Association of air quality index (AQI) with incidence of atopic dermatitis in Taiwan: A nationwide population-based cohort study.

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.

Psoriatic arthritis risk in psoriasis patients prescribed acitretin versus disease-modifying antirheumatic drugs: a nationwide cohort study.

OBJECTIVES: To compare the risk of psoriatic arthritis (PsA) in psoriasis (PsO) patients treated with acitretin vs disease-modifying antirheumatic drugs (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 non-steroidal anti-inflammatory drugs (NSAIDs) and comorbidities. RESULTS: The study included 1,948 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.

Risk of Psychiatric Disorders in Patients with Psoriasis Prescribed Acitretin versus Disease-Modifying Antirheumatic Drugs: A Nationwide Matched Cohort Study.

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.

Association between early life laxative exposure and risk of allergic diseases A nationwide matched cohort study.

BACKGROUND: The early life microbiome can shape human immunity. Recent studies have revealed gut dysbiosis after laxative administration. OBJECTIVE: To investigate the impact of infantile laxative exposure on subsequent allergic diseases. METHODS: This nationwide matched cohort study was conducted using Taiwan's National Health Insurance Research Database for the period 1997 to 2013. A total of 32,986 patients who had complete information of maternal history and delivery modes were identified. We included 291 children having laxatives for at least 7 days within the first 6 months of life and 1164 reference children not receiving laxatives, matching by sex, propensity score, number of hospital visits, and maternal age at delivery. Demographic characteristics and maternal factors were compared, and cumulative incidences of allergic diseases were calculated. Cox proportional hazard model was used to evaluate associations. RESULTS: The 5-year cumulative incidence of allergic diseases in the laxative cohort was significantly higher than that in the reference cohort (49.81% vs 41.68%; P = .01). Early life laxative exposure (adjusted hazard ratio, 1.61; 95% confidence interval, 1.32-1.97) was independently associated with allergic disease development. Other independent risk factors included preterm, male sex, maternal allergic diseases, and prenatal laxative use. Multivariable stratified analyses verified the association between early life laxative exposure and subsequent allergic disease development in all subgroups of children, including those born to mothers without allergic diseases or prenatal laxative use. CONCLUSION: Early life laxative exposure is associated with allergic disease development.

Fracture risks in patients with atopic dermatitis: A nationwide matched cohort study.

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.

Increasing Age and Nonliver Comorbidities in Patients with Chronic Hepatitis B in Taiwan: A Nationwide Population-Based Analysis.

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.

Infantile infection and antibiotic exposure in association with pediatric psoriasis development: A nationwide nested case-control study.

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.

An altered fecal microbial profiling in rosacea patients compared to matched controls.

BACKGROUND/PURPOSE: Rosacea has been linked to inflammatory bowel disease and small bowel bacterial overgrowth. We aimed to investigate the fecal microbial profiling and the potential gene functions between rosacea and non-rosacea subjects. METHODS: A case-control study. Fecal microbiome and predicted genetic function inferred from high-throughput 16S ribosomal RNA sequencing were analyzed between rosacea (n = 11) and age-, gender- and body mass index-matched non-rosacea subjects (n=110). The correlation between altered microbiome as well as lifestyle and diet were also investigated. RESULTS: A significant reduction of fecal microbial richness was found in rosacea patients. A distinct fecal microbial community structure was demonstrated in rosacea patients. The discriminating enriched genera in rosacea patients included Rhabdochlamydia, CF231, Bifidobacterium, Sarcina, Ruminococcus, belonging to the phylum of Chlamydiae, Bacteroidetes, Actinobacteria, and Lentisphaerae. The discriminating reduced abundant genera included Lactobacillus, Megasphaerae, Acidaminococcus, Hemophilus, Roseburia, Clostridium, belong to the phylum of Firmicutes; and Citrobacter, belonging to the phylum of Proteobacteria. The distinct fecal microbial composition might be related to sulfur metabolism, cobalamin, and carbohydrate transport. CONCLUSION: An altered fecal microbial richness and composition were observed in rosacea patients. The distinct microbial composition might be related to sulfur metabolism, cobalamin and carbohydrate transport.

Factors Associated With Rates of HBsAg Seroclearance in Adults With Chronic HBV Infection: A Systematic Review and Meta-analysis.

BACKGROUND & AIMS: Seroclearance of hepatitis B surface antigen (HBsAg) is a marker for clearance of chronic hepatitis B virus (HBV) infection, but reported annual incidence rates of HBsAg seroclearance vary. We performed a systematic review and meta-analysis to provide more precise estimates of HBsAg seroclearance rates among subgroups and populations. METHODS: We searched PubMed, Embase, and the Cochrane library for cohort studies that reported HBsAg seroclearance in adults with chronic HBV infection with more than 1 year of follow-up and at least 1 repeat test for HBsAg. Annual and 5-, 10-, and 15-year cumulative incidence rates were pooled using a random effects model. RESULTS: We analyzed 34 published studies (with 42,588 patients, 303,754 person-years of follow-up, and 3194 HBsAg seroclearance events), including additional and updated aggregated data from 19 studies. The pooled annual rate of HBsAg seroclearance was 1.02% (95% CI, 0.79-1.27). Cumulative incidence rates were 4.03% at 5 years (95% CI, 2.49-5.93), 8.16% at 10 years (95% CI, 5.24-11.72), and 17.99% at 15 years (95% CI, 6.18-23.24). There were no significant differences between the sexes. A higher proportion of patients who tested negative for HBeAg at baseline had seroclearance (1.33%; 95% CI, 0.76-2.05) than those who tested positive for HBeAg (0.40%; 95% CI, 0.25-0.59) (P < .01). Having HBsAg seroclearance was also associated with a lower baseline HBV DNA level (6.61 log10 IU/mL; 95% CI, 5.94-7.27) vs not having HBsAg seroclearance (7.71 log10 IU/mL; 95% CI, 7.41-8.02) (P < .01) and with a lower level of HBsAg at baseline (2.74 log10 IU/mL; 95% CI, 1.88-3.60) vs not having HBsAg seroclearance (3.90 log10 IU/mL, 95% CI, 3.73-4.06) (P < .01). HBsAg seroclearance was not associated with HBV genotype or treatment history. Heterogeneity was substantial across the studies (I2 = 97.49%). CONCLUSION: In a systematic review and meta-analysis, we found a low rate of HBsAg seroclearance in untreated and treated patients (pooled annual rate, approximately 1%). Seroclearance occurred mainly in patients with less active disease. Patients with chronic HBV infection should therefore be counseled on the need for lifelong treatment, and curative therapies are needed.

Systematic review and network meta-analysis: Comparative effectiveness of therapies for second-line Helicobacter pylori eradication.

BACKGROUND AND AIM: The eradication rate of Helicobacter pylori (H. pylori) has been declining over the past decades. A rescue plan is needed for increasing populations with treatment failure. However, the optimum second-line eradication regimen remains inconclusive. We conducted a network meta-analysis to assess the comparative effectiveness of second-line H. pylori eradication therapies and determine the optimum regimen. METHODS: We searched electronic databases from January 2005 to February 2018 for randomized controlled trials assessing the effectiveness of second-line regimens in patients with persistent H. pylori infection after first-line treatment. Bayesian network meta-analysis was performed to combine the direct and indirect evidence and to investigate the rank order of second-line therapies. We also appraised the quality of evidence using Grading of Recommendations Assessment, Development, and Evaluation guidance. RESULTS: Twenty-six trials with 3628 participants who received second-line eradication therapy were identified. All regimens showed pooled eradication rates < 90%. Compared with 7-day triple therapy, quinolone-based (odds ratio [OR] 4.29, 95% credible interval [CrI] 1.67-12.12, surface under the cumulative ranking [SUCRA] 0.95), non-quinolone-based bismuth-containing quadruple therapies for 10 days or more (OR 2.25, 95% CrI 1.10-4.62, SUCRA 0.78), and sequential therapy (OR 2.91, 95% CrI 1.16-7.65, SUCRA 0.66) showed significantly higher effectiveness. Overall, regimens with longer duration demonstrated higher eradication rates but higher rates of adverse events. More adverse events were reported in those patients treated with concomitant therapy. CONCLUSIONS: Quinolone-based bismuth-containing quadruple therapies for 10 days or more are the optimum second-line regimens for H. pylori eradication.

First-line Helicobacter pylori eradication therapies in countries with high and low clarithromycin resistance: a systematic review and network meta-analysis.

OBJECTIVE: To determine the optimal regimen of different first-line Helicobacter pylori eradication therapies according to the clarithromycin resistance rate. DESIGN: Electronic search for articles published between January 2005 and April 2016. Randomised, controlled trials that reported the effectiveness of first-line eradication therapies in treatment-naïve adults were included. Two independent reviewers performed articles screening and data extraction. Network and traditional meta-analyses were conducted using the random effect model. Subgroup analyses were performed to determine the ranking of regimens in countries with high (>15%) and low (<15%) clarithromycin resistance. Data including adverse events and therapeutic cure rate were also extracted and analysed. RESULTS: 117 trials (totally 32 852 patients) for 17 H. pylori eradication regimens were eligible for inclusion. Compared with 7-day clarithromycin-based triple therapy, sequential therapy (ST) for 14 days had the highest effectiveness (OR=3.74, 95% CrI 2.37 to 5.96). ST-14 (OR=6.53, 95% CrI 3.23 to 13.63) and hybrid therapy (HY) for 10 days or more (OR=2.85, 95% CrI 1.58 to 5.37) represented the most effective regimen in areas with high and low clarithromycin resistance, respectively. The effectiveness of standard triple therapy was below therapeutic eradication rate in most of the countries. Longer duration was associated with higher eradication rate, but with a higher risk of events that lead to discontinuation. CONCLUSIONS: ST and HY appeared to be the most effective therapies in countries with high and low clarithromycin resistance, respectively. The clinical decision for optimal regimen can be supported by referring to the rank ordering of relative efficacies stratified by local eradication rates, antibiotic resistance and safety profile. TRIAL REGISTRATION NUMBER: CRD42015025445.

Development of a scoring system to predict hepatocellular carcinoma in Asians on antivirals for chronic hepatitis B.

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.

Temporal trend and risk determinants of hepatocellular carcinoma in chronic hepatitis B patients on entecavir or tenofovir.

This study aimed to elucidate the temporal change and determinants for the risk of HCC in patients with chronic hepatitis B continuously receiving NUC. Through analysis of the national healthcare database in Taiwan, we screened a total of 65 426 infected patients receiving entecavir or tenofovir for at least 3 months and excluded those with lamivudine, adefovir or telbivudine exposure, malignancy, end-stage renal failure or a diagnosis of HCC within 3 months of starting treatment. Eligible patients (N = 27 820) were followed until HCC occurrence, completion of the allowed 3-year regimen or 31 December 2013. During a median follow-up of 25.1 (12.1-35.6) months, 802 patients developed HCC, with 1-, 2- and 3-year cumulative incidence of 1.82% (95% CI, 1.66-1.99%), 3.05% (95% CI, 2.82-3.28%) and 4.06% (95% CI, 3.77-4.36%), respectively. HCC annual incidence decreased with an adjusted IRR of 0.73 (95% CI, 0.66-0.80) per yearly interval and was associated with cirrhosis (IRR, 10.07; 95% CI, 6.00-16.90 in age <40 years; 4.69; 95% CI, 3.94-5.59 in age ≧40 years), age (IRR, 3.38; 95% CI, 2.10-5.47 for 40-50 years; 6.92; 95% CI, 4.27-11.21 for 50-60 years; 12.50; 95% CI, 7.71-20.25 for ≧60 years; <40 years as reference), male sex (IRR, 1.71; 95% CI, 1.44-2.04), HCV coinfection (IRR, 1.27; 95% CI, 1.02-1.58) and diabetes (IRR, 1.24; 95% CI, 1.05-1.45). In conclusion, the risk of HCC in patients with chronic hepatitis B receiving entecavir or tenofovir declines over time and is determined by cirrhosis, age, male sex, HCV coinfection and diabetes.

Intestinal microbiota profiling and predicted metabolic dysregulation in psoriasis patients.

OBJECTIVES: The intestinal microbiota has been known to involve in obesity and host immune response. We aimed to investigate the intestinal microbiota and potential genetic function in relation to clinical presentation in psoriasis patients. METHODS: Faecal microbiota and predicted genetic function inferred from high-throughput 16S ribosomal RNA sequencing were analysed between psoriasis (n = 32) and age-, gender- and body mass index (BMI)-matched non-psoriasis subjects (n = 64), from a referral medical centre. The correlation between altered microbiota and disease activity, arthritis and systemic anti-psoriatic drugs was also investigated. RESULTS: We observed a distinct faecal microbial community structure in psoriasis patients, with an increased abundance of phylum Firmicutes and decreased abundance of phylum Bacteroidetes, across different subgroup of subjects. Ruminococcus and Megasphaera, of the phylum Firmicutes, were the top-two genera of discriminant abundance in psoriasis. A number of functional genes and metabolic pathways involving bacterial chemotaxis and carbohydrate transport were predicted over-represented, whereas genes related to cobalamin and iron transport were predicted under-represented in faecal microbiota of psoriasis patients. CONCLUSIONS: The distinct faecal microbial composition in psoriasis might be associated with altered transport of carbohydrate, cobalamin and iron, as well as chemotaxis.

Prior gastroscopy and mortality in patients with gastric cancer: a matched retrospective cohort study.

BACKGROUND AND AIMS: The role of prior gastroscopy on the outcome of patients with gastric cancer remains unknown. This study determines the association between intervals of prior gastroscopy and mortality in patients with gastric cancer. METHODS: We identified 20,066 newly diagnosed patients with gastric cancer in the National Health Insurance Database of Taiwan between 2002 and 2007. After we excluded patients who had gastroscopies performed ≤6 months before the diagnosis of cancer, patients were matched into 3 cohorts according to the intervals of prior gastroscopy: 6 months to 2 years (<2 Y cohort), 2 to 5 years (2-5 Y cohort), and none within the previous 5 years (>5 Y cohort). The 3 cohorts were matched for age, curative treatment for gastric cancer, Helicobacter pylori therapy, and propensity scores comprised of sex, comorbidities, and concomitant medication usage. The primary outcome is the hazard ratio (HR) of all-cause mortality. RESULTS: After matching, we identified 1286, 1286, and 5144 patients for the <2 Y, 2 to 5 Y, and >5 Y cohorts. Compared with the >5 Y cohort, the HR of all-cause mortality for the <2 Y and 2 to 5 Y cohorts was 0.80 (95% confidence interval [CI], 0.72-0.89; P < .001) and 0.83 (95% CI, 0.76-0.91; P < .001), respectively. The HRs of gastric cancer-specific mortality were significantly lower in the <2 Y (0.80; 95% CI, 0.71-0.91; P < .001) and 2 to 5 Y cohorts (0.83; 95% CI, 0.75-0.93; P < .001). CONCLUSIONS: Patients with gastric cancer who had a gastroscopy performed within 5 years before the cancer diagnosis had significantly lower mortality. Our results may support the role of repeat endoscopic examination or surveillance endoscopy in selected patients.

Association between ultrasonography screening and mortality in patients with hepatocellular carcinoma: a nationwide cohort study.

OBJECTIVE: Current guidelines recommend screening for hepatocellular carcinoma (HCC) in high-risk populations. However, the effectiveness of screening in reducing mortality has been challenged. In addition, it is unclear which subgroups benefit most from HCC screening. DESIGN: This nationwide cohort study identified a total of 52,823 newly diagnosed HCC patients between 1 January 2002 and 31 December 2007. These HCC patients were classified into the following cohorts according to the time intervals in which they received ultrasonography screening: 0-6 months (6M), 7-12 months (12M), 13-24 months (24M), 25-36 months (36M) and not screened within 3 years (never screened). The chance to receive curative therapy and 5-year cumulative mortalities were calculated after adjusting for lead-time bias. RESULTS: Chances to receive curative therapy among the 6M, 12M, 24M, 36M and never screened cohorts were 24.3% (95% CI 23.7% to -24.9%), 26.9% (95% CI 25.7% to 28.2%), 22.9% (95% CI 21.8% to 24.1%), 21.3% (95% CI 19.9% to 22.8%) and 18.3% (95% CI 17.8% to 18.8%), respectively. Compared with the 6M cohort, adjusted HRs of mortality for the 12M, 24M, 36M and never screened cohorts were 1.11 (95% CI 1.07 to 1.15), 1.23 (95% CI 1.19 to 1.28), 1.31 (95% CI 1.26 to 1.37) and 1.47 (95% CI 1.43 to 1.51) (all p<0.001), respectively. On multivariable subgroup analyses, the associations between shorter screening intervals and better survival were observed in nearly all subgroups, especially in younger patients, patients without diabetes and patients with hepatitis B infection. CONCLUSIONS: Shorter ultrasonography screening intervals are associated with reduced overall mortality in HCC patients in a dose-dependent manner.

The Incidence of Gastric Adenocarcinoma Among Patients With Gastric Intestinal Metaplasia: A Long-term Cohort Study.

BACKGROUND AND AIMS: Gastric intestinal metaplasia (IM) has been known as a premalignant condition, but estimates of its cancer risk vary widely. We aimed to analyze cancer risk of gastric IM by a long-term cohort study. METHODS: We conducted a hospital-based study that included all patients with gastric IM between 1992 and 2010, and the development of gastric adenocarcinoma was evaluated until July 2011. Patients developing gastric cancer ≤180 days after the index diagnosis of IM were excluded. The incidence rate, the cumulative incidence, and the standardized incidence ratio (SIR) of gastric cancer were determined, and hazard ratios (HRs) of risk factors were calculated. RESULTS: We identified 7059 patients with a median follow-up duration of 5.1 years, and 81 patients developed gastric adenocarcinoma during the study period. The 5-, 10-, and 15-year cumulative incidences of gastric cancer were 0.9% [95% confidence interval (CI), 0.6-1.1), 2.0% (95% CI, 1.5-2.6), and 3.0% (95% CI, 2.0-4.0), respectively. On multivariate analysis, older age (eg, 75 y and above; HR=7.4; 95% CI, 2.8-19.6), low-grade dysplasia (HR=4.0; 95% CI, 2.1-7.9), and high-grade dysplasia (HR=18.8; 95% CI, 9.0-39.5) were independent risk factors. As compared with the risk in the general population, the SIR of gastric cancer among patients with gastric IM was 2.5 (95% CI, 2.0-3.1). However, the SIR was only 2.0 (95% CI, 1.5-2.6) in the nondysplasia subgroup, but was up to 35.2 (95% CI, 15.2-69.4) in the high-grade dysplasia subgroup. CONCLUSIONS: Gastric IM is an important risk factor for gastric cancer, but surveillance should be arranged only for those at an especially high risk.

Association between antiviral treatment and extrahepatic outcomes in patients with hepatitis C virus infection.

OBJECTIVE: To elucidate the association between antiviral therapy and extrahepatic outcomes in individuals infected with HCV. METHODS: This nationwide cohort study screened 293,480 Taiwanese residents with HCV infection and excluded those with substantial comorbidity. A total of 12,384 eligible patients who had received pegylated interferon plus ribavirin between 1 October 2003 and 31 December 2010 were enrolled in the treated cohort; they were matched 1 : 2 with 24,768 untreated controls in the propensity score and post-diagnosis treatment-free period. The incidences of end-stage renal disease (ESRD), acute coronary syndrome (ACS), ischaemic stroke and catastrophic autoimmune diseases were calculated after adjustment for competing mortality. RESULTS: The treated and untreated cohorts were followed up for a mean (±SD) duration of 3.3 (±2.5) and 3.2 (±2.4) years, respectively, until 31 December 2011. The calculated 8-year cumulative incidences of ESRD, ACS, ischaemic stroke and autoimmune catastrophes between treated and untreated patients were 0.15% vs. 1.32% (p<0.001), 2.21% vs. 2.96% (p=0.027), 1.31% vs. 1.76% (p=0.001) and 0.57% vs. 0.49% (p=0.816), respectively. Multivariate-adjusted Cox regression revealed that antiviral treatment was associated with lower risks of ESRD (HR 0.15; 95% CI 0.07 to 0.31; p<0.001), ACS (HR 0.77; 95% CI 0.62 to 0.97; p=0.026) and ischaemic stroke (HR 0.62; 95% CI 0.46 to 0.83; p=0.001), but unrelated to autoimmune catastrophes. These favourable associations were invalid in incompletely treated patients with duration <16 weeks. CONCLUSIONS: Antiviral treatment for HCV is associated with improved renal and circulatory outcomes, but unrelated to catastrophic autoimmune diseases.

Nonsteroidal anti-inflammatory drugs are associated with reduced risk of early hepatocellular carcinoma recurrence after curative liver resection: a nationwide cohort study.

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.