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AbstractOver the past two decades Canadian municipalities have seen the emergence of formalised systems-level collaborative approaches to addressing homelessness and housing issues. The implementation of such approaches has been widespread and to some extent standardised by the Canadian (federal) government through the mandated formation of ‘community advisory boards’ (CABs) and their associated ‘Community Entities (CEs) which direct the use of federal homelessness funding’. CABs have significantly affected systems-level strategic planning to address homelessness in urban, rural, and remote areas across the country. These groups have had impact and success, but also face challenges related to effective collaboration and governance. Despite the significant influence of these groups – in directing funding and resources to address homelessness – there is little independent research on these groups, their effectiveness, the relationships that constitute CABs or the degree to which they achieve their stated goals of cross-sectoral integration. Social Network Analysis (SNA) is an approach for understanding networked organizational relationships. It has been used in some limited housing and homelessness scholarship to document the quantitative and qualitative features of networks and for understanding the comparative successes and impacts of these efforts. In the broadest sense, SNA can be described as the investigation of relationships among individuals and/or groups in order to identify and interrogate social structures. In this paper, we utilize a case study approach to explore how SNA might contribute to a better understanding of cross-sectoral network building in a CAB with the aim of enhancing systems-level planning to end homelessness.

Abstract Weekend effect has been considered to be associated with poorer quality of care and patient’s survival. For acute myocardial infarction (AMI) patients, the question of whether patients admitted during off-hours have worse outcomes as compared with patients admitted during on-hours is still inconclusive. We conducted this study to explore the weekend effect in AMI patients, using a nationwide insurance database in Taiwan. Using Taiwan National Health Insurance (NHI) claims database, we designed a retrospective cohort study, and extracted 184,769 incident cases of AMI through the NHI claims database between January 2006 and December 2014. We divided the patients into weekend admission group and weekday admission group. Patients were stratified as ST elevation/non-ST elevation AMI and receiving/not receiving percutaneous coronary intervention (PCI). We used a logistic regression model to examine the relative risk of in-hospital mortality and 1-year mortality which were obtained from the Taiwan National Death Registry between study groups. We found no difference between weekend group and weekday group for risk of in-hospital mortality (15.8% vs 16.2%, standardized difference 0.0118) and risk of 1-year mortality (30.2% vs 30.9%, standardized difference 0.0164). There was no statistically significant difference among all the comparisons through the multivariate logistic regression analysis adjusting for all the covariates and stratifying by the subtypes of AMI and whether or not executing PCI during hospitalization. As for AMI patients in Taiwan, admission on weekends or weekdays did not have a significant impact on either in-hospital mortality or 1-year cumulative mortality.

Plastic waste accumulation in marine environments has complex, unintended impacts on ecology that cross levels of community organization. To measure succession in polyolefin-colonizing marine bacterial communities, an in situ time-series experiment was conducted in the oligotrophic coastal waters of the Bermuda Platform. Our goals were to identify polyolefin colonizing taxa and isolate bacterial cultures for future studies of the biochemistry of microbe-plastic interactions. HDPE, LDPE, PP, and glass coupons were incubated in surface seawater for 11 weeks and sampled at two-week intervals. 16S rDNA sequencing and ATR-FTIR/HIM were used to assess biofilm community structure and chemical changes in polymer surfaces. The dominant colonizing taxa were previously reported cosmopolitan colonizers of surfaces in marine environments, which were highly similar among the different plastic types. However, significant differences in rare community composition were observed between plastic types, potentially indicating specific interactions based on surface chemistry. Unexpectedly, a major transition in community composition occurred in all material treatments between days 42 and 56 (p

Summary: Background: While vaccines have established utility against COVID-19, phase 3 efficacy studies have generally not comprehensively evaluated protection provided by previous infection or hybrid immunity (previous infection plus vaccination). Individual patient data from US government-supported harmonized vaccine trials provide an unprecedented sample population to address this issue. We characterized the protective efficacy of previous SARS-CoV-2 infection and hybrid immunity against COVID-19 early in the pandemic over three-to six-month follow-up and compared with vaccine-associated protection. Methods: In this post-hoc cross-protocol analysis of the Moderna, AstraZeneca, Janssen, and Novavax COVID-19 vaccine clinical trials, we allocated participants into four groups based on previous-infection status at enrolment and treatment: no previous infection/placebo; previous infection/placebo; no previous infection/vaccine; and previous infection/vaccine. The main outcome was RT-PCR-confirmed COVID-19 >7–15 days (per original protocols) after final study injection. We calculated crude and adjusted efficacy measures. Findings: Previous infection/placebo participants had a 92% decreased risk of future COVID-19 compared to no previous infection/placebo participants (overall hazard ratio [HR] ratio: 0.08; 95% CI: 0.05–0.13). Among single-dose Janssen participants, hybrid immunity conferred greater protection than vaccine alone (HR: 0.03; 95% CI: 0.01–0.10). Too few infections were observed to draw statistical inferences comparing hybrid immunity to vaccine alone for other trials. Vaccination, previous infection, and hybrid immunity all provided near-complete protection against severe disease. Interpretation: Previous infection, any hybrid immunity, and two-dose vaccination all provided substantial protection against symptomatic and severe COVID-19 through the early Delta period. Thus, as a surrogate for natural infection, vaccination remains the safest approach to protection. Funding: National Institutes of Health.

Abstract Returning university students represent large-scale, transient demographic shifts and a potential source of transmission to adjacent communities during the COVID-19 pandemic. In this prospective longitudinal cohort study, we tested for IgG antibodies against SARS-CoV-2 in a non-random cohort of residents living in Centre County prior to the Fall 2020 term at the Pennsylvania State University and following the conclusion of the Fall 2020 term. We also report the seroprevalence in a non-random cohort of students collected at the end of the Fall 2020 term. Of 1313 community participants, 42 (3.2%) were positive for SARS-CoV-2 IgG antibodies at their first visit between 07 August and 02 October 2020. Of 684 student participants who returned to campus for fall instruction, 208 (30.4%) were positive for SARS-CoV-2 antibodies between 26 October and 21 December. 96 (7.3%) community participants returned a positive IgG antibody result by 19 February. Only contact with known SARS-CoV-2-positive individuals and attendance at small gatherings (20–50 individuals) were significant predictors of detecting IgG antibodies among returning students (aOR, 95% CI 3.1, 2.07–4.64; 1.52, 1.03–2.24; respectively). Despite high seroprevalence observed within the student population, seroprevalence in a longitudinal cohort of community residents was low and stable from before student arrival for the Fall 2020 term to after student departure. The study implies that heterogeneity in SARS-CoV-2 transmission can occur in geographically coincident populations.

Introduction Type 2 diabetes mellitus (T2DM) is a powerful risk factor for cardiovascular disease (CVD), conferring a greater relative risk in women than men. We sought to examine sex differences in cardiometabolic risk factors and management in the contemporary cohort represented by the Glycemia Reduction Approaches in Diabetes: A Comparative Effectiveness Study (GRADE).Research design and methods GRADE enrolled 5047 participants (1837 women, 3210 men) with T2DM on metformin monotherapy at baseline. The current report is a cross-sectional analysis of baseline data collected July 2013 to August 2017.Results Compared with men, women had a higher mean body mass index (BMI), greater prevalence of severe obesity (BMI≥40 kg/m2), higher mean LDL cholesterol, greater prevalence of low HDL cholesterol, and were less likely to receive statin treatment and achieve target LDL, with a generally greater prevalence of these risk factors in younger women. Women with hypertension were equally likely to achieve blood pressure targets as men; however, women were less likely to receive ACE inhibitors or angiotensin receptor blockers. Women were more likely to be divorced, separated or widowed, and had fewer years of education and lower incomes.Conclusions This contemporary cohort demonstrates that women with T2DM continue to have a greater burden of cardiometabolic and socioeconomic risk factors than men, particularly younger women. Attention to these persisting disparities is needed to reduce the burden of CVD in women.Trial registration number ClinicalTrials.gov (NCT01794143)

Extensive research in well-studied animal models underscores the importance of commensal gastrointestinal (gut) microbes to animal physiology. Gut microbes have been shown to impact dietary digestion, mediate infection, and even modify behavior and cognition. Given the large physiological and pathophysiological contribution microbes provide their host, it is reasonable to assume that the vertebrate gut microbiome may also impact the fitness, health and ecology of wildlife. In accordance with this expectation, an increasing number of investigations have considered the role of the gut microbiome in wildlife ecology, health, and conservation. To help promote the development of this nascent field, we need to dissolve the technical barriers prohibitive to performing wildlife microbiome research. The present review discusses the 16S rRNA gene microbiome research landscape, clarifying best practices in microbiome data generation and analysis, with particular emphasis on unique situations that arise during wildlife investigations. Special consideration is given to topics relevant for microbiome wildlife research from sample collection to molecular techniques for data generation, to data analysis strategies. Our hope is that this article not only calls for greater integration of microbiome analyses into wildlife ecology and health studies but provides researchers with the technical framework needed to successfully conduct such investigations.

Objective: Real‐world data on cardiopulmonary events among pregnant women receiving β‐agonist therapy are scarce. In the present study, we aimed to examine the absolute and relative risks of maternal cardiopulmonary events associated with the use of β‐agonist ritodrine during pregnancy. Methods: By linking Taiwan's National Birth Certificate Application Database with National Health Insurance data, 1 831 564 pregnancies at ≥20 weeks' gestation were identified. Age‐standardized incidence rates of cardiopulmonary events among pregnant women exposed to ritodrine were estimated. Nested case–control analyses were conducted to evaluate the relative risk of pulmonary edema, heart failure, and arrhythmia associated with prior ritodrine use. Cases and controls were matched using risk set sampling, and adjusted odds ratios were estimated using conditional logistic regression models. Results: A total of 189 cases of pulmonary edema, 126 cases of heart failure, and 162 cases of arrhythmia were identified (corresponding age‐standardized incidence rates: 20.90, 8.35, and 16.63 per 100 000 among pregnant women only exposed to oral ritodrine; 91.28, 36.01, and 14.61 per 100 000 among those ever exposed to intravenous ritodrine). Exposure to oral ritodrine was associated with a lower increased risk of pulmonary edema (aOR 1.76; 95% CI: 1.12–2.76) and arrhythmia (2.21; 1.47–3.32) whereas exposure to ritodrine injection was associated with a significantly higher risk of pulmonary edema (10.56; 6.39–17.45), arrhythmia (4.15; 1.99–8.64), and heart failure (5.58; 2.27–13.74). Conclusions: Pregnant women receiving intravenous ritodrine therapy had higher cardiopulmonary risks and should be intensively monitored. While the relative risk associated with oral ritodrine is not pronounced, it should be used judiciously among pregnant women as well. Synopsis: Oral ritodrine exposure in pregnancy doubles the risk of pulmonary edema and arrhythmia, while ritodrine injections pose a higher risk—11‐fold for pulmonary edema and four‐ to six‐fold for heart failure/arrhythmia. [ABSTRACT FROM AUTHOR]

There is a recognized need to better understand changes in the epidemiology of psoriasis and psoriatic arthritis (PsA) over time in Asia. Using the Taiwan National Health Insurance claim records this population-based study examined changes in the prevalence, incidence, and mortality rates in patients with psoriasis or psoriatic arthritis in Taiwan over 12 years. Patients with ≥1 diagnosis code for psoriasis or psoriatic arthritis, recorded either by dermatologists or rheumatologists, were identified. Annual age- and sex-standardized prevalence and incidence rates were calculated using the Taiwan general population as reference. To investigate mortality, each patient in the incident cohort was matched to 10 comparators from the general population by sex and age (at diagnosis). The risk of mortality between study cohorts and comparators was analysed by Cox proportional hazard regression. The prevalence of psoriasis (0.18–0.86%) and psoriatic arthritis (0.01–0.08%) increased steadily between 2006 and 2017. The incidence rates, however, remained stable (psoriasis: 62–65 per 100,000 person-years; psoriatic arthritis: 6–5 per 100,000 person-years). The risk of all-cause mortality for patients with psoriasis (hazard ratio 1.16; 95% confidence interval: 1.13–1.19) was higher than the general population, despite a decreasing trend over time in the all-cause mortality rates for both groups. The steady increase in the prevalence of psoriasis despite stable incidence rates suggests that improvements in life expectancy may be the key determinant of this increase.

Background: In an effort to optimize clinical outcomes and enhance stability, ultracongruent bearings have been increasingly used in primary total knee arthroplasty (TKA). The importance of the posterior cruciate ligament (PCL) and optimal sagittal tibial baseplate position in ultracongruent bearing TKA remains unknown. This study sought to determine whether these modifiable, surgical-technique-dependent variables meaningfully impact patient-reported outcome measures. Methods: A total of 759 primary TKAs of the same dual-pivot design performed using a consistent surgical technique between January 2016 and April 2019 were retrospectively reviewed. PCL status was recorded, and anteroposterior (AP) tibial baseplate position and posterior tibial slope were measured by two independent blinded raters. Patient-reported outcomes related to pain, function, satisfaction, and activity level were analyzed in relationship to PCL status, posterior tibial slope, and AP tibial baseplate position, in addition to other pertinent covariates. Results: Median age and body mass index of the cohort were 68.3 years and 33.4 kg/m2, respectively, with 73% being female. In multivariate analysis, partial or full release of the PCL was predictive of a knee “always” feeling normal (odds ratio 1.42, P = .041). Furthermore, tibial baseplate position closer to the middle of the tibia was associated with greater improvements in pain with level walking, pain while climbing stairs, and Knee Injury and Osteoarthritis Outcome Score for Joint Replacement total scores (P ≤ .079). Conclusion: In congruent dual-pivot bearing TKA, partially or fully releasing the PCL and AP tibial baseplate position closer to the middle of the tibia may provide greater improvement in pain and function scores at minimum 1-year follow-up.

Abstract Background Several studies have found a so-called weekend effect that patients admitted at the weekends had worse clinical outcomes than patients admitted at the weekdays. We performed this retrospective cohort study to explore the weekend effect in four major cardiovascular emergencies in Taiwan. Methods The Taiwan National Health Insurance (NHI) claims database between 2005 and 2015 was used. We extracted 3811 incident cases of ruptured aortic aneurysm, 184,769 incident cases of acute myocardial infarction, 492,127 incident cases of ischemic stroke, and 15,033 incident cases of pulmonary embolism from 9,529,049 patients having at least one record of hospitalization in the NHI claims database within 2006 ~ 2014. Patients were classified as weekends or weekdays admission groups. Dates of in-hospital mortality and one-year mortality were obtained from the Taiwan National Death Registry. Results We found no difference in in-hospital mortality between weekend group and weekday group in patients with ruptured aortic aneurysm (45.4% vs 45.3%, adjusted odds ratio [OR] 1.01, 95% confidence interval [CI] 0.87–1.17, p = 0.93), patients with acute myocardial infarction (15.8% vs 16.2%, adjusted OR 0.98, 95% CI 0.95–1.00, p = 0.10), patients with ischemic stroke (4.1% vs 4.2%, adjusted OR 0.99, 95% CI 0.96–1.03, p = 0.71), and patients with pulmonary embolism (14.6% vs 14.6%, adjusted OR 1.02, 95% CI 0.92–1.15, p = 0.66). The results remained for 1 year in all the four major cardiovascular emergencies. Conclusions We found no difference in either short-term or long-term mortality between patients admitted on weekends and patients admitted on weekdays in four major cardiovascular emergencies in Taiwan.

Abstract Background Real-world impact of extended-release formulations of oral drugs should ideally be evaluated in population-based health data. Objective To evaluate changes in utilization of the dopamine agonist pramipexole for Parkinson’s disease after the introduction of extended-release (ER) pramipexole in Taiwan. Patients and Methods Source data were derived from National Health Insurance claims. Patients with a diagnosis of Parkinson’s disease and pramipexole prescriptions were identified. Drug use patterns from 2009 through 2011 (only the immediate-release [IR] formulation was available) and from 2012 through 2017 (both the IR and ER formulations were available) were assessed. Outcomes of interest were levodopa equivalent dose per day (LEDD) and 1-year adherence, as measured by the medication possession ratio (MPR). Results LEDDs associated with pramipexole ER prescriptions were more than twice as large as that associated with pramipexole IR, both in pramipexole used in monotherapy and that used in combination therapy. One-year MPRs for pramipexole ER initiators were all larger than 73% from 2012 through 2016 and 1-year MPRs for pramipexole IR initiators were less than 65% in 2010 and 2011. Conclusion Introduction of pramipexole ER to Taiwan resulted in higher LEDD in prescriptions with pramipexole. Patients with Parkinson’s disease who were initiated on pramipexole ER had better adherence to the medication than those who were prescribed pramipexole IR.

Older adult populations are at risk for zinc deficiency, which may predispose them to immune dysfunction and age-related chronic inflammation that drives myriad diseases and disorders. Recent work also implicates the gut microbiome in the onset and severity of age-related inflammation, indicating that dietary zinc status and the gut microbiome may interact to impact age-related host immunity. We hypothesize that age-related alterations in the gut microbiome contribute to the demonstrated zinc deficits in host zinc levels and increased inflammation. We tested this hypothesis with a multifactor two-part study design in a C57BL/6 mouse model. The two studies included young (2 month old) and aged (24 month old) mice fed either (1) a zinc adequate or zinc supplemented diet, or (2) a zinc adequate or marginal zinc deficient diet, respectively. Overall microbiome composition did not significantly change with zinc status; beta diversity was driven almost exclusively by age effects. Microbiome differences due to age are evident at all taxonomic levels, with more than half of all taxonomic units significantly different. Furthermore, we found 150 out of 186 genera were significantly different between the two age groups, with Bacteriodes and Parabacteroides being the primary taxa of young and old mice, respectively. These data suggest that modulating individual micronutrient concentrations does not lead to comprehensive microbiome shifts, but rather affects specific components of the gut microbiome. However, a phylogenetic agglomeration technique (ClaaTU) revealed phylogenetic clades that respond to modulation of dietary zinc status and inflammation state in an age-dependent manner. Collectively, these results suggest that a complex interplay exists between host age, gut microbiome composition, and dietary zinc status.

Abstract Introduction The new user cohort design is widely used to assess the effects of a new drug, such as dabigatran, but inherently excludes some users due to prior use of the comparator drug, for example warfarin. The prevalent new-user design offers a solution that includes all eligible users of the new drug. Objective To evaluate the safety and effectiveness of dabigatran versus warfarin in non-valvular atrial fibrillation (NVAF) patients with prevalent new-user design. Methods Taiwan National Health Insurance and mortality data from 2011 through 2015 were utilized. From an incident NVAF cohort, we identified dabigatran initiators as either incident or prevalent (switchers from warfarin) new users. Time- and prescription-based exposure sets were formed for dabigatran initiators to account for prior warfarin prescriptions. A comparable warfarin user was matched on the time-conditional propensity score to the dabigatran initiator in each set. The matched patients were followed for clinical outcomes, with Cox proportional hazards model used to estimate hazard ratios (HRs). Results There were 10,811 dabigatran initiators, including 22% prevalent new users (switchers), who formed the exposure sets and were matched 1:1 to warfarin users. Dabigatran use was associated with lower risks of intracranial hemorrhage (HR 0.51; 95% confidence interval [CI] 0.39, 0.66) and gastrointestinal bleeding (HR 0.81; 95% CI 0.70, 0.92), compared with warfarin use. These effects were similar between the incident and prevalent new users. Conclusion Using a design that includes both incident and prevalent new users of dabigatran, the use of dabigatran is associated with lower major bleeding risk than warfarin use among patients with incident NVAF.

Abstract Backgrounds To examine the comparative effectiveness between dual and single antiplatelet therapies in real-world, medically managed elderly patients with acute myocardial infarction (AMI). Methods This retrospective study identified very elderly (> 85 years) patients, who were medically managed, with their first AMI from the Taiwan National Health Insurance claims database from 2007 to 2010. Patients were classified as dual antiplatelet therapy (DAPT) group, aspirin only group and clopidogrel only group. Study outcomes included all-cause death, cardiovascular death and gastrointestinal bleeding. Treating DAPT group as the reference, we employed a multivariable Cox regression model to compare the relative risks of outcomes between 3 groups using pairwise comparison approach. Results Among 1469 patients with incident ST-elevation myocardial infarction (STEMI, 14%) or non-STEMI (86%), 390 patients were prescribed DAPT, 549 aspirin only, and 530 clopidogrel only. After 9 months of follow-up, aspirin only group had similar risks of all-cause death (adjusted HR 1.21, 95% CI 0.77–1.89, p = 0.41), cardiovascular death (adjusted HR 1.16, 95% CI 0.66–2.04, p = 0.60) and gastrointestinal bleeding (adjusted HR 1.66, 95% CI 0.77–3.57, p = 0.20) in comparison with DAPT group. Clopidogrel users had a higher risk of all-cause death (adjusted HR 1.50, 95% CI 1.00–2.25, p = 0.049) but similar risks of cardiovascular death and gastrointestinal bleeding when compared with DAPT. Conclusions Among very elderly patients who were medically managed after AMI, single antiplatelet therapy had comparable protective effect as DAPT. But clopidogrel only strategy was associated with a higher risk of all-cause death.

Abstract Background Patients with symptoms of both asthma and chronic obstructive pulmonary disease (COPD) may be classified with the term asthma-COPD overlap (ACO). ACO is of considerable interest as it is currently poorly characterised and has been associated with worse health outcomes and higher healthcare costs compared with COPD or asthma alone. Patients with ACO in Asia remain poorly described, and there is limited information regarding their resource utilisation compared with patients with asthma or COPD only. This study investigated the characteristics, disease burden and medical resource utilisation of patients with ACO in Taiwan. Methods This was a retrospective cohort study of patients identified from National Health Insurance (NHI) claims data in Taiwan in 2009–2011. Patients were classified into incident ACO, COPD or asthma cohorts according to International Classification of Disease, ninth revision, clinical modification codes in claims. Eligible patients were ≥40 years of age with 12 months’ continuous enrolment in the NHI programme pre- and post-index date (date of the first relevant medical claim). Results Patients with ACO (N = 22,328) and COPD (N = 69,648) were older and more likely to be male than those with asthma (N = 50,293). Patients with ACO had more comorbidities and exacerbations, with higher medication use: short-acting β2-agonist prescriptions ranged from 30.4% of patients (asthma cohort) to 43.6% (ACO cohort), and inhaled corticosteroid/long-acting β2-agonist combination prescriptions ranged from 11.1% (COPD cohort) to 35.0% (ACO cohort) in the 12 months following index. Patients with ACO generally had the highest medication costs of any cohort (long-acting muscarinic antagonist costs ranged from $227/patient [asthma cohort] to $349/patient [ACO cohort]); they also experienced more respiratory-related hospital visits than patients with asthma or COPD (mean outpatient/inpatient visits per patient post-index: 9.1/1.9 [ACO cohort] vs 5.7/1.4 [asthma cohort] and 6.4/1.7 [COPD cohort]). Conclusions Patients with ACO in Taiwan experience a greater disease burden with greater healthcare resource utilisation, and higher costs, than patients with asthma or COPD alone.

Red cell distribution width (RDW) can effectively predict prognosis in coronary artery disease (CAD) patients following percutaneous coronary intervention (PCI). There is currently no relevant research to demonstrate a linear or non-linear association between RDW and mortality. This is a multi-center, retrospective cohort study, with data collected from 2006 to 2017. Source data included electronic medical records of the Integrated Medical Database of National Taiwan University Hospital, and health insurance claims from the National Health Insurance Administration. Patients were stratified into five groups according to RDW values (13.4%, 14.1%, 14.8%, and 15.9%). Multivariable logistic and Cox regression analyses were used to determine 1-year all-cause and cardiovascular (CV) mortalities. Data of 10,669 patients were analyzed and those with the lowest RDW (≤13.3%) served as the reference group. The adjusted odds ratios (ORs) of 1-year all-cause mortality from the second to fifth RDW group were 1.386, 1.589, 2.090, and 3.192, respectively (p for trend < 0.001). The adjusted ORs of 1-year CV mortality were 1.555, 1.585, 1.623, and 2.850, respectively (p for trend = 0.015). The adjusted hazard ratios (HRs) of 1-year all-cause mortality were 1.394, 1.592, 2.003, and 2.689, respectively (p for trend = 0.006). The adjusted HRs of 1-year CV mortality were 1.533, 1.568, 1.609, and 2.710, respectively (p for trend = 0.015). RDW was an independent predicting factor and had a linear relationship with the 1-year all-cause and CV mortalities in patients undergoing PCI. Thus, RDW may be a clinically useful parameter to predict the mortality in those patients.

Abstract Background Liver enzyme elevation is an important and common adverse effect among patients with immune-mediated diseases who receive tumour necrosis factor inhibitors (anti-TNF), and has various causes. Hence, we evaluated the relative risks of developing liver enzyme elevation in anti-TNF users with differing hepatitis B virus (HBV) infection status. Methods At a hospital in central Taiwan, 407 patients with rheumatoid arthritis, ankylosing spondylitis, or psoriasis/psoriatic arthritis received anti-TNF therapy between 1 January 2004 and 30 June 2012. We performed a nested case-control study (n = 368) of cases with serum alanine aminotransferase (ALT) > 40 international units/L ≤ 12 months after starting anti-TNF therapy, and corresponding controls without liver enzyme elevation. Conditional logistic regression was used to evaluate associations between liver enzyme elevation and HBV serostatus, as well as other risk factors. Results Thirty cases were compared to 338 controls. After adjustment for potential confounders, HBV surface antigen-positive (HBsAg+) serostatus was associated with substantially higher likelihood of developing elevated ALT (adjusted odds ratio 7.91, 95% confidence interval (CI) 2.16–31.31) relative to those with an uninfected HBV status; no such association was observed among HBsAg-negative/HBV core antibody-positive (HBsAg–/HBcAb+) patients (adjusted odds ratio 1.00, 95% CI 0.33–3.25). Increased risk of ALT elevation was associated with methotrexate used alone, without folic acid (adjusted odds ratio 11.60, 95% CI 2.52–56.46), and history of ALT elevation (adjusted odds ratio 13.71, 95% CI 4.32–45.75). Conclusions HBsAg+ patients with immune-mediated diseases who received anti-TNF therapy had an approximately eight-fold higher likelihood of liver enzyme elevation than those without HBV infection, whereas patients with HBsAg–/HBcAb+ serostatus had a risk similar to that of uninfected patients.

Background: The risks of serious infections that lead to hospitalization and mortality in patients with psoriasis in Asia have not been comprehensively studied. Objectives: We examined the incidence of serious infection and infection mortality in patients with psoriasis. Methods: This population‐based retrospective cohort study used the Taiwan National Health Insurance claims database from 2000 to 2017. Adult patients with psoriasis were identified by a relevant International Classification of Diseases (ICD) code and matched to six comparators without psoriasis on age and sex. Psoriasis patients were categorized as having moderate‐to‐severe disease once exposed to systemic therapies, phototherapy or biologic therapies. The incidence of serious infection and infection mortality were identified by ICD codes from inpatient hospitalization and death registration. Cox proportional hazard models were used to compare the risk, and the results were adjusted for covariates and presented as adjusted hazard ratios (aHR) and 95% confidence interval (95% CI). Results: Overall, 185,434 psoriasis patients and 1,112,581 comparators were included. A higher rate of serious infection (aHR: 1.21, 95% CI: 1.19–1.22) was found in patients with psoriasis compared to matched comparators without psoriasis, and the risk was enhanced when patients had moderate‐to‐severe psoriasis (aHR: 1.30, 95% CI: 1.27–1.34). Specifically, there was an increased risk of serious infection due to respiratory infections (aHR: 1.11, 95% CI: 1.09–1.13), skin/soft‐tissue infections (aHR: 1.57, 95% CI: 1.52–1.62), sepsis (aHR: 1.23, 95% CI: 1.19–1.27), urinary tract infections (aHR: 1.11, 95% CI: 1.08–1.14), hepatitis B (aHR: 1.18, 95% CI: 1.06–1.30) and hepatitis C (aHR: 1.49, 95% CI: 1.32–1.69). Furthermore, psoriasis patients were associated with a higher risk of infection‐related mortality (aHR: 1.15, 95% CI: 1.11–1.18) compared to matched comparators. Conclusion: Patients with psoriasis had a higher risk of serious infection and infection mortality, which was enhanced by moderate‐to‐severe psoriasis. Practitioners should be aware of the increased risk in patients with psoriasis, but it should not be a barrier to offering effective treatment. [ABSTRACT FROM AUTHOR]

BackgroundWidespread use of broad-spectrum antibiotics contributes to increasing rates of bacterial resistance to antibiotics. Second-generation macrolides have become popular for use among children because of their broad spectrum and favorable dosing and side-effect profiles, although experts do not generally recommend them for use as initial treatment of infections among younger children.ObjectiveTo assess trends in second-generation macrolide use from 1996 to 2000 among children treated as outpatients in 9 US health plans, including associated diagnoses and use as initial treatment.MethodsWe sampled claims data for 25000 children, 3 months to

BackgroundIsolated case reports of gastric ulcers after alendronate sodium use raised concern about the gastroduodenal safety of daily alendronate. This study was conducted to estimate the excess risk of hospitalizations for gastric or duodenal perforations, ulcers, and bleeding associated with alendronate use.Participants and methodsStudy subjects were 6432 men and women, 35 years or older. The subjects were members of 8 health maintenance organizations who were dispensed alendronate from October 1995 through September 1997. There was also a group of 33 176 age-, sex-, and health maintenance organization-matched unexposed persons. Because of concerns that osteoporosis might confound the association between alendronate use and perforation, ulcer, or bleeding, a second comparison group of 9776 women, 60 years or older, who had osteoporotic fractures was assembled. Hospitalizations for gastroduodenal events were identified by discharge diagnosis codes in automated claims records, and confirmed by manual record review.ResultsBased on the 14 confirmed events in the alendronate group and 35 in the unexposed group, the crude incidence rate ratio of gastroduodenal perforation, ulcer, or bleeding for the alendronate cohort was 3.0. The incidence rate ratio was 1.8 (95% confidence interval, 0.8-3.9) after control for prior hospitalizations, comorbidity, and recent exposure to prescription nonsteroidal anti-inflammatory drugs and oral corticosteroids. The crude incidence ratio rate for the age, sex, and health maintenance organizations-restricted cohort of alendronate users relative to the fracture cohort was 1.1 and the adjusted incidence rate ratio was 1.1 (95% confidence interval, 0.6-2.2).ConclusionsOsteoporosis and related factors appear to play an important role in the relationship between alendronate use and confirmed gastroduodenal perforation, ulcer, or bleeding; a substantial fraction of the increased risk we observed for alendronate users in the unadjusted analysis was the result of confounding.

The automated health plan data and data from medical chart abstractions from eight large health maintenance organizations were used to evaluate the positive predictive values (PPVs) of the International Classification of Diseases, 9th revision (ICD-9) codes for cases of peptic ulcers and upper gastrointestinal bleeding. Overall, 207 of 884 cases of peptic ulcers and upper gastrointestinal bleeding (23%) were confirmed by surgery, endoscopy, X-ray, or autopsy. The PPVs were 66% for hospitalizations with codes for duodenal ulcer (ICD-9-CM 532), 61% for gastric/gastrojejunal ulcer (ICD-9-CM 531, 534), 1% for peptic ulcer (ICD-9-CM 533), and 9% for gastrointestinal hemorrhage (ICD-9-CM578). The overall and diagnostic category-specific PPVs were generally similar for the various HMOs. This study, using data from a large number of health plans located in different geographical regions, underscores the importance of evaluating the accuracy of the diagnoses from automated health plan databases.

Viruses are of great concern in vineyards. They cost the California wine grape industry as much as $91,661 per acre over the life of a vineyard, according to a 2015 economic study of the North Coast wine-growing region. As a first step toward managing viruses, growers are encouraged to plant certified material regulated by the California Grapevine Registration and Certification program. There are risks in sourcing plant material from stocks that are not subject to the same level of regulation. We surveyed vineyards of varying ages for eight common viruses to demonstrate the value of selecting certified material for new plantings.

BackgroundInhibitors of hydroxymethylglutaryl-coenzyme A reductase (statins) increase new bone formation in rodents and in human cells in vitro. Statin use is associated with increased bone mineral density of the femoral neck. We undertook a population-based case-control study at six health-maintenance organisations in the USA to investigate further the relation between statin use and fracture risk among older women.MethodsWe investigated women aged 60 years or older. Exposure, outcome, and confounder information was obtained from automated claims and pharmacy data from October, 1994, to September, 1997. Cases had an incident diagnosis of non-pathological fracture of the hip, humerus, distal tibia, wrist, or vertebrae between October, 1996, and September, 1997. Controls had no fracture during this period. We excluded women with records of dispensing of drugs to treat osteoporosis.FindingsThere were 928 cases and 2747 controls. Compared with women who had no record of statin dispensing during the previous 2 years, women with 13 or more statin dispensings during this period had a decreased risk of non-pathological fracture (odds ratio 0.48 [95% CI 0.27-0.83]) after adjustment for age, number of hospital admissions during the previous year, chronic disease score, and use of non-statin lipid-lowering drugs. No association was found between fracture risk and fewer than 13 dispensings of statins or between fracture risk and use of non-statin lipid-lowering drugs.InterpretationStatins seem to be protective against non-pathological fracture among older women. These findings are compatible with the hypothesis that statins increase bone mineral density in human beings and thereby decrease the risk of osteoporotic fractures.

ABSTRACT Our knowledge of how the gut microbiome relates to mammalian evolution benefits from the identification of gut microbial taxa that are unexpectedly prevalent or unexpectedly conserved across mammals. Such taxa enable experimental determination of the traits needed for such microbes to succeed as gut generalists, as well as those traits that impact mammalian fitness. However, the punctuated resolution of microbial taxonomy may limit our ability to detect conserved gut microbes, especially in cases in which broadly related microbial lineages possess shared traits that drive their apparent ubiquity across mammals. To advance the discovery of conserved mammalian gut microbes, we developed a novel ecophylogenetic approach to taxonomy that groups microbes into taxonomic units based on their shared ancestry and their common distribution across mammals. Applying this approach to previously generated gut microbiome data uncovered monophyletic clades of gut bacteria that are conserved across mammals. It also resolved microbial clades exclusive to and conserved among particular mammalian lineages. Conserved clades often manifest phylogenetic patterns, such as cophylogeny with their host, that indicate that they are subject to selective processes, such as host filtering. Moreover, this analysis identified variation in the rate at which mammals acquire or lose conserved microbial clades and resolved a human-accelerated loss of conserved clades. Collectively, the data from this study reveal mammalian gut microbiota that possess traits linked to mammalian phylogeny, point to the existence of a core set of microbes that comprise the mammalian gut microbiome, and clarify potential evolutionary or ecologic mechanisms driving the gut microbiome’s diversification throughout mammalian evolution. IMPORTANCE Our understanding of mammalian evolution has become microbiome-aware. While emerging research links mammalian biodiversity and the gut microbiome, we lack insight into which microbes potentially impact mammalian evolution. Microbes common to diverse mammalian species may be strong candidates, as their absence in the gut may affect how the microbiome functionally contributes to mammalian physiology to adversely affect fitness. Identifying such conserved gut microbes is thus important to ultimately assessing the microbiome’s potential role in mammalian evolution. To advance their discovery, we developed an approach that identifies ancestrally related groups of microbes that distribute across mammals in a way that indicates their collective conservation. These conserved clades are presumed to have evolved a trait in their ancestor that matters to their distribution across mammals and which has been retained among clade members. We found not only that such clades do exist among mammals but also that they appear to be subject to natural selection and characterize human evolution.

Pericentromeric satellite repeats are enriched in 5-methylcytosine (5mC). Loss of 5mC at these sequences is common in cancer and is a hallmark of Immunodeficiency, Centromere and Facial abnormalities (ICF) syndrome. While the general importance of 5mC is well-established, the specific functions of 5mC at pericentromeres are less clear. To address this deficiency, we generated a viable animal model of pericentromeric hypomethylation through mutation of the ICF-gene ZBTB24. Deletion of zebrafish zbtb24 caused a progressive loss of 5mC at pericentromeres and ICF-like phenotypes. Hypomethylation of these repeats triggered derepression of pericentromeric transcripts and activation of an interferon-based innate immune response. Injection of pericentromeric RNA is sufficient to elicit this response in wild-type embryos, and mutation of the MDA5-MAVS dsRNA-sensing machinery blocks the response in mutants. These findings identify activation of the innate immune system as an early consequence of pericentromeric hypomethylation, implicating derepression of pericentromeric transcripts as a trigger of autoimmunity.Editorial note: This article has been through an editorial process in which the authors decide how to respond to the issues raised during peer review. The Reviewing Editor's assessment is that all the issues have been addressed (see decision letter).