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Summary: Background: Seladelpar is a potent and selective peroxisome proliferator‐activated receptor‐δ agonist that targets multiple cell types involved in primary biliary cholangitis (PBC), leading to anti‐cholestatic, anti‐inflammatory and anti‐pruritic effects. Aims: To evaluate the long‐term safety and efficacy of seladelpar in patients with PBC. Methods: In an open‐label, international, long‐term extension study, patients with PBC completing seladelpar lead‐in studies continued treatment. Seladelpar was taken orally once daily at doses of 5 or 10 mg with dose adjustment permitted for safety or tolerability. The primary analysis was for safety and the secondary efficacy analysis examined biochemical markers of cholestasis and liver injury. The study was terminated early due to the unexpected histological findings in a concurrent study for non‐alcoholic steatohepatitis, which were subsequently found to predate treatment. Safety and efficacy data were analysed through 2 years. Results: There were no serious treatment‐related adverse events observed among 106 patients treated with seladelpar for up to 2 years. There were four discontinuations for safety, one possibly related to seladelpar. Among 53 patients who completed 2 years of seladelpar, response rates increased from years 1 to 2 for the composite endpoint (alkaline phosphatase [ALP] <1.67 × ULN, ≥15% decrease in ALP, and total bilirubin ≤ULN) and ALP normalisation from 66% to 79% and from 26% to 42%, respectively. In those with elevated bilirubin at baseline, 43% achieved normalisation at year 2. Conclusions: Seladelpar was safe, and markedly improved biochemical markers of cholestasis and liver injury in patients with PBC. These effects were maintained or improved throughout the second year. Clinicaltrials.gov: NCT03301506; Clinicaltrialsregister.eu: 2017‐003910‐16. [ABSTRACT FROM AUTHOR]

This document is a featured cover image for the journal Alimentary Pharmacology & Therapeutics. The image is based on a clinical trial extension study on the safety and efficacy of seladelpar in patients with primary biliary cholangitis. The study was conducted by a team of authors and provides two-year results. The document does not provide any specific details or findings from the study, but it serves as a visual representation of the research. [Extracted from the article]

The first clinical case of persistent HEV infection in England was reported in 2009. We describe the demography, virology and outcomes of patients identified with persistent HEV infection in England and Wales between 2009 and 2017. A series of 94 patients with persistent HEV infection, defined by HEV viraemia of more than 12 weeks, was identified through routine reference laboratory testing. Virology, serology and clinical data were recorded through an approved PHE Enhanced Surveillance System. Sixty‐six cases (70.2%) were transplant recipients, 16 (17.0%) had an underlying haematological malignancy without stem cell transplantation, six (6.4%) had advanced HIV infection, five (5.3%) were otherwise immunosuppressed, and one patient (1.1%) had no identified immunosuppression. Retrospective analysis of 46 patients demonstrated a median 38 weeks of viraemia before diagnostic HEV testing. At initial diagnosis, 16 patients (17.0%) had no detectable anti‐HEV serological response. Of 65 patients treated with ribavirin monotherapy, 11 (16.9%) suffered virological relapse despite undetectable RNA in plasma or stool at treatment cessation. Persistent HEV infection remains a rare diagnosis, but we demonstrate that a broad range of immunocompromised patients are susceptible. Both lack of awareness and the pauci‐symptomatic nature of persistent HEV infection likely contribute to significant delays in diagnosis. Diagnosis should rely on molecular testing since anti‐HEV serology is insufficient to exclude persistent HEV infection. Finally, despite treatment with ribavirin, relapses occur even after cessation of detectable faecal shedding of HEV RNA, further emphasising the requirement to demonstrate sustained virological responses to treatment. [ABSTRACT FROM AUTHOR]

Authors featured in this department share anthropological perspectives and qualitative insights to redefine community in adolescent and adult literacy practice. [ABSTRACT FROM AUTHOR]

Summary: Background: Palliative care remains suboptimal in end‐stage liver disease. Aim: To inform a definitive study, we assessed palliative long‐term abdominal drains in end‐stage liver disease to determine recruitment, attrition, safety/potential effectiveness, questionnaires/interview uptake/completion and make a preliminary cost comparison. Methods: A 12‐week feasibility nonblinded randomised controlled trial comparing large‐volume paracentesis vs long‐term abdominal drains in refractory ascites due to end‐stage liver disease with fortnightly home visits for clinical/questionnaire‐based assessments. Study success criteria were attrition not >50%, <10% long‐term abdominal drain removal due to complications, the long‐term abdominal drain group to spend <50% ascites‐related study time in hospital vs large‐volume paracentesis group and 80% questionnaire/interview uptake/completion. Results: Of 59 eligible patients, 36 (61%) were randomised, 17 to long‐term abdominal drain and 19 to large‐volume paracentesis. Following randomisation, median number (IQR) of hospital ascitic drains (long‐term abdominal drain group vs large‐volume paracentesis group) were 0 (0‐1) vs 4 (3‐7); week 12 serum albumin (g/L) and serum creatinine (μmol/L) were 29 (26.5‐32.5) vs 30 (25‐35) and 104.5 (81‐115.5) vs 127 (63‐158) respectively. Total attrition was 42% (long‐term abdominal drain group 47%, large‐volume paracentesis group 37%). Median (IQR) fortnightly community/hospital/social care ascites‐related costs and percentage study time in hospital were lower in the long‐term abdominal drain group, £329 (253‐580) vs £843 (603‐1060) and 0% (0‐0.74) vs 2.75% (2.35‐3.84) respectively. Self‐limiting cellulitis/leakage occurred in 41% (7/17) in the long‐term abdominal drain group vs 11% (2/19) in the large‐volume paracentesis group; peritonitis incidence was 6% (1/17) vs 11% (2/19) respectively. Questionnaires/interview uptake/completion were ≥80%; interviews indicated that long‐term abdominal drains could transform the care pathway. Conclusions: The REDUCe study demonstrates feasibility with preliminary evidence of long‐term abdominal drain acceptability/effectiveness/safety and reduction in health resource utilisation. Trial registration: ISRCTN30697116, date assigned: 07/10/2015. [ABSTRACT FROM AUTHOR]

Background & Aims Hepatitis C virus ( HCV) is bound to plasma lipoproteins and circulates as an infectious lipoviral particle ( LVP). Experimental evidence indicates that LVPs have decreased susceptibility to antibody-mediated neutralisation and higher infectivity. This study tested the hypothesis that LVPs are required to establish persistent infection, and conversely, low levels of LVP in recent HCV infection increase the probability of spontaneous HCV clearance. Methods LVP in non-fasting plasma was measured using the concentration of HCV RNA bound to large >100 n m sized lipoproteins after ex vivo addition of a lipid emulsion, that represented the maximum concentration of LVP (maxi- LVP). This method correlated with LVP in fasting plasma measured using iodixanol density gradient ultracentrifugation. Maxi- LVP was measured in a cohort of 180 HCV participants with recent HCV infection and detectable HCV RNA from the Australian Trial in Acute Hepatitis C ( ATAHC) and Hepatitis C Incidence and Transmission Study in prison ( HITS-p) cohorts. Results Spontaneous clearance occurred in 15% (27 of 180) of individuals. In adjusted analyses, low plasma maxi- LVP level was independently associated with spontaneous HCV clearance (≤827 IU/ml; adjusted odds ratio 3.98, 95% CI: 1.02, 15.51, P = 0.047), after adjusting for interferon lambda-3 rs8099917 genotype, estimated duration of HCV infection and total HCV RNA level. Conclusions Maxi- LVP is a biomarker for the maximum concentration of LVP in non-fasting samples. Low maxi- LVP level is an independent predictor of spontaneous clearance of acute HCV. [ABSTRACT FROM AUTHOR]

Sober living houses ( SLHs) are alcohol and drug-free living environments for individuals in recovery. The goal of this study was to map the distribution of SLHs in Los Angeles ( LA) County, California ( N = 260) and examine neighborhood correlates of SLH density. Locations of SLHs were geocoded and linked to tract-level Census data as well as to publicly available information on alcohol outlets and recovery resources. Neighborhoods with SLHs differed from neighborhoods without them on measures of socioeconomic disadvantage and accessibility of recovery resources. In multivariate, spatially lagged hurdle models stratified by monthly fees charged (less than $1400/month vs. $1400/month or greater), minority composition, and accessibility of treatment were associated with the presence of affordable SLHs. Accessibility of treatment was also associated with the number of affordable SLHs in those neighborhoods. Higher median housing value and accessibility of treatment were associated with whether a neighborhood had high-cost SLHs, and lower population density was associated with the number of high-cost SLHs in those neighborhoods. Neighborhood factors are associated with the availability of SLHs, and research is needed to better understand how these factors affect resident outcomes, as well as how SLHs may affect neighborhoods over time. [ABSTRACT FROM AUTHOR]

Background & Aims Hepatitis C virus ( HCV) utilises cholesterol and lipoprotein metabolism for replication and infectivity. Statins and omega-3 (n-3) polyunsaturated fatty acids ( PUFA) have been shown to have antiviral properties in vitro. This open label pilot study evaluated the efficacy of fluvastatin (Lescol® 40-80 mg) and n-3 PUFA (Omacor®1 g and 2-4 g) on HCV- RNA and lipoviral particles ( LVP) in difficult to treat prior non-responders. Methods Patients ( n = 60) were randomly allocated in a factorial design to: no active drug; low-dose n-3 PUFA; high-dose n-3 PUFA; fluvastatin; low-dose n-3 PUFA + fluvastatin; or high-dose n-3 PUFA + fluvastatin. 50/60 completed study drugs for 12 weeks and followed up to week 24. Comparison was made between fluvastatin ( n = 24) vs no fluvastatin ( n = 26) and n-3 PUFA high-dose ( n = 17) vs low-dose ( n = 17) vs none ( n = 16). The primary outcomes were change in total HCV- RNA, LVP and ALT at week 12 compared with baseline. Secondary outcome was change in interferon-gamma-inducible protein-10 ( IP10) as a measure of interferon activation. Results 35% had compensated cirrhosis and 45% were prior null responders. There was no significant change in total HCV RNA, LVP, non-LVP or LVP ratio in patients receiving fluvastatin or n-3 PUFAs. ALT was not significantly different in those treated with fluvastatin or n-3 PUFAs. 12 weeks of low-dose n-3 PUFA decreased median IP10 concentration by −39 pg/ml (−111, 7.0 pg/ml Q1-Q3). Conclusions Fluvastatin and n-3 PUFAs have no effect on plasma HCV- RNA or LVP. The effect of low-dose n-3 PUFA on IP10 warrants further prospective evaluation as a supplemental therapy to enhance interferon sensitivity. [ABSTRACT FROM AUTHOR]

Studies suggest that headache accounts for approximately 1% of pediatric emergency department ( ED) visits. ED physicians must distinguish between primary headaches, such as a tension or migraine, and secondary headaches caused by systemic disease including neoplasm, infection, or intracranial hemorrhage. A recent study found that 40% of children presenting to the ED with headache were diagnosed with a primary headache, and 75% of these were migraine. Once the diagnosis of migraine has been made, the ED physician is faced with the challenge of determining appropriate abortive treatment. This review summarizes the most recent literature on pediatric migraine with an emphasis on diagnosis and abortive treatment in the ED. [ABSTRACT FROM AUTHOR]

Where have all the emergency paediatric mental health patients gone during COVID-19? Abbreviation ED emergency department INTRODUCTION The novel coronavirus that results in COVID-19 has significantly impacted the global healthcare system and economy since first reported in December 2019.1 Many countries and states have enacted stay-at-home orders and implemented social distancing guidelines to mitigate disease transmission. B, paediatric mental health census gl DISCUSSION Emergency departments increasingly provide urgent mental health care for youth.3 This study demonstrates a dramatic decrease in utilisation of a paediatric ED for paediatric mental health following a COVID-19 stay-at-home order. [Extracted from the article]

LINKED CONTENT This article is linked to Macken et al and Roy et al papers. To view these articles, visit https://doi.org/10.1111/apt.15802 and https://doi.org/10.1111/apt.15944 [ABSTRACT FROM AUTHOR]

LINKED CONTENT This article is linked to the Macken et al and Hudson papers. To view these articles, visit https://doi.org/10.1111/apt.15802 and https://doi.org/10.1111/apt.15894 [ABSTRACT FROM AUTHOR]

Although both Bcl-2/Bax ratio and Mcl-1 have been identified to be of clinical relevance in B-cell chronic lymphocytic leukemia (CLL), there is controversy regarding their role; further, their relative importance is not well delineated. Expression of Bcl-2, Bax, the Bcl-2/Bax ratio, and Mcl-1 in 51 consecutive previously untreated CLL patients and 16 controls was determined by Western blotting. Only 37 patients were treated, all with chlorambucil and prednisone initially. Six patients achieved complete response (CR), 14 were non-responders (NR), and 17 had a partial response (PR), as defined by NCI criteria. There was considerable inter-patient variability in protein expression and overlap with healthy volunteers (P > 0.05). All patients with CR had low Mcl-1 levels compared to the PR + NR group (0.07 +/- 0.02 vs. 0.14 +/- 0.07, P = 0.043). Higher Mcl-1 expression as determined by dichotomizing the data was associated with a failure to achieve CR (P = 0.021). The Bcl-2/Bax ratio was significantly associated with treatment response only when CR and PR were considered together (0.89 +/- 0.53 [CR + PR] vs. 3.38 +/- 4.47 [NR], P = 0.0118). There was no association with Rai stage. Low Mcl-1 appears to be a requirement for CR, while low Bcl-2/Bax ratio is indicative of some response to conventional treatment., (Copyright 2003 Wiley-Liss, Inc.)