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

BACKGROUND: The efficacy and safety of benralizumab, an interleukin-5 receptor alpha-directed cytolytic monoclonal antibody, for the prevention of exacerbations in patients with moderate to very severe chronic obstructive pulmonary disease (COPD) are not known.METHODS: In the GALATHEA and TERRANOVA trials, we enrolled patients with COPD (at a ratio of approximately 2:1 on the basis of eosinophil count [≥220 per cubic millimeter vs. RESULTS: In GALATHEA, the estimates of the annualized exacerbation rate were 1.19 per year (95% confidence interval [CI], 1.04 to 1.36) in the 30-mg benralizumab group, 1.03 per year (95% CI, 0.90 to 1.19) in the 100-mg benralizumab group, and 1.24 per year (95% CI, 1.08 to 1.42) in the placebo group; the rate ratio as compared with placebo was 0.96 for 30 mg of benralizumab (P = 0.65) and 0.83 for 100 mg of benralizumab (P = 0.05). In TERRANOVA, the estimates of the annualized exacerbation rate for 10 mg, 30 mg, and 100 mg of benralizumab and for placebo were 0.99 per year (95% CI, 0.87 to 1.13), 1.21 per year (95% CI, 1.08 to 1.37), 1.09 per year (95% CI, 0.96 to 1.23), and 1.17 per year (95% CI, 1.04 to 1.32), respectively; the corresponding rate ratios were 0.85 (P = 0.06), 1.04 (P = 0.66), and 0.93 (P = 0.40). At 56 weeks, none of the annualized COPD exacerbation rate ratios for any dose of benralizumab as compared with placebo reached significance in either trial. Types and frequencies of adverse events were similar with benralizumab and placebo.CONCLUSIONS: Add-on benralizumab was not associated with a lower annualized rate of COPD exacerbations than placebo among patients with moderate to very severe COPD, a history of frequent moderate or severe exacerbations, and blood eosinophil counts of 220 per cubic millimeter or greater (Funded by AstraZeneca [GALATHEA and TERRANOVA] and Kyowa Hakko Kirin [GALATHEA]; GALATHEA and TERRANOVA ClinicalTrials.gov numbers, NCT02138916 and NCT02155660.).

Pleural empyema is an important complication of pneumonia. Patients with stroke are at a higher risk developing pneumonia; however, the association between stroke and pleural empyema risk is largely unknown. We used the data from the National Health Insurance Research Database of Taiwan to establish a stroke group consisting of 466,170 patients diagnosed between 2000 and 2010, and a non-stroke group consisting of the same number of individuals matched by the propensity score. Incident pleural empyema was monitored toward the end of 2011. Adjusted hazard ratios (aHRs) of pleural empyema in the stroke group, compared to the non-stroke group, were estimated using the Cox proportional hazards model. We found that the incidence of pleural empyema is 2.69-fold higher in the stroke group than in the non-stroke group (15.2 vs. 5.59/10,000 person-years, p

Backgrounds Worldwide, the incidence of acute kidney injury (AKI) has been increasing. However, information on the long-term incidence of Parkinson disease (PD) in patients with AKI has not been reported. Methods A total of 9380 patients with AKI and 37,484 age- and sex-matched patients who did not have AKI were identified during 2003–2011. All patients were tracked until a diagnosis of PD, death, or the end of 2011. Cumulative incidences and hazard ratios (HRs) were calculated. Results The mean follow-up time for PD was 6.89 (SD = 3.30) years in the AKI cohort and 6.78 (SD = 3.29) years in the non-AKI cohort. The overall incidence densities of PD were significantly higher in the AKI cohort than in the non-AKI cohort (6.04 vs. 3.99/1000 person-years), with an adjusted HR of 1.47 (95% confidence interval [CI] = 1.18–1.83). Compared with the patients in the non-AKI cohort aged ≤ 64 years, the relative risk (95% CI) of PD was 2.17 (1.12–4.18), 14.1 (9.16–21.8), and 14.1 (8.43–23.6) for the patients in the AKI cohort aged ≤ 64, 65–79, and ≥ 80 years, respectively. Conclusion Patients with AKI were associated with a higher long-term risk of PD.

The objective of this nationwide cohort study was to investigate the risk of peptic ulcer disease (PUD) in living liver donors (LDs). A total of 1333 LDs and 5332 matched nondonors were identified during 2003-2011. Hospitalized patients identified as LDs were assigned to the LD cohort, and the non-LD comparison cohort comprised age- and sex-matched nondonors. Cumulative incidences and hazard ratios (HRs) were calculated. The overall incidence of PUD was 1.74-fold higher in the LD cohort than in the non-LD cohort (2.14 vs. 1.48 per 1000 person-years). After adjustment for age, sex, monthly income and comorbidities, we determined that the LD cohort exhibited a higher risk of PUD than did the non-LD cohort (adjusted HR 1.74, 95% confidence interval [CI] 1.45-2.09). The incidence of PUD increased with age; the risk of PUD was 2.53-fold higher in patients aged ≥35 years (95% CI 2.14-2.99) than in those aged ≤34 years. LDs with comorbidities of osteopathies, chondropathies and acquired musculoskeletal deformities exhibited a higher risk of PUD (adjusted HR 3.93, 95% CI 2.64-5.86) compared with those without these comorbidities. LDs are associated with an increased risk of PUD after hepatectomy.

Aims This study investigated whether patients with alcoholic cirrhosis have a high risk of hemorrhagic stroke. Methods In this study, 17,094 patients diagnosed with cirrhosis between 2000 and 2010 were identified using the Taiwan National Health Insurance claims data. Identified patients were randomly selected and propensity score matched with individuals without cirrhosis according to age, sex, comorbidities and index year. Results The overall incidence rate of stroke was 4.41 and 12.1 per 1000 person-years in the chronic liver disease and cirrhosis (CLDC) with hepatitis B virus (HBV) or hepatitis C virus (HCV) cohort and the alcoholic CLDC cohort, respectively. The alcoholic CLDC cohort exhibited a 4.53-fold higher risk of hemorrhagic stroke (adjusted subhazard ratio [aSHR] = 4.53, 95% confidence interval [CI] = 3.05-6.71) than did the non-CLDC cohort, and the CLDC with HBV or HCV cohort exhibited a 1.40-fold higher risk of hemorrhagic stroke (aSHR = 1.40, 95% CI = 1.10-1.78) than did the non-CLDC cohort. The alcoholic CLDC cohort and the CLDC with HBV or HCV cohort showed an aSHR of 1.80 (95% CI = 1.36-2.40) and 0.95 (95% CI = 0.83-1.07) for ischemic stroke, respectively, compared with the non-CLDC cohort. Conclusion Alcoholic patients with CLDC had a higher risk of hemorrhagic stroke compared with non-alcoholic patients with CLDC and patients without CLDC.

Background: Air pollution has been associated with autoimmune diseases. Nephrotic syndrome is a clinical manifestation of immune-mediated glomerulopathy. However, the association between nephrotic syndrome and air pollution constituents remains unknown. We conducted this nationwide retrospective study to investigate the association between PM2.5 and nephrotic syndrome. Methods: We used the Longitudinal Health Insurance Database (LHID) and the Taiwan Air Quality-Monitoring Database (TAQMD). We combined and stratified the LHID and the TAQMD data by residential areas of insurants linked to nearby air quality-monitoring stations. Air pollutant concentrations were grouped into four levels based on quartile. Univariable and multivariable Cox proportional hazard regression models were applied. Findings: Relative to Q1-level SO2, subjects exposed to the Q4 level were associated with a 2.00-fold higher risk of nephrotic syndrome (adjusted HR = 2.00, 95% CI = 1.66&ndash, 2.41). In NOx, relative to Q1 NOx concentrations, the adjusted HRs of nephrotic syndrome risk were 1.53 (95% CI = 1.23&ndash, 1.91), 1.30 (95% CI = 1.03&ndash, 1.65), and 2.08 (95% CI = 1.69&ndash, 2.56) for Q2, Q3, and Q4 levels, respectively. The results revealed an increasing trend for nephrotic syndrome risk correlating with increasing levels of NO, NO2, and PM2.5 concentrations. Interpretation: High concentrations of PM2.5, NO, NO2, and SO2 are associated with increased risk of nephrotic syndrome.

Meng-Jer Hsieh,1,2 Shu-Yi Huang,1 Tsung-Ming Yang,1 Chi-Wei Tao,3 Shih-Lung Cheng,4 Chao-Hsien Lee,5 Ping-Hung Kuo,6 Yao-Kuang Wu,7,8 Ning-Hung Chen,9 Wu-Huei Hsu,10 Jeng-Yuan Hsu,11 Ming-Shian Lin,12 Chin-Chou Wang,13 Yu-Feng Wei,14 Ying-Huang Tsai1,2 1Department of Pulmonary and Critical Care Medicine, Chiayi Chang Gung Memorial Hospital, Chang-Gung Medical foundation, Chiayi, Taiwan; 2Department of Respiratory Therapy, School of Medicine, Chang-Gung University, Taoyuan, Taiwan; 3Department of Internal Medicine, Cheng Hsin General Hospital, Taipei, Taiwan; 4Department of Internal Medicine, Far Eastern Memorial Hospital, Taipei; 5Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, MacKay Memorial Hospital, Taipei, Taiwan; 6Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan; 7Division of Pulmonary Medicine, Taipei Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, New Taipei City, Taiwan; 8School of Medicine, Tzu Chi University, Hualien, Taiwan; 9Department of pulmonary and critical care medicine, LinKou Chang Gung Memorial Hospital, Taoyuan, Taiwan; 10Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, China Medical University Hospital, Taichung, Taiwan; 11Division of Chest Medicine, Taichung Veterans General Hospital, Taiwan; 12Dpartment of Internal Medicine, Ditmanson Medical Foundation, Chia-Yi Cristian Hospital, Chia-Yi, Taiwan; 13Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital, Chang-Gung Medical Foundation, Kaohsiung, Taiwan; 14Department of Internal Medicine E-Da Hospital, I-Shou University, Kaohsiung, Taiwan Background: This nationwide study was performed to evaluate the evolution of distributions of patients with COPD according to the 2011 and 2017 Global Initiative for Chronic Obstructive Pulmonary Disease (GOLD) guidelines and to assess the concordance between the prescribed medications and the pharmacological management recommended by the two distinct classification systems in Taiwan.Subjects and methods: Data were retrospectively retrieved from stable COPD patients in 11 participating hospitals across Taiwan. Patients were grouped according to GOLD 2011 and 2017 guidelines respectively. Definitions of undertreatment and overtreatment were based on the pharmacological recommendations in the individual guidelines.Results: A total of 1,053 COPD patients were included. The percentages of patients in GOLD 2011 groups A, B, C and D were 18.4%, 40.6%, 6.7% and 34.2%, respectively. When reclassified according to the GOLD 2017, the percentages of group A and B increased to 23.3% and 63.2%, and groups C and D decreased to 1.9% and 11.6%, respectively. Up to 67% of patients in GOLD 2011 groups C and D were reclassified to GOLD 2017 groups A and B. The pharmacological concordance rate was 60.9% for GOLD 2011 and decreased to 44.9% for GOLD 2017. Overtreatment was found in 29.5% of patients according to GOLD 2011 and the rate increased to 46.1% when classified by the GOLD 2017. The major cause of overtreatment was unnecessary inhaled corticosteroids and the main cause of undertreatment was a lack of maintenance long-acting bronchodilators.Conclusion: The distribution of COPD patients in Taiwan was more uneven with the GOLD 2017 than with the GOLD 2011. A pharmacological discordance to the guidelines was identified. Updated guidelines with reclassification of COPD patients resulted in more discordance between prescribed medications and the guidelines. Physicians should make proper adjustments of the prescriptions according to the updated guidelines to ensure the mostly appropriate treatment for COPD patients. Keywords: chronic obstructive pulmonary disease, GOLD guidelines, inhaled corticosteroids, long-acting bronchodilators

Although experimental models have shown that statins could alleviate glomerular damage and decrease urinary protein excretion, the renal effects of statins remain unclear. A case-control study was conducted using data from Taiwan's National Health Insurance system.An end-stage renal disease (ESRD) group comprising 11,486 patients was established. Each patient was frequency-matched by age, sex, and comorbidities with one person without ESRD from the general population. Logistic regression analysis was performed to estimate the influence of statin use on ESRD risk.The overall adjusted odds ratios (ORs) of ESRD among patients who received statins was 1.59 (95% confidence interval=1.50-1.68). The raised ESRD risk of statin remained consolidated regardless of statin type (P.001), except lovastatin. Further, while stratified by cumulative define daily dose, the risk of ESRD increased with accumulative dosage of statins (P for trend.001).This population-based case-control study showed that statin use might be associated with increased ESRD risks. Large-scale randomized clinical trial encompassing statins of different kinds and populations of different comorbidities would be helpful to clarify the potential ESRD risks of statin users.

Background Previous studies have suggested that mycobacterial infections could trigger autoimmune diseases, including rheumatoid arthritis (RA). Objective To explore the association between previous tuberculosis (TB) and RA. Methods We conducted a case-control study using data obtained from the National Health Insurance (NHI) system of Taiwan. We identified 26 535 adults with RA from 2002 to 2011, with the date of diagnosis as the index date. This number was randomly selected and frequency-matched four times by age, sex and the year of index date from among non-RA individuals. Odds ratios (ORs) of RA were calculated for associations with TB. Results Compared with controls, RA patients had a crude OR of 1.77 for TB (95%CI 1.61-1.94). The strength of the association between RA and TB remained at the same level after controlling for other potential risk factors (adjusted OR 1.73, 95%CI 1.57-1.90), although RA patients tended to have a higher prevalence of hypertension, coronary artery disease and kidney disease. Conclusion TB was much more prevalent in RA patients than in control subjects. Prospective cohort studies are required to establish a causal relationship between previous TB and RA.

Type 1 diabetes mellitus (T1DM) has been linked to many autoimmune problems. The association between T1DM and urticaria warrants investigation. Data were extracted from the National Health Insurance Research Database (NHIRD) of Taiwan. Participants with T1DM were recruited as the case group, and that group was matched by sex and age at a ratio of 1:4 to the control group comprising those without T1DM. The study period was 1998&ndash, 2011. All participants were followed up to the diagnosis of urticaria, withdrawal from the insurance program, death, or the end of the study. A multivariable Cox proportional hazard model was used to calculate the adjusted and crude hazard ratios for urticaria. A total of 5895 participants (1179 in the case group and 4716 in the control group) were followed up in the study. The total incidence rate of urticaria in patients with type 1 DM was 26.6 per 1000 person-years, and that in controls was 6.85 per 1000 person-years. Compared with the control group, the hazard ratio of urticaria in the case group was 2.84 (95% CI = 2.27&ndash, 3.56). Compared with age-matched participants without T1DM, patients with type 1 DM aged &lt, 18 years had a 3.62-fold higher risk of urticaria (95% CI = 2.85&ndash, 4.59). The hazard ratio in patients with an adjusted Diabetes Complications Severity Index (aDCSI) score of 1.01&ndash, 2.00 per year was 2.57 (95% CI = 1.18&ndash, 5.57), and that in patients with an aDCSI score of &gt, 2.00 per year was 4.47 (95% CI = 2.68&ndash, 7.47). T1DM patients aged &lt, 18 years had an increased risk of urticaria, but a similar phenomenon was not observed among T1DM patients older than 18 years.

ObjectiveThoracic infection and pneumonia are prevalent in patients with schizophrenia; however, it is unclear whether patients with schizophrenia are at an increased risk of developing pleural empyema.DesignA retrospective cohort study with propensity-matched cohorts with and without schizophrenia.SettingUsing the National Health Insurance Research Database of Taiwan.ParticipantsWe identified 55 888 patients with schizophrenia newly diagnosed in 2000–2011 and same number of individuals without schizophrenia as the comparison cohort, frequency matched by propensity scores estimated using age, sex, occupation, income, urbanisation, year of diagnosis and comorbidities.Primary outcome measuresWe assessed incident pleural empyema by the end of 2011 and used the Cox proportional hazards model to calculate the schizophrenia cohort to comparison cohort HR of pleural empyema.ResultsThe overall incidence of pleural empyema was 2.44-fold greater in the schizophrenia cohort than in the comparison cohort (4.39vs1.80 per 10 000 person-years), with an adjusted HR of 2.87(95% CI 2.14 to 3.84). Stratified analyses by age, sex, occupation, income, urbanisation and comorbidity revealed significant hazards for pleural empyema associated with schizophrenia in all subgroups.ConclusionsPatients with schizophrenia are at an increased risk of developing pleural empyema and require greater attention and appropriate support.

Direct evidence of whether thyroid cancer patients have a higher risk of age-related macular degeneration (AMD) has yet to be investigated. Patients older than 50 years-old and newly diagnosed with thyroid cancer between 2000 and 2008 were identified from the national health insurance research database (NHIRD). We applied time-varying Cox proportional hazard models to assess the association between thyroid cancer and AMD. The multivariable models included conventional cardiovascular risk factors, myopia, vitreous floaters, hypothyroidism, hyperthyroidism, and treatment modality of thyroid cancer. The analysis process was stratified by age, gender, and comorbidity. In this study, 5253 patients were included in a thyroid cancer cohort (men 24.5%; median age 59.1 years (53.7–67.4 years), and 21,012 matched controls were included in a non-thyroid cancer cohort. The AMD incidence was 40.7 per 10,000 person/year in the thyroid cancer cohort. The thyroid cancer cohort had a higher risk (adjusted hazard ratio (aHR) = 1.38, 95% confidence interval, CI = 1.09–1.75) of AMD than the non-thyroid cohort. Thyroid cancer patients had a higher risk of AMD, especially the male patients (aHR = 1.92, 95% CI = 1.38–3.14) and the patients with comorbidities (aHR = 1.38, 95% CI = 1.09–1.74). In conclusion, thyroid cancer patients older than 50 years-old have increased risk of AMD.

Objective Data regarding the association between hypoglycemia and attention deficit hyperactivity disorder (ADHD) in children and adolescents with type 1 diabetes mellitus (T1DM) are limited. This study investigated whether hypoglycemia was associated with the risk of ADHD in young people with T1DM. Methods Children and adolescents with a diagnosis of T1DM were identified from the Longitudinal National Health Insurance Database in Taiwan from 1998 to 2011. Among them who were newly diagnosed with hypoglycemia during 2000 to 2007 were selected for the hypoglycemia cohort. The hypoglycemia diagnosis date was defined as the index date. Those who were diagnosed with ADHD before the index date were excluded. The main outcome was the development of ADHD. In total, 726 participants with hypoglycemia and 2852 participants without hypoglycemia were included in this study. Results The overall incidence density of ADHD was markedly increased among cohort with hypoglycemia compared with cohort without hypoglycemia (4.74 vs 1.65 per 1000 person-years), with an adjusted hazard ratio (aHR) of 2.73 (95% confidence interval [CI] = 1.50-4.98). Cohort with hypoglycemia who had experienced a hypoglycemic coma had a significantly higher risk of ADHD (aHR = 6.54, 95% CI = 1.89-22.7) compared with cohort without hypoglycemia. Conclusions Hypoglycemia, especially hypoglycemic coma, is significantly associated with a subsequent risk of ADHD in young people with T1DM.

Background & aims Until now, no study has investigated the risks of acute coronary syndrome (ACS) and peripheral arterial disease (PAD) in cirrhosis. Methods In this study, 57,214 patients diagnosed with cirrhosis between 2000 and 2010 were identified from the Taiwan National Health Insurance claims data. Each patient was randomly selected and frequency-matched with an individual without cirrhosis by age, sex, and index year. Results The overall incidence rates of ACS and PAD were 2.81 and 2.97 per 1000 person-years, respectively, in the cirrhosis cohort. The cirrhosis cohort had a higher risk of ACS [adjusted subhazard ratio (aSHR) = 1.12, 95% confidence interval (CI) = 1.03–1.22] and PAD (aSHR = 1.11, 95% CI = 1.02–1.21). The risk of ACS was highest among members of the cirrhosis cohort with ascites (aSHR = 1.09, 95% CI = 1.11–1.19). Conclusions Patients with chronic liver disease and cirrhosis have higher risks of ACS and PAD than those without chronic liver disease and cirrhosis.

Study objectives Previous literature lacks the analysis of non-apnea sleep disorder (NASD) and peripheral arterial disease (PAD). The aim of this study was to evaluate the association between NASD and risk of developing PAD using retrospective data from a national database in Taiwan. Design, setting, and participants We identified 46,064 patients with NASD using the catastrophic illness registry of the Taiwan National Health Insurance Research Database (NHIRD) from 1996 to 2010. We also selected a comparison cohort of 92,128 subjects who were randomly frequency-matched by age, sex, and entry year of the NASD cohort from the same database. Interventions non-apnea sleep disorders. Main outcome and measurements The study followed up all subjects from their entry date to the occurrence of PAD. We evaluated the risks of PAD using Cox proportional hazards regression models. The survival function for PAD was assessed using the Kaplan–Meier method. Results The risk of PAD was 1.49-fold in patients with NASD compared with patients without NASD after adjusting for age, sex, and comorbidities. Patients with NASD and diabetes or with NASD and hyperlipidemia had an increased risk of PAD compared to those without NASD and diabetes or hyperlipidemia. Conclusions We demonstrated the significantly increased risk of PAD in NASD patients through a nationwide population-based retrospective cohort study.

BACKGROUND Tuberculosis (TB) is an infectious disease involving multiple organs, including the eyes. We examined the risk of cataract among patients with TB using population data. METHOD Using data from the National Health Insurance (NHI) system of Taiwan, we established a TB cohort with 6994 patients newly diagnosed between 2000 and 2010. For each TB patient, four subjects without TB were randomly selected for the non-TB cohort, frequency matched by age, sex and diagnosis years. The incidence of cataract was measured by the end of 2011. The hazard ratio (HR) of cataract was estimated using Cox proportional hazards regression analysis. RESULTS The overall incidence rate of cataract was 21% greater in the TB cohort than in the non-TB cohort (22.9 vs. 18.8/1000 person-years, P < 0.001), with an adjusted HR (aHR) of 1.26 (95%CI 1.16-1.37). Cataract incidence increased with age, and was higher in men than women and much higher for those with comorbidity. The hazard of cataract was higher in the first 6 months after TB diagnosis. CONCLUSION TB patients are at elevated risk of developing cataract. Although the incidence decreased with time, the aHR remains statistically significant through the follow-up years.

Background & Aims We conducted a nationwide, population-based cohort study to evaluate the effects of inflammatory bowel disease (IBD) on the risks of developing deep vein thrombosis (DVT) and pulmonary embolism (PE) in Taiwan. Methods We randomly selected the study cohort with IBD from the National Health Insurance (NHI) database ( N =23.74 million) and the control cohort without IBD who was frequency-matched the study cohort based on age, sex, and index year to each IBD patient between 2000 and 2010. Using a follow-up period ending in 2011, we analyzed the risks of DVT and PE using Cox proportional hazard regression analyses. Results The 11 445 IBD patients and 45 780controls were followed 65 256 and 293 377 person-years, respectively. After adjusting for age, sex, and comorbidities, the risks of IBD patients developing DVT and PE was 1.98-fold and 1.80-fold higher, respectively, than those of the comparison cohort. The IBD patients presenting with 2 or more annual hospitalizations exhibited a significantly greater risk of developing DVT (adjusted hazard ratio [HR] 32.9, 95% confidence interval [CI] 20.5–52.8) and PE (adjusted HR=24.2, 95% CI=11.1–52.9) than did the comparison cohort. Women with IBD showed a significantly greater risk of DVT and PE than did the comparison cohort (adjusted HR=1.80, 95% CI=1.18–2.78 for DVT and adjusted HR=2.08, 95% CI=1.14–3.80 for PE respectively). Conclusion The risks of DVT and PE are significantly higher in IBD patients compared with risks in the general population. What is current knowledge Thromboembolic complications are easily overlooked in IBD patients. What is new here The risks of DVT and PE are significantly higher in IBD patients.

Background: Studies investigating the epidemiological relationship between Mycoplasma pneumonia (MP) and the subsequent development of acute coronary syndrome (ACS) are scant. We conducted a nationwide longitudinal cohort study in Taiwan to explore whether MP patients are at an increased risk of developing ACS. Methods: This study investigated the incidence and risk factors for ACS in 12 152 newly diagnosed MP patients from the Taiwan National Health Insurance Research Database between 2004 and 2011. The control group consisted of 48 600 individuals without MP. The follow-up period ran from the time of initial MP diagnosis to the date of an ACS event, censoring, or 31 December 2011. We analyzed the risk of ACS by using Cox proportional hazard regression models, including variables for sex, age and comorbidities. Results: The incidence of ACS was higher in MP patients than in comparison cohort (3.08 vs. 2.42 per 1000 person-years). The hazard ratio of developing ACS increased 37% in MP patients compared with that in the comparison cohort after adjustment for covariates. The effect of MP on subsequent ACS development appeared to 12 months after infection. Conclusion: This nationwide study determined that compared with the general population, MP patients exhibited a 37% increase in the risk of subsequently developing ACS. Clinicians should be aware of this risk in MP patients and provide appropriate cardiovascular management in addition to MP treatment.

Objective Studies investigating the relationship between sleep disorders (SDs) and the risk of venous thromboembolism (VTE) are scarce. The present study from Taiwan evaluated whether the risk of VTE was associated with SDs other than sleep apnea. Methods The present study investigated the incidence and risk of VTE in 46,371 people with SDs, compared with 92,742 controls without SDs. The follow-up period began from the date of entering the study cohort to the date of a VTE event, censoring, or December 31, 2011. A Cox proportional hazards regression analysis was conducted to estimate the effects of SDs on the risk of VTE. Results The SD cohort had a 1.79-fold adjusted hazard ratio (HR) of subsequent VTE, compared with the non-SD cohort (95% CI 1.49–2.16). The incidence of VTE increased with age for both cohorts but was higher for those in the SD cohort. However, the adjusted HRs for VTE were significantly higher for the people with SDs aged ≦49 years (HR 3.29, 95% CI 2.12–5.12) and 50–64 years (HR 2.43, 95% CI 1.76–3.35), but were not significant for the oldest group (HR 1.11, 95% CI 0.84–1.47), compared with the controls. The multiplicative increased risk of VTE was significant for the people with SDs with any comorbidity. Conclusion This nationwide cohort study determined that the VTE risk significantly increased in people with SDs compared with those of the general population.

Objectives Few studies have examined the risk of acute coronary syndrome (ACS) in asthmatics. We investigate the effects of asthma on the risk of ACS development in an Asian population. Methods Asthma patients aged ≥ 18 years were identified, and asthma-free controls were randomly selected from the general population and frequency-matched according to age, sex, index year, and baseline comorbidity by using the National Health Insurance Research Database. Both cohorts were followed up until the end of 2011 to measure the incidence of ACS. The risk of ACS was analyzed using Cox proportional hazards regression models. Results We observed the asthmatic patients for 97,506 person–years and followed the nonasthmatic people for 193,423 person–years. The incidence density rate of ACS increased in all groups of the asthmatic patients compared with those of the controls when the data were stratified according to sex, age, and comorbidities. The hazard ratio (HR) of ACS was 1.66-fold greater in the asthmatic cohort than in the nonasthmatic cohort, after adjusting for sex, age, and comorbidities (95% confidence interval [CI]: 1.31–2.11). The adjusted HR of developing ACS increased substantially as age and the frequency of asthmatic exacerbation and hospitalization increased. Conclusions Asthma is an independent risk factor of ACS, and poor control of asthma increases the risk of ACS development in a dose-dependent manner.

Background There is some evidence that the prevalence of depression in patients with tuberculosis (TB) is higher than those in the general population. However, the incidence of depression after Mycobacterium tuberculosis infection remains unknown. Our aim was to assess the association between TB and the subsequent risk of depression. Methods We conducted a retrospective cohort study using data from the National Health Insurance (NHI) system of Taiwan. The TB cohort included 9020 patients who were newly diagnosed and recruited between 2000 and 2010. Each patient was randomly frequency-matched for age, sex and the year of index date with four people without TB from the general population. The newly diagnosed depression was followed up until the end of 2011. The relative risks of depression were estimated using Cox proportional hazard models after adjusting for age, sex, index year and comorbidities. Results The overall incidence rate of depression was 1.54-fold higher in the TB cohort as compared with the controlled cohort (8.15 vs. 5.29 per 1000 person-years, 95% confidence interval [CI] = 1.45–1.64). Stratified analyses by gender, age group, monthly income and comorbidities revealed that the adjusted hazard ratio (HR) of depression was higher in males as well as individuals older than 65 years with a low monthly income and comorbidities. Conclusion People who have been diagnosed with TB have a significantly higher risk of developing depression compared with those in the general population. We should pay more attention to this group of individuals and ensure that they are offered appropriate support.

Purpose To clarify the relationship between asthma–chronic obstructive pulmonary disease overlap syndrome (ACOS) and depression. Methods We identified 10,911 patients who received an ACOS diagnosis and concurrent treatment between January 2000 and December 2009. Subjects without ACOS were included in the non-ACOS cohort (n = 10,911). Cox proportional hazard regression analysis was performed to compare the risk of depression between the ACOS and non-ACOS cohorts. Results The risk of depression was higher in the ACOS cohort than in the non-ACOS cohort (adjusted hazard ratios (aHRs) = 1.67, 95% confidence interval [CI] = 1.48–1.88). In the ACOS cohort, the aHRs for depression were [2.44 (95% CI = 1.45–4.11); 2.36 (95% CI = 1.58–3.52)] in patients [aged 20–39 years; without comorbidity]. In the ACOS cohort, the aHRs for depression were 1.70 (95% CI = 1.51–1.93) and 1.84 (95% CI = 1.55–2.19) in patients without inhaled corticosteroids (ICSs) and oral steroids (OSs) use, respectively. Moreover, the aHRs for the risk of depression were 1.16 (95% CI = 0.95–1.41) and 1.12 (95% CI = 0.96–1.29) in patients with ICSs and OSs use, respectively. Conclusion The risk of depression is higher in ACOS patients, even in those without comorbidities or in young adults. The events of the depression were not significant difference in patients receiving the ICSs/OSs between the ACOS and the non-ACOS cohorts.

Purpose Chronic exocrine pancreatic insufficiency can lead to osteoporosis. However, the incidence and risk of osteoporosis after acute inflammation of pancreas remained known. Thus, we conducted a population-based cohort study to clarify the association between acute pancreatitis (AP) and osteoporosis. Methods Patients newly diagnosed with AP with index date between 2000 and 2011 were identified from the National Health Insurance Research Database. Osteoporosis were defined according to the International Classification of Diseases, Ninth Revision, Clinical Modification codes. We applied age-, sex-, and comorbidities-adjusted variable Cox proportional hazard models for assessing the association between AP and osteoporosis. Moreover, these models were used to adjust for the influences of patient characteristics and comorbidities. Results In this study, 4,016 patients were included in the AP cohort (males, 67.9%; mean age, 51.8 years) and 4,016 matched controls in the non-AP cohort. After a mean follow-up period of 4.97 and 5.21 years in the AP and non-AP cohorts, respectively, the incidence of osteoporosis was 8.22 per 1000 person-years in the AP cohort. The AP cohort had a higher risk [adjusted hazard ratio (aHR) = 1.27, 95% confidence interval (CI) = 1.02-1.58] of osteoporosis than did the non-AP cohort. The risk of osteoporosis was highest in the female patients of the AP cohort (aHR = 2.26, 95% CI = 1.85-2.76) and patients aged 50-64 years (aHR = 4.14, 95% CI = 3.13-5.47). Conclusion AP patients are at a risk of osteoporosis, especially female gender and age 50-64 years. Those with > 3 episodes of AP had highest significant risk of developing osteoporosis.

Purpose Hepatitis C virus (HCV) infection is associated with increased systemic oxidative stress, which leads to cardiovascular events, diabetes, and chronic kidney disease. Similarly, cataract is also associated with increased oxidative stress. The association between HCV infection and increased risk of cataract remains unclear. Methods A total of 11,652 HCV-infected patients and 46,608 age- and sex-matched non-HCV infected patients were identified during 2003–2011. All patient data were tracked until a diagnosis of cataract, death, or the end of 2011. Cumulative incidences and hazard ratios (HRs) were calculated. Results The mean follow-up durations were 5.29 and 5.86 years for the HCV and non-HCV cohorts, respectively. The overall incidence density rate for cataract was 1.36 times higher in the HCV cohort than in the non-HCV cohort (1.86 and 1.37 per 100 person-y, respectively). After adjusting for age, sex, comorbidities of diabetes, hypertension, hyperlipidemia, asthma, chronic obstructive pulmonary disease, coronary artery disease, and anxiety, patients with HCV infection had an increased risk of cataract compared with those without HCV infection [adjusted HR = 1.23, 95% confidence interval (CI) = 1.14–1.32]. HCV-infected patients receiving interferon–ribavirin therapy had a 1.83 times higher (95% CI = 1.40–2.38) risk of cataract than non-HCV infected patients did. Conclusion HCV infection, even without the complication of cirrhosis, is associated with an increased risk of cataract, and this risk is higher in HCV-infected patients undergoing interferon–ribavirin therapy.

It is well known that patients with diabetes have higher extent and severity of periodontitis, but the backward relationship is little investigated. The relationship between periodontitis needing dental surgery and subsequent type 2 diabetes mellitus (DMT2) in those individuals without diabetes was assessed.This is a retrospective cohort study using data from the national health insurance system of Taiwan. The periodontitis cohort involved 22,299 patients, excluding those with diabetes already or those diagnosed with diabetes within 1 year from baseline. Each study participant was randomly frequency matched by age, sex, and index year with one individual from the general population without periodontitis. Cox proportional hazards regression analysis was used to estimate the influence of periodontitis on the risk of diabetes.The mean follow-up period is 5.47 ± 3.54 years. Overall, the subsequent incidence of DMT2 was 1.24-fold higher in the periodontitis cohort than in the control cohort, with an adjusted hazard ratio of 1.19 (95% confidence interval = 1.10 to 1.29) after controlling for sex, age, and comorbidities.This is the largest nation-based study examining the risk of diabetes in Asian patients with periodontitis. Those patients with periodontitis needing dental surgery have increased risk of future diabetes within 2 years compared with those participants with periodontitis not requiring dental surgery.

Objective.Studies of the risks of deep vein thrombosis (DVT) and pulmonary embolism (PE) in patients with Sjögren syndrome (SS) in Asia are scant. We evaluated the effect of SS on the incidences of DVT and PE in a nationwide, population-based cohort in Taiwan.Methods.We identified patients in Taiwan diagnosed with SS between 1998 and 2008 in the Catastrophic Illness Patient Database and the National Health Insurance Research Database. Each patient with SS was matched to 4 control patients based on age, sex, and index year, and all patients were followed up from the index date to December 31, 2010. We calculated the hazard ratios (HR) and 95% CI of DVT and PE in the SS and comparison cohorts by using Cox proportional hazards regression models.Results.We followed 8920 patients with SS and a comparison cohort of 35,680 for about 50,000 and 200,000 person-years, respectively. The mean age of the SS and comparison cohorts was 53.5 and 53.1 years, respectively, and 88.9% of the patients were women. The risks of DVT and PE among the patients with SS were a 1.83-fold and 3.29-fold greater, respectively, than those for the general population after adjusting for age, sex, comorbidities, and frequency of hospitalization. The patients with a secondary SS had a greater risk of PE (adjusted HR: 5.06; 95% CI: 1.22–21.1) than those with a primary SS (adjusted HR: 3.21; 95% CI: 1.96–5.23).Conclusion.Patients with SS have a significantly greater risk of developing DVT or PE than the general population.

Background: Several studies have indicated an association between venous thromboembolism (VTE) and a subsequent diagnosis of cancer in Western countries. However, information is scant on subsequent cancer incidence after idiopathic VTE events in Asian people. Through a nationwide cohort study, we evaluated the cancer prevalence of VTE and new cancer incidence in patients after the first episode of idiopathic VTE. Methods: To conduct a nationwide population cohort study on VTE, we retrieved data from the Taiwan National Health Insurance Database from 1998 to 2008, including a 2-year follow-up period extending to the end of 2010. The occurrence of cancer in the cohort was also determined by accessing the Registry for Catastrophic Illness Patient Database. Results: A total of 45 242 patients had the newly diagnosed VTE from 1998 to 2008. The incidence of VTE increased with age. Among 28 243 idiopathic VTE patients, 1944 patients (6.89%) had a subsequent cancer diagnosis within 2 years of the first idiopathic VTE episode. The three most common newly diagnosed cancers after idiopathic VTE were lung cancer, liver cancer and colorectal cancer (18.3%, 12.3% and 10.9%, respectively). Male sex and advanced age are independent risk factors of having an underlying malignant disorder among patients diagnosed with idiopathic VTE. Conclusion: Patients with symptomatic VTE without an identifiable risk factor have a 6.89% incidence of subsequent cancer diagnosis in Taiwan. An extensive screening for an occult cancer in an idiopathic VTE patient may be warranted.

Background We conducted a cohort study to determine the relationship between enterovirus (EV) infection and asthma. Materials and Methods From the National Health Insurance Research Database of Taiwan, we identified patients who received a new diagnosis of asthma and concurrent treatment between January 2000 and December 2011 (EV cohort: n = 208,213; non-EV cohort: n = 208,213). Cox proportional hazards regression analysis was performed to determine and compare the adjusted hazard ratios (aHRs) of asthma between these 2 cohorts. Kaplan–Meier analysis was conducted to assess the differences in the cumulative incidence curves of asthma between the 2 cohorts. Results The overall aHR of asthma was 1.48-fold higher in the EV cohort than in the non-EV cohort (95% confidence interval = 1.45–1.50). The aHR of asthma was higher in the EV cohort than in the non-EV cohort, comprising children aged ≤5 years, regardless of sex, sociodemographic factors (urbanization level and parental occupation), or comorbidities. The risk of asthma was higher in 1–3, 4–6, 7–9, and 10–12 months (all P 5 per year). Conclusion The incidence of asthma was higher in the EV cohort than in the non-EV cohort, comprising children aged ≤5 years, regardless of sex, urbanization level, parental occupation, or season. In particular, the risk of asthma was higher in children with a higher frequency of admission, even in the absence of atopy or other respiratory infections. This article is protected by copyright. All rights reserved.

Objective Sleep disorders are prevalent medical disorders in patients with rheumatoid arthritis (RA). However, whether patients with RA are at an increased risk of developing obstructive sleep apnoea (OSA) is unclear. Design Using population-based retrospective cohort study to examine the risk of OSA in patients with RA. Setting We used claims data of the National Health Insurance Research Database (NHIRD) of Taiwan. Participants We identified a RA cohort with 33 418 patients newly diagnosed in 2000–2010 and a randomly selected non-RA comparison cohort with 33 418 individuals frequency matched by sex, age and diagnosis year. Primary and secondary outcome measures Incident OSA was estimated by the end of 2011. The HRs of OSA were calculated using the Cox proportional hazards regression analysis. Results The overall incidence rate of OSA was 75% greater in the RA cohort than in the non-RA cohort (3.04 vs 1.73/10 000 person-years, p

1.97), breast cancer (HR=1.45, 95% CI=1.00, 2.09), and non-cervical gynecological cancer (HR=4.03, 95% CI=1.77, 9.17), compared with the general population. Conclusions: Physicians are at lower overall risk of cancer than the general population, apart from cancer of the thyroid, prostate, breast, and non-cervical gyne- cological cancer. (J Occup Health 2013; 55: 158−166) Abstract: A Comparison of Cancer Incidence among Physician Specialists and the General Population: A Taiwanese Cohort Study: Shih-Yi LIN, et al. Grad- uate Institute of Clinical Medical Science, College of Medicine, China Medical University, Taiwan— Background: Physicians are frequently studied as a population that experiences extremely high stress, burnout, and prolonged working hours that might harm one's health. However, they have sound medical knowl- edge and have easy access to medical resources. We studied the incidence of cancer among Taiwanese physi- cians using a nationwide cohort study design. Methods: Data were obtained from the National Health Insurance (NHI) system in Taiwan. The physician cohort contained 22,309 physicians, and each physician was randomly frequency-matched according to age and sex with 4 people from the general population. Results: The overall incidence ratio of cancer was 27% lower in the physician cohort than in the nonphysician comparison cohort (33.9 vs. 46.5 people per 10,000 person-years, crude hazard ratio (HR)=0.73, 95% CI=0.70, 0.76). The adjusted HR was 0.78 (95% CI=0.72, 0.84). Female physicians experienced a higher incidence rate ratio of overall cancer, compared to male physicians (crude HR=1.17, 95% CI=1.03, 1.33 vs. crude HR=0.70, 95% CI=0.67, 0.74, respectively). Physicians were at a significantly higher risk of thyroid cancer (HR 1.75, 95% CI=1.14, 2.68), prostate cancer (HR=1.54, 95% CI=1.21

Background Empyema is a rare but important complication among patients with end-stage renal disease (ESRD). However, a nationwide, propensity-matched cohort study has never been performed. Methods We conducted a retrospective cohort study using data from the National Health Insurance Research Database of Taiwan. The ESRD group consisted of 82 765 patients diagnosed between 2000 and 2008. The comparison group consisted of individuals without kidney disease selected at a 1:1 ratio matched by propensity score estimated with age, gender, year of diagnosis and comorbidities. The occurrence of empyema was monitored until the end of 2011. The hazard ratios (HRs) of empyema were estimated using the Cox proportional hazards model. Results The incidence of empyema was 2.76-fold higher in the ESRD group than in the comparison group (23.7 vs. 8.19/10 000 person-years, P

Background Empyema is an important complication for patients with chronic liver disease and cirrhosis (CLDC). However, no study has investigated this relationship by using a population-based cohort study. Methods We used the National Health Insurance Research Data of Taiwan to identify a cohort of 76,027 CLDC patients newly diagnosed in 2000−2010 and a comparison cohort without CLDC of same size matched by age, gender and the year of diagnosis. The occurrence of empyema was monitored until the end of 2011. The hazard ratios (HRs) of empyema were estimated using the Cox model. Results The overall incidence of empyema was 66% greater in the CLDC group than in the non-CLDC group (3.85 vs 2.32/10,000 person-years, p

Nephrolithiasis is highly prevalent and has been associated with vascular diseases such as cardiovascular events. Few studies have comprehensively associated renal stones with stroke. This study explored whether patients with renal stones were at a higher stroke risk than those without renal stones. A national insurance claim dataset of 22 million enrollees in Taiwan was used to identify 53,659 patients with renal stones, and 214,107 were selected as age-, sex-, and comorbidity-matched controls for a 13-year follow-up. The relative stroke risk for the RS cohort was 1.06-fold higher than that for the non-RS group (95% confidence interval [CI] = 1.01–1.11). Age-specific analysis revealed that the adjusted stroke risk for the RS cohort increased as age decreased, with the highest risk of 1.47-fold (95% CI = 1.10–1.96) in patients aged 20 to 34 years, followed by a 1.12-fold risk (95% CI = 1.00–1.25) in patients aged 35 to 50 years. Sex-specific analysis clarified that women in the RS group had a 1.12-fold stroke risk compared with women in the non-RS group (95% CI = 1.03–1.21). Patients who had undergone >4 surgeries had up to 42.5-fold higher risk of stroke (95% CI = 33.8–53.4). The study utilized the national database and demonstrated that patients, particularly women and the younger population, with nephrolithiasis have an increased risk of ischemic stroke development. Patients treated with medication or through surgery for RSs showed steady and higher risks of stroke than those without surgical or medical intervention.

Rats are used extensively in abdominal disease research. To monitor disease progress in vivo, high-frequency ultrasound (HFU) can be a powerful tool for obtaining high-resolution images of biological tissues. However, there is a paucity of data regarding the correlation between rat anatomy and corresponding HFU images. Twenty-four adult male Sprague–Dawley (SD) rats underwent abdominal scans using HFU (40 MHz) surgical procedures to identify abdominal organs and major vessels as well as in situ scanning to confirm the imaging results. The results were compared with those of human abdominal organs in ultrasonographic scans. The rat liver, paired kidneys, stomach, intestines, and major blood vessels were identified by HFU and the ultrasonic morphologies of the liver and kidneys showed clear differences between rats and humans. Clinically relevant anatomical structures were identified using HFU imaging of the rat abdomen, and these structures were compared with the corresponding structures in humans. Increased knowledge with regard to identifying the anatomy of rat abdominal organs by ultrasound will allow scientists to conduct more detailed intra-abdominal research in rodents.

Wan-Chun Huang,1 Ying-Huang Tsai,2 Yu-Feng Wei,3 Ping-Hung Kuo,4 Chi-Wei Tao,5 Shih-Lung Cheng,6 Chao-Hsien Lee,7 Yao-Kuang Wu,8 Ning-Hung Chen,9 Wu-Huei Hsu,10 Jeng-Yuan Hsu,11 Chin-Chou Wang,12 Ming-Shian Lin1,131Division of Pulmonary Medicine, Department of Internal Medicine, Ditmanson Medical Foundation Chia-Yi Christian Hospital, Chiayi, 2Department of Internal Medicine, Chang Gung Memorial Hospital, Chiayi, 3Department of Internal Medicine, E-Da Hospital/I-Shou University, Kaohsiung, 4Department of Internal Medicine, National Taiwan University Hospital, 5Department of Internal Medicine, Cheng-Hsin General Hospital, 6Division of Thoracic Medicine, Department of Internal Medicine, Far Eastern Memorial Hospital, 7Division of Pulmonary and Critical Care Medicine, Mackay Memorial Hospital, 8Division of Pulmonary Medicine, Department of Internal Medicine, Taipei Tzu Chi Hospital, Taipei, 9Department of Pulmonary and Critical Care Medicine, Chang Gung Memorial Hospital, Linkou, 10Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, China Medical University Hospital, 11Division of Chest Medicine, Taichung Veterans Genera Hospital, Taichung, 12Division of Pulmonary and Critical Care Medicine, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, 13Department of Respiratory Care, Chang Gung University of Science and Technology, Chiayi, Taiwan, Republic of ChinaBackground: COPD is an important public health challenge with significant heterogeneity of clinical presentation and disease progression. Clinicians have been trying to find phenotypes that may be linked to distinct prognoses and different therapeutic choices. Not all patients with COPD present with wheezing, a possible clinical phenotype that can help differentiate patient subgroups.Methods: The Taiwan Obstructive Lung Disease study was a retrospective, multicenter research study to investigate the treatment patterns of COPD after the implementation of the Global Initiative for Chronic Obstructive Lung Disease 2011 guidelines. Between November 2012 and August 2013, medical records were retrieved from patients with COPD aged ≥40years; patients diagnosed with asthma were excluded. Demographic data, lung function, symptom scores, and acute exacerbation were recorded and analyzed, and the differences between patients with and without wheezing were evaluated.Results: Of the 1,096 patients with COPD, 424 (38.7%) had the wheezing phenotype. The wheezing group had significantly higher COPD Assessment Test scores (12.4±7.8 versus 10.5±6.7, P

Squamous cell carcinoma (SCC) of the buccal mucosa accounts for 23% to 37% of all intraoral cancer cases in Taiwan. Because of the high recurrence rate and invasive tumor behavior, the prognosis is generally poor. The aim of this study was to evaluate the prognostic significance of clinicopathologic factors on survival rates for patients with buccal SCC in a medical center in central Taiwan.Between March 1995 and December 2002, patients admitted to hospital and diagnosed as having buccal SCC were enrolled in the study. There were 415 patients (406 men and 9 women) 25 to 84 years old (mean age, 51.1 ± 11.4 years). The chart records were retrospectively reviewed. Relevant clinical features in each patient, such as primary tumor size, tumor stage, initial treatment modalities, surgical margin status, cervical nodal metastasis status, and histopathologic grade, were compared for survival analysis.Three hundred ninety-four patients received surgical intervention. Univariate analysis of relevant prognostic factors showed that positive surgical margin, positive cervical nodal metastasis, positive extracapsular spread, larger tumor, and advanced tumor stage were associated with poor prognosis. Multivariate analysis identified the factors that independently influenced the survival rate as advanced stage disease (stage III: relative risk [RR], 3.09; P = .006; stage IV: RR, 4.64; P.001), positive surgical margin (RR, 2.02; P = .001), and extracapsular spread of cervical lymph node metastasis (RR, 6.89; P.001).This study represents the largest series in the literature and highlights the importance of tumor stage, surgical margin status, and extracapsular spread of cervical nodal metastasis as the most important prognostic factors in patients with buccal SCC.

T-lymphocyte (T-LC)-derived cytokines have been implicated in asthmatic pathogenesis. Proteomic technology is now widely accepted as a complementary technology to genetic profiling. We investigated the changes of proteins in T-LC of asthmatic patients from the no typical therapy (uncontrolled) to typical therapy (controlled) level by using standard proteome technology. Methods: The proteins of CD4+ T-LC were isolated from the whole blood of six asthmatic patients from uncontrolled to controlled levels over 3 months. Two-dimensional polyacrylamide gel electrophoresis was performed and coomassie blue stained protein spots were comparatively analyzed by using an image analyzer. Some differentially expressed spots were identified by liquid chromatography/mass spectrometry and database search. Our results showed that 13 proteins showed different expression. Six protein spots in the CD4+ T-LC of the uncontrolled asthmatic patients were increased and 7 spots were decreased compared to those of the controlled subjects. In conclusion, the proteomic examination of the CD4+ T-LC revealed some differentially expressed proteins in the uncontrolled and controlled asthmatic patients. The possibility of using the differentially expressed proteins as important biomarkers and therapeutic targets warrants further study.

Purpose There has been a paucity of data regarding the efficacy and safety of small-bore chest tubes (pigtail catheter) for the management of pneumothorax in mechanically ventilated patients. Methods We conducted a retrospective review of mechanically ventilated patients who underwent pigtail catheter drainage as their initial therapy for pneumothorax in the emergency department and intensive care unit from January 2004 through January 2007 in a university hospital. Results Among the 62 enrolled patients, there were 41 men (66%) and 21 women (34%), with a mean age of 63.8 ± 20.3 years. A total of 70 episodes of pneumothoraces occurred in the intensive care unit, and 48 episodes of pneumothoraces (68.6%) were successfully treated with pigtail catheters. The average duration of pigtail drainage was 5.9 days (1–27 days). No major complications occurred through use of this procedure, except for pleural infections (n = 3, 4.2%) and clogged tube (n = 1, 1.4%). Comparing the variables between the success and failure of pigtail treatment, the failure group had a significantly higher proportion of Fio 2 >60% requirement (45.5% vs. 14.6%, P = .005) and higher positive end-expiratory pressure levels (8.7 ± 3.0 vs. 6.2± 2.3 mm Hg, P = .001) at the time of pneumothorax onset than the success group. Further comparing the efficacy of pigtail drainage between barotraumas and iatrogenic pneumothorax, pigtail catheters for management of iatrogenic pneumothorax had a significantly higher success rate than barotraumas (87.5% vs. 43.3%, P Conclusion Pigtail catheter drainage is relatively effective in treating iatrogenic but less promising for barotraumatic pneumothoraces.

ObjectiveTruncal vagotomy is associated with a decreased risk of subsequent Parkinson disease (PD), although the effect of vagotomy on dementia is unclear. In response, we investigated the risk of dementia in patients who underwent vagotomy.SettingPopulation-based cohort study.ParticipantsA total of 155 944 patients who underwent vagotomy (vagotomy cohort) and 155 944 age-matched, sex-matched and comorbidity-matched controls (non-vagotomy cohort) were identified between 2000 and 2011.Primary and secondary outcome measuresAll patient data were tracked until the diagnosis of dementia, death or the end of 2011. The cumulative incidence of subsequent dementia and HRs were calculated.ResultsThe mean ages of the study patients in the vagotomy and non-vagotomy cohorts were 56.6±17.4 and 56.7±17.3 years, respectively. The overall incidence density rate for dementia was similar in the vagotomy and non-vagotomy cohorts (2.43 and 2.84 per 1000 person-years, respectively). After adjustment for age, sex and comorbidities such as diabetes, hypertension, hyperlipidaemia, stroke, depression, coronary artery disease and PD, the patients in the vagotomy cohort were determined to not be at a higher risk of dementia than those in the non-vagotomy cohort (adjusted HR=1.09, 95% CI 0.87 to 1.36). Moreover, the patients who underwent truncal vagotomy were not associated with risk of dementia (adjusted HR=1.04, 95% CI 0.87 to 1.25), compared with the patients who did not undergo vagotomy.ConclusionVagotomy, either truncal or selective, is not associated with risk of dementia.

Background The objective of this study was to assess the etiology, microbiology and outcome of hospital-acquired thoracic empyema (HATE) in adults. Methods From December 2001 to December 2006, 459 adult patients with a diagnosis of thoracic empyema in a tertiary hospital were screened for HATE. HATE was defined as a new pleural empyema which developed after 48 hours of hospitalization. Results In total, 56 adult (>or=18 years) patients who were diagnosed with HATE were enrolled in our series, including 35 men (62.5%) and 21 women (37.5%), with ages ranging from 22 to 87 years old (mean = 59). Causes of HATE were classified into two categories: hospital-acquired pneumonia (HAP) related (n = 25) and non-HAP related (n = 31). Causes of non-HAP related empyema were comprised of catheter-related infections (n = 20), hepatobiliary tract infections (n = 6), septic emboli (n = 4), and postpneumonectomy (n = 1). Comparing the bacteriology between the two categories, HAP-related empyema had a significantly higher incidence of aerobic Gram-negative organisms (76% vs. 38.7%, P = 0.005), polymicrobial pathogens (40% vs. 9.7%, P = 0.008), and anaerobic pathogens (20% vs. 0%, P = 0.009) than non-HAP related empyema. However, there was no significant difference in mortality rate (60% vs. 52%, P = 0.52) between the two categories. Conclusions Choice of antibiotic treatment for HATE should be based on the etiology of the pleural infection. In treating HAP-related empyema, antibiotics should cover aerobic Gram-negative, polymicrobial, and anaerobic pathogens.

Thoracic sonography has been advocated as being complementary to small-bore catheter drainage in pleural effusions. However, it is not known whether the initial sonographic appearances of empyemas or complicated parapneumonic effusions (CPPEs) can predict the outcomes of small-bore catheter drainage for these pleural insults. This retrospective study investigated the outcomes of patients who had been diagnosed with empyema and CPPE and had received ultrasound-guided small-bore catheter (size from 12F to 16F) drainage in a tertiary university hospital from September 2005 to August 2007. Patients were excluded when empyemas or CPPEs were traumatic, they were less than 18 years old or their charts were incomplete. We evaluated 141 small-bore catheters in 70 patients with empyemas and 71 patients with CPPEs over a two-year period. The mean age was 58+/-15 y and the male gender was more frequent (112 men, 79%). The overall successful rate of small-bore catheter drainage in empyemas or CPPEs was 63% (89/141). The sonographic appearances of these empyemas or CPPEs exhibited a complex septated pattern in 57% (81/141) of patients and a complex nonseptated pattern in 43% (60/141) of patients. The success rate in a complex nonseptated sonographic pattern was significantly higher than in a complex septated sonographic pattern (48/60, 80% vs. 41/81, 51%, respectively; p=0.001). Moreover, patients with complex septated sonographic patterns also had higher intensive care unit admission rates compared with nonseptated sonographic patterns (22/81, 27%, vs. 8/60, 13%, respectively; p=0.0047), as well as infection-related mortality rates (17/81, 21% vs. 4/60, 7%, respectively; p=0.018). The appearance of sonographic septation is a useful sign to help predict the outcome of small-bore catheter drainage in cases of empyemas or CPPEs. Patients with a complex septated sonographic pattern have a poorer prognosis for a successful outcome, higher ICU admission rate and a higher mortality rate.

To determine whether urinary 8-hydroxy-2′-deoxyguanosine (8-OHdG), an in vivo parameter of oxidative stress, is correlated with the outcome of critically septic patients. Clinical outcome study in an adult medical intensive care unit (ICU). 85 consecutive septic patients (59 men, 26 women). Patient characteristics and the clinical course were examined. Urinary 8-OHdG was analyzed using isotope-dilution liquid chromatography with tandem mass spectrometry (LC/MS/MS). ICU mortality was 25.9% (22/85) and hospital mortality 38.8% (33/85). Survivors' APACHE II scores on days 1 and 3 and the difference between them differed significantly from those of nonsurvivors (day 1, 21.0 ± 7.1 vs. 25.9 ± 8.0; day 3, 15.0 ± 5.8 vs. 23.2 ± 8.3; difference, 6.0 ± 5.5 vs. 1.7 ± 6.6). Urinary 8-OHdG was significantly lower in survivors than in nonsurvivors on day 1 (1.8 ± 2.4 vs. 3.0 ± 2.4). The area under receiver operating characteristic curve analysis for the association between day 1 urinary 8-OHdG and ICU mortality was 0.71. The comparison performed upon discharge from hospital revealed similar results. This is a preliminary study. Excretion of urinary 8-OHdG, as measured using isotope-dilution LC/MS/MS, and the APACHE II score were correlated with the outcome of critically septic patients in medical ICU.

Objectives Complicated parapneumonic effusion or empyema is a troublesome disease with a high mortality. The most common involved microorganisms seem to have changed over recent decades, influenced by the introduction of new antibiotics, and the increase of immunocompromised hosts, and the elderly population. More epidemiological studies on the current bacteriology are needed to help us to empirically select adequate antibiotics. Design A retrospective study via chart review in a university-affiliated tertiary medical center was conducted to assess the underlying bacterial pathogens and outcome of patients with complicated parapneumonic effusions or empyemas. Results During the 43-month study period (from December 2000 to June 2004), 304 patients were diagnosed with complicated parapneumonic effusions or empyemas and the mortality of these patients was 23% (69/304). Among these 304 patients, a total of 292 microorganisms were cultured from the pleural fluid samples of 207 patients (to yield a positive microbiological culture rate of 68% (207/304). Isolated bacteria included aerobic Gram-negative bacteria (n=129), aerobic Gram-positive bacteria (n=105), anaerobic bacteria (n=51), and M. tuberculosis (n=7). Of these aerobic bacterial infections, Gram-negative bacteria were isolated more frequently from the older population and involved a significantly higher mortality rate and longer stay, compared to those with other bacteria (p=0.001 and p

Yu-Feng Wei,1 Ping-Hung Kuo,2 Ying-Huang Tsai,3 Chi-Wei Tao,4 Shih-Lung Cheng,5,13 Chao-Hsien Lee,6 Yao-Kuang Wu,7 Ning-Hung Chen,8 Wu-Huei Hsu,9 Jeng-Yuan Hsu,10 Ming-Shian Lin,11 Chin-Chou Wang12 1Department of Internal Medicine, E-Da Hospital/I-Shou University, Kaohsiung, Taiwan; 2Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan; 3Department of Internal Medicine, Chang Gung Memorial Hospital, Chiayi, Taiwan; 4Department of Internal Medicine, Cheng-Hsin General Hospital, Taipei, Taiwan; 5Division of Thoracic Medicine, Department of Internal Medicine, Far Eastern Memorial Hospital, Taipei, Taiwan; 6Division of Pulmonary and Critical Care Medicine, Mackay Memorial Hospital, Taipei, Taiwan; 7Division of Pulmonary Medicine, Department of Internal Medicine, Taipei Tzu Chi Hospital, Taipei, Taiwan; 8Department of Pulmonary and Critical Care Medicine, Chang Gung Memorial Hospital, Linkou, Taiwan; 9Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, China Medical University and China Medical University Hospital, Taichung, Taiwan; 10Division of Chest Medicine, Taichung Veterans General Hospital, Taichung, Taiwan; 11Division of Pulmonary and Critical Care Medicine, Chia-Yi Christian Hospital, Chiayi, Taiwan; 12Division of Pulmonary and Critical Care Medicine, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan; 13Department of Chemical Engineering and Materials Science, Yuan-Ze University, Taoyuan, Taiwan Background and objective: The overprescription of inhaled corticosteroids (ICS) in the current Global Initiative for Chronic Obstructive Lung Disease (GOLD) group A and B patients with chronic obstructive pulmonary disease (COPD) is not uncommon in clinical practice. The aim of this study was to explore the factors associated with the use of ICS in these patients. Methods: The Taiwan obstructive lung disease (TOLD) study was a retrospective, observational nationwide survey of COPD patients conducted at 12 hospitals (n=1,096) in Taiwan. Multivariate logistic regression models were used to explore the predictors of ICS prescription in GOLD group A and B patients. Results: Among the group A (n=179) and group B (n=398) patients, 198 (34.3%) were prescribed ICS (30.2% in group A and 36.2% in group B, respectively). The wheezing phenotype was present in 28.5% of group A and 34.2% of group B patients. Wheezing was the most significant factor for an ICS prescription in group A (odds ratio [OR], 2.33; 95% confidence interval [CI], 1.14–4.75; P=0.020), group B (OR, 1.93; 95% CI, 1.24–2.99; P=0.004), and overall (OR, 2.04; 95% CI, 1.40–2.96; P

Previous studies investigating the relationship between Mycoplasma pneumoniae and incident asthma in the general population have been inconclusive.We conducted a nationwide cohort study to clarify this relationship.Using the National Health Insurance Research Database of Taiwan, we identified 1591 patients with M pneumoniae infection (International Classification of Diseases, Ninth Revision, Clinical Modification code 4830) given diagnoses between 2000 and 2008. We then frequency matched 6364 patients without M pneumoniae infection from the general population according to age, sex, and index year. Cox proportional hazards regression analysis was performed to determine the adjusted hazard ratio (aHR) of the occurrence of asthma in the M pneumoniae cohort compared with that in the non-M pneumoniae cohort.Regardless of comorbidities and the use of antibiotic or steroid therapies, patients with M pneumonia infection had a higher risk of incident asthma than those without it. The aHR of asthma was 3.35 (95% CI, 2.71-4.15) for the M pneumoniae cohort, with a significantly higher risk when patients were stratified by age, sex, follow-up time, and comorbidities, including allergic rhinitis, atopic dermatitis, or allergic conjunctivitis. Patients with M pneumoniae infection had a higher risk of having early-onset (age,12 years; aHR, 2.87) and late-onset (age, ≥12 years; aHR, 3.95) asthma. The aHR was also higher within the less than 2-year follow-up in the M pneumoniae cohort (aHR, 4.41; 95% CI, 3.40-5.74) than in the cohort without the infection.This study found that incident cases of early-onset and late-onset asthma are closely related to M pneumoniae infection, even in nonatopic patients.

Background The relationship between asthma and ankylosing spondylitis (AS) is controversial. We examined the risk of asthma among AS patients in a nationwide population. Methods We conducted a retrospective cohort study using data from the National Health Insurance (NHI) system of Taiwan. The cohort included 5,974 patients newly diagnosed with AS from 2000 to 2010. The date of diagnosis was defined as the index date. A 4-fold of general population without AS was randomly selected frequency matched by age, gender and the index year. The occurrence and hazard ratio (HR) of asthma were estimated by the end of 2011. Results The overall incidence of asthma was 1.74 folds greater in the AS cohort than in the non-AS cohort (8.26 versus 4.74 per 1000 person-years) with a multivariable Cox method measured adjusted HR of 1.54 (95% confidence interval (CI), 1.34–1.76). The adjusted HR of asthma associated with AS was higher in women (1.59; 95% CI, 1.33–1.90), those aged 50–64 years (1.66; 95% CI, 1.31–2.09), or those without comorbidities (1.82; 95% CI, 1.54–2.13). Conclusion Patients with AS are at a higher risk of developing asthma than the general population, regardless of gender and age. The pathophysiology needs further investigation.

Objectives The role of advanced bronchoscopic diagnostic techniques in the detection and staging of lung cancer has increased sharply in recent years. The development of endobronchial ultrasound (EBUS) improved minimally invasive mediastinal staging and diagnosis of peripheral lung lesions (PLLs). We investigated the impact of using EBUS as a diagnostic method for tissue acquisition in lung cancer patients. Methods In a single center observational retrospective study, 3712 subjects were diagnosed with lung cancer from 2003 to 2013 (EBUS was introduced in 2008). Thus, we divided the data into two periods: the conventional bronchoscopy period (2003 to 2007) and the EBUS period (2008 to 2013). Results A total of 3712 patients were included in the analysis. Comparing the conventional bronchoscopy period with the EBUS period data, there has been a significant reduction in the use of diagnostic modalities: CT-guided biopsy (P < 0.0001) and pleural effusion cytology (P < 0.0001). The proportion of subjects diagnosed using bronchoscopy significantly increased from 39.4% in the conventional period to 47.4% in the EBUS period (P < 0.0001). In the EBUS period, there has also been a significant increase in the proportion of patients proceeding directly to diagnostic surgery (P < 0.0001). Compared to bronchoscopy, the incidence of complications was higher in those who underwent CT guide biopsy. The incidence of iatrogenic pneumothorax significantly decreased in the EBUS period. Conclusions Advanced bronchoscopic techniques are widely used in the diagnosis of lung cancer. At our institution, the increasing use of EBUS for providing lung cancer diagnosis has led to a significant reduction in other diagnostic modalities, namely CT-guided biopsy and pleural effusion cytology. These changes in practice also led to a reduction in the incidence of complications.

The aim of this study was to determine whether pleural fluid C-reactive protein (CRP) is useful in distinguishing complicated parapneumonic pleural effusion (CPPE) and empyema from uncomplicated parapneumonic pleural effusions (UPPE). A total of 69 consecutive patients with parapneumonic effusions were enrolled in the study: 29 with UPPE, 29 with CPPE, and 11 with empyema. Concentrations of standard biochemical parameters together with CRP in the pleural fluid were measured using an immunoturbidimetric assay. Pleural CRP was significantly higher in CPPE (11.6 mg/dl) and in empyema (12.2 mg/dl) than in UPPE (3.9 mg/dl). A cutoff value of 8.7 mg/dl for pleural CRP in the diagnosis of CPPE and empyema resulted in a sensitivity, specificity, and area under the receiver-operating characteristic curve (AUC) of 0.80, 0.97 and 0.94, respectively. Traditional lactic dehydrogenase (LDH)or = 1000 U/L and glucoseor = 60 mg/dl can differentiate CPPE and empyema from UPPE, with the sensitivity, specificity, and AUC achieving 0.75/0.60.1.00/1.00,0.95/0.22, respectively. However, for the detection of CPPE and empyema, the combination of pleural fluid CRPor = 8.7 mg/dl and LDHor = 1000 U/L was valuable in achieving a sensitivity, specificity, and AUC of 0.97/1,00/0.95. This study suggests that measurement of pleural CRP can be useful in the workup of patients with a parapneumonic effusion in order to differentiate CPPE from UPPE.

Cutaneous angiosarcoma is a rare and invasive endothelial-derived sarcoma that occurs most frequently in the scalp and facial skin of elderly men. It is frequently accompanied by thin-walled cavitary pulmonary metastasis, and is often obscure on chest radiograph. We report a case of angiosarcoma of the scalp with cystic metastasis to the lung in a 63-year-old man, presenting as recurrent bilateral spontaneous pneumothorax. Lung metastasis was missed at the first episode of pneumothorax because the lung-expanded chest radiograph showed no significant abnormality. Two months later, bilateral pneumothorax recurred, and high-resolution computed tomography revealed multiple cystic, cavitary and nodular lesions. Pulmonary metastasis was confirmed by video-assisted thoracoscopic surgery, and pleurodesis was performed. After the operation, the patient received chemotherapy; no recurrence of pneumothorax was found during 6 months of follow-up. Pneumothorax in the elderly should be differentiated from malignant metastatic lung tumors.