Metformin use is associated with a lower risk of rotator cuff disease in patients with Type 2 diabetes mellitus.

AIMS: Metformin has been mentioned to be protective against inflammation, degeneration, and oxidative stress, conditions that are associated with rotator cuff disease. To access the association between metformin use and risk of rotator cuff disease in patients with type 2 diabetes mellitus (DM). METHODS: This was a retrospective cohort study utilizing Taiwan National Health Insurance Research Database between January 1, 2000, and December 31, 2012 to retrieved participants. Metformin and propensity score matched never metformin users were determined at baseline (between the date of onset of DM and the index date), and followed to December 31, 2013. Propensity scores were adopted to address measurable confounders (including demographic variables, Diabetes Complications Severity Index, relevant comorbidities and co-medication). A multivariable Cox proportional hazards regression model was applied to estimate the adjusted hazard ratios (HRs) for the risk of the first diagnosis of rotator cuff disease on the full cohort and on the propensity score matched cohort. RESULTS: In the propensity score matched cohort, a total of 34,964 individuals (19,416 [55.5%] men), 17,482 individuals were taking metformin, 559 [3.2%] of whom developed rotator cuff disease. Incidence of rotator cuff disease was 4.51 per 10,000 person-months in the metformin users and 5.11 in the controls. Among metformin group, the aHR (95% CI) was 0.879 (0.784-0.984) after full adjustment. The potential beneficial effect on the risk of rotator cuff disease was consistently observed across all subgroups, including sex, age, concomitant other glucose lowering drugs, and level of Diabetes Complications Severity Index (all P for interaction > 0.050). CONCLUSION: Metformin use was associated with a lower risk of rotator cuff disease in patients with type 2 DM.

Human Papillomavirus Infection and the Risk of Erectile Dysfunction: A Nationwide Population-Based Matched Cohort Study.

BACKGROUND: Male patients with genital warts are known for higher rates of sexual dysfunction. This study was conducted to investigate whether human papillomaviruses (HPV) infection is associated with an increased risk of erectile dysfunction (ED). METHODS: Patients aged over 18 with HPV infection (n = 13,296) and propensity score-matched controls (n = 53,184) were recruited from the Longitudinal Health Insurance Database (LHID). The primary endpoint was the diagnosis of ED. Chi-square tests were used to analyze the distribution of demographic characteristics. The Cox proportional hazards regression was used to estimate the hazard ratios (HRs) and 95% confidence intervals (CIs) for the development of ED in both groups, after adjusting for sex, age, relevant comorbidities, co-medication, and surgery. RESULTS: ED developed in 181 patients of the study group. The incidence density of ED was 2.53 per 1000 person-years for the HPV group and 1.51 per 1000 person-years for the non-HPV group, with an adjusted HR (95% CI) of 1.63 (1.37-1.94). In stratification analysis, adjusted HR of diabetes-, chronic obstructive pulmonary disease (COPD-), and stroke-subgroup were 2.39, 2.51, and 4.82, with significant p values for interaction, respectively. Sensitivity analysis yields consistent findings. CONCLUSIONS: The patients with HPV infection had a higher risk of subsequent ED in comparison to the non-HPV controls. The mechanism behind such association and its possible role in ED prevention deserves further study in the future.

Female Human Papillomavirus Infection Associated with Increased Risk of Ectopic Pregnancy: Early Evidence from Taiwan Population-Based Cohort Study.

BACKGROUND: This is an investigation of the human papillomavirus (HPV) infection and its correlation with the risk of ectopic pregnancy (EP). METHODS: The cohort study includes 11,239 patients with newly diagnosed HPV infections between 2000 and 2012, and by using computer-generated random numbers, patients who do not have HPV infections are selected randomly as the comparison cohort. The HPV infection cohort is matched to comparison individuals at a 1:10 ratio by age and index year. All individuals included in the study were followed up to the point they developed EP, pulled-out from the insurance program, lost to follow-up, or until the end of 2013. A Cox proportional-hazards regression analysis was used to analyze the risk of EP with the hazard ratios (HRs) and 95% confidence intervals (CIs) between the HPV and control cohort. RESULTS: The adjusted hazard ratio (aHR) of EP for HPV patients relative to controls is 1.70 (95% CI = 1.04, 2.78), indicating a positive correlation between EP and HPV in the 13-year follow-up period, after adjusting for age and relevant comorbidities. The sensitivity analyses yield similar results. CONCLUSIONS: A history of HPV infection is a potential risk factor associated with the development of subsequent EP in Taiwanese individuals, especially those diagnosed with an HPV infection within 3 years.

Syphilis and ischemic stroke: Old question revisited by a nationwide cohort study.

BACKGROUND AND PURPOSE: In the era of easily available antibiotic use, this study provides epidemiological evidence for a re-examination of the relationship between syphilis and ischemic stroke (IS). METHODS: Patients aged 18 years and older with newly diagnosed syphilis were included (n = 1585) from 2000 to 2012, and participants without syphilis in the control group (n = 6340) were matched by propensity score (age, sex, index year, insured amount, urbanization, seasons, and comorbidities). The Cox proportional hazard model was used to estimate the hazard ratio (HR) and 95% confidence interval (CI) of IS. Five different Cox regression models, sensitivity analyses, and negative control were conducted to test our findings. RESULTS: In all, 1585 patients (1055 (66.56%) men; mean (SD) age, 49.59 (20.32) years) had syphilis, and 3.8% had new-onset IS. The syphilis group had a higher risk of IS than the controls (adjusted HR, 1.35; 95% CI, 1.01-1.80; p value < 0.05) after full adjustment. Serial sensitivity analyses yielded consistent results. CONCLUSION: Syphilis patients have higher risk of IS, and our data raise the question of implementation of prophylactic treatment for IS.

Cytotoxic and Anti-Inflammatory Triterpenoids in the Vines and Leaves of Momordica charantia.

The vines and leaves of Momordica charantia L. are used as herbal medicines to treat inflammation-related disorders. However, their safety profile remains uncharacterized, and the constituents in their extracts that exert anti-inflammatory and adverse effects remain unclear. This study isolated the characteristic cucurbitane-type triterpenoid species in the vines and leaves of M. charantia L. and analyzed their cytotoxicity, anti-inflammatory effects, and underlying mechanisms. Four structurally related triterpenoids-momordicines I, II, IV, and (23E) 3ß,7ß,25-trihydroxycucurbita-5,23-dien-19-al (TCD)-were isolated from the triterpenoid-rich fractions of extracts from the vines and leaves of M. charantia. Momordicine I was cytotoxic on normal cells, momordicine II exerted milder cytotoxicity, and momordicine IV and TCD had no obvious adverse effects on cell growth. TCD had anti-inflammatory activity both in vivo and in vitro. In lipopolysaccharide-stimulated RAW 264.7 cells, TCD inhibited the inhibitor kappa B kinase/nuclear factor-κB pathway and enhanced the expression of nuclear factor erythroid 2-related factor 2, heme oxygenase-1, and glutamate-cysteine ligase modifier subunit through the extracellular signal-regulated kinase1/2 and p38. Thus, the vines and leaves of M. charantia should be used with caution. An extraction protocol that can enrich TCD but remove momordicine I would likely enhance the safety of the extract.

Association Between Severity of Leptospirosis and Subsequent Major Autoimmune Diseases: A Nationwide Observational Cohort Study.

Introduction: Infections play a role in autoimmune diseases (AD). Leptospirosis has been linked to the trigger of systemic lupus erythematosus. Objective: To investigate subsequent risk of major AD in hospitalized Taiwanese for Leptospirosis. Methods: Retrospective 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). Results: The 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. Conclusions: Symptomatic leptospirosis is associated with increased rate of subsequent major ADs, and the risk seems to be higher in severe cases.

The Potential Role of Human Papillomavirus Infection in Bell's Palsy: A Hypothesis-Generating Study Based on a Nationwide Cohort.

Objective: Our purpose was to investigate whether people with a previous human papillomavirus (HPV) infection were associated with an increased risk of Bell's palsy (BP). Methods: By using Taiwan population-based data, patients aged > 18 years with HPV infection (n = 22,260) from 2000 to 2012 were enrolled and compared with control subjects who had never been diagnosed with an HPV infection at a 1:4 ratio matched by sex, age, index date, and co-morbidities (n = 89,040). The index date was the first date of HPV diagnosis. All the patients were tracked until the occurrence of BP. Cox proportional hazards regression was applied to estimate the hazard ratios (HRs) for the development of BP in both groups. Results: The HPV group had 1.25 [95% confidence interval (CI) = 1.03-1.51] times higher risk of BP compared with the non-HPV group after adjusting for sex, age, and co-morbidities. The association of HPV and BP was significant in the sensitivity analyses. In the subgroup analysis, the impact of HPV infection on the risk of BP was more pronounced in the elderly > 50 years [adjusted hazard ratio (aHR) =1.86; 95% CI = 1.37-2.52], hypertension (aHR = 1.65; 95% CI = 1.17-2.31), and chronic obstructive pulmonary disease (aHR = 2.14, 95% CI 1.333.43) subgroups. Conclusions: Patients with HPV infection have a higher risk of subsequent BP compared with non-HPV patients. More rigorous studies are needed to confirm if and how specific HPV genotypes are associated with BP and the possible role of vaccines in disease prevention.

Non-Typhoidal Salmonella and the Risk of Kawasaki Disease: A Nationwide Population-Based Cohort Study.

Objective: The aim of this study was to investigate the relationship between non-typhoidal Salmonella (NTS) infection and the risk of Kawasaki disease (KD) by using a nationwide population-based data set in Taiwan. Methods: In 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. Results: After 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. Conclusions: NTS is associated with an increased risk of KD in Taiwanese children.

Absence of Association between Previous Mycoplasma pneumoniae Infection and Subsequent Myasthenia Gravis: A Nationwide Population-Based Matched Cohort Study.

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.

Risk of subsequent atrial fibrillation in patients with myasthenia gravis: A population-based cohort study.

ABSTRACT: 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.