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Summary Background and purpose Stroke is a rare complication of snakebites, but may lead to serious sequelae. We aimed to explore the relationship between venomous snakebite and the risk for acute stroke, in a nationwide population-based cohort study. Methods This retrospective cohort study used claims data between 1 January 2000 and 31 December 2012, from the Taiwan National Health Insurance Research Database. The study included data of patients aged 18 years or older with venomous snakebite (n = 535), matched for propensity score with controls without venomous snakebite (n = 2140). The follow-up period was the duration from the initial diagnosis of venomous snakebite and administration of antivenom to the date of an acute stroke, or until 31 December 2013. The competing risk model was used to estimate the hazard ratio (HR) and 95% confidence intervals (CIs) of stroke, ischemic stroke and hemorrhagic stroke, after adjusting for demographic and other possible stroke risk factors. Results The adjusted HR for the venomous snakebite group compared with the control group was 2.68 for hemorrhagic stroke (95% CI = 1.35-5.33). Stratified analysis showed that the older age group (>65 years old) had a higher risk of hemorrhagic stroke. A 2.72-fold significant increase in the risk for hemorrhagic stroke was observed following venomous snakebite with antivenom usage (95% CI = 1.41–5.26). Conclusion Venomous snakebite is associated with an increased risk of hemorrhagic stroke after the use of antivenom. Further study of the underlying mechanism is warranted.

Flat foot can alter the lower limb alignment and cause knee and back pain. To explore the association between flat foot and spinal degeneration.By using a claims dataset containing 1 million random samples, individuals with flat foot were identified between January 1, 2000, and December 31, 2013. The study assembled a flat foot group and a matched non-flat foot group. Definition of flat foot was according to International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM) codes. The diagnosis date was defined as the index date for follow-up initiation. The follow-up period was defined as the duration from the index date (or nested index date for controls) to the occurrence of spinal degenerative joint disease (DJD), or December 31, 2013. The primary outcome was record of spinal DJD retrieved from the same database. Cox proportional hazards models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs), with the control group as a reference.We identified 13,965 patients (most aged30 years, 88%); 2793 patients were assigned to the flat foot group and 11,172 individuals to the non-flat foot group matched by age, sex, and index year. The mean follow-up duration was approximately 74 months. In total, 329 (11.78%) patients in the study group and 931 (8.33%) patients in the comparison group developed spinal DJD. The adjusted HR (95% CI) of spinal DJD for study group was 1.423(1.250-1.619) compared with the control. Sensitivity analyses with propensity score match and different scenario about spinal DJD enrollment showed similar results. Subgroup analysis showed that in patients aged45 years with history of flat foot, the adjusted hazard ratios were 1.434, 3.065, 3.110, and 2.061 in association with spondylosis, intervertebral disc disorder, cervical stenosis, thoracic-lumbar-sacral stenosis, respectively.Flat foot was found to be an independent risk factor for subsequent spinal DJD.

Influenza infection could trigger acute myocardial infarction. Obstructive sleep apnea (OSA) increases risk for myocardial infarction. Evidence evaluating the risk of influenza in patients with OSA is limited. We aimed to investigate the association between OSA and influenza using a nationwide population-based data set.A total of 5483 individuals with OSA were enrolled from January, 2000, to December, 2012, and compared with a control group of 21,932 individuals who had never been diagnosed with OSA (at a 1:4 ratio propensity score matched by age, sex, index years, and comorbidities) in the context of subsequent influenza infection. Cox proportional hazard regression analysis was conducted to analyze the association between OSA and influenza incidence. We conducted sensitivity analyses to examine our finding.During the 1.81 (±2.12) years of the follow-up period, the incidence rate of influenza infection was higher in the OSA group compared with the non-OSA group (36.40 and 30.09 per 100 person-years). After adjusting for age, sex, comorbidities, outpatients visits, the risk of influenza infection among patients with OSA was significantly higher (hazard ratio = 1.18; 95% confidence interval = 1.14-1.23; P 0.001). Sensitivity analyses showed consistent positive association. Males with OSA had increased risk of influenza infection compared with males without OSA (adjusted HR, 1.21; 95% CI, 1.16-1.27; P value for interaction = 0.03).This study found a significantly higher risk of influenza infection in patients with OSA, and sex acted as an effect modifier between OSA and risk of influenza infection.

Background This study investigated the correlation between a history of human papillomavirus (HPV) infection and skin cancer risk. Materials and Methods The study cohort comprised 26,919 patients with newly diagnosed HPV infection between 2000 and 2012; with the use of computer-generated numbers, patients without previous HPV infection were randomly selected as the comparison cohort. The patients in the HPV infection cohort were matched to comparison individuals at a 1:4 ratio by demographic characteristics and comorbidities. All study individuals were followed up until they developed skin cancer, withdrew from the National Health Insurance program, were lost to follow-up, or until the end of 2013. The primary outcome was subsequent skin cancer development. Cox proportional hazards regression analysis was used to analyze the risk of skin cancer with hazard ratios (HRs) and 95% confidence intervals (CIs) between the HPV and control cohort. Results The adjusted HR of skin cancer for patients with HPV relative to controls was 2.45 after adjusting sex, age and comorbidities. (95% CI, 1.44–4.18, p < .01). The subgroup analysis indicated that a patient with HPV infection had a significantly greater risk of skin cancer if they were aged >40 years. Notably, a risk of skin cancer was found in the group diagnosed with HPV within the first 5 years after the index date (adjusted HR, 3.12; with 95% CI, 1.58–5.54). Sensitivity analysis by propensity score, matching with balanced sex, age, and comorbidities, showed consistent results. Conclusion A history of HPV infection is associated with the development of subsequent skin cancer in Taiwanese subjects, and the risk wanes 5 years later. Implications for Practice In this Taiwan nationwide cohort study, there was a 2.45-fold increased risk of developing new-onset skin cancers for patients with incident human papillomavirus (HPV) infection, compared with the matched controls. Furthermore, the risk was noticeably significant among patients aged >40 years. A prominent risk of skin cancers was found in the group diagnosed with HPV within the first 5 years after the index date in this study. The results of this analysis may raise consensus on the effect of HPV infection on the risk of skin cancers. Clinicians are encouraged to implement prudently on the differential diagnosis of skin cancers and HPV prevention and treatment, especially in older patients.

To explore whether newly diagnosed Candida infection increases the risk of developing ankylosing spondylitis (AS). We investigated 61,550 patients with newly diagnosed Candida infection between 199...

The research is to explore the association between nontyphoidal salmonellosis (NTS) and subsequent gastric cancer. We conducted a retrospective study by analyzing hospitalization dataset from the National Health Insurance Research Database in Taiwan. Patients aged 20 years and older with NTS (n = 9 097) admitted between January 1, 2000, and December 31, 2012, were enrolled and followed up until December 31, 2013. The primary outcome was the incidence of gastric cancer. Cox proportional hazards regression was used to estimate the risk of malignancy, accounting for the competing risk of death. In addition, we conducted a sensitivity analysis by propensity score matching and exclusion of malignancy within 1 year observation to minimize measurable confounding and protopathic bias. Negative controls were applied to examine the presence of possible unmeasured confounders in the study. The study included 18 194 patients (9097 in each NTS and non-NTS group). The median follow-up time was 7 years. The incidence density rate of gastric cancer was 0.72 per 1000 person-years for the NTS group and 0.40 per 1000 person-years for the non-NTS group. The NTS group had a modestly higher risk of gastric cancer (aHR, 2.02; 95% CI 1.18–3.45) than the non-NTS group. The sensitivity analyses revealed consistent results. Patients with NTS are associated with increased risk of subsequent gastric cancer compared with non-NTS patients. Future research is needed to examine whether NTS is parallel, reactive or causative to gastric cancer.

Summary Objectives: To explore the association between nontyphoidal salmonellosis (NTS) and the risk of acute ischemic stroke (IS) by using a nationwide, population-based study. Methods A retrospective cohort study using claim data from Taiwan's National Health Insurance Research Database (NHIRD), patients aged 18 years and older with histories of NTS (N = 1618) were included from January 1, 2000-December 31, 2012, and the non-NTS group (N = 6472) without NTS were matched by propensity score. The follow-up period was defined as the time from the initial diagnosis of NTS to the date of development of IS, death or 31 December, 2013. Patients previously diagnosed with stroke were excluded. The Cox proportional hazard model with robust sandwich estimator was used to estimate the hazard ratio (HR) and 95% confidence interval (CI) of IS after adjusting for demographic and clinical covariates. Results: The adjusted hazard ratio (aHR) for the NTS group compared with the non-NTS group was 1.34 (95% confidence interval [CI], 1.10–1.65) for overall stroke. Furthermore, the NTS cohort had an increased risk of IS compared to the non-NTS groups (aHR, 1.42; 95% CI, 1.14–1.78). Stratified analysis showed that compared with propensity score matched non-NTS group, subjects aged ≥65 years, female, those with hypertension, hyperlipidemia, COPD, cancer and heart failure had higher risk of developing stroke. A 1.93-fold significant increase risk for stroke was observed during the first 3–12 months of follow-up (95% CI, 1.07–3.48). Conclusions: Patients with NTS is associated with increased risk of developing ischemic stroke compared with non-NTS patients. Timely and mindful treatment plan about NTS may be a milestone to stroke prevention especially in some subpopulation.

Objective: To explore whether newly diagnosed iron deficiency anemia (IDA) is associated with subsequent systemic autoimmune disease onset.Methods: The study identified 22,440 patients who received...

ObjectiveWe investigated the correlation between nontyphoidal Salmonella (NTS) infection and systemic lupus erythematosus (SLE) risk.MethodsThis case-control study comprised 6,517 patients with newly diagnosed SLE between 2006 and 2013. Patients without SLE were randomly selected as the control group and were matched at a case-control ratio of 1:20 by age, sex, and index year. All study individuals were traced from the index date back to their NTS exposure, other relevant covariates, or to the beginning of year 2000. Conditional logistic regression analysis was used to analyze the risk of SLE with adjusted odds ratios (aORs) and 95% confidence intervals (CIs) between the NTS and control groups.ResultsThe mean age was 37.8 years in the case and control groups. Females accounted for 85.5%. The aOR of having NTS infection were significantly increased in SLE relative to controls (aOR, 9.20; 95% CI, 4.51-18.78) in 1:20 sex-age matching analysis and (aOR, 7.47; 95% CI=2.08-26.82) in propensity score matching analysis. Subgroup analysis indicated that the SLE risk was high among those who dwelled in rural areas; had rheumatoid arthritis, multiple sclerosis, or Sjogren’s syndrome; and developed intensive and severe NTS infection during admission.ConclusionsExposure to NTS infection is associated with the development of subsequent SLE in Taiwanese individuals. Severe NTS infection and other autoimmune diseases such as rheumatoid arthritis, multiple sclerosis, or Sjogren’s syndrome also contributed to the risk of developing SLE.

IntroductionInfections play a role in autoimmune diseases (AD). Leptospirosis has been linked to the trigger of systemic lupus erythematosus.ObjectiveTo investigate subsequent risk of major AD in hospitalized Taiwanese for Leptospirosis.MethodsRetrospective observational cohort study was employed. The enrolled period was from 2000 to 2012. In the main model, we extracted 4026 inpatients with leptospirosis from the Taiwan National Health Insurance Research Database (NHIRD) and 16,104 participants without leptospirosis at a 1:4 ratio propensity-score matched (PSM) by age, gender, index year, and comorbidities. The follow-up period was defined as the time from the initial diagnosis of leptospirosis to major AD occurrence or 2013. This study was re-analyzed by frequency-matching as a sensitivity analysis for cross-validation. Univariable and multivariable Cox proportional hazards regression models were applied to estimate hazard ratios (HRs) and 95% confidence intervals (CIs).ResultsThe adjusted HR (95% CI) of major ADs for the leptospirosis group was 4.45 (3.25–6.79) (p < 0.001) compared to the controls after full adjustment. The risk of major ADs was 5.52-fold (95% CI, 3.82–7.99) higher in leptospirosis patients hospitalized for seven days and above than the controls, while 2.80-fold (95% CI, 1.68–5.61) in those hospitalized less than seven days. The sensitivity analysis yields consistent findings. Stratified analysis revealed that the association between leptospirosis and major ADs was generalized in both genders, and all age groups.ConclusionsSymptomatic leptospirosis is associated with increased rate of subsequent major ADs, and the risk seems to be higher in severe cases.

Background: Gastric cancer (GC) is one of the leading malignancy diseases worldwide, especially in Asian. CAST is a potential oncogene in GC carcinogenesis process. The character of macrophage infiltration in GC microenvironment was also unaddressed. Methods: We first applied machine searching in gene candidate evaluation of GC. CAST expression was analyzed via the Human Protein Atlas (HPA) and Gene Expression Profiling Interactive Analysis 2 (GEPIA2) database. Protein-protein interaction (PPI) network was downloaded from STRING. We investigated the impact of CAST on clinical prognosis using Kaplan-Meier plotter. The correlations between CAST and Lgr5 and macrophage infiltration in GC was surveyed via TIMER 2.0. Finally, GeneMANIA was also used to evaluate the possible functional linkage between genes. Results: After machine-assisted searching, CAST expression was found signicant difference in the overall survival of GC patients. STRING revealed CAST related proteomics and transcriptomics associations, mainly about CAPN family. Moreover, CAST significantly impacts the prognosis of GC from other datasets validation. Notably, high CAST expression was correlated with worse overall survival in GC patients (hazard ratio = 1.59; logrank P = 9.4 x 10-8). CAST and Lgr5 expressions were both positively correlated with WNT 2 and WNT 2B. Among GC patients in several datasets, CAST and macrophage infiltration evaluated together showed no obvious trend toward poor clinical overall survival. Conclusion: CAST plays an important role in GC clinical prognosis and is associated with WNT 2/WNT 2B/Lgr5. Our study denmostrated that CAST in GC overall survival is regulated by macrophage infiltration.

Mycoplasma pneumoniae (M. pneumoniae) is not only one of the most common pathogenic bacteria for respiratory infection but also a trigger for many autoimmune diseases. Its infection process shared many similarities with the pathogenesis of myasthenia gravis (MG) at cellular and cytokine levels. Recent case reports demonstrated patients present with MG after M. pneumoniae infection. However, no epidemiological studies ever looked into the association between the two. Our study aimed to investigate the relationship between M. pneumoniae infection and subsequent development of MG. In this population-based retrospective cohort study, the risk of MG was analyzed in patients who were newly diagnosed with M. pneumoniae infection between 2000 and 2013. A total of 2428 M. pneumoniae patients were included and matched with the non-M. pneumoniae control cohort at a 1:4 ratio by age, sex, and index date. Cox proportional hazards regression analysis was applied to analyze the risk of MG development after adjusting for sex, age, and comorbidities, with hazard ratios and 95% confidence intervals. The incidence rates of MG in the non-M. pneumoniae and M. pneumoniae cohorts were 0.96 and 1.97 per 10,000 person-years, respectively. Another case–control study of patients with MG (n = 515) was conducted to analyze the impact of M. pneumoniae on MG occurrence as a sensitivity analysis. The analysis yielded consistent absence of a link between M. pneumoniae and MG. Although previous studies have reported that M. pneumoniae infection and MG may share associated immunologic pathways, we found no statistical significance between M. pneumoniae infection and subsequent development of MG in this study.

ObjectiveThe aim of this study was to investigate the relationship between non-typhoidalSalmonella(NTS) infection and the risk of Kawasaki disease (KD) by using a nationwide population-based data set in Taiwan.MethodsIn this retrospective cohort study, we enrolled 69,116 patients under 18 years of age, with NTS from January 1st, 2000, to December 31st, 2013, using the population-based National Health Insurance Research Database of Taiwan. A comparison group without NTS was matched (at a 1:4 ratio) by propensity score. The two cohorts were followed from the initial diagnosis of NTS until the date of KD development or December 31st, 2013. Cox proportional hazard regression analysis was conducted to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) after adjusting for covariates. Also, we conducted sensitivity analyses to examine our findings.ResultsAfter adjusting for covariates, the risk of KD for the children with NTS was significantly higher than that of the comparison group (hazard ratio = 1.31; 95% confidence interval = 1.03-1.66; p < 0.01). Stratified analysis showed that the associated risk of the investigated outcome was significant in children aged ≤2 years (aHR= 1.31, 95% C.I. 1.02-1.69), in female patients (aHR= 1.46, 95% C.I. 1.03-2.08), and in those without allergic diseases.ConclusionsNTS is associated with an increased risk of KD in Taiwanese children.

Endometriosis (EM) with chronic inflammation may accelerate the progression of atherosclerosis. Currently, no large or randomized clinical studies have assessed the incidence of cardiovascular events in patients with endometriosis in Asia to investigate whether incident EM is associated with a higher risk of new-onset coronary artery disease (CAD). In this study of a nationwide cohort in Taiwan, we identified 13,988 patients with newly diagnosed EM from 1 January, 2000, through 31 December, 2012. EM and non-EM groups were matched by propensity score at a ratio of 1:1. Of a total 27,976 participants, 358 developed CAD. The incidence rate in the EM group was higher than that in the non-EM group (1.8 per 1,000 person-years vs. 1.3 per 1,000 person-years) during the follow-up period. The adjusted hazard ratio (aHR) of CAD for the EM group was 1.52 with a 95% confidence interval (1.23–1.87, p < 0.001) after adjusting for demographic characteristics, comorbidities, surgical procedures, frequency of outpatient visits, and medications. Stratified analysis revealed that, among four age groups (20–39, 40–49, 50–54, and above 55 years), the 20–39 years sub-group was associated with a higher risk of CAD (aHR, 1.73; 95% CI, 1.16–2.59, p = 0.008). Several sensitivity analyses were conducted for cross-validation, and it showed consistent positive findings. In conclusion, this cohort study revealed that patients with symptomatic EM in Taiwan were associated with increased risk of subsequent CAD than patients without medical records of EM. Further prospective studies are needed to confirm this causal relationship.

The current study was designed to investigate the association between cholecystectomy and the risk of non-typhoidal Salmonella (NTS) infection.We obtained claims-based data from the Taiwan National Health Insurance Research Database (NHIRD) to perform a nationwide cohort study. A propensity score (PS)-matching analysis was performed with a ratio of 1:2 in the cholecystectomy cohort and cholecystectomy-free group to reduce selection bias. Both groups were followed until NTS diagnosis, a dropout from the insurance programme or the end of 2013. Cox proportional hazard regression analysis was used to estimate the hazard ratio (HR) and 95% confidence interval (CI) for the risk of NTS infection between the cholecystectomy and cholecystectomy-free groups.Our study enrolled 197 444 patients who had undergone cholecystectomy and 394 888 patients who did not receive cholecystectomy. The adjusted HR (aHR) of NTS infection was 1.34 (95% CI, 1.13-1.58; P .001) for the cholecystectomy group after adjusting for demographical characteristics and relevant comorbidities. The study population is predominantly female patients (55%) and older (58% older than 50 years). The subgroup analysis revealed that both sexes and notably, patients aged50, who underwent cholecystectomy had a higher risk of NTS infection than the matched controls. Follow-up of patients who underwent cholecystectomy showed that they had a significantly higher risk of NTS infection for more than 6 months after the procedure.Our study showed that cholecystectomy might be an independent risk factor for subsequent NTS infection.

The potential association between appendectomy and non-typhoidal Salmonella (NTS) infection has not been elucidated. We hypothesized that appendectomy may be associated with gut vulnerability to NTS. The data were retrospectively collected from the Taiwan National Health Insurance Research Database to describe the incidence rates of NTS infection requiring hospital admission among patients with and without an appendectomy. A total of 208,585 individuals aged ≥18 years with an appendectomy were enrolled from January 2000 to December 2012, and compared with a control group of 208,585 individuals who had never received an appendectomy matched by propensity score (1:1) by index year, age, sex, occupation, and comorbidities. An appendectomy was defined by the International Classification of Diseases, Ninth Revision, Clinical Modification Procedure Codes. The main outcome was patients who were hospitalized for NTS. Cox proportional hazards models were applied to estimate the hazard ratios (HRs) and 95% confidence intervals (CIs). Two sensitivity analyses were conducted for cross-validation. Of the 417,170 participants (215,221 (51.6%) male), 208,585 individuals (50.0%) had an appendectomy, and 112 individuals developed NTS infection requiring hospitalization. In the fully adjusted multivariable Cox proportional hazards regression model, the appendectomy group had an increased risk of NTS infection (adjusted HR (aHR), 1.61, 95% CI, 1.20–2.17). Females and individuals aged 18 to 30 years with a history of appendectomy had a statistically higher risk of NTS than the control group (aHR, 1.92, 95% CI, 1.26–2.93 and aHR, 2.67, 95% CI, 1.41–5.07). In this study, appendectomy was positively associated with subsequent hospitalization for NTS. The mechanism behind this association remains uncertain and needs further studies to clarify the interactions between appendectomy and NTS.

Background and Purpose: Preceding infection as an important risk factor for ischemic stroke has been reported but neglected for hemorrhagic stroke, especially in young and middle-aged patients. This study investigates whether newly diagnosed leptospirosis is associated with an increased risk of stroke. Methods: We identified 3699 in-patients who were aged ≥18 years and newly diagnosed with leptospirosis. We also randomly selected a comparison cohort 14 796 in-patients from the general population by using a propensity score matching method (at a 1:4 ratio). We analyzed the risks of stroke by using Cox proportional hazard regression models. Results: The adjusted hazard ratio (HR; 95% CI) of stroke for the leptospirosis group was 1.14 (0.93–1.38; P =0.200) as opposed to the comparison group after adjusting sex, age, and comorbidities. However, adjusted HR (95% CI) of ischemic stroke and hemorrhagic stroke was 1.01 (0.80–1.29) and 1.58 (1.12–2.23), respectively. The strength of association between leptospirosis and hemorrhagic stroke remained statistically significant after variation of leptospirosis and stroke definitions. The post hoc subgroup analysis indicated that a patient with leptospirosis had a significantly greater risk of hemorrhagic stroke in male (adjusted HR, 1.62 [95% CI, 1.08–2.44]) and individuals between age 18 and 39 (adjusted HR, 3.67 [95% CI, 1.33–10.14]). The risk of hemorrhagic stroke among people with leptospirosis was highest in the first 2 years after diagnosis (adjusted HR, 1.97 [95% CI, 1.15–3.38]). Conclusions: A 2.49-fold risk of stroke was found among the leptospirosis cohort of aged younger than 39 years. Age acted as an effect modifier between the leptospirosis and risk of new-onset stroke.

Background : This study investigated the correlation between a history of subconjunctival hemorrhages (SCH) and risk of systemic autoimmune diseases. Methods: We conducted a nationwide cohort study by our national insurance database. The study cohort comprised 16641 patients with incident SCH diagnosed by ophthalmologists between 2000 and 2012 and 16641 propensity score matched non-SCH comparison cohort by demographic characteristics and comorbidities. All study individuals were followed up until they developed systemic autoimmune diseases such as autoimmune hemolytic anemia, rheumatoid arthritis, systemic lupus erythematosus, Sjogren’s syndrome, systemic sclerosis , or dermatomyositis, withdraw from the insurance program, were lost to follow-up, or until the end of 2013. Cox proportional hazards regression analysis was used to analyze the risk of autoimmune diseases with hazard ratios (HRs) and 95% confidence intervals (CIs) between the NTS and comparison cohort. We also implemented a negative outcome control (motor vehicle traffic accident) to detect residual confounding. Results: 2,345 of all 33,282 patients developed autoimmune diseases during a 247,995 follow up person-years. The adjusted HRs (95% CI) of autoimmune diseases for SCH patients relative to controls was 1.61 (1.48, 1.75) after adjusting sex, age comorbidities and. (p

Background: We investigated whether taking methotrexate (MTX) is associated with a lower risk of new-onset cancers in patients with rheumatoid arthritis (RA). Methods: We conducted a 12-year retrospective cohort study from a population-based National Health Insurance Research Database in Taiwan. A total of 21,699 patients with newly diagnosed RA were enrolled during 2000–2009. The overall cancer rate was compared between 10,352 new users of MTX and 11,347 non-users. We used the WHO Defined Daily Dose (DDD) as a tool to assess drug exposure. Cox proportional hazard regression models were used to estimate the hazard ratio (HR) of disease after controlling for demographics and other comorbidities. Results: After adjusting for age, sex, cancer-related comorbidities, and RA-combined medication, the HR of cancer risk was 0.87 (95% CI = 0.74–1.02) for the MTX user group compared with the MTX non-user group. The cumulative incidence of cancer in the MTX non-user group was significantly higher than that of the MTX user group (log-rank test p Conclusion: MTX at middle and high accumulative doses might be associated with lower risk of new-onset cancers in patients with RA.

The purpose of this study was to explore the association between myasthenia gravis (MG) and the risk of atrial fibrillation (AF) in an Asian population. The risk was analyzed in a cohort of 5528 patients with history of MG and 5528 individuals without MG using a hospitalization claim dataset. Both groups were matched by age, sex, index year and baseline comorbidities as an original analysis. A Cox proportional hazard model was used to estimate the hazard ratio and 95% confidence interval of AF after adjusting for demographic and relevant clinical covariates. The adjusted hazard ratio of the MG group compared with that of the non-MG group was 1.03 (95% confidence interval, 0.76-1.38) for AF. A stratified analysis showed that compared with the propensity score matched non-MG group, there was no increased risk of developing AF based on age categories, gender, or comorbidities. Different time follow-up periods results showed no increased risk of AF compared with the non-MG group. Overall, in the Taiwanese cohort, MG is not associated with an increased risk of AF.

Background We investigated the correlation between a history of human papillomavirus (HPV) infection and alopecia areata risk. Methods The study cohort comprised 30,001 patients with newly diagnosed HPV infection between 2000 and 2012; and with use of computer-generated randomly numbers, patients not had HPV infection were randomly selected as the comparison cohort. HPV infection cohort were matched to comparison individuals at a 1:1 ratio by age, gender and index year. All study individuals were followed up until they developed alopecia areata, withdraw from the insurance program, lost to follow-up, or until the end of 2013. Cox proportional hazards regression analysis was used to analyze the risk of alopecia areata with hazard ratios (HRs) and 95% confidence intervals (CIs) between the HPV and control cohort. Results The adjusted hazard ratio (aHR) of alopecia areata for HPV patients relative to controls was 2.55 (95% C.I. = 1.88–3.47) after adjusting sex, age and comorbidities. Subgroup analysis indicated that patients with HPV infections had a significantly greater risk of alopecia areata for both genders, all age subgroups, and those with mental disorder diseases. Conclusions A history of HPV infection is associated with the development of subsequent alopecia areata in Taiwanese subjects.

This cohort study investigates the association of human papillomavirus infection status with development of end-stage kidney disease in Taiwan., Key Points Question What is the association of human papillomavirus (HPV) infection with subsequent development of end-stage kidney disease (ESKD) in the general population of Taiwan? Findings In this nationwide, population-based matched cohort study of 152 176 individuals, HPV infection was negatively associated with development of ESKD. Meaning These findings suggest that future detailed studies of the mechanisms involved in the association between HPV infection status and decreased risk of ESKD could yield targets for interventions to delay the development of ESKD., Importance The association between human papillomavirus (HPV) infection status and the natural process of kidney diseases has been neglected as an area of research. Further studies are needed to clarify factors that may alter the progression of end-stage kidney disease (ESKD). Objective To describe the rates of ESKD among patients with and without HPV infection. Design, Setting, and Participants In this nationwide, population-based retrospective cohort study, data were collected from the National Health Insurance Research Database of Taiwan. A total of 76 088 individuals with HPV infection were enrolled from January 1, 2000, to December 31, 2012, and compared with a control group of 76 088 individuals who had never been diagnosed with HPV infection (at a 1:1 ratio propensity-score matched by age, sex, index year, and comorbidities) in the context of the risk of developing ESKD. Statistical analysis was performed between November 2019 and July 2020. Exposures HPV infection was defined according to the International Classification of Diseases, Ninth Revision, Clinical Modification codes. Main Outcomes and Measures The main outcome was ESKD, as recorded in the Catastrophic Illness Patients database. Cox proportional hazards models were used to estimate hazard ratios (HRs) and 95% CIs, with the control group as a reference. Results Of 152 176 individuals (79 652 [52.3%] women; mean [SD] age, 34.4 [19.1] years), 76 088 individuals (50.0%) had HPV and 463 individuals (0.3%) developed ESKD. Incidence of ESKD was lower in individuals with HPV history than in those without HPV history (3.64 per 10 000 person-years vs 4.80 per 10 000 person-years). In the fully adjusted multivariate Cox proportional hazards regression model, individuals with a history of HPV infection had a significant decrease in risk of ESKD (adjusted HR, 0.72; 95% CI, 0.60-0.87) after adjusting for demographic characteristics, comorbidities, and comedications. In the subgroup analysis, individuals ages 50 to 64 years with HPV infection had a statistically significantly lower risk of ESKD compared with individuals ages 50 to 64 years with no HPV infection (adjusted HR, 0.48; 95% CI, 0.34-0.68; P

Objective. This study investigated whether women with a history of human papillomavirus (HPV) infection have an increased risk of infertility. Material and Methods. All patients with an HPV infection (n = 11,198) in Taiwan&rsquo, s National Health Insurance Research Database (2000&ndash, 2012) were propensity score matched with control subjects (n = 11,198) without an HPV infection by age, sex, index year, and relevant co-morbidities. Both groups were tracked until a diagnosis of infertility was recorded. The Chi-square test was used to analyze the distribution of demographic characteristics in the HPV group and non-HPV group. A Cox proportional hazards regression was used to estimate the hazard ratios (HRs) for the development of infertility, adjusting for age, sex, and co-morbidities. The Kaplan&ndash, Meier method was used to plot the cumulative incidence curves. We also performed negative controls to test for possible unmeasured confounding. Results. The HPV cohort had a higher risk of infertility. The adjusted HR (aHR) was found to be 1.39 (95% CI = 1.19&ndash, 1.63) after adjusting for demographic characteristics and relevant co-morbidities. In the age subgroup analysis, patients with an HPV infection had an increased risk of infertility compared to the non-HPV cohort in the group aged 26 to 35 years (aHR, 1.53, 95% CI = 1.24&ndash, 1.88). As we used propensity score matching to treat measurable confounders and negative controls to access unmeasured confounders, the findings of the study are robust. Conclusions. Among females of reproductive age, HPV infection is a potential risk factor that predisposes individuals to subsequent infertility.

OBJECTIVE To investigate the epidemiological relationship between dengue fever and the subsequent development of dementia. METHODS Using nationwide Taiwan registries from the National Health Insurance Research (NHIRD), we identified adults aged over 40 years who received a dengue fever diagnosis from 1 January 2000 to 31 December 2012 and who did not have a history of dementia. We used a propensity score match (PSM) to balance the baseline characteristics between groups. All eligible adults were sorted into either the dengue group or non-dengue group at a ratio of 1:4, matching by age, sex, index years, income level, and relevant comorbidities. Using Cox regression with proportional hazards models, we estimated the risk of dementia. The study period started from 1 January 2000 to 31 December 2013. We conducted sensitivity analyses to cross-validate study results. RESULTS With a median of 8.01 years of follow-up, patients in the dengue group were more at risk of developing dementia than the non-dengue group. The estimated cumulative incidence of dementia was 7.21% in the dengue group and 4.03% in the non-dengue group (adjusted hazard ratio (aHR), 1.71; 95% CI, 1.03 to 2.83). Sensitivity analyses yielded consistent findings. We excluded any stroke cases before the end of the study, and subgroup analysis by follow-up time showed that the dengue group has a significantly higher risk of new-onset dementia >6 years after the index date (aHR 3.24; 95% CI, 1.42 to 7.37). The P value for interaction was significant (

The purpose of this study was to evaluate the deep vein thrombosis (DVT) and pulmonary embolism (PE) risk among patients with a diagnosis of nontyphoidal salmonellosis (NTS) in an Asian population. The risk was analyzed in a cohort of 17,855 patients newly diagnosed with NTS and 71,420 individuals without NTS using a hospitalization claim dataset. Both groups were matched by age, sex, and index date as an original analysis. A Cox proportional-hazards regression model was applied to estimate the risk of DVT and PE, accounting for any competing event (death). With a follow-up of 4.94 (&plusmn, 3.93) years in the NTS group and 6.30 (&plusmn, 3.67) years in the non-NTS group, the adjusted subhazard ratios (SHRs) of DVT and PE were 1.83 (95% CI 1.44&ndash, 2.31) and 1.84 (95% CI 1.30&ndash, 2.60). The NTS group had an increased risk of DVT and PE compared with the control group in all of the age subgroups. Stratified analyses showed that patients aged 18&ndash, 39 years in the NTS group had significantly higher DVT and PE risks compared with patients of the same age in the non-NTS group (aHR, 5.95, 95% CI, 2.22&ndash, 15.91 for DVT, aHR 6.72, 95% CI, 2.23&ndash, 20.30 for PE). The P-value for interaction between age and exposure of NTS is &lt, 0.001 for DVT and 0.004 for PE in our sub-group analyses. The findings were cross-validated by a re-analysis with propensity score matching (PSM), and that revealed consistent results. Despite of low absolute risk, clinicians should be aware that patients with an NTS hospitalization history is at increased risk for VTE especially when assessing patients coincident with other VTE risk factors.

Objective: To explore the relationship between nontyphoidal salmonellosis (NTS) and the risk of acute ischemic stroke (IS) by using a nationwide, population-based study. Methods: A retrospective cohort study using claim data from Taiwan’s National Health Insurance Research Database, patients aged 20 years and older with NTS (N=1618) were included from January 1, 2000-December, 31, 2012, and the control group (N=6472) without NTS were matched by propensity score. The follow-up period was defined as the time from the initial diagnosis of NTS to the date of development of IS, or 31 December 2012. Patients previously diagnosed with stroke wer excluded. The Cox proportional hazard model was used to estimate the hazard ratio (HR) and 95% confidence interval (CI) of IS after adjusting for demographic and clinical covariate. Result: The adjusted hazard ratio for the NTS group compared with the control group was 1.34 (95% CI;1.10-1.65) for overall stroke. Furthermore, the NTS cohort had an increased risk of IS compared to the controls groups [adjusted HR 1.42(95% CI 1.14-1.78)]. Stratified analysis showed that NTS group aged ≥65 years (aHR= 1.37, 95% C.I. 1.05-1.78) and female (aHR= 1.41, 95% C.I. 1.06-1.88) had higher risk of stroke. The comorbidities subgroup analysis showed that NTS group with hyperlipidemia, hypertension, cancer, COPD, and heart failure, hade higher risks for stroke. A 1.79-fold significant increase in risk for stroke was observed especially during the first 2 years of follow-up (95% CI: 1.26-2.53). Conclusion: NTS is associated with increased risk of IS but not hemorrhagic stroke in the following 2 years. Early and mindful treatment plan about NTS may be a milestone to IS prevention especially in some subpopulation. Funding Statement: This study is supported in part by Taiwan Ministry of Health and Welfare Clinical Trial Center (MOHW108-TDU-B-212-133004), China Medical University Hospital, Academia Sinica Stroke Biosignature Project (BM10701010021), MOST Clinical Trial Consortium for Stroke (MOST 108-2321-B-039-003-), Tseng-Lien Lin Foundation, Taichung, Taiwan, and Katsuzo and Kiyo Aoshima Memorial Funds, Japan. Declaration of Interests: All of the authors declared no competing interests. Ethics Approval Statement: This study was approved by the Research Ethics Committee of China Medical University and Hospital in Taiwan (CMUH-104-REC2-115). As data used consisted of de-identified secondary data set released for research purposes and were analyzed anonymously, the need for informed consent was waived.

Objective: This nationwide study aimed to investigate the association between newly diagnosed systemic sclerosis (SSc) and previous appendicitis history. Methods: A total of 1595 patients who were newly diagnosed with SSc were recruited as the SSc cases from the 2003 to 2012 claims data of the entire population in Taiwan. The other 15,950 individuals who had never been diagnosed with SSc during 2003 and 2012 were selected as the non-SSc controls to match the SSc cases. We defined that the index date as the first date of SSc diagnosis of SSc cases and the first date of ambulatory visit for any reason of non-SSc controls. Conditional logistic regression analysis was applied for the association between appendicitis and the risk of the incident SSc, tested by estimating odds ratios (ORs) with 95% confidence intervals (CIs). Potential confounders, including the Charlson comorbidity index (CCI), a history of periodontal disease, salmonella infection, and intestinal infection, were controlled. We further designed sensitivity analyses by varying the definition of appendicitis according to the status of receiving primary appendectomy. Results: The mean age was 51 years in the case and control groups. Females accounted for 77.5%. A total of 17 (1.1%) out of 1595 SSc cases and 81 (0.5%) out of 15,950 non-SSc controls had a history of appendicitis before the index date had a history of appendicitis. A significant association between appendicitis and the risk of SSc was confirmed (OR, 2.03, 95% CI, 1.14–3.60) after adjusting potential confounders. CCI ≥ 1 (OR, 8.48, 95% CI, 7.50–9.58) and periodontal disease (OR, 1.55, 95% CI, 1.39–1.74) were also significantly associated with the risk of SSc. The association between appendicitis and SSc risk remained robust using various definitions of appendicitis. Conclusion: Our study demonstrated appendicitis was associated with the incident SSc. CCI ≥ 1 and periodontal disease also contributed to the risk of developing SSc.

Objective: To investigate the effect of dehydroepiandrosterone (DHEA) supplementation on women with poor ovarian response (POR). Materials and methods: Women with POR treated with flexible daily gonadotropin-releasing hormone antagonist in vitro fertilization (IVF) cycles at The Reproductive Center in Kaohsiung Veterans General Hospital between January 2013 and October 2013, were enrolled for this prospective study. When patients failed to become pregnant during the first IVF cycle, they were treated with DHEA supplementation (30 mg, 3 times a day, orally) for 3 months (mean 12.2 weeks) before the next IVF cycle. Parameters of biochemical, ultrasound and treatment outcomes were compared before and after DHEA supplementation. Results: Ten patients with a mean age of 36.6 ± 4.2 years were identified. After DHEA treatment, there was a significant increase in antral follicle count, from 2.8 ± 1.0 to 4.1 ± 1.2 (p

Objective: Our previous study showed the potential benefits of dehydroepiandrosterone (DHEA) supplementation in women with a poor ovarian response (POR). Because the connection between cumulus cells (CCs) and oocytes is a key step for oocyte maturation, we supposed that altered gene expression of CCs in women with POR after DHEA supplementation might favor oocyte maturation. Materials and methods: Women with POR treated with flexible daily gonadotropin-releasing hormone antagonist in vitro fertilization (IVF) cycles at The Reproductive Center in Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan between January 2013 and October 2013 were enrolled for this prospective study. CCs were isolated during IVF before and after DHEA (CPH-Formulation, Oakdale, CA, USA) supplementation. Nine genes of isolated CCs, including hyaluronan synthase (HAS2), versican (VCAN), thrombospondin 1 (THBS1), runt-related transcription factor 2 (RUNX2), chromobox homolog 3 (CBX3), tripartite motif-containing 28 (TRIM28), B-cell lymphoma 2 (BCL2), BCL2-associated X protein (BAX), and ankyrin repeat domain 57 (ANKRD57), were compared. Results: There was a significant difference in the expression of genes in women with POR before and after DHEA supplementation (all p

This study evaluated the prevalence of clinical multidrug-resistant organisms (MDROs) and analyzed correlations between MDROs and patient characteristics in a regional teaching hospital of Taiwan. A retrospective comparative case-control study was conducted from January 2016 to August 2018 by collecting data from 486 hospitalized and non-hospitalized patients (M = 286, F = 200), including patient gender and age, microbial species, and antibiotic susceptibility. The results indicated that at least one MDRO was isolated from 5.3&ndash, 6.3% of patients (p &lt, 0.05), with an average age of 61.08 years. Of the MDROs strains, vancomycin-resistant enterococcus and carbapenem-resistant acinetobacter baumannii increased annually (p &lt, 0.002 and p &lt, 0.012, respectively). Three factors of age (over 60 years), treatment in an intensive care unit (ICU), and specimen category were statistically significant (p &lt, 0.039, p &lt, 0.001 and p &lt, 0.001, respectively) and indicated that elderly patients in an ICU have a higher risk of being infected by MDROs. The outpatients infected by methicillin-resistant staphylococcus aureus (MRSA) were more frequent than inpatients, implying the existence of community-acquired MRSA strains. The results of this study could provide valuable information for the detection and colonization of multidrug-resistant organisms in hospital infection control systems.