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Objectives To compare the risk of PsA in psoriasis (PsO) patients treated with acitretin vs DMARDs. Methods This retrospective study used Taiwan's National Health Insurance Research Database from 1997 to 2013. Adult PsO patients without PsA prescribed acitretin or DMARDs for ≥30 days within a year were assigned to the acitretin cohort or DMARDs cohort, respectively. Patients in the acitretin cohort prescribed DMARDs for >7 days, or in the DMARDs cohort prescribed acitretin for >7 days, were excluded. Cumulative incidence of PsA were determined within both cohorts using the Kaplan–Meier method. The hazard ratio (HR) comparing acitretin to DMARDs was calculated with Cox regression models, adjusting for demographic and clinical covariates including the use of NSAIDs and comorbidities. Results The study included 1948 patients in each cohort. The 5-year cumulative incidence of PsA in the acitretin cohort was lower than that in the reference cohort (7.52% vs 9.93%; P  = 0.005), with a more pronounced difference in the subpopulation receiving NSAIDs treatment. However, in subpopulations without NSAIDs treatment, the 5-year cumulative incidence of PsA in the acitretin cohort was comparable to the DMARDs cohort (5.26% vs 6.98%; P  = 0.106). Acitretin was not associated with PsA development in PsO (HR 0.83, 95% confidence interval 0.65–1.05). This risk remained consistent regardless of adjustments for NSAID treatment and comorbidities. Other independent risk factors for PsA included female and NSAIDs treatment. Conclusion Compared with DMARDs, acitretin was not associated with increased PsA risk in PsO patients. [ABSTRACT FROM AUTHOR]

Introduction: Atopic dermatitis (AD) is a disease frequently occurring in children. The immune response is characterized by T-helper (Th)-2-dependent inflammation. Type 1 diabetes mellitus (T1DM) is an autoimmune disease that destroys pancreatic islet beta cells. In contrast, it is mainly mediated by a Th-1-dependent response. An inverted association has been hypothesized between T1DM and AD since Th1 and Th2 responses are mutually inhibitory. Methods: Data was retrieved from a nationwide healthcare database in Taiwan. A logistic regression model was used to evaluate the association of T1DM in patients with AD within a year. A Cox proportional hazards analysis was used to evaluate the subsequent risk of developing T1DM 1 year after AD diagnosis. Results: We identified 396,461 patients with AD and 1,585,844 age- and sex-matched controls. During the first year of follow-up, after adjusting variates, the association between T1DM and AD showed no statistical differences (odds ratio: 1.40; 95% confidence interval [CI]: 0.83–2.38, p = 0.207). After excluding those T1DM cases within 1 year of AD diagnosis and those with a follow-up duration of less than 1 year, AD did not significantly increase the risk of T1DM (hazard ratio [HR]: 1.02; 95% CI, 0.83–1.25, p = 0.843). Conclusions: Our study revealed that there was no significant association between AD and T1DM in the first year after AD diagnosis, and there was no increased risk of T1DM in AD patients in the average 5-year follow-up in our study. [ABSTRACT FROM AUTHOR]

In Taiwan, where relations with China define the major political cleavage, voters have distinct preferences on the issue of independence. Do Taiwanese favor a symbolic or pragmatic approach to the Taiwan independence issue? What are the factors that account for their political preferences? We identify two types of voters, symbolic and pragmatic, according to whether their preferences on independence are conditional or unconditional on China's potential counter actions. Specifically, symbolic voters have unconditional preferences on independence, while pragmatic voters are more agreeable to independence under more favorable conditions. Using multiple wave data from the Taiwan National Security Surveys (TNSS 2002–2022), we investigate the individual- and macro-level factors and find that gender, age, education level, ethnicity, partisan strength, and economic growth rate shape the types of voters in Taiwan. This paper contributes to the study of political attitudes in Taiwan, and have important implications on the regional stability in East Asia. [ABSTRACT FROM AUTHOR]

Background: Acitretin has been linked to the development of psychiatric disturbance. Objectives: The aim of this study was to assess the psychiatric hazards in patients with psoriasis prescribed acitretin compared with those prescribed disease-modifying antirheumatic drugs (DMARDs). Methods: This is a nationwide matched cohort study. From Taiwan's National Health Insurance Research Database, adult patients with psoriasis between 1997 and 2013 were screened. Patients prescribed acitretin for at least 30 days per year on average (acitretin cohort) were matched 1:2 with those prescribed DMARDs for at least 30 days per year on average (reference cohort), by means of age, gender, and psoriasis duration. Patients prescribed medication of the corresponding cohort for more than 7 days during the observation period were excluded. Cumulative incidences of psychiatric disorders in both cohorts were plotted with the Kaplan-Meier method. The modified Cox regression models were constructed to estimate hazard ratios (HRs). Results: In total, 1,152 and 2,304 patients in the acitretin and the reference cohorts, respectively, were included. The 4-year cumulative incidence of overall psychiatric disorders (19.62% vs. 12.06%; p < 0.001), mood disorders (12.81% vs. 7.67%; p < 0.001), and psychosis (7.21% vs. 4.63%; p < 0.001) in the acitretin cohort was significantly higher than that in the reference cohort. Acitretin was independently associated with psychiatric disorders (HR 1.51, 95% confidence interval [CI] 1.23–1.85). The risk is more accentuated in the subgroups of comorbid chronic liver disease (HR 2.60, 95% CI: 1.56–4.33) or psoriatic arthritis (HR 3.23, 95% CI: 1.75–5.97). Other independent risk factors included insomnia, acute coronary syndrome, females, and age. Conclusions: Compared with DMARDs, acitretin was associated with higher hazards of psychiatric disorders among psoriasis patients. [ABSTRACT FROM AUTHOR]

Although bullous pemphigoid (BP) and atopic dermatitis (AD) share pathogenic mechanisms, their relationship remains controversial. Therefore, we conducted a population-based case–control study to investigate the association between BP and AD in Taiwan. Based on the Taiwan National Health Insurance Research Database, 9344 patients with BP and 18,688 age- and sex-matched controls were enrolled between 2000 and 2013. Furthermore, the study included 7,196 BP patients and 14,392 controls, matched for age, sex, and propensity score of comorbidities, with a case to controls ratio of 1:2. Logistic regression analysis was performed to examine the association between AD and BP. In the age- and sex-matched cohorts, AD (odds ratio [OR], 1.71; 95% confidence interval [CI], 1.50–1.95) was independently associated with BP. In the age, sex, and comorbidities-matched cohorts, AD (OR 1.76, 95% CI 1.55–2.00) remained a significant risk factor for BP. Other significant risk factors included psoriasis, hypertension, diabetes mellitus, chronic kidney disease, chronic obstructive pulmonary disease, neuropsychiatric diseases, and autoimmune connective tissue disease. Limitations of this study include the lack of information on disease severity and phenotypes of BP and misclassification of diseases as potential sources of bias. In conclusion, AD increased the risk of developing BP by 76%, and this association was independent of many BP comorbidities. Further studies are warranted to investigate the clinical and pathophysiological relevance of factors contributing to BP and AD. [ABSTRACT FROM AUTHOR]

Large‐scale, real‐world studies on the side effects of systemic therapies (including biologics) in patients with psoriasis are limited. We aimed to calculate the risk of malignancy in patients with psoriasis who were treated with systemic medications. Nested case‐control analyses were performed among psoriasis patients without a history of malignancy. We recruited 4188 patients with newly diagnosed psoriasis and successive malignancies, and 8376 matched controls from the National Health Insurance Research Database in Taiwan. The therapy duration was within 5 years before malignancy onset and further stratified into two groups according to the duration of medication usage. Multivariate conditional logistic regression adjusted for potential confounders was used to estimate malignancy risk associated with systemic treatments. Among psoriasis patients, long‐term (> 12 months) treatment with cyclosporine increased the risk of malignancy compared with no exposure (odds ratio, 1.57; p = 0.01). Short‐term (≤ 12 months) or long‐term (> 12 months) use of other systemic treatments, including methotrexate, azathioprine, systemic retinoids, mycophenolate mofetil, sulfasalazine, etanercept, adalimumab, and ustekinumab, was not associated with an increased risk of malignancy in patients with psoriasis. Long‐term treatment with cyclosporine increased the risk of malignancy in patients with psoriasis by 1.57‐fold. [ABSTRACT FROM AUTHOR]

Background/purpose: Clostridium difficile infection (CDI) leads to a significant cause of hospital-acquired morbidity and mortality. Fecal microbiota transplantation (FMT) is effective to treat recurrent or refractory CDI (rCDI). However, the change of microbial composition contributed by FMT and its association with treatment outcomes is not well determined in Taiwan. We aimed to investigate the efficacy of FMT and the association with microbial alteration endemically.Methods: Twelve patients who received FMT for rCDI in Taipei Veterans General Hospital were prospectively enrolled from April 2019 to July 2020. The clinical assessments and fecal microbial analyses in comparison with fecal materials of unrelated donors were conducted before and after FMT.Results: The overall success rate of FMT for rCDI was 91.7%. A prominence of Proteobacteria, Gammaproteobacteria and Enterobacteriales were observed in the feces of patients with rCDI. Increased fecal phylogenetic diversities and a significant microbial dissimilarity were provided by successful FMT compared to patients before treatment. However, the distinctness was not obvious between patients' feces at baseline and after unsuccessful FMT. Moreover, dynamic change of fecal microbial composition after FMT was observed during follow-up but did not interrupt the treatment effects of FMT.Conclusion: Gut dysbiosis commonly co-exists in patients with rCDI. Restoration of gut microbial communities by FMT provides a promising strategy to treat antibiotic-failed CDI, and the extent of microbial change would be related to the treatment outcomes of FMT. Besides, the effectiveness of FMT for CDI could be maintained even the gut microbiota has diverged over time. [ABSTRACT FROM AUTHOR]

Background: Antibiotic-driven dysbiosis may impair immune function and reduce vaccine-induced antibody titers. Objectives: This study aims to investigate the impacts of early-life antibiotic exposure on subsequent varicella and breakthrough infections. Methods: This is a nationwide matched cohort study. From Taiwan's National Health Insurance Research Database, we initially enrolled 187,921 children born from 1997 to 2010. Since 2003, the Taiwan government has implemented a one-dose universal varicella vaccination program for children aged 1 year. We identified 82,716 children born during the period 1997 to 2003 (pre-vaccination era) and 48,254 children born from July 1, 2004, to 2009 (vaccination era). In the pre-vaccination era, 4,246 children exposed to antibiotics for at least 7 days within the first 2 years of life (Unvaccinated A-cohort) were compared with reference children not exposed to antibiotics (Unvaccinated R-cohort), with 1:1 matching for gender, propensity score, and non-antibiotic microbiota-altering medications. Using the same process, 9,531 children in the Vaccinated A-cohort and Vaccinated R-cohort were enrolled from the vaccination era and compared. The primary outcome was varicella. In each era, demographic characteristics were compared, and cumulative incidences of varicella were calculated. Cox proportional hazards model was used to examine associations. Results: In the pre-vaccination era, the 5-year cumulative incidence of varicella in the Unvaccinated A-cohort (23.45%, 95% CI 22.20% to 24.70%) was significantly higher than in the Unvaccinated R-cohort (16.72%, 95% CI 15.62% to 17.82%) (p<.001). In the vaccination era, a significantly higher 5-year cumulative incidence of varicella was observed in the Vaccinated A-cohort (1.63%, 95% 1.32% to 1.93%) than in the Vaccinated R-cohort (1.19%, 95% CI 0.90% to 0.45%) (p=0.006). On multivariate analyses, early-life antibiotic exposure was an independent risk factor for varicella occurrence in the pre-vaccination (adjusted hazard ratio [aHR] 1.92, 95% CI 1.74 to 2.12) and vaccination eras (aHR 1.66, 95% CI 1.24 to 2.23). The use of penicillins, cephalosporins, macrolides, or sulfonamides in infancy was all positively associated with childhood varicella regardless of vaccine administration. Conclusions: Antibiotic exposure in early life is associated with varicella occurrence and breakthrough infections. [ABSTRACT FROM AUTHOR]

Background: Bullous pemphigoid (BP) is a common autoimmune blistering skin disease with substantial mortality. Objective: To identify whether the use of immunosuppressants was associated with reduced mortality in BP patients. Methods: The data for this study were obtained from the National Health Insurance Research Database in Taiwan from January 1, 1997 to December 31, 2013. Those BP patients receiving any immunosuppressant for ≥28 days per month for 3 consecutive months were defined as the immunosuppressant cohort. In total, 452 BP patients on immunosuppressants were matched 1:4 by age, sex, propensity score of comorbidities, and use of tetracycline with 1,808 BP patients taking only corticosteroids. Results: The immunosuppressant cohort had a significantly lower 5-year mortality rate than the corticosteroid cohort (0.57 vs. 0.67). In the multivariable regression analysis adjusted for covariates, the use of immunosuppressants significantly reduced the risk of mortality (hazard ratio [HR]: 0.78, 95% confidence interval [CI]: 0.68–0.90, p < 0.001). Hyperlipidemia also reduced risk of mortality. However, age, diabetes, renal disease, chronic obstructive pulmonary disease, cerebrovascular disease, and dementia were significant risk factors for mortality. In the subgroup analysis, the risk of mortality decreased most substantially in those aged <70 years (HR: 0.45, 95% CI: 0.28–0.72). Conclusion: Immunosuppressant use was associated with a 22% reduced risk of BP mortality. The effects were more substantial in those aged <70 years, with a 55% reduced risk of mortality. [ABSTRACT FROM AUTHOR]

The relationship between cancer and vitiligo has been explored but with inconsistent results. To examine the long-term cancer risk in vitiligo patients, we conducted a retrospective nationwide cohort study. From the National Health Insurance Research Database of Taiwan, a total of 13,824 vitiligo patients were identified and matched with 55,296 reference subjects without vitiligo by age, gender, and propensity score estimated by major comorbidities from 1997 to 2013. Demographic characteristics and comorbidities were compared between these two groups. Incidence rate ratios and hazard ratios (HRs) were calculated to examine cancer risks. The 16-year incidence rates of overall cancers were 621.06 (566.56–675.55) and 726.99 (697.24–756.74) per 100,000 person-years in the vitiligo and reference groups. Patients with vitiligo showed a significantly decreased risk of overall cancers [adjusted HR, 0.85; 95% confidence interval (CI), 0.77 to 0.93, p < 0.001] compared with reference subjects without vitiligo after adjusting for age, sex, comorbidities, and treatments. The risks of basal cell carcinoma (BCC) and squamous cell carcinoma (SCC) were significantly reduced (adjusted HR 0.21, 95% CI 0.11–0.38, p < 0.001), as well as internal malignancies (adjusted HR 0.89, 95% CI 0.81–0.99, p = 0.026). The results were consistent across different subgroups of patients, including male gender, ages more than 40 years, and those receiving long-term systemic disease-modifying antirheumatic drugs and phototherapies. Information related to phenotype, disease duration, vitiligo lesion sites, family history of vitiligo or cancer, occupation, and personal lifestyle was not included in the database. Vitiligo is associated with reduced risks of BCC and SCC, as well as internal malignancies. [ABSTRACT FROM AUTHOR]

Background: Data from the USA suggest that chronic hepatitis B (CHB) patients have aged in the past decade. However, the burden of nonliver comorbidities has not been well characterized in Taiwan, where CHB is very prevalent. Aim: Our study examined this issue as it presented between 2001 and 2011 in Taiwan. Methods: This study identified adult patients (≥18 years) who were diagnosed with CHB in 2001, 2006, and 2011, from the Taiwan National Health Insurance Research Database (NHIRD). Changes in demographic characteristics, prevalence of nonliver comorbidities, and medication usage over the decade were examined. Non-CHB controls were adults without CHB diagnosis from the Longitudinal Health Insurance Database 2000 (LHID2000). Results: A total of 102,158, 252,809, and 338,200 eligible patients were identified in 2001, 2006, and 2011, respectively. The mean age significantly advanced from 45.4 to 52.3 years over the decade (p < 0.001). The prevalence of comorbidities, including diabetes mellitus, hypertension, stroke, chronic kidney disease, and bone fracture, significantly increased between 2001 and 2011 (all p < 0.001), as so were medication usage (all p < 0.001). Moreover, within each study period, compared to non-CHB controls, CHB patients were also older and more likely to have metabolic and cardiovascular comorbidities (all p < 0.001). In addition, the annual nonliver mortality in the CHB population significantly increased from 2001 to 2011. Conclusions: Over a decade, the CHB population in Taiwan has aged with a higher nonliver comorbidity burden and increasing nonliver mortality. These findings may provide information to care providers in the monitoring and management of CHB patients. [ABSTRACT FROM AUTHOR]

Taiwanese identity is distinct from and juxtaposed against the Chinese identity. What explains the emergence of a Taiwanese identity – specifically in the south? This identity formation is surprising considering the multiple decades of authoritarian rule where the government championed a Chinese identity. In this article, weargue that the Taiwanese identity manifested from a linguistic tension betweenHokloand Mandarinspeakers.And while the Kuomintang adopted a strict Mandarin monolingual policy, thehomogeneity of theHoklo speakers in the south – i.e., they constituted a minimal winningsizeand they were regionally concentrated –ensured the survival of theHoklovernacular. This vernacular would become the instrument for the formation of a Taiwanese identity. In contrast,we see initial push back from the Hakka speakers who were excluded from the narrative of Taiwanese identity. Likewise,in the north where there weregreater linguistic heterogeneity and increasing interethnic marriages, Taiwanese identity was not as coherent. [ABSTRACT FROM AUTHOR]

Objective Psoriasis is associated with ischemic heart disease (IHD). Results of prior studies have suggested that methotrexate (MTX) may improve vascular disease in patients with psoriasis and rheumatoid arthritis. The aim of this study was to assess the risk of new-onset IHDs in psoriasis patients, comparing those taking MTX with those taking other nonbiologic antipsoriatic drugs. Methods In this retrospective cohort study, we utilized claims data from the National Health Insurance Research Database of Taiwan to identify 179,200 subjects who had received a diagnosis of psoriasis, with or without psoriatic arthritis, on at least 3 visits. The risk of hospitalization for new-onset IHD was compared between psoriasis patients taking MTX monotherapy (n = 6,578; MTX case cohort) and psoriasis patients taking other nonbiologic antipsoriatic drugs (n = 5,471; reference control cohort) between January 1996 and December 2008. Additional adjustments were made for cardiovascular risk factors, number of hospital visits, Charlson comorbidity score, and use of other antiinflammatory drugs. Results The incidence rates of IHD were 666 cases per 100,000 person-years in the MTX case cohort and 830 cases per 100,000 person-years in the reference control cohort (unadjusted P = 0.027). Increasing age, male sex, presence of hypertension, presence of diabetes, Charlson comorbidity score, and use of phototherapies were independent risk factors for hospitalization related to a new IHD in the study cohorts. However, the multivariate-adjusted hazard ratio for IHD-related hospitalizations among patients receiving MTX, in comparison with those receiving other nonbiologic antipsoriatic drugs, was 0.97 (95% confidence interval 0.79-1.19), after adjustment for age, sex, comorbidity score, number of hospital visits, and other antiinflammatory treatments for psoriasis. Conclusion In patients with psoriasis with or without coexisting psoriatic arthritis, the adjusted risk of hospitalization for an IHD among individuals receiving MTX was comparable with that among individuals receiving other nonbiologic antipsoriatic drugs. [ABSTRACT FROM AUTHOR]

Background & Aims: The incidence of peptic ulcer diseases has decreased significantly during past decades. Despite several significant population-based studies in Western countries, studies of Asian populations are lacking. We therefore investigated the incidence of hospital admissions for peptic ulcer disease in Taiwan during a 10-year period. Methods: This nationwide population-based cohort study was based on data obtained from the Taiwan National Health Insurance Database (a population of 23 million). In total, 403,567 patients with peptic ulcer diseases were recruited for the study. Standardized incidences of admissions were calculated to estimate changes. Results: Hospitalization for peptic ulcer diseases decreased significantly between 1997 and 2006 in Taiwan. The incidences of admissions decreased from 68.3 to 39.6 per 100,000 for uncomplicated gastric ulcer, from 116.9 to 61.1 for bleeding gastric ulcer, and from 11.0 to 6.3 for perforated gastric ulcer. The incidences decreased from 46.4 to 13.6 per 100,000 for uncomplicated duodenal ulcer, from 108.0 to 40.1 for bleeding duodenal ulcer, and from 9.8 to 5.8 for perforated duodenal ulcer. The declines were observed in both genders, in all age groups, and at all hospital levels. Significant increases in Helicobacter pylori eradication therapy (202% increase) and proton pump inhibitor use (1071% increase) might have contributed to these decreases. Conclusions: The incidences of gastric and duodenal ulcer diseases decreased 42%–48% and 41%–71%, respectively, in Taiwan between 1997 and 2006. [Copyright &y& Elsevier]

Background/purpose: A better understanding of the risk factors for medical malpractice is essential for implementing long-term prevention strategies. Certain physician characteristics have been reported to be associated with malpractice litigation. However, patient characteristics have not been fully investigated.Methods: We conducted a hospital-based case-control study. We reviewed a total of 147 cases in the inpatient risk management file (RMF) and 44,045 inpatient controls. The RMF was opened if the patient's complaint may have led to legal action. We compared demographic data of RMF cases and controls to investigate the risk factors for filing a complaint. Outcomes of the RMF cases were classified as resolution, compensation, and lawsuit.Results: RMF cases were associated with admission via the emergency room (odds ratio [OR]=1.62, p=0.005), surgical specialty (OR=1.86, p=0.001) and living in an urban area (OR=1.93, p<0.001). Once RMF cases were filed, living in an urban area was the only independent factor for filing a lawsuit (OR=4.10, p=0.007). RMF cases with medical injury were more likely to reach compensation (OR=10.51, p<0.001) and to receive significantly higher compensation (p=0.007). The severity of medical injury was correlated positively with the likelihood of reaching compensation and the amount of compensation. Only 15.0% of RMF cases entered the litigation phase.Conclusion: Patients with certain characteristics tend to file complaints, receive compensation, or bring a case to court. Understanding of patient characteristics may be useful for predicting occurrence and outcome of complaints against physicians. [ABSTRACT FROM AUTHOR]

: PurposeTo determine the surgical outcomes of therapeutic penetrating keratoplasty (PKP) and its role in the management of microbial keratitis.: DesignInterventional case series.: MethodsWe retrospectively performed a chart review of the hospital records of all 151 patients undergoing therapeutic PKP for culture-proven microbial keratitis at the National Taiwan University Hospital during a 14 year-period (1987–2001). Patients were divided into three categories: (1) bacterial keratitis; (2) fungal keratitis; and (3) acanthamoebic keratitis. Each of the following criteria was evaluated: (1) graft clarity 1 month and 1 year postoperatively; (2) cure of the disease; and (3) anatomical success rate.: ResultsA total of 108 therapeutic PKP met the criteria. Therapeutic PKP eradicated the infection in 37/41 of patients with bacterial keratitis, 36/52 of patients with fungal keratitis, and 13/15 of patients with acanthamoebic keratitis. 22/32 of grafts of bacterial keratitis, 20/39 of fungal keratitis, and 11/14 of acanthamoebic keratitis remained clear at 1 year postoperatively. A higher percentage of graft clarity at 1 year postoperatively was achieved in all three categories when grafts were 8.5 mm or less compared with larger grafts. All five patients with secondary endophthalmitis observed at the time of therapeutic PKP experienced a progression of infection despite aggressive surgical treatment, and had to be enucleated.: ConclusionsTherapeutic PKP is valuable in the management of microbial keratitis that is unresponsive to medical therapy. A higher percentage of clear graft was found when grafts were smaller in all three categories. Surgical results are worse for patients with fungal keratitis, regardless of graft clarity, anatomical success, or infection eradication rate. [Copyright &y& Elsevier]

Background: Dialyzed patients are vulnerable to coronavirus infection disease 2019 (COVID-19). The incidence and outcome of COVID-19 in hemodialysis (HD) patients in Taiwan remain unclear. A series of preventive measures were executed to combat COVID-19 transmission among HD patients. Methods: We carried out a series of forward-looking and practical preventive strategies of COVID-19 control in our HD center. Incidences of COVID-19 of our HD unit were compared with those of national and local estimates from a community outbreak from 15 May to 30 June 2021. Prognostic factors associated with mortality were analyzed. Results: The national incidence of COVID-19 was 0.062%; being highest in Taipei City (0.173%), followed by New Taipei City (0.161%) and Keelung (0.083%). The overall incidence in Keelung HD patients was 0.666%. One patient of our HD center contracted COVID-19 from the household; however, we have contained secondary transmission in our HD center by implementing strict preventive measures. The mortality rate of HD patients in Keelung was 66.6%. The median Ct value of HD patients was 17.53 (11.75–27.90) upon diagnosis. The deceased patients had a higher cardiac/thoracic ratio than alive (0.61 vs. 0.55, p = 0.036). Conclusions: Taking aggressive and proactive infection preventive measures impedes the secondary transmission of COVID-19 in HD facilities. COVID-19-associated mortality was high in HD patients, being the high cardiac-thoracic ratio, an important prognostic factor for clinical outcome of infected HD patients. [ABSTRACT FROM AUTHOR]

Aims: Higher bullous pemphigoid (BP) risk has been reported to be associated with dipeptidyl peptidase 4 inhibitor (DPP4i). The aim of this study is to examine the association between BP risk and DPP4i treatment.Methods: We conducted a nationwide cohort study based on the Taiwan National Health Insurance Database between 2000 and 2015. 124,619 diabetic patients who were receiving DPP4i therapy were matched 1: 1 with diabetic patients who had never received DPP4i by age, sex, duration of diabetes, insulin usage, and propensity score-matching of comorbidities.Results: The 6-year cumulative incidence of BP in the DPP4i-treated cohort was significantly higher than that in the non-DPP4i group (0.74 per 1000 vs 0.38 per 1000, P = 0.001). Modified Cox regression analysis revealed that DPP4i treatment (HR: 2.15, 95% CI: 1.18-3.91, P = 0.01), age (HR: 1.06, P < 0.001), renal disease (HR: 2.32, P < 0.001), and metformin user (HR: 1.93, P = 0.006) were associated with increased BP risk.Conclusions: DPP4i users had a 2.2-fold increase in the risk of BP, and the risk was the highest in those with concomitant use of DPP4i and insulin. [ABSTRACT FROM AUTHOR]

Background & Aims: Previous observational studies reported that concomitant use of clopidogrel and proton pump inhibitors (PPIs) in patients with prior acute coronary syndrome (ACS) was associated with adverse cardiovascular outcomes. We investigated whether H2-receptor antagonist (H2RA) is an alternative to PPI in patients with ACS. Methods: We conducted a population-based retrospective cohort study of 6552 patients in Taiwan discharged for ACS between 2002 and 2005. Patients were divided into 5 cohorts: clopidogrel plus H2RA (n = 252), clopidogrel plus PPI (n = 311), clopidogrel alone (n = 5551), H2RA alone (n = 235), and PPI alone (n = 203). The primary outcome was rehospitalization for ACS or all-cause mortality within 3 month of rehospitalization. Results: The 1-year cumulative incidence of the primary outcome was 26.8% (95% CI: 21.5%–33.0%) in the clopidogrel plus H2RA cohort and 33.2% (95% CI: 27.8%–39.4%) in the clopidogrel plus PPI cohort, compared with 11.6% (95% CI: 10.8%–12.5%) in the clopidogrel alone cohort (P < .0001). No significant difference was observed between the PPI alone cohort (11.0%; 95% CI: 7.1%–16.8%), the H2RA alone cohort (11.8%; 95% CI: 8.2%–16.8%), and the clopidogrel alone cohort in terms of the primary outcome. The number needed to harm was 7 with concomitant H2RA and 5 with concomitant PPI. On multivariate analysis, concomitant H2RA and PPI were independent risk factors predicting adverse outcomes (adjusted hazard ratios, 2.48 and 3.20, respectively; P < .0001). Conclusions: Concomitant use of clopidogrel and H2RA or PPI after hospital discharge for ACS is associated with increased risk of adverse outcomes. [ABSTRACT FROM AUTHOR]

Background: Antiviral therapy for patients with non-cirrhotic chronic hepatitis B and minimally raised alanine aminotransferase (ALT) is controversial. We aimed to investigate the efficacy and safety of tenofovir disoproxil fumarate in reducing the risk of disease progression in this patient population.Methods: TORCH-B is a multicentre, double-blind, placebo-controlled, parallel-group, randomised trial done at six teaching hospitals in Taiwan that enrolled patients with chronic hepatitis B. Eligible patients were aged 25-70 years and had substantial viraemia (viral DNA >2000 IU/mL) and minimally raised serum ALT concentrations more than one-fold but less than two-fold the upper limit of normal (ULN). Exclusion criteria included liver cirrhosis and previous antiviral treatment. Eligible participants were randomly assigned (1:1), stratified by site with a fixed block size of ten, to receive either 300 mg of oral tenofovir disoproxil fumarate or placebo once daily for 3 years. The participants, investigators, research coordinators, pathologists, laboratory personnel, and staff involved in patient care or assessment were masked to treatment assignment. 0·5 mg/day of oral entecavir was added to rescue acute hepatitis flare. The coprimary outcomes were change in necroinflammation severity on the Knodell scale and change in fibrosis stage on the Ishak scale and were evaluated in the modified intention-to-treat population, which comprised all patients with paired liver biopsies. Safety was evaluated in all patients who were randomly assigned. This trial is registered at ClinicalTrials.gov, NCT01522625, and is completed.Findings: From Jan 30, 2012, to Nov 10, 2015, 875 patients were screened and 160 were randomly assigned to receive either tenofovir disoproxil fumarate (n=79) or placebo (n=81). The coprimary outcomes were assessed in 146 patients (73 in each group). Liver fibrosis progressed (an increase of ≥1 stage) in 19 (26%, 95% CI 17-38) of 73 patients in the tenofovir disoproxil fumarate group and in 34 (47%, 35-59) of 73 patients in the placebo group (relative risk [RR] 0·56, 95% CI 0·35-0·88; p=0·013), whereas necroinflammation progressed (an increase of ≥2 points) in five (7%, 95% CI 2-15) patients in the tenofovir disoproxil fumarate group and in 12 (16%, 9-27) patients in the placebo group (RR 0·42, 95% CI 0·15-1·12; p=0·084). Two (3%) of 79 patients in the tenofovir disoproxil fumarate group and 13 (16%) of 81 patients in the placebo group had acute hepatitis flare requiring add-on entecavir (RR 0·16, 95% CI 0·04-0·68; p=0·013). The two groups were otherwise similar in occurrences of adverse events. No patients died.Interpretation: Tenofovir disoproxil fumarate reduces the risk of progression in liver fibrosis in patients with chronic hepatitis B and minimally raised ALT, but its effect on necroinflammation is non-significant.Funding: The Taiwan Ministry of Science and Technology, E-Da Hospital, the Taipei Institute of Pathology, Gilead Sciences. [ABSTRACT FROM AUTHOR]

Abstract: Background: An increased risk of malignancy in patients with systemic lupus erythematosus has been reported, but rarely in Asian populations. We aimed to investigate the relative risk of cancer and to identify the high-risk group for cancer in patients with lupus. Methods: We conducted a retrospective, nationwide cohort study that included 11,763 patients with lupus without a history of malignancies, using the national health insurance database of Taiwan from 1996 to 2007. Standardized incidence ratios (SIRs) of cancers were analyzed. Results: A total of 259 cancers were observed in patients with lupus. An elevated risk of cancer among those with systemic lupus erythematosus was noted (SIR 1.76; 95% confidence interval [CI] 1.74-1.79), especially for hematologic malignancies (SIR 4.96; 95% CI 4.79-5.14). Younger patients had a greater risk ratio of cancer than the general population, and the risk ratio decreased with age. The risk ratio of cancer decreased with time, yet remained elevated compared with that of the general population. The risk of non-Hodgkin lymphoma was greatest (SIR 7.27) among hematologic cancers. Among solid tumors, the risk was greatest for cancers of the vagina/vulva (SIR 4.76), nasopharynx (SIR 4.18), and kidney (SIR 3.99). An elevated risk for less common cancers, including those of the brain, oropharynx, and thyroid glands, was also observed. Conclusion: Patients with lupus are at increased risk of cancers and should receive age- and gender-appropriate malignancy evaluations, with additional assessment for vulva/vagina, kidney, nasopharynx, and hematologic malignancy. Continued vigilance for development of cancers in follow-up is recommended. [Copyright &y& Elsevier]

Background: Vitiligo is reportedly associated with several ocular abnormalities. However, the relationship between vitiligo and retinal detachment (RD) remains unclear., Objectives: To examine the risk of RD in patients with vitiligo., Methods: A nationwide population-based cohort study was conducted using data from the Taiwan National Health Insurance Database from 2007 to 2018. A total of 21 132 patients with vitiligo were matched in a 1 : 4 ratio with people without vitiligo by age, sex and comorbidity propensity score. Cumulative incidence and Cox proportional hazard models were used to investigate the risk of RD in patients with vitiligo. Subgroup analysis was performed., Results: The cohort with vitiligo had a significantly higher rate of RD than the cohort without vitiligo [adjusted hazard ratio (aHR) 1.44, 95% confidence interval (CI) 1.20-1.72; P < 0.001]. Patients with vitiligo who required treatments such as phototherapy, systemic corticosteroids or immunosuppressants exhibited an even greater risk of RD (aHR 1.57, 95% CI 1.16-2.14; P = 0.004)., Conclusions: Our study revealed a 1.44-fold increased risk of RD in patients with vitiligo, with an even higher risk in patients receiving phototherapy, systemic corticosteroids or immunosuppressants. The risk remained consistently higher over a 10-year follow-up period., Competing Interests: Conflicts of interest The authors declare no conflicts of interest., (© The Author(s) 2024. Published by Oxford University Press on behalf of British Association of Dermatologists. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Background: Air pollutants may aggravate atopic dermatitis (AD). However, the association between Air Quality Index (AQI) and incidence of AD remains unknown., Objective: To investigate association between AQI and incidence of AD, using the nationwide cohort in the Taiwan National Health Insurance Research Database (NHIRD)., Methods: We included 21,278,938 participants from the NHIRD not diagnosed with AD before 2008. Long-term average AQI value, obtained from the Taiwan Air Quality Monitoring System Network, before AD diagnosis was calculated and linked for each participant., Results: 199,205 incident cases of AD were identified from 2008 to 2018. Participants were classified into 4 quantiles (Q) by AQI value. With the lowest quantile, Q1, as reference, the AD risk increased significantly in the Q2 group (adjusted hazard ratio [aHR]: 1.29, 95% confidence interval [CI]: 1.04-1.65), Q3 group (aHR: 4.71, 95% CI: 3.78-6.04), and was highest in the Q4 group (aHR: 13.20, 95% CI: 10.86-16.60). As AQI treated as a continuous variable, an increase of 1 unit of AQI value added 7% of AD risk (aHR, 1.07, 95% CI: 1.07-1.08)., Limitations: The NHIRD lacks detailed information on individual subjects., Conclusions: The results demonstrated a significant positive association between AQI and incidence of AD with a clear dose-response relationship., Competing Interests: Conflicts of interest None declared., (Copyright © 2024 American Academy of Dermatology, Inc. Published by Elsevier Inc. All rights reserved.)

Background: In the era of biologic therapy, phototherapy and methotrexate (MTX) are still commonly used for treatment in patients with moderate-to-severe psoriasis. However, the skin cancer risk following a combination of MTX and narrowband ultraviolet B (NB-UVB) has rarely been explored., Objectives: To investigate whether MTX plus NB-UVB increases skin cancer risk in patients with psoriasis., Methods: We conducted a retrospective cohort study of data in the Taiwan National Health Insurance Research Database from 1997 to 2013. Cumulative incidences and multivariate analysis were investigated using a competing risk regression model, comparing skin cancer risk between cohorts of people having combination therapy and those using NB-UVB alone, matched for relative confounders. We further conducted a sensitivity analysis for those receiving a higher MTX dose. Standardized incidence ratios (SIRs) were calculated for skin cancer risk., Results: We enrolled 3203 participants in each cohort. No significant differences in skin cancers were noted between the two cohorts for the cumulative incidences (log-rank test, P = 0.28) and for the hazard ratio (HRs) [adjusted HR 0.50, 95% confidence interval (CI) 0.15-1.63, P = 0.247] in the competing risk regression model. There were also no significant differences between those receiving higher-dose MTX and UVB alone in the cumulative incidences of skin cancers (P = 0.23) and the HR (adjusted HR = 0.29, 95% CI 0.04-2.21, P = 0.23) in the multivariate analysis. There was no significant difference in the SIR between the two cohorts compared with the general population., Conclusions: In the Taiwanese population, MTX does not increase skin cancer risk in patients with moderate-to-severe psoriasis receiving NB-UVB., Competing Interests: Conflicts of interest The authors declare no conflicts of interest., (© The Author(s) 2023. Published by Oxford University Press on behalf of British Association of Dermatologists.)

Psoriasis can affect individuals of all age groups. While the epidemiology of psoriasis in adults has been extensively studied, there is limited research specifically investigating pediatric cases. This study aimed to investigate the prevalence and incidence of skin psoriasis (PsO) and psoriatic arthritis (PsA) among pediatric patients in Taiwan. A nationwide cohort of 17 535 patients with psoriatic diseases under the age of 18 was enrolled from the National Health Insurance Research Database for the period 2000-2013, including 16 129 PsO patients and 2022 PsA patients. The age- and sex-standardized prevalence and incidence of pediatric PsO and PsA were calculated. The 2007 yearly reports of age- and sex-specific distribution of the general population was adopted as a standard. The results showed that between 2000 and 2013, the prevalence for pediatric PsO increased from 0.03% to 0.07%, and from 0.003% to 0.014% for pediatric PsA. During the same period, the incidence slightly decreased from 19.81 to 17.55 per 100 000 for pediatric PsO but increased from 1.02 to 5.06 per 100 000 for pediatric PsA. Adolescents (12 to <18 years) had higher prevalence and incidence rates of PsO and PsA than children (aged ≤ 12 years), with no sex difference observed in either age group. PsA preceding PsO was more common among children than adolescents (27.07% vs. 13.46%). This study provides important insights into the prevalence and incidence of psoriatic diseases in the pediatric population. Further research is needed to identify risk factors for pediatric psoriasis and to investigate its long-term health outcomes., (© 2023 Japanese Dermatological Association.)

Importance: The incidence of inflammatory bowel disease (IBD) is increasing in newly industrialized countries but disease etiologies remain unclear., Objective: To investigate the association between physical fitness and subsequent IBD risk among children and adolescents in Taiwan., Design, Setting, and Participants: This nationwide cohort study was conducted between January 1, 2010, and December 31, 2018. Data sources included the Taiwan National Health Insurance Research Database, the National Student Fitness Tests Database, and the Air Quality Monitoring System Database. This study included students who were aged 10 years, completed physical fitness tests between grades 4 and 13, and had at least 1 year of follow-up. Data analysis was last performed on January 15, 2023., Exposures: Physical fitness tests included cardiorespiratory endurance (CE; number of minutes to complete an 800-m run), musculoskeletal endurance (ME; number of bent-leg curl-ups in 1 minute), musculoskeletal power (MP; standing broad jump distance), and flexibility fitness (FF; 2-leg sit-and-reach distance)., Main Outcomes and Measures: Subsequent risk of IBD was compared among students based on physical fitness test results. Six-year cumulative incidences and hazard ratios (HRs) were calculated after adjusting for competing mortality. Performance was reported in quantiles, ranging from 1 (best) to 4 (poorest)., Results: There were 4 552 866 students who completed physical fitness tests between grades 4 and 13; among these students, 1 393 641 were aged 10 years and were included in the analysis. Six-year cumulative incidence of IBD risk was lowest among students in the best-performing quantile of CE (quantile 1, 0.74% [95% CI, 0.63%-0.86%]; P < .001), ME (0.77% [0.65%-0.90%]; P < .001), and MP (0.81% [0.68%-0.93%]; P = .005) compared with students in quantiles 2 through 4, respectively; however, no association was observed for quantiles of FF. After adjusting for competing HRs for mortality and other confounders, better CE was inversely associated with IBD risk (adjusted HR, 0.36 [95% CI, 0.17-0.75]; P = .007). Other measures of physical fitness were not independently associated with IBD risk., Conclusions and Relevance: The results of this study suggest that CE was inversely associated with IBD risk among children and adolescents, but ME, MP, and FF were not independently associated with IBD risk. Future studies that explore the mechanisms are needed.

Background: Up to 25% of patients with cutaneous lupus erythematosus (CLE) can develop systemic lupus erythematosus (SLE). However, the risk of autoimmune diseases other than SLE in CLE patients who have only skin manifestations (CLE-alone) has rarely been explored., Objective: To investigate the long-term risk and independent factors of non-SLE autoimmune diseases among CLE-alone patients., Method: A nationwide cohort study using the Taiwanese National Health Insurance Research Database 1997-2013. CLE patients and matched subjects were included. Cumulative incidences of autoimmune diseases after 1 year of CLE-alone diagnosis were compared. Cox proportional hazard model was also performed., Results: A total of 971 CLE-alone patients and 5,175 reference subjects were identified. The 10-year cumulative incidence of autoimmune diseases other than SLE was significantly elevated in the CLE-alone cohort (9.00%, 95% confidence interval [CI] 6.72-11.29) than in the reference cohort (4.20%, 95% CI 3.53-4.87%) (p < 0.001). CLE-alone was independently associated with non-SLE autoimmune diseases (adjusted hazard ratio 1.55, 95% CI 1.10-2.18). Among CLE-alone patients, females and those taking long-term systemic corticosteroids (a proxy for extensive disease) were associated with non-SLE autoimmune diseases after adjusting for the number of repeated autoimmune laboratory tests., Conclusion: CLE-alone is independently associated with future non-SLE autoimmune diseases., (© 2021 S. Karger AG, Basel.)

Background: The risk of osteoporosis has been explored in atopic dermatitis (AD). The long-term risk of fractures in patients with AD and the effects of various AD treatments on bone health remain to be elucidated., Objective: To evaluate the long-term risk of fractures in patients with AD., Methods: This nationwide matched cohort study was conducted using the National Health Insurance Research Database of Taiwan for the period 1997 to 2013. A total of 36,855 patients with AD and 147,420 reference subjects without AD were identified. Demographic characteristics and comorbidities were compared, and cumulative incidence of fractures was evaluated. Adjusted hazard ratios for fracture risks of AD and various AD treatments were calculated using the Cox proportional hazards model., Results: A total of 1518 patients (4.12%) in the AD cohort and 5579 patients (3.78%) in the reference cohort had fractures (P = .003). The mean ages were 22.6 years in both groups. The 16-year cumulative incidence of fractures in the AD cohort (8.043%) was significantly higher than that in the reference cohort (7.366%) (P = .002). Severe AD (adjusted hazard ratio [aHR], 1.31; 95% confidence interval [CI], 1.08-1.59) was independently associated with fractures. Other independent risk factors included exposure to topical (aHR, 1.21; 95% CI, 1.05-1.39) or systemic (≥10 mg/d; aHR, 1.62; 95% CI, 1.38-1.91) corticosteroids. Use of disease-modifying antirheumatic drugs (aHR, 0.71; 95% CI, 0.53-0.90) and phototherapy (aHR, 0.73; 95% CI, 0.56-0.95) was associated with a lower risk of fractures. The results were consistent across sensitivity analyses., Conclusion: Patients with AD have a higher incidence of fractures. Severe AD is independently associated with fractures., (Copyright © 2021 American College of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)

Background: Microbiol dysbiosis and antibiotic exposure have been implicated in the pathogenesis of pediatric inflammatory diseases., Objectives: To investigate the impacts of infantile infection and antibiotic exposure on pediatric psoriasis development., Methods: This is a nationwide nested case-control study. From the National Health Insurance Research Database of Taiwan, a total of 1527 patients with pediatric psoriasis were identified and matched with 15,270 reference individuals without psoriasis, for the period of 2000 to 2017. Demographic characteristics and comorbidities were compared. Conditional stepwise logistic regression analysis was conducted to examine the associations., Results: The mean ages were 9.9 ± 3.7 years in both groups. Atopic dermatitis (adjusted odds ratio [aOR], 2.07; 95% confidence interval [CI], 1.84-2.32) and family history of psoriasis, especially of the mother (aOR, 9.86; 95% CI, 6.89-14.10) or other first-degree relatives (aOR, 5.49; 95% CI, 3.91-7.70), were independently associated with pediatric psoriasis on multivariate analyses. Skin viral and bacterial infections (aOR, 1.35; 95% CI, 1.13-1.62) and fungal infections (aOR, 1.71; 95% CI, 1.44-2.04) in the first 2 years of life were significantly associated with pediatric psoriasis. Systemic antibiotic exposure was not. These results were consistent at different time periods across sensitivity analyses., Limitation: Information about diet and lifestyle was not available., Conclusion: Skin infections at an early age were associated with pediatric psoriasis development., Competing Interests: Conflicts of interest None disclosed., (Copyright © 2020 American Academy of Dermatology, Inc. Published by Elsevier Inc. All rights reserved.)

Coexistence of inflammatory bowel disease (IBD) in atopic dermatitis (AD) patients has been reported. The long-term risk of IBD in AD patients remains unclear. Our aim for the study is to examine the long-term risk of IBD in AD patients. This is a nationwide cohort study. From the National Health Insurance Research Database of Taiwan (1997-2013), a total of 36 400 AD patients were identified and matched with 364 000 reference subjects without AD by age, sex and number of hospital visits. Demographic characteristics and comorbidities were compared. Cox proportional hazards regression analysis was conducted to examine the risk of IBD. The 16-year cumulative incidences of IBD were 0.047% (95% confidence interval [CI], 0.040-0.054) and 0.047% (95% CI, 0.025-0.096) in non-AD and AD cohorts, respectively (P = 0.973). There were 17 cases of IBD (0.05%), including 10 ulcerative colitis and seven Crohn's disease, among AD patients compared with 169 IBD cases (0.05%) among controls (P > 0.999). Infections (adjusted hazard ratio [HR], 2.71; 95% CI, 1.96-3.95; P < 0.001) and age (adjusted HR, 1.03; 95% CI, 1.02-1.03; P < 0.001) were independently associated with IBD, after adjusting for major comorbidities and conducting multivariate analyses. AD was not associated with IBD development. In conclusion, AD is not independently associated with IBD development., (© 2020 Japanese Dermatological Association.)

The coexistence of inflammatory bowel disease (IBD) and bullous pemphigoid (BP) has been reported. No large-scale study to date has explored the relationship between these diseases. This population-based case-control study examined the association between IBD and BP by using a nationwide database. A total of 5,263 BP patients and 21,052 age- and gender-, hospital visit number-matched controls were identified in the National Health Insurance Research Database of Taiwan (1997-2013). Demographic characteristics and comorbidities including IBD were compared. Logistic regression was conducted to examine the predicting factors for BP. The mean age at diagnosis was 74.88 years and 54.3% of subjects were male. BP patients tended to have more cardiovascular risk factors, autoimmune and neurologic comorbidities, and hematologic cancers than matched controls. There were 20 cases of IBD (0.38%), mostly ulcerative colitis (N = 17, 0.32%) among BP patients, compared to 33 IBD cases (0.16%) among controls (p < 0.001). Ulcerative colitis was found to be significantly associated with BP [adjusted odds ratio (OR) 3.60, 95% confidence interval (CI) 1.91-6.77, p < 0.001] on multivariate analysis. Treatment for IBD was not associated with BP development. Information about diet, lifestyle, alcohol consumption, and smoking habit was not available. We concluded that UC is independently associated with BP.

Background: Narrowband ultraviolet B (NB-UVB) phototherapy is a widely used treatment for various dermatoses. The risk of skin cancer following long-term NB-UVB phototherapy has rarely been explored in skin phototypes III-V., Methods: We conducted a nationwide-matched cohort study and identified a total of 22 891 psoriasis patients starting NB-UVB phototherapy from the Taiwan National Health Insurance Database during the period 2000-2013. Cumulative incidences of skin cancers were compared between subjects receiving less than 90 UVB treatments (S-cohort, N = 13 260) and age- as well as propensity score-matched subjects receiving more than or equal to 90 UVB treatments (L-cohort, N = 3315)., Results: There were no significant differences in the overall cumulative incidences of skin cancers between the two cohorts (log-rank t test, P = 0.691) during the follow-up periods. The S-cohort had a significantly lower prevalence of actinic keratosis when compared with the L-cohort (0.54% vs 1.00%, P = 0.005)., Conclusion: Long-term NB-UVB phototherapy does not increase skin cancer risk compared with short-term NB-UVB phototherapy in psoriasis patients with skin phototypes III-V., (© 2018 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Importance: Antiviral therapy cannot erase hepatocellular carcinoma (HCC) risk in patients with chronic hepatitis B, and it is not indicated for most hepatitis B virus (HBV) carriers. Another effective way of reducing HCC risk needs to be developed. Aspirin may prevent cancer development, but clinical evidence in patients with HBV-related HCC remains limited., Objective: To investigate the association of daily aspirin therapy with HBV-related HCC risk., Design, Setting, and Participants: In this Taiwan nationwide cohort study, we screened 204 507 patients with chronic hepatitis B for the period January 1, 1997, to December 31, 2012. After excluding patients with confounding conditions, 2123 patients who continuously received daily aspirin for 90 or more days (treated group) were randomly matched 1:4 with 8492 patients who had never received antiplatelet therapy (untreated group) by means of propensity scores, consisting of the follow-up index date, baseline characteristics, and potentially chemopreventive drug use during follow-up. Data were analyzed from August 1 to November 30, 2018., Exposures: Daily aspirin therapy during the study period., Main Outcomes and Measures: Both cumulative incidence of and hazard ratios (HRs) for HCC development were analyzed after adjusting patient mortality as a competing risk event., Results: Of the 10 615 patients included in the analysis, 7690 (72.4%) were men; mean (SD) age was 58.8 (11.8) years. The cumulative incidence of HCC in the treated group was significantly lower than that in the untreated group in 5 years (5.20%; 95% CI, 4.11%-6.29% vs 7.87%; 95% CI, 7.15%-8.60%; P < .001). In the multivariable regression analysis, aspirin therapy was independently associated with a reduced HCC risk (HR, 0.71; 95% CI, 0.58-0.86; P < .001). Sensitivity subgroup analyses also verified this association (all HRs <1.0). In addition, older age (HR, 1.01 per year; 95% CI, 1.00-1.02), male sex (HR, 1.75; 95% CI, 1.43-2.14), and cirrhosis (HR, 2.89; 95% CI, 2.45-3.40) were independently associated with an increased HCC risk, but nucleos(t)ide analogue (HR, 0.54; 95% CI, 0.41-0.71) or statin (HR, 0.62; 95% CI, 0.42-0.90) use was correlated with a decreased HCC risk., Conclusions and Relevance: Daily aspirin therapy may be associated with a reduced risk of HBV-related HCC.

Background: A consensus on the management of Helicobacter pylori has been developed. We aimed to assess whether dissemination through continuing medical education (CME) could enhance the adoption of this consensus among clinicians and to explore potential barriers to acceptance., Materials and Methods: Four CME courses were held to disseminate the consensus. Adoption surveys were performed to evaluate participants' behavior in the past and their commitment to adopt the consensus in future clinical practice after CME. The gaps and barriers to adoption were also surveyed., Results: A total of 240 physicians had attended the CME courses and received surveys with the 22 statements/substatements of the consensus. Before CME, adoption was good in six, fair in ten, and poor in six. After CME, 21 statements had either an initial >90% adoption or improvement to good or fair (P < 0.001), but one still had poor even though it showed improvement (P = 0.02). Although commitment was good or fair after CME, there was a >20% gap between "commitment" and "no barrier" to adoption for 11 statements, ten of which had a main barrier of financial incentives. Among the statements with fair or poor commitment after CME, less commitment to adoption and more barriers related to financial incentives were pronounced in clinicians serving in regional/district hospitals or clinics compared to those serving in medical centers., Conclusions: Continuing medical education may improve the adoption of the H. pylori consensus. The financial incentives were shown to be a main barrier to adoption of the consensus and should be improved., (© 2018 John Wiley & Sons Ltd.)

Background & Aims: The risk of hepatocellular carcinoma (HCC) during antiviral therapy in patients with chronic hepatitis B (CHB) is inadequately predicted by the scores built from untreated patients. We aimed at developing and validating a risk score to predict HCC in patients with CHB on entecavir or tenofovir treatment., Methods: This study analysed population-wide data from the healthcare databases in Taiwan and Hong Kong to identify patients with CHB continuously receiving entecavir or tenofovir. The development cohort included 23,851 patients from Taiwan; 596 (2.50%) of them developed HCC with a three-year cumulative incidence of 3.56% (95% CI 3.26-3.86%). The multivariable Cox proportional hazards model found that cirrhosis, age (cirrhosis and age interacted with each other), male sex, and diabetes mellitus were the risk determinants. These variables were weighted to develop the cirrhosis, age, male sex, and diabetes mellitus (CAMD) score ranging from 0 to 19 points. The score was externally validated in 19,321 patients from Hong Kong., Results: The c indices for HCC in the development cohort were 0.83 (95% CI 0.81-0.84), 0.82 (95% CI 0.81-0.84), and 0.82 (95% CI 0.80-0.83) at the first, second, and third years of therapy, respectively. In the validation cohort, the c indices were 0.74 (95% CI 0.71-0.77), 0.75 (95% CI 0.73-0.78), and 0.75 (95% CI 0.72-0.77) during the first three years, and 0.76 (95% CI 0.74-0.78) and 0.76 (95% CI 0.74-0.77) in the extrapolated fourth and fifth years, respectively. The predicted and observed probabilities of HCC were calibrated in both cohorts. A score <8 and >13 points identified patients at distinctly low and high risks., Conclusions: The easily calculable CAMD score can predict HCC and may inform surveillance policy in patients with CHB during oral antiviral therapy., Lay Summary: This study analyses population-wide data from the healthcare systems in Taiwan and Hong Kong to develop and validate a risk score that predicts hepatocellular carcinoma during oral antiviral therapy in patients with chronic hepatitis B. The easily calculable CAMD score requires only simple information (i.e. cirrhosis, age, male sex, and diabetes mellitus) at the baseline of treatment initiation. With a scoring range from 0 to 19 points, the CAMD score discriminates the risk of hepatocellular carcinoma with a concordance rate of around 75-80% during the first three years on therapy. The risk prediction can be extrapolated to five years on treatment with similar accuracy. Patients with a score <8 and >13 points were exposed to distinctly lower and higher risks, respectively., (Copyright © 2018 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.)

Background & Aims: Chronic infection with hepatitis B virus (HBV) increases risk of intrahepatic cholangiocarcinoma (ICC), but it is not clear whether antiviral therapy reduces risk. We investigated the association between nucleos(t)ide analogue therapy and ICC risk., Methods: We performed a nationwide long-term cohort study using Taiwan's National Health Insurance Research Database to obtain data on 185,843 patients with chronic HBV infection from October 1, 2003 through December 31, 2012. We excluded patients with confounding disorders such as infection with hepatitis C virus, HIV, or other hepatitis-associated viruses; liver flukes; biliary stone diseases; cholangitis; congenital biliary anomalies; biliary tract surgeries; or cancer. We identified 10,062 patients who received nucleos(t)ide analogue therapy (the treated group), and used propensity scores to match them (1:1) with patients who received hepatoprotectants (the untreated group). Cumulative incidences of and hazard ratios (HRs) for ICC development were analyzed., Results: The cumulative incidence of ICC was significantly lower in the treated group after 3 years of therapy (1.28%; 95% CI, 0.56-2.01) than in the untreated group (3.14%; 95% CI, 2.02-4.27) and after 5 years of therapy (1.53%; 95% CI, 0.73-2.33 vs 4.32% in untreated group; 95% CI, 2.96-5.6869). In multivariable regression analysis, nucleos(t)ide analogue therapy was independently associated with a reduced risk of ICC (HR, 0.44; 95% CI, 0.25-0.78; P = .005). Older age (HR 1.05 per year; 95% CI, 1.03-1.07) and cirrhosis (HR, 2.80; 95% CI, 1.52-5.1415) were independently associated with an increased risk of ICC. Sensitivity analyses verified the association between nucleos(t)ide analogue therapy and a reduced ICC risk., Conclusion: A nationwide long-term cohort study in Taiwan showed that nucleos(t)ide analogue therapy for chronic HBV infection is significantly associated with a reduced ICC risk., (Copyright © 2018 AGA Institute. Published by Elsevier Inc. All rights reserved.)

Nonalcoholic fatty liver disease (NAFLD) may be a cause of hepatocellular carcinoma (HCC), but its high prevalence challenges current surveillance strategies. We aimed to evaluate HCC incidences in different risk stratifications for noncirrhotic NAFLD. Using Taiwan's National Health Insurance Research Database, we located 31,571 patients with NAFLD between the years 1998 and 2012. After excluding other causes of hepatitis, underlying cirrhosis or malignancy, 18,080 patients were recruited for final analysis. Cumulative incidences of HCC were analyzed after adjusting for competing mortality. With a median follow-up duration of 6.32 years in the study cohort, the 10-year cumulative incidence of HCC was 2.73% [95% confidence interval (CI): 1.69-3.76%]. Hepatoprotectant was used as a surrogate marker for elevated serum alanine transaminase (ALT). After adjusting for age, gender, hypertension, hypercholesterolemia, diabetes mellitus, gout, statin use, metformin use and aspirin use, elevated ALT was independently associated with an increased HCC risk [hazard ratio (HR) 6.80, 95% CI: 3.00-15.42; p < 0.001]. Multivariate stratified analysis verified this association in all subgroups (HR> 1.0). Moreover, increased age (HR 1.08 per year, 95% CI: 1.05-1.11) and statin use (HR 0.29, 95% CI: 0.12-0.68) were also identified as independent risk factors. The 10-year cumulative HCC incidence was highest in older (age >55 years) patients with ALT elevation (12.41%, 95% CI: 5.99-18.83%), but lowest in younger patients without ALT elevation (0.36%, 95% CI: 0-1.08%). The incidence of HCC was relatively low in patients with clinically noncirrhotic NAFLD, however, HCC risk was significantly increased in older patients experiencing an elevated serum ALT., (© 2017 UICC.)

Importance: Allopurinol, a first-line drug used for treating gout, is increasingly prescribed worldwide to patients with asymptomatic hyperuricemia and comorbid renal or cardiovascular diseases. Nevertheless, allopurinol use has been associated with fatal hypersensitivity reactions, including drug rash with eosinophilia and systemic symptoms, Stevens-Johnson syndrome, and toxic epidermal necrolysis. The overall risks of allopurinol use remain unclear., Objective: To investigate the incidence of, risk factors for, and mortality associated with allopurinol hypersensitivity in new users of allopurinol., Design, Setting, and Participants: A retrospective nationwide population study was conducted using data from the Taiwan National Health Insurance Research Database, which includes detailed medical records of more than 23 million insured enrollees. Data were collected from January 1, 2005, through December 31, 2011, using the Anatomical Therapeutic Chemical classification system and International Classification of Diseases, Ninth Revision, Clinical Modification codes. Among 1,613,719 patients receiving allopurinol prescriptions, 495,863 were identified as new users., Main Outcomes and Measures: Allopurinol hypersensitivity was identified within 3 months since the first prescription. The period for measuring related hospitalizations was 1 month since the episode, and the period for measuring renal complications or mortality was 2 months since the episode. Poisson regression test and multivariable logistic regression analysis were performed, and P < .01 was considered statistically significant., Results: Among the more than 23 million insured enrollees, the annual incidence rates were 4.68 per 1000 new users for allopurinol hypersensitivity, 2.02 per 1000 new users for related hospitalization, and 0.39 per 1000 new users for related mortality. The annual incidence of allopurinol hypersensitivity rose statistically significantly during the study period (P < .001). Risk factors for allopurinol hypersensitivity included female sex, age 60 years or older, initial allopurinol dosage exceeding 100 mg/d, renal or cardiovascular comorbidities, and use for treating asymptomatic hyperuricemia. Patients with asymptomatic hyperuricemia and renal or cardiovascular diseases had statistically significantly increased risk of allopurinol hypersensitivity (odds ratio [OR], 1.61; 95% CI, 1.33-1.94; P < .001 for renal diseases and OR, 1.52; 95% CI, 1.19-1.93; P < .001 for cardiovascular diseases). They also had statistically significantly increased risk of mortality (OR, 5.59; 95% CI, 2.61-11.94; P < .001 for renal diseases and OR, 3.57; 95% CI, 2.31-5.51; P < .001 for cardiovascular diseases)., Conclusions and Relevance: The use of allopurinol in patients with asymptomatic hyperuricemia accompanied by renal or cardiovascular diseases statistically significantly increased the risk of hypersensitivity reactions. Physicians should be cautious when prescribing allopurinol to high-risk populations and should consider the potential risks of fatal adverse reactions.

Objective: The Taiwan Government issued a policy to restrict antimicrobial usage since 2001. We aimed to assess the changes in the antibiotic consumption and the primary resistance of H. pylori after this policy and the impact of virulence factors on resistance., Methods: The defined daily dose (DDD) of antibiotics was analyzed using the Taiwan National Health Insurance (NHI) research database. H. pylori strains isolated from treatment naïve (N=1395) and failure from prior eradication therapies (N=360) from 9 hospitals between 2000 and 2012 were used for analysis. The minimum inhibitory concentration was determined by agar dilution test. Genotyping for CagA and VacA was determined by PCR method., Results: The DDD per 1000 persons per day of macrolides reduced from 1.12 in 1997 to 0.19 in 2008, whereas that of fluoroquinolones increased from 0.12 in 1997 to 0.35 in 2008. The primary resistance of amoxicillin, clarithromycin, metronidazole, and tetracycline remained as low as 2.2%, 7.9%, 23.7%, and 1.9% respectively. However, the primary levofloxacin resistance rose from 4.9% in 2000-2007 to 8.3% in 2008-2010 and 13.4% in 2011-2012 (p=0.001). The primary resistance of metronidazole was higher in females than males (33.1% vs. 18.8%, p<0.001), which was probably attributed to the higher consumption of nitroimidazole. Neither CagA nor VacA was associated with antibiotic resistance., Conclusions: The low primary clarithromycin and metronidazole resistance of H. pylori in Taiwan might be attributed to the reduced consumption of macrolides and nitroimidazole after the national policy to restrict antimicrobial usage. Yet, further strategies are needed to restrict the consumption of fluoroquinolones in the face of rising levofloxacin resistance.

Purpose: The efficacy of nonsteroidal anti-inflammatory drugs (NSAIDs) in reducing the risk of various de novo cancers has been reported; however, its role in reducing hepatocellular carcinoma (HCC) recurrence after liver resection still remains unknown., Methods: We have conducted a nationwide cohort study by recruiting all patients with a newly diagnosed HCC who had received curative liver resection as their initial treatment. The use of NSAIDs and the risk of early HCC recurrence have been examined by multivariate and stratified analyses. To avoid immortal time bias, the use of NSAIDs has been treated as a time-dependent variable in Cox proportional hazard ratio models., Results: Between January 1997 and December 2010, a total of 15,574 HCC patients who had received liver resection were enrolled in this study. The 1-, 3-, and 5-year overall survival rates were 90.4%, 73.2%, and 59.8%, respectively. The 1-, 3-, and 5-year disease-free survival rates were 80.5%, 59.4%, and 50.2%, respectively. NSAID use (hazard ratio, 0.81; 95% confidence interval, 0.73-0.90) and minor liver resection (hazard ratio, 0.83; 95% confidence interval, 0.78-0.89) were independently associated with a reduced risk of early HCC recurrence after liver resection. In the stratified analyses, NSAID usage was universally associated with reduced risks in most subgroups, particularly for those aged younger than 65 years, male, with underlying diabetes mellitus and receiving major liver resection., Conclusions: The use of NSAIDs can be associated with a reduced risk of early HCC recurrence within 2 years after curative liver resection, regardless of patients' age, extent of liver resection, viral hepatitis status, underlying diabetes, and liver cirrhosis.

Background & Aims: Patients with gastric ulcers have significantly higher risk of gastric cancer, especially within 2 years after diagnosis. We used data from a national database to develop a personalized risk prediction model for patients with peptic ulcer diseases., Methods: We collected data from Taiwan's National Health Insurance Research Database on 278,898 patients admitted for the first time with a primary diagnosis of peptic ulcer disease. We used the data to develop a nomogram, which we validated by discrimination and calibration, and in a test cohort. Cumulative incidences of study subjects predicted by the nomogram were examined., Results: In total, 1269 subjects developed gastric cancer. Age, sex, peptic ulcer sites, peptic ulcer complications, Helicobacter pylori eradication, nonsteroidal anti-inflammatory drug use, and surveillance endoscopy were independent factors associated with risk of gastric cancer (all P < .001). The concordance index for the nomogram developed on the basis of these factors was 0.78. Study subjects were divided into quartiles of predicted risk scores; from lowest score quartile to highest, cumulative incidences at 1 year were 7.4/10,000 people, 14.2/10,000 people, 25.5/10,000 people, and 86.6/10,000 people. The cumulative incidences at 2 years were 9.3/10,000 people, 20.9/10,000 people, 38.0/10,000 people, and 135.7/10,000 people for the same quartiles of risk scores. The nomogram was validated in an independent cohort, and similar incidence values were determined., Conclusions: We developed and validated a nomogram to predict risk for gastric cancer 1 and 2 years after diagnosis of peptic ulcer disease. The nomogram provides a prognostic tool that can be easily used for individuals and can help physicians explain risk levels to patients., (Copyright © 2015 AGA Institute. Published by Elsevier Inc. All rights reserved.)

Background: The risk of psoriasis in diabetic patients has rarely been explored., Objectives: We sought to investigate the association between antidiabetic therapies and psoriasis., Methods: The incidence of psoriasis was compared between a representative diabetic cohort and a matched nondiabetic cohort. We next conducted a nationwide cohort study with 1,659,727 diabetic patients using the National Health Insurance Research Database of Taiwan 1997 through 2011. Multivariate conditional logistic regression was used for nested case-control analyses., Results: Incidence rates of psoriasis among diabetic patients and nondiabetic matched control subjects were 70.2 (95% confidence interval [CI] 59.5-80.9) and 42.3 (95% CI 39.5-45.5) per 100,000 person-years, respectively (P < .0001). Frequent insulin use was associated with higher risk of incident psoriasis (adjusted odds ratio 1.29, 95% CI 1.18-1.42) after adjusting for comorbidities, disease duration, and number of hospital visits. Among diabetic patients without history of insulin use, frequent use of thiazolidinedione was associated with lower risk of psoriasis (adjusted odds ratio 0.87, 95% CI 0.77-0.99)., Limitations: The National Health Insurance Research Database did not contain information regarding disease severity, diet, body mass index, lifestyle, or family history., Conclusion: Among diabetic patients, regular insulin use is associated with psoriasis development. Frequent use of thiazolidinedione may be associated with modest reduction in psoriasis risk., (Copyright © 2014 American Academy of Dermatology, Inc. Published by Elsevier Inc. All rights reserved.)

Introduction: The association between cancer and use of biologic therapy among rheumatoid arthritis (RA) patients remains controversial. We aimed to compare the relative risk of cancer development between RA patients taking tumor necrosis factor α (TNFα) antagonists and those taking nonbiologic disease-modifying anti-rheumatic drugs (nbDMARDs)., Methods: We conducted a nationwide cohort study between 1997 and 2011 using the Taiwan National Health Insurance Research Database. The risk of newly diagnosed cancer was compared between patients starting TNF-α antagonists (biologics cohort) and matched subjects taking nbDMARDs only (nbDMARDs cohort). Cumulative incidences and hazard ratios (HR) were calculated after adjusting for competing mortality. Standardized incidence ratio (SIR) was calculated for cancer risk. Multivariate analyses were performed using Cox proportional hazards model., Results: We compared 4426 new users of TNF-α antagonists and 17704 users of nbDMARDs with similar baseline covariate characteristics. The incidence rates of cancer among biologics and nbDMARDs cohorts were 5.35 (95% confidence interval (CI) 4.23 to 6.46) and 7.41 (95% CI 6.75 to 8.07) per 1000 person-years, respectively. On modified Cox proportional hazards analysis, the risk of cancer was significantly reduced in subjects in biologics cohort (adjusted HR 0.63, 95% CI 0.49 to 0.80, P < .001), after adjusting for age, gender, disease duration, major co-morbidities, and prior use of DMARDs and corticosteroids. However, there was an increased risk for hematologic cancers in biologics cohort, yet without statistical significance. The effect of biologics was consistent across all multivariate stratified analyses and the association between biologics use and cancer risk was independent of dosage of concomitant nbDMARDs., Conclusion: These findings suggested that RA patients taking TNF-α antagonist are associated with a lower risk of cancer, but not for hematologic cancers, than RA patients taking nbDMARDs alone.

Aim: To evaluate the associations of serum folate level with development, invasiveness and patient survival of gastric cancer., Methods: In this nested case-control study, patients with newly diagnosed gastric cancer undergoing gastrectomy were enrolled, and patients receiving chemotherapy prior to surgery, with other concurrent malignancy, or of the aboriginal and alien populations were excluded. In total, 155 gastric cancer patients and 149 healthy controls were enrolled for determination of serum folate levels and their correlation with gastric cancer. Using the median value of serum folate computed among the overall population as the cutoff value, the associations between serum folate and gastric cancer in all cases and different age and gender subgroups were analyzed by multivariate logistic regression analysis. In the patient cohort of gastric cancer, receiver-operating characteristic analyses were performed to calculate the best cutoff values of serum folate, and the associations between serum folate levels and clinicopathological features were further analyzed by multivariate regression analysis. Survival analyses were conducted using the Cox proportional hazards model., Results: The mean serum folate level was significantly lower in gastric cancer patients than that in controls (3.71 ± 0.30 ng/mL vs 8.00 ± 0.54 ng/mL, P < 0.01), and folate levels were consistently lower in gastric cancer patients regardless of age and gender (all P < 0.01). Using the median serum folate value as the cutoff value, low serum folate was significantly associated with gastric cancer risk in the whole population (OR = 19.77, 95%CI: 10.54-37.06, P < 0.001) and all strata (age < 60 years OR = 17.39, 95%CI: 7.28-41.54, age ≥ 60 years (OR = 21.67, 95%CI: 8.27-56.80), males (OR = 17.95, 95%CI: 7.93-40.62), and females (OR = 20.95, 95%CI: 7.66-57.31); all P < 0.001. In the patient cohort of gastric cancer, the respective cutoff values showed that low serum folate levels were significantly associated with serosal invasion (OR = 2.54, 95%CI: 1.23-5.23), lymphatic invasion (OR = 2.23, 95%CI: 1.17-4.26), and liver metastasis (OR = 6.67, 95%CI: 1.28-34.91) of gastric cancer (all P < 0.05). Serum folate level below 1.90 ng/mL was associated with poor patient survival (HR = 1.84, 95%CI: 1.04-3.27, P < 0.05) in univariate analysis., Conclusion: Lower serum folate levels were significantly associated with gastric cancer development and invasive phenotypes. The role of folate depletion in gastric cancer invasion warrants further study.

Background & Aims: Treatment for hepatitis B virus infection reduces the risk of hepatocellular carcinoma (HCC). However, the long-term protective effects for subgroups of patients with chronic hepatitis B are unclear., Methods: We conducted a retrospective nationwide cohort study using data from Taiwan's National Health Insurance Research Database (from January 1, 1997, through December 31, 2010). Cumulative incidences were calculated and multivariable analyses were carried out after adjusting for competing mortality. Propensity scores were used to match 21,595 patients with chronic hepatitis B who received nucleoside analogue therapy for at least 90 days (treated cohort) with 21,595 untreated patients with chronic hepatitis B (controls), who received hepatoprotectants for at least 90 days. Data were collected from the treated cohort for a mean period of 3.46 years and from controls for 5.24 years., Results: The treated cohort had a significantly lower 7-year incidence of HCC (7.32%; 95% confidence interval [CI], 6.77%-7.87%) than controls (22.7%; 95% CI, 22.1%-23.3%; P < .001). After adjusting for competing mortality and other confounders, nucleos(t)ide analogue treatment was associated with a reduced risk of HCC, with an adjusted hazard ratio of 0.37 (95% CI, 0.34-0.39; P < .001). Sensitivity analyses confirmed the association between nucleos(t)ide analogue treatment and reduced risk of HCC. Age, sex, cirrhosis, and diabetes mellitus modified this association., Conclusions: Based on a retrospective, nationwide study in Taiwan, nucleoside analogue therapy use is associated with reduced risk of HCC in patients with chronic hepatitis B virus infection., (Copyright © 2014 AGA Institute. Published by Elsevier Inc. All rights reserved.)

Background and Aims: To compose upper gastrointestinal bleeding (UGIB) consensus from a nationwide scale to improve the control of UGIB, especially for the high-risk comorbidity group., Methods: The steering committee defined the consensus scope to cover preendoscopy, endoscopy, postendoscopy, and overview from Taiwan National Health Insurance Research Database (NHIRD) assessments for UGIB. The expert group comprised thirty-two Taiwan experts of UGIB to conduct the consensus conference by a modified Delphi process through two separate iterations to modify the draft statements and to vote anonymously to reach consensus with an agreement ≥80% for each statement and to set the recommendation grade., Results: The consensus included 17 statements to highlight that patients with comorbidities, including liver cirrhosis, end-stage renal disease, probable chronic obstructive pulmonary disease, and diabetes, are at high risk of peptic ulcer bleeding and rebleeding. Special considerations are recommended for such risky patients, including raising hematocrit to 30% in uremia or acute myocardial infarction, aggressive acid secretory control in high Rockall scores, monitoring delayed rebleeding in uremia or cirrhosis, considering cycloxygenase-2 inhibitors plus PPI for pain control, and early resumption of antiplatelets plus PPI in coronary artery disease or stroke., Conclusions: The consensus comprises recommendations to improve care of UGIB, especially for high-risk comorbidities.

Background: The association between uremia and survival outcomes of patients undergoing hepatic resection for hepatocellular carcinoma (HCC) has not been well investigated, particularly for perioperative complications. This nationwide cohort study aimed to compare survival outcomes as well as perioperative mortality and complications between uremia-HCC patients and non-uremia-HCC patients who underwent hepatic resection., Methods: Using Taiwan's National Health Institute Research Database, 149 uremia-HCC patients who underwent hepatic resection between 1996 and 2008 were enrolled. The control group comprised 596 HCC patients who also received hepatic resection during the same time period. The two groups were matched for age, gender, viral hepatitis status, and underlying liver cirrhosis. Disease-free survival, overall survival, and perioperative complications were compared between the two groups., Results: For the uremia-HCC cohort, the 1-, 5-, and 10-year overall and disease-free survival rates were 86, 52, and 38 %, as well as 77, 27, and 18 %, respectively. The survival outcomes were comparable between uremia-HCC cohort and the HCC cohort, regardless of extent of hepatic resection. As for perioperative complications, the uremia-HCC cohort had a higher risk of postoperative infections requiring invasive interventions as well as an increased risk of life-threatening heart-associated complications, compared to the HCC cohort., Conclusions: Uremia did not influence survival outcomes between the uremia-HCC and the HCC cohorts, irrespective of extent of hepatic resection. This study urges a better perioperative care strategy to avoid potential cardiac and infectious complications in uremia-HCC patients.

Background: Although the link between tuberculosis (TB) and biologics use is well established, the risk of TB among patients with psoriasis exposed to traditional systemic therapies remains elusive., Objectives: The aim is to investigate the association between traditional systemic therapies and TB among patients with psoriasis., Methods: We conducted a retrospective cohort study on the risk of active TB among patients with psoriasis and psoriatic arthritis, using the National Health Insurance Research Database of Taiwan, 1996 through 2008. Standardized incidence ratios of TB were analyzed in comparison with age- and gender-matched general population. Logistic regression was used in a nested case-control analysis to estimate the odds ratios of TB related to exposure to traditional systemic agents during the year before TB development., Results: Among the 81,266 patients in the psoriasis cohort, 497 new active TB cases were identified. The incidence rate of TB was 102 cases per 100,000 person-years among patients with psoriasis (standardized incidence ratio 1.22, 95% confidence interval 1.18-1.33). The risk of TB was higher in patients with severe disease (standardized incidence ratio 1.52, 95% confidence interval 1.46-1.74). To facilitate comparisons with the 497 active TB cases, a total of 1988 matched control subjects were selected for a nested case-control study. Patients taking systemic corticosteroids and nonsteroidal anti-inflammatory drugs were associated with higher incidence of TB, especially frequent users, after adjustment for multiple TB risk factors, drug exposures, hospital visits, and level of urbanization. Stratified analyses of current users and new users of these drugs revealed similar results. Finally, traditional systemic antipsoriatic treatment was not associated with TB on any of the analyses., Limitation: The National Health Insurance Research Database did not contain information regarding severity of psoriasis, smoking status, alcohol use, diet, laboratory parameters, chest radiograph, or history of recent contact with an individual with TB. Misclassification of disease cannot be ruled out in a registry-based database. The accessibility of health care may be associated with the level of urbanization, which could confound the effect of drugs in multivariate analyses., Conclusions: Severe psoriasis may be associated with an elevated TB risk. Traditional systemic therapies do not seem to be strongly associated with TB occurrence., (Copyright © 2012 American Academy of Dermatology, Inc. Published by Mosby, Inc. All rights reserved.)

Context: Tumor recurrence is a major issue for patients with hepatocellular carcinoma (HCC) following curative liver resection., Objective: To investigate the association between nucleoside analogue use and risk of tumor recurrence in patients with hepatitis B virus (HBV)--related HCC after curative surgery., Design, Setting, and Participants: A nationwide cohort study between October 2003 and September 2010. Data from the Taiwan National Health Insurance Research Database. Among 100 938 newly diagnosed HCC patients, we identified 4569 HBV-related HCC patients who received curative liver resection for HCC between October 2003 and September 2010., Main Outcome Measures: The risk of first tumor recurrence was compared between patients not taking nucleoside analogues (untreated cohort, n = 4051) and patients taking nucleoside analogues (treated cohort, n = 518). Cumulative incidences and hazard ratios (HRs) were calculated after adjusting for competing mortality., Results: The treated cohort had a higher prevalence of liver cirrhosis when compared with the untreated cohort (48.6% vs 38.7%; P < .001), but lower risk of HCC recurrence (n = 106 [20.5%] vs n = 1765 [43.6%]; P < .001), and lower overall death (n = 55 [10.6%] vs n = 1145 [28.3%]; P < .001). After adjusting for competing mortality, the treated cohort had a significantly lower 6-year HCC recurrence rate (45.6%; 95% CI, 36.5%-54.6% vs untreated, 54.6%; 95% CI, 52.5%-56.6%; P < .001). Six-year overall mortalities for treated cohorts were 29.0% (95% CI, 20.0%-38.0%) and for untreated 42.4% (95% CI, 40.0%-44.7%; P < .001). On modified Cox regression analysis, nucleoside analogue use (HR, 0.67; 95% CI, 0.55-0.81; P < .001), statin use (HR, 0.68; 95% CI, 0.53-0.87; P = .002), and nonsteroidal anti-inflammatory drugs or aspirin use (HR, 0.80; 95% CI, 0.73-0.88; P < .001) were independently associated with a reduced risk of HCC recurrence. Multivariable stratified analyses verified the association in all subgroups of patients, including those who were noncirrhotic (HR, 0.56; 95% CI, 0.42-0.76) and diabetic (HR, 0.52; 95% CI, 0.31-0.89)., Conclusion: Nucleoside analogue use was associated with a lower risk of HCC recurrence among patients with HBV-related HCC after liver resection.