Effects of empiric antibiotic treatment based on hospital cumulative antibiograms in patients with bacteraemic sepsis: a retrospective cohort study.

OBJECTIVES: To assess the effects of empiric antibiotics with different degrees of appropriateness based on hospital cumulative antibiograms in patients with bacteraemic sepsis presenting to the emergency department (ED). METHODS: This retrospective cohort study included adult patients with sepsis and positive blood culture reports in the ED from February 2016 to December 2018. Based on isolated pathogens and empiric antibiotics which the patients received, these patients were divided into two groups using a cut-off of 70% for overall antimicrobial susceptibility (OAS) on hospital cumulative antibiograms 6 months prior to ED admission. Multivariate regression and sensitivity analyses were performed. RESULTS: In this study, 1055 patients were included. We used multivariate regression models which were adjusted for age, sex, co-morbidities, site of infection, organ dysfunction, and septic shock. Empiric antibiotics with OAS of ≥70% were associated with reduced in-hospital deaths (adjusted odds ratio, 0.46; 95% CI, 0.28-0.77) and 30-day mortality (adjusted odds ratio, 0.53; 95% CI, 0.33-0.86). They were more likely to result in a shortened length of intensive care unit stay by 1.60 days (95% CI, -3.00 to -0.20). CONCLUSIONS: Treatment with empiric antibiotics with OAS of ≥70% based on hospital cumulative antibiograms is associated with lower mortality and shorter length of intensive care unit stay in patients with bacteraemic sepsis in the ED.

Aristolochic acid and the risk of cancers in patients with type 2 diabetes: Nationwide population-based cohort study.

BACKGROUND: Both aristolochic acid (AA) exposure and diabetic can increase risk of certain cancers,whetherAAexposureincreases cancer risk in diabetic patientsisunknown. The purpose of this study was to investigate the association between the use of Chinese herbal products containing AA and the risk of cancer in diabetic patients. METHODS: A cohort study was conducted using the National Health Insurance Research Database in Taiwan. Patients older than 18 years who were diagnosed with diabetes between 1997 and 2010 were enrolled in our cohort. The use of Chinese herbal products containing AA was recorded from the beginning of 1997 until the ban of herbs containing AA in November 2003. Patients were individually tracked to identify cancer incidence between 1997 and 2013. Only patients who visited traditional Chinese medicine clinics between 1997 and 1 year before the end of follow-up were included in the cohort to ensure comparability. Cox proportional hazards regression was used to calculate the hazard ratio for the association between the use of Chinese herbal products containing AA and the occurrence of cancer. RESULTS: Among the 430 377 male and 431 956 female patients with diabetes enrolled in our cohort, 37 554 and 31 535 cancer diagnoses were recorded during the study period, respectively. The use of AA-containing herbal products was associated with a significantly higher risk of liver, colorectum, kidney, bladder, prostate, pelvis, and ureter cancer in a dose-dependent manner. An increased risk of extrahepatic bile duct cancer in women was also associated with AA exposure at doses of more than 500 mg. CONCLUSIONS: Association between AA exposure and the risk of some cancers were found in this study. AA exposure might increase risk of kidney,bladder,pelvis, ureter,liver,colorectum,andprostatecancer in all patientsandextrahepatic bile duct cancerin women.

The association of aspirin use with overall survival of patients with inoperable non-small cell lung cancer: a retrospective study.

BACKGROUND: Studies have indicated that individuals taking aspirin have a reduced risk of cancers and have also established chemo-preventive benefit of aspirin in colorectal cancer. However, research on the association between aspirin use and the survival in patients with lung cancer has revealed inconsistent results. In this study, we investigated the effect of aspirin use on the survival of inoperable non-small cell lung cancer (NSCLC) patients. METHODS: We identified a cohort of 38,842 patients diagnosed with NSCLC between 2000 and 2012 using the Taiwan's National Health Insurance Research Database and used propensity score matching to reduce possible confounding factors. In total, 9864 patients (4932 matched pairs) were included in the matched cohort. Aspirin exposure was analyzed to identify a possible association with mortality in patients with inoperable NSCLC. Time-dependent Cox regression models were used to calculate the hazard ratios (HRs) and the 95% confidence intervals (95% CIs) that corresponded with aspirin exposure. RESULTS: A total of 4979 patients used aspirin at the time of diagnosis of NSCLC. The median overall survival (OS) of the aspirin users was 1.73 (interquartile range, 0.94-3.53) years compared with the 1.30 (interquartile range, 0.69-2.62) years of the non-aspirin users. The Cox proportional hazard model with the time-dependent covariate revealed that aspirin use was associated with a significantly longer OS (HR: 0.83, 95.0% CI: 0.80-0.86). After controlling the sociodemographic characteristics (age, sex, income, and level of urbanization) and lung cancer treatments by propensity score matching, the aspirin users still had a significantly longer OS than the non-aspirin users (HR: 0.79, 95.0% CI: 0.75-0.83). CONCLUSION: Aspirin use is associated with a longer OS in patients with inoperable NSCLC, suggesting that aspirin has a potential anticancer effect. These results warrant further randomized clinical trials to evaluate the actual role of aspirin in the treatment of NSCLC patients.

Herbal Medicine Containing Aristolochic Acid and the Risk of Primary Liver Cancer in Patients with Hepatitis C Virus Infection.

BACKGROUND: We investigated the association between taking herbal medicine (HM) containing aristolochic acid (AA) and the risk of primary liver cancer (PLC) among patients with hepatitis C virus (HCV) infection. METHODS: This is a prospective study for the long-term follow-up of a nationwide population-based cohort of patients ages 18 years or older diagnosed with HCV infection during 1997 to 2010. A total of 223,467 HCV-infected patients were identified using the National Health Insurance Research Database in Taiwan. The use of HM containing AA was evaluated among patients who had visited traditional Chinese medicine clinics beginning from 1997 to 1 year prior to the diagnosis of PLC or dates censored (2003). We tracked each individual patient from 1997 to 2013 to identify incident cases of PLC since 1999. RESULTS: During the follow-up period of 3,052,132 person-years, we identified 25,502 PLC cases; this corresponded to an overall incidence rate of 835.5 PLCs per 100,000 person-years. The adjusted HRs were 1.21 [95% confidence interval (CI), 1.18-1.24], 1.48 (95% CI, 1.37-1.59), 1.50 (95% CI, 1.34-1.68), and 1.88 (95% CI, 1.61-2.19) for estimated AA usage groups: 1 to 250, 251 to 500, 501 to 1,000, and more than 1,000 mg, respectively, relative to no AA exposure (reference group). CONCLUSIONS: The current findings suggest that among HCV-positive patients, increasing exposure to AA poses an increased risk of acquiring PLC. IMPACT: AA may increase the risk of PLC in HCV-positive populations.

Metformin Prolongs Survival in Type 2 Diabetes Lung Cancer Patients With EGFR-TKIs.

Background: Metformin use reportedly reduces cancer risk and improves survival in lung cancer patients. This study aimed to investigate the effect of metformin use in patients with diabetes mellitus (DM) and lung cancer receiving epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI) therapy. Methods: A nationwide, population-based cohort study was conducted using the Taiwan National Health Insurance Research Database. From January 1, 2004, to December 31, 2012, a total of 373 metformin and 1260 non-metformin lung cancer cohorts with type 2 DM and EGFR-TKI treatment were studied. Results: Metformin use was significantly associated with a reduced risk of death (hazard ratio: 0.73, 95% confidence interval [CI]: 0.62-0.85, P < .001), as well as a significantly longer median progression-free survival (9.2 months, 95% CI: 8.6-11.7, vs 6.4 months, 95% CI: 5.9-7.2 months, P < .001) and median overall survival (33.4 months, 95% CI: 29.4-40.2, vs 25.4 months, 95% CI: 23.7-27.2 months, P < 0.001). Conclusions: In conclusion, metformin may potentially enhance the therapeutic effect and increase survival in type 2 DM patients with lung cancer receiving EGFR-TKI therapy.

Real-world effectiveness of medications on survival in patients with COPD-heart failure overlap.

The appropriate treatment for patients with coexistent chronic obstructive pulmonary disease (COPD) and heart failure (HF) remains unclear. Data from the Taiwan National Health Insurance Research Database was used for this retrospective cohort study. Patients diagnosed with both diseases between 1997 and 2012 were enrolled as the COPD-heart failure overlap cohort. Patients were categorized as non-users and users of specific COPD and HF medications. Medication prescriptions in each 3-month and 1-year period served as time-dependent covariates. The primary endpoint was cumulative survival. The validation study confirmed the accuracy of definitions of COPD (94.0% sensitivity) and HF (96.3% sensitivity).The study included 275,436 patients with COPD-heart failure overlap, with a mean follow-up period of 9.32 years. The COPD-heart failure overlap cohort had more medical service use and higher mortality than did the COPD alone cohort. Use of inhaled corticosteroid (ICS)/long-acting ß2 agonist (LABA) combinations, long-acting muscarinic antagonist (LAMA), angiotensin receptor blockers (ARBs), ß blockers, aldosterone antagonists, and statins reduced mortality risk compared with non-use. Sensitivity and subgroup analyses confirmed the consistency and robustness of results.ICS/LABA combinations, LAMA, ARBs, ß blockers, aldosterone antagonists, and statins use was associated with a lower mortality risk in patients with COPD-heart failure overlap.

Stomach Cancer and Exposure to Talc Powder without Asbestos via Chinese Herbal Medicine: A Population-Based Cohort Study.

The present investigation was designed to explore the risk of stomach cancer by oral intake of talc powder without asbestos. We conducted a population-based cohort study on a randomly sampled cohort from Taiwan's health insurance database, with population of 1,000,000. The study participants were followed up through 2013. The outcome event of interest was the diagnosis of stomach cancer. The exposure of interest was the prescription of talc powder. Cox regression analyses were performed respectively. There were 584,077 persons without talc exposure and 21,575 talc users, 1849 diagnosed with stomach cancer. Persons with exposure of talc had a higher hazard ratio of stomach cancer (adjusted hazard ratio, 2.13; 95% confidence interval (CI), 1.54⁻2.94; p < 0.001). Classification by cumulative exposure of talc yielded adjusted hazard ratios of stomach cancer of 1.58 (95% CI, 0.79⁻3.17; p = 0.19) and 2.30 (95% CI, 1.48⁻3.57; p < 0.001) among persons with high (>21 g) and medium (6⁻21 g) exposure of talc, as compared to the low-exposure counterparts. Our data demonstrated positive association between increased risk of stomach cancer and oral intake of talc without asbestos. Despite the absence of dose-response effect, there might be a link between stomach cancer and talc.

Antidepressant Prescription and Risk of Lung Cancer: A Nationwide Case-Control Study.

INTRODUCTION: In recent decades, concern about safety of antidepressants has been raised but the risk between antidepressants and lung cancer has not yet been established. METHODS: A case-control study was conducted by using a nationwide database in Taiwan. The case groups were new onset lung cancer diagnosis during 1999-2008 and age- and gender-matched controls were selected among those without any cancer. The cumulative exposure dose before the lung cancer diagnosis was added and risks were calculated according to the levels of defined daily dose and classes of antidepressants. RESULTS: A total of 39,001 individuals with lung cancer and 189,906 individuals without lung cancer between 1999 and 2008 were included in the analysis. Antidepressants, of any class, were not associated with elevated risks for lung cancer with the exception of bupropion at high exposure levels (odds ratio=4.81, 95% confidence interval=1.39-16.71). DISCUSSION: Antidepressant prescription was not associated with elevation of lung cancer incidence using a nationally representative sample. The elevated risk for lung cancer with bupropion at high doses may be a bias by indication and warrant longitudinal investigation.

Thiazolidinediones and reduced risk of incident bacterial abscess in adults with type 2 diabetes: A population-based cohort study.

AIM: Previous research has suggested that peroxisome proliferator-activated receptor-gamma (PPAR-γ) may play an important role in immunomodulation. We aimed to examine the association between thiazolidinediones, PPAR-γ agonists and incidence of bacterial abscess among patients with type 2 diabetes. MATERIALS AND METHODS: This retrospective cohort study between 2000 and 2010 included 46 986 propensity (PS)-matched patients diagnosed with type 2 diabetes. We compared the incidence of bacterial abscess, including liver and non-liver abscesses, between patients treated with metformin plus a thiazolidinedione (M + T, N = 7831) or metformin plus a sulfonylurea (M + S, N = 39 155). Data were retrieved from a population-based Taiwanese database. We applied Cox proportional hazard regression models to estimate hazard ratios (HRs) and 95% confidence intervals (CIs), comparing M + T and M + S after PS matching. RESULTS: During a median follow-up of 4.5 years, the incidence rate of bacterial abscess was lower with M + T than with M + S treatment (1.89 vs 3.15 per 1000 person-years) in the PS-matched cohort. M + T was associated with a reduced risk of bacterial abscess (HRs after PS matching, 0.58; 95% CI, 0.42-0.80 for total bacterial abscess; 0.54; 95% CI, 0.28-1.07 for liver abscess; 0.59; 95% CI, 0.41-0.85 for non-liver abscess). Results did not change materially after accounting for unmeasured confounding factors using high-dimenional PS matching and differential censoring between regimen groups. Rosiglitazone and pioglitazone, in combination with metformin, produced similar reductions in risk of all abscess outcomes. CONCLUSION: We found that M + T may provide a protective benefit in reducing the incidence of bacterial abscesses. These findings merit further investigation.

Prescription patterns of traditional Chinese medicine amongst Taiwanese children: a population-based cohort study.

BACKGROUND: Traditional Chinese medicine (TCM) has been used by Chinese patients and in many other countries worldwide. However, epidemiological reports and prescription patterns on children are few. METHODS: A cohort of 178,617 children aged 18 and under from one million randomly sampled cases of the National Health Insurance Research Database was analyzed for TCM prescription patterns. SAS 9.1 was applied and descriptive medicine utilization patterns were presented. RESULTS: The cohort included 112,889 children treated by TCM, with adolescents (12- to 18-year-olds) as the largest group. In the children's TCM outpatient visits, Chinese herbal remedies were the main treatment. The top three categories of diseases treated with Chinese herbal remedies were respiratory system; symptoms, signs, and ill-defined conditions; and digestive system. The top three categories using acupuncture were: injury and poisoning, diseases of the musculoskeletal system and connective tissue, and diseases of the respiratory system. Of the top ten herbal medicines prescribed by TCM physicians, the top nine herbal formulae and the top ten single herbs were associated with diseases of the respiratory system. CONCLUSION: This study identified patterns of TCM prescriptions for children and common disease categories treated with TCM. The results provide a useful reference for health policy makers and for those who consider the usage of TCM for children.

Herbal medicine containing aristolochic acid and the risk of hepatocellular carcinoma in patients with hepatitis B virus infection.

It was suspected that aristolochic acid-induced mutations may be associated with hepatitis B virus (HBV), playing an important role in liver carcinogenesis. The purpose of this study was to investigate the association between the use of Chinese herbs containing aristolochic acid and the risk of hepatocellular carcinoma (HCC) among HBV-infected patients. We conducted a retrospective, population-based, cohort study on patients older than 18 years who had a diagnosis of HBV infection between January 1, 1997 and December 31, 2010 and had visited traditional Chinese medicine clinics before one year before the diagnosis of HCC or the censor dates. A total of 802,642 HBV-infected patients were identified by using the National Health Insurance Research Database in Taiwan. The use of Chinese herbal products containing aristolochic acid was identified between 1997 and 2003. Each patient was individually tracked from 1997 to 2013 to identify incident cases of HCC since 1999. There were 33,982 HCCs during the follow-up period of 11,643,790 person-years and the overall incidence rate was 291.8 HCCs per 100,000 person-years. The adjusted hazard ratios (HRs) were 1.13 (95% confidence interval [CI], 1.11-1.16), 1.21 (95% CI, 1.13-1.29), 1.37 (95% CI, 1.24-1.50) and 1.61 (95% CI, 1.40-1.84) for estimated aristolochic acid of 1-250, 251-500, 501-1,000 and more than 1,000 mg, respectively, relative to no aristolochic acid exposure. Our study found a significant dose-response relationship between the consumption of aristolochic acid and HCC in patients with HBV infection, suggesting that aristolochic acid which may be associated with HBV plays an important role in the pathogenesis of HCC.

Use of ICS/LABA Combinations or LAMA Is Associated with a Lower Risk of Acute Exacerbation in Patients with Coexistent COPD and Asthma.

BACKGROUND: Based on current guidelines, more research is urgently needed to guide appropriate treatment for patients with asthma-chronic obstructive pulmonary disease (COPD) overlap. OBJECTIVE: The objective of this study was to investigate medication effects on acute exacerbation in patients with coexistent COPD and asthma. METHODS: Using Taiwan's National Health Insurance Research Database, we conducted a nationwide population-based study to evaluate medication effects in patients with COPD and asthma. Patients diagnosed with both asthma and COPD between 1997 and 2012 were enrolled as the COPD + asthma cohort. The primary endpoint was acute exacerbation. The definitions of COPD and asthma were validated. The validation study confirmed the accuracy of definitions of COPD (86.2% sensitivity) and asthma (92.0% sensitivity). RESULTS: The study included 251,398 patients with COPD + asthma and 514,522 patients with COPD alone, with a mean follow-up period of 9.85 years. After adjustment, hazard ratios (HRs) for long-acting muscarinic antagonist (LAMA) and inhaled corticosteroid/long-acting ß2-agonist (ICS/LABA) combinations were lower (time-dependent model, 1 year: LAMA, HR 0.51, 95% confidence interval [CI] 0.49-0.54; ICS/LABA combinations, HR 0.61, 95% CI 0.60-0.62; all P < .0001) than were those for LABAs or ICSs in patients with COPD and asthma. CONCLUSIONS: The use of LAMA or ICS/LABA combinations was associated with a lower risk of acute exacerbation in patients with COPD and asthma in this study.

Danshen improves survival of patients with advanced lung cancer and targeting the relationship between macrophages and lung cancer cells.

In traditional Chinese medicine, Salvia miltiorrhiza Bunge (danshen) is widely used in the treatment of numerous cancers. However, its clinical effort and mechanism in the treatment of advanced lung cancer are unclear. In our study, the in vivo protective effort of danshen in patients with advanced lung cancer were validated using data from the National Health Insurance Research Database in Taiwan. We observed in vitro that dihydroisotanshinone I (DT), a bioactive compound in danshen, exerts anticancer effects through many pathways. First, 10 µM DT substantially inhibited the migration ability of lung cancer cells in both macrophage and macrophage/lung cancer direct mixed coculture media. Second, 10 µM DT repressed the phosphorylation of signal transducer and activator of transcription 3 (STAT3), the protein expression of S-phase kinase associated protein-2 (Skp2), and the mRNA levels of STAT3-related genes, including chemokine (C-C motif) ligand 2 (CCL2). In addition, 10 µM DT suppressed the macrophage recruitment ability of lung cancer cells by reducing CCL2 secretion from both macrophages and lung cancer cells. Third, 20 µM DT induced apoptosis in lung cancer cells. Furthermore, DT treatment significantly inhibited the final tumor volume in a xenograft nude mouse model. In conclusion, danshen exerts protective efforts in patients with advanced lung cancer. These effects can be attributed to DT-mediated interruption of the cross talk between lung cancer cells and macrophages and blocking of lung cancer cell proliferation.

Incidence and risk factors of depression after diagnosis of lung cancer: A nationwide population-based study.

This study aimed to explore the incidence and risk factors of depression after lung cancer diagnosis. Using the Taiwan National Health Insurance Research Database (NHIRD), incidences and risk factors of depression in lung cancer and nonlung cancer cohorts were analyzed.From 1998 to 2006, a total of 22,125 patients were included in each matched cohort of lung cancer and nonlung cancer patients from NHIRD. The incidence of depression was higher in the lung cancer cohort than in the nonlung cancer cohort (1545.8 vs 1366.6 per 100,000 person-years). An increased risk of depression was observed in the lung cancer cohort [adjusted hazard ratio (aHR): 1.16, 95% confidence interval (95% CI): 1.01-1.34, P = .0377]. In lung cancer patients, age ≤50 years (aHR: 2.72, 95% CI: 2.02-3.66, P < .0001), age 50 to 69 years (aHR: 2.34, 95% CI: 1.87-2.94, P < .0001), female gender (aHR: 1.50, 95% CI: 1.26-1.80, P < .0001), coronary artery disease (CAD) (aHR: 1.40, 95% CI: 1.08-1.82, P = .0113), and operation (aHR: 1.78, 95% CI: 1.46-2.16, P < .0001) were associated with an increased risk of depression. In addition, higher incidences of emergency room (ER) visit (4.76 vs 2.82, per person-year) and admission (5.73 vs 4.33, per person-year) were observed in lung cancer patients with depression than those without depression.Our results showed that early surveillance and intervention of depression should be advocated after a diagnosis of lung cancer.

Aristolochic Acid in the Etiology of Renal Cell Carcinoma.

BACKGROUND: Aristolochia species used in the practice of traditional herbal medicine contains aristolochic acid (AA), an established human carcinogen contributing to urothelial carcinomas of the upper urinary tract. AA binds covalently to genomic DNA, forming aristolactam (AL)-DNA adducts. Here we investigated whether AA is also an etiologic factor in clear cell renal cell carcinoma (ccRCC). METHODS: We conducted a population-based case-control study to investigate the linkage between Aristolochia prescription history, cumulative AA consumption, and ccRCC incidence in Taiwan (5,709 cases and 22,836 matched controls). The presence and level of mutagenic dA-AL-I adducts were determined in the kidney DNA of 51 Taiwanese ccRCC patients. The whole-exome sequences of ccRCC tumors from 10 Taiwanese ccRCC patients with prior exposure to AA were determined. RESULTS: Cumulative ingestion of more than 250 mg of AA increased risk of ccRCC (OR, 1.25), and we detected dA-AL-I adducts in 76% of Taiwanese ccRCC patients. Furthermore, the distinctive AA mutational signature was evident in six of 10 sequenced ccRCC exomes from Taiwanese patients. CONCLUSIONS: This study strongly suggests that AA contributes to the etiology of certain RCCs. IMPACT: The current study offers compelling evidence implicating AA in a significant fraction of the RCC arising in Taiwan and illustrates the power of integrating epidemiologic, molecular, and genetic data in the investigation of cancer etiology. Cancer Epidemiol Biomarkers Prev; 25(12); 1600-8. ©2016 AACR.

Use of an α-Glucosidase Inhibitor and the Risk of Colorectal Cancer in Patients With Diabetes: A Nationwide, Population-Based Cohort Study.

OBJECTIVE: Acarbose, an α-glucosidase inhibitor, has been shown to have antineoplastic effects on colorectal cancer in biomarker studies. We assessed the association between acarbose use in patients with diabetes and incident colorectal cancer. RESEARCH DESIGN AND METHODS: We conducted a nationwide, population-based study using a large cohort with diabetes in the Taiwan National Health Insurance Research Database. Patients with newly diagnosed diabetes (n = 1,343,484) were enrolled between 1998 and 2010. One control subject not using acarbose was randomly selected for each subject using acarbose after matching for age, sex, diabetes onset, and comorbidities. Cox proportional hazards regression with a competing risks analysis was used to calculate the hazard ratios (HRs) and 95% CIs for the association between acarbose use and incident colorectal cancer for each eligible case-control pair (n = 199,296). RESULTS: There were 1,332 incident cases of colorectal cancer in the cohort with diabetes during the follow-up period of 1,487,136 person-years. The overall incidence rate was 89.6 cases per 100,000 person-years. Patients treated with acarbose had a 27% reduction in the risk of colorectal cancer compared with control subjects. The adjusted HRs were 0.73 (95% CI 0.63-0.83), 0.69 (0.59-0.82), and 0.46 (0.37-0.58) for patients using >0 to <90, 90 to 364, and ≥365 cumulative defined daily doses of acarbose, respectively, compared with subjects who did not use acarbose (P for trend < 0.001). CONCLUSIONS: Acarbose use reduced the risk of incident colorectal cancer in patients with diabetes in a dose-dependent manner.

Frequency and co-prescription pattern of Chinese herbal products for hypertension in Taiwan: a Cohort study.

BACKGROUND: Chinese herbal products (CHPs) have been frequently used among patients with chronic diseases including hypertension; however, the co-prescription pattern of herbal formulae and single herbs remain uncharacterized. Thus, this large-scale pharmacoepidemiological study evaluated the frequency and co-prescription pattern of CHPs for treating hypertension in Taiwan from 2003 to 2009. METHODS: The database of traditional Chinese medicine (TCM) outpatient claims was obtained from the National Health Insurance in Taiwan. Patients with hypertension during study period were defined according to diagnostic codes in the International Classification of Disease Ninth Revision, Clinical Modification. The frequencies and percentages of herbal formula and single herb prescriptions for hypertension were analyzed. We also applied association rules to evaluate the CHPs co-prescription patterns. RESULTS: The hypertension cohort included 154,083 patients, 123,240 patients of which (approximately 80 %) had used TCM at least once. In total, 81,582 visits involving CHP prescriptions were hypertension related; Tian-Ma-Gou-Teng-Yin and Dan Shen (Radix Salvia Miltiorrhizae) were the most frequently prescribed herbal formula and single herb, respectively, for treating hypertension. CONCLUSIONS: This study elucidated the utilization pattern of CHPs for treating hypertension. Future studies on the efficacy and safety of these CHPs and on drug-herb interactions are warranted.

Frequencies and prescription patterns of traditional Chinese medicine use among elderly patients in Taiwan: A population-based study.

ETHNOPHARMACOLOGICAL RELEVANCE: Traditional Chinese medicine (TCM), one of the most commonly used complementary and alternative medicines, has been receiving increasing attention among elderly patients. However, epidemiological reports and prescription patterns of geriatric TCM users are few. The aim of this study is to use data from a nationwide cohort database to analyze TCM use by the geriatric population in Taiwan from 2005 to 2009. MATERIALS AND METHODS: TCM outpatient claims data was obtained from the Taiwan National Health Insurance database. Data for elderly patients aged 65 years and older were included in the analysis during the study period. The demographic data, disease distributions, and frequencies and prescription patterns of TCM use by the geriatric population were analyzed. RESULTS: The geriatric cohort included 97,210 patients, in which 46,883 patients (48%) had used TCM at least once, with a total of 723,478 TCM outpatient visits. Of these, 175,857 visits (24.3%) were prompted by "diseases of the musculoskeletal system and connective tissue"; more than half of patients with such diseases were treated using acupuncture and traumatology manipulative therapies. Overall, among the 552,835 visits during which Chinese herbal products (CHP) were prescribed, Shu-Jing-Huo-Xie-Tang and Dan Shen (Radix Salvia Miltiorrhizae) were the most frequently prescribed herbal formula and single herb, respectively, for elderly patients. In addition, Shu-Jing-Huo-Xie-Tang was also the most prescribed herbal formula for the most common disease categories of "diseases of the musculoskeletal system and connective tissue" among TCM elderly patients, followed by Du-Huo-Ji-Sheng-Tang, and Shao-Yao-Gan-Cao-Tang. CONCLUSION: This study elucidated the TCM utilization patterns of the geriatric population. However, additional studies are warranted to determine the safety and efficacy of these CHPs for use by elderly patients in further clinical trials.

Use of traditional Chinese medicine in patients with hyperlipidemia: A population-based study in Taiwan.

ETHNO-PHARMACOLOGICAL RELEVANCE: Chinese herbal products (CHPs) are commonly used in patients with hyperlipidemia in traditional Chinese medicine (TCM). Because hyperlipidemia and related disease are common issues worldwide, this study analyzed the prescription patterns and frequencies of CHPs for treating patients with hyperlipidemia in Taiwan. BACKGROUND: Traditional Chinese medicine (TCM) has become popular as a therapy for controlling symptoms in patients with hyperlipidemia. This study aimed to analyze the prescription patterns of TCM for patients with hyperlipidemia in Taiwan. METHODS: The study population was recruited from a random-sampled cohort of 1,000,000 people from the National Health Insurance Research Database between 2003 and 2009. We identified 30,784 outpatient visits related with hyperlipidemia diagnosis and collected these medical records. Association rules of data mining were conducted to explore the co-prescription patterns for Chinese herbal products (CHPs). RESULTS: The most commonly prescribed herbal formula for hyperlipidemia treatment was Xue-Fu-Zhu-Yu-Tang (16.1%), and Shan Zha (Crataegi fructus; 25.0%) was the most commonly prescribed single herb. The most commonly prescribed combination of an herbal formula and a single herb was Xue-Fu-Zhu-Yu-Tang and Dan Shen (Radix Salviae Miltiorrhizae), and the most commonly prescribed combination of couplet herbs was Dan Shen and Shan Zha. CONCLUSION: Xue-Fu-Zhu-Yu-Tang is the most frequently prescribed formula and is typically prescribed with Shan Zha, Dan Shen, and He Shou Wu for patients with hyperlipidemia. Clinical trials are warranted in future research to investigate the effects of the CHPs in terms of safety and efficacy and in particular to evaluate potential interactions with conventional treatments.

Chinese herbs containing aristolochic acid associated with renal failure and urothelial carcinoma: a review from epidemiologic observations to causal inference.

Herbal remedies containing aristolochic acid (AA) have been designated to be a strong carcinogen. This review summarizes major epidemiologic evidence to argue for the causal association between AA exposure and urothelial carcinoma as well as nephropathy. The exposure scenarios include the following: Belgian women taking slimming pills containing single material Guang Fang Ji, consumptions of mixtures of Chinese herbal products in the general population and patients with chronic renal failure in Taiwan, occupational exposure in Chinese herbalists, and food contamination in farming villages in valleys of the Danube River. Such an association is corroborated by detecting specific DNA adducts in the tumor tissue removed from affected patients. Preventive actions of banning such use and education to the healthcare professionals and public are necessary for the safety of herbal remedies.