The Gap to Fill: Rationale for Rapid Initiation and Optimal Titration of Comprehensive Disease-modifying Medical Therapy for Heart Failure with Reduced Ejection Fraction

There are gaps in the use of therapies that save lives and improve quality of life for patients with heart failure with reduced ejection fraction, both in the US and abroad. The evidence is clear that initiation and titration of guideline-directed medical therapy (GDMT) and comprehensive disease-modifying medical therapy (CDMMT) to maximally tolerated doses improves patient-focused outcomes, yet observational data suggest this does not happen. The purpose of this review is to describe the gap in the use of optimal treatment worldwide and discuss the benefits of newer heart failure therapies including angiotensin receptor-neprilysin inhibitors and sodium-glucose cotransporter 2 inhibitors. It will also cover the efficacy and safety of such treatments and provide potential pathways for the initiation and rapid titration of GDMT/CDMMT

The HTLV-1-encoded protein HBZ directly inhibits the acetyl transferase activity of p300/CBP

The homologous cellular coactivators p300 and CBP contain intrinsic lysine acetyl transferase (termed HAT) activity. This activity is responsible for acetylation of several sites on the histones as well as modification of transcription factors. In a previous study, we found that HBZ, encoded by the Human T-cell Leukemia Virus type 1 (HTLV-1), binds to multiple domains of p300/CBP, including the HAT domain. In this study, we found that HBZ inhibits the HAT activity of p300/CBP through the bZIP domain of the viral protein. This effect correlated with a reduction of H3K18 acetylation, a specific target of p300/CBP, in cells expressing HBZ. Interestingly, lower levels of H3K18 acetylation were detected in HTLV-1 infected cells compared to non-infected cells. The inhibitory effect of HBZ was not limited to histones, as HBZ also inhibited acetylation of the NF-κB subunit, p65, and the tumor suppressor, p53. Recent studies reported that mutations in the HAT domain of p300/CBP that cause a defect in acetylation are found in certain types of leukemia. These observations suggest that inhibition of the HAT activity by HBZ is important for the development of adult T-cell leukemia associated with HTLV-1 infection

A study protocol of a randomised controlled trial incorporating a health economic analysis to investigate if additional allied health services for rehabilitation reduce length of stay without compromising patient outcomes

Background Reducing patient length of stay is a high priority for health service providers. Preliminary information suggests additional Saturday rehabilitation services could reduce the time a patient stays in hospital by three days. This large trial will examine if providing additional physiotherapy and occupational therapy services on a Saturday reduces health care costs, and improves the health of hospital inpatients receiving rehabilitation compared to the usual Monday to Friday service. We will also investigate the cost effectiveness and patient outcomes of such a service. Methods/Design A randomised controlled trial will evaluate the effect of providing additional physiotherapy and occupational therapy for rehabilitation. Seven hundred and twelve patients receiving inpatient rehabilitation at two metropolitan sites will be randomly allocated to the intervention group or control group. The control group will receive usual care physiotherapy and occupational therapy from Monday to Friday while the intervention group will receive the same amount of rehabilitation as the control group Monday to Friday plus a full physiotherapy and occupational therapy service on Saturday. The primary outcomes will be patient length of stay, quality of life (EuroQol questionnaire), the Functional Independence Measure (FIM), and health utilization and cost data. Secondary outcomes will assess clinical outcomes relevant to the goals of therapy: the 10 metre walk test, the timed up and go test, the Personal Care Participation Assessment and Resource Tool (PC PART), and the modified motor assessment scale. Blinded assessors will assess outcomes at admission and discharge, and follow up data on quality of life, function and health care costs will be collected at 6 and 12 months after discharge. Between group differences will be analysed with analysis of covariance using baseline measures as the covariate. A health economic analysis will be carried out alongside the randomised controlled trial. Discussion This paper outlines the study protocol for the first fully powered randomised controlled trial incorporating a health economic analysis to establish if additional Saturday allied health services for rehabilitation inpatients reduces length of stay without compromising discharge outcomes. If successful, this trial will have substantial health benefits for the patients and for organizations delivering rehabilitation services

Why media representations of corporations matter for public health policy : a scoping review

BACKGROUND: Media representations play a crucial role in informing public and policy opinions about the causes of, and solutions to, ill-health. This paper reviews studies analysing media coverage of non-communicable disease (NCD) debates, focusing on how the industries marketing commodities that increase NCD risk are represented. METHODS: A scoping review identified 61 studies providing information on media representations of NCD risks, NCD policies and tobacco, alcohol, processed food and soft drinks industries. The data were narratively synthesized to describe the sample, media depictions of industries, and corporate and public health attempts to frame the media debates. RESULTS: The findings indicate that: (i) the limited research that has been undertaken is dominated by a focus on tobacco; (ii) comparative research across industries/risk-factors is particularly lacking; and (iii) coverage tends to be dominated by two contrasting frames and focuses either on individual responsibilities ('market justice' frames, often promoted by commercial stakeholders) or on the need for population-level interventions ('social justice' frames, frequently advanced by public health advocates). CONCLUSIONS: Establishing the underlying frameworks is crucial for the analysis of media representation of corporations, as they reflect the strategies that respective actors use to influence public health debates and decision making. The potential utility of media research lies in the insights that it can provide for public health policy advocates about successful framing of public health messages and strategies to counter frames that undermine public health goals. A better understanding of current media debates is of paramount importance to improving global health

Design for Mobile Mental Health:An Exploratory Review

A large number of mobile mental health apps are available to the public but current knowledge about requirements of designing such solutions is scarce, especially from sociotechnical and user centred points of view. Due to the significant role of mobile apps in the mental health service models, identifying the design requirements of mobile mental health solutions is crucial. Some of those requirements have been addressed individually in the literature, but there are few research studies that show a comprehensive picture of this domain. This exploratory review aims to facilitate such holistic understanding. The main search keywords of the review were identified in a cross-disciplinary requirements workshop. The search was started by finding some core references in the healthcare databases. A wider range of references then has been explored using a snowball method. Findings showed that there is a good understanding of individual design requirements in current literature but there are few examples of implementing a combination of different design requirements in real world products. The design processes specifically developed for mobile mental health apps are also rare. Most studies on operational mobile mental health apps address major mental health issues while prevention and wellbeing areas are underdeveloped. In conclusion, the main recommendations for designing future mobile mental health solutions include: moving towards sociotechnical and open design strategies, understanding and creating shared value, recognizing all dimensions of efficacy, bridging design and medical research and development, and considering an ecosystem perspective

Japan’s whaling plan under scrutiny

Eighteen years after initiating scientific whaling in Antarctic waters, Japan presented a new and more ambitious program to the International Whaling Commission (IWC); the proposal was made in early June during the IWC’s annual meeting in Ulsan, Korea. Japan now wishes to more than double its annual catch of Antarctic minke whales (from about 440 to 935), and to expand lethal sampling to include an additional yearly take of 50 humpback and 50 fin whales. Unlike catches for commercial whaling, scientific catches are unregulated. Since 1987, Japan has taken some 6,800 minke whales from Antarctic waters, despite ongoing criticism of the relevance and direction of Japan’s research. The IWC was set up to regulate commercial whaling and to conserve whale populations, under the authority of the 1946 International Convention for the Regulation of Whaling. Following a well-documented failure of management that led to the collapse of most global whale populations, the IWC set a zero quota for commercial whaling (the moratorium). This was made effective from 1986. Norway, the former Soviet Union and Japan initially objected to the moratorium, but Japan withdrew its objection and ceased commercial whaling in 1988