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Hate crimes committed against people with learning disabilities living in the community are causing increasing concern. A recent court case could prompt a rethink from English local authorities about when they should intervene to protect people with learning disabilities. Lawyer Searah Erwin-Jones reports. [ABSTRACT FROM AUTHOR]

We describe the case of an elderly albino man who presented with the typical features of a caecal malignancy and underwent a right hemi-colectomy. Histological assessment subsequently revealed the tumour to be a primary malignant melanoma of the colon. This unexpected diagnosis raises interesting questions regarding the embryology and aetiology of this rare tumour and the anticipated prognosis. To the best of our knowledge, this is the first reported case of a primary colonic melanoma associated with oculocutaneous albinism. [ABSTRACT FROM AUTHOR]

Biofabricating 3D cardiac tissues that mimic the native myocardial tissue is a pivotal challenge in tissue engineering. In this study, we fabricate 3D cardiac tissues with controlled, multidirectional cellular alignment and directed or twisting contractility. We show that multidirectional filamented light can be used to biofabricate high-density (up to 60 × 10 6 cells mL -1 ) tissues, with directed uniaxial contractility (3.8x) and improved cell-to-cell connectivity (1.6x gap junction expression). Furthermore, by using multidirectional light projection, we can partially overcome cell-induced light attenuation, and fabricate larger tissues with multidirectional cellular alignment. For example, we fabricate a tri-layered myocardium-like tissue and a bi-layered tissue with torsional contractility. The approach provides a new strategy to rapidly fabricate aligned cardiac tissues relevant to regenerative medicine and biohybrid robotics., (© 2024 The Author(s). Advanced Science published by Wiley‐VCH GmbH.)

The endangered population of humpback whales ( Megaptera novaeangliae ) breeding and calving off the Cape Verde Islands (CVI) are known to migrate to feeding areas located along the eastern margin of the North Atlantic Ocean (Iceland, and Norway). Here, we report for the first time a confirmed migration of an individual humpback whale from CVI breeding ground to a western North Atlantic feeding ground of West Greenland. This individual humpback, which was photographed and identified off the coast of West Greenland in 2021, was previously documented in CVI 22 years before (1999). An annual subsistence hunt for humpbacks occurs in West Greenland and the resighting at this location with a humpback whale from CVI has strong implications for the conservation efforts of the small CVI population., Competing Interests: The authors declare no competing interests., (© 2024 The Authors. Ecology and Evolution published by John Wiley & Sons Ltd.)

Antibiotic resistance is a significant global public health concern. Uropathogenic Escherichia coli sequence type (ST)131, a widely prevalent multidrug-resistant clone, is frequently associated with bacteraemia. This study investigates third-generation cephalosporin resistance in bloodstream infections caused by E. coli ST131. From 2013-2014 blood culture surveillance in Wales, 142 E. coli ST131 genomes were studied alongside global data. All three major ST131 clades were represented across Wales, with clade C/H30 predominant (n = 102/142, 71.8%). Consistent with global findings, Welsh strains of clade C/H30 contain β-lactamase genes from the bla CTX-M-1 group (n = 65/102, 63.7%), which confer resistance to third-generation cephalosporins. Most Welsh clade C/H30 genomes belonged to sub-clade C2/H30Rx (58.3%). A Wales-specific sub-lineage, named GB-WLS.C2, diverged around 1996-2000. An introduction to North Wales around 2002 led to a localised cluster by 2009, depicting limited genomic diversity within North Wales. This investigation emphasises the value of genomic epidemiology, allowing the detection of genetically similar strains in local areas, enabling targeted and timely public health interventions., (© 2024. The Author(s).)

Frailty and impaired functional status are associated with adverse outcomes on the liver transplant (LT) waitlist and after transplantation. Prehabilitation prior to LT has rarely been tested. We conducted a 2-arm patient-randomized pilot trial to evaluate the feasibility and efficacy of a 14-week behavioral intervention to promote physical activity prior to LT. Thirty patients were randomized 2:1 to intervention (n = 20) versus control (n = 10). The intervention arm received financial incentives and text-based reminders linked to wearable fitness trackers. Daily step goals were increased by 15% in 2-week intervals. Weekly check-ins with study staff assessed barriers to physical activity. The primary outcomes were feasibility and acceptability. Secondary outcomes included mean end-of-study step counts, short physical performance battery, grip strength, and body composition by phase angle. We fit regression models for secondary outcomes with the arm as the exposure adjusting for baseline performance. The mean age was 61, 47% were female, and the median Model for End-stage Liver Disease sodium (MELD-Na) was 13. One-third were frail or prefrail by the liver frailty index, 40% had impaired mobility by short physical performance battery, nearly 40% had sarcopenia by bioimpedance phase angle, 23% had prior falls, and 53% had diabetes. Study retention was 27/30 (90%; 2 unenrolled from intervention, 1 lost to follow-up in control arm). Self-reported adherence to exercise during weekly check-ins was about 50%; the most common barriers were fatigue, weather, and liver-related symptoms. End-of-study step counts were nearly 1000 steps higher for intervention versus control: adjusted difference 997, 95% CI, 147-1847; p = 0.02. On average, the intervention group achieved daily step targets 51% of the time. A home-based intervention with financial incentives and text-based nudges was feasible, highly accepted, and increased daily steps in LT candidates with functional impairment and malnutrition., (Copyright © 2023 American Association for the Study of Liver Diseases.)

Importance: Informal caregivers have valuable insights that occupational therapists can use to prevent and manage problems that may arise in people with spinal cord injury (SCI) because of a lack of physical activity and poor nutrition., Objective: To assess caregiver-identified facilitators of weight management in people with SCI., Design: Descriptive qualitative design using semistructured interviews and thematic analysis., Setting: Regional SCI Care Model System and Veterans Health Administration., Participants: Informal caregivers (n = 24) of people with SCI., Outcomes and Measures: Facilitators of successful weight management in care recipients with SCI., Results: Four themes were identified as weight management facilitators: healthy eating (subthemes: food content, self-control, self-management, and healthy preinjury lifestyle), exercise and therapy (subthemes: occupational and physical therapy, receiving assistance, and resources for exercise), accessibility, and leisure activity or activities of daily living, the latter described as a source of activity (because of required energy expenditure) to facilitate weight management for people with more severe injuries., Conclusions and Relevance: These findings can inform the development of successful weight management plans by occupational therapists by incorporating feedback from informal caregivers. Because caregivers are involved in many of the facilitators identified, occupational therapists should communicate with the dyad about sourcing accessible places to increase physical activity and assessing in-person assistance and assistive technology needs to promote healthy eating and physical activity. Occupational therapists can use informal caregiver-identified facilitators of weight management to help prevent and manage problems for people with SCI secondary to limited activity and poor nutrition. What This Article Adds: Occupational therapy practitioners provide therapeutic intervention to people with SCI; this includes attention to weight management from the time of initial injury throughout their lives. This article is novel in the presentation of informal caregivers' perceptions about successful facilitators of weight management among people with SCI, which is important because caregivers are intimately involved in the daily activities of people with SCI and can be a liaison for occupational therapists and other health care providers about ways to facilitate healthy eating and physical activity., (Copyright © 2023 by the American Occupational Therapy Association, Inc.)

Introduction  We created a virtual rotation to facilitate the exposure of ophthalmology to medical students and serve as a pilot program to help attract students from under-represented in medicine (URM) backgrounds. In addition to the rotation eliminating the financial burdens associated with in-person away rotations, we offered a not-for-credit (i.e., drop-in) option that included sessions outside the typical clinic hours. This option reduced scheduling conflicts as a barrier to enrollment and allowed junior medical students and postgraduates to participate and hopefully further develop an interest in ophthalmology. Methods  Before the rotation, participants completed a pre-test and a survey to collect data on learners' backgrounds and interest in applying for ophthalmology residency. The rotation included live lectures, case-based discussions, chart reviews, and guided self-study. Following the rotation, participants completed a post-test and a survey to query applicants on the online rotation's utility and delivery. Results  Eleven learners enrolled in the course and completed the prerotation survey and test. Approximately one-third (4/11; 36%) were URM students and two-thirds (7/11; 64%) were female. All responded they were planning to apply for ophthalmology residency. All responded they strongly agreed that the rotation increased their general knowledge in ophthalmology, and 89% (9/11) strongly agreed that it improved their ability to diagnose and manage actual patients. Nearly all (7/8; 87.5%) strongly agreed the rotation provided the opportunity to seek support for the residency application process, and all found the online platform reliable and easy to access. Exam scores improved significantly from pre- to post-tests (60 vs. 79%; p  < 0.01). Conclusions  The rotation attracted a substantial proportion of URM students. Learners reported that the virtual rotation effectively taught and supported their endeavors to become ophthalmologists. Virtual rotations for visiting students can reduce barriers such as travel, financial costs, and time constraints that might otherwise hinder exposure to specialty training that is not offered or is underrepresented at students' home institutions. Increasing exposure and offering mentorship through this novel platform deserves further study to enhance diversity and inclusion in medicine., Competing Interests: Conflict of Interest No authors have any conflict of interest., (The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution-NonDerivative-NonCommercial License, permitting copying and reproduction so long as the original work is given appropriate credit. Contents may not be used for commercial purposes, or adapted, remixed, transformed or built upon. ( https://creativecommons.org/licenses/by-nc-nd/4.0/ ).)

Summary: 10.6% patients were CRE positive. Only 27% patients were prescribed at least 1 antibiotic to which infecting pathogen was susceptible. Burn and ICU admission and antibiotics exposures facilitate CRE acquisition. Escherichia coli ST167 was the dominant CRE clone., Background: Given the high prevalence of multidrug resistance (MDR) across South Asian (SA) hospitals, we documented the epidemiology of carbapenem-resistant Enterobacterales (CRE) infections at Dhaka Medical College Hospital between October 2016 and September 2017., Methods: We enrolled patients and collected epidemiology and outcome data. All Enterobacterales were characterized phenotypically and by whole-genome sequencing. Risk assessment for the patients with CRE was performed compared with patients with carbapenem-susceptible Enterobacterales (CSE)., Results: 10.6% of all 1831 patients with a clinical specimen collected had CRE. In-hospital 30-day mortality was significantly higher with CRE [50/180 (27.8%)] than CSE [42/312 (13.5%)] (P = .001); however, for bloodstream infections, this was nonsignificant. Of 643 Enterobacterales isolated, 210 were CRE; blaNDM was present in 180 isolates, blaOXA-232 in 26, blaOXA-181 in 24, and blaKPC-2 in 5. Despite this, ceftriaxone was the most commonly prescribed empirical antibiotic and only 27% of patients were prescribed at least 1 antibiotic to which their infecting pathogen was susceptible. Significant risk factors for CRE isolation included burns unit and intensive care unit admission, and prior exposure to levofloxacin, amikacin, clindamycin, and meropenem. Escherichia coli ST167 was the dominant CRE clone. Clustering suggested clonal transmission of Klebsiella pneumoniae ST15 and the MDR hypervirulent clone, ST23. The major trajectories involved in horizontal gene transfer were IncFII and IncX3, IS26, and Tn3., Conclusions: This is the largest study from an SA public hospital combining outcome, microbiology, and genomics. The findings indicate the urgent implementation of targeted diagnostics, appropriate antibiotic use, and infection-control interventions in SA public institutions., Competing Interests: Potential conflicts of interest. The authors: No reported conflicts of interest. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest., (© The Author(s) 2022. Published by Oxford University Press on behalf of the Infectious Diseases Society of America.)

Introduction: Remote delivery of assessment, consultation and therapy via digital communication technologies in mental health services is important in rural locations, and has rapidly increased due to the COVID-19 pandemic., Methods: This UK-based research investigated what factors should be considered in the development and evaluation of digitally mediated service provision for children and young people with social, emotional and mental health (SEMH) needs using two approaches: (1) a focus group with five young people (aged 16-19 years) and (2) an online survey with 18 parents/carers of primary-age children with SEMH difficulties., Results: Getting help quickly was most important to both young people and parents/carers when accessing services, with having a say in their care of equal importance to young people but not parents/carers. Analysis identified participants' preferences and perceived positives and negatives of digitally mediated service provision., Conclusion: Digitally mediated service provision should be timely and patient-centred to be considered acceptable by young people with SEMH needs and their parents/carers. Evaluations should include comprehensive measures of service efficiency and service user experience to better understand the benefits of digital mediation.

Digital communication technologies can be used for team consultation, case management, and information sharing in health and mental health services for children and young people (CYP). The objective of the systematic review was to investigate the evidence as to whether digitally-mediated team communication for CYP improves outcomes. We searched PsycINFO, PubMed, Web of Science, and Cochrane Library for relevant studies. Results were synthesised narratively. Seven studies were identified from 439 initial records. Analysis highlighted that digitally-mediated team communication is generally valued by professionals for supporting practice and that there is overall satisfaction with the process. There was preliminary evidence (from one study) that clinical outcomes from digitally-mediated team communication are comparable to those achieved by a collaborative service model with direct specialist care to service users via digital communication technology. There is a need for further high-quality research into clinical outcomes and service user experience, as well as financial implications., (© 2021. The Author(s).)

Background: Spinal cord injury (SCI) healthcare providers are aware of the harmful consequences of overweight/obesity in persons with SCI, but many are unaware of available information and lack training to guide weight management care in the SCI population., Objective: Describe the development and content of an educational curriculum for healthcare providers to help individuals with SCI prevent or manage overweight/obesity., Methods: The biopsychoecological framework guided curriculum planning, data collection, and product development. Thematic analysis of interviews conducted with individuals with SCI, informal caregivers, and SCI healthcare providers pinpointed central educational curriculum topics. SCI healthcare providers evaluated the curriculum., Results: Seven comprehensive topics were developed: 1. Scope and consequences of overweight/obesity in SCI; 2. Classifying and measuring overweight/obesity in SCI; 3. Guidelines related to weight management in SCI; 4. Identifying challenges (and solutions) to weight management in SCI; 5. Strategies for providers to facilitate weight management; 6. Understanding goals, motivators, and desired feedback for weight management; and 7. Knowing how informal caregivers are affected by weight and weight management of care recipients with SCI. High ratings (>80% strong agreement) were achieved on content, word choice, organization, relevance, and actionability. Modification needs were identified and subsequently made to layout, visual aids, and provision of tangible resources. Providers described the curriculum as a scientifically rigorous resource that addresses a knowledge gap, provides population-specific content, and is useful across interdisciplinary teams., Conclusion: We developed a self-directed learning educational curriculum addressing topics most salient to stakeholders involved in overweight/obesity management of persons with SCI., (Published by Elsevier Inc.)

Lymphoma of the urinary bladder is quite rare, accounting for a small percentage of all bladder neoplasms. Here we discuss the case of a 68-year-old male patient who initially presented with acute renal failure and severe bilateral hydronephrosis on ultrasound. Cross-sectional imaging further revealed a diffusely thickened bladder wall with extensive retroperitoneal and mesenteric lymphadenopathy. Bladder biopsies ultimately led to a diagnosis of stage IV chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL). This is a rare instance of upper tract dilatation being the first sign of a widely disseminated hematologic malignancy.

In this work, we present an injection molded soft total artificial heart (sTAH) produced from high-temperature vulcanizing silicone using an industrial metal injection mold. At 60 beats per minute, the sTAH exhibited a total cardiac output of over 16 L/min against physiological pressures on a mock circulation and was pumped continuously for 110,000 actuation cycles. Finite element analysis was used to identify stress concentrations within the sTAH, allowing an optimized design to be proposed.

Objectives: To explore the personal meanings of healthy eating and physical activity among individuals living with spinal cord injury (SCI) and the information and resources they find beneficial. Methods: We conducted in-depth semistructured individual interviews to understand the personal meanings of healthy eating and physical activity among individuals with SCI. We completed a thematic analysis of qualitative data. Results: Participants were 11 Veterans and 14 civilians, predominantly male, non-Hispanic White, and with paraplegia. Data were described across two categories, including the personal meaning of healthy eating and the personal meaning of physical activity/exercise. Individuals with SCI described their meaning of healthy eating around four themes: types of food, amounts/portions of food, conscious/mindful eating, and eating to enhance health. Individuals wanted information on tailored diets for individuals with paraplegia and tetraplegia and healthy foods that are easy to prepare by people with SCI. Their personal meaning of physical activity/exercise focused on four themes: types of physical activity and exercise, staying active, moving/movement, and differences from non-SCI. Desired information around physical activity included cardiovascular workouts that are effective and possible to do in a wheelchair so that people with SCI can burn enough of the calories they consume to lose or maintain weight. Conclusion: Results provide a better understanding of what healthy eating and physical activity mean to people with SCI and information they desire toward these goals, which can be used to guide patient-provider discussions, develop health promotion programs, and tailor interventions to capitalize on meaningful concepts and beliefs that facilitate healthy behaviors., Competing Interests: Disclosures The views expressed in this article are those of the authors and do not necessarily reflect the position or policy of the Department of Veterans Affairs or the United States government., (© 2021 American Spinal Injury Association.)

Objective: To gain a fuller understanding, in the context of biopsychoecological factors, of drivers/motivators, goal setting, and feedback, individuals with spinal cord injury (SCI) find helpful to gauge their weight management progress. Research Method/Design: We conducted in-depth interviews around weight management in SCI. Participants included veterans and civilians with SCI. Thematic analysis methodology was used to categorize data into relevant recurrent and/or conceptually significant themes. Results: Twenty-five individuals identified three primary reasons they wanted to participate in weight management, including overall health and wellness, appearance, and functional mobility. Their self-identified weight management goals included reaching/maintaining a specific body weight and/or trimming a focused body part; engaging in any or more physical activity/exercise; gaining strength and endurance; participating in life and activities; and alleviating weight-related health symptoms (e.g., pain). Individuals identified progress assessments, recognition, regular check-ins, and encouragement as helpful feedback toward weight management achievement. Conclusions/Implications: Our work identified what drives weight management in individuals with SCI, what is important to them in terms of goal setting, and what feedback they would find helpful. These findings may be used in intervention planning and program development to facilitate participation and behavior modification. Weight management efforts and interventions are needed that 1) incorporate motivators for weight management that are important to individuals with SCI; 2) help them identify actionable process and performance goals to facilitate achievement of self-identified meaningful outcome goals; and 3) provide person-centered weight management progress feedback such as those identified in this study (progress assessments, recognition, regular check-ins, and encouragement). (PsycInfo Database Record (c) 2021 APA, all rights reserved).

The Stanford Integrated Psychosocial Assessment for Transplant (SIPAT) is a standardized psychosocial evaluation tool used in liver transplantation (LT) evaluation. We assessed the impact of the SIPAT score and subdomains on transplant waitlisting decisions and post-LT outcomes including immunosuppression (IS) nonadherence, biopsy-proven rejection, andmortality/graft failure. We conducted a single-center observational cohort study of 1430 patients evaluated for LT. Patients were divided in 2 groups based on a SIPAT cutoff score of <21 or ≥21 (higher SIPAT scores indicate higher psychosocial risk). Regression models assessed relationships between total SIPAT score and domain scores and waitlisting decisions, IS nonadherence, allograft rejection, and death/graft failure. Elevated total SIPAT and SIPAT domain scores were associated not being added to the waitlist (total SIPAT core ≥21 adjusted odds ratio [aOR], 1.78 [95% confidence interval, CI, 1.36-2.33]; readiness score ≥5 aOR, 2.01 [95% CI, 1.36-2.76]; social support score ≥4aOR, 1.50 [95% CI, 1.15-1.94]; psychopathology score ≥7 aOR, 1.45 [95% CI, 1.07-1.94]; lifestyle/substance abuse score ≥12 aOR, 1.72 [95%CI, 1.23-2.39]) and were more likely to experience IS nonadherence as measured by the tacrolimus coefficient of variation (CoV) (total SIPAT score ≥21 aOR, 2.92 [95% CI, 1.69-5.03]; readiness score ≥5 aOR, 3.26 [95% CI, 1.63-6.52]; psychopathology score ≥7 aOR, 1.88 [95% CI, 1.00-3.50]; lifestyle substance abuse score ≥12 aOR, 3.03 [95% CI, 1.56-5.86]). SIPAT readinessscore ≥5 was associated with biopsy-proven allograft rejection (aOR, 2.66; 95% CI, 1.20-5.91). The SIPAT score was independently associated with LT listing decisions and IS nonadherence, and the readiness domain was associated with the risk of allograft rejection. These findings offer insights into higher risk recipients who require additional support before and aftertransplantation., (Copyright © 2020 by the American Association for the Study of Liver Diseases.)

Objective: Despite the numerous health benefits of physical activity, inactivity is endemic among adults with knee osteoarthritis (OA). Because sleep quality may be a target in order to improve physical activity behavior, we investigated the cross-sectional relationship between restless sleep and physical activity in participants with or at risk for knee OA., Methods: We analyzed accelerometer-measured physical activity and clinical data of participants included in the Osteoarthritis Initiative (OAI). We used multiple regression analysis to evaluate physical activity for participants, who were grouped by the reported frequency of restless sleep, and adjusted for demographic and medical confounders., Results: Of the 1,892 OAI participants for whom complete data were available, 300 participants (16%) reported restless sleep ≥3 days in the past week. Participants who reported restless sleep for much of the time (3-4 days/week) and most of the time (5-7 days/week) had 11.9% and 23.7% less weekly minutes of moderately vigorous activity, respectively, compared to participants who reported rarely restless sleep (<1 day/week) (P for trend 0.021). These differences persisted after accounting for age, sex, race, body mass index, medical comorbidity, and knee OA severity and pain (P for trend 0.023). Differences related to restless sleep were largely attenuated by the presence of high depressive symptoms and low energy levels., Conclusion: Poor sleep quality is associated with less physical activity in persons with or at risk for knee OA. Future studies are needed to determine the mechanisms of how poor sleep and physical activity are related, how energy and depression mediate these relationships, and whether interventions that improve sleep quality might result in increased physical activity., (© 2018, American College of Rheumatology.)

The worldwide outbreak of COVID-19 has drastically increased pressure on medical resources and highlighted the need for rapidly available, large-scale, and low-cost personal protective equipment (PPE). In this work, an alternative full-face mask is adapted from a modified snorkel mask to be used as PPE with two medical-grade filters and a 3D-printed adapter. Since the mask covers the eyes, mouth, and nose, it acts as a full-face shield, providing additional protection to healthcare workers. The SARS-CoV-2 has a size between 60 nm and 140 nm, and airborne viral particles can be carried by larger droplets with sizes up to several millimeters. The minimum filtration efficiency of mechanical and electrostatic filters is usually reached between 30 nm and 300 nm. The filtration efficiency of different medical filters is measured for particles below 300 nm to cover the size of the SARS-CoV-2 and small virus-laden droplets, and determine the minimum efficiency. The filtration performance of the adapted full-face mask is characterized using NaCl particles below 500 nm and different fitting scenarios to determine the minimum protection efficiency. The mask is compared to a commercial respirator and characterized according to the EN 149 standard, demonstrating that the protection fulfills the requirements for the FFP2 level (filtering face-piece 2, stopping at least 94% of airborne particles). The device shows a good resistance to several cycles of decontamination (autoclaving and ethanol immersion), is easy to be produced locally at low cost, and helps to address the shortage in FFP2 masks and face shields by providing adequate protection to healthcare workers against particles <500 nm in size.

Purpose of Review: We provide an overview of the recent evidence on the prevalence, risk factors, and consequences of medication non-adherence (NA) in liver transplant (LT) recipients., Recent Findings: NA in LT is associated with socio-demographic and medication-related factors, low social support, and poor health literacy. Patient-reported adherence is one of the most common methods to measure NA using validated assessments; immunosuppression (IS) drug levels and electronic monitoring may also be used. Simplification of IS regimens such as the conversion from twice daily to once daily has been shown to be safe, effective, and improves adherence. Relatively few studies have prospectively investigated NA predictors or interventions to reduce NA in LT., Summary: Medication non-adherence is a multi-faceted issue that is common among LT recipients and associated with adverse outcomes. NA in LT recipients warrants further study as only a few interventions have been published focused on reducing NA in LT., Competing Interests: Conflict of Interest Disclosures Dr. Marina Serper received personal fees from BioVie, Inc. unrelated to the submitted workStudent Doctor Lauren Jones has no conflicts of interest to disclose

Background: Alcohol-related liver disease (ALD) is the leading indication for liver transplantation (LT) in the USA. Alcohol relapse post-LT can negatively impact long-term outcomes, and prognostic scoring systems are available for further study., Aims: Our study aims were to: (1) evaluate the relationship between alcohol relapse and rejection and mortality, (2) investigate risk factors for relapse, and (3) assess predictive validity of the SIPAT (Stanford Integrated Psychosocial Assessment for Transplant) and SALT (Sustained Alcohol Use Post-Liver Transplant) scores on post-LT alcohol relapse., Methods: We conducted a retrospective chart review of 155 patients transplanted for chronic ALD at a single transplant center. Cox proportional hazard models assessed the relationship between alcohol relapse and allograft rejection and psychosocial risk factors for relapse., Results: 20% of patients met criteria for alcohol relapse. Alcohol relapse was associated with allograft rejection (HR 2.33, 95% CI 1.11-4.91, p = .03). Three variables most strongly associated with alcohol relapse: prior relapse, failure to engage in recommended alcohol treatment, and continued drinking with liver disease, which were combined into a psychosocial model. SIPAT score≥ 21 and SALT score ≥ 7 were associated with alcohol relapse (HR 6.40, 95% CI 1.36-30.18, p = .019 and HR 2.30, 95% CI 1.12-4.75, p = .024). Receiver operator characteristic analysis compared predictive ability of our psychosocial model to SIPAT (C-statistic .83 compared to .71) and SALT (C-statistic = .77 compared to .62)., Conclusion: We identified important psychosocial predictors of post-LT alcohol relapse and validated SIPAT and SALT scores as pre-transplant risk factors for alcohol relapse.

Kidney transplant recipients (KTRs) and liver transplant recipients (LTRs) have significant post-transplant weight gain and low physical activity. We conducted a home-based, remotely monitored intervention using wearable accelerometer devices to promote post-transplant physical activity. We randomized 61 KTRs and 66 LTRs within 24 months of transplant to: (i) control, (ii) accelerometer or (iii) intervention: accelerometer paired with financial incentives and health engagement questions to increase steps by 15% from baseline every 2 weeks. The primary outcome was weight change. A co-primary outcome for the two accelerometer arms was steps. Participants were recruited at a median of 9.5 [3-17] months post-transplant. At 3 months, there were no significant differences in weight change across the three arms. The intervention arm was more likely to achieve ≥7000 steps compared to control with device (OR 1.99, 95% CI: 1.03-3.87); effect remained significant after adjusting for demographics, allograft, time from transplant and baseline weight. Adherence to target step goals was 74% in the intervention arm, 84% of health engagement questions were answered correctly. A pilot study with financial incentives and health engagement questions was feasible and led KTRs and LTRs to walk more, but did not affect weight. A definitive trial is warranted., (© 2020 Steunstichting ESOT.)

Background: Burkholderia cepacia complex (Bcc) is a group of serious pathogens in cystic fibrosis patients and causes life threatening infections in immunocompromised patients. Species within the Bcc are widely distributed within the environment, can survive in the presence of disinfectants and antiseptics, and are inherently multidrug resistant (MDR)., Methods: Dhaka Medical College Hospital (DMCH) patients with a B. cepacia positive blood culture between 20 October 2016 to 23rd September 2017 were considered as outbreak cases. Blood stream infections (BSIs) were detected using BacT/ALERT 3D at DMCH. B. cepacia was isolated on chromogenic UTI media followed by MALDI-TOF. Minimum inhibitory concentration (MIC) of clinically relevant antibiotics was determined by agar dilution. Whole genome sequencing was performed on an Illumina MiSeq platform. Patients' demographic and clinical data were collected. Patients' clinical history and genomic data of the outbreak strains were merged to investigate possible outbreaks. Ninety-one B. cepacia genomes were downloaded from 'Burkholderia Genome Database' and the genomic background of the global strains were compared with our outbreak strains., Results: Among 236 BSIs, 6.35% (15/236) were B. cepacia. Outbreak cases were confined to the burn critical care unit and, to a lesser extent, the paediatrics department. There was a continuum of overlapping cases at DMCH between 23 October 2016 to 30 August 2017. Core genome SNPs showed that the outbreak strains were confined to a single clade, corresponded to a common clone (ST1578). The strains were shown to be MDR and associated with a mortality of 31% excluding discharge against medical advice. MIC profiles of the strains suggested that antibiotics deployed as empirical therapy were invariably inappropriate. The genetic background of the outbreak strains was very similar; however, a few variations were found regarding the presence of virulence genes. Compared to global strains from the Burkholderia Genome Database, the Bangladeshi strains were genetically distinct., Conclusions: Environmental surveillance is required to investigate the aetiology and mode of transmission of the B. cepacia outbreak. Systematic management of nosocomial outbreaks, particularly in resource limited regions, will mitigate transmission and will improve patients' outcomes., Competing Interests: The authors have declared that no competing interests exist.

Lung cancer screening with low-dose computed tomography (LDCT) reduces lung cancer mortality, yet few eligible high-risk patients receive it annually. This protocol describes a community-partnered intervention (Toolkit) designed to support primary care practices in making referrals for lung screening and guiding patients into appropriate screening pathways. This study uses a stepped-wedge implementation design. Screening centers are randomized by readiness level to enter the intervention phase in three-month "steps" with pre-intervention data serving as the control. The primary outcome is whether delivery of the Toolkit to primary care practices results in a monthly increase in number of initial LDCT screenings. Six participating centers will identify 10 practices and reach 2-3 providers per practice to train them to use the Toolkit. The Toolkit will address known barriers to screening and referral at the patient and provider levels and provide support for required elements of screening. Toolkit components include adaptable evidence-based interventions to maximize compatibility with workflows. We hypothesize that after nine months of intervention delivery, the number of initial screening per center will double. Involving 60 practices achieves 80% power at 5% level of significance. Implementation outcomes such as adoption, acceptability, feasibility, adaptation, and sustainability will be assessed through field-notes and activity logs. LDCT for lung cancer screening currently reaches a small fraction of eligible adults. To reach the full potential to reduce mortality, primary care practices are an important venue for increasing appropriate referrals. This multidisciplinary trial will encourage acceptability and sustainability by using local knowledge and promoting partnership between providers and patients. Trial registration: ClinicalTrials.gov, NCT03958253., Competing Interests: Declaration of Competing Interest The authors declare that they have no competing interests., (Copyright © 2020 Elsevier Inc. All rights reserved.)

The emergence of mobilized colistin resistance genes ( mcr ) has become a serious concern in clinical practice, compromising treatment options for life-threatening infections. In this study, colistin-resistant Klebsiella pneumoniae harboring mcr-8.1 was recovered from infected patients in the largest public hospital of Bangladesh, with a prevalence of 0.3% (3/1,097). We found mcr-8.1 in an identical highly stable multidrug-resistant IncFIB(pQil) plasmid of ∼113 kb, which belonged to an epidemiologically successful K. pneumoniae clone, ST15. The resistance mechanism was proven to be horizontally transferable, which incurred a fitness cost to the host. The core genome phylogeny suggested the clonal spread of mcr-8.1 in a Bangladeshi hospital. Core genome single-nucleotide polymorphisms among the mcr-8.1 -positive K. pneumoniae isolates ranged from 23 to 110. It has been hypothesized that mcr-8.1 was inserted into IncFIB(pQil) with preexisting resistance loci, bla TEM-1b and bla CTX-M-15 , by IS 903B Coincidentally, all resistance determinants in the plasmid [ mcr-8.1 , ampC , sul2 , 1d-APH(6) , APH(3'')-Ib , bla TEM-1b , bla CTX-M-15 ] were bracketed by IS 903B , demonstrating the possibility of intra- and interspecies and intra- and intergenus transposition of entire resistance loci. This is the first report of an mcr -like mechanism from human infections in Bangladesh. However, given the acquisition of mcr-8.1 by a sable conjugative plasmid in a successful high-risk clone of K. pneumoniae ST15, there is a serious risk of dissemination of mcr-8.1 in Bangladesh from 2017 onwards. IMPORTANCE There is a marked paucity in our understanding of the epidemiology of colistin-resistant bacterial pathogens in South Asia. A report by Davies and Walsh (Lancet Infect Dis 18:256-257, https://doi.org/10.1016/S1473-3099(18)30072-0, 2018) suggests the export of colistin from China to India, Vietnam, and South Korea in 2016 was approximately 1,000 tons and mainly used as a poultry feed additive. A few reports forecast that the prevalence of mcr in humans and livestock will increase in South Asia. Given the high prevalence of bla CTX-M-15 and bla NDM in India, Bangladesh, and Pakistan, colistin has become the invariable option for the management of serious infections, leading to the emergence of mcr -like mechanisms in South Asia. Systematic scrutiny of the prevalence and transmission of mcr variants in South Asia is vital to understanding the drivers of mcr genes and to initiate interventions to overcome colistin resistance., (Copyright © 2020 Farzana et al.)

Comorbid depression is common in adolescents with chronic illness. We aimed to design and test a linguistic coding scheme for identifying depression in adolescents with chronic fatigue syndrome/myalgic encephalomyelitis (CFS/ME), by exploring features of e-consultations within online cognitive behavioural therapy treatment. E-consultations of 16 adolescents (aged 11-17) receiving FITNET-NHS (Fatigue in teenagers on the interNET in the National Health Service) treatment in a national randomized controlled trial were examined. A theoretically driven linguistic coding scheme was developed and used to categorize comorbid depression in e-consultations using computerized content analysis. Linguistic coding scheme categorization was subsequently compared with classification of depression using the Revised Children's Anxiety and Depression Scale published cut-offs (t-scores ≥65, ≥70). Extra linguistic elements identified deductively and inductively were compared with self-reported depressive symptoms after unblinding. The linguistic coding scheme categorized three (19%) of our sample consistently with self-report assessment. Of all 12 identified linguistic features, differences in language use by categorization of self-report assessment were found for "past focus" words (mean rank frequencies: 1.50 for no depression, 5.50 for possible depression, and 10.70 for probable depression; p < .05) and "discrepancy" words (mean rank frequencies: 16.00 for no depression, 11.20 for possible depression, and 6.40 for probable depression; p < .05). The linguistic coding profile developed as a potential tool to support clinicians in identifying comorbid depression in e-consultations showed poor value in this sample of adolescents with CFS/ME. Some promising linguistic features were identified, warranting further research with larger samples., (© 2019 John Wiley & Sons, Ltd.)

Background: Staphylococcus aureus is among the most commonly identified causes of invasive bacterial infection in children; however, reliable results from cultures of sterile-site samples often cannot be obtained, which necessitates prescription of a broad empiric antimicrobial agent(s). Children with invasive S aureus infection rapidly generate high antibody titers to the cytotoxin LukAB; therefore, the aim of this study was to assess the diagnostic utility of an anti-LukAB antibody assay for children with musculoskeletal infection (MSKI)., Methods: We conducted a 2-year prospective study of all eligible children admitted to Vanderbilt Children's Hospital with an MSKI. Acute and convalescent sera were obtained, and antibodies that target LukAB were measured by an enzyme-linked immunosorbent assay., Results: Forty-two children were enrolled. The median concentrations of LukAB antibodies for children with S aureus infection were 130.3 U/mL in the acute phase and 455 U/mL in the convalescent phase (P < .001). The median concentrations of LukAB antibodies in children with a non-S aureus MSKI were 8.6 U/mL in the acute phase and 9.7 U/mL in the convalescent phase. The assay discriminated between S aureus and non-S aureus infection with areas under the receiver operating characteristic curve of 0.81 (95% confidence interval, 0.67-0.95; P < .001) and 0.95 (95% confidence interval, 0.86-1; P < .001) for samples tested in the acute and follow-up periods, respectively. With no false-negative results, the assay accurately ruled out S aureus in samples obtained during the convalescent phase., Conclusion: Culture-independent diagnostics have the potential to improve care by narrowing antimicrobial therapy on the basis of the likelihood of S aureus infection. The results of this proof-of-concept study suggest that a LukAB serologic assay might be useful in the diagnosis of invasive bacterial infections, and larger-scale validation studies are warranted., (© Crown copyright 2018.)

We report a clonal outbreak of multidrug-resistant (MDR) Klebsiella variicola (sequence type [ST] 771) in a Bangladeshi neonatal unit from October 2016 to January 2017, associated with high mortality (54.5%). During the outbreak, K. variicola ST771 acquired an MDR plasmid harboring blaNDM-1, linked to high exposure to ceftriaxone and amikacin., (© Crown copyright 2018.)

Objective: To investigate the relationship between sedentary behavior and quality-adjusted life years (QALYs) among participants in the Osteoarthritis Initiative., Design: Longitudinal, observational design., Setting: Osteoarthritis Initiative cohort., Participants: Individuals (N=1794) from a prospective, multicenter longitudinal cohort were classified into quantile groups based on average daily sedentary time (most sedentary, quartile 1 [Q1] ≥11.6h; 10.7h≤ Q2 <11.6h; 9.7h≤ Q3 <10.7h; least sedentary, Q4 <9.7h)., Interventions: Not applicable., Main Outcome Measures: Individual QALYs were estimated over 2 years from the area under the curve of health-related utility scores derived from the Medical Outcomes Study 12-Item Short-Form Health Survey versus time. The relationship between baseline sedentary behavior and median 2-year QALYs was estimated using quantile regression adjusted for socioeconomic factors and body mass index., Results: Lower QALYs over 2 years were more frequently found among the most sedentary (Q1, median 1.59), and QALYs increased as time spent in baseline sedentary behavior decreased (median QALYs for Q2, 1.64; Q3, 1.65; Q4, 1.65). The relationship of sedentary time and median QALY change was only significant for the most sedentary Q1 group, where an additional hour of sedentary behavior significantly reduced QALYs by -.072 (95% confidence interval, -.121 to -.020)., Conclusions: Our findings suggest that individuals with the most extreme sedentary profiles may be vulnerable to additional losses of quality of life if they become more sedentary. Targeting these individuals to decrease sedentary behavior has the potential to be cost-effective., (Copyright © 2017 American Congress of Rehabilitation Medicine. Published by Elsevier Inc. All rights reserved.)

The pathogenesis of Staphylococcus aureus is mediated by an array of important virulence factors, including the two-component leukocidin family of toxins. LukAB (also known as LukGH), the most recently discovered leukocidin, is potently lethal to phagocytes, produced during invasive human disease, and present in all known clinical isolates of S. aureus Intravenous immunoglobulin (IVIg) is often used clinically in severe S. aureus infections. The primary aim of this study was to assess the binding and neutralization potential of IVIg against LukAB. A secondary aim was to examine the lot-to-lot variability of IVIg in the binding and neutralization of LukAB. We studied 24 distinct lots of IVIg and compared them to serum from children with invasive S. aureus infection (in the acute and convalescent phases) and from healthy, uninfected controls. We found that all lots of IVIg contained functional antibodies targeting LukAB. After adjusting for total antibody content per sample, we found that the amount of anti-LukAB antibody in IVIg was similar to that seen with healthy controls and less than that seen with patients with invasive S. aureus infection. IVIg samples had lower neutralization capacity than samples from healthy controls and children with invasive infection. IVIg had remarkably little lot-to-lot variation in LukAB binding but had significantly more variation in toxin neutralization. These results represent the first report of functional antibodies against the important S. aureus leukocidin LukAB in IVIg. Given the frequent clinical use of IVIg for severe S. aureus infections, improving our understanding of functional antibody properties exhibited by this therapeutic is essential., (Copyright © 2017 American Society for Microbiology.)

Importance: Suboptimal overlap in outcomes reported in clinical trials and systematic reviews compromises efforts to compare and summarize results across these studies., Objectives: To examine the most frequent outcomes used in trials and reviews of the 4 most prevalent eye diseases (age-related macular degeneration [AMD], cataract, diabetic retinopathy [DR], and glaucoma) and the overlap between outcomes in the reviews and the trials included in the reviews., Design, Setting, and Participants: This cross-sectional study examined all Cochrane reviews that addressed AMD, cataract, DR, and glaucoma; were published as of July 20, 2016; and included at least 1 trial and the trials included in the reviews. For each disease, a pair of clinical experts independently classified all outcomes and resolved discrepancies. Outcomes (outcome domains) were then compared separately for each disease., Main Outcomes and Measures: Proportion of review outcomes also reported in trials and vice versa., Results: This study included 56 reviews that comprised 414 trials. Although the median number of outcomes per trial and per review was the same (n = 5) for each disease, the trials included a greater number of outcomes overall than did the reviews, ranging from 2.9 times greater (89 vs 30 outcomes for glaucoma) to 4.9 times greater (107 vs 22 outcomes for AMD). Most review outcomes, ranging from 14 of 19 outcomes (73.7%) (for DR) to 27 of 29 outcomes (93.1%) (for cataract), were also reported in the trials. For trial outcomes, however, the proportion also named in reviews was low, ranging from 19 of 107 outcomes (17.8%) (for AMD) to 24 of 89 outcomes (27.0%) (for glaucoma). Only 1 outcome (visual acuity) was consistently reported in greater than half the trials and greater than half the reviews., Conclusions and Relevance: Although most review outcomes were reported in the trials, most trial outcomes were not reported in the reviews. The current analysis focused on outcome domains, which might underestimate the problem of inconsistent outcomes. Other important elements of an outcome (ie, specific measurement, specific metric, method of aggregation, and time points) might have differed even though the domains overlapped. Inconsistency in trial outcomes may impede research synthesis and indicates the need for disease-specific core outcome sets in ophthalmology.

The 2-component leukotoxin LukAB is critical for Staphylococcus aureus targeting and killing of human neutrophils ex vivo and is produced in the setting of human infection. We report 3 LukAB-specific human monoclonal antibodies (mAbs) with distinct mechanisms of toxin neutralization and in vivo efficacy. Three hybridomas secreting mAbs with anti-LukAB activity (designated SA-13, -15, and -17) were generated from B cells obtained from a 12-year-old boy with S. aureus osteomyelitis. Each of the 3 mAbs neutralized LukAB-mediated neutrophil toxicity, exhibited differing levels of potency, recognized different antigenic sites on the toxin, and displayed at least 2 distinct mechanisms for cytotoxic inhibition. SA-15 bound exclusively to the dimeric form of the toxin, suggesting that human B cells recognize epitopes on the dimerized form of LukAB during natural infection. Both SA-13 and SA-17 bound the LukA monomer and the LukAB dimer. Although all 3 mAbs potently neutralized cytotoxicity, only SA-15 and SA-17 significantly inhibited toxin association with the cell surface. Treatment with a 1:1 mixture of mAbs SA-15 and SA-17 resulted in significantly lower bacterial colony counts in heart, liver, and kidneys in a murine model of S. aureus sepsis. These data describe the isolation of diverse and efficacious antitoxin mAbs., (© The Author 2017. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.)

Background: Physical inactivity is a leading risk factor for developing disability. Although randomized clinical trials have demonstrated improving physical activity can reduce this risk in older adults with arthritis, these studies did not specifically evaluate inactive adults., Objectives: The aim of this study was to evaluate the relationship of changes in physical activity with disability changes among initially inactive adults with or at high risk of knee osteoarthritis from Osteoarthritis Initiative., Methods: Inactive persons were identified at baseline based on the US Department of Health and Human Services classification (no [zero] 10-minute session of moderate-to-vigorous [MV] activity over 1 week) from objective accelerometer monitoring. Two years later, physical activity change status was classified as follows: (1) met Federal physical activity guidelines (≥150 MV minutes/week acquired in bouts ≥10 minutes), (2) insufficiently increased activity (some but <150 MV bout minutes/week), or (3) remained inactive. Disability at baseline and 2 years was assessed by Late Life Disability Instrument limitation and frequency scores. Multiple regression evaluated the relationship of physical activity change status with baseline-to-2-year changes in disability scores adjusting for socioeconomics, health factors, and baseline disability score., Results: Increased physical activity showed a graded relationship with improved disability scores in Late Life Disability Instrument limitation (P < 0.001) and frequency scores (P = 0.027). While increasing MV activity to guideline levels showed the greatest reduction, even insufficiently increased physical activity was related to reduced disability., Conclusions: Findings support advice to increase MV physical activity to reduce disability among inactive adults with or at high risk of knee osteoarthritis, even when guidelines are not met., Competing Interests: All authors report no disclosures or conflicts of interest.