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Background: Liver disease is an increasing cause of premature mortality. Early detection of liver disease in primary care gives opportunity to intervene and change outcomes. Engagement in liver disease care by NHS bodies responsible for primary care pathway development could drive improvements. The formation of integrated care systems (ICS) in England provides an opportunity to reassess engagement with liver disease nationally., Aim: To update the level of engagement with community chronic liver disease management among ICSs and health authorities across the UK., Design & Setting: A cross-sectional follow-up survey to ICS and UK health boards., Method: Questions used for a previous survey in 2020 were adapted and sent electronically to NHS bodies responsible for health care across the UK, using a freedom of information request. Quantitative analysis was undertaken using Microsoft Excel., Results: There were 67 responses from 68 possible ICS and health board areas, representing 99% UK coverage. Twenty-seven per cent had a named individual responsible for liver disease. Monitoring of local liver disease health statistics happened in 34% of all UK areas. Comprehensive care pathways were available in n = 24/67 (36%) of areas, an increase from 26% in the 2020 survey. Areas with no liver pathways in place fell from 58% to 36% between the two surveys. Regional variations persist, with Wales and Scotland moving towards comprehensive coverage. Almost double the number of areas were making use of transient elastography within community pathways of care, up from 25% to 46%., Conclusion: The results of this re-survey highlight improvements, but emphasise the need to build on regional success to further reduce inequality in care commissioning., (Copyright © 2025, The Authors.)

Regular exercise benefits learning and memory in older adults, but the neural mechanisms mediating these effects remain unclear. Evidence in young adults indicates that acute exercise creates a favourable environment for synaptic plasticity by enhancing cortical disinhibition. As such, we investigated whether plasticity-related disinhibition mediated the relationship between cardiorespiratory fitness and memory function in healthy older adults (n = 16, mean age = 66.06). Participants completed a graded maximal exercise test and assessments of visual and verbal memory, followed by two counterbalanced sessions involving 20 min of either high-intensity interval training exercise or rest. Disinhibition was measured following intermittent theta burst stimulation via paired-pulse transcranial magnetic stimulation. In line with our hypotheses, we observed a positive correlation between cardiorespiratory fitness and verbal memory, which was mediated by plasticity-related cortical disinhibition. Our novel finding implicates cortical disinhibition as a mechanism through which the effects of acute bouts of exercise may translate to improved memory in older adults. This finding extends current understanding of the physiological mechanisms underlying the positive influence of cardiorespiratory fitness for memory function in older adults, and further highlights the importance of promoting exercise engagement to maintain cognitive health in later life. KEY POINTS: There are well established benefits of regular exercise for memory function in older adults, but the mechanisms are unclear. Cortical disinhibition is important for laying down new memories, and is enhanced following acute exercise in young adults, suggesting it is a potential mechanism underlying these benefits in ageing. Older adults completed a fitness test and assessments of memory, followed by two sessions involving either 20 min of exercise or rest. Disinhibition was measured following intermittent theta burst stimulation via paired-pulse transcranial magnetic stimulation. Cardiorespiratory fitness was positively associated with memory performance. Higher fitness was associated with enhanced cortical disinhibition following acute exercise. Cortical disinhibition completely mediated the relationship between fitness and memory. This novel finding provides a mechanistic account for the positive influence of cardiorespiratory fitness on memory in later life, and emphasises the importance of regular exercise for cognitive health in older populations., (© 2024 The Authors. The Journal of Physiology published by John Wiley & Sons Ltd on behalf of The Physiological Society.)

The American, European, and Latin American liver societies have proposed a change in the nomenclature we use to describe alcohol-related liver disease and non-alcoholic fatty liver disease. Additionally, a term encompassing both is now advocated: steatotic liver disease, which includes metabolic dysfunction associated steatotic liver disease (MASLD) and MASLD with greater alcohol consumption (MetALD). These classifications offer increased relevance for clinicians, researchers, and patients alike. In this Viewpoint, we discuss the basis for this nomenclature shift and how it was developed. We also explore the challenges that will be faced in the adoption of such change. The proposed change seeks to banish stigma associated with phrasing such as alcoholic and fatty. However stigma, particularly related to the term fatty, is culturally nuanced, and reflects different entities depending on location. If such a change is internationally accepted, there will be wide-reaching effects on practitioners in primary care and metabolic medicine, and on patients. We discuss those effects and the opportunities the nomenclature change could offer, particularly for patients with alcohol and metabolic risk factors who represent a group previously ignored by clinical trials., (Crown Copyright © 2024 Published by Elsevier Ltd. All rights reserved.)

Background: We aimed to assess factors associated with patients' confidence in the ability of screening mammography to detect breast cancer., Methods: Data were analyzed from a cross-sectional, prospective survey conducted in 2017 of women without a breast cancer history who were undergoing screening mammography at our institution., Results: In total, 390 women completed the survey questions relevant to this study. Most respondents were 46 years or older (89.7%), White (87.6%), and college-educated (66.1%). Approximately 80% of respondents reported having confidence in the ability of screening mammography to detect breast cancer. Factors significantly associated with lower confidence in screening mammography were higher education ( P = .01 ) and dense breast tissue ( P < .001 ). Age ( P = .12 ), race ( P = .64 ), family history of breast cancer ( P = .17 ), prior abnormal mammogram ( P = .07 ), and mammogram frequency ( P = .42 ) were nonsignificant. Women with a college education or higher were less likely to report confidence in routine mammography than women with less education (odds ratio [OR]= 0.43; 95% CI, 0.20-0.84; P = .02 ). Compared with women who reported their breast tissue as not dense, women who were aware they had increased breast density (OR = 0.16; 95% CI, 0.04-0.49; P = .004 ) or were unaware whether they had increased breast density (OR = 0.17; 95% CI, 0.04-0.51; P = .005 ) reported less confidence in screening mammography., Discussion: Most respondents were confident in the ability of screening mammography to detect breast cancer. Confidence was inversely associated with education level and self-reported increased breast density., Conclusions: These findings highlight the importance of continued patient education about the effectiveness of screening mammography for patients with dense breast tissue., Competing Interests: Conflict of interest: The authors have no conflicts of interest to declare., (© Copyright by the American Board of Family Medicine.)

Objectives: Skeletal fluorosis is a metabolic bone disease caused by excessive exposure to fluoride, predominantly through contamination of drinking water. This study aimed to identify all cases of skeletal fluorosis in Tindigani village situated in Northern Tanzania. This was done following changes in drinking water sources after a previous prevalence study in 2009 in this population., Methods: In a door-to-door cross-sectional study of Tindigani village, a sample of residents was assessed for skeletal fluorosis and dental fluorosis. Diagnosis of skeletal fluorosis was based on pre-defined angles of deformity of the lower limbs. Dental fluorosis was diagnosed and graded using the Thylstrup and Fejerskov Index. Samples from current drinking water sources underwent fluoride analysis., Results: Tindigani village had a population of 1,944 individuals. Of the 1,532 individuals who were screened, 45 had skeletal fluorosis, giving a prevalence of 3.3% (95% CI=2.4, 4.3). Dental fluorosis was present in 82.5% of those examined (95% CI=79.8, 85.3). Dental fluorosis was present in all individuals with skeletal fluorosis and at higher grades than in the rest of the population. Drinking water samples were collected from 28 sources. These included piped, surface, well, and borehole water sources. Fluoride concentrations ranged from 0.45-38.59 mg/L of fluoride., Conclusions: Skeletal fluorosis is an ongoing but preventable health problem in the current population. The delivery of sustainable low fluoride piped water to this community would be of clear health benefit. This has been addressed at a local level., (© Foat et al.)

Objectives: COVID-19 studies report on hospital admission outcomes across SARS-CoV-2 waves of infection but knowledge of the impact of SARS-CoV-2 variants on the development of Long COVID in hospital survivors is limited. We sought to investigate Long COVID outcomes, aiming to compare outcomes in adult hospitalised survivors with known variants of concern during our first and second UK COVID-19 waves, prior to widespread vaccination., Design: Prospective observational cross-sectional study., Setting: Secondary care tertiary hospital in the UK., Participants: This study investigated Long COVID in 673 adults with laboratory-positive SARS-CoV-2 infection or clinically suspected COVID-19, 6 weeks after hospital discharge. We compared adults with wave 1 (wildtype variant, admitted from February to April 2020) and wave 2 patients (confirmed Alpha variant on viral sequencing (B.1.1.7), admitted from December 2020 to February 2021)., Outcome Measures: Associations of Long COVID presence (one or more of 14 symptoms) and total number of Long COVID symptoms with SARS-CoV-2 variant were analysed using multiple logistic and Poisson regression, respectively., Results: 322/400 (wave 1) and 248/273 (wave 2) patients completed follow-up. Predictors of increased total number of Long COVID symptoms included: pre-existing lung disease (adjusted count ratio (aCR)=1.26, 95% CI 1.07, 1.48) and more COVID-19 admission symptoms (aCR=1.07, 95% CI 1.02, 1.12). Weaker associations included increased length of inpatient stay (aCR=1.02, 95% CI 1.00, 1.03) and later review after discharge (aCR=1.00, 95% CI 1.00, 1.01). SARS-CoV-2 variant was not associated with Long COVID presence (OR=0.99, 95% CI 0.24, 4.20) or total number of symptoms (aCR=1.09, 95% CI 0.82, 1.44)., Conclusions: Patients with chronic lung disease or greater COVID-19 admission symptoms have higher Long COVID risk. SARS-CoV-2 variant was not predictive of Long COVID though in wave 2 we identified fewer admission symptoms, improved clinical trajectory and outcomes. Addressing modifiable factors such as length of stay and timepoint of clinical review following discharge may enable clinicians to move from Long COVID risk stratification towards improving its outcome., Competing Interests: Competing interests: JRH, SM and AS report personal fees, and JRH, SM, AS and AJS report non-financial support from pharmaceutical companies that make medicines and medical devices to treat respiratory disease, outside the submitted work., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Introduction: The increasing availability of non-invasive tests (NITs) has created the opportunity to explore their use in improving risk stratification of advanced liver disease. The study aimed to determine the attitudes and practices among UK secondary care specialists, focusing primarily on attitudes to fibrosis assessment and the use of NITs., Methods: Two web-based surveys were circulated, first between 2014 and 2015 (survey 1), and again in 2021 (survey 2). The surveys were promoted via the British Society of Gastroenterology, the British Association for the Study of the Liver and using Twitter., Results: In survey 1, 215 healthcare professionals (HCPs) completed the online survey. 112 HCPs completed survey 2. 71 acute UK trusts were represented in survey 1 compared with 60 trusts in survey 2. Between the two surveys, the proportion of HCPs performing fibrosis assessment in all or nearly all cases rose from 45.1% to 74.1% (χ 2 =25.01; p<0.0001). 46.5% (n=33/71) respondents in acute services reported the use of NITs in clinical pathways in survey 1, rising to 70.0% (n=42/60) in survey 2 (χ 2 =7.35; p=0.007). Availability of tests has increased but is not universal. The proportion reporting availability as a barrier to uptake fell from 57.2% of responses in survey 1 to 38.4% in 2021 χ 2 =11.01; p=0.0009)., Conclusion: Between 2014 and 2021, the role of NITs in fibrosis assessment has risen substantially, as has the proportion of clinicians using NITs in clinical pathways to assess risk of liver disease. Poor access to NITs remains the predominant barrier., Competing Interests: Competing interests: WR is an inventor of the ELF test. WR has received speaker fees from Siemens Healthineers. WR has received grant support from Siemens Healthineers. KWMA has received lecturer honorarium from Advanz Pharma., (© Author(s) (or their employer(s)) 2023. No commercial re-use. See rights and permissions. Published by BMJ.)

Research in computational psychiatry is dominated by models of behavior. Subjective experience during behavioral tasks is not well understood, even though it should be relevant to understanding the symptoms of psychiatric disorders. Here, we bridge this gap and review recent progress in computational models for subjective feelings. For example, happiness reflects not how well people are doing, but whether they are doing better than expected. This dependence on recent reward prediction errors is intact in major depression, although depressive symptoms lower happiness during tasks. Uncertainty predicts subjective feelings of stress in volatile environments. Social prediction errors influence feelings of self-worth more in individuals with low self-esteem despite a reduced willingness to change beliefs due to social feedback. Measuring affective state during behavioral tasks provides a tool for understanding psychiatric symptoms that can be dissociable from behavior. When smartphone tasks are collected longitudinally, subjective feelings provide a potential means to bridge the gap between lab-based behavioral tasks and real-life behavior, emotion, and psychiatric symptoms., Competing Interests: Competing interests The authors declare no competing interests., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Introduction: Undiagnosed fatty liver disease is prevalent in the community, due to high rates of harmful alcohol consumption and/or obesity. Fatty liver disease can progress to cirrhosis and its complications. Early identification of liver disease and treatment may prevent progression to cirrhosis. Biomarkers including FIB-4, enhanced liver fibrosis (ELF), PRO-C3 and vibration controlled transient elastography (VCTE) can stage liver fibrosis, but it is not known how well they perform in a primary care population. Moreover, no assessment of long-term prognostic ability of these biomarkers has been conducted in primary care. We aim to evaluate the performance of fibrosis biomarkers in primary care to develop a pathway to detect advanced fibrosis., Methods and Analysis: This prospective, observational cohort study will recruit 3000 individuals with fatty liver disease risk factors (obesity, type 2 diabetes or hazardous alcohol consumption) at their primary care 'annual chronic disease review'. Participants will have a 'liver health check'. Two pathways will be evaluated: (1) all have FIB-4, ELF and VCTE performed, and (2) patients have an initial assessment with FIB-4 and ELF, followed by VCTE in only those with increased FIB-4 and/or ELF. Individuals with suspected significant/advanced liver fibrosis (liver stiffness measurement>8 kPa), will be reviewed in secondary care to confirm their fibrosis stage and institute treatment. The performance of FIB-4, ELF, PRO-C3, VCTE and novel biomarkers alone or in combination for advanced fibrosis/cirrhosis will be evaluated. Participants will be followed longitudinally via their electronic health records to assess long-term clinical outcomes., Ethics and Dissemination: Ethical approval was obtained from the London-Chelsea Research Ethics Committee (22/PR/0535; 27 June 2022). Recruitment began on 31 October 2022. Outcomes of this study will be published in peer-reviewed journals and presented at scientific meetings. A lay summary of the results will be available for study participants and will be disseminated widely by LIVErNORTH., Competing Interests: Competing interests: SMc has received consultancy/speakers fees from Abbvie, Allergan, BMS, Gilead, Intercept, MSD, Novo Nordisk, Norgine, Novartis and Sequana. QMA reports research grant funding from Boehringer Ingelheim, Intercept; consultancy on behalf of Newcastle University for Alimentiv, Akero, AstraZeneca, Axcella, 89Bio, Boehringer Ingelheim, Bristol Myers Squibb, Galmed, Genfit, Genentech, Gilead, GlaxoSmithKline, Hanmi, HistoIndex, Intercept, Inventiva, Ionis, IQVIA, Janssen, Madrigal, Medpace, Merck, NGMBio, Novartis, Novo Nordisk, PathAI, Pfizer, Poxel, Resolution Therapeutics, Roche, Ridgeline Therapeutics, RTI, Shionogi, Terns; speaker for Fishawack, Integritas Communications, Kenes, Novo Nordisk, Madrigal, Medscape, Springer Healthcare; royalties from Elsevier Ltd., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY. Published by BMJ.)

Background: Morbidity from liver disease is rising in the UK. Most cases are caused by alcohol or non-alcoholic fatty liver disease (NAFLD) and treatable if caught early. Liver disease pathways have been shown to increase detection in the community, but have not been adopted into routine primary care work., Aim: To explore primary care healthcare professional (HCP) experiences and understanding of chronic liver disease, and where it might fit into management of long-term conditions., Design and Setting: Qualitative interview study with 20 HCPs in primary care in the north of England., Method: A semi-structured approach informed by a theory of implementation (normalisation process theory [NPT]). Data collection and analysis were concurrent. Interview data were analysed using thematic analysis., Results: Participants identified the following key areas for action: incentivised frameworks and protocols to drive understanding, organise, and sustain practice; inclusion of common liver diseases into multimorbidity care to reduce complexity and workload; a need to define the GP role within a lifestyle-focused treatment pathway; and education/local champions to initiate and legitimise individual and organisational participation in change., Conclusion: To embed chronic liver disease management in routine primary care work, researchers and policymakers must be aware of the implementation challenges. These findings can guide the adoption of effective pathways and help bridge the implementation gap., (© The Authors.)

Humans routinely learn the value of actions by updating their expectations based on past outcomes - a process driven by reward prediction errors (RPEs). Importantly, however, implementing a course of action also requires the investment of effort. Recent work has revealed a close link between the neural signals involved in effort exertion and those underpinning reward-based learning, but the behavioral relationship between these two functions remains unclear. Across two experiments, we tested healthy male and female human participants ( N = 140) on a reinforcement learning task in which they registered their responses by applying physical force to a pair of hand-held dynamometers. We examined the effect of effort on learning by systematically manipulating the amount of force required to register a response during the task. Our key finding, replicated across both experiments, was that greater effort increased learning rates following positive outcomes and decreased them following negative outcomes, which corresponded to a differential effect of effort in boosting positive RPEs and blunting negative RPEs. Interestingly, this effect was most pronounced in individuals who were more averse to effort in the first place, raising the possibility that the investment of effort may have an adaptive effect on learning in those less motivated to exert it. By integrating principles of reinforcement learning with neuroeconomic approaches to value-based decision-making, we show that the very act of investing effort modulates one's capacity to learn, and demonstrate how these functions may operate within a common computational framework. SIGNIFICANCE STATEMENT Recent work suggests that learning and effort may share common neurophysiological substrates. This raises the possibility that the very act of investing effort influences learning. Here, we tested whether effort modulates teaching signals in a reinforcement learning paradigm. Our results showed that effort resulted in more efficient learning from positive outcomes and less efficient learning from negative outcomes. Interestingly, this effect varied across individuals, and was more pronounced in those who were more averse to investing effort in the first place. These data highlight the importance of motivational factors in a common framework of reward-based learning, which integrates the computational principles of reinforcement learning with those of value-based decision-making., (Copyright © 2022 the authors.)

Objectives: To describe the most recent 7 year experience with 137 Indiana pouch patients at a single institution and provide data on complications with this type of urinary diversion during the first postoperative year., Methods: We queried our bladder cancer database to identify all patients who underwent cystectomy with continent catheterizable urinary reservoir between 2012 and 2018. Pre-, intra-, and postoperative data were collected. Complications were stratified into early (within 90 days) and midterm (90-365 days). The primary outcomes were postoperative complications, and overall and cancer-specific mortality., Results: A total of 137 patients underwent open cystectomy with Indiana pouch creation. Of these, 93% were radical cystectomies. On average, the operation took 422 minutes. There were 53 (39%) patients who experienced any type of complication during the first postoperative year (Clavien II-V). Twenty-five patients (18.2%) readmitted in the early postoperative period vs 18 (13.1%) patients midterm. There were 10 (7.3%) patients that required early reoperation and 11 (8%) in the midterm period. The overall mortality rate was 1.5% early and 3.7% midterm, with the majority of the mortality rate attributed to cancer progression (85.7%)., Conclusion: Patients undergoing continent catheterizable reservoir urinary diversion appear to have comparable complication rates to other urinary diversions published in the literature. At high-volume urologic institutions, Indiana Pouch creation is a suitable option for select patients desiring a continent diversion., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Non-alcoholic fatty liver disease (NAFLD) is common, affecting approximately 25% of the general population. The evidence base for the investigation and management of NAFLD is large and growing, but there is currently little practical guidance to support development of services and delivery of care. To address this, we produced a series of evidence-based quality standard recommendations for the management of NAFLD, with the aim of improving patient care. A multidisciplinary group of experts from the British Association for the Study of the Liver and British Society of Gastroenterology NAFLD Special Interest Group produced the recommendations, which cover: management of people with, or at risk of, NAFLD before the gastroenterology or liver clinic; assessment and investigations in secondary care; and management in secondary care. The quality of evidence for each recommendation was evaluated by the Grading of Recommendation Assessment, Development and Evaluation tool. An anonymous modified Delphi voting process was conducted individually by each member of the group to assess the level of agreement with each statement. Statements were included when agreement was 80% or greater. From the final list of statements, a smaller number of auditable key performance indicators were selected to allow services to benchmark their practice. It is hoped that services will review their practice against our recommendations and key performance indicators and institute service development where needed to improve the care of patients with NAFLD., Competing Interests: Declaration of interests SM personal fees outside the submitted work from Gilead, Intercept, and Novo Nordisk. MJA has received fees for consultancy, advisory boards, and speaking from Novo Nordisk and Norgine. JFC has received fees for consultancy, advisory boards, and speaking from Intercept, Novo Nordisk, canNASH, and AstraZeneca. EAT has received fees for advisory boards and speaking from Falk Pharma, Intercept, Gilead, and Pfizer. AS has received fees for consultancy and speaking from Siemens. STB has received payment for advisory boards and speaking from AbbVie, Gilead, and Intercept. RJA has received honoraria for speaking and advisory board membership from Falk Pharma, Gilead, Intercept, Novartis, and Norgine. DM has received fees for consultancy from Intercept. PNB has received speaking and educational fees from Takeda. RP has received speaking fees and advisory board fees from Siemens, Norgine, Novo Nordisk, and Shionogi. AY has taken part in advisory boards and consultancy for Intercept and Novo Nordisk. HJ has received speaker fees from Intercept. WA has received fees for consultancy and lecturing from AstraZeneca, Janssen, Novo Nordisk, Gilead Science, Intercept, and Coherus and has received competitive grant funding from GSK and Gilead Science. LC has received personal fees outside the submitted work from Norgine, Intercept, and Novo Nordisk. JT has received personal fees outside the submitted work from Novartis and Poxel. QMA is coordinator of the IMI2 LITMUS consortium, which is funded by the EU Horizon 2020 programme and EFPIA. He reports research grant funding from Allergan/Tobira, AstraZeneca, GlaxoSmithKline, Glympse Bio, Novartis Pharma AG, Pfizer Ltd, and Vertex, consultancy on behalf of Newcastle University for 89Bio, Allergan/Tobira, Altimmune, AstraZeneca, Axcella, Blade, BMS, BNN Cardio, Cirius, CymaBay, EcoR1, E3Bio, Eli Lilly & Company, Galmed, Genentech, Genfit, Gilead, Grunthal, HistoIndex, Indalo, Intercept, Inventiva, IQVIA, Janssen, Madrigal, MedImmune, Medpace, Metacrine, NGMBio, North Sea Therapeutics, Novartis, Novo Nordisk A/S, PathAI, Pfizer Ltd, Poxel, ProSciento, Raptor Pharma, Roche, Servier, Terns, The Medicines Company, and Viking Therapeutics, and speaker fees from Abbott Laboratories, Allergan/Tobira, BMS, Clinical Care Options, Falk, Fishawack, Genfit SA, Gilead, Integritas Communications, Kenes, and MedScape. All other authors declared no competing interests., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Background: Hypertension is a leading cause of cardiovascular disease in the United States and is costing the health care system billions of dollars annually. A health program that combines education, empowerment, and monitoring has shown to improve clinical outcomes and decrease overall health care costs., Objective: To describe the implementation and effectiveness of a self-measured blood pressure (SMBP) program in a community pharmacy., Practice Description: An independent community pharmacy located within rural Southeast Missouri. On-site community pharmacists provide medication therapy management, adherence monitoring, immunizations, and reimbursed clinical services., Practice Innovation: Patients were eligible if they were older than 18 years of age and fell into one of the following categories: self-reported a new hypertension diagnosis, self-reported a desire to SMBP, were referred by a provider, or had a medication change within the 3 months before enrollment. The program consisted of 4 patient sessions. The first session obtained an initial blood pressure and provided patient education and behavior counseling. Follow-up sessions obtained average SMBP readings and reinforced previously learned concepts., Evaluation Methods: Implementation was evaluated using time and patient satisfaction. Effectiveness was evaluated using number and type of clinical problems identified, BP measurements, and test scores., Results: A total of 20 patients enrolled and completed the study. The program took 63 minutes (SD ± 18) of staff time per patient for recruitment, sessions, reminder calls, and documentation. All patients received education and monitoring and 11 additional clinical problems were documented. Systolic BP decreased an average of 17 mm Hg (P = 0.002), and diastolic BP decreased an average of 12 mm Hg (P < 0.001). Patient confidence scores increased by 14%, and 7 more patients correctly answered the post-test knowledge question. All patients reported overall satisfaction with the program as "satisfied" or "very satisfied.", Conclusion: This standardized SMBP program effectively improved hypertension control and patient confidence in managing BP., (Copyright © 2022 American Pharmacists Association®. Published by Elsevier Inc. All rights reserved.)

Background: While community pharmacies are an ideal setting for social needs screening and referral programs, information on social risk assessment within pharmacy practice is limited., Objectives: Our primary objective was to describe 2 social determinant of health (SDOH) practice models implemented within community pharmacies. The secondary objective was to evaluate implementation practices utilizing the Reach, Effectiveness, Adoption, Implementation, and Maintenance (RE-AIM) framework., Practice Description: Two pharmacy groups participated in a 3-month study, one in New York (9 pharmacies) and another in Missouri (1 pharmacy). The New York pharmacies implemented an SDOH specialist practice model, in which pharmacy staff members facilitate the program. The Missouri pharmacy implemented a community health worker (CHW) model by cross training their technicians. Each pharmacy developed their program using the Community Pharmacy Enhanced Services Network Care Model., Practice Innovation: Both programs expanded the technician role to take on additional responsibilities. The SDOH specialist model partnered with a local independent practice association to create a social needs referral program using a technology platform for closed-loop communication. All workflow steps of the self-contained CHW program were completed within the pharmacy, placing additional responsibility on the CHW and pharmacy staff., Evaluation Methods: RE-AIM framework dimensions of Reach, Effectiveness, and Adoption., Results: Social challenges were identified in 49 of 76 (65%) generated SDOH screenings. The most prevalent social needs reported were affordability of daily needs (33%) and health care system navigation (15%). While most pharmacy staff indicated that workflow steps were clearly defined, assessments and referral tools were identified as potential gaps. While approximately 50% of pharmacy staff were comfortable with their assigned roles and in addressing SDOH challenges, physical and mental health concerns required additional education for intervention., Conclusion: The successful implementation of community pharmacy SDOH programs connected patients with local resources. Community pharmacies are ideally positioned to expand their public health footprint through SDOH interactions that consequently improve patient care., (Copyright © 2022 American Pharmacists Association®. Published by Elsevier Inc. All rights reserved.)

Background: The ease of contemporary hepatitis C virus (HCV) therapy has prompted a global drive towards simplified and decentralised treatment pathways. In some countries, primary care has become an integral component of community-based HCV treatment provision. In the UK, however, the role of primary care providers remains largely focused on testing and diagnosis alone., Aim: To develop a primary care-initiated HCV treatment pathway for people who use drugs, and recommend theory-informed interventions to help embed that pathway into practice., Design and Setting: A qualitative study informed by behaviour change theory. Semi-structured interviews were undertaken with key stakeholders ( n = 38) primarily from two large conurbations in Scotland., Method: Analysis was three-stage. First, a broad pathway structure was outlined and then sequential pathway steps were specified; second, thematic data were aligned to pathway steps, and significant barriers and enablers were identified; and, third, the Theoretical Domains Framework and Behaviour Change Wheel were employed to systematically develop ideas to enhance pathway implementation, which stakeholders then appraised., Results: The proposed pathway structure spans broad, overarching challenges to primary care-initiated HCV treatment. The theory-informed recommendations align with influences on different behaviours at key pathway steps, and focus on relationship building, routinisation, education, combating stigmas, publicising the pathway, and treatment protocol development., Conclusion: This study provides the first practicable pathway for primary care-initiated HCV treatment in Scotland, and provides recommendations for wider implementation in the UK. It positions primary care providers as an integral part of community-based HCV treatment, providing workable solutions to ingrained barriers to care., (© The Authors.)

Background: Patients with some types of immunodeficiency can experience chronic or relapsing infection with severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). This leads to morbidity and mortality, infection control challenges, and the risk of evolution of novel viral variants. The optimal treatment for chronic coronavirus disease 2019 (COVID-19) is unknown., Objective: Our aim was to characterize a cohort of patients with chronic or relapsing COVID-19 disease and record treatment response., Methods: We conducted a UK physician survey to collect data on underlying diagnosis and demographics, clinical features, and treatment response of immunodeficient patients with chronic (lasting ≥21 days) or relapsing (≥2 episodes) of COVID-19., Results: We identified 31 patients (median age 49 years). Their underlying immunodeficiency was most commonly characterized by antibody deficiency with absent or profoundly reduced peripheral B-cell levels; prior anti-CD20 therapy, and X-linked agammaglobulinemia. Their clinical features of COVID-19 were similar to those of the general population, but their median duration of symptomatic disease was 64 days (maximum 300 days) and individual patients experienced up to 5 episodes of illness. Remdesivir monotherapy (including when given for prolonged courses of ≤20 days) was associated with sustained viral clearance in 7 of 23 clinical episodes (30.4%), whereas the combination of remdesivir with convalescent plasma or anti-SARS-CoV-2 mAbs resulted in viral clearance in 13 of 14 episodes (92.8%). Patients receiving no therapy did not clear SARS-CoV-2., Conclusions: COVID-19 can present as a chronic or relapsing disease in patients with antibody deficiency. Remdesivir monotherapy is frequently associated with treatment failure, but the combination of remdesivir with antibody-based therapeutics holds promise., (Copyright © 2021 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)

Objectives: Liver disease is a leading cause of premature death, partly driven by the increasing incidence of non-alcohol-related fatty liver disease (NAFLD). Many people with a diagnosis of NAFLD drink moderate amounts of alcohol. There is limited guidance for clinicians looking to advise these patients on the effect this will have on their liver disease progression. This review synthesises the evidence on moderate alcohol consumption and its potential to predict liver disease progression in people with diagnosed NAFLD., Methods: A systematic review of longitudinal observational cohort studies was conducted. Databases (Medline, Embase, The Cochrane Library and ClinicalTrials.gov) were searched up to September 2020. Studies were included that reported progression of liver disease in adults with NAFLD, looking at moderate levels of alcohol consumption as the exposure of interest. Risk of bias was assessed using the Quality in Prognostic factor Studies tool., Results: Of 4578 unique citations, 6 met the inclusion criteria. Pooling of data was not possible due to heterogeneity and studies were analysed using narrative synthesis. Evidence suggested that any level of alcohol consumption is associated with worsening of liver outcomes in NAFLD, even for drinking within recommended limits. Well conducted population based studies estimated up to a doubling of incident liver disease outcomes in patients with NAFLD drinking at moderate levels., Conclusions: This review found that any level of alcohol intake in NAFLD may be harmful to liver health.Study heterogeneity in definitions of alcohol exposure as well as in outcomes limited quantitative pooling of results. Use of standardised definitions for exposure and outcomes would support future meta-analysis.Based on this synthesis of the most up to date longitudinal evidence, clinicians seeing patients with NAFLD should currently advise abstinence from alcohol., Prospero Registration Number: The protocol was registered with PROSPERO (#CRD42020168022)., Competing Interests: Competing interests: HJ reports grants from National Institute for Health research (NIHR), during the conduct of the study; personal fees from Intercept Pharma, personal fees from Norgine, outside the submitted work; QMA reports grants from European Commission, during the conduct of the study; other from Acuitas Medical, grants, personal fees and other from Allergan/Tobira, other from E3Bio, other from Eli Lilly & Company Ltd, other from Galmed, grants, personal fees and other from Genfit SA, personal fees and other from Gilead, other from Grunthal, other from Imperial Innovations, grants and other from Intercept Pharma Europe Ltd, other from Inventiva, other from Janssen, personal fees from Kenes, other from MedImmune, other from NewGene, grants and other from Pfizer Ltd, other from Raptor Pharma, grants from GlaxoSmithKline, grants and other from Novartis Pharma AG, grants from Abbvie, personal fees from BMS, grants from GSK, other from NGMBio, other from Madrigal, other from Servier, outside the submitted work., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY. Published by BMJ.)

Background: Liver disease is an increasing cause of premature mortality in the UK. Its management in primary care is not well understood. It is unclear what role commissioning bodies are playing in liver disease in the UK., Aim: To assess the level of engagement with community chronic liver disease management among clinical commissioning groups (CCGs) and health authorities across the UK., Design & Setting: A cross-sectional survey to all UK CCGs and health authorities., Method: Survey questions were developed by the British Liver Trust, in collaboration with topic experts, and evaluated structures in place relating to liver disease management at commissioning and health board level., Results: There were 159 responses representing 99% UK coverage of CCGs and health boards. Twenty per cent reported an individual responsible for liver disease within their organisation, with 40% and 29% reporting having pathways in place to respond to abnormal liver blood tests and liver disease more generally, respectively. All those reporting use of pathways reported using national guidelines to guide content. Twenty-five per cent made use of transient elastography (FibroScan) and 16% of direct serum fibrosis markers (for example, enhanced liver fibrosis [ELF] score), which are both part of current National Institute for Health and Care Excellence (NICE) guidelines. There was marked regional variation in all areas of engagement surveyed, with Wales having exceptionally high levels of engagement in all areas in contrast to the other nations., Conclusion: The results of this survey should be used as a catalyst to highlight necessary regional improvements to the primary care management of chronic liver disease across the UK., (Copyright © 2021, The Authors.)

Rationale: Suboptimal vaccine immunogenicity and antigenic mismatch, compounded by poor uptake, means that influenza remains a major global disease. T cells recognizing peptides derived from conserved viral proteins could enhance vaccine-induced cross-strain protection. Objectives: To investigate the kinetics, phenotypes, and function of influenza virus-specific CD8 + resident memory T (Trm) cells in the lower airway and infer the molecular pathways associated with their response to infection in vivo . Methods: Healthy volunteers, aged 18-55, were inoculated intranasally with influenza A/California/4/09(H1N1). Blood, upper airway, and (in a subgroup) lower airway samples were obtained throughout infection. Symptoms were assessed by using self-reported diaries, and the nasal viral load was assessed by using quantitative PCR. T-cell responses were analyzed by using a three-color FluoroSpot assay, flow cytometry with MHC I-peptide tetramers, and RNA sequencing, with candidate markers being confirmed by using the immunohistochemistry results for endobronchial biopsy specimens. Measurements and Main Results: After challenge, 57% of participants became infected. Preexisting influenza-specific CD8 + T cells in blood correlated strongly with a reduced viral load, which peaked at Day 3. Influenza-specific CD8 + T cells in BAL fluid were highly enriched and predominantly expressed the Trm markers CD69 and CD103. Comparison between preinfection CD8 + T cells in BAL fluid and blood by using RNA sequencing revealed 3,928 differentially expressed genes, including all major Trm-cell markers. However, gene set enrichment analysis of BAL-fluid CD8 + T cells showed primarily innate cell-related pathways and, during infection, included upregulation of innate chemokines ( Cxcl1 , Cxcl10 , and Cxcl16 ) that were also expressed by CD8 + cells in bronchial tissues. Conclusions: CD8 + Trm cells in the human lung display innate-like gene and protein expression that demonstrates blurred divisions between innate and adaptive immunity. Clinical study registered with www.clinicaltrials.gov (NCT02755948).

Social determinants of health (SDoH) account for up to 90% of health outcomes, whereas medical care accounts for only 10%-15%; despite this disparity, only 24% of hospitals and 16% of physician practices screen for the 5 social needs. Community-embedded and highly accessible, pharmacies are uniquely positioned to connect individuals to local community and social resources and thereby address SDoH. In this article, we explore novel community pharmacy practice models that address SDoH, provide real-world examples of these models, and discuss pathways for reimbursement and sustainability. A number of innovative community pharmacy practice models that focus on social issues are currently being explored. These include integrating community health workers (CHWs) or SDoH specialists, wherein CHWs are frontline public health workers who can effectively bridge the health care system and their community, whereas SDoH specialists are pharmacy team members trained with substantial SDoH knowledge and how to use it to connect pharmacy patients to community resources. Three community pharmacy networks have implemented pilot programs using either a CHW or SDoH specialist model. An essential component for program success in all cases has been partnership development and increased interdependence between the pharmacies, local community organizations, and the public health sector. New payment models and financial incentives will be necessary to expand and sustain these programs. A potential Approach may be the use of Z codes, a subset of ICD-10-CM codes specific to assessing SDoH. Although opportunities are developing for community pharmacies to play a major role in sustainably addressing SDoH, additional work is needed before there is a widespread acceptance of pharmacies becoming service referral destinations for patients with social needs. Evaluation of these models on a wider scale will be necessary to fully evaluate their effectiveness, costs, and implementation within different community pharmacy settings., (Copyright © 2021 American Pharmacists Association®. Published by Elsevier Inc. All rights reserved.)

Testicular cancer is a rare malignancy that demonstrates variability in histopathologic features, treatment protocols, and outcomes based on a patient's age at presentation. In the pediatric population, puberty provides an important timestamp for evaluating and understanding the disease process. Prepubertal males, often designated as < 11 years of age, are more likely to present with benign disease. In contrast, the majority of post-pubertal testicular masses are malignant. Other factors, such as race/ethnicity, family history, and personal medical history can influence a patient's risk for malignancy as well. Serum tumor markers (STM) and histologic evaluation are key for diagnosis and for determining management. While normal STMs in a pre-pubertal patient likely qualify a patient for testis-sparing surgery, radical orchiectomy is the gold standard for post-pubertal patients, regardless of STM levels. Cross-sectional imaging is essential for staging and may be done before or after surgical intervention depending on the clinical scenario. Excellent survival outcomes are often achieved regardless of disease risk, with low-stage disease managed safely with surveillance. Surveillance usually consists of STM and imaging monitoring. If adjuvant therapy is indicated, a multi-disciplinary team approach is paramount. This approach should include following pediatric vs. adult protocols based of the patient's pubertal status in order to achieve optimal oncologic outcomes., (Copyright © 2021. Published by Elsevier Inc.)

The ease of direct-acting antiviral (DAA) medications for hepatitis C virus (HCV) has provided an opportunity to decentralize HCV treatment into community settings. However, the role of non-specialist clinicians in community-based pathways has received scant attention to date. This study examined barriers and enablers to expanding the role of general practitioners (GPs) in HCV treatment provision, using simple behaviour change theory as a conceptual framework. A maximum variation sample of 22 HCV treatment providers, GPs and HCV support workers participated in semi-structured interviews. Data were inductively coded, and the resulting codes deductively mapped into three principal components of behaviour change: capability, opportunity and motivation (COM-B). By this process, a number of provider- and systemic-level barriers and enablers were identified. Key barriers included the pre-treatment assessment of liver fibrosis, GP capacity and the 'speciality' of HCV care. Enablers included the simplicity of the drugs, existing GP/patient relationships and the provision of holistic care. In addition to these specific factors, the data also exposed an overarching provider understanding of 'HCV treatment' as triumvirate in nature, incorporating the assessment of liver fibrosis, the provision of holistic support and the treatment of disease. This understanding imposes a further fundamental barrier to GP-led treatment as each of these three components needs to be individually addressed. To enable sustainable models of HCV treatment provision by GPs, a pragmatic re-examination of the 'HCV treatment triumvirate' is required, and a paradigm shift from the 'refer and treat' status quo., (© 2020 The Authors. Journal of Viral Hepatitis published by John Wiley & Sons Ltd.)

Competing Interests: Competing interests: None declared.

Background: Non-alcoholic fatty liver disease (NAFLD) is a leading cause of chronic liver disease worldwide. Many individuals have risk factors associated with NAFLD, but the majority do not develop advanced liver disease: cirrhosis, hepatic decompensation, or hepatocellular carcinoma. Identifying people at high risk of experiencing these complications is important in order to prevent disease progression. This review synthesises the evidence on metabolic risk factors and their potential to predict liver disease outcomes in the general population at risk of NAFLD or with diagnosed NAFLD., Methods and Findings: We conducted a systematic review and meta-analysis of population-based cohort studies. Databases (including MEDLINE, EMBASE, the Cochrane Library, and ClinicalTrials.gov) were searched up to 9 January 2020. Studies were included that reported severe liver disease outcomes (defined as liver cirrhosis, complications of cirrhosis, or liver-related death) or advanced fibrosis/non-alcoholic steatohepatitis (NASH) in adult individuals with metabolic risk factors, compared with individuals with no metabolic risk factors. Cohorts selected on the basis of a clinically indicated liver biopsy were excluded to better reflect general population risk. Risk of bias was assessed using the QUIPS tool. The results of similar studies were pooled, and overall estimates of hazard ratio (HR) were obtained using random-effects meta-analyses. Of 7,300 unique citations, 22 studies met the inclusion criteria and were of sufficient quality, with 18 studies contributing data suitable for pooling in 2 random-effects meta-analyses. Type 2 diabetes mellitus (T2DM) was associated with an increased risk of incident severe liver disease events (adjusted HR 2.25, 95% CI 1.83-2.76, p < 0.001, I2 99%). T2DM data were from 12 studies, with 22.8 million individuals followed up for a median of 10 years (IQR 6.4 to 16.9) experiencing 72,792 liver events. Fourteen studies were included in the meta-analysis of obesity (BMI > 30 kg/m2) as a prognostic factor, providing data on 19.3 million individuals followed up for a median of 13.8 years (IQR 9.0 to 19.8) experiencing 49,541 liver events. Obesity was associated with a modest increase in risk of incident severe liver disease outcomes (adjusted HR 1.20, 95% CI 1.12-1.28, p < 0.001, I2 87%). There was also evidence to suggest that lipid abnormalities (low high-density lipoprotein and high triglycerides) and hypertension were both independently associated with incident severe liver disease. Significant study heterogeneity observed in the meta-analyses and possible under-publishing of smaller negative studies are acknowledged to be limitations, as well as the potential effect of competing risks on outcome., Conclusions: In this review, we observed that T2DM is associated with a greater than 2-fold increase in the risk of developing severe liver disease. As the incidence of diabetes and obesity continue to rise, using these findings to improve case finding for people at high risk of liver disease will allow for effective management to help address the increasing morbidity and mortality from liver disease., Trial Registration: PROSPERO CRD42018115459., Competing Interests: I have read the journal's policy and the authors of this manuscript have the following competing interests: QMA is coordinator of the LITMUS (Liver Investigation: Testing Biomarker Utility in Steatohepatitis) consortium funded by the IMI2 H2020 Framework Program of the European Union under Grant Agreement 777377; has been a consultant for 89Bio, Abbott Laboratories, Acuitas Medical, Allergan/Tobira, Altimmune, AstraZeneca, Axcella, Blade, BMS, BNN Cardio, Celgene, Cirius, CymaBay, EcoR1, E3Bio, Eli Lilly & Company Ltd., Galmed, Genentech, Genfit SA, Gilead, Grunthal, HistoIndex, Indalo, Imperial Innovations, Intercept Pharma Europe Ltd., Inventiva, IQVIA, Janssen, Madrigal, MedImmune, Metacrine, NewGene, NGMBio, North Sea Therapeutics, Novartis, Novo Nordisk A/S, Pfizer Ltd., Poxel, ProSciento, Raptor Pharma, Servier, Terns, Viking Therapeutics; and has received research support from Abbvie, Allergan/Tobira, AstraZeneca, GlaxoSmithKline, Glympse Bio, Novartis Pharma AG, Pfizer Ltd., Vertex. The other authors have declared that no competing interests exist.

Background: Levels of physical activity and physical fitness are low after stroke. Interventions to increase physical fitness could reduce mortality and reduce disability through increased function., Objectives: The primary objectives of this updated review were to determine whether fitness training after stroke reduces death, death or dependence, and disability. The secondary objectives were to determine the effects of training on adverse events, risk factors, physical fitness, mobility, physical function, health status and quality of life, mood, and cognitive function., Search Methods: In July 2018 we searched the Cochrane Stroke Trials Register, CENTRAL, MEDLINE, Embase, CINAHL, SPORTDiscus, PsycINFO, and four additional databases. We also searched ongoing trials registers and conference proceedings, screened reference lists, and contacted experts in the field., Selection Criteria: Randomised trials comparing either cardiorespiratory training or resistance training, or both (mixed training), with usual care, no intervention, or a non-exercise intervention in stroke survivors., Data Collection and Analysis: Two review authors independently selected studies, assessed quality and risk of bias, and extracted data. We analysed data using random-effects meta-analyses and assessed the quality of the evidence using the GRADE approach. Diverse outcome measures limited the intended analyses., Main Results: We included 75 studies, involving 3017 mostly ambulatory participants, which comprised cardiorespiratory (32 studies, 1631 participants), resistance (20 studies, 779 participants), and mixed training interventions (23 studies, 1207 participants). Death was not influenced by any intervention; risk differences were all 0.00 (low-certainty evidence). There were few deaths overall (19/3017 at end of intervention and 19/1469 at end of follow-up). None of the studies assessed death or dependence as a composite outcome. Disability scores were improved at end of intervention by cardiorespiratory training (standardised mean difference (SMD) 0.52, 95% CI 0.19 to 0.84; 8 studies, 462 participants; P = 0.002; moderate-certainty evidence) and mixed training (SMD 0.23, 95% CI 0.03 to 0.42; 9 studies, 604 participants; P = 0.02; low-certainty evidence). There were too few data to assess the effects of resistance training on disability. Secondary outcomes showed multiple benefits for physical fitness (VO 2 peak and strength), mobility (walking speed) and physical function (balance). These physical effects tended to be intervention-specific with the evidence mostly low or moderate certainty. Risk factor data were limited or showed no effects apart from cardiorespiratory fitness (VO 2 peak), which increased after cardiorespiratory training (mean difference (MD) 3.40 mL/kg/min, 95% CI 2.98 to 3.83; 9 studies, 438 participants; moderate-certainty evidence). There was no evidence of any serious adverse events. Lack of data prevents conclusions about effects of training on mood, quality of life, and cognition. Lack of data also meant benefits at follow-up (i.e. after training had stopped) were unclear but some mobility benefits did persist. Risk of bias varied across studies but imbalanced amounts of exposure in control and intervention groups was a common issue affecting many comparisons., Authors' Conclusions: Few deaths overall suggest exercise is a safe intervention but means we cannot determine whether exercise reduces mortality or the chance of death or dependency. Cardiorespiratory training and, to a lesser extent mixed training, reduce disability during or after usual stroke care; this could be mediated by improved mobility and balance. There is sufficient evidence to incorporate cardiorespiratory and mixed training, involving walking, within post-stroke rehabilitation programmes to improve fitness, balance and the speed and capacity of walking. The magnitude of VO 2 peak increase after cardiorespiratory training has been suggested to reduce risk of stroke hospitalisation by ˜7%. Cognitive function is under-investigated despite being a key outcome of interest for patients. Further well-designed randomised trials are needed to determine the optimal exercise prescription, the range of benefits and any long-term benefits., (Copyright © 2020 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.)

This final report of the Lancet Commission into liver disease in the UK stresses the continuing increase in burden of liver disease from excess alcohol consumption and obesity, with high levels of hospital admissions which are worsening in deprived areas. Only with comprehensive food and alcohol strategies based on fiscal and regulatory measures (including a minimum unit price for alcohol, the alcohol duty escalator, and an extension of the sugar levy on food content) can the disease burden be curtailed. Following introduction of minimum unit pricing in Scotland, alcohol sales fell by 3%, with the greatest effect on heavy drinkers of low-cost alcohol products. We also discuss the major contribution of obesity and alcohol to the ten most common cancers as well as measures outlined by the departing Chief Medical Officer to combat rising levels of obesity-the highest of any country in the west. Mortality of severely ill patients with liver disease in district general hospitals is unacceptably high, indicating the need to develop a masterplan for improving hospital care. We propose a plan based around specialist hospital centres that are linked to district general hospitals by operational delivery networks. This plan has received strong backing from the British Association for Study of the Liver and British Society of Gastroenterology, but is held up at NHS England. The value of so-called day-case care bundles to reduce high hospital readmission rates with greater care in the community is described, along with examples of locally derived schemes for the early detection of disease and, in particular, schemes to allow general practitioners to refer patients directly for elastography assessment. New funding arrangements for general practitioners will be required if these proposals are to be taken up more widely around the country. Understanding of the harm to health from lifestyle causes among the general population is low, with a poor knowledge of alcohol consumption and dietary guidelines. The Lancet Commission has serious doubts about whether the initiatives described in the Prevention Green Paper, with the onus placed on the individual based on the use of information technology and the latest in behavioural science, will be effective. We call for greater coordination between official and non-official bodies that have highlighted the unacceptable disease burden from liver disease in England in order to present a single, strong voice to the higher echelons of government., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Improving our understanding of the complex relationship between health and social care utilisation is vital as populations age. This systematic review aimed to synthesise evidence on the relationship between older adults' use of social care and their healthcare utilisation. Ten databases were searched for international literature on social care (exposure), healthcare use (outcome) and older adults (population). Searches were carried out in October 2016, and updated May 2018. Studies were eligible if they were published after 2000 in a high income country, examined the relationship between use of social care and healthcare utilisation by older adults (aged ≥60 years), and controlled for an indicator of need. Study quality and bias were rated using the National Institute of Health (NIH) Quality Assessment Tool for Observational Cohort and Cross-Sectional Studies. Study data were extracted and a narrative synthesis was conducted. Data were not suitable for quantitative synthesis. Thirteen studies were identified from 12,065 citations. Overall, the quality and volume of evidence was low. There was limited evidence to suggest that longer lengths of stay in care homes were associated with a lower risk of inpatient admissions. Residents of care homes with onsite nursing had fewer than expected admissions to hospital, compared to people in care homes without nursing, and adjusting for need. Evidence for other healthcare use outcomes was even more limited and heterogeneous, with notable gaps in primary care. We conclude that older adults' use of care homes may moderate inpatient admissions. In particular, the presence of registered nurses in care homes may reduce the need to transfer residents to hospital. However, further evidence is needed to add weight to this conclusion. Future research should build on this evidence and address gaps regarding the influence of community based social care on older adults' healthcare use. A greater focus on primary care outcomes is imperative., (© 2019 John Wiley & Sons Ltd.)

Background: Chondrosarcomas account for approximately 20% of bone sarcomas, with the most common site being the lower limb. Hemipelvectomies that involve hindquarter amputation have previously been the treatment of choice for pelvic tumors. However, with advances in chemotherapy, radiotherapy, imaging and surgical techniques more patients are now being treated with limb salvage surgery. The rehabilitation outcomes following an internal hemipelvectomy have not been well identified and there is currently little, if any, gait analysis data on rehabilitation following hemipelvectomy in limb salvage patients. Case description: A 53-year-old male underwent an internal hemipelvectomy with limb salvage followed by a 2-year rehabilitation program. The aim of this case study is to describe temporal and spatial parameters, metabolic energy expenditure and joint kinematics of a patient with an internal hemipelvectomy who underwent a wide excision of a chondrosarcoma followed by intensive rehabilitation. Outcomes: Walking speed (1.6 m/s), stride length (1.7 m), stride width (0.13 m) and good symmetry in step length (right 0.85 m and left data 0.80 m) and stance time (right 62% and left 59%) indicate a walking pattern similar to the asymptomatic able bodied. Oxygen consumption was 16.6 ml/kg/min and oxygen cost 0.17 ml/kg/m. Discussion: Following the intensive 2-year rehabilitation program this patient's gait pattern was similar to a control group with no statistically significant difference in the movement of the left and right knee and ankle joints. Some differences were identified against the control group in respect of the movement of the pelvis and hips, but this is partly to be expected. This case study highlights the functional outcomes that can be achieved following limb salvage surgery with intensive rehabilitation and a high level of motivation from the individual. Implications for rehabilitation Advancements in chemotherapy, imaging and surgical techniques have allowed more patients to be treated with internal hemipelvectomy. The rehabilitation outcomes following an internal hemipelvectomy have not been well identified and there is little gait analysis data. This case study highlights the functional outcomes that can be achieved following limb salvage surgery with intensive rehabilitation and motivation from the individual. Rehabilitation following internal hemipelvectomy should include goal setting, lymphoedema management, physiotherapy and an exercise program.

Background:: Reduced function and health in individuals with lower limb amputation is well documented. Step count measurement could facilitate rehabilitation and help monitor functional health outcomes., Objectives:: To determine whether mean daily step count changed between in-patient rehabilitation and consecutive leave periods., Study Design:: Observational study., Methods:: Nine individuals with bilateral traumatic amputations attending rehabilitation at the Defence Medical Rehabilitation Centre during a 4-month period were invited to participate in the study (two bilateral transfemoral, two bilateral transfemoral/knee disarticulation, two transfemoral/transtibial, one bilateral transfemoral plus transradial, one bilateral transfemoral plus transhumeral and one transfemoral/transtibial/transradial). Prostheses worn by each participant were fitted with an activity monitor (LAM2 TM ; PAL Technologies Ltd, Glasgow). Mean daily step count was analysed for each participant following 2 weeks in-patient rehabilitation and consecutive 2 weeks away from rehabilitation., Results:: Nine participants completed the study (time since injury: 19 ± 7 months, age: 26 ± 6 years). Mean daily step count significantly decreased from 2258 ± 192 during in-patient rehabilitation to 1387 ± 363 at home ( p < 0.01)., Conclusion:: The step count decreased when away from rehabilitation, confirming the hypothesis that the mean daily step count would change between in-patient rehabilitation and consecutive leave period., Clinical Relevance: These data provide an indication of the step count achievable by young, military male personnel with bilateral lower limb amputations and highlights differences between intensive in-patient rehabilitation and consecutive leave periods. It is suggested that further investigation and support of clinical monitoring could facilitate rehabilitation tailored to the individual.

Objectives: To investigate the proportion of potentially relevant undisclosed financial ties between clinical practice guideline writers and pharmaceutical companies., Design: Cross-sectional study of a stratified random sample of Australian guidelines and writers., Setting: Guidelines available from Australia's National Health and Medical Research Council guideline database, 2012-2014, stratified across 10 health priority areas., Population: 402 authors of 33 guidelines, including up to four from each area, dependent on availability: arthritis/musculoskeletal (3); asthma (4); cancer (4); cardiovascular (4); diabetes (4); injury (3); kidney/urogenital (4); mental health (4); neurological (1); obesity (1). For guideline writers with no disclosures, or who disclosed no ties, a search of disclosures in the medical literature in the 5 years prior to guideline publication identified potentially relevant ties, undisclosed in guidelines. Guidelines were included if they contained recommendations of medicines, and writers included if developing or writing guidelines., Main Outcome Measures: Proportions of guideline writers with potentially relevant undisclosed financial ties to pharmaceutical companies active in the therapeutic area; proportion of guidelines including at least one writer with a potentially relevant undisclosed tie., Results: 344 of 402 writers (86%; 95% CI 82% to 89%) either had no published disclosures (228) or disclosed they had no ties (116). Of the 344 with no disclosed ties, 83 (24%; 95% CI 20% to 29%) had potentially relevant undisclosed ties. Of 33 guidelines, 23 (70%; 95% CI 51% to 84%) included at least one writer with a potentially relevant undisclosed tie. Writers of guidelines developed and funded by governments were less likely to have undisclosed financial ties (8.1%vs30.6%; risk ratio 0.26; 95% CI 0.13 to 0.53; p<0.001)., Conclusions: Almost one in four guideline writers with no disclosed ties may have potentially relevant undisclosed ties to pharmaceutical companies. These data confirm the need for strategies to ensure greater transparency and more independence in relationships between guidelines and industry., Competing Interests: Competing interests: HJ was an employee of NHMRC. SG and GD are employees of NHMRC. LB is an employee of The University of Sydney and had no funding specifically for this work., (© Author(s) (or their employer(s)) 2019. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Objective: to investigate the impact of the availability and supply of social care on healthcare utilisation (HCU) by older adults in high income countries., Design: systematic review and meta-analysis., Data Sources: medline, EMBASE, Scopus, Health Management Information Consortium, Cochrane Database of Systematic Reviews, NIHR Health Technology Assessment, NHS Economic Evaluation Database, Database of Abstracts of Reviews of Effectiveness, SCIE Online and ASSIA. Searches were carried out October 2016 (updated April 2017 and May 2018). (PROSPERO CRD42016050772)., Study Selection: observational studies from high income countries, published after 2000 examining the relationship between the availability of social care (support at home or in care homes with or without nursing) and healthcare utilisation by adults >60 years. Studies were quality assessed., Results: twelve studies were included from 11,757 citations; ten were eligible for meta-analysis. Most studies (7/12) were from the UK. All reported analysis of administrative data. Seven studies were rated good in quality, one fair and four poor. Higher social care expenditure and greater availability of nursing and residential care were associated with fewer hospital readmissions, fewer delayed discharges, reduced length of stay and expenditure on secondary healthcare services. The overall direction of evidence was consistent, but effect sizes could not be confidently quantified. Little evidence examined the influence of home-based social care, and no data was found on primary care use., Conclusions: adequate availability of social care has the potential to reduce demand on secondary health services. At a time of financial stringencies, this is an important message for policy-makers.

Background: The incidence of liver disease is increasing in the UK and primary care is a key setting where improvement in the detection and management of liver disease is required. Little is known about GPs' understanding and confidence in detecting liver disease., Aim: To explore GPs' experiences of liver disease with a focus on early detection and interpretation of liver function tests (LFTs)., Design and Setting: A qualitative study employing semi-structured interviews of a purposive sample of GPs from five UK primary care study sites., Method: Telephone and face-to-face interviews of GPs were undertaken. Data were analysed thematically, using a constant comparative approach., Results: From a total of 25 GP interviews ( N = 25), four themes were identified from the data: test-requesting behaviour, confidence and challenges in diagnosing disease, access to specialist tests, and guidance and education. Participants' descriptions of how they request and interpret LFTs varied widely. Concern over missing diagnoses was a common reason for requesting blood tests; patients with mildly abnormal LFTs and those at risk of non-alcoholic fatty liver disease (NAFLD) were a particular cause of concern. GPs saw themselves as generalists, with a reluctance to take on specialist investigations. Guidelines promoted confidence for some clinicians, but others felt that liver disease was too complex to be amenable to simple instructions. Most felt that they did not have access to relevant, focused education on liver disease., Conclusion: Liver disease is not perceived as a priority in primary care. If GPs are to take on a greater role in identification and management of liver disease, support is needed to promote awareness, knowledge, and confidence., (© British Journal of General Practice 2018.)

The prefrontal cortex (PFC) is a heterogeneous area that is critical to reward-based decision-making. In particular, the dorsal anterior cingulate cortex, ventromedial PFC and orbitofrontal cortex are frequently implicated in different aspects of choice behaviour. These regions receive projections from midbrain dopamine (DA) neurons and, in turn, project to other key dopaminergic regions such as the striatum. However, our current understanding of the role of DA in reward-based processes is based mainly on studies of midbrain dopaminergic neurons and striatal DA release from nonhuman animal models. An important gap in the literature surrounds the precise functions of DA release in the PFC, particularly in humans. A priority for future research will be to integrate, both computationally and biologically, the seemingly disparate value representations across different nodes within the reward-processing network. Such models should aim to define the functional interactions between the PFC and basal ganglia, through which dopaminergic neurotransmission guides reward-based behaviour.

Swimming is one of the inaugural sports within the Olympic and Paralympic Games, the key difference between the Olympic and Paralympic games being the classification system. The aim of this study was to investigate how effective the current classification system creates clearly differentiated Paralympic competition classes, based on performance time for all swimming strokes and events. Based on the performance characteristics of swimmers within the current classification system, the relationship between impairment and swimming performance is inconsistent, potentially disadvantaging some athletes. Appropriate sports medicine tests are required for the development of an evidence-based swimming classification system., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Early events in the human airways determining whether exposure to Mycobacterium tuberculosis (Mtb) results in acquisition of infection are poorly understood. Epithelial cells are the dominant cell type in the lungs, but little is known about their role in tuberculosis. We hypothesised that human primary airway epithelial cells are part of the first line of defense against Mtb-infection and contribute to the protective host response in the human respiratory tract. We modelled these early airway-interactions with human primary bronchial epithelial cells (PBECs) and alveolar macrophages. By combining in vitro infection and transwell co-culture models with a global transcriptomic approach, we identified PBECs to be inert to direct Mtb-infection, yet to be potent responders within an Mtb-activated immune network, mediated by IL1β and type I interferon (IFN). Activation of PBECs by Mtb-infected alveolar macrophages and monocytes increased expression of known and novel antimycobacterial peptides, defensins and S100-family members and epithelial-myeloid interactions further shaped the immunological environment during Mtb-infection by promoting neutrophil influx. This is the first in depth analysis of the primary epithelial response to infection and offers new insights into their emerging role in tuberculosis through complementing and amplifying responses to Mtb.

Background: Liver disease is the third most common cause of premature death in the UK. The symptoms of terminal liver disease are often difficult to treat, but very few patients see a palliative care specialist and a high proportion die in hospital. Primary care has been identified as a setting where knowledge and awareness of liver disease is poor. Little is known about general practitioners' (GPs) perceptions of their role in managing end-stage liver disease., Objective: To explore GPs' experiences and perceptions of how primary care can enhance end-of-life care for patients with liver disease., Design: Qualitative interview study, thematic analysis., Participants: Purposive sample of 25 GPs from five regions of England., Results: GPs expressed a desire to be more closely involved in end-of-life care for patients with liver disease but identified a number of factors that constrained their ability to contribute. These fell into three main areas; those relating directly to the condition, (symptom management and the need to combine a palliative care approach with ongoing medical interventions); issues arising from patients' social circumstances (stigma, social isolation and the social consequences of liver disease) and deficiencies in the organisation and delivery of services. Collaborative working with support from specialist hospital clinicians was regarded as essential, with GPs acknowledging their lack of experience and expertise in this area., Conclusions: End-of-life care for patients with liver disease merits attention from both primary and secondary care services. Development of care pathways and equitable access to symptom relief should be a priority., Competing Interests: Competing interests: None declared., (© Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.)

Fibrosing mediastinitis (FM) is a rare disease where there is thickening of the fibrous tissue in the mediastinum. While histoplasmosis is the the most common recognised cause, the link with tuberculosis (TB) has been rarely documented. We review the link between TB and FM, and describe a case of probable TB-related FM.Our case is of a 74-year-old man who presented with breathlessness 3 years after fully treated TB. Scans revealed a calcified soft tissue mass within the mediastinum, and a diagnosis of fibrosing mediastinitis resulting in pulmonary hypertension was made. Tests for histoplasmosis and IgG4 staining were negative. Surgical intervention was not felt to be beneficial, and he was treated with prednisolone and mycophenolate mofetil.In the review, we highlight the two forms of mediastinitis-granulomatous versus fibrous, and how these two entities may be on a spectrum of disease progression. We also explore the prevalence, clinical presentation, pathogenesis, imaging techniques and treatment options of TB-related FM., Competing Interests: Competing interests: None declared.

Home oxygen therapy is a highly technical service tailored to patients' particular needs. My job is to advise professional colleagues and patients about the range of respiratory therapies that Air Products offers in partnership with the NHS to help patients live independently at home.