Traits of Patients With Pituitary Tumors in Multiple Endocrine Neoplasia Type 1 and Comparing Different Mutation Status.

CONTEXT: Recent studies suggest that the clinical characteristics and biological behavior of pituitary tumors (PITs) in patients with multiple endocrine neoplasia type 1 (MEN1) may not be as aggressive as previously reported. Increased imaging of the pituitary as recommended by screening guidelines identifies more tumors, potentially at an earlier stage. However, it is unknown if these tumors have different clinical characteristics in different MEN1 mutations. OBJECTIVE: To assess characteristics of patients with MEN1 with and without PITs, and compare among different MEN1 mutations. METHODS: Data of patients with MEN1 in a tertiary referral center from 2010 to 2023 were retrospectively analyzed. RESULTS: Forty-two patients with MEN1 were included. Twenty-four patients had PITs, 3 of which were invasive and managed with transsphenoidal surgery. One PIT enlarged during follow-up. Patients with PITs had a higher median age at MEN1 diagnosis than those without PITs. MEN1 mutations were identified in 57.1% of patients, including 5 novel mutations. In patients with PITs, those with MEN1 mutations (mutation+/PIT+ group) had more additional MEN1-associated tumors than those without (mutation-/PIT+ group). The mutation+/PIT+ group had a higher incidence of adrenal tumors and a lower median age at initial manifestation of MEN1 than the mutation-/PIT+ group. The most common neuroendocrine neoplasm was nonfunctional in the mutation+/PIT+ group and insulin-secreting in the mutation-/PIT+ group. CONCLUSION: This is the first study comparing characteristics of patients with MEN1 with and without PITs harboring different mutations. Patients without MEN1 mutations tended to have less organ involvement and it might be reasonable for them to receive less intensive follow-up.

Incidence of hospitalization for infection among patients with hepatitis B or C virus infection without cirrhosis in Taiwan: A cohort study.

BACKGROUND: Infection is a major complication in liver cirrhosis and causes major morbidity and mortality. However, the incidence and mortality related to these conditions in patients infected with hepatitis C virus (HCV) are unclear, as is whether antiviral therapy could change their infection risk. METHODS AND FINDINGS: In this community-based cohort study, a total of 115,336 adults (mean age 52.2 years; 35.6% men) without cirrhosis participating in the New Taipei City Health Screening in 2005-2008 were classified as having noncirrhotic HCV (NC-HCV) (n = 2,839), noncirrhotic hepatitis B virus (NC-HBV) (n = 8,316), or no HBV or HCV infection (NBNC) (n = 104,181). Participants were followed to their first hospitalization for infection or death after data linkage with the Taiwan National Health Insurance Research Database (NHIRD) and Death Registry. A Cox proportional hazard regression model, adjusted for age, sex, body mass index (BMI), smoking, alcohol consumption, education level, diabetes, renal function, systemic steroids, and history of hospitalization, was used to calculate hazard ratios (HRs) and 95% confidence intervals (CIs) for overall and individual sites of infection and infection-related mortality. The reference group was NBNC participants with normal to mildly elevated alanine aminotransferase (ALT) (<1.5 times upper normal limit [UNL]) levels. To further address the impact of antiviral treatment on infection risk, we conducted analyses of data from the nationwide NHIRD and compared the risks for hospitalization because of infections and infection-related deaths between patients with HCV who received antiviral therapy (n = 20,264) and those who remained untreated (n = 104,360). During a median 8.2-year follow-up, the incidence of hospitalization for infection was substantially higher in NC-HCV patients. Compared to the reference group, NC-HCV was associated with a significantly higher risk for hospitalization because of overall infections (adjusted HR: 1.22; 95% CI: 1.12-1.33), but we observed no increased risk for patients in the NC-HBV (adjusted HR: 0.94; 95% CI: 0.88-1.01) or NBNC group with moderate to markedly elevated ALT levels (adjusted HR: 1.03; 95% CI: 0.93-1.14). For specific sites of infection, the NC-HCV group had increased risks for septicemia and lower respiratory tract, reproductive, and urinary tract infections. We noted no increased risk for infection-related death among patients with NC-HCV. Patients with HCV who received antiviral therapy had significantly reduced infection-related hospitalization and death risks (adjusted HR: 0.79; 95% CI: 0.73-0.84 for infection-related hospitalization and adjusted HR: 0.08; 95% CI: 0.04-0.16 for infection-related deaths). Study limitations include the exclusion of patients with cirrhosis from the cohort, the possibility of unmeasured confounding, and the lack of information on direct-acting antiviral agents (DAAs). CONCLUSIONS: In this study, patients with NC-HCV were at increased risk for hospitalization for infection, while no increased risk was observed for NC-HBV-infected patients.

Sleep Duration and Proteinuria Progression: A Population-Based Cohort Study.

BACKGROUND: Extensive studies have demonstrated that sleep is an important modulator of cardiovascular and metabolic diseases. However, its impact on renal function remains uncertain. METHODS: A total of 26,249 adults aged ≥20 years were recruited through voluntary health examinations in Taiwan. Sleep duration was self-reported by questionnaire. Proteinuria was graded semi-quantitatively by dipstick urine test. The associations of sleep duration with proteinuria and estimated glomerular filtration rate (eGFR) were analyzed. RESULTS: After an average follow-up period of 2.62 years, the crude hazard ratio (HR) for proteinuria progression were 1.92 (95% CI 1.22-3.03), 1.23 (95% CI 1.09-1.39), and 1.18 (95% CI 1.00-1.39) for those with sleep duration < 4, 4-6, and > 8 h compared to those with sleep duration of 6-8 h (the reference group), respectively. The HR remained significant for those with sleep duration < 4 h (adjusted HR 1.65 [95% CI 1.05-2.61]) and 4-6 h (adjusted HR 1.19 [95% CI 1.06-1.35]) after adjustment for age, sex, blood pressure, fasting glucose, body mass index, cholesterols, triglycerides, uric acids, physical activity, smoking, alcohol consumption, income/educational levels, and baseline eGFR. However, eGFR was not significantly different among different sleep duration groups. DISCUSSION: This result indicates short sleep duration is independently associated with the progression of proteinuria.

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.

The association between new onset atrial fibrillation and incident cancer-A nationwide cohort study.

A recent analysis showed an association with new onset atrial fibrillation (NOAF) and incident cancer among women. We aimed to examine the risk of cancer among patients with NOAF in general population. A retrospective cohort of 5130 patients with NOAF was identified from a random sample of one million subjects between 2005 and 2010 from Taiwan National Health Insurance Research Database. The standard incidence ratio of incident cancer and hazard ratios were calculated by modeling cumulative incidence with competing risk of death. During a mean follow-up duration of 3.4 years, 330 patients developed cancer. The standard incidence ratio of all malignancies was 1.41 (95% confidence interval 1.26-1.57), suggesting a 41% increase in cancer risk compared with the general population. The risk of cancer was higher among men or the elderly with NOAF after adjusting for confounding factors and after considering the competing risk of death. The risk of cancer was not associated with CHA2DS2-VASc score (p = 0.32) among patients with NOAF. In conclusion, patients with NOAF were associated with a higher risk of cancer. Within this group, the risk of ischemic stroke (in terms of CHADS2-VASc score) did not reflect the risk of incident cancer.

Stent revascularization versus bypass surgery for peripheral artery disease in type 2 diabetic patients - an instrumental variable analysis.

The objective of this study was to use instrumental variable (IV) analyses to evaluate the clinical effectiveness of percutaneous stent revascularization versus bypass surgery in the treatment of peripheral artery disease (PAD) among type 2 diabetic patients. Type 2 diabetic patients who received peripheral artery bypass surgery (n = 5,652) or stent revascularization (n = 659) for lower extremity arterial stenosis between 2000 and 2007 were identified from the Taiwan National Health Insurance claims database. Patients were followed from the date of index hospitalization for 2 years for lower-extremity amputation, revascularization, and hospitalization for medical treatment. Analysis using treatment year, patients' monthly income level, and regional difference as IVs were conducted to reduce unobserved treatment selection bias. The crude analysis showed a statistically significant risk reduction in favor of stent placement in lower extremity amputation and in the composite endpoint of amputation, revascularization, or hospitalization for medical treatment. However, peripheral artery stent revascularization and bypass surgery had similar risk of lower limb amputation and composite endpoints in the analyses using calendar year or patients' monthly income level as IVs. These two treatment modalities had similar risk of lower limb amputation among DM patients with PAD.

Survival Analysis After Extracorporeal Membrane Oxygenation in Critically Ill Adults: A Nationwide Cohort Study.

BACKGROUND: Extracorporeal membrane oxygenation (ECMO) provides circulatory and respiratory support for patients with severe acute cardiopulmonary failure. The objective of this study was to examine the survival outcomes for patients who received ECMO. METHODS AND RESULTS: Adult patients who received ECMO from September 1, 2002, to December 31, 2012, were identified from the Taiwan National Health Insurance Database associated with coronary artery bypass graft surgery, myocardial infarction/cardiogenic shock, injury, and infection/septic shock. A Cox regression model was used to determine hazard ratios and to compare 30-day and 1-year survival rates with the myocardial infarction/cardiogenic shock group used as the reference. The mean±SD age of the 4227-patient cohort was 57±17 years, and 72% were male. The overall mortalities were 59.8% and 76.5% at 1 month and 1 year. Survival statistics deteriorated sharply when ECMO was required for >3 days. Acute (30-day) survival was more favorable in the infection/septic shock (n=1076; hazard ratio, 0.61; 95% confidence interval, 0.55-0.67), coronary artery bypass graft surgery (n=1077; hazard ratio, 0.68; 95% confidence interval, 0.61-0.75), and injury (n=369, hazard ratio, 0.82; 95% confidence interval, 0.70-0.95) groups. The extended survival rapidly approached an asymptote near 20% for the infection/septic shock, myocardial infarction/cardiogenic shock (n=1705), and coronary artery bypass graft surgery groups. The pattern of survival for the injury group was somewhat better, exceeding 30% at year-end. CONCLUSIONS: Regardless of initial pathology, patients requiring ECMO were critically ill with similar guarded prognoses. Those in the trauma group had somewhat better outcomes. Determining the efficacy and cost-effectiveness of ECMO should be a critical future goal.

Fetal exposure to parental smoking and the risk of type 2 diabetes: Are lifestyle-related factors more important?

Current evidence suggests that although fetal exposure to smoking might increase the risk of type 2 diabetes in later life, lifestyle factors either during pregnancy or in adulthood may play a more important role. A 'family-based association study' design might be helpful to detangle the relation among intrauterine exposure, lifestyle factors, and risk of diabetes in later life.

Antihypertensive agents and the risk of breast cancer in women aged 55 years and older: a nested case-control study.

OBJECTIVE: The study aimed to investigate the association of long-term use of different antihypertensive agents with incident breast cancer. METHODS: A total of 794 ,533 women aged at least 55 years were identified from Taiwan National Health Insurance claims database during 2001-2011. As of 31 December 2011, incident breast cancer patients were included as cases, and 1 : 4 age-matched controls were selected by risk-set sampling scheme. Logistic regression models were applied to estimate the odds ratios (ORs) and 95% confidence intervals (CIs) of breast cancer incidence associated with different durations of use of angiotensin-converting enzyme inhibitors/angiotensin receptor blockers, ß-blockers, and dihydropyridine calcium channel blockers (DHP CCBs). Different restriction rules were applied to reveal the potential effects of confounding by indication. RESULTS: Among the 9397 incident breast cancer patients and 37 ,588 controls, a significantly elevated risk was found for relatively short-term use of DHP CCBs (<6 years) but not in those observed for more than 6 years. There was no association between either angiotensin-converting enzyme inhibitors/angiotensin receptor blockers or ß-blockers use and breast cancer. Although restricting our analyses to those with any prescription of antihypertensive medications in 2001 or those with diagnosis of hypertension, there was no longer a statistically significant association between any use of DHP CCBs and breast cancer (OR: 1.21, 95% CI: 0.88-1.67 for the former, and OR: 1.71, 95% CI: 0.99-2.95 for the latter). CONCLUSION: The results demonstrated the potential effect of confounding by indication, and thus, did not suggest any association of the use of antihypertensive medication and breast cancer risk.

Risks of hypertension associated with cyclosporine, nonsteroidal anti-inflammatory drugs, and systemic glucocorticoids in patients with psoriasis: a nationwide population-based nested case-control study in Taiwan.

PURPOSE: Patients with psoriasis and/or psoriatic arthritis (PsA) are known to have increased cardiovascular morbidity and mortality. Hypertension, an important risk factor for cardiovascular disease, is highly prevalent in patients with psoriasis and/or PsA. The effects of anti-psoriatic medications - including cyclosporine, nonsteroidal anti-inflammatory drugs, and glucocorticoids - on hypertension remain unclear. We examined whether such medication exposure was associated with hypertension in psoriasis patients. METHODS: This population-based, nested case-control study analyzed data from an inception psoriasis cohort identified from Taiwan's National Health Insurance Research Database, 2000-2010. A total of 1530 patients with newly diagnosed hypertension and 4542 age- and gender-matched controls were included in the analysis. Conditional logistic regressions were applied to estimate the effects of drug of interest on hypertension. RESULTS: After adjusting for potential confounders, patients with current use of cyclosporine [odds ratio (OR) = 7.13; 95% confidence interval (CI) 1.85-27.49], nonsteroidal anti-inflammatory drugs (OR = 2.2; 95% CI 1.95-2.49), or systemic glucocorticoids (OR = 1.42; 95% CI 1.23-1.64) showed an increased risk of hypertension as compared to those not exposed to these drugs. Moreover, an increasing dose or combined use of nonsteroidal anti-inflammatory drugs and glucocorticoids was associated with increased hypertension risk. The risk of hypertension associated with glucocorticoids, or combined use was greatest among patients aged 49 years or less. CONCLUSIONS: The use of cyclosporine, nonsteroidal anti-inflammatory drugs, or glucocorticoid was associated with hypertension in patients with psoriasis and/or PsA. These study results inform physicians on the importance of early identification of hypertension during therapy with such medication.

Time trends in the prevalence and incidence of Parkinson's disease in Taiwan: A nationwide, population-based study.

BACKGROUND/PURPOSE: Identifying trends in the prevalence and incidence of Parkinson's disease (PD) may yield information that supports public health goals. Our aim was to evaluate time-trend changes in the prevalence and incidence of PD in Taiwan between 2004 and 2011. METHODS: This retrospective, nationwide, longitudinal study used the Taiwan National Health Insurance Research Database to identify patients with PD from 2004 to 2011 based on having ICD-9-CM diagnostic codes, which were assigned by neurologists, and being prescribed PD medication. Annual incidence and prevalence were calculated, and time-trend analyses were estimated assuming a Poisson distribution. RESULTS: Over the study period, 19,302 patients in 2004 and 41,606 patients in 2011 fulfilling the study criteria for PD were included in the analysis. The average age-standardized prevalence of PD per 100,000 of population was 84.8 in 2004 and 147.7 in 2011, with a 7.9% yearly increase. Increasing prevalence trends of PD were statistically significant (p < 0.001) in all age groups, with the steepest rate among those aged ≥ 80 years. In contrast, the average age-standardized incidence of PD decreased steadily from 35.3 per 100,000 in 2005 to 28.8 per 100,000 in 2011. The incidence rate was higher in men than in women, and increased with age. CONCLUSION: We identified an increasing trend in the annual prevalence rates of PD from 2004 to 2011; however, the substantial decline in the incidence of PD suggests that some major environmental risk factors for PD were removed from this population during this time period.

Anaemia and related nutrient deficiencies after Roux-en-Y gastric bypass surgery: a systematic review and meta-analysis.

OBJECTIVE: To obtain a pooled risk estimate on the long-term impact of anaemia and related nutritional deficiencies in patients receiving Roux-en-Y gastric bypass (RYGB) surgery. DESIGN: Systematic review and meta-analysis. DATA SOURCES: MEDLINE, EMBASE and Cochrane databases were searched to identify English reports published before 16 May 2014. ELIGIBILITY CRITERIA: Articles with case numbers >100, follow-up period >12 months, and complete data from both before and after surgery were selected. Outcomes of interest were changes in baseline measurements of proportion of patients with anaemia, by haemoglobin, haematocrit, ferritin, iron, vitamin B12 and folate levels. DATA COLLECTION AND ANALYSIS: Two reviewers independently reviewed data and selected six prospective and nine retrospective studies with a total of 5909 patients. A random effect model with inverse variance weighting was used to calculate summary estimates of outcomes at 6, 12, 24 and 36 months postoperatively. RESULTS: Proportion of patients with anaemia was 12.2% at baseline, which, respectively, increased to 20.9% and 25.9% at 12 and 24 months follow-up, consistent with decreases in haemoglobin and haematocrit levels. Although the serum iron level did not change substantially after surgery, the frequency of patients with ferritin deficiency increased from 7.9% at baseline to 13.4% and 23.0% at 12 and 24 months, respectively, postoperation. Vitamin B12 deficiency increased from 2.3% at baseline to 6.5% at 12 months after surgery in those subjects receiving RYGB. There was no obvious increase in folate deficiency. CONCLUSIONS: RYGB surgery is associated with an increased risk of anaemia and deficiencies of iron and vitamin B12, but not folate. Ferritin is more sensitive when serum iron level is within normal range.

Secular trends were considered in the evaluation of universal hepatitis B vaccination in Taiwan.

OBJECTIVES: The objective was to evaluate time-trend bias in the context of a series of studies reporting that a national hepatitis B virus vaccination program (launched in mid-1980s) substantially reduced childhood hepatocellular carcinoma (HCC) incidence. STUDY DESIGN AND SETTING: We applied an age-period-cohort model to evaluate the relative importance of age, time-trend (period), and vaccination (cohort) effect, respectively, on the incidence and mortality rate of HCC in boys and girls in Taiwan from 1980 to 2009. RESULTS: HCC incidence increased with age. The period effect analysis revealed that the incidence of HCC started to decrease in 1980s, leveled off in mid-1990s, and declined again in mid-2000s among boys. The period effect was flat among girls. Cohort effect analysis demonstrated that among boys, the incidence of HCC started to decrease by those born in 2000-2004, which was 15 years later than the first vaccinated cohort. Among girls, the incidence rate started to decline before the mass vaccination program was initiated. The analysis showed a decline in mortality for boys and girls born in 1980s. CONCLUSION: Time trend may play a more important role than the universal vaccination program in interpretation of the observed early decreasing trend in HCC in children, especially among boys.

Effectiveness and safety of extracranial carotid stent placement: a nationwide self-controlled case-series study.

BACKGROUND: Carotid angioplasty and stent (CAS) placement has emerged as an attractive revascularization strategy for patients with internal carotid artery stenosis. However, the effectiveness and safety of CAS were not fully evaluated, mainly because of methodological difficulties in finding an appropriate comparison group. METHODS: Patients who underwent CAS were identified from Taiwan's National Health Insurance claims database between 2005 and 2008. The incidence rate of ischemic stroke after CAS was compared with that of the year prior to the procedure using a self-controlled case series analysis and a conditional Poisson regression model. Logistic regression was conducted to identify factors associated with poor outcome. RESULTS: A total of 1258 patients who had undergone CAS were included, and 73 cases (5.8%) of death or ischemic stroke occurred during the index hospitalization. Within 1 year after CAS, 74 patients died and 80 experienced an ischemic stroke. Of the 1184 patients who were followed for 360 days, the rate ratio for ischemic stroke decreased to 0.21 (95% CI: 0.08-0.51) between 31 and 180 days, and 0.10 (95% CI: 0.03-0.32) between 181 and 360 days. Statin therapy was associated with a reduced risk of death or ischemic stroke in the 1(st) month (odds ratio of 0.53; 95% CI: 0.32-0.90). Conversely, the use of nonsteroidal anti-inflammatory agents, possibly histamine-2 receptor blockers, and CAS performed by low-volume operators were associated with a twofold increased risk. CONCLUSION: CAS reduced the long-term risk for ischemic stroke. Self-controlled case series analysis might be an appropriate design for evaluating device safety and effectiveness.

Risk of Parkinson's disease following severe constipation: a nationwide population-based cohort study.

INTRODUCTION: Constipation is a non-motor symptom of Parkinson's disease (PD). We investigated the association between the severity of constipation and subsequent risk of PD in a population-based sample. METHODS: 551,324 participants free of PD, dementia, and stroke were retrospectively ascertained between January 1, 2005 and December 31, 2005 using the Taiwan National Health Insurance Research Database. The association between constipation at the beginning of the study and the incidence of PD was examined using a Cox regression model. Information regarding comorbidities and concomitant medications use was adjusted in the proportional hazards models. RESULTS: After an average follow-up of 5.5 years, 2336 incident PD cases were diagnosed. The crude incidence rate of PD per 1,000,000 person-days was 1.57 for subjects without constipation and 4.04, 5.28, and 12.67 for mild, moderate, and severe constipation, respectively. After adjusting for age, sex, comorbidities, and concomitant medication use, patients with constipation were more likely to develop PD than subjects without constipation; the adjusted hazard ratio (aHR) was 3.28 (95% CI: 2.14-5.03), 3.83 (2.51-5.84), and 4.22 (2.95-6.05) for individual constipation severity categories. Constipation severity was also associated with an increased likelihood of PD in the time-varying analysis; the aHR was 2.84 (2.43-3.33), 5.22 (4.61-5.92), and 10.47 (9.46-11.58) for mild, moderate, and severe constipation, respectively (P < 0.0001). After excluding PD patients diagnosed within 3 years of constipation, the association remained significant. CONCLUSIONS: Our study suggests that the severity of constipation is associated with a future diagnosis of PD in a dose-dependent manner.

Infection, antibiotic therapy and risk of colorectal cancer: a nationwide nested case-control study in patients with Type 2 diabetes mellitus.

Patients with Type 2 diabetes mellitus are at a higher risk of colorectal cancer (CRC). The objective of our study was to examine the inter-relationship among infection sites, systemic antibiotic use and risk of CRC among patients with Type 2 diabetes mellitus. From a diabetic cohort from the Taiwan's National Health Insurance claims database, we identified 3,593 incident colon cancer cases, 1,979 rectal cancer cases and 22,288 controls and conducted a nested case-control study to examine the association between antibiotic use and CRC incidence. Logistic regression models were applied to estimate the odds ratio (OR) and the 95% confidence interval (95% CI) between infection sites, antibiotic use and CRC incidence. Patients with intra-abdominal infection were significantly associated with increased risk for colon cancer (OR = 2.01, 95% CI = 1.73-2.35) and rectal cancer (OR = 1.59, 95% CI = 1.26-2.00). Any antianaerobic antibiotic use was associated with a higher risk of colon cancer (OR = 2.31, 95% CI = 2.12-2.52) and rectal cancer (OR = 1.69, 95% CI = 1.50-1.90) but without an obvious dose-response relationship for cumulative use. Antianaerobic antibiotics also increased the risks for those with nonintra-abdominal infection. No association was found between antiaerobic agent use and the CRC risk. The results suggest intra-abdominal infections and antianaerobic antibiotic use may be a marker for precancerous lesions or early CRC, although the possibility of antianaerobic antibiotics playing an additional role cannot be excluded. Further research examining the relationship between intra-abdominal infection, antianaerobic antibiotics use and possible change of microbiota leading to colorectal carcinogenesis is warranted.

Examining the association between statins and lung cancer incidence in patients with type 2 diabetes mellitus.

BACKGROUND/PURPOSE: The relationship between statin use and lung cancer remains unclear. Patients with diabetes mellitus, who are at higher risks for both cancer and atherosclerosis, are usually indicated for statin use. The objective was to explore the relationship between statins, lung squamous cell carcinoma (SCC), and lung adenocarcinoma incidence in diabetic patients. METHODS: A cohort of 596,812 type 2 diabetic patients was identified from the Taiwan National Health Insurance claims database in the year 2000, and followed until the earliest of lung cancer diagnosis, death, or December 31, 2007. A Cox regression model with time-varying statin use was applied to estimate the hazard ratio (HR) of lung cancer incidence comparing use and nonuse of statins. A sensitivity analysis was applied to examine the association after adjustment for smoking effect. RESULTS: In the original diabetic cohort, 60,969 statin users and 535,843 statin nonusers were identified. In a median follow-up time of 7.9 years, a total of 1182 incident SCC cases and 2345 adenocarcinoma cases developed. Initial analysis showed a decreased risk of SCC if statins were ever used (HR, 0.69; 95% confidence interval, 0.60-0.81). However, the relative risk would be 0.92 for males and 0.90 for females for statins after adjusting for smoking effect. There was no association between statin use and adenocarcinoma (HR, 0.97; 95% confidence interval, 0.88-1.07), with similar findings after controlling for smoking effect. CONCLUSION: There is no statistically significant association between statin use with lung cancer incidence in diabetic patients after adjustment for the confounding effect attributed to cigarette smoking.

National antiviral treatment program and the incidence of hepatocellular carcinoma and associated mortality in Taiwan: a preliminary report.

BACKGROUND: Taiwan's Bureau of National Health Insurance launched the National Antiviral Treatment Program (NATP) in 2003 to reimburse patients for antiviral drugs and interferons for chronic hepatitis B and C. The objective was to examine the impact of the NATP on the incidence and mortality due to hepatocellular carcinoma (HCC). METHODS: The cumulative numbers of NATP participants were retrieved from the National Health Insurance claims database. The national incidence and mortality rates of HCC were obtained from the Taiwan Cancer Registry in each quarter from 1979 to 2009. An interrupted time-series analysis was applied to test the temporal trend change before and after NATP. RESULTS: From 1979 to 1995, the HCC incidence increased in men and women of all age groups. From 2003 to 2009, 31,155 men and 10,769 women received anti-hepatitis B virus therapy, whereas 13,939 men and 10,721 women received anti-hepatitis C virus therapy. The incidence of HCC reached a plateau and then started to decline in men aged 30-39 (slope change P=0.003), 50-59 (P=0.051), and 60-69 years (P<0.001). A similar trend was noted in women aged 50-59 (P=0.035), 60-69 (P=0.006), and 70-79 years (P=0.052). The HCC mortality rate had been decreasing since 1996 and a further decline was observed after 2004 in men aged 60-69 years and women aged 60-79 years. CONCLUSIONS: There is a strong temporal relationship between NATP and the stabilization of the HCC incidence and related mortality. The cost-effectiveness of the NATP needs further evaluation.

Oseltamivir use and outcomes during the 2009 influenza A H1N1 pandemic in Taiwan.

BACKGROUND: The Taiwan CDC provided free oseltamivir to all patients with influenza infections confirmed by rapid testing or who had clinical warning symptoms during the 2009 H1N1 influenza pandemic in Taiwan. However, oseltamivir utilization patterns, cost, and outcomes among oseltamivir-treated patients remained unclear. METHOD: A population-level, observational cohort study was conducted using the Taiwan National Health Insurance Database from January to December 2009 to describe the use of oseltamivir. RESULT: Prescription trend over weeks increased after a change in government policy and responded to the influenza virus activity. The overall prescription rate was 22.33 per 1000 persons, with the highest prescription rate of 116.5 for those aged 7-12 years, followed by 69.0 for those aged 13-18 years, while the lowest rate was 1.7 for those aged ≥ 65 years. As influenza virus activity increased, the number of prescriptions for those aged ≤18 years rose significantly, whereas no substantial change was observed for those aged ≥65 years. There were also regional variations in terms of oseltamivir utilization and influenza complication rates. CONCLUSIONS: Oseltamivir was widely used in the 2009 H1N1 influenza pandemic in Taiwan, particularly in those aged 7-18 years. The number of prescriptions for oseltamivir increased with a change in government policy and with increasing cases of pandemic influenza. Further study is needed to examine whether there is an over- or under-use of anti-influenza drugs in different age groups or regions and to examine the current policy of public use of anti-influenza drugs to reduce influenza-associated morbidity and mortality.

Statin use and cataract surgery: a nationwide retrospective cohort study in elderly ethnic Chinese patients.

BACKGROUND: Since a report of lenticular opacities in dogs treated with high dosages of statins, the debate on the relationship between statin therapy and cataracts has not reached a conclusion. OBJECTIVE: The aim of this study was to evaluate the association between statin therapy and the risk of cataract surgery in an elderly ethnic Chinese population using time-dependent analysis to minimize immortal time bias. METHODS: A retrospective cohort study using the Longitudinal Health Insurance Database 2005 randomly sampled from the National Health Insurance Research Database, Taiwan, was conducted. A total of 50,165 adults aged between 65 and 90 years in 1998 without records of statin therapy or diagnosis of cataracts between July 1997 and December 1997 were included in the analysis. The first record of lens extraction within the follow-up period (1998-2009) was set as the study endpoint. A propensity score was derived using a logistic regression model to model the receipt of statin therapy as a function of the baseline characteristics for every subject. We used the time-dependent Cox regression model to test the relative hazard of undergoing cataract surgery between statin users and non-users, while use of statins was treated as a time-dependent variable, controlling for baseline age and individual propensity score. RESULTS: Of the 50,165 enrolled subjects, 17,670 individuals with an incident lens extraction were identified during a median follow-up of 10.7 years. The incidence of cataract surgery was 49.7/1,000 person-years in the statin-using period compared with 38.5/1,000 person-years in the statin-non-using period. The adjusted hazard ratio of cataract surgery was 1.20 (95 % CI 1.14-1.27; P < 0.001) in statin users compared with statin non-users. CONCLUSION: Statin therapy was associated with a modestly increased risk of cataract surgery. We suggest regular checks for lens opacity in statin users.