'We're like a gang, we stick together': Experiences of Ventricular Assist Device (VAD) communities

Background: VADs are relatively new developments in the management of advanced heart failure. In the UK, VAD recipients comprise a unique group of less than 200 patients. This is the first paper to explore the experience of VAD communities, the extent to which communities are developed around the device, and how these influence the experience of living with the VAD. Methods: Qualitative interviews were conducted with 20 VAD recipients (implanted as bridge to transplantation), 11 interviews also included the VAD recipients’ partners. Interpretive phenomenology was employed as the theoretical basis guiding the analysis of the interviews. Results: Four key themes emerged from the data: the existence of VAD communities; experiential knowledge and understanding; social comparisons; and the impacts of deaths within the VAD community. Many of the interviewees valued the VAD communities and the relationships they had formed with fellow recipients. Beneficial impacts of the VAD communities included offering recently implanted patients a realistic view of what to expect from life with a VAD, this could aid them in accepting and adapting to the changes imparted by the device. However, negative impacts of the VAD communities were also reported, in particular following deaths within the group which were a source of distress for many of the interviewees. Conclusions: In general, the VAD communities appeared to be a beneficial source of support for the majority of interviewees. Consideration should be given to how these communities could be supported by clinicians

Better sexual acceptability of agomelatine (25 and 50 mg) compared to escitalopram (20 mg) in healthy volunteers. A 9-week, placebo-controlled study using the PRSexDQ scale

The present double-blind, placebo-controlled study evaluates the effects of agomelatine and the selective serotonin reuptake inhibitor escitalopram on sexual dysfunction in healthy men and women

Application of a lifestyle-based score to predict cardiovascular risk in African Americans: The Jackson heart study

Cardiovascular disease (CVD) primordial prevention tools applicable to diverse popula-tions are scarce. Our aim was to assess the performance of a lifestyle-based tool to estimate CVD risk in an African American population. The Jackson Heart Study is a prospective cohort including 5306 African American participants in Jackson, Mississippi (2000–2004), with a mean follow up of 12 years. The Healthy Heart Score is a lifestyle-based CVD risk prediction model based on nine components: body mass index (BMI), physical activity, smoking, and a 5-component diet score. Gender-specific beta coefficients from its derivation cohorts were used to assess the performance of the Healthy Heart Score. Model discrimination was assessed using Harrell’s C-Index for survival data and time dependent Area Under the Curve. Model calibration was evaluated through calibration plots. A total of 189 CVD events occurred. The Healthy Heart Score showed high-moderate discrimination for CVD events (C-statistic 0.75 [95% CI, 0.71–0.78]) but with little improvement over the age-only model. Both the age-only and Healthy Heart Score models had better performance in participants without diabetes at baseline and showed good calibration. In African Americans, the Healthy Heart Score does not improve prediction of mid-life CVD events beyond what is obtained by age alone.This research was funded by the National Heart, Lung, and Blood Institute, and the National Institute on Minority Health and Health Disparities, contract numbers HHSN268201300046C, HHSN268201300047C, HHSN268201300048C, HHSN268201300049C, HHSN268201300050C. M.S.-P. holds a Ramón y Cajal contract (RYC-2018-025069-I) from the Ministry of Science, Innovation and Universities and FEDER/FSE and a FIS grant PI20/00896 (Instituto de Salud Carlos III, State Secretary of R+D+I and FEDER/FSE). Preparation of this manuscript was supported by The Robert Wood Johnson Foundation (Harold Amos Medical Faculty Development Program ID# 76236, J.J.J.) and the National Institute of Diabetes and Digestive and Kidney Diseases (K23DK117041, J.J.J.) of the National Institutes of Healt

Limitations of current in vitro models for testing the clinical potential of epigenetic inhibitors for treatment of pediatric ependymoma

Background: Epigenetic modifications have been shown to play an important role in the classification and pathogenesis of the pediatric brain tumor ependymoma, suggesting they are a potential therapeutic target.Results: Agents targeting epigenetic modifications inhibited the growth and induced the death of ependymoma cells with variable efficiency. However, this was often not at clinically achievable doses. Additionally, DNA methylation profiling revealed a lack of similarity to primary ependymomas suggesting alterations were induced during culture. Toxicity to fetal neural stem cells was also seen at similar drug concentrationsConclusions: Agents targeting epigenetic modifications were able to inhibit the growth and induced the death of ependymoma cells grown in vitro. However, many agents were only active at high doses, outside clinical ranges, and also resulted in toxicity to normal brain cells. The lack of similarity in DNA methylation profiles between cultured cells and primary ependymomas questions the validity of using in vitro cultured cells for pre-clinical analysis of agents targeting epigenetic mechanisms and suggests further investigation using models that are more appropriate should be undertaken before agents are taken forward for clinical testing.Materials and Methods: The effects of agents targeting epigenetic modifications on the growth and death of a panel of ependymoma cell lines was investigated, as well as toxicity to normal fetal neural stem cells. The ependymoma cell lines were characterized using DNA methylation profiling

Niraparib maintenance treatment improves time without symptoms or toxicity (TWiST) versus routine surveillance in recurrent ovarian cancer: a TWiST analysis of the ENGOT-OV16/NOVA trial

Purpose: this study estimated time without symptoms or toxicity (TWiST) with niraparib compared with routine surveillance (RS) in the maintenance treatment of patients with recurrent ovarian cancer. Patients and methods: mean progression-free survival (PFS) was estimated for niraparib and RS by fitting parametric survival distributions to Kaplan-Meier data for 553 patients with recurrent ovarian cancer who were enrolled in the phase III ENGOT-OV16/NOVA trial. Patients were categorized according to the presence or absence of a germline BRCA mutation-gBRCAmut and non-gBRCAmut cohorts. Mean time with toxicity was estimated based on the area under the Kaplan-Meier curve for symptomatic grade 2 or greater fatigue, nausea, and vomiting adverse events (AEs). Time with toxicity was the number of days a patient experienced an AE post-random assignment and before disease progression. TWiST was estimated as the difference between mean PFS and time with toxicity. Uncertainty was explored using alternative PFS estimates and considering all symptomatic grade 2 or greater AEs. Results: in the gBRCAmut and non-gBRCAmut cohorts, niraparib treatment resulted in a mean PFS benefit of 3.23 years and 1.44 years, respectively, and a mean time with toxicity of 0.28 years and 0.10 years, respectively, compared with RS. Hence, niraparib treatment resulted in a mean TWiST benefit of 2.95 years and 1.34 years, respectively, compared with RS, which is equivalent to more than four-fold and two-fold increases in mean TWiST between niraparib and RS in the gBRCAmut and non-gBRCAmut cohorts, respectively. This TWiST benefit was consistent across all sensitivity analyses, including modeling PFS over 5-, 10-, and 15-year time horizons. Conclusion: patients who were treated with niraparib compared with RS experienced increased mean TWiST. Thus, patients who were treated with niraparib in the ENGOT-OV16/NOVA trial experienced more time without symptoms or symptomatic toxicities compared with control

Using intervention mapping to develop evidence-based toolkits that provide mental wellbeing support to workers and their managers whilst on long-term sick leave and following return-to-work

Background Managing long-term sickness absence is challenging in countries where employers and managers have the main responsibility to provide return to work support, particularly for workers with poor mental health. Whilst long-term sick leave and return to work frameworks and guidance exist for employers, there are currently no structured return to work protocols for employers or for their workers encompassing best practice strategies to support a positive and timely return to work outcome. Purpose To utilise the intervention mapping (IM) protocol as a framework to develop return to work toolkits that are underpinned by relevant behaviour change theory targeting mental health to promote a positive return to work experience for workers on long-term sick leave. Methods This paper provides a worked example of intervention mapping (IM) to develop an intervention through a six-step process to combine theory and evidence in the development of two toolkits – one designed for managers and one to be used by workers on long-term sick leave. As part of this process, collaborative planning techniques were used to develop the intervention. A planning group was set up, through which researchers would work alongside employer, worker, and mental health professional representatives to develop the toolkits. Additionally, feedback on the toolkits were sought from the target populations of workers and managers and from wider employer stakeholders (e.g., human resource specialists). The implementation and evaluation of the toolkits as a workplace intervention were also planned. Results Two toolkits were designed following the six steps of intervention mapping. Feedback from the planning group (n = 5; psychologist, psychiatrist, person with previous experience of poor mental health, employer and charity worker) and participants (n = 14; employers = 3, wellbeing director = 1; human resources = 2, managers = 2, employees with previous experience of poor mental health = 5) target populations indicated that the toolkits were acceptable and much needed. Conclusion Using IM allowed the development of an evidence-based practical intervention, whilst incorporating the views of all the impacted stakeholder groups. The feasibility and acceptability of the toolkits and their supporting intervention components, implementation process and methods of assessment will be evaluated in a feasibility pilot randomised controlled trial

Conservation physiology of marine fishes: state of the art and prospects for policy

The state of the art of research on the environmental physiology of marine fishes is reviewed from the perspective of how it can contribute to conservation of biodiversity and fishery resources. A major constraint to application of physiological knowledge for conservation of marine fishes is the limited knowledge base; international collaboration is needed to study the environmental physiology of a wider range of species. Multifactorial field and laboratory studies on biomarkers hold promise to relate ecophysiology directly to habitat quality and population status. The 'Fry paradigm' could have broad applications for conservation physiology research if it provides a universal mechanism to link physiological function with ecological performance and population dynamics of fishes, through effects of abiotic conditions on aerobic metabolic scope. The available data indicate, however, that the paradigm is not universal, so further research is required on a wide diversity of species. Fish physiologists should interact closely with researchers developing ecological models, in order to investigate how integrating physiological information improves confidence in projecting effects of global change; for example, with mechanistic models that define habitat suitability based upon potential for aerobic scope or outputs of a dynamic energy budget. One major challenge to upscaling from physiology of individuals to the level of species and communities is incorporating intraspecific variation, which could be a crucial component of species' resilience to global change. Understanding what fishes do in the wild is also a challenge, but techniques of biotelemetry and biologging are providing novel information towards effective conservation. Overall, fish physiologists must strive to render research outputs more applicable to management and decision-making. There are various potential avenues for information flow, in the shorter term directly through biomarker studies and in the longer term by collaborating with modellers and fishery biologists.EU COST Action FA1004 Conservation Physiology of Marine Fishesinfo:eu-repo/semantics/publishedVersio