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Background: Patients with psoriasis are less physically active compared to age-matched controls, due to psoriasis-specific barriers, which significantly limits their ability to benefit from health-promoting levels of physical activity (PA). In addition, long-term health outcomes for people with psoriasis are poor and include depression, metabolic syndrome and cardiovascular disease (CVD); presenting a significant challenge to healthcare services., Objectives: We designed a PA intervention in partnership with patients with psoriasis hypothesising this may have therapeutic utility in the management of psoriasis., Methods: Participants with chronic plaque psoriasis were recruited to a single-centre, 20-week, prospective cohort study. A wrist-worn accelerometer (GENEActiv Original; Activinsights Ltd) and a hip-worn pedometer (Onwalk 900; Decathlon Group) were used objectively measure levels of PA. Our 10-week PA intervention comprised twice weekly 60-min walks within three different greenspaces in Greater Manchester, each led by a Sports and Exercise Scientist to deliver a pre-specified volume/dose of activity. During weeks-11-20 of the study, participants followed independent activities. Clinical evaluation, including assessment of psoriasis severity, cardiometabolic parameters, psychological wellbeing and functional capacity was made at baseline, week-10 and -20., Results: Sixteen patients with psoriasis completed the study. We observed significantly reduced Psoriasis Area and Severity Index at week-10 ( p  = 0.01) and -20 ( p  = 0.001) compared to baseline, with 50% of participants achieving PASI-50 at week-20. Dermatology Life Quality Index (DLQI) was significantly reduced at week-20 ( p  = 0.04), compared to baseline. Significant reduction in blood pressure at week-10 (systolic: -7.4 mmHg, p  = 0.002; diastolic: -4.2 mmHg, p  = 0.03) and -20 (systolic: -8.8 mmHg, p  = 0.001; diastolic: 4.1 mmHg, p  = 0.008) was observed and pulse wave velocity was significantly reduced by week-20 ( p  = 0.02), suggesting improvement in cardiovascular health. Despite high prevalence of anxiety and depression at baseline, we documented a significant improvement in wellbeing and psychological health. Functional capacity was significantly enhanced following completion of the study., Conclusion: Increasing PA constitutes a promising therapeutic intervention in the management of psoriasis. Evaluation of our intervention in a clinical trial would help determine clinical utility and establish PA guidelines for patients with psoriasis., Competing Interests: The authors declare no conflicts of interest., (© 2024 The Author(s). Skin Health and Disease published by John Wiley & Sons Ltd on behalf of British Association of Dermatologists.)

Advancements in cancer treatment have led to improved survival rates, with early phase clinical trials (EPCTs) serving as important initial steps in evaluating novel therapies. Recent studies have shown that response rates in these trials have doubled in the last twenty years. Patients who enroll on EPCTs have advanced cancer and heightened symptomatology yet maintain a robust performance status that qualifies them for clinical trial participation. It is well established that many of these patients have needs that can be addressed by palliative care, including symptom management, value assessments, advance care planning, and psychosocial and spiritual support. Several small studies have aimed to identify the most beneficial palliative care intervention for this cohort of patients, ranging from formal clinic-based multidisciplinary palliative care interventions to home-based interventions. While outcomes have trended towards benefit for patients, especially pertaining to psychological well-being, most studies were not powered to detect additional benefits for improved physical symptom management, reduction in care utilization or increased length of time on trial. In this review, we discuss the unique palliative care needs of this population and what we can learn from results of past interventional studies. We advocate for a tailored palliative care approach that acknowledges the time toxicity experienced by patients enrolled in EPCTs and address challenges posed by shortages within the palliative care workforce., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Trauma-informed care (TIC) is an approach to care emerging in research and in practice that involves addressing the needs of individuals with histories of trauma. The aim of this scoping review was to examine the current literature relating to TIC interventions used in pediatric mental health inpatient and residential settings. We sought to answer the following two research questions: (a) What are the TIC interventions used in pediatric inpatient and residential treatment mental healthcare settings and what are their components? and (b) What are the implementation goals and strategies used with these TIC interventions? We conducted this scoping review according to JBI (formerly Joanna Briggs Institute) methodology for scoping reviews. We included any primary study describing a TIC intervention that was implemented at a specific site which identified and described implementation strategies used. Of 1,571 identified citations and 54 full-text articles located by handsearching, 49 met the eligibility criteria and were included, representing 21 distinct TIC interventions. We present the reported aim, ingredients, mechanism, and delivery (AIMD) of TIC interventions as well as the implementation goals and strategies used, which varied in detail, ranging from very little information to more detailed descriptions. In the context of these findings, we emphasize the complexity of TIC and of TIC interventions, and the importance of identifying and clearly reporting TIC intervention goals, intervention details, and implementation strategies. We suggest applying intervention frameworks or reporting guidelines to support clear and comprehensive reporting, which would better facilitate replication and synthesis of published TIC interventions., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Objective: To describe and compare the recruitment methods employed in a randomized controlled trial targeting long-term care workers, and resulting participant baseline characteristics., Design: We used a multifaceted recruitment process to enroll long-term care workers in our 3-arm randomized controlled trial comparing 2 interventions to enhanced usual practice, for improving COVID-19 vaccine confidence and other outcomes., Setting and Participants: Adult long-term care workers living in the United States employed within the last 2 years were invited to join the study. Participants also had to meet specific screening criteria related to their degree of worry about the vaccine and/or their vaccination status., Methods: We used a participatory approach to engage our long-term care stakeholders in codesigning and executing a combination of recruitment methods, including targeted e-recruitment, paid e-recruitment, and in-person recruitment. Participants were screened, consented, and enrolled online. We implemented a participant verification process to ensure the integrity of our study data, and used a tailored participant management platform to manage enrollment., Results: We enrolled 1930 long-term care workers between May 2022 and January 2023. We met our enrollment target, despite each recruitment method having limitations. Total variable costs of approximately $102,700 were incurred and differed on a per-enrolled participant basis across methods: $25.73 for targeted e-recruitment, $57.12 for paid e-recruitment, and $64.92 for in-person methods. Our sample differed from the national population in age, gender, race/ethnicity, education, and role in long-term care. Differences were also observed between online and in-person recruitment methods., Conclusions and Implications: Our results support the feasibility of enrolling a large number of long-term care workers in a randomized controlled trial to increase COVID-19 vaccine confidence. Findings build upon the evidence base for engaging this important population in research, a critical step to improving long-term care resident health and well-being. Results from our trial are anticipated in 2024., Competing Interests: Disclosure Glyn Elwyn and Marie-Anne Durand have developed the Option Grid patient decision aids, which are licensed to EBSCO Health. They receive consulting and royalty income from EBSCO Health. Other authors report no competing interests., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Olmesartan is an angiotensin II receptor blocker licensed for the treatment of hypertension. It can cause a sprue-like enteropathy (SLE), characterised by chronic diarrhoea, weight loss and villous atrophy. Transiently raised anti-tissue transglutaminase (ATTG) antibody has also been rarely reported in the literature.We describe the case of a woman in her mid-50s, who presented with a history of intermittent loose stools over 1 year, associated with significant weight loss. She had two marginally raised serum ATTG antibody tests during her work-up.After extensive investigations, she was diagnosed with olmesartan-induced enteropathy. On subsequent follow-up, her symptoms had resolved with cessation of her olmesartan therapy.This case adds to existing literature, highlighting the importance of considering olmesartan as a possible differential diagnosis for SLE. It also reports the presence of a raised ATTG antibody which is infrequently reported in this context., Competing Interests: Competing interests: None declared., (© BMJ Publishing Group Limited 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

Aims: To explore youth, caregiver and staff perspectives on their vision of trauma-informed care, and to identify and understand potential considerations for the implementation of a trauma-informed care programme in an inpatient mental health unit within a paediatric hospital., Design and Methods: We applied the Interpretive Description approach, guided by complexity theory and the Implementation Roadmap, and used Applied Thematic Analysis methods., Findings: Twenty-five individuals participated in individual or group interviews between March and June 2022, including 21 healthcare professionals, 3 youth and 1 caregiver. We identified two overarching themes. The first theme, 'Understanding and addressing the underlying reasons for distress', related to participants' understanding and vision of TIC in the current setting comprising: (a) 'Participants' understanding of TIC'; (b) 'Trauma screening and trauma processing within TIC'; (c) 'Taking "a more individualized approach"'; (d) 'Unit programming'; and (e) "Connecting to the community". The second theme, 'Factors that support or limit successful TIC implementation' comprises: (a) 'The need for a broad "cultural shift"'; (b) 'The physical environment on the unit'; and (c) 'Factors that may limit successful implementation'., Conclusion: We identified five key domains to consider within trauma-informed care implementation: (a) the centrality of engagement with youth, caregivers and staff in trauma-informed care delivery and implementation, (b) trauma-informed care core programme components, (c) factors that may support or limit success in implementing trauma-informed care within the mental health unit and (d) hospital-wide and (e) the importance of intersectoral collaboration (partnering with external organizations and sectors)., Impact: When implementing TIC, there is an ongoing need to increase clarity regarding TIC interventions and implementation initiatives. Youth, caregiver and healthcare professional participants shared considerations important for planning the delivery and implementation of trauma-informed care in their setting. We identified five key domains to consider within trauma-informed care implementation: (a) the centrality of relational engagement, (b) trauma-informed care programme components, (c) factors that may support or limit successful implementation of trauma-informed care within the mental health unit and (d) hospital-wide and (e) the importance of intersectoral collaboration. Organizations wishing to implement trauma-informed care should consider ongoing engagement with all relevant knowledge user groups throughout the process., Reporting Method: Standards for Reporting Qualitative Research (SRQR)., Patient or Public Contribution: The local hospital research institute's Patient and Family Advisory Committee reviewed the draft study methods and provided feedback., (© 2024 The Authors. Journal of Advanced Nursing published by John Wiley & Sons Ltd.)

Background: The effects of spinal versus general anesthesia on long-term outcomes have not been well studied. This study tested the hypothesis that spinal anesthesia is associated with better long-term survival and functional recovery than general anesthesia., Methods: A prespecified analysis was conducted of long-term outcomes of a completed randomized superiority trial that compared spinal anesthesia versus general anesthesia for hip fracture repair. Participants included previously ambulatory patients 50 yr of age or older at 46 U.S. and Canadian hospitals. Patients were randomized 1:1 to spinal or general anesthesia, stratified by sex, fracture type, and study site. Outcome assessors and investigators involved in the data analysis were masked to the treatment arm. Outcomes included survival at up to 365 days after randomization (primary); recovery of ambulation among 365-day survivors; and composite endpoints for death or new inability to ambulate and death or new nursing home residence at 365 days. Patients were included in the analysis as randomized., Results: A total of 1,600 patients were enrolled between February 12, 2016, and February 18, 2021; 795 were assigned to spinal anesthesia, and 805 were assigned to general anesthesia. Among 1,599 patients who underwent surgery, vital status information at or beyond the final study interview (conducted at approximately 365 days after randomization) was available for 1,427 (89.2%). Survival did not differ by treatment arm; at 365 days after randomization, there were 98 deaths in patients assigned to spinal anesthesia versus 92 deaths in patients assigned to general anesthesia (hazard ratio, 1.08; 95% CI, 0.81 to 1.44, P = 0.59). Recovery of ambulation among patients who survived a year did not differ by type of anesthesia (adjusted odds ratio for spinal vs. general, 0.87; 95% CI, 0.67 to 1.14; P = 0.31). Other outcomes did not differ by treatment arm., Conclusions: Long-term outcomes were similar with spinal versus general anesthesia., (Copyright © 2023 American Society of Anesthesiologists. All Rights Reserved.)

Introduction: The effect of spinal versus general anesthesia on the risk of postoperative delirium or other outcomes for patients with or without cognitive impairment (including dementia) is unknown., Methods: Post hoc secondary analysis of a multicenter pragmatic trial comparing spinal versus general anesthesia for adults aged 50 years or older undergoing hip fracture surgery., Results: Among patients randomized to spinal versus general anesthesia, new or worsened delirium occurred in 100/295 (33.9%) versus 107/283 (37.8%; odds ratio [OR] 0.85; 95% confidence interval [CI] 0.60 to 1.19) among persons with cognitive impairment and 70/432 (16.2%) versus 71/445 (16.0%) among persons without cognitive impairment (OR 1.02; 95% CI 0.71 to 1.47, p = 0.46 for interaction). Delirium severity, in-hospital complications, and 60-day functional recovery did not differ by anesthesia type in patients with or without cognitive impairment., Discussion: Anesthesia type is not associated with differences in delirium and functional outcomes among persons with or without cognitive impairment., (© 2023 the Alzheimer's Association.)

Background Frailty is prevalent in older adults with heart failure and is associated with poor outcomes; however, there remains uncertainty on how to measure frailty in clinical practice. Methods and Results A multicentric prospective cohort study was assembled at 4 heart failure clinics to compare the prognostic value of 3 physical frailty scales in ambulatory patients with heart failure. Outcomes were all-cause death or hospitalization and health-related quality of life using the 36-Item Short Form survey questionnaire (SF-36) at 3 months. Multivariable regression was adjusted for age, sex, Meta-Analysis Global Group in Chronic Heart Failure score, and baseline SF-36 score. The cohort included 215 patients (mean age 77.6 years). All 3 frailty scales were independently associated with death or hospitalization at 3 months; the adjusted odds ratios standardized per 1 SD worsening of the Short Physical Performance Battery; Fried, and strength, assistance with walking, rising from a chair, climbing stairs, and falls scales were 1.67 (95% CI, 1.09-2.55), 1.60 (95% CI, 1.04-2.46), and 1.55 (95% CI, 1.03-2.35), respectively, with C statistics of 0.77 to 0.78. All 3 frailty scales were independently associated with worsening SF-36 scores, especially the Short Physical Performance Battery, for which 1 SD worsening of frailty translated to a decrement of -5.86 (-8.55 to -3.17) and -5.51 (-7.82 to -3.21) points in the Physical Component Score and Mental Component Score. Conclusions All 3 physical frailty scales were associated with death, hospitalization, and reduced health-related quality of life in ambulatory patients with heart failure. Questionnaire or performance-based physical frailty scales can be used to offer prognostic value and a therapeutic target in this vulnerable population. Registration URL: https://www.clinicaltrials.gov; Unique identifier: NCT03887351.

Background: Clinical and real-world effectiveness data for the COVID-19 vaccines have shown that they are the best defense in preventing severe illness and death throughout the pandemic. However, in the US, some groups remain more hesitant than others about receiving COVID-19 vaccines. One important group is long-term care workers (LTCWs), especially because they risk infecting the vulnerable and clinically complex populations they serve. There is a lack of research about how best to increase vaccine confidence, especially in frontline LTCWs and healthcare staff. Our aims are to: (1) compare the impact of two interventions delivered online to enhanced usual practice on LTCW COVID-19 vaccine confidence and other pre-specified secondary outcomes, (2) determine if LTCWs' characteristics and other factors mediate and moderate the interventions' effect on study outcomes, and (3) explore the implementation characteristics, contexts, and processes needed to sustain a wider use of the interventions., Methods: We will conduct a three-arm randomized controlled effectiveness-implementation hybrid (type 2) trial, with randomization at the participant level. Arm 1 is a dialogue-based webinar intervention facilitated by a LTCW and a medical expert and guided by an evidence-based COVID-19 vaccine decision tool. Arm 2 is a curated social media web application intervention featuring interactive, dynamic content about COVID-19 and relevant vaccines. Arm 3 is enhanced usual practice, which directs participants to online public health information about COVID-19 vaccines. Participants will be recruited via online posts and advertisements, email invitations, and in-person visits to care settings. Trial data will be collected at four time points using online surveys. The primary outcome is COVID-19 vaccine confidence. Secondary outcomes include vaccine uptake, vaccine and booster intent for those unvaccinated, likelihood of recommending vaccination (both initial series and booster), feeling informed about the vaccines, identification of vaccine information and misinformation, and trust in COVID-19 vaccine information provided by different people and organizations. Exploration of intervention implementation will involve interviews with study participants and other stakeholders, an in-depth process evaluation, and testing during a subsequent sustainability phase., Discussion: Study findings will contribute new knowledge about how to increase COVID-19 vaccine confidence and effective informational modalities for LTCWs., Trial Registration: NCT05168800 at ClinicalTrials.gov, registered December 23, 2021., (© 2023. The Author(s).)

Background: Patients with psoriasis do not exercise to the extent recommended for cardiovascular health, which may contribute to the increased risk of cardiovascular disease (CVD) and metabolic syndrome observed in this patient group. We previously identified that patients with psoriasis have significant disease-specific barriers to exercise. Others have reported that individuals with psoriasis develop higher heart rates and systolic blood pressure during bouts of exercise, followed by a slower recovery than healthy control subjects., Aims: We hypothesized that a bespoke, evidenced-based, exercise programme could be developed for patients with psoriasis., Methods: We convened a multidisciplinary Working Group comprising key stakeholders, including patients with psoriasis, along with sports scientists and clinicians, to develop the programme., Results: To allow for different levels of fitness, lifestyle and motivation a 10-week intervention comprising two group walking sessions per week each of 1 h duration [led by a sports scientist (RS)] was designed using the Mapometer website. Walking distance was validated by a Walkmeter application, which uses global positioning system technology. The volume of exercise per session was calculated so that participants could incrementally progress to heart-healthy levels of exercise over the course of the programme. Maps of 20 unique walking routes were developed. A GENEactiv Original accelerometer and Newfeel Onwalk 900 pedometer were selected as wearable devices., Conclusion: We developed an exercise programme which specifically removed barriers to exercise for those with psoriasis, in partnership with patients. Regular exercise may offer significant health benefits for patients with psoriasis, including reduced CVD risk and increased psychosocial functioning, and this programme merits further investigation., (© The Author(s) 2022. Published by Oxford University Press on behalf of British Association of Dermatologists.)

Machine learning has recently been applied and deployed at several light source facilities in the domain of accelerator physics. Here, an approach based on machine learning to produce a fast-executing model is introduced that predicts the polarization and energy of the radiated light produced at an insertion device. This paper demonstrates how a machine learning model can be trained on simulated data and later calibrated to a smaller, limited measured data set, a technique referred to as transfer learning. This result will enable users to efficiently determine the insertion device settings for achieving arbitrary beam characteristics., (open access.)

Background: The REGAIN (Regional versus General Anesthesia for Promoting Independence after Hip Fracture) trial found similar ambulation and survival at 60 days with spinal versus general anesthesia for hip fracture surgery. Trial outcomes evaluating pain, prescription analgesic use, and patient satisfaction have not yet been reported., Objective: To compare pain, analgesic use, and satisfaction after hip fracture surgery with spinal versus general anesthesia., Design: Preplanned secondary analysis of a pragmatic randomized trial. (ClinicalTrials.gov: NCT02507505)., Setting: 46 U.S. and Canadian hospitals., Participants: Patients aged 50 years or older undergoing hip fracture surgery., Intervention: Spinal or general anesthesia., Measurements: Pain on postoperative days 1 through 3; 60-, 180-, and 365-day pain and prescription analgesic use; and satisfaction with care., Results: A total of 1600 patients were enrolled. The average age was 78 years, and 77% were women. A total of 73.5% (1050 of 1428) of patients reported severe pain during the first 24 hours after surgery. Worst pain over the first 24 hours after surgery was greater with spinal anesthesia (rated from 0 [no pain] to 10 [worst pain imaginable]; mean difference, 0.40 [95% CI, 0.12 to 0.68]). Pain did not differ across groups at other time points. Prescription analgesic use at 60 days occurred in 25% (141 of 563) and 18.8% (108 of 574) of patients assigned to spinal and general anesthesia, respectively (relative risk, 1.33 [CI, 1.06 to 1.65]). Satisfaction was similar across groups., Limitation: Missing outcome data and multiple outcomes assessed., Conclusion: Severe pain is common after hip fracture. Spinal anesthesia was associated with more pain in the first 24 hours after surgery and more prescription analgesic use at 60 days compared with general anesthesia., Primary Funding Source: Patient-Centered Outcomes Research Institute .

Background: It is difficult to improve compliance with hand hygiene (HH), and underlying behaviours are not clearly understood among healthcare workers., Aim: To study HH behaviours among healthcare workers., Methods: This was a prospective observational study. A Sanibit electronic HH system was installed in a 10-bed surgical intensive care unit (ICU) that detected HH opportunities automatically when healthcare workers entered or exited a patient room, and tracked the HH compliance of healthcare workers. The HH compliance rate and patient contact time were calculated and analysed at both ICU level and individual level over time., Findings: In total, 27,692 HH opportunities were recorded over this 6-month trial period. The HH compliance rate was significantly higher when healthcare workers exited patient rooms than when they entered patient rooms (37.3% vs 26.1%; P<0.001). Full, partial and total HH compliance rates of 'quick in and quick out' (in room for <3 s) events were significantly lower than those of 'long in and long out' (in room for >30 s) events (23.45% vs 32.77%, 21.44% vs 35.03% and 44.88% vs 67.81%, respectively; P<0.001). There were also significant differences in HH compliance between individual healthcare workers (P<0.001). No significant differences in overall HH compliance rate and patient contact time were found between hours of the day or days of the week, except partial HH compliance rates., Conclusion: Patterns of HH behaviours among healthcare workers are complex and variable, which could facilitate targeted and personalized interventions to improve HH compliance., Clinical Trial Registration: NCT03948672., (Copyright © 2022 The Healthcare Infection Society. Published by Elsevier Ltd. All rights reserved.)

Dysregulation of the epigenome is associated with the onset and progression of several diseases, including cancer, autoimmune, cardiovascular, and neurological disorders. Members from the three families of epigenetic proteins (readers, writers, and erasers) have been shown to be druggable using small-molecule inhibitors. Increasing knowledge of the role of epigenetics in disease and the reversibility of these modifications explain why pharmacological intervention is an attractive strategy for tackling epigenetic-based disease. In this review, we provide an overview of epigenetics drug targets, focus on approaches used for initial hit identification, and describe the subsequent role of structure-guided chemistry optimisation of initial hits to clinical candidates. We also highlight current challenges and future potential for epigenetics-based therapies., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Background: The effects of spinal anesthesia as compared with general anesthesia on the ability to walk in older adults undergoing surgery for hip fracture have not been well studied., Methods: We conducted a pragmatic, randomized superiority trial to evaluate spinal anesthesia as compared with general anesthesia in previously ambulatory patients 50 years of age or older who were undergoing surgery for hip fracture at 46 U.S. and Canadian hospitals. Patients were randomly assigned in a 1:1 ratio to receive spinal or general anesthesia. The primary outcome was a composite of death or an inability to walk approximately 10 ft (3 m) independently or with a walker or cane at 60 days after randomization. Secondary outcomes included death within 60 days, delirium, time to discharge, and ambulation at 60 days., Results: A total of 1600 patients were enrolled; 795 were assigned to receive spinal anesthesia and 805 to receive general anesthesia. The mean age was 78 years, and 67.0% of the patients were women. A total of 666 patients (83.8%) assigned to spinal anesthesia and 769 patients (95.5%) assigned to general anesthesia received their assigned anesthesia. Among patients in the modified intention-to-treat population for whom data were available, the composite primary outcome occurred in 132 of 712 patients (18.5%) in the spinal anesthesia group and 132 of 733 (18.0%) in the general anesthesia group (relative risk, 1.03; 95% confidence interval [CI], 0.84 to 1.27; P = 0.83). An inability to walk independently at 60 days was reported in 104 of 684 patients (15.2%) and 101 of 702 patients (14.4%), respectively (relative risk, 1.06; 95% CI, 0.82 to 1.36), and death within 60 days occurred in 30 of 768 (3.9%) and 32 of 784 (4.1%), respectively (relative risk, 0.97; 95% CI, 0.59 to 1.57). Delirium occurred in 130 of 633 patients (20.5%) in the spinal anesthesia group and in 124 of 629 (19.7%) in the general anesthesia group (relative risk, 1.04; 95% CI, 0.84 to 1.30)., Conclusions: Spinal anesthesia for hip-fracture surgery in older adults was not superior to general anesthesia with respect to survival and recovery of ambulation at 60 days. The incidence of postoperative delirium was similar with the two types of anesthesia. (Funded by the Patient-Centered Outcomes Research Institute; REGAIN ClinicalTrials.gov number, NCT02507505.)., (Copyright © 2021 Massachusetts Medical Society.)

Background: Peripartum cardiomyopathy (PPCM) occurs in ≈1:2000 deliveries in the United States and worldwide. The genetic underpinnings of PPCM remain poorly defined. Approximately 10% of women with PPCM harbor truncating variants in TTN (TTNtvs). Whether mutations in other genes can predispose to PPCM is not known. It is also not known if the presence of TTNtvs predicts clinical presentation or outcomes. Nor is it known if the prevalence of TTNtvs differs in women with PPCM and preeclampsia, the strongest risk factor for PPCM., Methods: Women with PPCM were retrospectively identified from several US and international academic centers, and clinical information and DNA samples were acquired. Next-generation sequencing was performed on 67 genes, including TTN , and evaluated for burden of truncating and missense variants. The impact of TTNtvs on the severity of clinical presentation, and on clinical outcomes, was evaluated., Results: Four hundred sixty-nine women met inclusion criteria. Of the women with PPCM, 10.4% bore TTNtvs (odds ratio=9.4 compared with 1.2% in the reference population; Bonferroni-corrected P [ P *]=1.2×10 -46 ). We additionally identified overrepresentation of truncating variants in FLNC (odds ratio=24.8, P *=7.0×10 -8 ), DSP (odds ratio=14.9, P *=1.0×10 -8 ), and BAG3 (odds ratio=53.1, P *=0.02), genes not previously associated with PPCM. This profile is highly similar to that found in nonischemic dilated cardiomyopathy. Women with TTNtvs had lower left ventricular ejection fraction on presentation than did women without TTNtvs (23.5% versus 29%, P =2.5×10 -4 ), but did not differ significantly in timing of presentation after delivery, in prevalence of preeclampsia, or in rates of clinical recovery., Conclusions: This study provides the first extensive genetic and phenotypic landscape of PPCM and demonstrates that predisposition to heart failure is an important risk factor for PPCM. The work reveals a degree of genetic similarity between PPCM and dilated cardiomyopathy, suggesting that gene-specific therapeutic approaches being developed for dilated cardiomyopathy may also apply to PPCM, and that approaches to genetic testing in PPCM should mirror those taken in dilated cardiomyopathy. Last, the clarification of genotype/phenotype associations has important implications for genetic counseling.

Background: Left ventricular (LV) epicardial pacing results in slowly propagating paced wavefronts. We postulated that this effect might limit cardiac resynchronization therapy efficacy in patients with LV enlargement using conventional biventricular pacing with single-site LV pacing, but be mitigated by LV stimulation from 2 widely spaced sites using MultiPoint pacing with wide anatomic separation (MPP-AS: ≥30 mm). We tested this hypothesis in the multicenter randomized MPP investigational device exemption trial., Methods: Following implant, quadripolar biventricular single-site pacing was activated in all patients (n=506). From 3 to 9 months postimplant, among patients with available baseline LV end-diastolic volume (LVEDV) measures, 188 received biventricular single-site pacing and 43 received MPP-AS. Patients were dichotomized by median baseline LVEDV indexed to height (LVEDVI Median ). Outcomes were measured by the clinical composite score (primary efficacy end point), quality of life, LV structural remodeling (↑EF >5% and ↓ESV 10%) and heart failure event/cardiovascular death., Results: LVEDVI Median was 1.1 mL/cm. Baseline characteristics differed in patients with LVEDVI >Median versus LVEDVI ≤Median . Among patients with LVEDVI >Median , biventricular single-site pacing was less efficacious compared to patients with LVEDVI ≤Median (clinical composite score, 65% versus 79%). In contrast, MPP-AS programming generated greater clinical composite score response (92% versus 65%, P =0.023) and improved quality of life (-31.0±29.7 versus -15.7±22.1, P =0.038) versus biventricular single-site pacing in patients with LVEDVI >Median . Reverse remodeling trended better with MPP-AS programming. In patients with LVEDVI >Median , heart failure event rate increased following the 3-month randomization point with biventricular single-site pacing (0.0150±0.1725 in LVEDVI >Median versus -0.0190±0.0808 in LVEDVI ≤Median , P =0.012), but no heart failure event occurred in patients with MPP-AS programming between 3 and 9 months in LVEDVI >Median . All measured outcomes did not differ in patients receiving MPP-AS and biventricular single-site pacing with LVEDVI ≤Median ., Conclusions: Conventional biventricular single-site pacing, even with a quadripolar lead, has reduced efficacy in patients with LV enlargement. However, the greatest response rate in patients with larger hearts was observed when programmed to MPP-AS pacing.

Introduction: Kinetic military units operate in austere training environments and deprivation not commonly experienced by competitive athletes. Nutritional strategies to protect against decrements in performance and potential injury risk may differ for these two groups. A cross sectional analysis was conducted to determine energy and macronutrient characteristics associated with performance metrics., Materials and Methods: 78 male subjects (age: 28.4 ± 6.0 years, height: 178.3 ± 6.7 cm, mass: 84.3 ± 9.4 kg, 8.5 ± 5.8 years of service) assigned to Marine Corps Forces Special Operations Command completed a 1-day performance assessment. Body mass, lean body mass, fat mass (FM), aerobic capacity (VO2max), lactate inflection point (LT), anaerobic power, anaerobic capacity, knee flexion strength, knee extension strength, peak knee flexion strength, and peak knee extension strength outcome values were recorded. Dietary intake was collected using automated self-administered 24-hour dietary recall (ASA24). Performance assessment scores were compared with macronutrient intake and controlled for energy intake using analysis of covariance., Results: Differences in knee flexion strength, knee extension strength, peak knee flexion strength, and peak knee extension strength were significant across low (LPRO), medium (MPRO), and high (HPRO) protein intake groups (p < 0.05) with LPRO performance metrics significantly lower than both MPRO and HPRO and MPRO significantly lower than HPRO. FM was significantly higher in LPRO than MPRO or HPRO (p < 0.05). Low carbohydrate intake (LCHO) was associated with greater body mass and FM compared with high (HCHO) (p < 0.05). There was no association between fat intake and any variable., Conclusions: Increases in protein intake may have beneficial performance effects independent of total energy intake, while moderate increases in carbohydrate intake may not be sufficient to enhance physical performance in a special operations population., (© The Association of Military Surgeons of the United States. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Purpose: Cardiac rehabilitation (CR) is effective at reducing further cardiac events. However, dropout rates are high, and maintenance of behavioral change post-CR is challenging. Health literacy (HL) may influence self-management of cardiac risk, yet few studies have explored this association. This study aimed to describe HL among CR attendees; first to describe the HL profiles of people commencing CR and second to examine HL changes between program entry and completion., Methods: CR attendees in Melbourne, Australia, completed the Health Literacy Questionnaire (HLQ) at program admission and completion. The HLQ measures HL across 9 scales. Cluster analysis grouped participants according to their HL profile. Effect sizes were used to determine changes in HLQ scores. Post-program interviews explored the role of HL in participant recovery., Results: Participants completed baseline (n = 60) and post-program (n = 38) data collection. Mean age was 60.3 ± 11.7 yr, and 38.3% had myocardial infarction and/or percutaneous coronary intervention. Approximately 18% of participants did not complete the program. Five HL clusters were revealed. The clusters most likely to drop out were confident users of the health system. The cluster least likely to drop out reported lower confidence in their ability to find health information and navigate services. Information-seeking ability improved over time, but no other HL improvements were seen., Conclusion: There is a wide range of HL profiles in people attending CR. Findings suggest that CR programs should consider a variety of approaches to meet the diverse HL requirements of attendees.

Many human cancers over-express B cell lymphoma 2 (Bcl-2) or X-linked inhibitor of apoptosis (IAP) proteins to evade cell death. The pro-apoptotic ARTS (Sept4&#95;i2) protein binds directly to both Bcl-2 and XIAP and promotes apoptosis by stimulating their degradation via the ubiquitin-proteasome system (UPS). Here we describe a small molecule, A4, that mimics the function of ARTS. Microscale thermophoresis assays showed that A4 binds XIAP, but not cellular inhibitor of apoptosis protein 1 (cIAP1). A4 binds to a distinct ARTS binding pocket in the XIAP-BIR3 (baculoviral IAP repeat 3) domain. Like ARTS, A4 stimulated poly-ubiquitylation and UPS-mediated degradation of XIAP and Bcl-2, but not cIAP1, resulting in caspase-9 and -3 activation and apoptosis. In addition, over-expression of XIAP rescued HeLa cells from A4-induced apoptosis, consistent with the idea that A4 kills by antagonizing XIAP. On the other hand, treatment with the SMAC-mimetic Birinapant induced secretion of tumour necrosis factor-α (TNFα) and killed ~50% of SKOV-3 cells, and addition of A4 to Birinapant-treated cells significantly reduced secretion of TNFα and blocked Birinapant-induced apoptosis. This suggests that A4 acts by specifically targeting XIAP. The effect of A4 was selective as peripheral blood mononuclear cells and normal human breast epithelial cells were unaffected. Furthermore, proteome analysis revealed that cancer cell lines with high levels of XIAP were particularly sensitive to the killing effect of A4. These results provide proof of concept that the ARTS binding site in XIAP is "druggable". A4 represents a novel class of dual-targeting compounds stimulating apoptosis by UPS-mediated degradation of important anti-apoptotic oncogenes.

Strange or bad metallic transport, defined by incompatibility with the conventional quasiparticle picture, is a theme common to many strongly correlated materials, including high-temperature superconductors. The Hubbard model represents a minimal starting point for modeling strongly correlated systems. Here we demonstrate strange metallic transport in the doped two-dimensional Hubbard model using determinantal quantum Monte Carlo calculations. Over a wide range of doping, we observe resistivities exceeding the Mott-Ioffe-Regel limit with linear temperature dependence. The temperatures of our calculations extend to as low as 1/40 of the noninteracting bandwidth, placing our findings in the degenerate regime relevant to experimental observations of strange metallicity. Our results provide a foundation for connecting theories of strange metals to models of strongly correlated materials., (Copyright © 2019 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.)

Background: Adult Basic Education (ABE) is the national system that offers adults with low literacy and/or limited English with educational services in reading, writing, math, technology, and communications from basic levels to high school equivalency, with specialty programs in transition to community colleges and family literacy., Brief Description of Activity: To show the role of ABE in increasing health literacy in low literate and/or limited English populations through partnership with community health organizations (CHOs)., Implementation: This article was developed through a collaborative thought process over a period of 8 months with experts from the field of ABE in development of health literacy within low literate and/or limited English populations. It describes the research that links low literacy and/or limited English with poor health, and introduces how ABE and CHOs have addressed these issues together. It also introduces research on the impact on learners of integrating health into ABE., Results: ABE learners have consistently shown a strong interest in learning about health for themselves and their families, and health content energizes ABE instruction. Learners report improvements of basic health knowledge, their confidence communicating with health care professionals, enhanced self-efficacy, and intention to make changes in such health behaviors as diet and tracking blood pressure. Partnerships between ABE programs and their local CHOs strengthen the teaching/learning process and can be mutually beneficial. ABE provides access to hard-to-reach populations, a safe learning environment, and teaching expertise. CHOs provide health expertise, preventive health screenings, and access to treatments., Lessons Learned: The link between low literacy and poor health is no longer disputed. ABE programs and many CHOs share a common mission and commitment to serving vulnerable populations. Stronger partnerships between these organizations should be viewed as a viable strategy for addressing health disparities. A coordinated effort of community health centers across the nation is required to meaningfully respond to health disparities as a national social issue. [ HLRP: Health Literacy Research and Practice . 2019;3(Suppl.):S1-S7.] ., Plain Language Summary: This article introduces ABE and the role this system plays in improving health literacy within populations with low health literacy and/or limited English populations. It details the educational services the system provides, how health content has been integrated into instruction, the impact on learners, and how partnerships between ABE programs and community health services strengthen the work., (© 2019 Hohn, Lawrence, McKinney, et al.)

The limitations in the transport of oxygen, nutrients, and metabolic waste products pose a challenge to the development of bioengineered bone of clinically relevant size. This paper reports the design and characterization of hierarchical macro/microporous scaffolds made of poly(lactic-co-glycolic) acid and nanohydroxyapatite (PLGA/nHA). These scaffolds were produced by combining additive manufacturing (AM) and thermally induced phase separation (TIPS) techniques. Macrochannels with diameters of ~300 μm, ~380 μm, and ~460 μm were generated by embedding porous 3D-plotted polyethylene glycol (PEG) inside PLGA/nHA/1,4-dioxane or PLGA/1,4-dioxane solutions, followed by PEG extraction using deionized (DI) water. We have used an I-optimal design of experiments (DoE) and the response surface analysis (JMP® software) to relate three responses (scaffold thickness, porosity, and modulus) to the four experimental factors affecting the scaffold macro/microstructures ( e.g ., PEG strand diameter, PLGA concentration, nHA content, and TIPS temperature). Our results indicated that a PEG strand diameter of ~380 μm, a PLGA concentration of ~10% w/v, a nHA content of ~10% w/w, and a TIPS temperature around -10°C could generate scaffolds with a porosity of ~90% and a modulus exceeding 4 MPa. This paper presents the steps for the I-optimal design of these scaffolds and reports on their macro/microstructures, characterized using scanning electron microscopy (SEM) and micro-computed tomography (micro-CT)., Competing Interests: Conflict of Interest Disclosure The authors declare no competing financial interest.

Importance: The prevalence of nonischemic dilated cardiomyopathy (DCM) is greater in individuals of African ancestry than in individuals of European ancestry. However, little is known about whether the difference in prevalence or outcomes is associated with functional genetic variants., Objective: We hypothesized that Bcl2-associated anthanogene 3 (BAG3) genetic variants were associated with outcomes in individuals of African ancestry with DCM., Design: This multicohort study of the BAG3 genotype in patients of African ancestry with dilated cardiomyopathy uses DNA obtained from African American individuals enrolled in 3 clinical studies: the Genetic Risk Assessment of African Americans With Heart Failure (GRAHF) study; the Intervention in Myocarditis and Acute Cardiomyopathy Trial-2 (IMAC-2) study; and the Genetic Risk Assessment of Cardiac Events (GRACE) study. Samples of DNA were also acquired from the left ventricular myocardium of patients of African ancestry who underwent heart transplant at the University of Colorado and University of Pittsburgh., Main Outcomes and Measures: The primary end points were the prevalence of BAG3 mutations in African American individuals and event-free survival in participants harboring functional BAG3 mutations., Results: Four BAG3 genetic variants were identified; these were expressed in 42 of 402 African American individuals (10.4%) with nonischemic heart failure and 9 of 107 African American individuals (8.4%) with ischemic heart failure but were not present in a reference population of European ancestry (P < .001). The variants included 2 nonsynonymous single-nucleotide variants; 1 three-nucleotide in-frame insertion; and 2 single-nucleotide variants that were linked in cis. The presence of BAG3 variants was associated with a nearly 2-fold (hazard ratio, 1.97 [95% CI, 1.19-3.24]; P = .01) increase in cardiac events in carriers compared with noncarriers. Transfection of transformed adult human ventricular myocytes with plasmids expressing the 4 variants demonstrated that each variant caused an increase in apoptosis and a decrease in autophagy when samples were subjected to the stress of hypoxia-reoxygenation., Conclusions and Relevance: This study demonstrates that genetic variants in BAG3 found almost exclusively in individuals of African ancestry were not causative of disease but were associated with a negative outcome in patients with a dilated cardiomyopathy through modulation of the function of BAG3. The results emphasize the importance of biological differences in causing phenotypic variance across diverse patient populations, the need to include diverse populations in genetic cohorts, and the importance of determining the pathogenicity of genetic variants.

Aim: To evaluate the impact of AGTR1 A1166C (rs5186) on the response to candesartan in patients with heart failure., Materials & Methods: Prospective, multicentre, open-label study. We studied 299 symptomatic patients with heart failure presenting a left ventricular ejection fraction ≤40%., Results: Reductions in the primary end points of natriuretic peptides were not significantly associated with AGTR1 A1166C. Nevertheless, carrying the 1166C allele was associated with a greater compensatory increase in renin activity (p = 0.037) after 16 weeks of treatment with candesartan and a more modest effect on aldosterone concentrations (p = 0.022)., Conclusion: AGTR1 1166C carriers may experience a greater long-term compensatory renin-angiotensin-aldosterone system activation following treatment with candesartan. Whether these associations ultimately influence clinical outcomes requires investigation. Clinicaltrials.gov : NCT00400582.

Objectives: This study reports the rate of unmet needs for professional mental health care in a large multi-state sample of adolescents. We also sought to describe barriers to professional help, informal help seeking and future help-seeking intentions among adolescents with wholly unmet needs for counselling for mental illness., Methods: We collected measures of mental health, help-seeking and unmet needs in 1599 students (817 males and 781 females) in 16 schools (mean age = 17.7 years, standard deviation = 0.42 years). Adolescents meeting 'case' criteria for high psychological distress were classified as having no need, fully met needs, partially met needs or wholly unmet needs. Participants were asked about actual service use, perceived unmet needs, barriers to professional help, help seeking from other sources, use of self-management strategies and future help seeking intentions., Results: In all, 35.7% ( n = 571) of the sample met criteria to be designated 'cases' with high psychological distress. Of these, 25.9% ( n = 148) were classified as having 'wholly unmet needs' (cases of untreated prevalence with self-perceived unmet needs), translating into 9.3% of the original sample. Compared to cases with partially met needs, adolescents with wholly unmet needs engaged in significantly less self-help, used less informal help from family/friends and reported lower future help-seeking intentions. Common barriers to care included a preference for self-management and concerns regarding stigma., Conclusions: A concerning proportion of adolescents have untreated high psychological distress with wholly unmet mental health needs. This group is rendered particularly vulnerable by low rates of access to non-professional sources of help and low engagement in self-management strategies. Further research is needed to support this vulnerable group to access needed professional mental health help.

Objectives: The MultiPoint Pacing (MPP) trial assessed the safety and efficacy of pacing 2 left ventricular sites with a quadripolar lead in patients with heart failure indicated for a CRT-D device., Background: Cardiac resynchronization therapy nonresponse is a complex problem where stimulation of multiple left ventricular sites may be a solution., Methods: Enrolled patients were indicated for a CRT-D system. Bi-ventricular (Bi-V) pacing was activated at implant. Three months later, clinical response was assessed and the patient was randomized (1:1) to receive Bi-V pacing or MPP. Patients were followed for 6 months post-randomization and clinical response was again assessed., Results: The CRT-D system was successfully implanted in 455 of 469 attempted implants (97%). A total of 381 patients were randomized to Bi-V or MPP at 3 months. The primary safety endpoint was met with freedom from system-related complications of 93.2%. The primary efficacy endpoint of the noninferiority comparison of nonresponder rates between the 2 arms was met. Patients randomized to MPP arm and programmed to pace from anatomically distant poles (MPP-AS) responded to therapy at significantly higher rates than MultiPoint pacing-other programmed settings (MPP-Other). Within this group, 87% were responders at 9 months, 100% designated as nonresponders at 3 months converted to responders at 9 months, and 54% experienced an incremental response compared to MPP-Other. Also within MPP-AS, 92% of patients with de novo CRT-D implant were classified as responders compared with patients with MPP-Other., Conclusions: MPP is safe and effective for treating heart failure. The study met the pre-specified hypothesis that response to MPP is noninferior to Bi-V pacing with a quadripolar left ventricular lead. (MultiPoint Pacing IDE Study [MPP IDE]; NCT01786993)., (Copyright © 2017 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Background: Although the majority of Class III congestive heart failure (HF) patients treated with cardiac resynchronization therapy (CRT) show a clinical benefit, up to 40% of patients do not respond to CRT. This paper reports the design of the MultiPoint Pacing (MPP) trial, a prospective, randomized, double-blind, controlled study to evaluate the safety and efficacy of CRT using MPP compared to standard biventricular (Bi-V) pacing., Methods: A maximum of 506 patients with a standard CRT-D indication will be enrolled at up to 50 US centers. All patients will be implanted with a CRT-D system (Quartet LV lead Model 1458Q with a Quadra CRT-D, Abbott) that can deliver both MPP and Bi-V pacing. Standard Bi-V pacing will be activated at implant. At 3 months postimplant, patients in whom the echocardiographic parameters during MPP are equal or better than during Bi-V pacing are randomized (1:1) to either an MPP or Bi-V arm., Results: The primary safety endpoint is freedom from system-related complications at 9 months. Each patient's response to CRT will be evaluated using a heart-failure clinical composite score, consisting of a change in NYHA functional class, patient global assessment score, HF events, and cardiovascular death. The primary efficacy endpoint is the proportion of responders in the MPP arm compared with the Bi-V arm between 3 and 9 months., Conclusion: This trial seeks to evaluate whether MPP via a single quadripolar LV lead improves hemodynamic and clinical responses to CRT, both in clinical responders and nonresponders., (© 2017 Wiley Periodicals, Inc.)

Background: Among various cardiac autoantibodies (AAbs), those recognizing the β 1 -adrenergic receptor (β 1 AR) demonstrate agonist-like effects and induce myocardial damage that can be reversed by β-blockers and immunoglobulin G3 (IgG3) immunoadsorption., Objectives: The goal of this study was to investigate the role of β 1 AR-AAbs belonging to the IgG3 subclass in patients with recent-onset cardiomyopathy., Methods: Peripheral blood samples were drawn at enrollment in patients with recent-onset cardiomyopathy (left ventricular ejection fraction [LVEF] ≤0.40; <6 months). The presence of IgG and IgG3-β 1 AR-AAb was determined, and echocardiograms were assessed, at baseline and 6 months. Patients were followed up for ≤48 months., Results: Among the 353 patients who had blood samples adequate for the analysis, 62 (18%) were positive for IgG3-β 1 AR-AAbs (IgG3 group), 58 (16%) were positive for IgG but not IgG3 (non-IgG3 group), and the remaining were negative. There were no significant differences in baseline systolic blood pressure, heart rate, or LVEF among the groups at baseline. Left ventricular end-diastolic and end-systolic diameters were significantly larger in the non-IgG3 group compared with the other groups (left ventricular end-diastolic diameter, p < 0.01; left ventricular end-systolic diameter, p = 0.03). At 6 months, LVEF was significantly higher in the IgG3 group (p = 0.007). Multiple regression analysis showed that IgG3-β 1 AR-AAb was an independent predictor of LVEF at 6 months and change in LVEF over 6 months, even after multivariable adjustment (LVEF at 6 months, β = 0.20, p = 0.01; change in LVEF, β = 0.20, p = 0.008). In patients with high New York Heart Association functional class (III or IV) at baseline, the IgG3 group had a lower incidence of the composite endpoint of all-cause death, cardiac transplantation, and hospitalization due to heart failure, whereas the non-IgG3 group had the highest incidence of the composite endpoint., Conclusions: IgG3-β 1 AR-AAbs were associated with more favorable myocardial recovery in patients with recent-onset cardiomyopathy., (Copyright © 2017 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Rationale: The austere setting of the intensive care unit (ICU) can suppress expressions of spirituality., Objectives: To describe how family members and clinicians experience and express spirituality during the dying process in a 21-bed medical-surgical ICU., Methods: Reflecting the care of 70 dying patients, we conducted 208 semistructured qualitative interviews with 76 family members and 150 clinicians participating in the Three Wishes Project. Interviews were recorded and transcribed verbatim. Data were analyzed by three investigators using qualitative interpretive description., Measurements and Main Results: Participants characterize dying as a spiritual event. Spirituality is an integral part of the life narrative of the patient before, during, and after death. Experiences and expressions of spirituality for patients, families, and clinicians during end-of-life care in the ICU are supported by eliciting and implementing wishes in several ways. Eliciting wishes stimulates conversations for people of diverse spiritual orientations to respond to death in personally meaningful ways that facilitate continuity and closure, and ease emotional trauma. Soliciting wishes identifies positive aspirations, which provide comfort in the face of death. The act of soliciting wishes brings clinician humanity to the fore. Wishing makes individual spiritual preferences and practices more accessible. Wishes may be grounded in spiritual goals, such as peace, comfort, connections, and tributes; they may seek a spiritually enhanced environment or represent specific spiritual interventions., Conclusions: Family members and clinicians consider spirituality an important dimension of end-of-life care. The Three Wishes Project invites and supports the expression of myriad forms of spirituality during the dying process in the ICU.

Objective: The Word Cloud is a frequent wish in the 3 Wishes Project developed to nurture peace and ease the grieving process for dying critically ill patients. The objective was to examine whether Word Clouds can act as a heuristic approach to encourage a narrative orientation to medicine. Narrative medicine is an approach which can strengthen relationships, compassion and resilience., Design: Word Clouds were created for 42 dying patients, and we interviewed 37 family members and 73 clinicians about their impact. We conducted a directed qualitative content analysis, using the 3 stages of narrative medicine (attention, representation, affiliation) to examine the narrative medicine potential of Word Clouds., Results: The elicitation of stories for the Word Cloud promotes narrative attention to the patient as a whole person. The distillation of these stories into a list of words and the prioritisation of those words for arrangement in the collage encourages a representation that did not enforce a beginning, middle or end to the story of the patient's life. Strong affiliative connections were achieved through the honouring of patients, caring for families and sharing of memories encouraged through the creation, sharing and discussion of Word Clouds., Conclusions: In the 3 Wishes Project, Word Clouds are 1 way that families and clinicians honour a dying patient. Engaging in the process of making a Word Cloud can promote a narrative orientation to medicine, forging connections, making meaning through reminiscence and leaving a legacy of a loved one. Documenting and displaying words to remember someone in death reaffirms their life., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.)

Aims: Patients with recent onset non-ischaemic cardiomyopathy have a variable clinical course with respect to recovery of left ventricular ejection fraction (LVEF). The aim of this study was to understand whether temporal changes in diastolic function (DF) are associated with clinical outcomes independent of LVEF recovery., Methods and Results: The Intervention in Myocarditis and Acute Cardiomyopathy (IMAC)-2 study was a prospective, multicentre trial investigating myocardial recovery in subjects with symptoms onset of <6 months and LVEF ≤40% of non-ischaemic dilated cardiomyopathy related to idiopathic cardiomyopathy or myocarditis. LVEF and DF were measured at presentation and at 6-month follow-up. Of 147 patients (mean age 46 ± 14 years, 40% female), baseline LVEF was 23 ± 8%. At 6 months, LVEF improved to 41 ± 12%, with 71% increasing by at least 10% ejection fraction units. DF improved in 58%, was unchanged in 28%, and worsened in 14%. Over a mean follow-up of 1.8 ± 1.2 years, there were 18 events: 11 heart failure (HF) hospitalizations, 3 deaths, and 4 heart transplants. LVEF (HR = 0.94, 95% CI 0.91-0.98, P = 0.002) and DF improvements at 6 months (HR = 0.32, 95% CI 0.11-0.92, P = 0.03) were independently associated with lower likelihood for the combined end point of death, transplantation, and HF hospitalization. Diastolic functional improvement at 6-month follow-up was as prognostically important as LVEF recovery for these patients, and provided incremental prognostic value to the risk stratification (X(2) increased from 12.6 to 18, P = 0.02)., Conclusion: In patients with recent onset non-ischaemic cardiomyopathy, DF recovery was associated with favourable outcomes independent of LVEF improvement, adding incremental prognostic value to these patients., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2015. For permissions please email: journals.permissions@oup.com.)

Background: Peripartum cardiomyopathy has variable disease progression and left ventricular (LV) recovery. We hypothesized that baseline right ventricular (RV) size and function are associated with LV recovery and outcome., Methods and Results: Investigations of Pregnancy-Associated Cardiomyopathy was a prospective 30-center study of 100 peripartum cardiomyopathy women with LV ejection fraction (LVEF) <45% within 13 weeks after delivery. Baseline RV function was assessed by echocardiographic end-diastolic area, end-systolic area, fractional area change, tricuspid annular plane excursion, and RV speckle-tracking longitudinal strain. LV recovery was defined as LVEF of ≥50% at 1 year, persistent severe LV dysfunction as LVEF of ≤35%, and major events as death, transplant, or LV assist device implantation. RV measurements were feasible for 90 of the 96 patients (94%) with echocardiograms available. Mean baseline LVEF was 36±9%. RV fractional area change was <35% in 38% of patients. Of 84 patients with 1-year follow-up data, 63 (75%) had LV recovery and 11 (13%) had LVEF of ≤35% or a major event (4 LV assist devices and 2 deaths). Tricuspid annular plane excursion and RV strain did not predict outcome. Baseline RV fractional area change by multivariable analysis was independently associated with subsequent LV recovery and clinical outcome., Conclusions: Peripartum cardiomyopathy patients had a high incidence of LV recovery, but a significant minority had persistent LV dysfunction or a major clinical event by 1 year. RV function per echocardiographic fractional area change at presentation was associated with subsequent LV recovery and clinical outcomes and thus is prognostically important., (© 2016 American Heart Association, Inc.)

Background: Black women are at greater risk for peripartum cardiomyopathy (PPCM). The guanine nucleotide-binding proteins β-3 subunit (GNB3) has a polymorphism C825T. The GNB3 TT genotype more prevalent in blacks is associated with poorer outcomes. We evaluated GNB3 genotype and myocardial recovery in PPCM., Methods and Results: A total of 97 women with PPCM were enrolled and genotyped for the GNB3 T/C polymorphism. Left ventricular ejection fraction (LVEF) was assessed by echocardiography at entry, 6 and 12 months postpartum. LVEF over time in subjects with the GNB3 TT genotype was compared with those with the C allele overall and in black and white subsets. The cohort was 30% black, age 30+6, LVEF 0.34+0.10 at entry 31+25 days postpartum. The % GNB3 genotype for TT/CT/CC=23/41/36 and differed markedly by race (blacks=52/38/10 versus whites=10/44/46, P<0.001). In subjects with the TT genotype, LVEF at entry was lower (TT=0.31+0.09; CT+CC=0.35+0.09, P=0.054) and this difference increased at 6 (TT=0.45+0.15; CT+CC=0.53+0.08, P=0.002) and 12 months (TT=0.45+0.15; CT+CC=0.56+0.07, P<0.001.). The difference in LVEF at 12 months by genotype was most pronounced in blacks (12 months LVEF for GNB3 TT=0.39+0.16; versus CT+CC=0.53+0.09, P=0.02) but evident in whites (TT=0.50++0.11; CT+CC=0.56+0.06, P=0.04)., Conclusions: The GNB3 TT genotype was associated with lower LVEF at 6 and 12 months in women with PPCM, and this was particularly evident in blacks. Racial differences in the prevalence and impact of GNB3 TT may contribute to poorer outcomes in black women with PPCM., (© 2016 American Heart Association, Inc.)

Background Peripartum cardiomyopathy shares some clinical features with idiopathic dilated cardiomyopathy, a disorder caused by mutations in more than 40 genes, including TTN, which encodes the sarcomere protein titin. Methods In 172 women with peripartum cardiomyopathy, we sequenced 43 genes with variants that have been associated with dilated cardiomyopathy. We compared the prevalence of different variant types (nonsense, frameshift, and splicing) in these women with the prevalence of such variants in persons with dilated cardiomyopathy and with population controls. Results We identified 26 distinct, rare truncating variants in eight genes among women with peripartum cardiomyopathy. The prevalence of truncating variants (26 in 172 [15%]) was significantly higher than that in a reference population of 60,706 persons (4.7%, P=1.3×10(-7)) but was similar to that in a cohort of patients with dilated cardiomyopathy (55 of 332 patients [17%], P=0.81). Two thirds of identified truncating variants were in TTN, as seen in 10% of the patients and in 1.4% of the reference population (P=2.7×10(-10)); almost all TTN variants were located in the titin A-band. Seven of the TTN truncating variants were previously reported in patients with idiopathic dilated cardiomyopathy. In a clinically well-characterized cohort of 83 women with peripartum cardiomyopathy, the presence of TTN truncating variants was significantly correlated with a lower ejection fraction at 1-year follow-up (P=0.005). Conclusions The distribution of truncating variants in a large series of women with peripartum cardiomyopathy was remarkably similar to that found in patients with idiopathic dilated cardiomyopathy. TTN truncating variants were the most prevalent genetic predisposition in each disorder.

Frailty is increasingly recognized in older adults with cardiovascular disease, particularly in those with heart failure (HF). A growing body of evidence has shown that frailty has a negative effect on survival, hospitalizations, disability, and quality of life. Beyond frailty, additional domains captured by a comprehensive geriatric assessment contribute incremental value in predicting outcomes and identifying treatment targets. Exercise training is ideally suited to this setting as it can concomitantly improve physical frailty and HF symptoms. Multidisciplinary disease management programs offer a number of benefits for frail HF patients; invasive procedures carry a higher risk of morbidity than in non-frail counterparts, and evidence-based drugs and devices have an uncertain value and warrant further research. While more data accrues, difficult therapeutic decisions should be individualized using a shared patient-centered decision making approach.

The term food literacy is emergent, and as a result the literature reflects a great variety of definitions. Simultaneously, new research and food literacy programming is being developed without an agreed upon definition of what food literacy is and how food skills, food security, and health literacy may fit with the definition. We undertook a scoping review and conceptual analysis to identify how the term is understood and to determine shared components of definitions. We found that although most definitions included a nutrition and food skills component, there was great variation in how the ability to access, process, and enjoy food was affected by our complex food system. We propose a definition of food literacy that includes the positive relationship built through social, cultural, and environmental experiences with food enabling people to make decisions that support health. We offer a framework that situates food literacy at the intersection between community food security and food skills, and we assert that behaviours and skills cannot be separated from their environmental or social context. The proposed definition and framework are intended to be guiding templates for academics and practitioners to position their work in education and advocacy, bringing together separate spheres for collective action.

Background: Dying in the complex, efficiency-driven environment of the intensive care unit can be dehumanizing for the patient and have profound, long-lasting consequences for all persons attendant to that death., Objective: To bring peace to the final days of a patient's life and to ease the grieving process., Design: Mixed-methods study., Setting: 21-bed medical-surgical intensive care unit., Participants: Dying patients and their families and clinicians., Intervention: To honor each patient, a set of wishes was generated by patients, family members, or clinicians. The wishes were implemented before or after death by patients, families, clinicians (6 of whom were project team members), or the project team., Measurements: Quantitative data included demographic characteristics, processes of care, and scores on the Quality of End-of-Life Care-10 instrument. Semistructured interviews of family members and clinicians were transcribed verbatim, and qualitative description was used to analyze them., Results: Participants included 40 decedents, at least 1 family member per patient, and 3 clinicians per patient. The 159 wishes were implemented and classified into 5 categories: humanizing the environment, tributes, family reconnections, observances, and "paying it forward." Scores on the Quality of End-of-Life Care-10 instrument were high. The central theme from 160 interviews of 170 persons was how the 3 Wishes Project personalized the dying process. For patients, eliciting and customizing the wishes honored them by celebrating their lives and dignifying their deaths. For families, it created positive memories and individualized end-of-life care for their loved ones. For clinicians, it promoted interprofessional care and humanism in practice., Limitation: Impaired consciousness limited understanding of patients' viewpoints., Conclusion: The 3 Wishes Project facilitated personalization of the dying process through explicit integration of palliative and spiritual care into critical care practice., Primary Funding Source: Hamilton Academy of Health Science Research Organization, Canadian Intensive Care Foundation.

Background: Several echocardiographic measures have prognostic value in heart failure (HF). However, no definitive data exist on how changes in these parameters with treatment affect survival in this patient population. We hypothesized that early improvement on echocardiography could predict long-term survival., Methods and Results: We conducted a retrospective review of 404 patients seen in the HF clinic from 2002 to 2008 (6.5 years). Patients had one echocardiogram ≤1 year before and another ≥1 month (10 ± 7 months) after treatment onset. We studied changes in standard echocardiographic parameters, including left (LV) and right (RV) ventricular size and/or function (systolic and/or diastolic), valvular (mitral and tricuspid) function, and pulmonary artery pressure. Survival curves and hazard ratios were generated for patients showing improvement on the 2nd echocardiogram versus those who did not. Multivariable analyses were performed adjusting for age, sex, ischemic etiology, and significant baseline echocardiographic parameters. Average follow-up was 2.9 ± 1.5 years. Improvement in LV end-systolic dimension, RV function, and mitral regurgitation were independent predictors of 5-year survival (P < .05) and, importantly, more predictive than baseline values of these parameters alone (higher hazard ratios)., Conclusions: Early echocardiographic improvement is strongly associated with 5-year survival in patients with HF. Serial echocardiography may aid in stratifying patient care., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Peripartum cardiomyopathy (PPCM) is a well-established complication of pregnancy. Criteria include heart failure that presents with reduced left ventricular function, signs and symptoms of heart failure either late in pregnancy or early in the postpartum period. The incidence varies widely depending geography and ethnicity. The pathophysiology of PPCM is still an area of active investigation, but includes immune and inflammatory mechanisms, which are the subject of several investigations. Therapies for chronic heart failure from PPCM are similar to those patients with nonischemic cardiomyopathy from different etiologies, however novel therapies may include bromocriptine, pentoxifylline or other potential therapies influencing the immune system. The need for implantable defibrillators, left ventricular assist devices and cardiac transplant in women with PPCM is rare, and prognosis is better than other forms of nonischemic cardiomyopathy. Despite this, further information about the epidemiology, prognosis and potential therapies are required to better manage and diagnose PPCM in women with signs and symptoms of heart failure.

The process of validating an assay for high-throughput screening (HTS) involves identifying sources of variability and developing procedures that minimize the variability at each step in the protocol. The goal is to produce a robust and reproducible assay with good metrics. In all good cell-based assays, this means coefficient of variation (CV) values of less than 10% and a signal window of fivefold or greater. HTS assays are usually evaluated using Z' factor, which incorporates both standard deviation and signal window. A Z' factor value of 0.5 or higher is acceptable for HTS. We used a standard HTS validation procedure in developing small interfering RNA (siRNA) screening technology at the HTS center at Southern Research. Initially, our assay performance was similar to published screens, with CV values greater than 10% and Z' factor values of 0.51 ± 0.16 (average ± standard deviation). After optimizing the siRNA assay, we got CV values averaging 7.2% and a robust Z' factor value of 0.78 ± 0.06 (average ± standard deviation). We present an overview of the problems encountered in developing this whole-genome siRNA screening program at Southern Research and how equipment optimization led to improved data quality., Competing Interests: The authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Background: Persons with heart failure (HF) at high risk for adverse events should be followed by specialized HF clinics, since follow-up by specialized HF clinics improves outcomes for HF patients. The objective was to determine whether there were disparities for gender and other factors associated with referral of patients to specialized HF clinics., Methods: In this prospective cohort study, patients with a confirmed primary diagnosis of HF were recruited by nurses at 8 hospital emergency departments (ED) in Québec, Canada. They were interviewed by telephone at 6 weeks post ED discharge and subsequently at 3 months and 6 months. Pertinent clinical variables were extracted from medical charts by trained nurses. Bivariate analysis and multiple logistic regression were used to identify whether gender and other potential factors were associated with referral to the HF clinic., Results: We enrolled 549 patients (mean age 75.5±11.0 years; 51% males). By 6 months after their ED visit for HF, 37.6% of the cohort were referred to specialized HF clinics. Men were more likely to be referred (odds ratio [OR] 2.04; 95% confidence interval [CI] 1.12, 3.74). Other factors associated with referral were younger age (OR 0.95; 95% CI 0.92, 0.98), and systolic dysfunction HF (left ventricle ejection fraction <40%) (OR 3.08; 95% CI 1.77, 5.46)., Conclusion: There are disparities in referral with respect to gender, age, and type of HF. These disparities in referral need to be addressed.

Background: The Canadian Cardiology Society recommends that patients should be seen within 2 weeks after an emergency department (ED) visit for heart failure (HF). We sought to investigate whether patients who had an ED visit for HF subsequently consult a physician within the current established benchmark, to explore factors related to physician consultation, and to examine whether delay in consultation is associated with adverse events (AEs) (death, hospitalization, or repeat ED visit)., Methods: Patients were recruited by nurses at 8 hospital EDs in Québec, Canada, and interviewed by telephone within 6 weeks of discharge and subsequently at 3 and 6 months. Clinical variables were extracted from medical charts by nurses. We used Cox regression in the analysis., Results: We enrolled 410 patients (mean age 74.9 ± 11.1 years, 53% males) with a confirmed primary diagnosis of HF. Only 30% consulted with a physician within 2 weeks post-ED visit. By 4 weeks, 51% consulted a physician. Over the 6-month follow-up, 26% returned to the ED, 25% were hospitalized, and 9% died. Patients who were followed up within 4 weeks were more likely to be older and have higher education and a worse quality of life. Patients who consulted a physician within 4 weeks of ED discharge had a lower risk of AEs (hazard ratio 0.59, 95% CI 0.35-0.99)., Conclusion: Prompt follow-up post-ED visit for HF is associated with lower risk for major AEs. Therefore, adherence to current HF guideline benchmarks for timely follow-up post-ED visit is crucial., (Copyright © 2013 Mosby, Inc. All rights reserved.)

Introduction: The Quartet(®) left ventricular (LV) lead is the first with 4 pacing electrodes (tip and 3 rings) that enables pacing from 10 different pacing vectors. Postoperative performance of this lead was evaluated in a prospective, nonrandomized, multicenter IDE study., Methods: Patients with standard indications for CRT-D were enrolled. Electrical performance and presence of phrenic nerve stimulation (PNS) were assessed during pacing from each of 10 vectors at predischarge (within 7 days), 1 month, and 3 months postimplant., Results: The Quartet LV lead was implanted successfully in 170 patients (95.5% implant success rate, 68 ± 11 years, 68.5% male, LVEF: 25 ± 7%, NYHA class III: 98.3% and class IV: 1.7%). Mean follow-up was 4.7 ± 1.9 months. Capture threshold and impedance for each of the 10 LV lead pacing vectors remained stable during follow-up. LV lead dislodgement occurred in 6 (3.5%) patients and PNS was observed in 23 (13.5%) patients. PNS was resolved noninvasively in all 23 (100%) patients, either by reprogramming to pace from the additional LV lead pacing vectors alone (13 pts, 56.5%), reprogramming to pace from the additional LV lead pacing vectors and reprogramming pacing output (4 pts, 17.4%), or by reprogramming pacing output alone (6 pts, 26.1%)., Conclusions: The Quartet LV lead electrical performance was stable and was associated with a high implant success and low dislodgement rate during 3-month follow-up. In all patients with PNS, the 10 pacing vectors combined with reduced output programming enabled the elimination of PNS noninvasively., (© 2013 Wiley Periodicals, Inc.)

The Seattle Heart Failure Model (SHFM) is 1 of the most widely used tools to predict survival in patients with heart failure. However, it does not accommodate very elderly patients. We decided to assess the applicability of the SHFM in patients >80 years old enrolled in a tertiary care heart failure clinic. We evaluated the difference between observed survival and mean life expectancy as predicted by the SHFM on 261 patients >80 years old enrolled in a heart failure clinic at the Jewish General Hospital, Montreal, Quebec, Canada from January 2002 through March 2010. Average age of the patient population was 85 ± 4 years (range 80 to 105). Sixty-two percent of the population consisted of men, 63% had ischemic cardiomyopathy (ICM), and average ejection fraction was 36 ± 18%. Median observed survival was 1.91 years (interquartile range 0.68 to 5.53) for the total population (n = 261). The SHFM (predicted median survival 6.7 years, interquartile range 3.8 to 11.2) overestimated life expectancy by an average of 4.79 years. For patients with ICM (n = 164) versus non-ICM (n = 97), the score overestimated survival by 4.29 versus 5.69 years, respectively. In conclusion, the SHFM overestimates life expectancy in elderly patients followed in a tertiary care heart failure clinic. Further studies are needed to more accurately estimate prognosis in this patient population., (Copyright © 2012 Elsevier Inc. All rights reserved.)

Background: Given the potential for recovery in recent onset nonischemic cardiomyopathy (ROCM), the timing and need for implantable cardioverter-defibrillator (ICDs) remains controversial. We examined the utilization of ICDs and the impact on survival for subjects with ROCM., Methods and Results: An National Heart, Lung, and Blood Institute sponsored registry enrolled 373 subjects with ROCM, all with a left ventricular ejection fraction (LVEF) ≤0.40 and ≤6 months of symptoms. The mean age was 45 ± 14 years, 38% were female, 21% black, 75% New York Heart Association II/III, and the mean LVEF was 0.24 ± 0.08. Survival was comparable for subjects with an ICD within 1 month of entry (n = 43, 1/2/3 year % survival = 97/97/92) and those with no ICD at 1 month (n = 330, % survival = 98/97/95, P = .30) and between those with and without an ICD at 6 months (ICD, n = 73, 1/2/3 year % survival = 98/98/95; no ICD, n = 300, % survival = 98/96/95, P = .95). There were only 6 sudden cardiac deaths (SCD) noted (% survival free from SCD = 99/98/97) and these occurred in 1.9% of subjects without ICD and 0.9% of those with a device (P = .50)., Conclusions: In a multicenter cohort of ROCM the risk of SCD was low at 1% per year. Early ICD placement did not impact survival and can be deferred while assessing potential for myocardial recovery., (Copyright © 2012 Elsevier Inc. All rights reserved.)

Background: Although prevalence of heart failure (HF) is similar in women and men, more men are admitted to specialized HF clinics, possibly owing to a perception that men benefit more. Our aim was to describe 1-year outcomes in men and women attending specialized HF clinics., Methods and Results: We enrolled 531 newly referred patients (mean age 66 years, 26% women) to 1 of 6 HF multidisciplinary clinics in Quebec. Data were collected at time of entry to the clinic and 6 and 12 months later. The 3 main outcomes, mortality, disease evolution (New York Heart Association functional class, quality of life, 6-minute walk), and number of hospital admissions/emergency department visits were analyzed separately. Survival was higher in women than in men (adjusted hazard ratio 2.53, 95% confidence interval 1.10-5.80). Both women and men improved over the 12-month period in terms of quality of life, 6-minute walk, and lower use of hospital and emergency department. Persons who at entry to the clinic had more severe disease showed more improvement. Deterioration over the year was associated with higher number of comorbidities, but not with age or gender., Conclusions: Both men and women with HF who attend specialized HF clinics improved, including those with more severe disease., (Copyright © 2011 Elsevier Inc. All rights reserved.)

The present report is the first to describe a case of hemoptysis caused by an endocardial pacemaker lead. In addition, the patient presented with endocarditis and tricuspid valve stenosis. Aggressive treatment consisted of surgical extraction of two pacemaker leads and one pacemaker battery, replacement of the tricuspid valve and implantation of a DDD-R epicardial pacemaker.

Background: We compared severity of heart failure (HF) between men and women at entry to the multidisciplinary HF clinic based on 3 measures: New York Heart Association functional class, norm-referenced 6-minute walk distance, and health-related quality of life., Methods: Newly admitted patients to 1 of 6 HF clinics were enrolled. Data were collected from a clinical database, questionnaires were administered to patients, and tests were administered by clinic nurses. We compared men and women with respect to the 3 severity indicators at entry to the clinic., Results: In adjusted analyses, women had a lower health-related quality of life (P = 0.04) but did not have lower norm-referenced 6-minute walk distance or lower New York Heart Association functional class on entry to the clinic. Having more comorbid conditions, being on medication, and having visited the emergency department or been admitted to hospital in the past 6 months were associated with higher severity at entry according to all 3 indicators., Conclusions: Women report a lower health-related quality of life at entry to the clinic, although functional capacity does not seem to differ between women and men. Reasons for these discrepancies will need to be elucidated to better address women's health needs., (Copyright © 2011 Elsevier Inc. All rights reserved.)