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.

The epidemiology of pediatric psoriasis: A nationwide cohort study in Taiwan.

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.

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.

Daily aspirin associated with a reduced risk of hepatocellular carcinoma in patients with non-alcoholic fatty liver disease: a population-based cohort study.

Background: Emerging laboratory and animal studies suggest that aspirin may prevent non-alcoholic fatty liver disease (NAFLD)-related hepatocellular carcinoma (HCC), however clinical evidence remains lacking. Methods: Using Taiwan's National Health Insurance Research Database, we screened 145,212 NAFLD patients from 1997 through 2011. After excluding any confounding conditions, 33,484 patients who continuously received a daily dose of aspirin for 90 days or more (treated group), along with 55,543 patients who had not received antiplatelet therapy (untreated group), were respectively recruited. Inverse probability of treatment weighting using the propensity score was applied to balance the baseline characteristics. Cumulative incidence of, and hazard ratio (HR) for HCC occurrence were analyzed after adjusting competing events. The high-risk patients, who were defined as age ≥ 55 years & elevated serum alanine aminotransferase, were further analyzed. Findings: The 10-year cumulative incidence of HCC in the treated group was significantly lower than that in the untreated group (0.25% [95% CI, 0.19-0.32%] vs. 0.67% [95% CI, 0.54-0.81%]; P < 0.001). Aspirin therapy was significantly associated with a reduced HCC risk (adjusted HR [aHR] 0.48 [95% CI, 0.37-0.63]; P < 0.001). In the high-risk patients, the 10-year cumulative incidence of HCC in the treated group was significantly lower than that in the untreated group (3.59% [95% CI, 2.99-4.19%] vs. 6.54% [95% CI, 5.65-7.42%]; P < 0.001). Aspirin therapy remained associated with a reduced HCC risk (aHR 0.63 [95% CI, 0.53-0.76]; P < 0.001). Subgroup sensitivity analyses verified this significant association in nearly all subgroups. In the time-varying model amongst aspirin users, HCC risk was significantly lower through the use of aspirin for ≥ 3 years (aHR 0.64 [95% CI, 0.44-0.91]; P = 0.013), when compared with short-term use (< 1 year). Interpretation: Daily aspirin therapy is significantly associated with a reduced HCC risk in NAFLD patients. Funding: Ministry of Science and Technology, Ministry of Health and Welfare, and Taichung Veterans General Hospital, Taiwan.

Severe hepatitis B flares with hepatic decompensation after withdrawal of nucleos(t)ide analogues: A population-based cohort study.

BACKGROUND: Finite nucleos(t)ide analogue (NUC) therapy has been proposed as an alternative treatment strategy for chronic hepatitis B (CHB). AIM: To quantify the incidence of severe hepatitis flares following NUC cessation in everyday clinical practice. METHODS: This population-based cohort study enrolled 10,192 patients (male 71.7%, median age 50.9 years, cirrhosis 10.7%) who had received first-line NUCs for at least 1 year before discontinuing treatment. The primary outcome was severe flare with hepatic decompensation. We used competing risk analyses to assess event incidences and associated risk factors. RESULTS: During a median follow-up of 2.2 years, 132 patients developed severe flares with hepatic decompensation, yielding a 4-year cumulative incidence of 1.8% (95% confidence interval [CI], 1.5%-2.2%). Significant risk factors were cirrhosis (adjusted sub-distributional hazard ratio [aSHR], 2.74; 95% CI, 1.82-4.12), manifestations of portal hypertension (aSHR, 2.46; 95% CI, 1.45-4.18), age (aSHR, 1.21 per 10 years; 95% CI, 1.03-1.42) and male sex (aSHR, 1.58; 95% CI, 1.04-2.38). In patients without cirrhosis or portal hypertension (n = 8863), the 4-year cumulative incidence of severe withdrawal flares stood at 1.3% (95% CI, 1.0%-1.7%). For those patients with available data confirming adherence to the standard stopping rules (n = 1274), the incidence was 1.1% (95% CI, 0.6%-2.0%). CONCLUSIONS: Severe flares with hepatic decompensation were observed in 1%-2% of patients with CHB after stopping NUC therapy in daily practice. Risk factors included older age, cirrhosis, portal hypertension and male sex. Our findings argue against NUC cessation as part of routine clinical care.

Physical Fitness and Inflammatory Bowel Disease Risk Among Children and Adolescents in Taiwan.

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.

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.

Early-Life Antibiotic Exposure Associated With Varicella Occurrence and Breakthrough Infections: Evidence From Nationwide Pre-Vaccination and Post-Vaccination Cohorts.

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.

Compositions of gut microbiota before and shortly after hepatitis C viral eradication by direct antiviral agents.

It is unclear whether dysbiosis in hepatitis C virus (HCV) infected patients results from the viral infection per se or develops as a result of hepatic dysfunction. We aimed to characterize compositions in gut microbiome before and shortly after HCV clearance. In this prospective cohort study, adult patients with confirmed HCV viremia were screened before receiving direct antiviral agents. Those with recent exposure to antibiotics or probiotics (within one month), prior abdominal surgery, or any malignancy were ineligible. Stool was collected before antiviral therapy started and at 12 weeks after the treatment completed. From the extracted bacterial DNA, 16 s rRNA gene was amplified and sequenced. Each patient was matched 1:2 in age and sex with uninfected controls. A total of 126 individuals were enrolled into analysis. The gut microbiome was significantly different between HCV-infected patients (n = 42), with or without cirrhosis, and their age-and sex-matched controls (n = 84) from the levels of phylum to amplicon sequence variant (all p values < 0.01 by principal coordinates analysis). All patients achieved viral eradication and exhibited no significant changes in the overall composition of gut microbiome following viral eradication (all p values > 0.5), also without significant difference in alpha diversity (all p values > 0.5). For the purpose of exploration, we also reported bacteria found differently abundant before and after HCV eradication, including Coriobacteriaceae, Peptostreptococcaceae, Staphylococcaceae, Morganellaceae, Pasteurellaceae, Succinivibrionaceae, and Moraxellaceae. Gut microbiota is altered in HCV-infected patients as compared with uninfected controls, but the overall microbial compositions do not significantly change shortly after HCV eradication.

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.

Reduced risk of skin cancer and internal malignancies in vitiligo patients: a retrospective population-based cohort study in Taiwan.

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.

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.

COVID-19 case doubling time associated with non-pharmaceutical interventions and vaccination: A global experience.

BACKGROUND: Evidence has revealed that nonpharmaceutical interventions (NPIs) were effective in attenuating the spread of COVID-19. However, policymakers have encountered difficulty in identifying the most effective policies under different circumstances. This study investigated the relative effectiveness of different NPIs and vaccination in prolonging COVID-19 case doubling time (DT). METHODS: The study sample consisted of observations from 137 countries during 1 January 2020 to 13 June 2021. DT was calculated on a daily basis per country. Data were retrieved from the Oxford COVID-19 Government Response Tracker, World Development Indicators, and Worldwide Governance Indicators. To capture policy intervention dynamics, we combined a random-effect growth-curve model with nonstandard interrupted time series analysis. We also evaluated the association of policy measures with DT for different outbreak stages and levels of government effectiveness. RESULTS: Vaccine rollouts, workplace closures, and school closures were relatively effective. For each day that these measures were implemented, the DT increased by 1.96% (95% confidence interval (CI) = 0.63 to 3.29; P = 0.004), 1.41% (95% CI = 0.88 to 1.95%; P < 0.001) and 1.38% (95% CI = 0.95 to 1.81%; P < 0.001), respectively. Workplace and school closures were positively associated with DT at all stages; however, the associations weakened in later stages, where vaccine rollouts appeared to be most effective in prolonging DT (95% CI = 1.51% to 3.04%; P < 0.05). For countries with a high level of government effectiveness, most of the containment measures evaluated were effective; vaccine rollouts had the greatest effect size. For countries with medium or low levels of government effectiveness, only the closure of workplaces was consistently associated with prolonged DT. CONCLUSIONS: The effectiveness of vaccine rollouts outweighed that of NPIs, especially in the later outbreak stages. However, vaccination was not associated with prolonged case DT in countries with lower levels of government effectiveness, probably due to low vaccine coverage. Among the NPIs examined, workplace closures were highly effective across all outbreak stages and levels of government effectiveness. Our findings suggest that mass vaccination is critical to reducing SARS-CoV-2 transmission, especially in countries where NPIs are less effective.

COVID-19 vaccinations are associated with reduced fatality rates: Evidence from cross-country quasi-experiments.

BACKGROUND: Scientists have demonstrated the efficacy of vaccines against severe acute respiratory syndrome coronavirus 2 in randomized controlled trials. However, the extent to which reductions in COVID-19 case fatality ratio (CFR) are attributable to mass vaccination in the real world remains unclear. This study evaluated the association of COVID-19 vaccine coverage with CFR on a global scale. METHODS: The sample was a longitudinal data set of 90 countries over 25 weeks, from the first week of November 2020 to the third week of April 2021. CFR was measured in deaths per 100 COVID-19 confirmed cases; vaccine coverage was defined as the number of people who received at least one vaccine dose per 10 people in the total population. Data were retrieved from open-access databases, including Our World in Data and the Oxford COVID-19 Government Response Tracker. A country-level random effects model was used; a comprehensive set of variables for country characteristics and nonpharmaceutical interventions were included. RESULTS: A 10% increase in vaccine coverage was associated with a 7.6% reduction in the CFR (95% confidence interval (CI = -12.6 to -2.7%, P = 0.002). This association was stronger in countries with more effective governments (-8.3%; 95% CI = -13.6 to -3.1%, P = 0.002) and higher transport infrastructure quality (-8.1%; 95% CI = -13.3 to -2.9%, P = 0.002). Moreover, the vaccine coverage was associated with a reduced CFR in a dose-dependent manner. When vaccine coverage achieved 0.8 to 1.6, 1.6 to 3.2 and ≥3.2 per 10 people, the CFR reduced by 12.7% (95 CI = -21.8 to -3.6%, P = 0.006), 21.2% (95 CI = -33.9 to -8.5%, P = 0.001) and 31.3% (95 CI = -51.5 to -11.0%, P = 0.002), respectively as compared with no vaccination. CONCLUSIONS: Our results provide supporting evidence that vaccination is critical to preventing deaths among infected people. Vaccination programmes have yielded significant health benefits in certain countries. However, globally, a large gap remains between observed and achievable fatality reductions. Continuous improvement in vaccine coverage will be critical to transforming efficacious vaccines into desired health outcomes.

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.

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.

Atopic dermatitis does not increase the risk of inflammatory bowel disease: A nationwide cohort study.

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.

Incidence, Factors, and Patient-Level Data for Spontaneous HBsAg Seroclearance: A Cohort Study of 11,264 Patients.

INTRODUCTION: Spontaneous hepatitis B surface antigen (HBsAg) seroclearance, the functional cure of hepatitis B infection, occurs rarely. Prior original studies are limited by insufficient sample size and/or follow-up, and recent meta-analyses are limited by inclusion of only study-level data and lack of adjustment for confounders to investigate HBsAg seroclearance rates in most relevant subgroups. Using a cohort with detailed individual patient data, we estimated spontaneous HBsAg seroclearance rates through patient and virologic characteristics. METHODS: We analyzed 11,264 untreated patients with chronic hepatitis B with serial HBsAg data from 4 North American and 8 Asian Pacific centers, with 1,393 patients with HBsAg seroclearance (≥2 undetectable HBsAg ≥6 months apart) during 106,192 person-years. The annual seroclearance rate with detailed categorization by infection phase, further stratified by hepatitis B e antigen (HBeAg) status, sex, age, and quantitative HBsAg (qHBsAg), was performed. RESULTS: The annual seroclearance rate was 1.31% (95% confidence interval: 1.25-1.38) and over 7% in immune inactive patients aged ≥55 years and with qHBsAg <100 IU/mL. The 5-, 10-, 15-, and 20-year cumulative rates were 4.74%, 10.72%, 18.80%, and 24.79%, respectively. On multivariable analysis, male (adjusted hazard ratio [aHR] = 1.66), older age (41-55 years: aHR = 1.16; >55 years: aHR = 1.21), negative HBeAg (aHR = 6.34), and genotype C (aHR = 1.82) predicted higher seroclearance rates, as did lower hepatitis B virus DNA and lower qHBsAg (P < 0.05 for all), and inactive carrier state. DISCUSSION: The spontaneous annual HBsAg seroclearance rate was 1.31%, but varied from close to zero to about 5% among most chronic hepatitis B subgroups, with older, male, HBeAg-negative, and genotype C patients with lower alanine aminotransferase and hepatitis B virus DNA, and qHBsAg independently associated with higher rates (see Visual Abstract, Supplementary Digital Content 2, http://links.lww.com/CTG/A367).