The effect of colchicine on cancer risk in patients with immune-mediated inflammatory diseases: a time-dependent study based on the Taiwan's National Health Insurance Research Database.

BACKGROUND: To determine the effect of colchicine on cancer risk in patients with the immune-mediated inflammatory diseases (IMIDs)-related to colchicine use. METHODS: This is a time-dependent propensity-matched general population study based on the National Health Insurance Research Database (NHIRD) of Taiwan. We identified the IMIDs patients (n = 111,644) newly diagnosed between 2000 and 2012 based on the International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM)-274,712, 135, 136.1, 279.49, 518.3, 287.0, 696.0, 696.1, 696.8, 420, 429.4, 710.0, 710.1, 710.3, 710.4, 714.0, 720, 55.0, 55.1, 55.9, 556. INCLUSION CRITERIA: aged ≧ 20 years, if a patient had at least these disease diagnosis requirements within 1 year of follow-up, and, these patients had at least two outpatient visits or an inpatient visit. After propensity-matched according to age, sex, comorbidities, medications and index date, the IMIDs patients enter into colchicine users (N = 16,026) and colchicine nonusers (N = 16,026). Furthermore, time-dependent Cox models were used to analyze cancer risk in propensity-matched colchicine users compared with the nonusers. The cumulative cancer incidence was analyzed using Cox proportional regression analysis. We calculated adjusted hazard ratios (aHRs) and their 95% confidence intervals (95% CIs) for cancer after adjusting for sex, age, comorbidities, and use of medicine including acetylcysteine, medication for smoking cessation such as nicotine replacement medicines (the nicotine patch) and pill medicines (varenicline), anti-inflammatory drugs and immunosuppressant drugs. RESULTS: Comparing the colchicine nonusers, all cancer risk were mildly attenuated, the (aHR (95% CI)) of all cancer is (0.84 (0.55, 0.99)). Meanwhile, the colchicine users were associated with the lower incidence of the colorectal cancer, the (aHRs (95% CI)) is (0.22 (0.19, 0.89)). Those aged < 65 years and male/female having the colchicine users were associated with lower risk the colorectal cancer also. Moreover, the colchicine > 20 days use with the lower aHR for colorectal cancer. CONCLUSION: Colchicine was associated with the lower aHR of the all cancer and colorectal cancer formation in patients with the IMIDs.

Relationship between Glucagon-like Peptide-1 Receptor Agonists and Cardiovascular Disease in Chronic Respiratory Disease and Diabetes.

The purpose of this paper is to assess the effect of glucagon-like peptide-1 receptor agonists (GLP-1RAs) on stroke or heart disease in patients having chronic respiratory disease and diabetes (CD) with underlying diseases related to COVID-19. From 1998 to 2019, we adjusted competing risk by assessing the effect of GLP-1RAs on stroke or heart disease in a CD cohort after propensity matching based on the Taiwan National Health Insurance Research Database. We also used the time-dependent method to examine the results. GLP-1 RA and non-GLP-1 RA user groups included 15,801 patients (53% women and 46% men with a mean age of 52.6 ± 12.8 years). The time between the diagnoses of DM and the initial use of the GLP-1 RA among the stroke subcohort (<2000 days) was shorter than that of the heart disease subcohort (>2000 days) (all p-values < 0.05). The overall risks of stroke, ischemic, and hemorrhagic stroke were significantly lower in GLP-1 RA users than nonusers. The adjusted subhazard ratio (aSHR) was 0.76 [95% CI 0.65-0.90], 0.77 [95% CI 0.64-0.92], and 0.69 [95% CI 0.54-0.88] (p < 0.05 for all). Furthermore, a ≥351-day use had a significantly lower stroke risk than GLP-1 RA nonusers (aSHR 0.35 [95% CI 0.26-0.49]). The time-dependent method revealed the same result, such as lower stroke, and ischemic or hemorrhagic stroke risk. In contrast, the cardiac arrhythmia incidence was higher in GLP-1 RA users with an aSHR of 1.36 [95% CI 1.16-1.59]. However, this risk disappeared after the ≥351-day use with 1.21 (0.98, 1.68) aSHR. Longer GLP-1 RA use was associated with a decreased risk of ischemic or hemorrhagic stroke and the risk of cardiac arrhythmia disappears in a CD cohort. Both a shorter lag time use of the GLP-1 RA and a longer time use of GLP-1 RA were associated with a decreased risk of ischemic or hemorrhagic stroke in the CD cohort. The GLP-1 RA use in the early stage and optimal time use in the CD cohort may avoid the stroke risk.

Colchicine Is a Weapon for Managing the Heart Disease Among Interstitial Lung Disease With Viral Infection: Have We Found the Holy Grail?

Background: This study investigated the effect of colchicine use on the risks of heart disease (HD), pericarditis, endocarditis, myocarditis, cardiomyopathy, cardiac arrhythmia, and cardiac failure in patients having interstitial lung disease (ILD) with virus infection (ILD cohort). Methods: We retrospectively enrolled ILD cohort between 2000 and 2013 from the Longitudinal Health Insurance Database and divided them into colchicine users (n = 12,253) and colchicine non-users (n = 12,253) through propensity score matching. The event of interest was the diagnosis of HD. The incidence of HD was analyzed using multivariate Cox proportional hazards models between colchicine users and the comparison cohort after adjustment for age, sex, medication, comorbidities, and index date based on the time-dependent analysis. Results: Colchicine users had a significantly lower risk of HD (aHR = 0.87, 95% confidence interval (CI]) = 0.82-0.92) than did the colchicine non-user. For colchicine non-users as the reference, the aHR (95% CI) of the patients who received colchicine of 2-7, 8-30, 31-150, and > 150 days were 0.89 (0.81-0.98), 0.84 (0.76-0.94), 090 (0.80-0.99), and 0.83 (0.74-0.93), respectively; regardless of duration use, the lower risk of HD persisted in colchicine users. The cumulative incidence of HD in colchicine users was significantly lower than that in the colchicine non-users (log-rank p < 0.001). Conclusion: The addition of short-term or long-term colchicine to standard medical therapy may have benefits to prevent the HD among the ILD patients concurrent with a virus infection or comorbidities even in elderly patients.

Hydroxychloroquine on the Pulmonary Vascular Diseases in Interstitial Lung Disease: Immunologic Effects, and Virus Interplay.

To investigate the effects of hydroxychloroquine (HCQ) drug use on the risk of pulmonary vascular disease (PVD) in an interstitial lung disease cohort (ILD cohort, ILD+ virus infection), we retrospectively enrolled the ILD cohort with HCQ (HCQ users, N = 4703) and the ILD cohort without HCQ (non-HCQ users, N = 4703) by time-dependence after propensity score matching. Cox models were used to analyze the risk of PVD. We calculated the adjusted hazard ratios (aHRs) and their 95% confidence intervals (CIs) for PVD after adjusting for sex, age, comorbidities, index date and immunosuppressants, such as steroids, etc. Compared with the HCQ nonusers, in HCQ users, the aHRs (95% CIs) for PVD were (2.24 (1.42, 3.54)), and the women's aHRs for PVD were (2.54, (1.49, 4.35)). The aHRs based on the days of HCQ use for PVD of 28−30 days, 31−120 days, and >120 days were (1.27 (0.81, 1.99)), (3.00 (1.81, 4.87)) and (3.83 (2.46, 5.97)), respectively. The medium or long-term use of HCQ or young women receiving HCQ were associated with a higher aHR for PVD in the ILD cohort. These findings indicated interplay of the primary immunologic effect of ILD, comorbidities, women, age and virus in the HCQ users.

Effects of colchicine use on ischemic and hemorrhagic stroke risk in diabetic patients with and without gout.

This study aimed to determine the effect of colchicine use on the risk of stroke among patients with diabetes mellitus (DM). We retrospectively enrolled patients with DM between 2000 and 2013 from the Longitudinal Health Insurance Database and divided them into a colchicine cohort (n = 8761) and noncolchicine cohort (n = 8761) by using propensity score matching (PSM). The event of interest was a stroke, including ischemic stroke and hemorrhagic stroke. The incidence of stroke was analyzed using multivariate Cox proportional hazards models between the colchicine cohort and the comparison cohort after adjustment for several confounding factors. The subdistribution hazard model was also performed for examination of the competing risk. The colchicine cohort had a significantly lower incidence of stroke [adjusted hazard ratios (aHR), 95% confidence intervals (95%CI)] (aHR = 0.61, 95%CI = 0.55-0.67), ischemic stroke (aHR = 0.59, 95%CI = 0.53-0.66), and hemorrhagic stroke (aHR = 0.66, 95%CI = 0.53-0.82) compared with the noncolchicine cohort. Drug analysis indicated that patients in the colchicine cohort who received colchicine of cumulative daily defined dose (cDDD) > 14 and duration > 28 days had a lower risk of stroke and ischemic stroke compared with nonusers. The colchicine cohort (cDDD > 150, duration > 360 days) also had a lower risk of stroke, ischemic stroke, and hemorrhagic stroke. The cumulative incidence of stroke, ischemic stroke, and hemorrhagic stroke in the colchicine cohort was significantly lower than that in the noncolchicine cohort (log-rank P < 0.001). However, the subdistribution hazard model reveal the colchicine was not associated with the hemorrhagic stroke in DM patients without gout (aHR = 0.69, 95%CI = 0.47-1.00). Colchicine use with cDDD > 14 and duration > 28 days was associated with lower risk of stroke and ischemic stroke, and colchicine use with cDDD > 150 and duration > 360 days played an auxiliary role in the prevention of stroke, ischemic stroke, and hemorrhagic stroke in patients with DM. The colchicine for the hemorrhagic stroke in DM patients without gout seem to be null effect.

Effects of statins on the risks of ischemic stroke and heart disease in human immunodeficiency virus infection, influenza and severe acute respiratory syndrome-associated coronavirus: respiratory virus infection with steroid use.

OBJECTIVES: We sought to fill the research gap on the effects of statins on the risks of ischemic stroke and heart disease among individuals with human immunodeficiency virus infection, influenza, and severe acute respiratory syndrome associated-coronavirus (HIS) disorders. METHODS: We enrolled a HIS cohort treated with statins (n = 4921) and a HIS cohort not treated with statins (n = 4921). The cumulative incidence of ischemic stroke and heart disease was analyzed using a time-dependent Cox proportional regression analysis. We analyzed the adjusted hazard ratio (aHR) and 95% confidence interval (CI) of ischemic stroke and heart disease for statins users relative to nonusers based on sex, age, comorbidities and medications. RESULTS: The aHR (95% CI) was 0.38 (0.22-0.65) for ischemic stroke. The aHR (95% CI) of heart disease was 0.50 (0.46-0.55). The aHRs (95% CI) of statin users with low, medium, and high adherence (statin use covering <33%, 33%-66%, and >66%, respectively, of the study period) for the risks of ischemic stroke were 0.50 (0.27-0.92), 0.31 (0.10-1.01), and 0.16 (0.04-0.68) and for heart disease were 0.56 (0.51-0.61), 0.40 (0.33-0.48), and 0.44 (0.38-0.51), respectively, compared with statin nonusers. CONCLUSION: Statin use was associated with lower aHRs for ischemic stroke and heart disease in those with HIS disorders with comorbidities.

Asthma Therapies on Pulmonary Tuberculosis Pneumonia in Predominant Bronchiectasis-Asthma Combination.

Background: It is sometimes difficult to distinguish between asthma and bronchiectasis as their symptoms overlap, and these two diseases are associated with pulmonary tuberculosis (PTB) or pneumonia. Objective: The purpose of this study is to determine the effects of bronchodilator drugs, steroids, antidepressants drugs, and antianxiety drugs on the risks of PTB or pneumonia in patients with bronchiectasis-asthma combination or bronchiectasis-asthma-chronic obstructive pulmonary disease combination-BCAS cohort. Methods: After propensity score matching, we retrospectively studied patients with BCAS (N = 620) and without BCAS (N = 2,314) through an analysis. The cumulative incidence of PTB or pneumonia was analyzed through Cox proportional regression. After adjustment for sex, age, comorbidities, and medications [including long-acting beta2 agonist/muscarinic antagonists (LABAs/LAMAs), short-acting beta2 agonist/muscarinic antagonists (SABAs/SAMAs), leukotriene receptor antagonist, montelukast, steroids (inhaled corticosteroids, ICSs; oral steroids, OSs), anti-depressants (fluoxetine), and anti-anxiety drugs (benzodiazepines, BZDs)], we calculated the adjusted hazard ratios (aHR) and their 95% confidence intervals (95% CI) for these risks. Similar to OSs, ICSs are associated with an increased risk of PTB or pneumonia, lumping these two as steroids (ICSs/OSs). Results: For the aHR (95% CI), with non-LABAs/non-OSs as the reference 1, the use of LABAs [0.70 (0.52-0.94)]/OSs [0.35 (0.29-0.44)] was associated with a lower risk of PTB or pneumonia. However, the current use of LABAs [2.39 (1.31-4.34)]/SABAs [1.61 (1.31-1.96)], steroids [ICSs 3.23 (1.96-5.29)]/OSs 1.76 (1.45-2.14)], and BZDs [alprazolam 1.73 (1.08-2.75)/fludiazepam 7.48 (1.93-28.9)] was associated with these risks. The current use of LAMAs [0.52 (0.14-1.84)]/SAMAs [1.45 (0.99-2.11)] was not associated with these risks. Conclusion: The current use of LAMAs/SAMAs is relatively safe with respect to PTB or pneumonia risks, but LABAs/SABAs, steroids, and BZDs could be used after evaluation of the benefit for the BCAS cohort. However, we must take the possible protopathic bias into account.

Relationships Between Bronchodilators, Steroids, Antiarrhythmic Drugs, Antidepressants, and Benzodiazepines and Heart Disease and Ischemic Stroke in Patients With Predominant Bronchiectasis and Asthma.

OBJECTIVE: We investigated the effects of medication on heart disease and ischemic stroke (HDS) risk in patients with predominant bronchiectasis-asthma combination (BCAS). METHODS: BCAS and non-BCAS cohorts (N = 588 and 1,118, respectively) were retrospectively enrolled. The cumulative incidence of HDS was analyzed using Cox proportional regression; propensity scores were estimated using non-parsimonious multivariable logistic regression. Adjusted hazard ratios (aHRs) and 95% confidence intervals (CIs) for HDS were calculated, adjusting for sex, age, comorbidities, and medication {long- and short-acting ß2 agonists and muscarinic antagonists (LABAs/SABAs and LAMAs/SAMAs), steroids [inhaled corticosteroid steroids (ICSs), oral steroids (OSs)], antiarrhythmics, antidepressants (fluoxetine), benzodiazepines (alprazolam, fludiazepam), statins and antihypertensive drugs (diuretics, cardioselective beta blockers, calcium channel blockers (CCBs) and angiotensin converting enzyme inhibitors (ACEi), angiotensin II blockers)}. RESULTS: Compared with the non-BCAS cohort, the BCAS cohort taking LABAs, SABAs, SAMAs, ICSs, OSs, antiarrhythmics, and alprazolam had an elevated HDS risk [aHRs (95% CIs): 2.36 (1.25-4.33), 2.65 (1.87-3.75), 2.66 (1.74-4.05), 2.53 (1.61-3.99), 1.76 (1.43-2.18), 9.88 (3.27-30.5), and 1.73 (1.15-2.58), respectively except fludiazepam 1.33 (0.73-2.40)]. The aHRs (95% CIs) for LABAs ≤ 30 days, DDDs <415, ICSs ≤ 30 days were 1.10 (0.38-3.15), 2.95 (0.22-38.8), 1.45 (0.76-2.77). The aHRs (95% CIs) for current and recent alprazolam were 1.78 (1.09-2.93) and 777.8 (1.34-451590.0); for current and past fludiazepam were 1.39 (0.75-2.59) and 1.29 (0.42-4.01) and for past alprazolam was 1.57 (0.55-4.46); respectively. The aHRs (95% CIs) for alprazolam >30 DDDs, fludiazepam >20 DDDs, ICSs ≦415 DDDs, and OSs DDDs ≦15 were 1.60 (0.78-3.29), 2.43 (0.90-6.55), 5.02 (1.76-14.3), and 2.28 (1.43-3.62), respectively. CONCLUSION: The bronchodilators, steroids, and antiarrhythmics were associated with higher risk of HDS, even low dose use of steroids. However, the current use of LABAs/ICSs were not associated with HDS. Benzodiazepines were relatively safe, except for current or recent alprazolam use. Notably, taking confounders into account is crucial in observational studies.

Time-dependent propensity-matched general population study of the effects of statin use on cancer risk in an interstitial lung disease and pulmonary fibrosis cohort.

OBJECTIVE: To determine the effect of statins on risk of cancer in patients with interstitial lung disease (ILD) and pulmonary fibrosis. SETTING: We retrospectively enrolled patients with ILD and pulmonary fibrosis and divided them into two cohorts by statin use (statin users (n=10 036) and statin non-users (n=10 036)). PARTICIPANTS: We selected patients with ILD and pulmonary fibrosis (N=53 862) from Taiwan's National Health Insurance Research Database. Time-dependent Cox models were used to compare risk of cancer of propensity-matched statin users and non-users. Cumulative cancer incidence was analysed through Cox proportional regression. We calculated adjusted HRs (aHRs) and their 95% CIs for cancer after adjusting for sex, age, comorbidities, and use of inhaled corticosteroids, oral steroids and statins. RESULTS: Compared with statin non-users, the aHRs (95% CIs) for statin users were 0.60 (0.55 to 0.65) for cancer, 0.52 (0.35 to 0.78) for haematological malignancy, 0.52 (0.38 to 0.72) for cancer of the head and neck, 0.73 (0.59 to 0.89) for colorectal cancer, 0.34 (0.26 to 0.43) for liver cancer, 0.39 (0.23 to 0.67) for pancreatic cancer, 0.40 (0.17 to 0.96) for skin cancer, 0.67 (0.52 to 0.87) for breast cancer, 0.27 (0.14 to 0.54) for cervical cancer, 0.37 (0.30 to 0.46) for other immunological cancers, 0.73 (0.54 to 0.98) for bladder/kidney cancer and 0.88 (0.71 to 1.09) for lung cancer. CONCLUSION: Statin use is associated with lower risk of cancer in the ILD and pulmonary fibrosis cohort.

Effects of statins and steroids on coronary artery disease and stroke in patients with interstitial lung disease and pulmonary fibrosis: A general population study.

PURPOSE: To determine the effects of statins and steroids on the risk of coronary artery disease (CAD) and stroke in patients with interstitial lung disease and pulmonary fibrosis (ILD-PF). METHODS: We retrospectively enrolled patients with ILD-PF who were using statins (statin cohort, N = 11,567) and not using statins (nonstatin cohort, N = 26,159). Cox proportional regression was performed to analyze the cumulative incidence of CAD and stroke. Adjusted hazard ratios (aHRs) and 95% confidence intervals (CIs) of CAD and stroke were determined after sex, age, and comorbidities, as well as the use of inhaler corticosteroids (ICSs), oral steroids (OSs), and statins, were controlled for. RESULTS: Compared with those of patients without statin use, the aHRs (95% CIs) of patients with statin use for CAD and ischemic stroke were 0.72 (0.65-0.79) and 0.52 (0.38-0.72), respectively. For patients taking single-use statins but not ICSs/OSs, the aHRs (95% CIs) for CAD and ischemic stroke were 0.72 (0.65-0.79)/0.69 (0.61-0.79) and 0.54 (0.39-0.74)/0.50 (0.32-0.79), respectively. For patients using ICSs/OSs, the aHRs (95% CIs) for CAD and ischemic stroke were 0.71 (0.42-1.18)/0.74 (0.64-0.85) and 0.23 (0.03-1.59)/0.54 (0.35-0.85), respectively. CONCLUSIONS: The findings demonstrate that statin use, either alone or in combination with OS use, plays an auxiliary role in the management of CAD and ischemic stroke in patients with ILD-PF.

Polymyositis/dermatomyositis is a potential risk factor for acute respiratory failure: a pulmonary heart disease.

BACKGROUND: Studies on the association between polymyositis/dermatomyositis (PM/DM) and acute respiratory failure (ARF) are considerably limited. We investigated whether ARF is associated with PM/DM using a nationwide cohort study. METHODS: We identified 1,374 patients with newly diagnosed PM/DM and 13,740 comparison individuals without PM/DM (non-PM/DM) randomly selected from the general population; frequency matched by age, sex, and index year using the National Health Insurance Research Database; and followed up until the end of 2011 to measure the incidence of ARF. Cox proportional hazards regression analysis was used to measure the hazard ratio (HR) of ARF for the PM/DM cohort in comparison with the non-PM/DM cohort. RESULTS: The adjusted HR of ARF was 5.05 for the PM/DM cohort compared with the non-PM/DM cohort after adjusting for sex, age, comorbidities, Charlson comorbidity index (CCI) score and medicine. The risk of ARF significantly increased irrespective of age, sex, comorbidities and medicine. Meanwhile, the PM/DM cohort with comorbidities, such as cardiac disease (hypertension), pulmonary disease (chronic obstructive pulmonary disease and pneumonia), and pulmonary vascular diseases had additive effects on the incident ARF. CONCLUSIONS: This study determined the cross-reaction of pulmonary heart disease in the PM/DM cohort with incident ARF even without comorbidities.

Associations among chronic obstructive pulmonary disease with asthma, pneumonia, and corticosteroid use in the general population.

PURPOSE: To evaluate the association among chronic obstructive pulmonary disease (COPD) with asthma, steroid use, and pneumonia in the general population. METHODS: Using Taiwan's National Health Insurance Research Database to identify patients with incident pneumonia, we established a COPD with asthma cohort of 12,538 patients and a COPD cohort of 25,069 patients. In both cohorts, the risk of incident pneumonia was assessed using multivariable Cox proportional hazards models. RESULTS: The adjusted hazard ratio (aHR) with 95% confidence interval (CI) for incident pneumonia was 2.38 (2.14, 2.66) in the COPD with asthma cohort, regardless of age, sex, comorbidities, and drug use. COPD cohort without inhaled corticosteroids (ICSs) use served as a reference. The aHR (95% CI) for COPD cohort with ICSs use was 1.34 (0.98, 1.83); that for COPD with asthma cohort without ICSs use was 2.46 (2.20, 2.76); and that for COPD with asthma cohort with ICSs use was 2.32 (1.99, 2.72). COPD cohort without oral steroids (OSs) use served as a reference; the aHR (95% CI) for COPD with asthma cohort without OSs use and with OSs use was 3.25 (2.72, 3.89) and 2.38 (2.07, 2.74), respectively. CONCLUSIONS: The COPD with asthma cohort had a higher risk of incident pneumonia, regardless of age, sex, comorbidities, and ICSs or OSs use. COPD cohort with ICSs use did not have a notable risk of incident pneumonia. The COPD with asthma cohort had a higher risk of incident pneumonia, even without ICSs/OSs use.

Effect of Bronchodilator and Steroid Use on Heart Disease and Stroke Risks in a Bronchiectasis-Chronic Obstructive Pulmonary Disease Overlap Cohort: A Propensity Score Matching Study.

Background: To determine the effects of bronchodilator, steroid, and anti-arrhythmia drug use on the risk of heart disease/stroke (HDS) in patients with bronchiectasis-chronic obstructive pulmonary disease overlap syndrome (BCOS). Methods: We retrospectively enrolled patients with BCOS (BCOS cohort, n = 1,493) and patients without bronchiectasis and chronic obstructive pulmonary disease (COPD) (non-BCOS cohort, n = 5,972). The cumulative incidence of HDS was analyzed through Cox proportional regression. We calculated adjusted hazard ratios (aHRs) and their 95% confidence intervals (CIs) for HDS after adjustments for sex, age, comorbidities, long-acting ß2-agonist or long-acting muscarinic antagonist (LABAs/LAMAs) use, short-acting ß2-agonist or short-acting muscarinic antagonist (SABAs/SAMAs) use, oral steroid (OSs) or inhaled corticosteroid steroid (ICSs) use, and anti-arrhythmia drugs use. Results: The aHR (95% CI) for HDS was 1.08 (0.28-4.06) for patients using LAMAs compared with those not using drugs. Regarding drug use days, the aHRs (95% CIs) were 32.2 (1.79-773.0), 1.85 (1.01-3.39), and 31.1 (3.25-297.80) for those with recent SABAs use, past ICSs use, and past anti-arrythmia drugs use, respectively. Regarding cumulative drug dose, the aHRs (95% CIs) were 2.12 (1.46-3.10), 3.48 (1.13-10.6), 3.19 (2.04-4.99), 28.1 (1.42-555.7), 2.09 (1.32-3.29), 2.28 (1.53-3.40), and 1.93 (1.36-2.74) for those with a low dose of SABAs, medium dose of SABAs, low dose of SAMAs, low dose of ICSs, medium dose of ICSs, low dose of OSs, and medium dose of OSs, respectively. Conclusions: Compared with patients without bronchiectasis and COPD, BCOS patients with recent SABAs, past ICSs, and past anti-arrhythmia drugs use; a low or medium SABAs ICSs, and OSs dose; and a low SAMAs dose had a higher risk of HDS. LAMAs were not associated with HDS.

Statin use and Vital Organ Failure in Patients With Asthma-Chronic Obstructive Pulmonary Disease Overlap: A Time-Dependent Population-Based Study.

Objective: The effects of statins on the risk of hepatic, renal, respiratory, and heart failure among patients with asthma-chronic obstructive pulmonary disease overlap (ACO) have not been reported. Design: Time-dependent population-based study. Setting: Patient data from 2000 to 2010 were retrieved from the Taiwan National Health Insurance Research Database. Patients: We divided patients with ACO into cohorts of statin use (N = 1,211) and nonuse (N = 7,443). Measurements and Main Results: The cumulative incidence rates of hepatic, renal, respiratory, and heart failure were analyzed through Cox proportional regression analysis with time-dependent variables. After adjustment for multiple confounding factors, including age, sex, comorbidities, and medications [statins, inhaled corticosteroid (ICS), or oral steroid (OS)], the adjusted hazard ratios (aHRs) [95% confidence intervals (CIs)] for hepatic, renal, respiratory, and heart failure were 0.50 (0.40-0.64), 0.49 (0.38-0.64), 0.61 (0.27-2.21), and 0.47 (0.37-0.60), respectively. The aHRs (95% CIs) for statin use with [ICS, OS] for hepatic, renal, and heart failure were [0.36 (0.20-0.66), 0.52 (0.39-0.70)]; [0.82 (0.51-1.34), 0.46 (0.33-0.63)]; and [0.66 (0.40-1.07), 0.48 (0.37-0.64)], respectively. Conclusions: The ACO cohort with statin use exhibited lower risk of hepatic, renal, and heart failure than any other cohort, regardless of age, sex, comorbidities, or ICS or OS use. Regarding the combined use of statins and ICS, the risks of hepatic failure were lower. For the combined use of statins and OS, hepatic, renal, and heart failure were less frequent.

The Relationship Between Occupational Exposure to Low-dose Ionizing Radiation and Changes in Thyroid Hormones in Hospital Workers.

BACKGROUND: The effects of ionized radiation on the thyroid have been extensively studied. However, most studies have focused on high-dose radiation received accidentally or through therapy, and few were on low-dose occupational exposure. METHODS: Using a retrospective cohort study design, we collected health examination reports from employees who worked on jobs with occupational exposure to radiation at a hospital to evaluate possible changes in the serum thyroid hormones and determine whether there is a dose-response effect. After excluding those with diseases that may affect thyroid function and who were pregnant at any given examination during the study periods we followed the remaining 326 workers for 12 years and evaluated the associations between radiation exposure and changes in serum thyroid hormones using the generalized estimating equation for repeated measures. Data from an external comparison cohort were used to adjust for changes over time. RESULTS: We observed declines in triiodothyronine (T3) and thyroxine (T4) over the study period, but not in thyroid-stimulating hormone (TSH). In addition, we found negative dose-response relationships between exposure duration and declines in the serum levels of T3 (a change of -0.037 ng/ml/year after adjusting for sex and age at the beginning of follow-up; 95% confidence interval [CI] = -0.042, -0.032 ng/ml/year) and T4 (-0.115 µg/dl/year; 95% CI = -0.140, -0.091 µg/dl/year). We also observed an increase in the TSH level (0.683 µIU/ml/year; 95% CI = 0.151, 1.214 µIU/ml/year) after the ninth year of follow-up. CONCLUSIONS: We concluded that despite low exposure doses, occupational exposure to ionizing radiation in healthcare workers still may be associated with the declines in the serum levels of T3 and T4.

Effects of statins on anxiety and depression in patients with asthma-chronic obstructive pulmonary disease overlap syndrome.

BACKGROUND: The effects of statins on anxiety and depression in patients with asthma-chronic obstructive pulmonary disease overlap syndrome (ACOS) have not been reported. This population-based study investigated these effects. METHODS: Taiwan's National Health Insurance Research Database between 2000 and 2010. We enrolled two ACOS cohorts, one of statin users (n = 1252) and one of nonstatin users matched by age, sex, and index date (n = 7887). The cumulative incidence of anxiety and depression was analyzed using time-dependent Cox proportional regression analysis. RESULTS: After adjustment for multiple confounding factors, including age, sex, comorbidities, and medications-statins, inhaled corticosteroids (ICSs), and oral steroids (OSs)-the ACOS cohort with statin use had significantly lower risks of anxiety and depression (anxiety: adjusted hazard ratio [aHR] = 0.34, 95% confidence interval [CI] = 0.28-0.42; depression: aHR = 0.36, 95% CI = 0.25-0.53). The aHRs (95% CIs) for statin use with ICSs or OSs were 0.32 (0.13-0.78) and 0.37 (0.24-0.57), respectively. CONCLUSION: The ACOS cohort with statin use had lower risks of anxiety and depression, regardless of age, sex, commodities, or ICSs and OSs. The incidences of anxiety and depression were relatively low among users of statins with ICSs or OSs in the ACOS cohort.

Predictors of Initial Smear-Negative Active Pulmonary Tuberculosis with Acute Early Stage Lung Injury by High-Resolution Computed Tomography and Clinical Manifestations: An Auxiliary Model in Critical Patients.

This study evaluated the diagnostic use of high-resolution computed tomography (HRCT), chest X-ray (CXR), and clinical manifestations (CM) to identify initial smear-negative (iSN) active pulmonary tuberculosis (aPTB) [iSN-aPTB] in patients with iSN-pulmonary diseases (PD) and acute lung injury (ALI). In the derivation cohort, the [iSN-PD] with ALI patients were divided into the [iSN-aPTB] (G1, n = 26) and [non-aPTB-PD] (G2, n = 233) groups. Lung morphology, number, and lobar (segmental) distribution were evaluated using CXR and HRCT. A multivariate analysis was performed to identify independent variables associated with G1, which were used to generate predictive score models for G1. The predictive model was validated in a separate population of patients (n = 372) with [iSN-PD] and (ALI). The validated model for [HRCT (CXR + Hypoalbuminemia)] had 93.5% (25.8%) sensitivity, 99.5% (89.4%) specificity, and a negative predictive value of 99.5% (93.0%). For [iSN-aPTB], the post-test probability in the derivation cohort (prevalence = 10%), validation cohort (prevalence = 8.3%), and the given prevalence (prevalence = 1%) was 88.7%, 94.4%, and 41.5%, respectively. The HRCT model effectively identified the [iSN-aPTB] subjects among the [iSN-PD] with ALI, regardless of CM. The [non-aPTB-PD] were also correctly classified by the HRCT and [CXR + Hypoalbuminemia] models.

Associations between statins and coronary artery disease and stroke risks in patients with asthma-chronic obstructive pulmonary disease overlap syndrome: A time-dependent regression study.

BACKGOUND AND AIMS: We aimed at determining the effects of statin use on coronary artery disease (CAD) and stroke risks in patients with asthma-chronic obstructive pulmonary disease overlap syndrome (ACOS). METHODS: We retrospectively enrolled patients with ACOS treated with (N = 916) and without (N = 6338) statins. The cumulative incidence of CAD and stroke (ischemic and hemorrhagic) was analyzed through time-dependent Cox proportional regression. After adjustment for sex, age, comorbidities, inhaled corticosteroid steroid (ICS) use, and oral steroid (OS) use, we calculated the adjusted hazard ratios (aHRs) and their 95% confidence intervals (CIs) for CAD or stroke in the statin users (long-term [>600 days] and short-term [≤600 days]) compared with the non-users. RESULTS: Among the statin users, aHRs (95% CIs) for CAD and stroke were 0.50 (0.41-0.62) and 0.83 (0.63-1.09), respectively; moreover, aHRs were 0.30 (0.09-0.99) and 0.90 (0.68-1.20) for ischemic and hemorrhagic stroke, respectively. aHRs (95% CIs) for CAD and stroke were 0.58 (0.47-0.71) and 0.93 (0.70-1.23), respectively, in the short-term users and 0.23 (0.13-0.41) and 0.42 (0.19-0.89), respectively, in the long-term users. CONCLUSIONS: CAD risk was lower in all statin users, regardless of the duration of use, whereas ischemic stroke risk was lower only in the long-term statin users. No association was observed between hemorrhagic stroke risk and statin use.

Relationship between pneumonia and cardiovascular diseases: A retrospective cohort study of the general population.

AIMS: To evaluate the relationship between cardiovascular diseases (CVDs) and pneumonia in the general population. METHODS: This retrospective observational study included two cohorts, namely CVD (n = 28,363) and non-CVD (n = 28,363) cohorts, which were matched by propensity score and examined for cases of pneumonia. Data were obtained from 2000 to 2011. In both cohorts, pneumonia risk was measured using multivariable Cox proportional hazard models. RESULTS: With the non-CVD cohort as reference, the corresponding adjusted hazard ratios (aHRs) [95% confidence intervals (CIs)] of pneumonia were 2.03 [1.77-2.31] for coronary artery disease, 4.11 [3.15-5.36] for heart failure, 3.21 [2.70-3.81] for cerebrovascular disease, 1.46 [1.07-1.98] for peripheral vascular disease, and 2.27 [2.01-2.56] for the CVD cohort. The cohort with comorbidities had a higher risk (all p < .05) of pneumonia compared with that without comorbidities, except for patients with the comorbidities of hypertension, hyperlipidemia, obesity, and liver disease. The aHR (95% CI) of pneumonia for antibiotic use was 1.26 (1.09-1.47). The aHRs of community-acquired pneumonia (CAP) and hospital-acquired pneumonia (HAP) were 3.25 (95% CI = 1.04-10.1) and 2.95 (95% CI = 2.25-3.88), respectively. The aHRs (95% CI) were 1.78 (1.05-3.03) for intensive care unit (ICU) risk and 0.98 (0.96-0.99) for length of admission. CONCLUSION: Pneumonia risk was associated with CVDs, especially heart failure, regardless of age, gender, comorbidities, and antibiotic use, particularly in elderly male patients. In addition, Patients with CVDs had a higher risk of CAP and HAP. The CVD cohort had a higher frequency of ICU admissions, but shorter admission lengths.

Association between neurodegenerative diseases and pneumonia: a retrospective population-based study.

PURPOSE: The association between pneumonia and neurodegenerative diseases (NDs) has never been reported in detail. We address this relationship with reference to the general population. METHODS: Using Taiwan's National Health Insurance Research Database to identify a pneumonia cohort (including the typical and atypical), we established an ND cohort of 19,062 patients and a non-ND cohort of 76,227 people. In both cohorts, the risk of pneumonia was measured using multivariable Cox proportional hazards models. RESULTS: The adjusted hazard ratio (aHR) (95% confidence interval [CI]) for the pneumonia cohort was 2.10 (1.96-2.24), regardless of age, sex, comorbidities or drug use in the ND cohort. The aHR (95% CI) for adults aged 20-49 years was 2.08 (1.58-2.75), men 2.20 (2.01-2.40). However, older subjects were at greatest risk of pneumonia, (3.41 [2.99-3.88]) if the 20-49 years age group is used as the reference. For the ND and non-ND cohorts, those with comorbidities (with the exception of hyperlipidemia) had higher risk; aHR (95% CI) 2.35 (2.30-2.52). The aHR (95% CI) for those without comorbidities is 3.28 (2.52-4.26). No significant difference was observed in incidence of pneumonia between those who were and were not using statin medications; the aHR (95% CI) was 1.03 (0.93-1.14). CONCLUSION: The ND cohort had a higher risk of pneumonia, regardless of age, sex, comorbidities or statin use. The risk of pneumonia was higher in elderly and male patients in the ND cohort.