain intensity reported by the neck pain subjects after the neck pain inducing protocol was similar to that experienced by the subjects in previous pain attacks. Significant differences in the absolute neck joint positioning error were observed between the mechanical neck pain group and the control group. Prolonged tablet computer use with head forward and neck flexion posture did not significantly increase the joint positioning error in the mechanical neck pain group. However, prolonged tablet computer use with head forward and neck flexion posture resulted in a poorer static standing balance performance in the subjects with mechanical neck pain than in the healthy controls. The subjects with mechanical neck pain exhibited a decreased cervical range of motion, a harder neck tissue status and greater neck joint position errors than the healthy controls. In addition, prolonged tablet computer use with head forward and neck flexion posture reproduced the neck pain severity and reduced the balance control ability of the mechanical neck pain subjects.

Elderly long-term care facility residents typically have musculoskeletal conditions that may lead to long-term disability and increased mortality. Our main objective was to explore the relationship between body mass index (BMI), albumin levels, and mortality in elderly individuals with limited performance status. Among 182 participants (mean age, 78.8 years; 57% women), 11%, 64%, and 25% had serum albumin levels of 3.5 g/dL, respectively. After multivariate adjustments, diastolic blood pressure >90 mmHg was associated with all-cause mortality [hazard ratio (HR) = 2.08, 95% confidence interval (CI) = 1.13-3.82; P = 0.018]. In addition, BMI 3.5 g/dL (HR = 1.80, 95% CI = 1.11-2.94 and HR = 2.54, 95% CI 1.22-5.30, respectively; P = 0.018 and 0.013, respectively). Highest mortality was noted in participants with albumin levels

Background/aim The present study aimed at evaluating the contribution of IL-4 promoter T-1099G (rs2243248), C-589T (rs2243250), C-33T (rs2070874) genotypes to the risk of breast cancer in Taiwanese. Materials and methods A total of 1232 breast cancer patients and 1232 age-matched controls were genotyped by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) methodology. Results Genotypic frequencies of IL-4 rs2243248, rs2243250 and rs2070874 were not differentially distributed between case and control groups. Consistently, there was no difference in the distribution of allelic frequencies among patients and controls. Conclusion IL-4 rs2243248, rs2243250 and rs2070874 do not confer breast cancer susceptibility in Taiwanese.

Aim Diabetes is a primary cause of hospitalization and in-hospital mortality. However, studies exploring the relationships between body mass index (BMI) and hospitalization-related and mortality-related outcomes in patients with type 2 diabetes are lacking. Methods Our data were obtained from two independent retrospective cohort studies, namely, the Taiwan Diabetes Study (Taiwan DS), providing hospitalization outcome measures, and the Taichung Diabetes Study (Taichung DS) that can be linked with the National Death Registry dataset. BMI and hospitalization, in-hospital mortality, and all-cause and cause-specific death events were analyzed by Cox proportional hazard regression model. Results A total of 3,541, 38,779, and 10,399 patients died during hospitalization, hospitalized for all-cause and diabetes-related events, respectively, in the Taiwan DS cohort. Moreover, 685 deaths were identified in the Taichung DS cohort. Compared with patients with increasing-but-acceptable-risk obesity, multivariable-adjusted hazard ratios (HRs) of in-hospital mortality, all-cause hospitalization, hospitalization due to diabetes, hypoglycaemia, and renal failure for patients who were underweight were 2.09 (95% confidence interval 1.73, 2.51), 1.39 (1.28, 1.50), 1.69 (1.49, 1.90), 1.87 (1.34, 2.61), and 1.55 (1.26, 1.91). Adjusted HRs of all-cause mortality and non-expanded CVD-related mortality in patients with underweight were 2.02 (1.28, 3.21), and 2.27 (1.28, 4.03). Conclusions The BMI associated with the best survival and less hospitalization was the higher-high-risk obesity (≥ 27.5 kg/m2) category. We observed obesity paradox for mortality outcomes, which should be addressed by further research, particularly on whether randomized controlled trials of adopting a healthy lifestyle for patients with obesity can improve type 2 diabetes patients’ survival.

We evaluated whether genetic information could offer improvement on risk prediction of diabetic nephropathy (DN) while adding susceptibility variants into a risk prediction model with conventional risk factors in Han Chinese type 2 diabetes patients. A total of 995 (including 246 DN cases) and 519 (including 179 DN cases) type 2 diabetes patients were included in derivation and validation sets, respectively. A genetic risk score (GRS) was constructed with DN susceptibility variants based on findings of our previous genome-wide association study. In derivation set, areas under the receiver operating characteristics (AUROC) curve (95% CI) for model with clinical risk factors only, model with GRS only, and model with clinical risk factors and GRS were 0.75 (0.72–0.78), 0.64 (0.60–0.68), and 0.78 (0.75–0.81), respectively. In external validation sample, AUROC for model combining conventional risk factors and GRS was 0.70 (0.65–0.74). Additionally, the net reclassification improvement was 9.98% (P = 0.001) when the GRS was added to the prediction model of a set of clinical risk factors. This prediction model enabled us to confirm the importance of GRS combined with clinical factors in predicting the risk of DN and enhanced identification of high-risk individuals for appropriate management of DN for intervention.

Elevated glucose level is one of the risk factors for lower extremity amputation (LEA), but whether glycaemic variability confers independent risks of LEA remains to be elucidated. This study aimed to investigate the association between visit-to-visit glycaemic variability and minor and major LEA risks during 8 years of follow-up in type 2 diabetic individuals aged 50 years and older. This retrospective cohort study included 27,574 ethnic Chinese type 2 diabetic individuals aged ≥50 years from the National Diabetes Care Management Program in Taiwan. Glycaemic variability measures were presented as the CVs of fasting plasma glucose (FPG-CV) and of HbA1c (A1c-CV). The effect of glycaemic variability on the incidence of LEA events was analysed using Cox proportional hazards models. After a median follow-up of 8.9 years, 541 incident cases of LEA with a crude incidence density rate of 2.4 per 1000 person-years were observed. After multivariate adjustment, FPG-CV and A1c-CV were found to be significantly associated with minor LEA, with corresponding HRs of 1.53 (95% CI 1.15, 2.04) and 1.34 (95% CI 1.02, 1.77) for the third tertiles of FPG-CV and A1c-CV, respectively. In addition, these associations were stronger amongst older adults with longer diabetes duration (≥3 years) than amongst those with shorter duration (

BackgroundDyslipidemia is a major cardiovascular risk factor and common in diabetes patients. Most guidelines focus on optimal lipid levels, while variation of lipid profiles is far less discussed. This study aims to investigate the association of visit-to-visit variability in blood lipids with all-cause, cardiovascular, and non-cardiovascular mortality in patients with type 2 diabetes.MethodsWe identified 10,583 type 2 diabetes patients aged ≥ 30 years with follow-up ≥ 3 years and who participated in the Diabetes Care Management Program at a medical center in Taiwan. Variability in lipid profiles within 3 years after entry was calculated using coefficient of variation. Cox proportional hazard models were used to evaluate lipid variability in relation to subsequent mortality.ResultsOver a mean follow-up of 6.4 years, 1838 all-cause deaths (809 cardiovascular deaths) were observed. For each 10% increase in variability in high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, and total cholesterol, the hazard ratios (95% confidence intervals) of all-cause mortality were 1.30 (1.22–1.37), 1.05 (1.01–1.09), and 1.10 (1.03–1.16), respectively; those of cardiovascular mortality were 1.27 (1.16–1.39), 1.08 (1.02–1.15), and 1.16 (1.07–1.27), respectively. Each 10% increase in high-density lipoprotein cholesterol variability conveyed 31% greater risk of non-cardiovascular mortality. High variability in total cholesterol and low-density lipoprotein cholesterol increased all-cause mortality in subgroups of nonsmoking, regular exercising, non-dyslipidemia, and more severe status of diabetes at baseline.ConclusionsBlood lipid variability except for triglyceride variability was associated with all-cause and cardiovascular mortality in patients with type 2 diabetes.

This study aimed to explore the associations between renal-related and arterial stiffness biomarkers with all-cause and expanded cardiovascular disease (CVD) mortality in a general Taiwanese population. This prospective community-based cohort study included 4883 subjects aged ≥ 20 years who were followed up until December 31, 2016. Renal-related biomarkers consisted of blood urea nitrogen (BUN), estimated glomerular filtration rate (eGFR), and urine albumin-to-creatinine ratio (UACR). Arterial stiffness biomarker consisted of brachial-ankle pulse wave velocity (baPWV). The death status of the subjects was ascertained by matching information from death records with the identification number and date of birth of the subjects. Cox proportional hazard models with restricted cubic splines estimated the hazard ratios and 95% confidence intervals for all-cause mortality and expanded CVD mortality. During a mean 8.3 years of follow up, 456 deaths were recorded, 146 of which were due to expanded CVD mortality. The multivariable-adjusted hazard ratios of all-cause mortality was 1.53 (95% CI 1.21–1.94) for BUN (≥ 20 mg/dL vs. 2 vs. ≥ 90 mL/min/1.73 m2), 1.55 (1.25–1.92) for UACR (≥ 30 mg/g vs. 2 vs. ≥ 90 mL/min/1.73 m2), 2.13 (1.52–2.99) for UACR (≥ 25 mg/g vs.

Background We aimed to identify associations between the risk of acute respiratory failure (ARF) and types of antihypertensive agents in patients with viral pneumonia. Methods In this case-control study, data extracted from the Taiwan National Health Insurance Research Database were analysed. The base population comprised patients with viral pneumonia treated from 2000 to 2013. The case group comprised patients with ARF and the control group comprised participants without ARF. Adjusted odds ratios (ORs) were calculated using a multivariable logistic regression model. Results In total, 4427 viral pneumonia patients with ARF and 4427 matched control participants without ARF were recruited. Patients with diabetes, alcohol-related disease, asthma, chronic kidney disease or end-stage renal disease, chronic obstructive pulmonary disease, cancer, congestive heart failure, stroke, acute pulmonary oedema and shock had increased odds of developing ARF, especially shock (adjusted OR = 49.3; 95% CI = 27.4, 88.7), cancer (12.6; 8.67, 18.2) and stroke (7.51; 5.32, 10.6). Increasing odds of developing ARF were noted in patients using potassium-sparing diuretics (2.95; 1.54, 5.64), loop diuretics (68.2; 48.1, 96.6), calcium channel blockers (1.64; 1.26, 2.13) and angiotensin-converting enzyme inhibitors (1.70; 1.15, 2.53). Patients with prescriptions of α-blockers (0.44; 0.26, 0.74), β-blockers (0.37; 0.26, 0.52), thiazides (0.38; 0.25, 0.59) and angiotensin receptor blockers (0.65; 0.51, 0.83) had lower odds of having ARF. Conclusion Patients with viral pneumonia who received α-blockers, β-blockers, thiazides or angiotensin receptor blockers during hospitalisation had a lower risk of developing ARF.

Hypertension (HTN), which frequently co‐exists with diabetes mellitus, is the leading major cause of cardiovascular disease and death globally. This study aimed to develop and validate a risk scoring system considering the effects of glycemic and blood pressure (BP) variabilities to predict HTN incidence in patients with type 2 diabetes. This research is a retrospective cohort study that included 3416 patients with type 2 diabetes without HTN and who were enrolled in a managed care program in 2001–2015. The patients were followed up until April 2016, new‐onset HTN event, or death. HTN was defined as diastolic BP (DBP) ≥ 90 mm Hg, systolic BP (SBP) ≥ 140 mm Hg, or the initiation of antihypertensive medication. Cox proportional hazard regression model was used to develop the risk scoring system for HTN. Of the patients, 1738 experienced new‐onset HTN during an average follow‐up period of 3.40 years. Age, sex, physical activity, body mass index, type of DM treatment, family history of HTN, baseline SBP and DBP, variabilities of fasting plasma glucose, SBP, and DBP and macroalbuminuria were significant variables for the prediction of new‐onset HTN. Using these predictors, the prediction models for 1‐, 3‐, and 5‐year periods demonstrated good discrimination, with AUC values of 0.70–0.76. Our HTN scoring system for patients with type 2 DM, which involves innovative predictors of glycemic and BP variabilities, has good classification accuracy and identifies risk factors available in clinical settings for prevention of the progression to new‐onset HTN.

Background: Air pollution is speculated to affect the reproductive health of women. However, a longitudinal association between exposure to air pollution and dysmenorrhea has not been identified, which this study aimed to examine this point.Methods: Two nationwide databases, namely the Taiwan Air Quality Monitoring database and the Taiwan National Health Research Institutes database were linked. Women with a history of dysmenorrhea (International Classification of Disease, Ninth Revision, Clinical Modification code 625.3) before 2000 were excluded. All participants were followed from January 1, 2000 until the diagnosis of dysmenorrhea, withdrawal from National Health Insurance, or December 31, 2013. Furthermore, air pollutants were categorized into quartiles with three cut-off points (25th, 50th, and 75th percentiles). The Cox regression model was used to calculate the hazard ratios of dysmenorrhea.Results: This study enrolled 296,078 women. The mean concentrations of yearly air pollutants were 28.2 (±12.6) ppb for nitric oxides (NOx), 8.91 (±7.93) ppb for nitric oxide (NO), 19.3 (±5.49) ppb for nitrogen dioxide (NO2), 0.54 (±0.18) ppm for carbon monoxide (CO), and 31.8 (±6.80) μg/m3 for PM2.5. In total, 12,514 individuals developed dysmenorrhea during the 12-year follow-up. Relative to women exposed to Q1 concentrations of NOx, women exposed to Q4 concentrations exhibited a significantly higher dysmenorrhea risk [adjusted hazard ratio (aHR)= 27.9, 95% confidence interval (CI) = 21.6–31.3]; similarly higher risk was found for exposure to NO (aHR = 16.7, 95% CI = 15.4–18.4) and NO2 (aHR = 33.1, 95% CI = 30.9–37.4). For CO, the relative dysmenorrhea risk in women with Q4 level exposure was 28.7 (95% CI = 25.4–33.6). For PM2.5, women at the Q4 exposure level were 27.6 times (95% CI = 23.1–29.1) more likely to develop dysmenorrhea than those at the Q1 exposure level.Conclusion: Our results showed that women would have higher dysmenorrhea incidences while exposure to high concentrations of NO, NO2, NOx, CO, and PM2.5.

Background: An unstable ankle along with plantar flexor muscle fatigue may exacerbate landing performance. External support may be an option to control the ankle motion and protect joints from injuries. Research goal: To investigate the immediate changes in the joint motion of a lower extremity under ankle plantar flexors fatigue conditions in athletes with unstable ankles using different external supports. Methods: A total of 44 participants were allocated to a control (Cn) group, an ankle brace (AB) group, and a kinesio tape (KT) group, and were asked to perform a lateral drop landing before and after a fatigue protocol. The outcome measures were fatigue-induced changes in the maximal joint angle and changes in the angle ranges of the hip, knee, and ankle. Results: Smaller changes in the maximal hip abduction were found in the AB group (p = 0.025), and the KT group exhibited smaller changes in the maximal ankle dorsiflexion (p = 0.009). The AB group landed with a smaller change in the range of hip flexion and knee flexion (p = 0.008 and 0.006). The Cn group had greater fatigue-induced changes in the COM range than AB and KT group (p = 0.002 and 0.028). Significance: Despite the beneficial effect in the postural control in the frontal plane, the use of AB might constrain the distal joint motion which might lead to an extended knee landing posture resulting in secondary injuries to the knee joint. Therefore, the use of AB in conjunction with an additional training of landing strategy might be recommended from the injury prevention perspective.

This study aimed to explore the combined effects of having sleep problems and taking sleeping pills on the skeletal muscle mass and performance of community-dwelling elders. A total of 826 participants who have complete information regarding dual-energy X-ray absorptiometry examination, questionnaire, and physical performance tests were included. The status of having sleep problems and taking sleeping pills was assessed with a self-reported questionnaire. The prevalence rates of sleep problems among older men and women were 37.4% and 54.5%, respectively. After multivariate adjustment, the mean height-adjusted skeletal muscle indices for elders having sleep problems and taking sleeping pills among men and women were 7.29 and 5.66 kg/m2, respectively, which were lower than those without sleep problems (P = 0.0021 and P = 0.0175). The performance of the older men having sleep problems and taking sleeping pills in terms of walking speed, grip strength, and number of squats, was poorer than those of the older men without sleep problems. The status of having sleep problems and taking sleeping pills was correlated with low skeletal muscle mass and poor physical performance in community-dwelling elders. These findings suggest that having sleep problems and taking sleeping pills are associated with having sarcopenia among community elderly.

We investigated the association between blood pressure variability measured by the coefficient of variation (CV) of blood pressure and hip fracture in older persons with diabetes. After excluding patients with acute complications and comorbidities, a positive association with similar magnitude of strength was found between BP variability and hip fracture, compared with that in the original analysis. Hypertension is a risk factor of osteoporosis and hip fracture, but studies have yet to investigate whether blood pressure variability measured by the CV of blood pressure can predict hip fracture in older persons with diabetes. We conducted a retrospective cohort study on 21,160 patients who suffered from type 2 diabetes (age ≥ 50 years) and participated in the National Diabetes Care Management Program in Taiwan. The patients’ 1-year variability in systolic blood pressure (SBP) and diastolic blood pressure (DBP) at the baseline and subsequent hip fracture incidence for 8.2 years were analyzed. There were 937 recorded incident hip fractures. SBP-CV and DBP-CV were classified based on their tertiles. After multivariate adjustment was conducted, SBP-CV found to be a predictor of hip fracture, and its hazard ratio was 1.18 (95% CI 1.00–1.40) for the third tertile compared with the first tertile. Our study suggests SBP stability is a predictor for hip fracture incidence in older persons with type 2 diabetes.

The purposes of this study were to develop the Chinese-version betel quid dependence instrument (BQDI) and to test its reliability and validity. An item pool relevant to betel quid dependence was generated. A panel of three experts assessed content validity including content relevance, clarity, and domain coverage. A cross-sectional study was conducted, consisting of 113 participants from a construction site, betel quid stalls, and a teaching hospital in Taichung, Taiwan. Construct validity was assessed by hypothesizing a significant correlation between the BQDI score and number of pieces-years for betel quid chewing and betel quid biomarkers. The overall Cronbach's alpha coefficient was 0.94. Factor analysis indicated the BQDI consisted of a three-factor structure, including physical and psychological cravings, lack of resistance to betel quid, and maladaptive use. We observed significant associations of BQDI total and factor scores with arecaidine (adjusted odds ratio [OR] for medium total BQDI score: 12.87, 95% CI: 1.45–114.5; high total BQDI score: 28.9, 3.53–236.6) and N-methylnipecotate (medium total BQDI score: 6.18, 1.21–31.62; high total BQDI score: 13.10, 2.72–63.03, respectively). Our results provide preliminary good internal consistency and construct validation of the Chinese-version BQDI as a measure of betel quid dependence in community adults.

The evidence indicates that the optimal observation period following renal biopsy ranges between 6 and 8 h. This systematic review and meta-analysis explored whether differences exist in the complication rates of renal biopsies performed in outpatient and inpatient settings. Methods: We searched the MEDLINE, EMBASE, and the Cochrane Database of Systematic Reviews from 1985 to February 2020. Two reviewers independently selected studies evaluating the bleeding risk from renal biopsies performed in outpatient and inpatient settings and reviewed their full texts. The primary and secondary outcomes were risks of bleeding and major events (including mortality) following the procedure, respectively. Subgroup analysis was conducted according to the original study design (i.e., prospective or retrospective). Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated using a random effect meta-analysis. Heterogeneity was assessed using the I2 test. Results:Data from all 10 eligible studies, which included a total of 1801 patients and 203 bleeding events, were included for analysis. Renal biopsies in outpatient settings were not associated with a higher bleeding risk than those in inpatient settings (OR = 0.81, 95% CI, 0.59–1.11, I2 = 0%). The risk of major events was also comparable across both groups (OR = 0.45, 95% CI, 0.16–1.29, I2 = 4 %). Conclusions:Similar rates of bleeding and major events following renal biopsy in outpatient and inpatient settings were observed.

Background Few large-scale cohort studies have investigated the association between community acquired pneumonia and the use of angiotensin-converting enzyme inhibitors (ACEIs) or angiotensin II receptor blockers (ARBs). We aimed to study whether using ACEIs or ARBs had protective effects for community acquired pneumonia. Methods This database cohort study was conducted retrospectively in Taiwan. The hypertensive patients were the target population of this study. Patients with ARB use were defined as our first study cohort. The second study cohort comprised patients who used ACEI. Propensity-score matching at 1:1 was used between ARB users and non-ARB users. We recruited 67 944 participants for the ARB study and 58 062 participants for the ACEI study. The same matching was also performed between ACEI users and non-ACEI users. Cox proportional hazard regression was used to analyze the risk of the outcome of viral pneumonia. Results The hazard ratio of community acquired pneumonia for ARB users relative to non-ARB users was 0.33. The hazard ratio of community acquired pneumonia was 0.71 times in ACEI users compared with ACEI nonusers. In stratification analysis, both ARB and ACEI both exhibited a protective effect for community acquired pneumonia in each age and sex group. In the analysis of the effects of therapy duration, patients using ARB for fewer than 100 days exhibited a greater reduction in the risk of community acquired pneumonia (adjusted HR = 0.58) compared with the non-ARB cohort. For the ACEI study, patients who used ACEI for 121 to 450 days were more likely to exhibit reduced risks of community acquired pneumonia (adjusted HR = 0.5). Conclusion Both ACEI and ARB uses were associated with decreased risk of community acquired pneumonia infection.

Objectives We aimed to investigate whether the risk of diabetes mellitus (DM) is heightened in patients with prostate cancer receiving injection therapy. Methods Men diagnosed with prostate cancer between 2000 and 2012 were included in the case cohort, and men without prostate cancer were included as controls. Each patient with prostate cancer was matched with a control patient with the same index year, demographic variables and comorbidities, and comparisons were made using propensity score matching. The hazard ratio of DM was estimated using the Cox proportional hazards model. Results This cohort study consisted of 1213 patients with prostate cancer and 1213 control patients. The risk of DM in patients with prostate cancer was 1.60 times (95% CI = 1.12, 2.27) that of patients without prostate cancer. Compared with the controls, the hazard ratios of DM for patients with prostate cancer not receiving oral hormone therapy, patients with prostate cancer receiving oral hormone therapy, and patients with prostate cancer not receiving injection hormone therapy were 1.65 (95% CI = 1.01, 2.70), 1.57 (95% CI = 1.07, 2.70), and 1.94 (95% CI = 1.34, 2.81), respectively. The risk of DM in patients who received injection hormone therapy was 0.45 times (95% CI = 0.25, 0.82) that of patients who did not receive injection hormone therapy. Conclusion Patients with prostate cancer had an increased risk of DM compared with patients without prostate cancer. Patients with prostate cancer who received injection therapy had a lower risk of DM compared with those who did not.

Our study used data collected in Chung-Hsing Village in Taiwan in May 1998 to evaluate the distribution of triglycerides and the association between hypertriglyceridemia and its correlates in elderly people. All individuals aged 65 and over were recruited as study subjects. A total of 1093 persons, out of 1774 registered residents, were contacted in face-to-face interviews. The response rate was 61.6%. However, only 586 respondents had blood tests and completed questionnaires. Analysis in this study was based on these 586 subjects. To study the significant correlates of hypertriglyceridemia, t-tests, ANOVAs, chi-square analysis and multivariate logistic regression were used. Among the study population, 66.0% were men and 34.0% were women. The mean age was 73.1 ± 5.3 years. The mean triglyceride values were 1.65 ± 0.93 mmol/L in men and 2.02 ± 1.44 mmol/L in women (p < 0.01). The proportions of hypertriglyceridemia were 18.7% in men and 27.6% in women (p < 0.05). After controlling the other covariates, analysis by multivariate logistic regression showed that the factors significantly related to hypertriglyceridemia were high systolic pressure, abnormal glutamic pyruvic transaminase, hypercholesterolemia and hyperglycemia. Thus, these results support the hypothesis that it is important to examine the other cardiovascular risk factors if one cardiovascular risk factor is observed. The data also suggest one should determine the triglyceride level when abnormal glutamic pyruvic transaminase is identified in an elderly subject.

Aim This study aims to evaluate the associations between 3-year trajectories of metabolic risk factors and subsequent mortality in patients with type 2 diabetes. Methods A total of 6400 persons aged ≥ 30 years with type 2 diabetes and ≥ 3 years of follow-up period were included. The cluster analysis determined the patterns of 3-year trajectories, and Cox proportional hazards models evaluated the associations between patterns and mortality. Results Three trajectory subgroups of metabolic risk factors, namely, cluster 1, normal; cluster 2, high–stable or reducing with high level at baseline; and cluster 3, fluctuation: elevated and decreasing, were generated. The clusters 2 and 3 of body mass index (BMI), fasting plasma glucose (FPG), HbA1c, and triglyceride (TG) trajectories were associated with increased risks of all-cause mortality compared with cluster 1 (hazard ratio = 1.27, 95% confidence interval = 1.06–1.51 and 1.45, 1.19–1.78 for BMI; 1.41, 1.22–1.62 and 1.81, 1.38–2.38 for FPG; 1.42, 1.23–1.64 and 1.47, 1.23–1.75 for HbA1c; 1.34, 1.10–1.63 and 2.40, 1.30–4.37 for TG, respectively). For the systolic blood pressure trajectory, only cluster 3 was associated with an increased mortality risk relative to cluster 1 (1.76, 1.13–2.77). Conclusions Long-term metabolic risk factor trajectories may be associated with subsequent mortality.

Carotid intima&ndash, media thickness (IMT), plaque, and stenosis are widely used as early surrogate markers of subclinical atherosclerosis and strong predictors of future deaths and cardiovascular events. Albuminuria is an indicator of generalized endothelial dysfunction that speeds up atherosclerosis. However, previous studies reporting these associations cannot rule out the confounding effect of albuminuria. We aimed to examine the independent and joint relationships between IMT markers and 10-year mortality in community-dwelling Taiwanese adults. This work was a community-based prospective cohort study consisting of 2956 adults aged at least 30 years recruited in 2007 and followed up through 2019. Cox proportional hazard regression models were used to examine associations of these subclinical atherosclerosis markers with mortality. During an average of 9.41 years of follow up, 242 deaths occurred. The mortality rate was 8.70 per 1000 person-years. Compared with those with carotid IMT less than 1.0 mm, persons with severely increased carotid IMT (&ge, 2.0 mm) had an increased risk for death (hazard ratio (HR): 1.79, 95% confidence interval (CI): 1.07, 3.00). Compared with those without carotid plaque, persons with carotid plaque were more likely to have an increased risk for death (1.65, 1.21&ndash, 2.32). Compared with those with carotid stenosis less than 25%, persons with carotid stenosis of 25&ndash, 36% had a significant increased risk for death (1.57, 1.12&ndash, 2.22). Considering these three IMT markers along with the traditional risk factors (c-statistic: 0.85) significantly increased their predictive ability of mortality compared with any individual variable&rsquo, s predictive ability (all p-values &lt, 0.001 for comparisons of c-statistic values). Carotid IMT measures, including IMT thickness, carotid plaque, and carotid stenosis were significant independent predictors of mortality. Our study supports evidence of blood pressure-related media thickening markers to assess future mortality risks in Chinese adults of general population.

Aims A model has yet to be developed for predicting mortality in relation to the effect of glycemic and blood pressure variabilities, which are important clinical predictors of the mortality of patients, especially those with diabetes. This study aimed to develop and validate risk score systems by examining the effects of glycemic and blood pressure variabilities on the all-cause and expanded cardiovascular-specific mortality of persons with type 2 diabetes. Materials and methods This retrospective cohort study consisted of 9,692 patients aged 30-85 years, diagnosed with type 2 diabetes, and enrolled in a managed care program of a medical center from 2002 to 2016. All the patients were randomly allocated into two groups, namely, training and validation sets (2:1 ratio), and followed up until death or August 2019. Cox's proportional hazard regression was performed to develop all-cause and expanded cardiovascular-specific mortality prediction models. The performance of the prediction model was assessed by using the area under the receiver operating characteristic curve (AUROC). Results Overall, 2,036 deaths were identified after a mean of 8.6 years of follow-up. The AUROC-measured prediction accuracies of 3-, 5-, 10-, and 15-year all-cause mortalities based on a model containing the identified traditional risk factors, biomarkers, and variabilities in fasting plasma glucose, HbA1c, and blood pressure in the validation set were 0.79 (0.76-0.83), 0.78 (0.76--0.81), 0.80 (0.78--0.82), and 0.80 (0.78--0.82), respectively. The corresponding values of the expanded cardiovascular-specific mortalities were 0.85 (0.80--0.90), 0.83 (0.79--0.86), 0.80 (0.77--0.83), and 0.79 (0.77--0.82), respectively. Conclusions Our prediction models considering glycemic and blood pressure variabilities had good prediction accuracy for the expanded cardiovascular-specific and all-cause mortalities of patients with type 2 diabetes. This article is protected by copyright. All rights reserved.

Background Whether patients with end-stage renal disease (ESRD) have a higher risk of idiopathic polyneuropathy (IPN) than those without ESRD remains unclear. We hypothesised that carpal tunnel syndrome (CTS) is a prodrome of IPN in patients with ESRD. Methods Data were collected from the Taiwan National Health Insurance research database (NHIRD) for the 2000-2011 period. Two matching strategies, age- and sex-matching and propensity matching, were used, which yielded 2596 age- and sex-matched patients with ESRD and 2210 propensity-matched patients with ESRD. The comparison cohort was chosen in a 1:4 ratio for the age- and sex-matched method and in a 1:1 ratio for the propensity-matching method. The primary outcome was the incidence of IPN. Cox proportional hazards modelling was used. Results In the age- and sex-matched cohort, the IPN incidence was 7.64 and 2.88 per 1000 person-years for the ESRD and controls cohorts, respectively. After we adjusted for age, sex, comorbidities and medications relative to controls, having ESRD was significantly associated with increased risk of IPN (hazard ratio [HR] = 2.45, 95% confidence interval [CI] = 1.76-3.41). Competing risk of death as sensitivity analysis revealed that having ESRD with CTS was still associated with higher risk of IPN than having CTS without ESRD (HR = 2.85, 95% CI = 1.87-4.34). Conclusion Patients with ESRD with CTS had higher incidences of idiopathic peripheral neuropathy than those without ESRD with CTS.

Background Cognitive impairment is accompanied with high rates of comorbid conditions, leading ultimately to death. Few studies examine the relation between cognitive transition and mortality, especially in Asian population. This study evaluated baseline cognition and cognitive transition in relation to all-cause mortality among community-dwelling older adults. Methods We conducted a community-based prospective cohort study among 921 participants of Taichung Community Health Study for Elders in 2009. Cognitive function was evaluated by the Mini-Mental State Examination. Cognitive impairment was considered if the total score is less than 27, 24, and 21 for a participant’s educational level of more than 6 years, equal or less than 6 years, and illiteracy, respectively. One-year transition in cognitive function was obtained among 517 individuals who were assessed in both 2009 and 2010. Mortality was followed up until 2016. Cox proportional hazards models were applied to estimate the adjusted hazard ratios of mortality for baseline cognitive impairment and one-year transition in cognitive status. Results After a follow-up of 6.62 years, 160 deaths were recorded. The multivariate adjusted hazard ratio (95% confidence interval) for baseline cognitive impairment was 2.08 (1.43, 3.01). Significantly increased mortality risk was observed for cognitively impaired–normal and impaired–impaired subgroups over 1 year as compared with those who remained normal [2.87 (1.25, 6.56) and 3.79 (1.64, 8.73), respectively]. The area under the receiver operating characteristic curves demonstrated that baseline cognition and one-year cognitive transition had no differential predictive ability for mortality. Besides, there was an interaction of cognitive impairment and frailty, with an additive mortality risk [5.41 (3.14, 9.35)] for the elders who presented with both. Conclusion Baseline cognitive impairment rather than one-year progression is associated with mortality in a six-year follow-up on older adults.

Background There is emerging interest in multimorbidity in type 2 diabetes (T2D), which can be either concordant (T2D related) or discordant (unrelated), as a way of understanding the burden of disease in T2D. Current diabetes guidelines acknowledge the complex nature of multimorbidity, the management of which should be based on the patient’s individual clinical needs and comorbidities. However, although associations between multimorbidity, glycated haemoglobin (HbA1c), and mortality in people with T2D have been studied to some extent, significant gaps remain, particularly regarding different patterns of multimorbidity, including concordant and discordant conditions. This study explores associations between multimorbidity (total condition counts/concordant/discordant/different combinations of conditions), baseline HbA1c, and all-cause mortality in T2D. Methods and findings We studied two longitudinal cohorts of people with T2D using the UK Biobank (n = 20,569) and the Taiwan National Diabetes Care Management Program (NDCMP) (n = 59,657). The number of conditions in addition to T2D was used to quantify total multimorbidity, concordant, and discordant counts, and the effects of different combinations of conditions were also studied. Outcomes of interest were baseline HbA1c and all-cause mortality. For the UK Biobank and Taiwan NDCMP, mean (SD) ages were 60.2 (6.8) years and 60.8 (11.3) years; 7,579 (36.8%) and 31,339 (52.5%) were female; body mass index (BMI) medians (IQR) were 30.8 (27.7, 34.8) kg/m2 and 25.6 (23.5, 28.7) kg/m2; and 2,197 (10.8%) and 9,423 (15.8) were current smokers, respectively. Increasing total and discordant multimorbidity counts were associated with lower HbA1c and increased mortality in both datasets. In Taiwan NDCMP, for those with four or more additional conditions compared with T2D only, the mean difference (95% CI) in HbA1c was −0.82% (−0.88, −0.76) p < 0.001. In UK Biobank, hazard ratios (HRs) (95% CI) for all-cause mortality in people with T2D and one, two, three, and four or more additional conditions compared with those without comorbidity were 1.20 (0.91–1.56) p < 0.001, 1.75 (1.35–2.27) p < 0.001, 2.17 (1.67–2.81) p < 0.001, and 3.14 (2.43–4.03) p < 0.001, respectively. Both concordant/discordant conditions were significantly associated with mortality; however, HRs were largest for concordant conditions. Those with four or more concordant conditions had >5 times the mortality (5.83 [4.28–7.93] p, Jason Chiang and colleagues reveal the relationship between multimorbidity, HbA1c and all-cause mortality in 2 large cohorts., Author summary Why was this study done? People with type 2 diabetes (T2D) commonly have other coexisting chronic medical conditions (‘multimorbidity’). These conditions can be either concordant (T2D related) or discordant (T2D unrelated). Multimorbidity is associated with higher mortality and hypoglycaemia; however, the effect of multimorbidity on glycaemia (measured by glycated haemoglobin [HbA1c]) is mixed. Significant knowledge gaps remain, particularly regarding the prevalence and impacts of different patterns of multimorbidity, including concordant and discordant conditions, and their associations with HbA1c and mortality. What did the researchers do and find? We assessed the associations between different counts of multimorbidity, including concordant and discordant conditions, and HbA1c and the effects of different combinations of conditions on all-cause mortality in people with T2D. In two large community cohorts of people with T2D (UK Biobank and Taiwan National Diabetes Care Management Program [NDCMP]), we found that increasing multimorbidity is significantly associated with increased mortality and with lower HbA1c. The combinations of conditions with the greatest association with mortality differed between UK Biobank, a population predominantly comprising people of European descent, and the Taiwan NDCMP, a predominantly ethnic Chinese population. What do these findings mean? To our knowledge, this is the first study to assess and compare the relationship between total, concordant, and discordant multimorbidity counts; HbA1c; and all-cause mortality in people with T2D or to look at the effects of such a range of combinations of comorbid conditions. Our findings suggest the need for further research to explore the effects of different combinations of conditions on outcomes in those with T2D across different ethnic groups. Our findings suggest that poor glycaemic control is unlikely to explain the increased mortality seen in those with increasing multimorbidity count.

Background: Ankle support has been utilized for athletes with functional ankle instability (FAI), however, its effect on the landing performance during muscle fatigue is not well understood. This study aimed to examine the effects of ankle supports (ankle brace vs. Kinesio tape) on athletes with FAI following fatigued single-leg landing. Methods: Thirty-three young FAI athletes (CAIT scores &lt, 24) were randomly allocated to control (Cn), ankle brace (AB) and Kinesio tape (KT) groups. All athletes performed single-leg lateral drop landings following ankle fatigue protocol. The fatigue-induced changes in kinetic parameters were measured among three groups. Results: A significant increase in peak vertical ground reaction force (vGRF) was found in the AB group (0.12% body weight (BW)) compared to that of the KT (0.02% BW) and Cn (median = 0.01% BW) groups. Significant decrease in both COP medial-lateral (ML) and anterior-posterior (AP) ranges were also found in the KT group (median = &minus, 0.15% foot width (FW) &amp, median = &minus, 0.28% foot length (FL)) than those of the Cn group (median = 0.67% FW&amp, median = 0.88% FL). Conclusions: Ankle braces might hamper the ability to absorb the impact force during landing. On the other hand, Kinesio tape might be beneficial for the postural control during landing.

Aims This study compared the incidence rates of patients with diabetes mellitus (DM) and patients without DM with percutaneous coronary intervention (PCI) in a national population-based cohort to determine if the patients with DM have an increased risk of adverse outcomes. Methods We performed a retrospective cohort study among 92,624 patients with and without DM, who underwent PCI for the first time in 2000–2008. The patients were identified from National Health Insurance Program Database through propensity score matching. Endpoints were the occurrence of PCI adverse outcomes, including myocardial infarction (MI), need for target vessel revascularization by either bypass surgery or repeat PCI, all-cause mortality or 2011/12/31. Incidence rate was calculated and hazard ratios of PCI adverse events were estimated using Cox’s proportional hazard regression model. Results During the mean six-year follow up, the rates of MI (incidence rate 20.96 vs. 15.59 per 1,000 person-years), bypass surgery (incidence rate 8.15 vs. 5.15 per 1,000 person-years), all-cause mortality (incidence rate 6.20 vs. 4.72 per 1,000 person-years), and the composite measure of MI, repeat PCI, bypass surgery, all-cause mortality (incidence rate 37.31 vs. 28.14 per 1,000 person-years) were higher in patients with DM. The corresponding hazard ratios (HRs) and their 95% confidence intervals (CIs) were 1.34 (95% CI: 1.29, 1.39), 1.46 (1.38, 1.56), 1.34 (1.25, 1.44), and 1.31 (1.27, 1.35). However, the repeat PCI rate (incidence rate 2.65 vs. 2.70 per 1,000 person-years; with an adjusted HR of 0.97 (0.88, 1.07) was not statistically different. Conclusions This nationwide retrospective cohort study determined a positive correlation between PCI adverse events and DM. As the prevalence of DM and PCI continues to increase, novel treatments and intensified surveillance coronary angiography for high risk patients are needed.

Background: Direct evidence of lung cancer risk in Asian users of angiotensin-converting enzyme inhibitors (ACEIs) is lacking. Methods: The ACEI cohort comprised 22,384 patients aged &ge, 18 years with a first prescription of ACEI. The comparison angiotensin receptor blocker (ARB) cohort consisted of age-, sex- and comorbidity-matched patients at a ratio of 1:1. The primary outcome was the incidence of lung cancer, which was evaluated using a proportional hazard model. Results: The overall incidence rates of lung cancer in the ACEI and ARB cohorts were 16.6 and 12.2 per 10,000 person-years, respectively. The ACEI cohort had a significantly higher risk of lung cancer than the ARB cohort (adjusted hazard ratio [aHR]. = 1.36, 95% confidence interval [CI]. = 1.11&ndash, 1.67). Duration&ndash, response and dose&ndash, response analyses revealed that compared with patients who did not receive ACEIs, patients who received ACEIs for more than 45 days per year (aHR = 1.87, 95% CI = 1.48&ndash, 2.36) and patients who received more than 540 defined daily doses of ACEIs per year (aHR =1.80, 95% CI = 1.43&ndash, 2.27) had a significantly higher risk of lung cancer. The cumulative incidence of lung cancer was also significantly higher in the ACEI cohort than in the ARB cohort (log-rank test, p = 0.002). Conclusions: ACEI use is associated with an increased risk of lung cancer compared with ARB use. Patients using ARBs have a significantly lower risk of lung cancer than non-ARB users.

Background: The objective of this study was aimed to investigate whether sleep apnea patients had a higher risk of traumatic brain injury. Methods: Data were collected from the Taiwan Longitudinal Health Insurance Database during the period of 2000–2012. The study cohort comprised 6,456 patients aged ≥20 years with a first diagnosis of sleep apnea. The primary outcome was the incidence of traumatic brain injury. Kaplan-Meier survival analysis and Cox proportional-hazards modeling were used. Results: After adjustments for associated comorbidities and hypnotic medications, sleep apnea patients were associated with a 1.19-fold higher risk of traumatic brain injury (95% CI, 1.07–1.33) compared with patients without sleep apnea. Sleep apnea patients who took benzodiazepine (BZD) had a 1.30-fold increased risk of traumatic brain injury compared with patients without sleep apnea (95% CI, 1.14–1.49). However, this risk was not statistically significant, with a 1.03-fold risk of traumatic brain injury in sleep apnea patients without BZD use (95% CI, 0.84–1.25) compared with patients without sleep apnea. Compared with patients without sleep apnea, the risk of traumatic brain injury in sleep apnea patients aged 65–79 years old was higher (adjusted hazard ratio, 1.36; 95% CI, 1.06–1.74). Conclusion: Sleep apnea patients, regardless of hypnotic use, had a higher risk of traumatic brain injury compared with patients without sleep apnea.

Background This study investigated whether visit-to-visit fasting plasma glucose (FPG) variability, as measured by the coefficient of variation (CV), increased peripheral artery disease (PAD) risk. Methods Individuals with type 2 diabetes from the National Diabetes Care Management Program during the period 2002–2004, ≥ 30 years of age, and free of PAD (n = 30,932) were included and monitored until 2011. Cox proportional hazards regression models were implemented to analyze related determinants of PAD. Results A total of 894 incident cases of PAD were identified during an average 8.2 years of follow-up, resulting in a crude incidence rate of 3.53 per 1000 person-years. Both FPG-CV and HbA1c were significantly associated with PAD after multivariate adjustment, with corresponding hazard ratios of 1.24 [95% confidence interval (CI) 1.04–1.47] for FPG-CV in the third tertile and 1.50 (95% CI 1.10–2.04) for HbA1c ≥ 10%. The findings of the sensitivity analysis remained consistent after excluding potential confounders, demonstrating the consistency of the results. Conclusions The associations between HbA1c, variability in FPG-CV, and PAD suggest a linked pathophysiological mechanism, suggesting the crucial role of glycemic variability in clinical management and therapeutic goals in preventing PAD in type 2 diabetes.

Background: Association between hydroxychloroquine (HCQ) and bacterial infections required to be determined. Whether hydroxychloroquinehad use could reduce lesser risk of bacterial infections are unknown. We aimed to conduct a retrospective cohort propensity-matching study to investigate the association between HCQ use and the incidence of bacterial pneumonia in rheumatic patients. Methods: The Longitudinal Health Insurance Database (LHID), a one million extract from Taiwan National Health Insurance Research Database (NHIRD) of 23 million Taiwanese populations was used. We included patients who newly diagnosed rheumatic and immune disease (ICD-9-CM codes 696.0, 710, 714) within 2000-2012.HCQ users and nonusers were then matched according to age, sex, urbanization level, monthly income, comorbidities and medications in the ratio of 1:1 by the propensity score matching. Cox proportional hazard model was used to evaluate the risk of bacterial pneumonia in rheumatic patients who used HCQ and who did not use HCQ. Results: There were total 3285 patients with rheumatic and immune disease enrolled. The cumulative incidence curve of patients with the use of HCQ sulfate had no difference to that of patient without the use of HCQ sulfate in propensity score matched cohort, (Log-rank test: p-value=0.5). However, patients used HCQ sulfate for more than 1400 average use days had a lesser risk of bacterial pneumonia (adjusted HR=0.55, 95% CI=0.35, 0.89) in the cohort matched, with regarding HCQ nonusers as a reference. Conclusion: Rheumatic patients taking HCQ had no overall significant differences of bacterial pneumonia incidences compared with rheumatic patients not taking HCQ. HCQ used more than >1400 days was associated with lower risk of bacteria pneumonia. Funding Statement: This study is supported in part by Taiwan Ministry of Health and Welfare Clinical Trial Center (MOHW109-TDU-B-212-114004), China Medical University Hospital (CMU107-ASIA-19, DMR-109-231); MOST Clinical Trial Consortium for Stroke (MOST 108-2321-B-039-003-), Tseng-Lien Lin Foundation, Taichung, Taiwan. No additional external funding was received for this study. Declaration of Interests: The authors declare no conflict of interest. Ethics Approval Statement: This study was approved by the Institutional Review Board of the China Medical University Hospital (CMUH104-REC2-115(AR-4)).

Prediction model mainly focused on specific diseases, such as diabetes, hypertension, cardiovascular disease, or patients with cancer, or populations of Europe and America, thereby limiting its generalization. This study aimed to develop and validate a 10-year mortality risk score by using data from a population-representative sample of adults. Data were collected from 2,221 Taichung Community Health study participants aged ≥40 years. The baseline period of the study was 2004, and all participants were followed up until death or in 2016. Cox’s proportional hazards regression analyses were used to develop the prediction model. A total of 262 deaths were ascertained during the 10-year follow-up. The all-cause mortality prediction model calculated the significant risk factors, namely, age, sex, marital status, physical activity, tobacco use, estimated glomerular filtration rate, and albumin-to-creatinine ratio, among the baseline risk factors. The expanded cardiovascular disease (CVD) mortality prediction model consisted of six variables: age, sex, body mass index, heart disease plus heart disease medication use, stroke plus medication use, and ankle–brachial index. The areas under receiver operating curves of the 3-, 5- and 10-year predictive models varied between 0.97, 0.96, and 0.88 for all-cause mortality, and between 0.97, 0.98, and 0.84 for expanded CVD mortality. These mortality prediction models are valid and can be used as tools to identify the increased risk for mortality.

Aim This study aims to develop and validate a lower extremity amputation (LEA) risk score system in persons with type 2 diabetes. Methods A retrospective population-based cohort study was conducted among eligible 21,484 participants in the derivation set and 10,742 participants in the validation set who were enrolled in the Taiwan National Diabetes Care Management Program. The risk score system was developed following the steps proposed by the Framingham Heart Study with a Cox proportional hazards model algorithm. Discrimination ability was assessed by the receiver operating characteristic curve, and calibration was performed by Hosmer–Lemeshow test. Results A total of 504 patients developed LEA at an average follow-up of 7.4 years. The point scores were derived from 15 predictors as follows: age, gender, duration of type 2 diabetes, body mass index, HbA1c, triglyceride, eGFR, variation of fasting blood glucose, comorbidities of stroke, diabetes retinopathy, hypoglycemia and foot ulcer, anti-diabetes medication, and use of diuretics and nitrates. The c-statistics for predicting 3-, 5-, and 8-year LEA risks were 0.80 [95% confidence interval (CI) 0.76–0.83], 0.78 (0.75–0.81), and 0.76 (0.74–0.79) in the derivation set, respectively, and 0.81 (0.76–0.85), 0.77 (0.73–0.81), and 0.74 (0.71–0.77) in the validation set, respectively. Conclusions A new risk score for LEA was developed and validated in the clinical setting with good discriminatory ability. Poor glycemic control, glucose variation, comorbidities, and medication use were identified as predictive factors for LEA in patients with type 2 diabetes.

Objectives Diabetes is a major cause of hospitalization and in-hospital mortality. However, a scoring system that can be used to identify diabetic patients at risk of diabetes-related hospitalization and in-hospital mortality is lacking. Methods We included 32,653 patients in this retrospective cohort study. All recruited patients had type 2 diabetes, were 30–84 years of age, and were enrolled in the National Diabetes Care Management Program over the period of 2001–2003. We used the Cox proportional hazard regression model to derive risk scores. The predictive accuracy of the models was evaluated using receiver operating characteristic curves. We conducted the Hosmer–Lemeshow test to assess the agreement between predicted and observed risks. Results Over a follow-up period of eight years, 6243 patients were hospitalized for diabetes-related events, and 2048 deaths were registered in hospital records. For the one-, three-, five-, and eight-year periods, the areas under the curve (AUC) for diabetes-related hospitalization in the validation set were 0.80, 077, 0.76, and 0.74, respectively. The corresponding values for in-hospital mortality in the validation set were 0.87, 080, 0.77, and 0.76. The goodness-of-fit test showed that the predicted and observed probabilities in the one-, three-, five-, and eight-year periods were similar for diabetes-related hospitalization and in-hospital mortality in the validation set (all p values > 0.05). Conclusion We developed models for the estimation of the risks of diabetes-related hospitalization and in-hospital mortality in patients with type 2 diabetes. The models may be used to identify diabetic patients who are at high risk for hospital admission and in-hospital mortality.

Aims The study evaluated associations between 3-year eGFR trajectory patterns and adverse renal event in diabetic patients. Methods Adverse renal event was defined as sustained eGFR 300 mg/g creatinine. Cox proportional hazards models evaluated association between eGFR trajectory patterns and adverse renal event. Results We detected six clusters. Cluster 1 had a stable but relatively low baseline eGFR level (n = 823, 20.52%), cluster 2 had a high baseline eGFR level, but slightly decreased afterwards (n = 1708, 42.59%), cluster 3 had an increasing eGFR during the first 15-month follow-up and then a decline rate (n = 505, 12.59%), cluster 4 decreased during the first 9-month follow-up and then remained stable (n = 774, 19.30%), cluster 5 had a sharp decline and then was elevated after 21 months until the end of follow-up (n = 135, 3.37%), and cluster 6 had an extremely fluctuating eGFR and then a sharp increase at the last 12-month period (n = 65, 1.62%). Clusters 1, 3, and 4 show increased adverse renal risks compared with cluster 2 (2.24, 1.69–2.97; 2.70, 2.02–3.61; and 2.15, 1.64–2.83, respectively). Conclusions Patients with sustained low-level renal function, renal decline, or increasing trend in eGFR trajectory encountered an increased CKD risk.

Background: Air pollutants cause endocrine disorders and hormone disruption. The relationship between air pollutants and polycystic ovary syndrome (PCOS) must be carefully investigated using a nationwide cohort. Methods: Data were extracted from two nationwide databases, namely Longitudinal Health Insurance Database and Taiwan Air Quality Monitoring Database, and analyzed. The study considered a range of data that began on 1 January 2000 and ended on 31 December 2013. Women diagnosed with PCOS were excluded. From the residential data, the study assessed the daily concentrations of sulfur dioxide (SO2), nitrogen oxides (NOx), nitrogen monoxide (NO), nitrogen dioxide (NO2), and PM2.5 the women were exposed to. A Cox proportional hazard regression model was applied to assess PCOS risk. Results: In total, 91,803 women were enrolled in this study, of those women, 2072 developed PCOS after 12 years of follow-up. The mean daily concentrations of SO2, NOx, NO, NO2, and PM2.5 women were exposed to were 4.25 (&plusmn, 1.44) ppb, 20.41 (&plusmn, 6.65) ppb, 9.25 (&plusmn, 4.36) ppb, 20.99 (&plusmn, 3.33) ppb, and 30.85 (&plusmn, 6.16) &mu, g/m3, respectively. Compared with the first-quartile levels of exposure, the fourth-quartile levels of exposure to SO2, NOx, NO, NO2, and PM2.5 increased PCOS risk by 10.31 times (95% CI = 8.35&ndash, 12.7), 3.37 times (95% CI = 2.86&ndash, 3.96), 4.18 times (95% CI = 3.57&ndash, 4.89), 7.46 times (95% CI = 6.38&ndash, 8.71), and 3.56 times (95% CI = 3.05&ndash, 4.15), respectively. Conclusion: Women exposed to a high concentrations of air pollutants, namely SO2, NO, NO2, NOx, and PM2.5, had a high PCOS risk.

Background Multiple sclerosis (MS) is the most common inflammatory demyelinating disease of the central nervous system. Few studies focused on the relationship between septicemia and MS. Aim To evaluate the potential impact of septicemia on risk for MS. Design Two cohorts of patients with septicemia and without septicemia were followed up for the occurrence of MS. Methods Patients of 482 790 with septicemia was enrolled from the National Health Insurance Research Database between 2001 and 2011 as the study group to match the 1 892 820 individuals, as the control group, by age and gender. Incidence of MS in both groups was calculated. Cox proportional-hazards regressions were performed for investigating hazard ratios (HR) for MS between groups. Results Septicemia patients had a 3.06-fold (95% CI: 2.16-4.32, P

Background and purpose No study has established a prediction dementia model in the Asian populations. This study aimed to develop a prediction model for dementia in Chinese type 2 diabetes patients. Methods The retrospective cohort study included 27 540 Chinese type 2 diabetes patients (aged 50-94 years) enrolled in the Taiwan National Diabetes Care Management Program. Participants were randomly allocated into derivation and validation sets at a 2:1 ratio. Cox proportional hazards regression models were used to identify risk factors for dementia in the derivation set. Steps proposed by the Framingham Heart Study were used to establish a prediction model with a scoring system. Results The average follow-up was 8.09 years, with a total of 853 incident dementia cases in the derivation set. The dementia risk score summed up the individual scores (from 0 to 20). The areas under the curve of 3-, 5- and 10-year dementia risks were 0.82, 0.79 and 0.76 in the derivation set and 0.84, 0.80 and 0.75 in the validation set, respectively. Conclusions The proposed score system is the first dementia risk prediction model for Chinese type 2 diabetes patients in Taiwan.

Organic–inorganic hybrid two-dimensional (2D) perovskites have recently attracted great attention in optical and optoelectronic applications due to their inherent natural quantum-well structure. We report the growth of high-quality millimeter-sized single crystals belonging to homologous two-dimensional (2D) hybrid organic–inorganic Ruddelsden–Popper perovskites (RPPs) of (BA)2(MA)n−1PbnI3n+1 (n = 1, 2, and 3) by a slow evaporation at a constant-temperature (SECT) solution-growth strategy. The as-grown 2D hybrid perovskite single crystals exhibit excellent crystallinity, phase purity, and spectral uniformity. Low-threshold lasing behaviors with different emission wavelengths at room temperature have been observed from the homologous 2D hybrid RPP single crystals. Our result demonstrates that solution-growth homologous organic–inorganic hybrid 2D perovskite single crystals open up a new window as a promising candidate for optical gain media.

Aims A risk scoring system for predicting ischemic stroke incidence may identify type 2 diabetes patients at high risk for ischemic stroke who can benefit from preventive intervention programs. Such a risk scoring system can serve as a benchmark to test novel putative risk factors. Methods The study adopted a retrospective cohort, including 28,124 Chinese patients with type 2 diabetes aged 30–84 years during 2001–2004. Participants were randomly assigned to the derivation and validation sets at a 2:1 ratio. Cox’s proportional hazard regression model was used to identify risk factors of ischemic stroke incidence in the derivation set. And then the steps proposed by the Framingham Heart Study for establishing an ischemic stroke prediction model with a scoring system was used. Results Among 9374 patients in the validation set, 1076 subjects (11.48%) developed ischemic stroke with a mean follow up period of 8.0 years. We identified the following risk factors: age, gender, smoking habit, duration of type 2 diabetes, blood pressure, HbA1c level, total cholesterol to high-density lipoprotein ratio, creatinine, fasting plasma glucose variation (FPG-CV), arterial embolism and thrombosis, diabetes retinopathy, hypoglycemia, anti-diabetes medication use, and cardiovascular medication. The area under receiver operating characteristic curve of the 3-year, 5-year, and 8-year ischemic stroke incidence risks were 0.72, 0.71, and 0.68 for the validation set, respectively. Conclusions This proposed ischemic stroke incidence risk prediction model is the first model established for Chinese patients with type 2 diabetes recruited from nationwide clinical settings.