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Abstract Objectives To explore the short- and long-term effects of glycemic management—through glycemic treatment and blood glucose monitoring (BGM)—on stroke recurrence and mortality specifically in patients experiencing a first-ever ischemic stroke (FIS) with hyperglycemia (FISHG) who have not previously been diagnosed with diabetes mellitus (DM). Methods We gathered data on patients who were registered on Taiwan’s National Health Insurance Research Database from 2000 to 2015. We one-fold propensity-score-matched (by sex, age, and index date) 207,054 patients into 3 cohorts: those with FIS (1) without hyperglycemia, (2) hyperglycemia without glycemic treatment, and (3) hyperglycemia with glycemic treatment. We used Cox proportional hazard regression to evaluate the short- (within 1 year after FIS) and long-term (9.3 ± 8.6 years after FIS) prognostic effects of glycemic management on stroke recurrence and mortality of FISHG. Results Stroke recurrence and mortality were significantly more likely in the patients with FISHG than their counterparts without hyperglycemia (p 0.05). Integrating BGM with glycemic treatment in the FISHG cohort significantly reduced the risk of stroke recurrence compared to patients receiving only glycemic treatment at 1-month, 3-month, 6-month, and 1-year post-stroke follow-ups (adjusted hazard ratios = 0.84, 0.90, 0.88, and 0.92, respectively); additionally, this approach significantly decreased mortality risk at each post-stroke follow-up period (p

Abstract Infectious intestinal diseases (IIDs) pose a significant health and economic burden worldwide. Recent observations at the Tri-Service General Hospital, Taiwan, suggest a potential association between IIDs and neurodegenerative diseases, prompting an investigation into this relationship. This study explored interactions between IIDs and neurodegenerative diseases. We conducted a population-based retrospective cohort analysis using data from the National Health Insurance Research Database (NHIRD) of Taiwan. Patients diagnosed with IIDs between 2000 and 2015 were identified along with a matched control group. Covariates, including demographics, comorbidities, and healthcare utilization were considered. The hazard ratios (HRs) of neurodegenerative diseases were assessed using a Cox proportional regression analysis. This study included 297,438 patients: 99,146 and 198,292 patients in the IID and control groups, respectively. Patients with IIDs showed a significantly higher overall risk of neurodegenerative diseases (adjusted hazard ratio [aHR] = 1.144, P

Background Pandemic influenza virus is a public health issue, and the neuraminidase inhibitors (NIs) “Oseltamivir” and “Zanamivir” are effective treatments. While teenagers use NIs, there are concerns regarding neuropsychiatric adverse events (NPAEs). Aim We aimed to use the Taiwan National Health Insurance Research Database to identify the correlation between NPAEs and NIs use in teenagers aged 13–19 years. Methods The final population between 2000 and 2015 included in this study was 3698 individuals, with 2287 individuals having received “Oseltamivir” and “Zanamivir” (study cohort group) and 9148 individuals not receiving “Oseltamivir” and “Zanamivir” (comparison cohort group). We initially used a multivariate Cox regression analysis during the tracking period to determine the cumulative incidence of NPAEs. Results Our findings revealed no significant increase in the likelihood of developing NPAEs in the study group. The Kaplan–Meier survival curve demonstrated that individuals who received “Oseltamivir” and “Zanamivir” were not associated with statistically significantly increased NPAEs compared with controls (log-rank test, P = 0.724). Conclusion No more risk in comparison of the normal population in our study, and the safety of “Oseltamivir” and “Zanamivir” is established treatments for influenza.

BackgroundEctopic pregnancy (EP) occurs when a fertilized ovum is implanted outside the uterine cavity. Its incidence is 2% of all pregnancies and is known to decrease fertility. This study aimed to measure pregnancy rates after EP, identify the various parameters influencing pregnancy, and compare these variables in women with and without a history of EP, as well as determine in which medical facilities women with EP seek medical help.MethodsThe data was extracted from the National Health Insurance Research Database during 2000–2013. The study group included of women with a history of one EP (study group) and women without EP (control group). The chi-square/Fisher exact test was performed for categorical variables, and t-tests were used for continuous variables.ResultsThe EP group had a higher cumulative pregnancy rate (41.55%) than the control group (37.14 %), and a 1.16 times higher rate in developing pregnancy (p < 0.001). While the pregnancy rate in the EP group was initially lower than in the control group during the first 5 years, it surpassed the control group’s rate between the 10th and 14th years.ConclusionsFecundability after EP was lower at the beginning but increased at long-term follow-up.

Abstract Background Hearing loss has been shown to be a risk factor for psychiatric disorders. In addition, long-term hearing loss is associated with increased hospitalization and mortality rates; however, the increased risk and duration of effect of hearing loss in combination with other chronic diseases on each psychiatric disorder are still not clearly defined. The purpose of this article is to clarify the risk of hearing loss for each disorder over time. Methods This was a retrospective cohort study, and a national health insurance research database in Taiwan was utilized. All (n = 1,949,101) Taiwanese residents who had a medical visit between 2000 and 2015 were included. Patients with hearing loss and a comparative retrospective cohort were analyzed. Every subject was tracked individually from their index date to identify the subjects who later received a diagnosis of a psychiatric disorder. The Kaplan‒Meier method was used to analyze the cumulative incidence of psychiatric disorders. Cox regression analysis was performed to identify the risk of psychiatric disorders. Results A total of 13,341 (15.42%) and 31,250 (9.03%) patients with and without hearing loss, respectively, were diagnosed with psychiatric disorders (P

Background/Objectives: According to the 2023 Ministry of Health and Welfare statistics, the suicide rate among adolescents aged 15 to 24 has steadily increased since 2018, from 3.7 to 5.5 per 100,000 populations, reaching a recent high. Although previous studies have pointed out that the future risk of suicide of those who had suffered from abuse was higher than that of the general population, researchers seldom focused on adolescent groups. Therefore, the aim of this study was to explore the risk of suicide after youth violence and the impact of subsequent comorbid mental illness and suicide risk. Methods: This retrospective matched cohort study analyzed data from the NHIRD, covering the period from 2000 to 2015. A total of 976 cases aged 10–18 who had experienced violence were included in this study. Controlled grouping was conducted by 1:10 matching based on gender, age, and the time of medical treatment, and a control group who had not experienced violence was selected for comparison. We used the Cox proportional hazards model to analyze the risk of suicide among adolescents after exposure to violence. Results: The suicide rate among adolescents who have experienced violence was significantly higher than that of the control group after 15 years of follow-up (1.0% vs. 0.5%). The prevalence of mental illness or disorders in adolescents exposed to violence was significantly higher than in the control group (45.2% vs. 40.1%). Among adolescents who had experienced violence, the methods of suicide included poisoning (solid and liquid) (53.6% vs. 43.2%), hanging (1.2% vs. 0.6%), firearms (2.4% vs. 0%), and cutting instruments (27.4% vs. 22.8%), all of which were significantly higher than in the control group. After adjusting for gender, age, residential area, and mental health comorbidities, the risk of suicide in those who had experienced violence was 1.475 times that of the control group (95% CI = 1.125–1.933; p = 0.005). Conclusions: In this study, female, younger age, and comorbid mental disorders were identified as risk factors for suicide among the adolescent victims of violence. Exposure to youth violence was associated with an increased prevalence of emotional disorders, including depression and social isolation, which subsequently elevated the suicide risk. These findings underscore the urgent need for governmental attention to the mental health of adolescent victims of violence. Implementing targeted psychological support and intervention programs could play a crucial role in mitigating the risk of suicide among this vulnerable population.

BackgroundDementia poses a growing global mental health impact, with variations in prevalence by gender, possibly influenced by reproductive factors. Ectopic pregnancy (EP), known for its association with cardiovascular diseases and depression, which are also predictors of dementia, prompted an exploration of their interplay.MethodsUsing Taiwan’s National Health Insurance Research Database, this nationwide cohort study examined 53,096 individuals to investigate the link between EP and dementia. Covariates included age, insured premiums, comorbidity by Charlson Comorbidity Index revised by excluding dementia, level of care, and residence. Surgical approaches, number of EP episodes, and dementia subtypes were considered in outcomes analysis using Cox regression.ResultsAmong 13,274 women diagnosed with EP, 791 developed dementia over a 15-year follow-up, particularly vascular dementia. Adjusting for the covariates, the adjusted sub-distribution Hazard Ratio (asHR) with competing risks was 1.644 (95% CI, 1.394–2.053; p < 0.001). For patients with more than one episode, it was even higher (asHR=1.670 [95% CI, 1.419–2.092; p < 0.001]). Post-ectopic depression, prevalent in 62.2% within four weeks, was associated with a greater dementia risk compared to those without (asHR=1.702 [95% CI, 1.444-2.125; p

Abstract Introduction Hypothyroidism is a rare and possible cause of hyponatremia. However, the clinical epidemiology and risk of mortality (ROM) when they coexist still remain elusive. Objectives We assessed the epidemiology and ROM among index patients with coexisting hypothyroidism and hyponatremia via a national population database. Patients and methods This retrospective cohort study utilized Taiwan’s National Health Insurance program database. Distributions of definite sociodemographic factors were analyzed. The annual incidence among the overall group and sex-subgroups was investigated. In addition, potential factors influencing the ROM were also evaluated. Results Of 4,549,226 patients from 1998 to 2015, a total of 3,140 index patients with concurrent hypothyroidism and hyponatremia were analyzed. The incidence rate increased tenfold from 1998 to 2015; average annual incidence rate was 174. Among the total participants, 57.1% were women; mean age was 72.6 ± 14.7 years and 88.8% were aged > 55 years. Although average length of stay (LOS) was 13.1 ± 15.4 days, the mortality group had significantly longer LOS than that in the survival group (12.9 days vs 22.2 days). Old age, catastrophic illness, cardiac dysrhythmia, and low hospital hierarchy were independent predictors of hospital mortality. The optimal LOS cutoff value for ROM prediction was 16 days. Index patients with LOS > 16 days increased ROM by 2.3-fold. Conclusions Coexistent hypothyroidism and hyponatremia is rare, although the incidence increased gradually. Factors influencing the ROM, such as old age, underlying catastrophic status, cardiac dysrhythmia, hospital hierarchy, and LOS should be considered in clinical care.

Abstract Background and aims Domestic violence (DV) are one of the important risk factors for women’s health outcomes. The aim of this study was explored the risk of DV association with the poor pregnancy outcomes (PPOs), including premature delivery, abortion, and stillbirth. Methods A nested case–control study was applied. Data from the Taiwan National Health Insurance Research Database were collected from 2000 to 2015. A total of 41,730 participants were included in this study, including 8,346 participants in the case group and 33,384 age- and index year-matched control group. Assessments of DA and PPOs were determined according to the International Classification of Diseases, 9th Revision. We conducted a conditional logistic regression analysis to estimate the effect of DV on PPOs. Results The mean age was 35.53 in the 41,730 female participants. The overall incidence rate of PPOs of the participants, who had experienced DV, was 84.05 per 100,000 person-years. which was significantly higher than that for the controls (18.19 per 100,000 person-years). The risk of PPOs was higher in the participants who had experienced DV than in the controls (adjusted odds ratio [AOR] = 3.31; 95% confidence interval [CI] [95% CI]: 2.83–3.86), including for premature delivery (AOR = 3.57; 95% CI: 3.05–4.17), abortion (AOR = 3.31; 95% CI: 2.83–3.86) and stillbirth (AOR = 2.98; 95% CI: 2.55–3.47). The results showed that the longer a participant has been suffering DV, the risk of PPOs was higher. Conclusions Present results reaved the risk of PPOs associated with DV. Especially, the longer a woman has been experiencing DV, the risk of PPOs was higher, showed a dose–response effect.

Objectives To evaluate whether nephrotic syndrome (NS) and further corticosteroid (CS) use increase the risk of osteoporosis in Asian population during the period January 2000–December 2010.Design Nationwide population-based retrospective cohort study.Setting All healthcare facilities in Taiwan.Participants A total of 28 772 individuals were enrolled.Interventions 26 614 individuals with newly diagnosed NS between 2000 and 2010 were identified and included in out study. 26 614 individuals with no NS diagnosis prior to the index date were age matched as controls. Diagnosis of osteoporosis prior to the diagnosis of NS or the same index date was identified, age, sex and NS-associated comorbidities were adjusted.Primary outcome measure To identify risk differences in developing osteoporosis among patients with a medical history of NS.Results After adjusting for covariates, osteoporosis risk was found to be 3.279 times greater in the NS cohort than in the non-NS cohort, when measured over 11 years after NS diagnosis. Stratification revealed that age older than 18 years, congestive heart failure, hyperlipidaemia, chronic kidney disease, liver cirrhosis and NS-related disease including diabetes mellitus, hepatitis B infection, hepatitis C infection, lymphoma and hypothyroidism, increased the risk of osteoporosis in the NS cohort, compared with the non-NS cohort. Additionally, osteoporosis risk was significantly higher in NS patients with CS use (adjusted HR (aHR)=3.397). The risk of osteoporosis in NS patients was positively associated with risk of hip and vertebral fracture (aHR=2.130 and 2.268, respectively). A significant association exists between NS and subsequent risk for osteoporosis.Conclusion NS patients, particularly those treated with CS, should be evaluated for subsequent risk of osteoporosis.

(1) Background: Diabetes mellitus (DM) induces oxidative stress and inflammation with negative effect on pregnancy outcomes. This study aimed to determine whether DM increases the risk of pregnancy loss and to identify other potential risk factors; (2) Methods: We identified female patients diagnosed with DM from 2000–2015 in the Taiwanese National Health Insurance Research Database according to the International Classification of Diseases, Ninth Edition, Clinical Modification (ICD-9 CM) code 250. The event was pregnancy loss, defined as ICD-9 CM codes 630–639, which was tracked until 31 December 2015. The control group included 4-fold more non-DM female patients who were matched for age and disease severity. Multivariate Cox regression was employed to determine the risk factors associated with pregnancy loss; (3) Results: The hazard ratio (HR) for the risk of pregnancy loss due to DM was 1.407 (95% confidence interval: 1.099–1.801, p = 0.007), and the risk factors for older age, gynecological disorders and inflammation disorders were included. (4) Conclusions: The study concluded that women with DM have a greater risk of experiencing pregnancy loss. Healthcare providers should proactively manage and educate diabetic patients to reduce their risk of pregnancy loss. Understanding other probable risk factors can help in developing targeted interventions and support systems for women to improve pregnancy outcomes.

Gay, bisexual, and other men who have sex with men (GBMSM) are associated with the widespread human immunodeficiency virus (HIV) transmission in Taiwan. Additionally, little is known about disclosure patterns and rates, as well as factors influencing disclosure, among GBMSM living with HIV in the country. HIV prevention for GBMSM is effective when HIV status is disclosed. For instance, GBMSM disclosing their HIV status can result in early pre-exposure prophylaxis with a serodiscordant partner. In this cross-sectional study of 200 GBMSM living with HIV conducted from June to November 2020, we assessed internalized homophobia (IHP Scale) and social support (Multidimensional Scale of Perceived Social Support), as well as self-reported disclosure and non-disclosure. Among the participants, 75.5% revealed their HIV status within 3 months of diagnosis. Younger age, occupation type, and number of sexual partners were some factors associated with disclosure. Those receiving more social support and who experienced less IHP were more likely to reveal their HIV status. On the contrary, older GBMSM and GBMSM living with HIV who worked in educational enterprises still experienced severe IHP. Policymakers and healthcare practitioners should be aware of the problems faced by GBMSM living with HIV and offer practical assistance to improve their mental health.

IntroductionChildren and adolescents with autism spectrum disorder (ASD) may be particularly vulnerable to the impact of traumatic events, yet the association between ASD and the risk of developing acute stress disorder and post-traumatic stress disorder (PTSD) remains uncertain. This study aims to investigate this association, addressing the gap in large-scale evidence on the subject.MethodsConducted as a retrospective and matched cohort study, data was sourced from the National Health Insurance Research Database (NHIRD) in Taiwan, spanning from January 1, 2000, to December 31, 2015. The study included patients aged 18 years or under newly diagnosed with ASD (n=15,200) and compared them with a matched control group (n=45,600). The Cox proportional regression model was employed to assess the risk of acute stress disorder and PTSD.ResultsOver the 15-year follow-up period, a total of 132 participants developed either acute stress disorder or PTSD. Among them, 105 cases (0.691% or 64.90 per 100,000 person-years) were in the ASD group, while 27 cases (0.059% or 5.38 per 100,000 person-years) were in the control group. The adjusted hazard ratio for the ASD group was significantly higher compared to the control group (25.661 with 95% CI = 15.913-41.232; P < .001).DiscussionThis study provides compelling evidence that individuals with ASD face an elevated risk of developing acute stress disorder and PTSD. The findings underscore the importance of clinicians recognizing and addressing this vulnerability in ASD individuals exposed to traumatic events. This emphasizes the need for heightened attention to the risk of PTSD and acute stress disorder in the ASD population.

BackgroundStudies have confirmed that osteoporosis has been considered as one of the complications of diabetes, and the health hazards to patients are more obvious. This study is mainly based on the Taiwan National Health Insurance Database (TNHID). Through the analysis of TNHID, it is shown that the combined treatment of traditional Chinese medicine (TCM) medicine in patients of diabetes with osteoporosis (T2DOP) with lower related risks.MethodsAccording to the study design, 3131 patients selected from TNHID who received TCM treatment were matched by 1-fold propensity score according to gender, age, and inclusion date as the control group. Cox proportional hazards analyzes were performed to compare fracture surgery, hospitalization, and all-cause mortality during a mean follow-up from 2000 to 2015.ResultsA total of 1055/1469/715 subjects (16.85%/23.46%/11.42%) had fracture surgery/inpatient/all-cause mortality of which 433/624/318 (13.83%/19.93%/10.16%) were in the TCM group) and 622/845/397 (19.87%/26.99%/12.68%) in the control group. Cox proportional hazards regression analysis showed that subjects in the TCM group had lower rates of fracture surgery, inpatient and all-cause mortality (adjusted HR = 0.467; 95% CI = 0.225-0.680, PConclusionThis study provides longitudinal evidence through a cohort study of the value of integrated TCM for T2DOP. More research is needed to fully understand the clinical significance of these results.

BackgroundThe integration of wearable devices into fitness routines, particularly in military settings, necessitates a rigorous assessment of their accuracy. This study evaluates the precision of heart rate measurements by locally manufactured wristbands, increasingly used in military academies, to inform future device selection for military training activities. ObjectiveThis research aims to assess the reliability of heart rate monitoring in chest straps versus wearable wristbands. MethodsData on heart rate and acceleration were collected using the Q-Band Q-69 smart wristband (Mobile Action Technology Inc) and compared against the Zephyr Bioharness standard measuring device. The Lin concordance correlation coefficient, Pearson product moment correlation coefficient, and intraclass correlation coefficient were used for reliability analysis. ResultsParticipants from a Northern Taiwanese medical school were enrolled (January 1-June 31, 2021). The Q-Band Q-69 demonstrated that the mean absolute percentage error (MAPE) of women was observed to be 13.35 (SD 13.47). Comparatively, men exhibited a lower MAPE of 8.54 (SD 10.49). The walking state MAPE was 7.79 for women and 10.65 for men. The wristband’s accuracy generally remained below 10% MAPE in other activities. Pearson product moment correlation coefficient analysis indicated gender-based performance differences, with overall coefficients of 0.625 for women and 0.808 for men, varying across walking, running, and cooldown phases. ConclusionsThis study highlights significant gender and activity-dependent variations in the accuracy of the MobileAction Q-Band Q-69 smart wristband. Reduced accuracy was notably observed during running. Occasional extreme errors point to the necessity of caution in relying on such devices for exercise monitoring. The findings emphasize the limitations and potential inaccuracies of wearable technology, especially in high-intensity physical activities.

Abstract Objective Past vegetarians research has often found that they have lower blood pressure (BP). Effects may include their lower BMI and higher intake levels of fruit and vegetables. Besides, the study pursues to extend this evidence in a diverse population containing vegans, lacto-ovo vegetarians and omnivores. Design The study analyzed data on five hundred vigorous individuals aged 20 years or older from a standard medical screening program and provided validated questionnaire. Criteria were established for vegan, lacto-ovo vegetarian, partial vegetarian and omnivorous dietary patterns. Setting Health screening programs were conducted at a standard medical screening program in Taiwan between 2006 and 2017. Dietary data were gathered by self-administered questionnaire. Subjects Five hundred Taiwanese subjects representing the cohort. Results Multiple regression analyses confirmed that the vegan vegetarians had lower systolic and diastolic BP (mmHg) than omnivorous Taiwanese (β = − 6.8, p 139 mmHg or diastolic BP > 89 mmHg or routine of antihypertensive medications, the odds ratio of hypertension compared with omnivores was 0.37 (95% CI = 0.19–0.74), 0.57 (95% CI = 0.36–0.92) and 0.92 (95% CI = 0.50–1.70), respectively, for vegans, lacto-ovo vegetarians and partial vegetarians. Results were reduced after adjustment for BMI. Conclusions The study concludes from this relatively large study that vegetarians, especially vegans, with otherwise diverse characteristics but stable diets, do have lower systolic and diastolic BP and less hypertension than omnivores.

Abstract Traumatic brain injury (TBI) is a silent epidemic that has been easily ignored. The safety and efficacy of restarting antiplatelet therapy after encountering traumatic brain injury (TBI) events remain a challenge. We explored the outcomes of restarting aspirin use on secondary stroke and mortality in patients with chronic stroke 4 weeks after suffering from a TBI episode in Taiwan. This study analyzed data from the National Health Insurance Research Database from January 2000 to December 2015. Overall, 136,211 individuals diagnosed with chronic stroke who suffered from acute TBI and received inpatient service were enrolled. The study outcomes were a competing risk of secondary stroke (ischemic and hemorrhagic) hospitalization and all-cause mortality. We identified a case group of 15,035 patients with chronic stroke (mean [SD] age of 53.25 [19.74] years; 55.63% male) who restarted aspirin use 4 weeks after suffering from TBI and a control group of 60,140 patients with chronic stroke (mean [SD] age of 53.12 [19.22] years; 55.63% male) who discontinued aspirin use after suffering from TBI. The risk of hospitalization of secondary ischemic stroke [adjusted hazard ratio (aHR) 0.694; 95% confidence interval (CI) 0.621–0.756; P

Abstract The sterilisation of surgical instruments is a major factor in infection control in the operating room (OR). All items used in the OR must be sterile for patient safety. Therefore, the present study evaluated the effect of far-infrared radiation (FIR) on the inhibition of colonies on packaging surface during the long-term storage of sterilised surgical instruments. From September 2021 to July 2022, 68.2% of 85 packages without FIR treatment showed microbial growth after incubation at 35 °C for 30 days and at room temperature for 5 days. A total of 34 bacterial species were identified, with the number of colonies increasing over time. In total, 130 colony-forming units were observed. The main microorganisms detected were Staphylococcus spp. (35%) and Bacillus spp. (21%) , Kocuria marina and Lactobacillus spp. (14%), and mould (5%). No colonies were found in 72 packages treated with FIR in the OR. Even after sterilisation, microbial growth can occur due to movement of the packages by staff, sweeping of floors, lack of high-efficiency particulate air filtration, high humidity, and inadequate hand hygiene. Thus, safe and simple far-infrared devices that allow continuous disinfection for storage spaces, as well as temperature and humidity control, help to reduce microorganisms in the OR.

Abstract Pioglitazone is an insulin resistance inhibitor widely used as monotherapy or combined with metformin or insulin in treating type 2 diabetes mellitus (T2DM). This study further investigated the relationship between pioglitazone use and the risk of developing Alzheimer's disease (AD) in patients newly diagnosed with T2DM, and examined the potential impact of insulin use on this association. Data were extracted from the National Health Insurance Research Database (NHIRD) of Taiwan. Our data exhibited that the risk of developing AD in the pioglitazone group was 1.584-fold (aHR = 1.584, 95% CI 1.203–1.967, p

Abstract Objective To investigate whether adults suffering from violence were at risk of substance abuse and provides insight into the relationship between male and female abusers and substance abuse from 2000 to 2015 in Taiwan. Methods This study used data on outpatient, emergency, and inpatient visits for 2 million people enrolled in universal health insurance from 2000 to 2015. ICD-9 diagnosis codes 995.8 (abused adult) and E960–E969 (homicide and injury purposely inflicted by other persons) were defined in this case study, analyzing first-time violence in adults aged 18–64 (study group). Non-abused patients (control group) were matched in a 1:4 ratio, and the paired variables were gender, age (± 1 year), pre-exposure Charlson Comorbidity Index, and year of medical treatment. SAS 9.4 and Cox regression were used for data analysis. Results A total of 8,726 people suffered violence (control group: 34,904 people) over 15 years. The prevalence of substance abuse among victims of violence was 78.3/104, 61.9/104, and 51.5/104 for tobacco use disorder, alcoholism, and alcohol abuse, respectively. The risk (adults, overall) of drug abuse, drug dependence, and alcoholism after exposure to violence (average 9 years) was 7.47, 7.15, and 6.86 times (p

Abstract Background To investigate the risk of poor prognosis regarding schizophrenic disorders, psychotic disorders, suicide, self-inflicted injury, and mortality after adult violence from 2000 to 2015 in Taiwan. Methods This study used data from National Health Insurance Research Database (NHIRD) on outpatient, emergency, and inpatient visits for two million people enrolled in the National Health Insurance (NHI) from 2000 to 2015. The case study defined ICD-9 diagnosis code N code 995.8 (abused adult) or E code E960-E969 (homicide and intentional injury of another). It analyzed first-time violence in adults aged 18–64 years (study group). 1:4 ratio was matched with injury and non-violent patients (control group). The paired variables were sex, age (± 1 year), pre-exposure to the Charlson comorbidity index, and year of medical treatment. Statistical analysis was conducted using SAS 9.4 and Cox regression for data analysis. Results In total, 8,726 individuals experienced violence (case group) while34,904 did not experienced violence (control group) over 15 years. The prevalence of poor prognosis among victims of violence was 25.4/104, 31.3/104, 10.5/10,4 and 104.6/104 for schizophrenic disorders, psychotic disorders, suicide or self-inflicted injury and mortality, respectively. Among adults, the risks of suicide or self-inflicted injury, schizophrenic disorders, psychotic disorders, and mortality after exposure to violence (average 9 years) were 6.87-, 5.63-, 4.10-, and 2.50-times (p

Abstract Trichomonas vaginalis infection is one of the most widespread sexually transmitted infections in the world. There are approximately 276 million cases worldwide. Most men remain undiagnosed and untreated because they are asymptomatic. The chronic inflammation induced by persistent infection may increase the risk of developing genitourinary cancers. In this study, we aimed to investigate the association between trichomoniasis and benign prostate hyperplasia (BPH), prostate cancer (PCa), and bladder cancer (BC) in Taiwan. We designed a case–control study by using the database of the National Health Insurance program in Taiwan. We used the International Classification of Diseases, 9th Revision classifications to classify all the medical conditions in the case and control groups. All odds ratios (ORs) and 95% confidence intervals (CIs) were analyzed using multivariable logistic regression to adjust for all comorbidities and variables. From 2000 to 2015, we enrolled a total of 62,544 individuals as the case group and 187,632 as the control group. Trichomoniasis exposure had a significant association with BPH and PCa (adjusted OR: BPH = 2.685, 95% CI = 1.233–4.286, P = 0.013; PCa = 5.801, 95% CI = 1.296–26.035, P = 0.016). The relative risk was much higher if patients had both trichomoniasis and depression (adjusted OR = 7.682, 95% CI = 5.730–9.451, P

Purpose:Purpose: Some evidence suggests that male infertility increases the risk of cardiovascular diseases (CVDs). However, the evi-dence in Asian populations is relatively scarce. The aim of this study is to determine whether male infertility increases the risk of CVDs. Materials and Methods:Materials and Methods: We used inpatient and outpatient data for the years 2000 to 2015 from the Taiwanese Longitudinal Health Insurance Database. We enrolled 7,016 males over 18 years old and diagnosed with male infertility. Of these, 2,326 matched our inclusion criteria and were assigned to the study group. For each infertility patient, four comparison patients were frequency-matched by age and index date to form a control cohort comprising 9,304 patients. Cox proportional haz-ards analysis was used to estimate the association between male infertility and CVDs. Results:Results: After a 15-year follow-up, the incidence rate of CVDs was higher in the infertility group than the control group (1,460.23 and 1,073.70 per 100,000 person-years, respectively). The Cox proportional hazards regression analysis revealed that the adjusted HR for CVDs was 1.472 for the infertility group (95% CI, 1.288–1.683; p

Abstract This retrospective cohort study aimed to evaluate the association between acetylcholinesterase inhibitors (AChEI) usage and the risk of lung cancer. Data from 116,106 new users of AChEI and 348,318, at a ratio of 1:3, matched by age, sex, and index-year, between 2000 and 2015 controls were obtained from the Taiwan Longitudinal Health Insurance Database in this cohort study. The Cox regression model was used to compare the risk of lung cancer. The adjusted hazard ratio (aHR) of lung cancer for AChEI users was 1.198 (95% confidence interval [CI] = 0.765–1.774, p = 0.167). However, the adjusted HR for patients aged ≥ 65 was adjusted to HR: 1.498 (95% CI = 1.124–1.798, p

Background: The aim of the study is to compare the incidence of sudden sensorineural hearing loss (SSNHL) in Northern and Southern Taiwan, areas with different levels of air pollution. Methods: This was a retrospective, cross-sectional, 15-year nationwide study of SSNHL diagnoses between 2000 and 2015 in Taiwan National Health Insurance Research Database. Results: In total, 12,497 patients were included, 5584 in Northern Taiwan and 2532 in Southern Taiwan. In Northern and Southern Taiwan, the mean patients' age was 50.94 ± 16.62 and 50.70 ± 15.86 years, respectively; males (53.56% vs. 53.48%) were more frequently diagnosed than females (46.44% vs. 46.52%). The crude incidence was 41.13/100,000 and 49.45/100,000 in Northern and Southern Taiwan. The increasing trend was significantly higher in Southern than in Northern Taiwan. The maximal difference between Northern and Southern Taiwan, 44.31 versus 77.01/100,000 people/year, occurred in 2012. Mean particulate matter (PM2.5) annual concentration steadily decreased from 25.5 μg/m3 in 2010 to 19.20 μg/m3 in 2015 in Northern Taiwan, 37.10 μg/m3 in 2010 to 26.50 μg/m3 in 2015 in Southern Taiwan, Tainan City area, and 38.20 μg/m3 in 2010 to 25.10 μg/m3 in 2015 in Southern Taiwan, Kaohsiung City area. Cumulative PM2.5 exposure (PM2.5-year) from 2000 to 2015 was 441.1 μg/m3 × year in Northern Taiwan, 563.3 μg/m3 × year in Southern Taiwan – Tainan City area, and 684.3 μg/m3 × year in Southern Taiwan – Kaohsiung City area. Conclusion: SSNHL incidence increased from 2000 to 2015 and was higher in Southern than in Northern Taiwan. Cumulative PM2.5 exposure was higher in Southern than in Northern Taiwan. The relationship between cumulative PM2.5 exposure and SSNHL pathogenesis needs further investigation.

Background: Beta-blockers are widely used for the treatment of arrhythmia, hypertension, and congestive heart failure. Major trauma causes significant blood loss and subsequent tachycardia and hypotension. Although beta-blockers may induce negative compensatory sympathetic responses to hemorrhagic shock, the effects of beta-blocker use before major trauma on posttrauma outcomes are controversial. Aim: We examined the association between the use of beta-blockers before major trauma and posttrauma outcomes using a nationwide population-based database. Methods: The data for this nationwide population-based retrospective cohort study were obtained from the National Health Insurance Research Database in Taiwan. A total of 2245 beta-blocker users were assigned to the study cohort, and another 8980 patients matched for age, sex, comorbidity, and medication use by inverse probability of treatment weighting formed the comparison cohort. The major outcome assessed was all-cause mortality during a 30-day follow-up period in major trauma patients with or without pretrauma beta-blocker use. Results: Our study included 2245 patients who used beta-blockers before major trauma. Individuals who used beta-blockers did not have a significantly higher cumulative risk of mortality than individuals who did not use beta-blockers (beta-blockers users: 17.19%, nonbeta-blockers users: 16.70%, P = 0.662). Conclusion: Pretrauma beta-blocker users did not have a higher mortality rate after a major trauma even after adjusting for several comorbidities and medications in a nationwide population database.

Abstract This study investigates an association between oral cancers and the risk of developing depression. We conducted a total of 3031 patients with newly diagnosed oral cancers and 9093 age-, sex-, and index year-matched controls (1:3) from 2000 to 2013 were selected from the National Health Insurance Research Database (NHIRD) of Taiwan. After adjusting for confounding factors, multivariate Cox proportional hazards analysis was used to compare the risk of depression over a 13-year follow-up. Of the patients with oral cancer, 69 (2.28%, or 288.57 per 105 person-years) developed depression compared to 150 (1.65%, 135.64 per 105 person-years) in the control group. The Cox proportional hazards regression analysis showed that the adjustment hazard ratio (HR) for subsequent depression in patients with oral cancer diagnosed was 2.224 (95% Confidence Interval [CI] 1.641–3.013, p

IntroductionOxidative stress is involved in numerous inflammatory diseases, including trauma. Micronutrients, such as selenium (Se), which contribute to antioxidant defense, exhibit low plasma levels during critical illness. This study aimed to investigate the impact of early Se supplementation on trauma patients.Materials and methodsA total of 6,891 trauma patients were registered at a single medical center from January 2018 to December 2021. Twenty trauma patients with Se supplemented according to the protocol were included in the study group. Subsequently, 1:5 propensity score matching (PSM) analysis was introduced. These patients received 100 mcg three times a day for 5 days. The primary outcome was overall survival (OS); the secondary outcomes were hospital/intensive care unit (ICU) length of stay (LOS), serologic change, ventilator dependence days, and ventilation profile.ResultsThe hospital LOS (20.0 ± 10.0 vs. 37.4 ± 42.0 days, p = 0.026) and ICU LOS (6.8 ± 3.6 vs. 13.1 ± 12.6 days, p < 0.006) were significantly shorter in the study group. In terms of serology, improvement in neutrophil, liver function, and C-reactive protein (CRP) level change percentile indicated better outcomes in the study group as well as a better OS rate (100 vs. 83.7%, p = 0.042). Longer ventilator dependence was found to be an independent risk factor for mortality and pulmonary complications in 6,891 trauma patients [odds ratio (OR) = 1.262, 95% confidence interval (CI) = 1.039–1.532, p < 0.019 and OR = 1.178, 95% CI = 1.033–1.344, p = 0.015, respectively].ConclusionEarly Se supplementation after trauma confers positive results in terms of decreasing overall ICU LOS/hospital LOS and mortality. Organ injury, particularly hepatic insults, and inflammatory status, also recovered better.

Abstract There is little comprehensive education for people with end-stage renal disease (ESRD) progress. We investigated the differences in terms of outcomes between patients with CKD stages 3–5 who enrolled and did not enroll in the pre-ESRD care education in Taiwan. This retrospective cohort study was conducted using data from the National Health Insurance Research Database (NHIRD). All patients diagnosed with CKD stages 3–5 who received the pre-ESRD care education through the pay for performance (P4P) program were enrolled. Based on whether or not they participated in the program, they were categorized into P4P or non-P4P groups. All analyses were performed from January 2006 through December 2015. Study outcomes were risk of hemodialysis dependency, hospitalization, and all-cause mortality. In this study of 29,337 patients, those with CKD stages 3–5 in the P4P group had lower events of hemodialysis, hospitalization, and all-cause mortality compared to patients in the non-P4P group. This study suggested that pre-ESRD care education is associated with increased patient outcomes, resulting in lower hemodialysis and hospitalization events and a higher overall survival rate in patients with CKD stages 3–5. Patient education could raise opportunities to improve pre-ESRD care by reaching patients outside the traditional health care setting.

Highlights Utilizing a nationwide, population-based database, the Longitudinal Health Insurance Database in 2000–2015 in Taiwan, which comprised 2 million people, we conducted a study to clarify the association between posttraumatic stress disorder and erectile dysfunction. Posttraumatic stress disorder was associated with the risk of erectile dysfunction. Psychotropic medications in the subjects with PTSD were not associated with the risk of erectile dysfunction.

Background: Numerous studies have shown that dipeptidyl peptidase-4 inhibitors (DPP-4i) may regulate immunological pathways implicated in asthma. The association between DPP-4i use and risk of asthma development is limited, however. Aim: We aimed to evaluate if DPP-4i treatment in individuals with type 2 diabetes mellitus (T2DM) is associated with a lower risk and severity of asthma. Methods: We performed a population-based retrospective cohort study using the Longitudinal National Health Insurance Research database between 2008 and 2015. After one-to-four propensity score matching from 1,914,201 patients with defined criteria, we enrolled 3001 patients who were on DPP-4i (DPP-4i group) for a diagnosis of T2DM but without a diagnosis of asthma for further analysis. Cox proportional hazards regression analysis was performed to estimate and compare the risk of developing and severity of asthma, including no acute exacerbations event (No-AE), acute exacerbations (AEs), status asthmaticus (Status), and required endotracheal intubation (ET-tube intubated), between the two groups. Results: The participants had a mean age of 66.05 ± 17.23 years and the mean follow-up time was 4.96 ± 4.39 years. The risk of asthma development was significantly lower in the DPP-4i group than in the non-DPP-4i group [adjusted hazard ratio (HR) = 0.65; 95% confidence interval (CI) = 0.29–0.83; p

Ankylosing spondylitis (AS) is known to increase the risk of stroke. Among patients with AS, uveitis is the most common extra-articular manifestation. However, no previous investigations have discussed the association between uveitis and the risk for developing stroke in patients with AS. This retrospective cohort study aimed to explore the relationship between uveitis and the incidence of stroke in patients with AS by obtaining medical records from January 1, 2000, to December 31, 2015, from the National Health Insurance Research Database, according to the International Classification of Diseases, 9th Revision, Clinical Modification diagnosis codes. The primary outcome was the incidence of stroke. Pearson’s chi-square test and Fisher’s exact test were used to analyze variables. Kaplan–Meier survival curves and univariate and multivariate Cox proportional hazard regression models with and without Fine and Gray’s competing risk model were used to analyze data. Total 828 AS patients with uveitis and 3,312 AS patients without uveitis were identified. During the follow-up period, 137 patients in the uveitis group and 344 in the non-uveitis group developed stroke. Uveitis is a significant risk factor for stroke development in patients with AS (adjusted hazard ratio = 1.846, p < 0.001). Age, diabetes mellitus, hyperlipidemia, hypertension, congestive heart failure, chronic obstructive pulmonary disease, asthma, coronary artery disease, and atrial fibrillation were associated with a higher risk of stroke. After subgroup analysis, both anterior uveitis and posterior segment involvement were found to increase the risk of stroke in patients with AS. Uveitis is associated with an increased risk in both ischemic and hemorrhagic strokes in patients with AS. Therefore, when uveitis is identified, clinicians should pay more attention to the cerebrovascular risk in patients with AS, especially in those with underlying comorbidities.

Background and purposeEvidence increasingly suggests that Helicobacter pylori infection (HPI) is associated with movement disorders such as Parkinson's disease (PD). However, the relationship between HPI and sleep-related movement disorders (SRMD) remains unknown. This nationwide population-based study tried to demonstrate whether patients with HPI have a higher risk of developing SRMD in a general adult population.MethodsThe study cohort enrolled 9,393 patients who were initially diagnosed with HPI between 2000 and 2013. Notably, 37,572 age- and sex-matched controls without prior HPI were selected as the reference. A Cox proportional hazard regression analysis was performed for multivariate adjustment.ResultsPatients with HPI had a higher risk of developing SRMD (adjusted hazard ratio [HR] = 2.18, 95% confidence interval [CI] = 1.26–3.82, p < 0.01). Patients with HPI aged ≥65 years exhibited the highest risk (HR = 3.01, 95% CI = 1.90–5.30, p < 0.001), followed by patients aged 45–64 years (HR = 1.69, 95% CI = 1.26–2.90, p

Abstract Background Approximately 25–30% of individuals worldwide are infected with Toxoplasma gondii (T. gondii), which is difficult to detect in its latent state. We aimed to evaluate the association between toxoplasmosis, the risk of dementia, and the effects of antibiotics in Taiwan. Methods This nationwide, population-based, retrospective cohort study was conducted using the Longitudinal Health Insurance Database containing the records of 2 million individuals retrieved from Taiwan’s National Health Insurance Research Database. Fine–Gray competing risk analysis was used to determine the risk for the development of dementia in the toxoplasmosis cohort relative to the non-toxoplasmosis cohort. A sensitivity analysis was also conducted. The effects of antibiotics (sulfadiazine or clindamycin) on the risk of dementia were also analyzed. Results We enrolled a total of 800 subjects, and identified 200 patients with toxoplasmosis and 600 sex- and age-matched controls without toxoplasmosis infection in a ratio of 1:3, selected between 2000 and 2015. The crude hazard ratio (HR) of the risk of developing dementia was 2.570 [95% confidence interval (CI) = 1.511–4.347, P

Abstract One recent study showed that atomoxetine-oxybutynin combination (AOC) use is effective in reducing obstructive sleep apnea (OSA) severity. We used a nationwide database to examine the association between AOC use and the risk of OSA incidence. This retrospective cohort study used Taiwan’s National Health Insurance Research Database between the years 2000 and 2015. The patients who used atomoxetine or oxybutynin were included as an exposed cohort. The exposed and unexposed groups were selected in a ratio of 1:3 with sex, age, and index year matching. We used the multivariate Cox proportional regression model to evaluate the association between AOC use and the risk of an incident diagnosis of OSA. The incidence rates of OSA in the exposed cohort (N = 8940) and the unexposed cohort (N = 26,820), were 21.92 and 22.93 per 100,000 person-years, respectively. The adjusted hazard ratio of oxybutynin use only and AOC with a treatment duration of ≥ 366 days were 0.307 (95% CI 0.204–0.995, P = 0.045) and 0.299 (95% CI 0.102–0.933, P = 0.002), respectively. Long-term atomoxetine-oxybutynin combination therapy may be beneficial to reduce the risk of obstructive sleep apnea. Further studies to examine these mechanisms are warranted.

Some antituberculosis agents may cause hypothyroidism, and thyroid hormones play a vital role in Mycobacterium tuberculosis infection. However, the relationship between tuberculosis (TB) and hypothyroidism has not been clearly established. Therefore, this retrospective, longitudinal cohort study aimed to investigate the association between these two diseases using the 2000–2017 data from the Taiwan's National Health Insurance Research Database. The hypothyroidism and TB cohorts were matched with the control group in a 1:4 ratio. Adjusted hazard ratios (aHRs) were assessed using Cox proportional hazards regression analysis in each cohort. In total, 3,976 individuals with hypothyroidism and 35 120 individuals with TB were included in this study. The risk of developing TB in patients with hypothyroidism was 2.91 times higher than that in those without hypothyroidism (95% confidence interval [CI], 1.50–3.65). The subgroup of thyroxine replacement therapy (TRT) had a 2.40 times higher risk (95% CI, 1.26–3.01), whereas the subgroup of non-TRT had a 3.62 times higher risk of developing TB than those without hypothyroidism (95% CI, 2.19–4.84). On the other hand, the risk of developing hypothyroidism in patients with TB was 2.01 times higher than that in those without TB (95% CI, 1.41–2.38). Our findings provide evidence that TB and hypothyroidism are interrelated. Thus, clinicians and public health authorities should monitor the association between these two diseases to reduce the relevant disease burden.

Background: Diabetic patients are at high risk of developing cancer. Traditional Chinese medicine (TCM) has become increasingly popular as an adjuvant treatment for patients with chronic diseases, and some studies have identified its beneficial effect in diabetic patients with cancer. The purpoes of this study was to outline the potential of TCM to attenuate hospitalization and mortality rates in diabetic patients with carcinoma in situ (CIS). Methods: A total of 6,987 diabetic subjects with CIS under TCM therapy were selected from the National Health Insurance Research Database of Taiwan, along with 38,800 of 1:1 sex-, age-, and index year-matched controls without TCM therapy. Cox proportional hazard analysis was conducted to compare hospitalization and mortality rates during an average of 15 years of follow-up. Results: A total of 3,999/1,393 enrolled-subjects (28.62%/9.97%) had hospitalization/mortality, including 1,777/661 in the TCM group (25.43%/9.46%) and 2,222/732 in the control group (31.80%/10.48%). Cox proportional hazard regression analysis showed a lower rate of hospitalization and mortality for subjects in the TCM group (adjusted HR=0.536; 95% CI=0.367–0.780, P

BackgroundUveitis, a sight-threatening ocular inflammatory state, is associated with autoimmune diseases and systemic inflammation. This prolonged systemic inflammation may cause plaque formation in coronary arteries, subsequently resulting in acute coronary syndrome (ACS).MethodsThis retrospective, population-based study (15-year period) used the Longitudinal Health Insurance Database based on the National Health Insurance Research Database in Taiwan. Chi-square and Student’s t-tests were used to examine differences between the study and comparison cohorts for categorical and continuous variables, respectively. Fine and Gray’s competing risk model was used to determine the hazard ratio of the risk of ACS. Furthermore, the cumulative risk of ACS was determined using Kaplan-Meier analysis.ResultsA total of 1,111 patients with AS and uveitis were enrolled in this study cohort, and 4,444 patients with AS without uveitis were enrolled in the comparison cohort. After adjustment for age, sex, and comorbidities, patients with AS and uveitis demonstrated an increased risk of ACS compared to those without uveitis (adjusted hazard ratio: 1.675, p

Abstract We aimed to investigate whether females with psychosexual disorders were associated with the risk of affective and other psychiatric disorders. A total of 2240 enrolled individuals, with 560 patients with psychosexual disorders and 1680 subjects without psychosexual disorders (1:3) matched for age and index year, from the Longitudinal Health Insurance Database, retrieved from the National Health Insurance Research Database (NHIRD), between 2000 and 2015 in Taiwan. The multivariate Cox regression model was used to compare the risk of developing psychiatric disorders during the 15 years of follow-up. There were 98 in the cohort with psychosexual disorders (736.07 per 100,000 person-year) and 119 in the non-cohort without psychosexual disorders (736.07 per 100,000 person-year) that developed psychiatric disorders. The multivariate Cox regression model revealed that the adjusted hazard ratio (HR) was 9.848 (95% CI = 7.298 — 13.291, p

Purpose: The purpose of this study was to evaluate the radiographic and clinical outcomes of hook plate fixation with and without coracoclavicular (CC) ligament augmentation with suture anchors for acute acromioclavicular (AC) joint dislocation. Methods: The study included 67 patients (48 males and 19 females; average age: 45.5 years) with acute AC joint dislocation (Rockwood types III and V) treated with hook plate fixation. The patients were divided into two groups: those treated with hook plate fixation with or without CC ligament augmentation with suture anchors. We used the CC distance and ratio as radiographic outcomes. We evaluated the American Shoulder and Elbow Surgeons (ASES) score and the Constant Shoulder Score as functional outcomes. The following were considered major complications: symptomatic acromial osteolysis, peri-implant fracture, acromial cut-out, and hook plate disengagement. Results: Among the Rockwood type III patients, there was no significant difference between the two subgroups in terms of the functional outcome after adjusting for sex and age. However, among the type V patients, treatment with CC ligament augmentation with suture anchors revealed a superior outcome in terms of the ASES score (P = 0.01). There was no difference in the risk of developing major complications between the two subgroups among type III and type V patients. The risk of residual subluxation of the AC joint was significantly lower in the CC augmentation subgroup among the type III patients (P = 0.04), and a similar result was obtained among the type V patients with borderline significance (P = 0.06). Conclusions: Hook plate fixation with CC suture anchor augmentation provided radiographic benefits in both type III and type V patients and yielded better functional outcomes in type V patients after implant removal but had no significant influence on the complication rate. Additional CC suture anchor augmentation may prevent residual subluxation and yield better functional outcomes.

Abstract Objective We have conducted a study to clarify the association between amphetamine‐related disorders (ARD) and the risk of developing dementia. Methods This study used a retrospective cohort design by using Taiwan’s National Health Research Institute Database. A random sample of 68,300 subjects between January 1, 2000, and December 31, 2015, was obtained, comprising of 17,075 patients with ARD, and 51,225 controls without ARD (1:3), matched for gender and age group. After adjusting for covariates, a Fine and Gray’s survival analysis (competing with mortality) was used to compare the risk of dementia during a 15‐year follow‐up period. Results In the present study, 1,751 of 17,075 patients with ARD and 2,147 of 51,225 in the control group without ARD (883.10 vs 342.83 per 100,000 person‐years) developed dementia. ARD cohort was more likely to develop dementia (hazard ratio = 4.936 [95% CI: 4.609–5.285, P

Abstract Background The incidence of female stroke has increased gradually and has begun occurring at a younger age in recent years. Given that women live longer than men, stroke would cause more negative and longer-term impacts on the rest of the lives of women. There are few related studies on Asian women. We aimed to evaluate stroke risk in Asian women following hypertensive pregnancy disorders. Methods Using the Taiwan National Health Insurance database, we designed a retrospective study that included pregnant women between 2000 and 2013. We selected an age-matched control group of women without hypertensive pregnancy disorders at a 1:3 ratio. The endpoint was any episode of stroke; otherwise, the patients were tracked until December 31, 2013. After the index date until the end of 2013, Cox proportional hazards analysis was used to compare the risk of incident stroke. The risk factors for stroke were determined using Cox proportional regression to calculate the hazard ratio (HR) compared with the control group. Results During the follow-up period, the Kaplan-Meier analysis indicated that patients with hypertensive pregnancy disorders had a significantly higher risk of developing stroke than did patients without hypertensive pregnancy disorders (log-rank test P

Purpose: This nationwide population-based retrospective cohort study evaluated the protective effect of N-acetylcysteine against prosthetic joint infection after hip or knee joint replacement. Methods: Patients receiving N-acetylcysteine after hip or knee joint replacement between 2000 and 2015 were identified from the Taiwan National Health Insurance Research Database. Each patient receiving N-acetylcysteine was matched to four controls based on age, sex, and index year. All subjects were followed-up from the index date to December 31, 2015. The Cox proportional hazards regression model was used to assess the risk of prosthetic joint infection. Results: A total of 1478 patients were included in the study group, and 5912 matched subjects not receiving N-acetylcysteine were included in the control group. After adjusting for age, sex, insured premium, comorbidities, and immunosuppressive agent use, no significant difference in the risk of prosthetic joint infection was found between the two groups. A higher N-acetylcysteine dose (>360 cumulative defined daily dose) significantly decreased the risk of prosthetic joint infection (adjusted hazard ratio = 0.891; 95% confidence interval = 0.599–0.989; p = 0.042). The protective effect of N-acetylcysteine was observed only in the group of prosthetic joint infection within 5 years (adjusted hazard ratio = 0.801; 95% confidence interval = 0.581–0.980; p = 0.040). Conclusions: High cumulative dose of N-acetylcysteine (>360 cumulative defined daily dose) can effectively reduce the risk of prosthetic joint infection in patients undergoing knee or hip joint replacement surgery within 5 years. Keywords: Biofilm, N-acetylcysteine, Prosthetic joint infection

Background: Therapeutic phlebotomy, known as scheduled bloodletting, has been the main method for managing erythrocytosis symptoms and thrombocytosis-associated complications in various blood disorders. One of the major indications for phlebotomy is polycythemia vera (PV). The main goal of current treatment strategies for patients who require phlebotomy is to prevent thrombohemorrhagic complications rather than to prolong survival or lessen the risk of myelofibrotic or leukemic progression. Additional cytoreductive therapy is recommended for high-risk PV, for which the common first-line drug is hydroxyurea. However, recent evidence suggests that phlebotomy may not reduce the risk of thrombosis in patients with PV. Further evidence suggests that patients with PV treated with hydroxyurea who require three or more phlebotomy procedures per year have a higher risk of thrombotic complications.Methods: We hypothesized that a drug-repurposing strategy of utilizing antineoplastic drugs for patients who require phlebotomy would result in greater benefits than would phlebotomy. The antihypertensive hydralazine and the anticonvulsant valproate, which have both been reported to have antineoplastic activity that mimics cytoreductive agents, were selected as candidates for the drug-repositioning strategy in a retrospective cohort study. We measured the hazard ratios (HR) and the frequencies of phlebotomy in patients with prescriptions for hydralazine or valproate or the two drugs in combination by using data from Taiwan’s National Health Insurance Research Database from 2000 to 2015 (n = 1,936,512).Results: The HRs of undergoing phlebotomy in groups with hydralazine, valproate, and combination hydralazine–valproate prescriptions were reduced to 0.729 (p = 0.047), 0.887 (p = 0.196), and 0.621 (p = 0.022), respectively. The frequency of undergoing phlebotomy decreased from 2.27 to 1.99, 2.01, and 1.86 per person-year (p = 0.015), respectively. However, no significant differences were observed for the hydralazine group or the hydralazine–valproate combination group.Conclusion: Whether a repurposed drug can serve as a cytoreductive agent for patients who require phlebotomy depends on its risk–benefit balance. We suggest that hydralazine, instead of the hydralazine–valproate combination, is a reasonable alternative for patients who require regular phlebotomy.

PurposeAnkylosing spondylitis (AS) is a risk factor for acute coronary syndrome (ACS). However, the influence of infectious insults, such as endophthalmitis, on the risk of ACS among AS patients has not been studied yet. In this study, we aimed to investigate the relationship between endophthalmitis in patients with AS and the incidence of ACS.MethodsThis retrospective cohort study extracted medical records from the Taiwan Longitudinal Health Insurance Database (LHID) from January 1, 2000, to December 31, 2015. The primary outcome was the incidence of ACS. Univariate and multivariate Cox regression analyses with and without Fine and Gray’s competing risk model and Kaplan–Meier survival curve were used for the analyses. Spearman’s rank correlation coefficient was performed for sensitivity analysis.ResultsWe identified 530 AS patients with endophthalmitis and 2,120 AS patients without endophthalmitis for comparison. The incidence rate of endophthalmitis in our study population was 2.66%. The overall incidence rate of ACS was 1,595.96 per 100,000 person-years in AS patients with endophthalmitis and 953.96 per 100,000 person-years in AS patients without endophthalmitis (adjusted HR = 1.787; 95% CI: 1.594–2.104, p < 0.001). In comparison to those without comorbidities, higher adjusted HRs were found in AS patients with endophthalmitis and comorbidities such as diabetes mellitus, hyperlipidemia, hypertension, cerebrovascular accident, congestive heart failure, chronic obstructive pulmonary disease, asthma, and coronary artery disease. Besides, the age ≥ 60 years revealed a high risk for ACS in AS patients with endophthalmitis.ConclusionEndophthalmitis was found to be an independent risk factor for ACS in patients with AS. Further clinical studies are required to elucidate the underlying mechanisms and status of systemic inflammation during endophthalmitis.

BackgroundTo explore the association between leptospirosis, the risk of dementia, and the potential protective role of antibiotic treatment.MethodsWe conducted a retrospective cohort nationwide, population-based study, from Taiwan’s National Health Insurance Research Database (NHIRD). We enrolled 1,428 subjects aged 50 years or above, in the index year of 2000, which included those retrieved from the NHIRD record. Dementia diagnosis and incidence over 16 years follow-up was retrieved from the NHIRD records. The Fine and Gray survival analysis was used to determine the risk of dementia, and the results were presented as a sub-distribution hazard ratio (SHR) with a 95% confidence interval.ResultsIn the study period, 43 of the 357 leptospirosis patients developed dementia, as compared to 103 of the control group (930.90 vs. 732.49 per 105 person-years). By the Fine and Gray survival analysis, the leptospirosis was associated with the risk of dementia, and the adjusted SHR was 1.357 (95% confidence interval [CI]: 1.213–1.519, P < 0.001), across 16-year of the follow-up period. To exclude the protopathic bias, the sensitivity analysis was conducted. This analysis revealed that the leptospirosis was associated with the increased risk of dementia, even after excluding the dementia diagnosis within the first year (adjusted SHR = 1.246, 95%CI: 1.114–1.395, P < 0.001) or within the first 5 years (adjusted SHR = 1.079, 95%CI: 1.023–1.152, P = 0.028), antibiotic treatment for leptospirosis was associated with the reduced risk of dementia (P = 0.001).ConclusionLeptospirosis was associated with an increased risk for dementia, and antibiotic treatment was associated with a reduced risk. Further research will be necessary to explore the underlying mechanisms of this association.

BackgroundThe histamine type 1 receptor antagonist (H1RA) has been commonly used. This study aimed to examine the association between the usage of H1RA and the risk of dementia.MethodsA total of 8,986 H1RA users aged ≥50 and 26,958 controls matched a ratio of 1:3 for age, sex, and comorbidity, were selected between January 1, and December 31, 2000, from Taiwan’s National Health Insurance Research Database. Fine and Gray’s survival analysis (competing with mortality) was used to compare the risk of developing dementia during a 15-year follow-up period (2000–2015).ResultsIn general, the H1RA usage was not significantly associated with dementia (adjusted subdistribution hazard ratio [SHR] = 1.025, 95% confidence interval [CI] = 0.883–1.297, p = 0.274) for the H1RA cohort. However, a differential risk was found among the groups at risk. The patients with the usage of H1RA aged ≥65 years (adjusted SHR: 1.782, 95% CI = 1.368–2.168, p < 0.001) were associated with a higher risk of dementia, in comparison to the control groups. Furthermore, the patients with the usage of H1RA that were male, or had more comorbidities, were also associated with an increased risk of dementia.ConclusionThe usage of H1RA was associated with the risk of developing dementia in the patients aged ≥ 65 years.

Introduction: Fluoroquinolone exposure is reportedly associated with a higher risk of tendon disorders, tendonitis, or tendon rupture. However, studies in East Asian populations have not confirmed these risks in patients with comorbidities or concomitant medication use. This cohort study was designed to investigate the associations among fluoroquinolone exposure, comorbidities, medication use, and tendon disorders in Taiwan.Materials and Methods: This population-based, nationwide, observational, cohort study used data from the National Health Insurance Research database in Taiwan, a nationwide claims database that covers more than 99% of the Taiwanese population. The study period was from January 2000 to December 2015, and the median follow-up time was 11.05 ± 10.91 years. Patients who were exposed to fluoroquinolones for more than three consecutive days were enrolled, and patients without fluoroquinolone exposure who were matched by age, sex, and index year were enrolled as controls. The associations of comorbidities and concomitant medication use with tendon disorder occurrence were analyzed using Cox regression models.Results: The incidence of tendon disorders were 6.61 and 3.34 per 105 person-years in patients with and without fluoroquinolone exposure, respectively (adjusted hazard ratio, 1.423; 95% confidence interval [1.02,1.87]; p = 0.021). Sensitivity analyses yielded similar results. Patients under 18 and over 60 years with fluoroquinolone exposure; those with chronic kidney disease, diabetes, rheumatologic disease, cardiac disease, lipid disorder, or obesity; and those who concomitantly used statins, aromatase inhibitors, or glucocorticoids, had a significantly higher risk of tendon disorders.Conclusion: The long-term risk of tendon disorders was higher in patients with fluoroquinolone exposure than in those without fluoroquinolone exposure. Clinicians should assess the benefits and risks of fluoroquinolone use in patients at high risk of tendon disorders who require fluoroquinolone administration.

BackgroundBlepharitis is a common eye disorder that may be overlooked by patients and clinical practitioners. The symptoms of blepharitis often manifest as irritation, a burning sensation, grittiness, and itchiness and may decrease visual acuity if not treated promptly. Meibomian gland dysfunction (MGD), a common cause of blepharitis, is believed to be associated with increased inflammatory marker levels that may disrupt the composition of lipids produced by the sebaceous glands in the eyelids and ultimately cause tear film instability.MethodsThis is a retrospective, population-based study using National Health Insurance Research Database (NHIRD) data from a 14-year period (2000–2015). Pearson chi-squared and Student's t-tests were used to assess the differences in categorical and continuous variables, respectively, between statin users and non-statin users. Univariate and multivariate Cox regression analyses were performed to calculate the hazard ratios (HRs) after adjusting for confounders. Kaplan-Meier analysis was used to assess the cumulative risk of blepharitis between the two cohorts.ResultsA total of 67,014 patients who used statins were enrolled as the study cohort, and 268,056 patients who did not use statins were enrolled as the comparison cohort. The incidence of blepharitis was 3.04% with statin treatment and 3.72% without statin treatment (p < 0.001). Patients who used statins had a lower risk of developing blepharitis [adjusted hazard ratio (aHR): 0.746, p < 0.001] than those who did not. In addition, diabetes mellitus (DM), hypertension, coronary heart disease (CHD), stroke, chalazion, rosacea, Sjogren syndrome, psoriasis and atopy were found to be possible risk factors for blepharitis.ConclusionStatin use can decrease the risk of developing blepharitis. However, further prospective studies are needed to evaluate statin treatment for various subtypes of blepharitis and to identify the associated mechanism.