Germline mutations of homologous recombination genes and clinical outcomes in pancreatic cancer: a multicenter study in Taiwan.

BACKGROUND: Cancer susceptibility germline mutations are associated with pancreatic ductal adenocarcinoma (PDAC). However, the hereditary status of PDAC and its impact on survival is largely unknown in the Asian population. METHODS: Exome sequencing was performed on 527 blood samples from PDAC individuals and analyzed for mutations in 80 oncogenic genes. Pathogenic and likely pathogenic (P/LP) germline variants were diagnosed according to the ACMG variant classification categories. The association between germline homologous recombination gene mutations (gHRmut, including BAP1, BRCA1, BRCA2, PALB2, ATM, BLM, BRIP1, CHEK2, NBN, MUTYH, FANCA and FANCC) and the treatment outcomes was explored in patients with stage III/IV diseases treated with first-line (1L) platinum-based versus platinum-free chemotherapy. RESULTS: Overall, 104 of 527 (19.7%) patients carried germline P/LP variants. The most common mutated genes were BRCA2 (3.60%), followed by ATR (2.66%) and ATM (1.9%). After a median follow-up duration of 38.3-months (95% confidence interval, 95% CI 35.0-43.7), the median overall survival (OS) was not significantly different among patients with gHRmut, non-HR germline mutations, or no mutation (P = 0.43). Among the 320 patients with stage III/IV disease who received 1L combination chemotherapy, 32 (10%) had gHRmut. Of them, patients receiving 1L platinum-based chemotherapy exhibited a significantly longer median OS compared to those with platinum-free chemotherapy, 26.1 months (95% CI 12.7-33.7) versus 9.6 months (95% CI 5.9-17.6), P = 0.001. However, the median OS of patients without gHRmut was 14.5 months (95% CI 13.2-16.9) and 12.6 months (95% CI 10.8-14.7) for patients receiving 1L platinum-based and platinum-free chemotherapy, respectively (P = 0.22). These results were consistent after adjusting for potential confounding factors including age, tumor stage, performance status, and baseline CA 19.9 in the multivariate Cox regression analysis. CONCLUSIONS: Our study showed that nearly 20% of Taiwanese PDAC patients carried germline P/LP variants. The longer survival observed in gHRmut patients treated with 1L platinum-based chemotherapy highlights the importance of germline testing for all patients with advanced PDAC at diagnosis.

No association between alcohol consumption and pancreatic cancer even among individuals genetically susceptible to the carcinogenicity of alcohol.

Inconsistent results have been reported for the association between alcohol use and pancreatic cancer, particularly at low levels of alcohol consumption. Individuals genetically susceptible to the carcinogenic effect of alcohol might have higher pancreatic cancer risk after drinking alcohol. The current study investigated the association between alcohol use and pancreatic cancer with 419 pancreatic cancer cases and 963 controls recruited by a hospital-based case-control study in Taiwan. Gene-environment interaction between alcohol use and polymorphisms of two ethanol-metabolizing genes, ADH1B and ALDH2, on pancreatic risk was evaluated. Our results showed no significant association between alcohol drinking and an increased pancreatic cancer risk, even at high levels of alcohol consumption. Even among those genetically susceptible to the carcinogenic effect of alcohol (carriers of ADH1B*2/*2(fast activity) combined with ALDH2*1/*2(slow activity) or ALDH2*2/*2(almost non-functional)), no significant association between alcohol use and pancreatic cancer was observed. Overall, our results suggested that alcohol drinking is not a significant contributor to the occurrence of pancreatic cancer in Taiwan.

Validation of genome-wide association study-identified single nucleotide polymorphisms in a case-control study of pancreatic cancer from Taiwan.

BACKGROUND: Due to differences in genetic background, it is unclear whether the genetic loci identified by the previous genome-wide association studies (GWAS) of pancreatic cancer also play significant roles in the development of pancreatic cancer among the Taiwanese population. METHODS: This study aimed to validate the 25 pancreatic cancer GWAS-identified single nucleotide polymorphisms (SNPs) in a case-control study (278 cases and 658 controls) of pancreatic cancer conducted in Taiwan. Statistical analyses were conducted to determine the associations between the GWAS-identified SNPs and pancreatic cancer risk. Gene-environment interaction analysis was conducted to evaluate the interactions between SNPs and environmental factors on pancreatic cancer risk. RESULTS: Among the 25 GWAS-identified SNPs, 7 (rs2816938 (~ 11 kb upstream of NR5A2), rs10094872 (~ 28 kb upstream of MYC), rs9581943 (200 bp upstream of PDX1) and 4 chromosome 13q22.1 SNPs: rs4885093, rs9573163, rs9543325, rs9573166) showed a statistically significant association with pancreatic cancer risk in the current study. Additional analyses showed two significant gene-environment interactions (between poor oral hygiene and NR5A2 rs2816938 and between obesity and PDX1 rs9581943) on the risk of pancreatic cancer. CONCLUSIONS: The current study confirmed the associations between 7 of the 25 GWAS-identified SNPs and pancreatic risk among the Taiwanese population. Furthermore, pancreatic cancer was jointly influenced by lifestyle and medical factors, genetic polymorphisms, and gene-environment interaction. Additional GWAS is needed to determine the genetic polymorphisms that are more relevant to the pancreatic cancer cases occurring in Taiwan.

The Epidemiology of Gastric Cancers in the Era of Helicobacter pylori Eradication: A Nationwide Cancer Registry-Based Study in Taiwan.

BACKGROUND: Helicobacter pylori eradication has been shown to decrease gastric adenocarcinoma risk. The epidemiology of gastric lymphoma, which is also associated with H. pylori, and other rare subtypes of gastric cancer is less clear. This study comprehensively evaluated the incidence trend and the survival of gastric cancer in Taiwan by histologic subtype. METHODS: The incidence trends of gastric cancer in Taiwan from 1996 and 2013 were evaluated using data from the Taiwan Cancer Registry. The life-table method and the Cox proportional hazards analysis were used to evaluate the survival of gastric cancer. RESULTS: The incidence of all gastric cancers in Taiwan decreased from 15.97 per 100,000 in 1996 to 11.57 per 100,000 in 2013. The most frequent histologic subtype of gastric cancer in Taiwan was adenocarcinoma, followed by lymphoma and sarcoma (mainly gastrointestinal stromal tumor). The best survival was in patients with sarcoma, followed by lymphoma, neuroendocrine tumor, and adenocarcinoma. Generally, women had a better survival than men. The incidence of adenocarcinoma significantly decreased from 13.56 per 100,000 in 1996 to 9.82 per 100,000 in 2013 (P < 0.0001). In contrast, the incidences of mucosa-associated lymphoid tissue lymphoma and diffuse large B-cell lymphoma did not decrease. CONCLUSIONS: The incidence of adenocarcinoma and lymphoma, both of which are associated with H. pylori, showed diverging trends. The survival of gastric cancer differed by histologic subtype and sex. IMPACT: The disparity in the incidence trends between gastric lymphoma and adenocarcinoma, both associated with H. pylori, warranted the need to search for additional risk factors of gastric lymphoma.

The incidence and survival of pancreatic cancer by histology, including rare subtypes: a nation-wide cancer registry-based study from Taiwan.

Studies have indicated a significant rise in the incidence of pancreatic adenocarcinoma. However, the epidemiology of other rare histologic subtypes of pancreatic cancer is not well understood. This study analyzed the incidence and survival of pancreatic cancer in Taiwan by histologic subtype, sex, age group, and year of diagnosis. The incidence trends of pancreatic cancer in Taiwan from 2002 to 2013 were calculated using data from the Taiwan Cancer Registry. The survival of pancreatic cancer patients was assessed using the life-table method and Cox proportional hazards analysis. The incidence of pancreatic cancer increased from 4.62 per 100,000 in 2002 to 6.04 per 100,000 in 2013 in Taiwan. The most common histologic subtype of pancreatic cancer was adenocarcinoma followed by carcinoma and neuroendocrine tumors (NETs). Adenocarcinoma and NETs showed a rapid increase in incidence, while the incidences of other subtypes did not change significantly. Patients with adenocarcinoma showed a poor survival with a 5-year survival of 5.2%. Patients with endocrinomas, NETs, and lymphoma displayed a better survival than those with adenocarcinoma, with a 5-year survival ranging from 41.8% to 59.1%. The survival of adenocarcinoma, lymphoma, and NETs improved after the introduction of novel therapies. Understanding the risk factors and identifying the biomarkers for the early diagnosis of pancreatic cancer are important to prevent the development and improve the survival of pancreatic cancer.

Investigating the Association Between Periodontal Disease and Risk of Pancreatic Cancer.

OBJECTIVE: Periodontal disease (PD) is increasingly recognized as an emerging risk factor for various systemic diseases, including diabetes, cardiovascular diseases, and cancer. The current study examined the association between PD (periodontitis, gingivitis, and others) and pancreatic cancer. METHODS: A total of 139,805 subjects with PD and 75,085 subjects without PD were identified from the National Health Insurance Research Database of Taiwan. Cox proportional hazards regression was performed to compare the incidence of pancreatic cancer between the 2 groups. RESULTS: Periodontal disease was positively associated with pancreatic cancer risk (hazard ratio [HR], 1.55; 95% confidence interval [CI], 1.02-2.33). This positive association occurred predominantly among those aged 65 years or older (HR, 2.17; 95% CI, 1.03-4.57) and was not observed among those aged younger than 65 years (HR, 0.83; 95% CI, 0.52-1.34). Further analysis showed that PD is a risk factor for pancreatic cancer independent of diabetes, hyperlipidemia, allergies, viral hepatitis, peptic ulcer, pancreatitis, chronic obstructive pulmonary disease (as a proxy for cigarette smoking), and alcoholic-related conditions (as a proxy for alcohol drinking). CONCLUSIONS: Our results indicated a significantly positive association between PD and risk of pancreatic cancer. The underlying biological mechanisms for the positive association between PD and pancreatic cancer require further investigation.

Comprehensive Analysis of the Incidence and Survival Patterns of Lung Cancer by Histologies, Including Rare Subtypes, in the Era of Molecular Medicine and Targeted Therapy: A Nation-Wide Cancer Registry-Based Study From Taiwan.

Lung cancer is the third most common cancer in the world and has the highest cancer mortality rate. A worldwide increasing trend of lung adenocarcinoma has been noted. In addition, the identification of epidermal growth factor receptor (EGFR) mutations and the introduction of EGFR inhibitors to successfully treat EGFR mutated non-small cell lung cancers are breakthroughs for lung cancer treatment. The current study evaluated the incidence and survival of lung cancer using data collected by the Taiwan Cancer Registry between 1996 and 2008. The results showed that the most common histologic subtype of lung cancer was adenocarcinoma, followed by squamous cell carcinoma, small cell carcinoma, large cell carcinoma, neuroendocrine tumors, lymphoma, and sarcoma. Overall, the incidence of lung cancer in Taiwan increased significantly from 1996 to 2008. An increased incidence was observed for adenocarcinoma, particularly for women, with an annual percentage change of 5.9, whereas the incidence of squamous cell carcinoma decreased. Among the subtypes of lung cancer, the most rapid increase occurred in neuroendocrine tumors with an annual percentage change of 15.5. From 1996-1999 to 2005-2008, the 1-year survival of adenocarcinoma increased by 10% for men, whereas the 1-, 3-, and 5-year survivals of adenocarcinoma for women increased by 18%, 11%, and 5%, respectively. Overall, the incidence of lung cancer has been increasing in Taiwan, although the trends were variable by subtype. The introduction of targeted therapies was associated with a significantly improved survival for lung adenocarcinoma in Taiwan; however, more studies are needed to explain the rising incidence of lung adenocarcinoma. In addition, it is important to investigate the molecular pathogenesis of the various subtypes of lung cancer to develop novel therapeutic agents.

Incidence trends of human papillomavirus-related head and neck cancer in Taiwan, 1995-2009.

Recent studies suggested that human papillomavirus (HPV) is an emerging risk factor of head and neck cancer (HNC), particularly for oropharyngeal cancer. Studies from the West showed a rising trend of HPV-related HNC despite a decrease of the overall HNC incidence. In contrast, the overall HNC incidence in Taiwan has continued to rise. It is not clear whether the incidence trends of HPV-related HNC in Taiwan have a similar pattern to those from countries with an overall decreasing incidence of HNC. This study examined the incidence trends of HPV-related and HPV-unrelated HNC in Taiwan using data from the Taiwan Cancer Registry. Our results showed that the incidence trends of HPV-related and HPV-unrelated HNC in Taiwan both rose during 1995-2009. The incidence of HPV-related HNC (1.3 per 100,000 in 1995 to 3.3 in 2009, annual percentage change (APC) = 6.9, p < 0.0001) rose more rapidly than the incidence of HPV-unrelated HNC (10.4 per 100,000 in 1995 to 21.7 in 2009, APC = 5.0, p < 0.0001). The rising trend of HPV-related HNC was particularly prominent for HNC occurring in tonsil (APC = 8.2, p < 0.0001), in men (APC = 7.5, p < 0.0001), and in those aged between 40 and 50 years (APC = 8.5, p < 0.0001). Although the overall incidence of HNC in Taiwan has continued to increase, the most rapid rise is in the HPV-related HNC. This suggests that similar to the Western world, HPV-related HNC is becoming an important public health issue in Taiwan.

The epidemiology of gastrointestinal stromal tumors in Taiwan, 1998-2008: a nation-wide cancer registry-based study.

BACKGROUND: To investigate the incidence of gastrointestinal stromal tumors (GISTs) in Taiwan and the impact of imatinib on the overall survival (OS) of GIST patients. METHODS: GISTs were identified from the Taiwan Cancer Registry (TCR) from 1998 to 2008. The age-adjusted incidence rates and the observed OS rates were calculated. Cox proportional hazards models were applied to examine the mortality risk in three time periods (1998-2001, 2002-2004, 2005-2008) according to the application and availability of imatinib. RESULTS: From 1998 to 2008, 2,986 GISTs were diagnosed in Taiwan. The incidence increased from 1.13 per 100,000 in 1998 to 1.97 per 100,000 in 2008. The most common sites were stomach (47-59%), small intestine (31-38%), and colon/rectum (6-9%). The 5-year observed OS was 66.5% (60.3% for men, 74.2% for women, P < .0001). GISTs in the stomach had a better 5-year observed OS (69.4%) than those in the small intestine (65.1%) (P < .0001). The outcome of GIST improved significantly after the more widespread use of imatinib; the 5-year observed OS increased from 58.9% during 1998-2001 to 70.2% during 2005-2008 (P < .0001). Younger age, female sex, stomach location, and later diagnostic years were independent predictors of a better survival. CONCLUSIONS: The incidence of GIST has been increasing in Taiwan, partially due to the advancement of diagnostic technology/method and the increased awareness by physicians. The outcome of GIST has improved significantly with the availability and the wider use of imatinib.

Medical risk factors associated with cholangiocarcinoma in Taiwan: a population-based case-control study.

BACKGROUND: Cholangiocarcinoma, including intra- and extrahepatic cholangiocarcinoma, is a rare but highly lethal cancer. Despite effort in finding the risk factors of cholangiocarcinoma, the causes of most cholangiocarcinoma remain unknown. This study utilized a population-based case-control design using data from the National Health Insurance Research Database (NHIRD) of Taiwan to assess the medical conditions associated with cholangiocarcinoma. METHODS: 5,157 incident cases of cholangiocarcinoma diagnosed during 2004 to 2008 and 20,628 controls matched to the cases on sex, age, and time of diagnosis (reference date for the controls) were identified from the NHIRD. Medical risk factors were ascertained from the NHIRD for each individual. Conditional logistic regression was performed to evaluate the association between cholangiocarcinoma and each medical risk factor. RESULTS: The results showed that factors associated with an increased risk of cholangiocarcinoma included cholangitis, cholelithiasis, cholecystitis, cirrhosis of liver, alcoholic liver disease, chronic non-alcoholic liver disease, hepatitis B, hepatitis C, diabetes, chronic pancreatitis, inflammatory bowel disease, and peptic ulcer. In addition, sex and age differences were observed. CONCLUSIONS: This study confirms the association between cholangiocarcinoma and several less established risk factors, including diabetes, inflammatory bowel disease, hepatitis B, hepatitis C, and peptic ulcer (proxy for the presence of Helicobacter Pylori). Future studies should focus on finding additional environmental and genetic causes of cholangiocarcinoma.

The epidemiology of neuroendocrine tumors in Taiwan: a nation-wide cancer registry-based study.

BACKGROUND: The epidemiology of neuroendocrine tumors (NETs) is not well illustrated, particularly for Asian countries. METHODS: The age-standardized incidence rates and observed survival rates of NETs diagnosed in Taiwan from January 1, 1996 to December 31, 2008 were calculated using data of the Taiwan Cancer Registry (TCR) and compared to those of the Norwegian Registry of Cancer (NRC) and the US Surveillance, Epidemiology, and End Results (SEER) program. RESULTS: During the study period, a total of 2,187 NET cases were diagnosed in Taiwan, with 62% males and a mean age of 57.9 years-old. The age-standardized incidence rate of NETs increased from 0.30 per 100,000 in 1996 to 1.51 per 100,000 in 2008. The most common primary sites were rectum (25.4%), lung and bronchus (20%) and stomach (7.4%). The 5-year observed survival was 50.4% for all NETs (43.4% for men and 61.8% for women, P<0.0001). The best 5-year observed survivals for NETs by sites were rectum (80.9%), appendix (75.7%), and breast (64.8%). CONCLUSIONS: Compared to the data of Norway and the US, the age-standardized incidence rate of NETs in Taiwan is lower and the major primary sites are different, whereas the long-term outcome is similar. More studies on the pathogenesis of NETs are warranted to devise preventive strategies and improve treatment outcomes for NETs.

Second cancers in patients with neuroendocrine tumors.

BACKGROUND: Second cancers have been reported to occur in 10-20% of patients with neuroendocrine tumors (NETs). However, most published studies used data from a single institution or focused only on specific sites of NETs. In addition, most of these studies included second cancers diagnosed concurrently with NETs, making it difficult to assess the temporality and determine the exact incidence of second cancers. In this nationwide population-based study, we used data recorded by the Taiwan Cancer Registry (TCR) to analyze the incidence and distribution of second cancers after the diagnosis of NETs. METHODS: NET cases diagnosed from January 1, 1996 to December 31, 2006 were identified from the TCR. The data on the occurrence of second cancers were ascertained up to December 31, 2008. Standardized incidence ratios (SIRs) of second cancers were calculated based on the cancer incidence rates of the general population. Cox-proportional hazards regression analysis was performed to estimate the hazard ratio (HR) and 95% confidence interval (CI) for the risk of second cancers associated with sex, age, and primary NET sites. RESULTS: A total of 1,350 newly diagnosed NET cases were identified according to the selection criteria. Among the 1,350 NET patients, 49 (3.63%) developed a second cancer >3 months after the diagnosis of NET. The risk of second cancer following NETs was increased compared to the general population (SIR = 1.48, 95% CI: 1.09-1.96), especially among those diagnosed at age 70 or older (HR = 5.08, 95% CI = 1.69-15.22). There appeared to be no preference of second cancer type according to the primary sites of NETs. CONCLUSIONS: Our study showed that the risk of second cancer following NETs is increased, especially among those diagnosed at age 70 or older. Close monitoring for the occurrence of second cancers after the diagnosis of NETs is warranted.

Allergy and risk of childhood acute lymphoblastic leukemia: a population-based and record-based study.

A deficit of normal immune stimulation in early childhood is a suspected risk factor for both childhood acute lymphoblastic leukemia (ALL) and allergies. The present study utilized a population-based case-control design using medical claims data from the National Health Insurance Research Database of Taiwan to evaluate the association between allergy and childhood leukemia. Eight hundred forty-six childhood ALL patients who were newly diagnosed during 2000 to 2008 and were older than 1 but less than 10 years of age were individually matched with 3,374 controls based on sex, birth date, and time of diagnosis (reference date for the controls). Conditional logistic regression was performed to assess the association between childhood ALL and allergies. An increased risk of ALL was observed with having an allergy less than 1 year before the case's ALL diagnosis (odds ratio (OR) = 1.7, 95% confidence interval (CI): 1.5, 2.0), more than 1 year before the case's diagnosis (OR = 1.3, 95% CI: 1.1, 1.5), and before the age of 1 year (OR = 1.4, 95% CI: 1.1, 1.7). These results suggest that the pathogenesis of childhood ALL and allergy share a common biologic mechanism.

Medically diagnosed infections and risk of childhood leukaemia: a population-based case-control study.

BACKGROUND: Previous studies on the association between childhood infections and childhood leukaemia have produced inconsistent results, likely due to the recall error/bias of infection data reported by the parents. The current study used a population-based and record-based case-control design to evaluate the association between childhood leukaemia and infections using the National Health Insurance Research Database of Taiwan. METHODS: In all, 846 childhood acute lymphoblastic leukaemia (ALL) and 193 acute myeloid leukaemia (AML) patients newly diagnosed between 2000 and 2008, aged >1 and <10 years, were included. Up to four controls (3374 for ALL and 766 for AML) individually matched to each case on sex, birth date and time of diagnosis (reference date for the controls) were identified. Conditional logistic regression was performed to assess the association between childhood leukaemia and infections. RESULTS: Having any infection before 1 year of age was associated with an increased risk for both childhood ALL (odds ratio = 3.2, 95% confidence interval 2.2-4.7) and AML (odds ratio = 6.0, 95% confidence interval 2.0-17.8), with a stronger risk associated with more episodes of infections. Similar results were observed for infections occurring >1 year before the cases' diagnosis of childhood leukaemia. CONCLUSIONS: Children with leukaemia may have a dysregulated immune function present at an early age, resulting in more episodes of symptomatic infections compared with healthy controls. However, confounding by other infectious measures such as birth order and day care attendance could not be ruled out. Finally, the results are only relevant to the medically diagnosed infections.

Effect of Helicobacter pylori eradication therapy on risk of hospitalization for a major ulcer event.

STUDY OBJECTIVE: To compare Helicobacter pylori eradication therapy with antisecretory therapy alone on the risk of hospitalization for a major ulcer event. DESIGN: Retrospective, population-based cohort study. DATA SOURCE: The 2000-2006 National Health Insurance database in Taiwan. PATIENTS: A total of 838,176 patients diagnosed with a gastrointestinal ulcer and who filled at least one prescription for antiulcer therapy, either H. pylori eradication therapy (331,364 patients [39.53%]) or antisecretory therapy alone (506,812 patients [60.47%]), between January 1, 2001, and December 31, 2006. MEASUREMENTS AND MAIN RESULTS: The primary outcome was hospitalization for a major ulcer event, defined as a gastrointestinal ulcer with hemorrhage and/or perforation. Cox proportional hazards models, adjusted for demographic and clinical characteristics, were used to compare the risk of hospitalization for a major ulcer event between the group receiving H. pylori eradication therapy (triple or quadruple combination therapy that includes an antisecretory agent) and the group receiving antisecretory therapy alone (histamine2-receptor blocker or proton pump inhibitor). The H. pylori eradication therapy group was divided into initial users (combination therapy received immediately after gastrointestinal ulcer diagnosis) and late users (combination therapy received after antisecretory therapy with time lag ≤ 180 days, 181-365 days, or > 365 days from ulcer diagnosis). A secondary analysis was conducted in the three late H. pylori eradication therapy subgroups to determine if risk of hospitalization for major ulcer events differed by timing of receipt of therapy. Compared with the antisecretory therapy alone group, the H. pylori therapy group (initial users) had a significantly decreased risk of hospitalization for major ulcer events (adjusted hazard ratio [AHR] 0.57, 95% confidence interval [CI] 0.54-0.59, p<0.001). However, later use of H. pylori therapy was associated with a higher risk of hospitalization for major ulcer events (time lag 181-365 days, AHR 1.68, 95% CI 1.51-1.86, p<0.001; > 365 days, AHR 1.74, 95% CI 1.67-1.80, p<0.001) compared with those who received H. pylori therapy within 6 months (≤ 180 days) after gastrointestinal ulcers were diagnosed. CONCLUSION: Helicobacter pylori therapy given within 6 months of a diagnosis of gastrointestinal ulcer was associated with a reduced risk of hospitalization for major ulcer events. Our findings extend the evidence from clinical trials that report the value of H. pylori eradication therapy in reducing ulcer recurrence by documenting the real-world benefit of reducing the risk of hospitalization for major gastrointestinal ulcer events.

Diffusion patterns of new anti-diabetic drugs into hospitals in Taiwan: the case of thiazolidinediones for diabetes.

BACKGROUND: Diffusion of new drugs in the health care market affects patients' access to new treatment options and health care expenditures. We examined how a new drug class for diabetes mellitus, thiazolidinediones (TZDs), diffused in the health care market in Taiwan. METHODS: Assuming that monthly hospital prescriptions of TZDs could serve as a micro-market to perform drug penetration studies, we retrieved monthly TZD prescription data for 580 hospitals in Taiwan from Taiwan's National Health Insurance Research Database for the period between March 1, 2001 and December 31, 2005. Three diffusion parameters, time to adoption, speed of penetration (monthly growth on prescriptions), and peak penetration (maximum monthly prescription) were evaluated. Cox proportional hazards model and quantile regressions were estimated for analyses on the diffusion parameters. RESULTS: Prior hospital-level pharmaceutical prescription concentration significantly deterred the adoption of the new drug class (HR: 0.02, 95%CI = 0.01 to 0.04). Adoption of TZDs was slower in district hospitals (HR = 0.43, 95%CI = 0.24 to 0.75) than medical centers and faster in non-profit hospitals than public hospitals (HR = 1.79, 95%CI = 1.23 to 2.61). Quantile regression showed that penetration speed was associated with a hospital's prior anti-diabetic prescriptions (25%Q: 18.29; 50%Q: 25.57; 75%Q: 30.97). Higher peaks were found in hospitals that had adopted TZD early (25%Q: -40.33; 50%Q: -38.65; 75%Q: -32.29) and in hospitals in which the drugs penetrated more quickly (25%Q: 16.53; 50%Q: 24.91; 75%Q: 31.50). CONCLUSIONS: Medical centers began to prescribe TZDs earlier, and they prescribed more TZDs at a faster pace. The TZD diffusion patterns varied among hospitals depending accreditation level, ownership type, and prescription volume of Anti-diabetic drugs.

Osteoporosis treatment and atrial fibrillation: alendronate versus raloxifene.

OBJECTIVES: Concerns have been raised about bisphosphonate use and risk of atrial fibrillation (AF) in women with osteoporosis. This study compares the risk of AF and of flutter or acute myocardial infarction (AMI) in women with osteoporosis taking alendronate or raloxifene. METHODS: Using Taiwan's National Health Insurance database to conduct a population-based retrospective cohort study, we reviewed the medical and prescription histories of 27,257 women with osteoporosis (21,037 receiving alendronate and 6,220 receiving raloxifene) between 2001 and 2007. Mean (SD) follow-up was 303.62 (422.87) days. For the main outcome measures, we calculated the adjusted relative risk of AF and AMI using the Cox proportional hazards model, adjusting for various confounders. RESULTS: Incidence rates (per patient-year) of AF in the alendronate group (1.00%) and the raloxifene group (1.02%) were similar. Alendronate use was not associated with risk of AF (hazard ratio [HR], 1.06; 95% CI, 0.85-1.32) and AMI (HR, 1.02; 95% CI, 0.86-1.19) compared with raloxifene use. However, alendronate users who had previous cardiovascular events and had taken their medications for more than 1 year were at significantly greater risk of AMI than were the group taking raloxifene (HR, 2.24; 95% CI, 1.07-4.71). Users who received 70 mg of alendronate once a week were at significantly lower risk of AF than were those taking 10 mg daily (HR, 0.56; 95% CI, 0.47-0.68). CONCLUSIONS: Compared with raloxifene, alendronate did not increase the risk of AF and flutter in women with osteoporosis. Medical history contributed most to the development of AF or AMI in the women who received either raloxifene or alendronate. Long-term treatment with alendronate is not suggested for women with a history of cardiovascular events because they are at increased risk of AMI.

Peer pressure, psychological distress and the urge to smoke.

BACKGROUND: Psychology and addiction research have found that cigarette smokers react with subjective and automatic responses to stimuli associated with smoking. This study examines the association between the number of cigarettes smokers consume per month and their response to cues derived from peer and psychological distress. METHODS: We studied 1,220 adult past and current smokers drawn from a national face-to-face interview survey administered in 2004. We defined two types of cues possibly triggering a smoker to have a cigarette: peer cues and psychological cues. We used ordinary least square linear regressions to analyze smoking amount and response to peer and psychological distress cues. RESULTS: We found a positive association between amount smoked and cue response: peer cues (1.06, 95%CI: 0.74-1.38) and psychological cues (0.44, 95%CI = 0.17-0.70). Response to psychological cues was lower among male smokers (-1.62, 95%CI = -2.26-(-)0.98), but response to psychological cues were higher among those who had senior high school level education (0.96, 95%CI = 0.40-1.53) and who began smoking as a response to their moods (1.25, 95%CI = 0.68-1.82). CONCLUSIONS: These results suggest that both peer cues and psychological cues increase the possibility of contingent smoking, and should, therefore, be addressed by anti-smoking policies and anti-smoking programs. More specifically, special attention can be paid to help smokers avoid or counter social pressure to smoke and to help smokers resist the use of cigarettes to relieve distress.