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Background Cluster headache (CH) is well known to show a seasonal predilection; however, the impact of temperature and other meteorological factors on cluster periods (or bouts) has not been established. Methods This nationwide survey included 758 patients with episodic CH retrieved from the Taiwan National Health Insurance Research Database from 2005 to 2009. Corresponding meteorological recordings were obtained from the Central Weather Bureau. A case-crossover study design was used to investigate the association between cluster periods and meteorological factors. Results A total of 2452 episodes of cluster periods were recorded. The cluster periods were most frequent in the autumn and least frequent in the winter. Seasonal changes from winter to spring and from autumn to winter also increased the frequency of cluster periods. The risk of cluster periods increased when there was a higher mean temperature on event days (odds ratio (OR), 1.014, 95% confidence interval (CI), 1.005–1.023, p = 0.003) or within seven to 56 days. Either an increase or a decrease in temperature (0.05℃/day) following a warm period (mean temperature ≥26℃) was associated with the onset of cluster periods. In contrast, a greater increase in temperature (0.15℃/day) following a cold period (mean temperature Discussion Our study shows that temperature is associated with precipitating or priming cluster periods. The influence depends on the temperature of the preceding periods.

The association between selective serotonin receptor inhibitors (SSRIs) and risk of upper gastrointestinal bleeding remains controversial. Previous studies have generally evaluated the issue for approximately 3 months, even though the SSRI-mediated inhibition of platelet serotonin concentrations occurs within 7-14 days. The authors explored the risk of upper gastrointestinal bleeding after short-term SSRI exposure by a case-crossover design.The records of psychiatric inpatients with upper gastrointestinal bleeding were retrieved from the Taiwan National Health Insurance Database (1998-2009). Rates of antidepressant use were compared for case and control periods with time windows of 7, 14, and 28 days. The adjusted self-matched odds ratios from a conditional logistic regression model were used to determine the association between SSRI use and upper gastrointestinal bleeding.A total of 5,377 patients with upper gastrointestinal bleeding were enrolled. The adjusted odds ratio for the risk of upper gastrointestinal bleeding after SSRI exposure was 1.67 (95% CI=1.23-2.26) for the 7-day window, 1.84 (95% CI=1.42-2.40) for the 14-day window, and 1.67 (95% CI=1.34-2.08) for the 28-day window. SSRIs with high and intermediate, but not low, affinity for serotonin transporter were associated with upper gastrointestinal bleeding. An elevated risk of upper gastrointestinal bleeding after SSRI exposure was seen in male but not female patients.Short-term SSRI use (7-28 days) is significantly associated with upper gastrointestinal bleeding. Gender differences may exist in the relationship between SSRI use and upper gastrointestinal bleeding. Physicians should carefully monitor signs of upper gastrointestinal bleeding even after short-term exposure to SSRIs, as is done with nonsteroidal anti-inflammatory drugs and aspirin.

Background This study assessed whether cholecystectomy can decrease recurrent cholangitis and all-cause mortality in patients who received endoscopic retrograde cholangiopancreatography (ERCP) with sphincterotomy and successful clearance of bile duct (BD) stones after gallstone-related cholangitis. Methods We analyzed data from the National Health Insurance research database of Taiwan. Patients who had gallstone-related cholangitis and underwent successful endoscopic clearance of BD stones were eligible for enrollment. This population-based, propensity score (PS)-matched cohort study involved 2 cohorts; (1) patients who underwent cholecystectomy after ERCP with BD stone clearance as the study group; and (2) those who had no cholecystectomy after ERCP with BD stone clearance as the control group. The primary endpoint was recurrent cholangitis, and the secondary endpoint was all-cause mortality. Results During a mean 5.7-year follow-up, the incidence rates of recurrent cholangitis were 20.47 per 1000 person-years in the cholecystectomy cohort, and 34.60 per 1000 person-years in the PS-matched control cohort. The risk of recurrent cholangitis was significantly lower in the cholecystectomy cohort than in the control cohort (HR, 0.62; 95% confidence interval [CI], 0.45–0.87; P = 0.006). The HR for all cause mortality among the cholecystectomy cohort was 0.70 (95% CI, 0.54–0.90; P = 0.006) compared with the control cohort. Conclusion Cholecystectomy decreased the recurrent cholangitis and all-cause mortality in patients with endoscopic sphincterotomy and successful clearance of BD stones after gallstone-related cholangitis.

Background and objectives We aimed to investigate the benefits and risks of dual antiplatelet therapy (DAPT) after coronary drug-eluting stent (DES) implantation in patients undergoing hemodialysis. Design, setting, participants, & measurements A nested case-control analysis of patients on hemodialysis after receipt of DES and DAPT treatment was conducted using data from Taiwan’s National Health Insurance Research Database for the period 2007–2011. Cases of myocardial infarction or death within 1 year after DES implantation were matched one-to-one with control patients. Odds ratios were calculated to compare DAPT continuation with discontinuation. Additionally, a propensity score–adjusted 6-month landmark cohort analysis was also conducted to evaluate the long-term benefits and risks of prolonged (>6 months) compared with ≤6 months of DAPT use. The primary outcomes were death and myocardial infarction. The secondary outcomes were ischemic stroke, revascularization, and major bleeding. Results In the nested case-control analysis, patients who continued DAPT had a lower rate of death or myocardial infarction within 1 year after receipt of a DES (adjusted odds ratio, 0.54; 95% confidence interval, 0.36 to 0.81; P =0.003), whereas this association became statistically nonsignificant when compared with patients who discontinued DAPT for the period between 6 and 12 months after receipt of a DES (adjusted odds ratio, 1.51; 95% confidence interval, 0.75 to 3.04). In the propensity score–adjusted cohort analysis, >6 months of DAPT use was not associated with different primary or secondary outcomes than shorter-term use. Conclusions Our findings support that the clinical effectiveness of extended DAPT in a hemodialysis population may be tempered after 6 months post-DES implantation.

The present study aimed to evaluate the association between influenza vaccination and the secondary prevention of cardiovascular disease (CVD) among elderly persons. This retrospective cohort study used the Geriatric Dataset of Taiwan’s National Health Insurance Research Database (2000–2013). Patients aged ≥ 65 years who had been hospitalized for the first episodes of myocardial infarction were eligible. The vaccinated cohort comprised patients who received one dose of influenza vaccine within 180 days after discharge. The unvaccinated cohort included those who did not receive influenza vaccination and was propensity score–matched (1:1) for known CVD risk factors. All-cause death, acute myocardial infarction or cardiovascular death, and hospitalization for heart failure were assessed 1 year after the 181st day after hospital discharge. Compared with the matched cohort (n = 4,350), the vaccinated cohort (n = 4,350) had significantly lower incidences of all-cause death (hazard ratios [HR] 0.82, 95% CI [confidence interval] 0.73–0.92), myocardial infarction or cardiovascular death (HR 0.84, 95% CI 0.74–0.96), and hospitalization for heart failure (HR 0.83, 95% CI 0.74–0.92). The association between influenza vaccination and reduction of CVDs was similar across different subgroups. Cumulative incidence curves of the CVDs of interest for the two cohorts separated within the initial 3 months of follow-up (P < 0.05). Influenza vaccination was associated with a reduced risk of CVD in the elderly population with previous myocardial infarction.

Background An association between use of oral fluoroquinolones (FQs) and retinal detachment remains controversial. This study was to determine the association of recent use of oral FQs and rhegmatogenous retinal detachment (RRD) after adjustment for confounding factors known to be associated with RRD. Methods This retrospective population-based cohort study with parallel groups included adults treated with an oral FQ (FQ cohort = 178 179 prescriptions) and propensity score-matched adults treated with oral amoxicillin (amoxicillin cohort = 178 179 prescriptions). The data were extracted from the Taiwan National Health Insurance Research Database from 1998 to 2010. Interaction terms were used to identify populations at risk. RRD was defined according to the International Classification of Diseases, Ninth Revision, Clinical Modification. Results During the 90-day follow-up period, 96 patients (0.054%) in the FQ cohort developed RRD compared to 46 (0.026%) among the matched amoxicillin cohort. The overall adjusted hazard ratio (HR) for FQ use and RRD was 2.07 (95% confidence interval [CI], 1.45-2.96). The interval between use of oral FQs and onset of RRD was 35.5 days (interquartile range, 14-57 days). Interaction terms were not significant for age, sex, diabetes, indications for antimicrobials, or underlying ophthalmic conditions. The adjusted HRs differed for specific FQs. These were 10.68 (95% CI, 3.28-34.82) for ciprofloxacin, 2.41 (95% CI, .76-7.68) for levofloxacin, 2.00 (95% CI, 1.06-3.79) for norfloxacin, and 1.17 (95% CI, .59-2.31) for ofloxacin. Conclusions The use of oral FQs was associated with the subsequent occurrence of RRD. The FQ risk was independent of age, sex, diabetes, indications for antimicrobials, and underlying ophthalmic conditions. Certain FQs carried higher risk of RRD.

The objective of this study was to evaluate the risks of acute cholecystitis among end-stage renal disease patients and compare the incidence between two dialysis modality.In this retrospective cohort study, records of fifty thousand end-stage renal disease patients older than 20 years of age from 1998 to 2007 and an age, gender, Charlson's score, diabetes, and dyslipidemia matched control cohort were retrieved from Taiwan National Health Insurance Research Database. Hospitalizations for acute cholecystitis were retrieved using ICD-9-CM diagnosis codes and ICD-9-CM operation codes from in-patient claims.The incidence rates were 5.8 per 1000 patient-years in the end-stage renal disease patients and 0.92 per 1000 patient-years in the control group. End-stage renal disease was an independent risk factor for acute cholecystitis. In the end-stage renal disease patients, independent risk factors were old age, higher Charlson's score, diabetes, severe liver disease, atrial fibrillation, and haemodialysis (all p0.05). However, the peritoneal dialysis patients had a higher mortality rate after developing acute cholecystitis.Acute cholecystitis is not uncommon in end-stage renal disease patients. The independent risk factors were older age, higher Charlson's score, atrial fibrillation, severe liver disease, diabetes, and dialysis modality. Haemodialysis patients had a higher risk of acute cholecystitis than PD patients.

Background There has been no large-scale population-based study on the incidence and clinical manifestations of second primary cancer (SPC) after diagnosis of hepatocellular carcinoma (HCC). Aims This study aimed to evaluate the incidence and the risk factors of SPC following HCC diagnosis. Method This study used data from the National Health Insurance Research Database of Taiwan to identify all HCC patients from 1 January 1997 to 31 December 2006. Cases of SPC were gathered using the ICD9-CM codes of 140–208.91. Standardized incidence ratios (SIRs) were conducted for incidence of SPC in HCC survivors. Competing-risks regression with adjustment of death was used to analyse the risk factors of SPC. Results From 45 976 HCC patients, 749 (1.6%) developed SPC after 90 days of HCC diagnosis. Male HCC patients had higher risks of gastric, biliary, urinary bladder, kidney and haematological cancers compared to the general male population. Female patients had higher incidences of biliary tract, kidney and bone and soft tissue cancers. Older age and chronic kidney disease (CKD) were independent factors predicting SPC. Conclusions SPC in patients with HCC is not rare in Taiwan. Urinary bladder cancer and renal cancer are more specific SPC for HCC patients. Better surveillance strategies for SPC should be established for HCC survivors, especially in the elderly or those with CKD.

Background Patients with end-stage renal disease (ESRD) are at high risk of cardiovascular disease and elevated serum homocysteine levels. Although folic acid supplementation has been documented to reduce serum homocysteine levels in ESRD patients, most trials of folic acid therapy for reducing cardiovascular diseases in ESRD patients have failed, mainly because of limited patient numbers. Methods We used the Taiwan National Health Insurance Research Database (NHIRD) to conduct a matched-pair retrospective cohort study to clarify whether folic acid supplementation benefits ESRD patient survival. Patients were divided into a folic acid supplementation group and a control group. All-cause and cardiovascular-related mortality rates between groups were compared. Results In total, 55,636 stable incident hemodialysis patients were identified from the database. Using a propensity score-matched method and intention-to-treat analysis, the survival rate of 17,000 patients with folic acid supplementation was compared with a 1:1 matched control group. The baseline demographic data and comorbid disease incidence between the 2 groups were comparable. During the study period, the mortality rate in the matched pair cohort was 35.5% (n = 6,030) over a mean follow-up period of 3.0 years, corresponding to a mortality rate of 12.8/100 patient-years. The all-cause mortality rates were 12.3 and 13.4/100 patient-years in the folic acid group and control group, respectively (p = 0.005). Conclusions In adult hemodialysis patients, folic acid supplementation improves cardiovascular and all-cause mortality rates.

Objective To investigate whether cluster headache (CH) was a risk factor for depression in a nationwide population-based follow-up study. Background There are few studies about the relationship between CH and depression, and prior research has been limited by cross-sectional studies or small sample sizes. Methods We identified 673 CH patients from the Taiwan National Health Insurance database between 2005 and 2009. The two comparison cohorts included age-, sex- and Charlson’s score-matched migraine patients ( n = 2692) and controls (patients free from migraine or CH, n = 2692). The cumulative incidence of depression was compared among these three cohorts until the end of 2009. We also calculated predictors of depression in the CH cohort. Results After the median 2.5-year follow-up duration, the CH cohort had a greater risk for developing depression compared to the control cohort (adjusted hazard ratio; aHR = 5.6, 95% CI 3.0–10.6, p Conclusion Our results showed that CH is associated with an increased risk for depression. The strength of this association is similar to that of migraine.

Summary Background The aim of this study is to investigate the "weekend effect" and early mortality of patients with severe sepsis. Methods Using the Taiwanese National Healthcare Insurance Research Database, all patients who were hospitalized for the first time with an episode of severe sepsis between January 2000 and December 2011 were identified and the short-term mortality of patients admitted on weekdays was compared to those admitted on weekends. The primary endpoint was 7-day mortality. The secondary endpoints were 14 and 28-day mortality. Results A total of 398,043 patients were identified to have had the diagnosis of severe sepsis. Compared with patients admitted on weekends, patients admitted on weekdays had a lower 7-day mortality rate (adjusted odds ratio [OR] 0.89, 95% confidential interval [CI] 0.87–0.91), 14-day mortality rate (adjusted OR 0.92, 95% CI 0.90–0.93), and 28-day mortality rate (adjusted OR 0.97, 95% CI 0.95–0.98). This "weekend effect" was maintained every year throughout the 11-year study period. Conclusions Patients with severe sepsis are more likely to die in the hospital if they were admitted on weekends than if they were admitted on weekdays.

Background Pleiotropic effects on cardiovascular protection have been suggested in several oral antidiabetic drugs (OAD). The impacts of OADs on aortic aneurysm (AA) growth have been found in animal studies, but the evidence of their beneficial effects for AA protection in human are lacking. We investigated the relationship between OAD therapy and the risk of developing AA. Methods We conducted a nested case–control analysis using the database extracted from Taiwan’s National Health Insurance Research Database. The database consists of 1.2 million diabetic patients representing the majority of the type 2 diabetes population in Taiwan from 2000 to 2013. Cases were identified as those with either inpatient or outpatient diagnosis code of AA. One control was selected for each case matching on duration of follow-up, age, sex, urbanization, monthly income, severity of diabetes, and risk factor for AA. We identified variable classes of OADs, including metformin, sulfonylureas, thiazolidinedione (TZD), alpha-glucosidase inhibitors, meglitinide, dipeptidyl peptidase-4 (DPP-4) inhibitors prior to the development of AA. Results A total of 4468 cases diagnosed with AA and 4468 matched controls were identified. Metformin use, sulfonylurea use, and TZD were associated with lower risk of developing AA, odds ratio [OR] 0.72 (95 % confidence interval [CI] 0.64–0.80), 0.82 (95 % CI 0.74–0.92), and 0.82 (95 % CI 0.69–0.98), respectively. The effects of metformin and sulfonylurea on AA were dose responsive. Neither alpha-glucosidase inhibitors (OR 0.95; 95 % CI 0.81–1.11) nor DPP-4 inhibitors (OR 0.85; 95 % CI 0.68–1.07) was significantly associated with AA events. Conclusions Metformin, sulfonylurea, and TZD treated patients were associated with lower risks of AA development, but not DPP-4 inhibitors or alpha-glucosidase inhibitor. The protective effects of hypoglycemic agents are further confirmed by the dose responsive relations in metformin and sulfonylurea groups.

BACKGROUND We aimed to examine the risk of subsequent cardiovascular events in patients with CKD discharged after sepsis. METHODS Using the data on CKD patients from Taiwan9s National Health Insurance Research Database, we identified sepsis subjects who survived between 2000 and 2010, and each survivor was propensity-score-matched to one nonsepsis hospitalized controls.Cox regression models were used to estimate the hazard ratios of clinical outcomes, including major adverse cardiovascular events, all-cause death and hospitalization for heart failure. RESULTS Among 66,961 sepsis survivors,. sepsis survivors in comparison to matched hospitalized nonsepsis control subjects, had greater risks of major adverse cardiovascular events (HR, 1.35; 95% confidence interval [CI], 1.31–1.38), myocardial infarction (HR, 1.39; 95% CI, 1.32–1.47) ischemic stroke (HR, 1.46; 95% CI, 1.40–1.52), all-cause mortality (HR, 1.56; 95% CI, 1.54–1.58), and hospitalization for heart failure (HR, 1.55; 95% CI, 1.51–1.59). CONCLUSIONS Our findings highlight that sepsis in CKD population was associated with significantly increased risk of cardiovascular events among survivors.

The aim of this study was to assess whether cholecystectomy can decrease the recurrent pancreatitis in the elderly patients who received endoscopic retrograde cholangiopancreatography (ERCP) with endoscopic sphincterotomy (EST) and successful clearance of bile duct (BD) stones after gallstone-related acute pancreatitis. We analyzed data from National Health Insurance Research Database of Taiwan. Elderly patients (age ≧70 years old) who had gallstone-related acute pancreatitis and underwent successful EST with BD stones clearance were eligible for enrollment. This nationwide, population-based, propensity score (PS)-matched cohort study involved two cohorts: (1) patients who underwent cholecystectomy after ERCP with BD stone clearance as study group and (2) those who adopted wait-and-see strategy (without cholecystectomy) after ERCP with BD stone clearance as control group. The primary and secondary endpoints were recurrent acute pancreatitis and all-cause mortality, respectively. During the study period, a total of 670 elderly patients (male 291, female 379) with a mean age of 79.1 was enrolled for analysis after PS matching. The incidence rate of recurrent acute pancreatitis was 12.39 per 1000 person-years in the cholecystectomy cohort and 23.94 per 1000 person-years in the PS-matched control cohort. The risk of recurrent acute pancreatitis was significantly lower in the cholecystectomy cohort (HR, 0.56; 95 % confidence interval [CI], 0.34–0.91; P = 0.021). The HR for all-cause mortality among the cholecystectomy cohort was 0.75 (95 % CI, 0.59–0.95; P = 0.016) compared with the control cohort. Cholecystectomy decreased the subsequent recurrent acute pancreatitis and the all-cause mortality in elderly patients with EST and clearance of BD stones after gallstone-related acute pancreatitis.

Hemodialysis (HD) is the most commonly-used renal replacement therapy for patients with end-stage renal disease worldwide. Arterio-venous fistula (AVF) is the vascular access of choice for HD patients with lowest risk of infection and thrombosis. In addition to environmental factors, genetic factors may also contribute to malfunction of AVF. Previous studies have demonstrated the effect of genotype polymorphisms of angiotensin converting enzyme on vascular access malfunction. We conducted a multicenter, cross-sectional study to evaluate the association between genetic polymorphisms of renin-angiotensin-aldosterone system and AVF malfunction. Totally, 577 patients were enrolled. Their mean age was 60 years old and 53% were male. HD patients with AVF malfunction had longer duration of HD (92.5 ± 68.1 vs. 61.2 ± 51.9 months, p < 0.001), lower prevalence of hypertension (44.8% vs. 55.3%, p = 0.025), right-sided (31.8% vs. 18.4%, p = 0.002) and upper arm AVF (26.6% vs. 9.7%, p < 0.001), and higher mean dynamic venous pressure (DVP) (147.8 ± 28.3 vs. 139.8 ± 30.0, p = 0.021). In subgroup analysis of different genders, location of AVF and DVP remained significant clinical risk factors of AVF malfunction in univariate and multivariate binary logistic regression in female HD patients. Among male HD patients, univariate binary logistic regression analysis revealed that right-side AVF and upper arm location are two important clinical risk factors. In addition, two single nucleotide polymorphisms (SNPs), rs275653 (Odds ratio 1.90, p = 0.038) and rs1492099 (Odds ratio 2.29, p = 0.017) of angiotensin II receptor 1 (AGTR1), were associated with increased risk of AVF malfunction. After adjustment for age and other clinical factors, minor allele-containing genotype polymorphisms (AA and CA) of rs1492099 still remained to be a significant risk factor of AVF malfunction (Odds ratio 3.63, p = 0.005). In conclusion, we demonstrated that rs1492099, a SNP of AGTR1 gene, could be a potential genetic risk factor of AVF malfunction in male HD patients.

Summary Sleep disorders are common non-motor symptoms in patients with Parkinson's disease. Our study aims to explore the relationship between non-apnea sleep disorders and future Parkinson's disease. This is a cohort study using a nationwide database. The participants were recruited from the Taiwan National Health Insurance Research Database between 2000 and 2003. A total of 91 273 adult patients who had non-apnea sleep disorders without pre-existing Parkinson's disease were enrolled. An age-, gender-, income-, urbanization- and Charlson comorbidity index score-matched control cohort consisting of 91 273 participants was selected for comparison. The two cohorts were followed for the occurrence of Parkinson's disease, death or until the end of 2010, whichever came first. The Kaplan–Meier analyses revealed patients with non-apnea sleep disorders tended to develop Parkinson's disease (log-rank test, P

Background Recent clinical trials have evaluated the cardiovascular outcomes of dipeptidyl peptidase-4 ( DPP-4) inhibitors in patients with type 2 diabetes mellitus (T2DM), but those with end-stage renal disease (ESRD) were ineligible for participation in these trials. We aimed to characterize the impact of DPP-4 inhibitors on major adverse cardiovascular events (MACEs) in patients with T2DM and ESRD undergoing chronic dialysis. Methods This nationwide observational study utilized data from 3556 patients aged ≥20years with T2DM and ESRD who initiated treatment with DPP-4 inhibitors between 1 March 2009 and 31 June 2013, retrieved from Taiwan's National Health Insurance Research Database. Each DPP-4 inhibitor user was matched to a non-user control subject using propensity scores. The primary outcomes were all-cause mortality and MACEs (ischemic stroke and myocardial infarction). The secondary outcomes were hospitalization for heart failure and hypoglycemia. All subjects were followed until death or 31 December 2013. Results Compared with non-users, DPP-4 inhibitor users had lower risks of all-cause mortality (hazard ratio [HR] 0.43, 95% confidence interval [CI] 0.39–0.47), MACEs (HR 0.76, 95% CI 0.65–0.90), and ischemic stroke (HR 0.77, 95% CI 0.61–0.97); the risks of myocardial infarction and hospitalization for heart failure and hypoglycemia did not differ. This treatment effect remained consistent in subgroup analyses according to age, sex, comorbidities, dialysis modality, and insulin use. Conclusions In this nationwide ESRD cohort, DPP-4 inhibitor use was associated with reduced risks of all-cause mortality and ischemic stroke.

Background: Angiotensin-converting-enzyme (ACE) inhibitors and angiotensin II receptor blockers (ARBs) are effective treatments for diabetic retinopathy, but randomized trials and meta-analyses comparing their effects on macrovascular complications have yielded conflicting results. We compared the effectiveness of these drugs in patients with pre-existing diabetic retinopathy in a large population-based cohort. Methods: We conducted a propensity score–matched cohort study using Taiwan’s National Health Insurance Research Database. We included adult patients prescribed an ACE inhibitor or ARB within 90 days after diagnosis of diabetic retinopathy between 2000 and 2010. Primary outcomes were all-cause death and major adverse cardiovascular events (myocardial infarction, ischemic stroke or cardiovascular death). Secondary outcomes were hospital admissions with acute kidney injury or hyperkalemia. Results: We identified 11 246 patients receiving ACE inhibitors and 15 173 receiving ARBs, of whom 9769 patients in each group were matched successfully by propensity scores. In the intention-to-treat analyses, ARBs were similar to ACE inhibitors in risk of all-cause death (hazard ratio [HR] 0.94, 95% confidence interval [CI] 0.87–1.01) and major adverse cardiovascular events (HR 0.95, 95% CI 0.87–1.04), including myocardial infarction (HR 1.03, 95% CI 0.88–1.20), ischemic stroke (HR 0.94, 95% CI 0.85–1.04) and cardiovascular death (HR 1.01, 95% CI 0.88–1.16). They also did not differ from ACE inhibitors in risk of hospital admission with acute kidney injury (HR 1.01, 95% CI 0.91–1.13) and hospital admission with hyperkalemia (HR 1.01, 95% CI 0.86–1.18). Results were similar in as-treated analyses. Interpretation: Our study showed that ACE inhibitors were similar to ARBs in risk of all-cause death, major adverse cardiovascular events and adverse effects among patients with pre-existing diabetic retinopathy.

Background.—The link between arterial thromboembolism and migraine is well-documented; however, few studies investigated the link between venous thromboembolism (VTE) and migraine. We aimed to evaluate the association between migraine and VTE and to examine whether demographics or comorbid risk factors modulate VTE development. Methods.—We conducted a cohort study accessing a nationwide claims-based database with an adult cohort of 102,159 neurologist-diagnosed migraine patients, and 102,159 nonheadache comparison subjects, matched on sex and propensity score for the diagnosis of migraine. Both cohorts were followed until the end of 2010, death, or VTE development. Adjusted hazard ratios (aHRs) and 95% confidence intervals (CIs) were calculated based on Cox proportional hazards regression analyses and compared between the two groups. Results.—During a mean follow-up period of 4.2 years, VTE developed in 226 patients (460,047 person-years) in the migraine cohort and in 203 subjects (462,401 person-years) in the comparison cohort. Overall, likelihood of VTE for the migraine cohort did not differ from that in the comparison cohort (aHR 1.12; 95% CI, 0.92–1.35; P = .251). However, subgroup analysis by migraine subtypes (P = .004 for interaction) revealed an elevated risk of VTE in patients with migraine with aura (aHR 2.42; 95% CI, 1.40–4.19; P = .002), but not in those with migraine without aura. The association was not altered in subsequent subgroup analyses and sensitivity analyses. Conclusions Risk of VTE development is elevated specifically in patients diagnosed with migraine with aura. This association suggests a linked disease mechanism and warrants further exploration.

Acute appendicitis in patients with end-stage renal disease (ESRD) poses a diagnostic challenge. Delayed surgery can contribute to higher morbidity and mortality rates. However, few studies have evaluated this disease among ESRD patients. Our study focused on the lack of data on the incidence and risk factors of acute appendicitis among ESRD patients and compared the outcomes in patients who underwent different dialysis modalities. This national survey was conducted between 1997 and 2005 and included ESRD patients identified from the Taiwan National Health Insurance database. The incidence rate of acute appendicitis in ESRD patients was compared with that in randomly selected age-, sex-, and Charlson comorbidity score-matched non-dialysis controls. A Cox regression hazard model was used to identify risk factors. Among 59,781 incident ESRD patients, matched one-to-one with controls, there were 328 events of acute appendicitis. The incidence rate of 16.9 per 10,000 person-years in the ESRD cohort was higher than that in the control cohort (p = 0.003). The independent risk factors were atrial fibrillation (hazard ratio [HR], 2.08), severe liver disease (HR, 1.74), diabetes mellitus (HR, 1.58), and hemodialysis (HR, 1.74). Compared with the control cohort, subsequent perforation and mortality rates of acute appendicitis were also higher in the ESRD cohorts. There was no effect of dialysis modality on the patient outcomes. ESRD patients had a higher risk for acute appendicitis and poorer outcomes than non-dialysis populations. A careful examination of ESRD patients presenting with atypical abdominal pain to avoid misdiagnosis is extremely important to prevent delayed surgery.

Urolithiasis is a worldwide disease which has affected humans from ancient eras to modern times. Recently, societal changes have altered the epidemiology of urinary calculi. The incidence of urolithiasis is higher in industrialized countries. Obese people are known to have a higher risk of stone formation. Metabolic syndrome has resulted in an increasing rate of nephrolithiasis among women. There are many useful tools for diagnosing urolithiasis, including conventional plain radiography, intravenous urography, ultrasonography, computed tomography (CT), and nuclear medicine. Nonenhanced CT has high sensitivities and specificities. It can be rapidly performed without intravenous administration of contrast material and can therefore be used in patients with severely impaired renal function. Beyond that, it can reveal extraurinary causes of flank pain. However, concerns about radiation exposure and costs remain. Since ancient times, hundreds of natural plant extracts and more recently, synthetic chemicals have been proposed to eliminate urinary calculi. Clinical trials demonstrated that calcium channel blockers and adrenergic antagonists are effective in enhancing stone passage. Shock wave lithotripsy (SWL) can successfully treat renal calculi. A meta-analysis study revealed that SWL is more effective in treating urinary calculi with a lower-frequency mode. Highly dense stones are more refractory to SWL. The stone composition can be evaluated by preoperative CT attenuation values. Patients with preoperative Houndsfield units (HUs) of >750 have a 10.5-times greater chance of needing three or more sessions of SWL treatment compared to patients whose HUs are

Purpose Sepsis is a major health burden worldwide. Preclinical investigations in animals and retrospective studies in patients have suggested that inhibition of platelets may improve the outcome of sepsis. In this study we investigated whether chronic antiplatelet therapy impacts on the presentation and outcome of sepsis, and the host response. Methods We performed a prospective observational study in 972 patients admitted with sepsis to the mixed intensive care units (ICUs) of two hospitals in the Netherlands between January 2011 and July 2013. Of them, 267 patients (27.5 %) were on antiplatelet therapy (95.9 % acetylsalicylic acid) before admission. To account for differential likelihoods of receiving antiplatelet therapy, a propensity score was constructed, including variables associated with use of antiplatelet therapy. Cox proportional hazards regression was used to estimate the association of antiplatelet therapy with mortality. Results Antiplatelet therapy was not associated with sepsis severity at presentation, the primary source of infection, causative pathogens, the development of organ failure or shock during ICU stay, or mortality up to 90 days after admission, in either unmatched or propensity-matched analyses. Antiplatelet therapy did not modify the values of 19 biomarkers providing insight into hallmark host responses to sepsis, including activation of the coagulation system, the vascular endothelium, the cytokine network, and renal function, during the first 4 days after ICU admission. Conclusions Pre-existing antiplatelet therapy is not associated with alterations in the presentation or outcome of sepsis, or the host response. Electronic supplementary material The online version of this article (doi:10.1007/s00134-015-4171-9) contains supplementary material, which is available to authorized users.

Nitric oxide (NO) is a pivotal vasoactive substance modulating arteriovenous fistula (AVF) patency for hemodialysis (HD). Since genetic background could be the predicting factor of AVF malfunction, we aimed to investigate whether the NO-related genotype polymorphisms determine AVF survival rates.This is a retrospective, observational, multi-center study involving eight HD units in Taiwan, enrolled 580 patients initiating maintenance HD via AVFs. Genotype polymorphisms of NO-biosynthesis regulating enzymes (DDAH-1, DDAH-2, eNOS and PRMT1) were compared between HD patients with (n = 161) and without (n = 419) history of AVF malfunction. Subgroup analyses by gender were performed to evaluate the genetic effect in difference sexes.In overall population, statistically significant associations were not found between AVF malfunction and the genetic polymorphisms. In the male subgroup (n = 313), a single nucleotide polymorphism (SNP) of PRMT1, rs10415880 (IVS9-193 A/G), showed a significant association with AVF malfunction. Male patients with AA/AG genotype had inferior AVF outcomes compared to GG genotype, regarding primary patency (70.6% vs. 40.9%, p = 0.001), assisted primary patency (81.0% vs. 58.4%, p 0.001) and secondary patency (83.7% vs. 63.3%, p 0.001) at a 5-year observation period. From multivariate Cox regression model, the AA/AG genotypes of PRMT1 were an independent risk factor for AVF malfunction in men (HR: 4.539, 95% CI 2.015-10.223; p 0.001). However, such associations were not found in women.rs10415880, the SNP of PRMT1 could be a novel genetic marker associated with AVF malfunction risk in male HD patients. Those with AA and AG genotypes of rs10415880 may predict a poorer long-term patency of AVF.

Although the association of hyperuricemia and cardiovascular diseases is well established by previous research studies, the relationship between gout and deep vein thrombosis (DVT) remains unclear. We conducted a nationwide longitudinal cohort study to investigate the relationship between gout and DVT. We used the Taiwan National Health Insurance Research Database to identify patients with gout diagnosed in Taiwan during 2000–2011, and we followed up these patients to determine the incidence of DVT among them. The association between gout and DVT was analyzed by cox proportional hazard model. The study cohort included 35,959 patients with history of gout attack and 35,959 matched controls without gout attack. During the median follow-up of 7.5 ± 3.6 years, the incidence rate of DVT was significantly higher in patients with gout than that in control group (13.48 versus 9.77 per 104 person-years, p

Objectives The elderly (aged ≥65 years) population with type 2 diabetes (T2D) is growing substantially, but evidence for associations between the use of dipeptidyl peptidase-4 inhibitors (DPP-4is), novel incretin-based antidiabetic drugs, and clinical hard endpoints in this group remains inconclusive. We aimed to assess the safety and cardiovascular effects of DPP-4i use in a nationally representative sample of elderly adults with T2D. Design, setting, and participants We conducted a nationwide, observational, propensity score–matched study using Taiwan's National Health Insurance Research Database. Of a total of 414,213 patients aged ≥65 years with T2D, 58,485 patients receiving initial DPP-4i prescriptions between March 1, 2009, and June 31, 2013, were included. Each DPP-4i user was matched with a nonuser control using propensity scores. The endpoints were all-cause mortality and major adverse cardiovascular events (MACEs), including ischemic stroke and myocardial infarction. Potential adverse effects of hospitalization for heart failure and hypoglycemia were also evaluated. Results Compared with the matched control cohort, the risks of all-cause mortality (hazard ratio [HR] 0.54, 95% confidence interval [CI] 0.52–0.56), MACEs (HR 0.79, 95% CI 0.75–0.83), myocardial infarction (HR 0.79, 95% CI 0.72–0.87), and ischemic stroke (HR 0.79, 95% CI 0.75–0.84) were lower in the DPP-4i cohort. DPP-4i use did not affect the risks of hospitalization for heart failure and hypoglycemia. Stratified analyses produced consistent results across age, sex, and comorbidity subgroups. Conclusions Prescription of DPP-4is was associated with reduced risks of all-cause mortality and MACEs in patients aged ≥65 years with T2D.

• The risk of hypoglycemia within a very short time in patients co-prescribed antimicrobials and sulfonylureas were analyzed.

Background: Compared to the general population, patients with end-stage renal disease (ESRD) have increased peptic ulcer and upper GI bleeding complication rates. However, the risk factors for peptic ulcer among ESRD patients are unknown. Methods: In this retrospective study, we enrolled 827 incident dialysis patients and diagnosed peptic ulcer on the basis of endoscopic findings; information on the morbidities and medical prescription were obtained directly from medical records. A Cox regression hazard model was used to identify risk factors for peptic ulcer. Results: During the 10-year study period, 481 patients underwent an endoscopic exam. Peptic ulcers were detected in 153 patients. Age (p = 0.025), peritoneal dialysis (p = 0.022), diabetes mellitus (p = 0.020), congestive heart failure (p = 0.015), low serum albumin (p = 0.008) and high gamma-glutamyl transpeptidase (γ-GT) levels (p = 0.002) are risk factors for peptic ulcers among ESRD patients. Ulcer severity (p = 0.004) and aspirin prescription (p = 0.043), but not Helicobacter pylori infection, influenced the ulcer recurrence rate. Conclusion: The risk factors for peptic ulcer have some differences between ESRD patients and general population. In patients with high risk of upper GI bleeding, peritoneal dialysis and aspirin should be prescribed with caution.

To the editor: Dysregulation in platelet production and abnormal platelet counts have been well known as a predictor of adverse outcomes in patients with infection, cancer, and end-stage renal disease.[1][1][⇓][2]-[3][3] The prevalence rates of thrombocytopenia and thrombocytosis among people

Recent observational studies have shown that sleep apnoea (SA) is associated with increased risk of incident CKD. However, the contribution of SA relative to common traditional CKD risk factors remains unknown. The aims of this study were to investigate the long-term risk of incident CKD events following SA diagnosis and compare the relative contributions of SA, diabetes and hypertension.Data were retrieved from Taiwan's National Health Insurance Research Database during the period between 2000 and 2010 for this retrospective cohort study. The cohorts are composed of patients (age ≥ 20 years) newly diagnosed with SA and matched subjects without SA. The two cohorts were followed until the occurrence of CKD, death or the end of 2010.The sample is composed of 43,434 individuals (8687 patients with SA and 34,747 matched non-SA subjects). A total of 157 new CKD events in patients with SA and 298 events in the matched non-SA cohort were recorded during a mean follow-up period of 3.9 years (incidence rates, 4.5 and 2.2/per 1000 person-years). The risk of CKD development was greater among patients with SA than in the matched non-SA cohort (adjusted hazard ratio (aHR) 1.58, 95% confidence interval ( CI): 1.29-1.94). The contribution of SA to the CKD hazard was similar to that of hypertension (aHR 1.17, 95% CI: 0.68-2.01, P = 0.56), whereas that of diabetes remained significantly higher (aHR 2.17, 95% CI: 1.21-3.90, P = 0.01).SA was associated with an increase in the risk of CKD incidence similar to that of hypertension. See article, page 578.

Although oral antidiabetic drugs (OADs) have been associated with immunomodulation in preclinical studies, little is still known about the association between the use of OADs and the risk of sepsis. Using a cohort of patients, extracted from Taiwan’s National Health Insurance Research Database, with type 2 diabetes who were newly diagnosed between 2010 and 2012 and treated with OADs, we conducted a nested case-control study involving 43,015 cases (patients who were first hospitalized for sepsis) and 43,015 matched controls. Compared with non-use, metformin use was associated with a decreased risk of developing sepsis (adjusted odds ratio [OR] 0.80, 95% confidence interval [CI] 0.77–0.83, P P

Although accumulating evidence suggests urinary calculi may be associated with an increased risk of cardiovascular disease (CVD), the number of longitudinal studies linking urolithiasis to CVD events is limited. We investigated the association between urinary calculi and the risk of development of myocardial infarction (MI) and/or stroke in a nationwide, population-based cohort database in Taiwan.Our analyses were conducted using information from a random sample of 1 million people enrolled in the nationally representative Taiwan National Health Insurance Research Database. A total of 81,546 subjects aged 18 years or above, including 40,773 subjects diagnosed with urinary calculi during the study period and a propensity score-matched 40,773 subjects without urinary calculi were enrolled in our study.During a 10-year follow-up period, 501 MI events and 1295 stroke events were identified. By comparison, the urinary calculi group had a higher incidence rate of MI occurrence (11.79 vs 8.94 per 10,000 person-years) and stroke (31.41 vs 22.45 per 10,000 person-years). Cox proportional hazard regression model analysis showed that development of urinary calculi was independently associated with higher risk of developing future MI (HR, 1.31; 95% CI, 1.09-1.56, p=0.003), stroke (HR, 1.39; 95% CI, 1.24-1.55, p0.001), and total cardiovascular events (HR, 1.38; 95% CI, 1.25-1.51, p0.001).Urinary calculi were associated with an increased risk of future cardiovascular events in the Asian population, which was consistent with the recent epidemiologic evidence in Western countries.

Background The spot urine protein/creatinine ratio (UPCR) is proposed to be a substitute for 24-hour urinary protein (24 h-UP). This study is aimed to determine whether the predictive accuracy of 24 h-UP using UPCR can be improved by simply multiplying estimated daily urine creatinine excretion (eUCr) and UPCR together. Methods This study enrolled 120 participants to investigate the correlation between spot UPCR and 24 h-UP. Three sets of spot urine samples were randomly collected throughout the day and night, along with the first morning void. UPCR was weighted by eUCr to investigate the improvement of accuracy in using spot urine samples to predict 24 h-UP. Results There were strong correlation and concordance between UPCR and 24 h-UP irrespective of the time of spot urine sampling, and the correlation, concordance and agreement were improved after multiplying the UPCR value by the eUCr. Greater improvement was found in the subgroups with measured daily urine creatinine excretion ≤ 0.8 g/d and ≥ 1.2 g/d. Conclusions This investigation demonstrated that multiplying UPCR by eUCr can improve the accuracy of only using UPCR to predict 24 h-UP.

article i nfo Background:Guidelinesforhypertensionmanagementrecommendeitherangiotensin-convertingenzymeinhib- itors (ACEIs) or angiotensin II receptor blockers (ARBs) as first-line therapies for diabetes population. No head- to-head trial has been conducted to determine the priority of ACEI/ARB use for major adverse cardiac events (MACEs) in diabetes mellitus. Methods: Data on patients with newly diagnosed diabetes treated with ACEIs or ARBs were collected from Taiwan's National Health Insurance Research Database for the period 2000-2010. A total of 30,777 ARB users and 21,436 ACEI users were identified. One ARB user was matched to one ACEI user by propensity score. Intention-to-treat (ITT) and as-treated (AT) models were used. The primary outcomes were myocardial infarc- tion, ischemic stroke, and all-cause mortality. The secondary outcomes were hospitalization for acute kidney in- jury and hyperkalemia. Findings: Compared with ACEI users (n = 21,436), ARB users (n = 30,777) showed no significant difference in the outcomes of myocardial infarction (hazard ratio (HR): 0.92; 95% confidence interval (CI): 0.80 to 1.07), ische- mic stroke (HR: 0.95; 95% CI: 0.87 to 1.04), or all-cause mortality (HR: 0.95; 95% CI: 0.89 to 1.01) in the ITT anal- ysis. The risks of hospitalization for acute kidney injury and hyperkalemia also did not differ between groups. ACEI and ARB use also had similar effects on MACEs and adverse effects in the AT analysis. Conclusions: This large cohort study supports the comparative effectiveness of ACEIs and ARBs in terms of MACE outcomes in patients with incident diabetes.

To determine whether migraine is associated with an increased risk of developing ocular motor cranial nerve palsies (OMCNP).Nationwide retrospective cohort study.Medical records of patients with migraine who were entered in the National Health Insurance Research Database (NHIRD) between 2005 and 2009 were retrieved from the NHIRD in Taiwan. Two cohorts were selected: patients with migraine (n = 138 907) and propensity score-matched controls (n = 138 907).Cohorts were followed until the end of 2010, death, or occurrence of cranial nerve (CN)3, CN4, or CN6 palsies. A Cox proportional hazards regression model was used to calculate the hazard ratios (HRs) and 95% confidence intervals (CIs), which were used to compare to the risk of developing CN3, CN4, and CN6 palsy between cohorts.After a mean follow-up period of 3.1 years (range, 1-6 years), the migraine cohort exhibited a greater risk of developing subsequent CN3, CN4, and CN6 palsies compared with the control cohort (HR, 2.67, P0.001; HR, 4.23, P0.001; HR, 3.37; P0.001). This finding was maintained after excluding potential confounders during sensitivity tests. Moreover, the significant association between migraine and OMCNP remained after we adjusted for potential risk factors of microvascular ischemia. However, different migraine subtypes showed no significant differences.Migraine is an unrecognized risk factor for OMCNP development in adults. Further studies are needed to validate our findings and to delineate the exact pathophysiologic mechanisms linking migraine and OMCNP.

Study objectives To explore the association between the non-apnea sleep disorder (NSD) and autoimmune diseases. Design Cohort study. Setting Nationwide database research. Participants 84,996 adult patients with NSD diagnoses recorded in the Taiwan National Health Insurance Research Database between 2000 and 2003, after excluding those with antecedent autoimmune diseases. A comparison cohort of 84,996 participants was formed by age-, gender-, income-, and urbanization-matched controls. Interventions None. Measurements and results The two cohorts were followed up for occurrence of autoimmune diseases, including rheumatoid arthritis (RA), ankylosing spondylitis (AS), systemic lupus erythematosus (SLE), Sjogren's syndrome (SS), and systemic sclerosis (SSc). A Cox proportional hazards regression model was used for muti-variate adjustment. In patients with NSD, the overall risk for incident autoimmune diseases was significantly higher than in controls (adjusted hazard ratio [HR] = 1.47, 95% confidence interval [CI] = 1.41-1.53). With regard to individual diseases, the risks for SLE, RA, AS and SS among NSD patients were also significantly higher than in controls (HR [95% CI] for SLE, RA, AS, and SS were 1.81 [1.50-2.18], 1.45 [1.36-1.54], 1.53 [1.38-1.70], and 1.51 [1.43-1.60], respectively), whereas the increased risk for SSc did not reach statistical significance (HR: 1.36 [0.82-2.26]). Conclusion Patients with non-apnea sleep disorder were associated with a higher risk for developing autoimmune diseases.

SummaryBackground Controversy exists regarding glucocorticoids therapy and the risk of peptic ulcer bleeding (PUB). Aim The present study was undertaken to determine whether short-term use of glucocorticoids is associated with the occurrence of peptic ulcer bleeding. Methods The records of adult patients hospitalised for newly diagnosed peptic ulcer bleeding from 2000 to 2012 were retrieved from the Taiwan National Health Insurance Research Database, a nationwide population-based registry system. The association between systemic glucocorticoids usage and peptic ulcer bleeding was determined with a conditional logistic regression model comparing cases and controls during time windows of 7, 14 and 28 days using a case-crossover design. Results Of the 8894 enrolled patients, the adjusted self-matched odds ratios for peptic ulcer bleeding after exposure to the glucocorticoids were 1.37 (95% CI: 1.12–1.68, P = 0.003) for the 7-day window, 1.66 (95% CI: 1.38–2.00, P

Background & Aims Studies concerning seasonal variations and the impact of air temperature on oesophageal variceal bleeding have yielded conflicting results. We aimed to explore the impact of air temperature on the occurrence of variceal bleeding. Methods A case-crossover study design was employed, and two cohorts were used, including the NHI-EVB cohort from the National Health Insurance Research Database of Taiwan from 1 January 1999 to 31 December 2010, and the VGH-EVB cohort from the Taipei Veterans General Hospital, from 4 May 2002 to 31 December 2010. A conditional logistic regression model was used to estimate odds ratios (ORs) and 95% confidence intervals (CIs). Results In total, 2542 cases from the NHI-EVB cohort and 220 cases from the VGH-EVB cohort were analysed. Our analysis showed that low air temperature (LAT) increased the risk of variceal bleeding regardless of age, sex, decompensated cirrhosis, Child-Pugh classification, aetiology of liver disease and concomitant hepatocellular carcinoma; the lag effect was also observed. The ORs per 5°C decrease in daily mean air temperature were 1.144 (95% CI, 1.060–1.235) for the NHI-EVB cohort and 1.307 (95% CI: 1.031–1.658) for the VGH-EVB cohort. Oesophageal variceal bleeding in patients with small varices, end-stage liver disease score ≧15 or those using non-selective beta blockers was not influenced by air temperature. Conclusions Patients have higher risk of oesophageal variceal bleeding at low air temperature regardless of age, sex, aetiology of cirrhosis, Child-Pugh classification, decompensated cirrhosis and concomitant hepatocellular carcinoma and can be protected by use non-selective beta blockers.

Background The relationship between congenital heart disease (CHD) and malignancies has not been determined. This study aimed to explore the association of CHD with malignancies and examine the risk factors for the development of cancer after a diagnosis of CHD. Patients and methods This nationwide, population-based cohort study on cancer risk evaluated 31,961 patients with newly diagnosed CHD using the Taiwan National Health Insurance Research Database (NHIRD) between 1998 and 2006. The standardized incidence ratios (SIRs) for all and specific cancer types were analyzed, while the Cox proportional hazard model was used to evaluate risk factors of cancer occurrence. Results Among patients with newly diagnosed CHD regardless of ages, 187 (0.6%) subsequently developed cancers after a diagnosis of CHD. Patients with CHD had increased risk of cancer (SIR, 1.45; 95% CI, 1.25-1.67), as well as significantly elevated risks of hematologic (SIR, 4.04; 95% CI, 2.76-5.70), central nervous system (CNS) (SIR, 3.51; 95% CI, 1.92-5.89), and head and neck (SIR, 1.81; 95% CI, 1.03-2.94) malignancies. Age (HR, 1.06; 95% CI, 1.05-1.06) and co-morbid chronic liver disease (HR, 1.91; 95% CI, 1.27-2.87) were independent risk factors for cancer occurrence among CHD patients. Conclusion Patients with CHD have significantly increased cancer risk, particularly hematologic, CNS, and head and neck malignancies. Physicians who care for patients with CHD should be aware of their predisposition to malignancy after the diagnosis of CHD. Further studies are warranted to clarify the association between CHD and malignancies.

To evaluate the association between migraine and Bell palsy and to examine the effects of age, sex, migraine subtype, and comorbid risk factors for Bell palsy.This nationwide cohort study was conducted using data from the Taiwan National Health Insurance Research Database. Subjects aged 18 years or older with neurologist-diagnosed migraine from 2005 to 2009 were included. A nonheadache age- and propensity score-matched control cohort was selected for comparison. All subjects were followed until the end of 2010, death, or the occurrence of a Bell palsy event. Cox proportional hazards regression was used to calculate the adjusted hazard ratios and 95% confidence intervals to compare the risk of Bell palsy between groups.Both cohorts (n = 136,704 each) were followed for a mean of 3.2 years. During the follow-up period, 671 patients (424,372 person-years) in the migraine cohort and 365 matched control subjects (438,677 person-years) were newly diagnosed with Bell palsy (incidence rates, 158.1 and 83.2/100,000 person-years, respectively). The adjusted hazard ratio for Bell palsy was 1.91 (95% confidence interval, 1.68-2.17; p0.001). The association between migraine and Bell palsy remained significant in sensitivity analyses, and tests of interaction failed to reach significance in all subgroup analyses.Migraine is a previously unidentified risk factor for Bell palsy. The association between these 2 conditions suggests a linked disease mechanism, which is worthy of further exploration.

Background Previous studies have demonstrated that high estimated glomerular filtration rate (eGFR) is paradoxically associated with an increased risk of mortality, and the association becomes more predominant in older people. However, the role of malnutrition–inflammation–cachexia syndrome (MICS) in the association between eGFR and mortality has never been explored. Methods We conducted a community‐based cohort study using data from the Taipei City Elderly Health Examination Database, collected during the period 2001–10. All participants aged ≥65 years were included and stratified by the absence or presence of MICS, which is defined as the presence of at least one of the following markers: body mass index

A 66-year-old man underwent hand-assisted laparoscopic radical nephrectomy (HALN) for a 10 x 7-cm, stage T(2)N(0)M(0) right-sided renal-cell carcinoma. Nine months later, tumor recurrence was noted at the previous hand port site. This is the first case report of such a metastasis. Possible mechanisms for tumor metastasis are reviewed, and preventive strategies are suggested.

Purpose: We assessed the efficacy and safety of the mid term use of α1-adrenergic blockers for treating primary bladder neck obstruction in young and middle-aged men.Materials and Methods: Between May 1998 and February 2001 primary bladder neck obstruction was diagnosed by videourodynamic study in 28 men younger than 55 years. The degree of obstruction was graded by the Schafer nomogram. Mean patient age and mean symptom duration were 39.3 years and 18.1 months, respectively. The presenting symptom was frequency in 22 cases (78.6%), urgency in 10 (35.7%), weak stream in 9 (32.1%), nocturia greater than 2 times in 7 (25%) and hesitancy in 7 (25%). A dose of 1 to 2 mg. doxazosin was administered at bedtime for at least 3 months. International Prostate Symptom Score (I-PSS), quality of life, uroflowmetry and post-void residual urine were assessed before and 3 months after medication. Improved urine flow was defined as at least a 2.5 ml. per second increase in the maximum flow rate. Improved symptoms was defi...

Intensive care unit (ICU)-acquired weakness is a common issue for sepsis survivors that is characterized by impaired muscle strength and causes functional disability. Although inpatient rehabilitation has not been found to reduce in-hospital mortality, the impact of postdischarge rehabilitation on sepsis survivors is uncertain.To investigate the benefit of postdischarge rehabilitation to long-term mortality in sepsis survivors.We conducted a nationwide, population-based, high-dimensional propensity score-matched cohort study using Taiwan's National Health Insurance Research Database. The rehabilitation cohort comprised 15,535 ICU patients who survived sepsis and received rehabilitation within 3 months after discharge between 2000 and 2010. The control cohort consisted of 15,535 high-dimensional propensity score-matched subjects who did not receive rehabilitation within 3 months after discharge. The endpoint was mortality during the 10-year follow-up period.Compared with the control cohort, the rehabilitation cohort had a significantly lower risk of 10-year mortality (adjusted hazard ratio, 0.94; 95% confidence interval, 0.92-0.97; P0.001), with an absolute risk reduction of 1.4 per 100 person-years. The frequency of rehabilitation was inversely associated with 10-year mortality (≥3 vs. 1 course: adjusted hazard ratio, 0.82; P0.001). Compared with the control cohort, improved survival was observed in the rehabilitation cohort among ill patients who had more comorbidities, required more prolonged mechanical ventilation, and had longer ICU or hospital stays, but not among those with the opposite conditions (i.e., less ill patients).Postdischarge rehabilitation may be associated with a reduced risk of 10-year mortality in the subset of patients with particularly long ICU courses.

Background Head injury has been suggested to correlate with meningioma. However, results of studies investigating the relationship between head injury and meningioma were inconsistent. Therefore, we conducted this study to assess the association between head injury and meningioma, and to determine the possible risk factors. Methods Head injury patients aged 18 years and older, without antecedent diagnosis of brain tumor, and who were followed up for more than 30 days between January 1, 2001, and December 31, 2010, were recruited from the Taiwan National Health Insurance Research Database. Hazard ratios (HRs) of meningioma risk for head injury patients compared with an age- and sex-matched cohort were calculated by Cox proportional regression analysis. The difference in cumulative incidence between head injury patients and the matched cohort was analyzed using the Kaplan–Meier method and tested with the log-rank test. Results Each cohort (i.e., the head injury cohort and the matched cohort) consisted of 75,292 individuals with a mean age of 44.7 years, and 52.3% of these patients were male. The incidence rates of meningioma were 3.99/105 person-years and 3.23/105 person-years in the head injury cohort and the comparison cohort, respectively, with a Charlson Comorbidity Index score-adjusted HR of 1.27 (p = 0.514). There were no associations between head injury and risk of meningioma, neither overall nor in stratified analyses according to severity of head injury, age, and sex of patients. ConclusionHead injury, regardless of severity, patient sex, or age, is unlikely to be a cause of meningioma.

Nontyphoid salmonellosis (NTS) is one of the most common foodborne diseases worldwide, affecting millions of persons each year [1, 2]. Usually acquired by consumption of contaminated food, especially eggs and poultry products, NTS may cause gastroenteritis, bacteremia, and focal infections [3]. Predisposing host factors include gastric hypoacidity [1], diabetes [3, 4], autoimmune diseases [1, 4], cancer [5], hepatic cirrhosis [3], gallstones [1], previous gastrointestinal surgery [6], AIDS [7, 8], and prior use of antimicrobial agents [3, 7, 8]. Proton pump inhibitors (PPIs) have also been associated with NTS [9–11]. This association is thought to be due to disruption of the natural gut microbial ecology [12] caused by inhibition of gastric acid secretion, mucosal permeability [13], and neutrophil bactericidal activity [14]. Most studies have shown an association between PPI use and susceptibility to NTS but failed to consider the confounding effects of host factors that enhance susceptibility to NTS [9–11]. A recent study, which controlled for individual confounding factors by using the patients as their own control over a 12-month period, found no association between PPIs use and NTS, suggesting that predisposing factors other than PPIs may contribute to the increased rate of NTS [15]. Because of the conflicting results in the literature, problems of selection bias [16], and differences in the intervals of time between the use of a PPI and onset of NTS we believed that a large, community-based study was needed to adjust for the effect of predisposing host factors and to determine the critical interval between use of a PPI and the onset of NTS. To accomplish this we conducted a nested case-control study, matching for demographic and predisposing host factors for NTS. The Taiwan National Health Insurance Research Database (NHIRD) 2000–2010 was used to identify a large number of case patients and controls during an 11-year period.

Background There is substantial debate regarding the development of acute coronary syndrome in patients using proton pump inhibitors (PPIs) combined with clopidogrel. However, data remain limited to address the effect of PPIs alone on the subsequent risk of myocardial infarction (MI). We aimed to explore the subsequent risk of MI in PPI users who had no previous history of MI. Methods The records of inpatients and outpatients with PPI prescriptions were retrieved from the Taiwan National Health Insurance Research Database between 2000 and 2009. We conducted two different study designs, the first using propensity score (PS)-matching analyses and the second using case-crossover analyses. The risk of developing MI for PPI users was analyzed in the PS-matched study. The association between risk of MI and prior PPI exposure was further validated in the case-crossover study. Results In the PS-matched study, we included 126,367 PPI users and 126,367 PS-matched PPI non-users. After 120days of follow-up, PPI use was associated with a 1.58-fold greater risk of MI (adjusted hazard ratio [HR]=1.58, 95% confidence interval [CI]=1.11 to 2.25). In the case-crossover study, adjusted odds ratios of PPI for MI risk were 4.61 (95% CI=1.76 to 12.07) for the 7-day window and 3.47 (95% CI=1.76 to 6.83) for the 14-day window. Conclusions Use of PPIs may be independently associated with an increased risk of MI. However, the benefits of PPIs may greatly outweigh the risks of adverse cardiovascular effects, with number needed to harm of 4357.

Background Older patients with advanced chronic kidney disease (CKD) face the decision of whether to undergo dialysis. Currently available data on this issue are limited because they were generated by small, short-term studies with statistical drawbacks. Further research is urgently needed to provide objective information for dialysis decision making in older patients with advanced CKD. Methods This nationwide population-based cohort study was conducted using Taiwan’s National Health Insurance Research Database. Data from 2000 to 2010 were extracted. A total of 8,341 patients ≥70 years old with advanced CKD and serum creatinine levels >6 mg/dl, who had been treated with erythropoiesis-stimulating agents were included. Cox proportional hazard models in which initiation of chronic dialysis was defined as the time-dependent covariate were used to calculate adjusted hazard ratios for mortality. The endpoint was all-cause mortality. Results During a median follow-up period of 2.7 years, 6,292 (75.4%) older patients chose dialysis therapy and 2,049 (24.6%) received conservative care. Dialysis was initiated to treat kidney failure a median of 6.4 months after enrollment. Dialysis was associated with a 1.4-fold increased risk of mortality compared with conservative care (adjusted hazard ratio 1.39, 95% confidence interval 1.30 to 1.49). In subgroup analyses, the risk of mortality remained consistently increased, independent of age, sex and comorbidities. Conclusions In older patients, dialysis may be associated with increased mortality risk and healthcare cost compared with conservative care. For patients who are ≥70 years old with advanced CKD, decision making about whether to undergo dialysis should be weighted by consideration of risks and benefits. Electronic supplementary material The online version of this article (doi:10.1186/s12916-014-0169-3) contains supplementary material, which is available to authorized users.