Influence of Participant Perceptions of Adherence-Related Interactions with Study/Study Team on Drug Levels: HPTN069 Analysis of Self-Reported Adherence Experiences While on Study.

Adherence to HIV pre-exposure prophylaxis (PrEP) study drug is critical for safety, tolerability, and efficacy trials, and may be affected by how adherence is communicated by the study staff to trial participants. Increasingly, clinical trials investigating PrEP are creating and implementing 'participant-centered' approaches that discuss potential non-adherence neutrally (without negative judgement) and support efforts to adhere versus insisting on perfect adherence. In the HPTN069/ACTG A5305 study, we evaluated participant experiences of potentially negative adherence-related interactions with study teams using ten items to characterize the frequency of such experiences. We related these individual items and a combined set of seven negative experience items (total negative experience score) to drug concentrations (detectable or consistent with daily-dosing). The exploratory analyses used logistic regression for each experience item on the full sample and disaggregated by sex. Several experiences were related to drug detection and to daily-dosing, although more so for participants identifying as men than women. Total negative experience scores associated with not having detection drug concentrations for the full sample, and remained significant even when controlling for sex, age, and race. Daily dosing was associated with total negative experience score for men in the sample. Additional investigations into adherence-related interactions with study teams that are most problematic or helpful in general and uniquely for men and women are warranted.

Phospholamban ablation rescues the enhanced propensity to arrhythmias of mice with CaMKII-constitutive phosphorylation of RyR2 at site S2814.

KEY POINTS: Mice with Ca(2+) -calmodulin-dependent protein kinase (CaMKII) constitutive pseudo-phosphorylation of the ryanodine receptor RyR2 at Ser2814 (S2814D(+/+) mice) exhibit a higher open probability of RyR2, higher sarcoplasmic reticulum (SR) Ca(2+) leak in diastole and increased propensity to arrhythmias under stress conditions. We generated phospholamban (PLN)-deficient S2814D(+/+) knock-in mice by crossing two colonies, S2814D(+/+) and PLNKO mice, to test the hypothesis that PLN ablation can prevent the propensity to arrhythmias of S2814D(+/+) mice. PLN ablation partially rescues the altered intracellular Ca(2+) dynamics of S2814D(+/+) hearts and myocytes, but enhances SR Ca(2+) sparks and leak on confocal microscopy. PLN ablation diminishes ventricular arrhythmias promoted by CaMKII phosphorylation of S2814 on RyR2. PLN ablation aborts the arrhythmogenic SR Ca(2+) waves of S2814D(+/+) and transforms them into non-propagating events. A mathematical human myocyte model replicates these results and predicts the increase in SR Ca(2+) uptake required to prevent the arrhythmias induced by a CaMKII-dependent leaky RyR2. ABSTRACT: Mice with constitutive pseudo-phosphorylation at Ser2814-RyR2 (S2814D(+/+) ) have increased propensity to arrhythmias under ß-adrenergic stress conditions. Although abnormal Ca(2+) release from the sarcoplasmic reticulum (SR) has been linked to arrhythmogenesis, the role played by SR Ca(2+) uptake remains controversial. We tested the hypothesis that an increase in SR Ca(2+) uptake is able to rescue the increased arrhythmia propensity of S2814D(+/+) mice. We generated phospholamban (PLN)-deficient/S2814D(+/+) knock-in mice by crossing two colonies, S2814D(+/+) and PLNKO mice (SD(+/+) /KO). SD(+/+) /KO myocytes exhibited both increased SR Ca(2+) uptake seen in PLN knock-out (PLNKO) myocytes and diminished SR Ca(2+) load (relative to PLNKO), a characteristic of S2814D(+/+) myocytes. Ventricular arrhythmias evoked by catecholaminergic challenge (caffeine/adrenaline) in S2814D(+/+) mice in vivo or programmed electric stimulation and high extracellular Ca(2+) in S2814D(+) /(-) hearts ex vivo were significantly diminished by PLN ablation. At the myocyte level, PLN ablation converted the arrhythmogenic Ca(2+) waves evoked by high extracellular Ca(2+) provocation in S2814D(+/+) mice into non-propagated Ca(2+) mini-waves on confocal microscopy. Myocyte Ca(2+) waves, typical of S2814D(+/+) mice, could be evoked in SD(+/+) /KO cells by partially inhibiting SERCA2a. A mathematical human myocyte model replicated these results and allowed for predicting the increase in SR Ca(2+) uptake required to prevent the arrhythmias induced by a Ca(2+) -calmodulin-dependent protein kinase (CaMKII)-dependent leaky RyR2. Our results demonstrate that increasing SR Ca(2+) uptake by PLN ablation can prevent the arrhythmic events triggered by SR Ca(2+) leak due to CaMKII-dependent phosphorylation of the RyR2-S2814 site and underscore the benefits of increasing SERCA2a activity on SR Ca(2+) -triggered arrhythmias.

Improving Organ Utilization to Help Overcome the Tragedies of the Opioid Epidemic.

Death rates from drug overdoses have nearly doubled since 2003, with over 47 000 deaths in 2014. This is largely attributable to the opioid epidemic. If the unfortunate deaths of otherwise healthy people have yielded an increase in organ donors, then this might serve as perhaps the only comforting factor among this tragic and unnecessary loss of life. In this viewpoint, we present data from the Organ Procurement and Transplantation Network (OPTN) that show how the greatest relative increases in the mechanism of death among deceased donors from 2003 to 2014 were drug overdoses. Unfortunately, despite the absolute increase in the number of donors who died from a drug overdose, the mean organ yield was significantly lower than in other categories, in part due to concerns about disease transmission. In this paper, we present data on the changes in donation from donors with a drug overdose as a result of the opioid epidemic and discuss the need to educate transplant candidates and their physicians about the low risk of disease transmission compared to the greater risk of dying on a transplant waitlist.

Assessing opinions in community leadership networks to address health inequalities: a case study from Project IMPACT.

This study demonstrates a novel approach that those engaged in promoting social change in health can use to analyze community power, mobilize it and enhance community capacity to reduce health inequalities. We used community reconnaissance methods to select and interview 33 participants from six leadership sectors in 'Milltown', the New England city where the study was conducted. We used UCINET network analysis software to assess the structure of local leadership and NVivo qualitative software to analyze leaders' views on public health and health inequalities. Our main analyses showed that community power is distributed unequally in Milltown, with our network of 33 divided into an older, largely male and more powerful group, and a younger, largely female group with many 'grassroots' sector leaders who focus on reducing health inequalities. Ancillary network analyses showed that grassroots leaders comprise a self-referential cluster that could benefit from greater affiliation with leaders from other sectors and identified leaders who may serve as leverage points in our overall program of public agenda change to address health inequalities. Our innovative approach provides public health practitioners with a method for assessing community leaders' views, understanding subgroup divides and mobilizing leaders who may be helpful in reducing health inequalities.

Motion-induced interruptions and postural equilibrium in linear lateral accelerations.

This study assesses lateral tipping motion-induced interruptions (MIIs) in a simulated motion environment. The objective is to revisit MII occurrence and sway motion relationship by focusing on the frequency and acceleration of the lateral motion stimulus. Results verify that MIIs increase with increasing peak sway acceleration, but the effect of sway frequency is not as clear as that of acceleration. Complex multidirectional motions create more tipping MIIs than unidirectional motion. Research should incorporate acceleration, frequency and motion complexity as factors influencing MII occurrence. To describe a temporary loss of balance without tipping, the term 'probable' MII is introduced. This term fills the gap between the theoretical definition and a human-centred perception of an MII where loss of balance is not a binary phenomenon. The 'probable' MIIs were 16-67% more common than the 'definite' MIIs. The developed mathematical model of MII occurrence versus sway acceleration (amplitude, frequency) approximated the observed MIIs with less than 9% difference.

The social group influences of US health journalists and their impact on the newsmaking process.

The news media play a vital role in disseminating health information, yet little is known about the social characteristics of health journalists or the impact they have on the newsmaking process. This study examines how the social group influences of US health journalists impact two important aspects of news production--'media agenda-setting' and 'framing'. Using data from a national survey of health and medical science journalists, the authors conducted multivariable logistic regression analyses to study the links between the gender, age and race/ethnicity of respondents, and the ways in which they utilized news sources, other resources, news priorities and story angles. Female respondents were more likely than males to say that educating people to make informed decisions and disseminating new, accurate information are important priorities. Female and minority journalists were more likely than white males to use a variety of sources, and to say it is important to develop the health and scientific literacy of audiences and influence public health behaviors. The gender and race/ethnicity of journalists play an important role in the production of health news. Health educators can foster improved coverage by learning more about the life experiences of health journalists and developing better working relationships with them.

Systematic review of cnidarian microbiomes reveals insights into the structure, specificity, and fidelity of marine associations.

Microorganisms play essential roles in the health and resilience of cnidarians. Understanding the factors influencing cnidarian microbiomes requires cross study comparisons, yet the plethora of protocols used hampers dataset integration. We unify 16S rRNA gene sequences from cnidarian microbiome studies under a single analysis pipeline. We reprocess 12,010 cnidarian microbiome samples from 186 studies, alongside 3,388 poriferan, 370 seawater samples, and 245 cultured Symbiodiniaceae, unifying ~6.5 billion sequence reads. Samples are partitioned by hypervariable region and sequencing platform to reduce sequencing variability. This systematic review uncovers an incredible diversity of 86 archaeal and bacterial phyla associated with Cnidaria, and highlights key bacteria hosted across host sub-phylum, depth, and microhabitat. Shallow (< 30 m) water Alcyonacea and Actinaria are characterized by highly shared and relatively abundant microbial communities, unlike Scleractinia and most deeper cnidarians. Utilizing the V4 region, we find that cnidarian microbial composition, richness, diversity, and structure are primarily influenced by host phylogeny, sampling depth, and ocean body, followed by microhabitat and sampling date. We identify host and geographical generalist and specific Endozoicomonas clades within Cnidaria and Porifera. This systematic review forms a framework for understanding factors governing cnidarian microbiomes and creates a baseline for assessing stress associated dysbiosis.

Establishing a physical health monitoring service for patients on depot antipsychotic medication.

INTRODUCTION: Patients with major mental illness are recognised to be at risk of premature death for a multitude of reasons. This initiative aimed to improve the physical health monitoring of patients prescribed depot antipsychotic medication in a catchment area of ~36 000 in Ireland. OBJECTIVES: International best practice recommends monitoring of blood tests, physical parameters such as weight, BMI, waist circumference and blood pressure, and side effects of patients prescribed antipsychotic medication. A clinic was established to target these interventions. METHODS: A cohort of patients receiving antipsychotics in long-acting injectable form was chosen. A twice-yearly, multidisciplinary health monitoring clinic was established. Evaluation involved an audit of medical records which measured the proportion of those attending the clinic who had blood test monitoring and physical parameters recorded. RESULTS: Before the clinic's implementation, 30% of patients had evidence of some blood test monitoring, 9% had evidence of complete blood testing and one patient had evidence of physical health parameters having been recorded. One year after the implementation 78% of patients had evidence of some blood test monitoring, 61% had evidence of full blood test monitoring and 100% had evidence of physical parameters recorded. CONCLUSIONS: The clinic was positively received by patients, and led to improved teamwork. Recommendations include organising concurrent psychiatric and phlebotomy clinics so that patients may avail of psychiatric review and blood testing at a single appointment. As a result of the increased focus on physical health monitoring, a similar project is planned to target all patients prescribed antipsychotics.

Patients prefer a continuity model of inpatient psychiatric consultant care: a patient survey in the Louth Mental Health Service.

OBJECTIVES: The objective of the paper was to survey patients' preference in relation to a continuity, or split, model of inpatient consultant care in the Louth Mental Health Service. METHODS: A written survey was administered to all patients attending the Louth Mental Health Service over a 2-week period. Participants were asked for their preferred model of care and clinical information was obtained from their clinical notes. RESULTS: In total, 149 patients completed the survey questionnaire and 103 respondents (69%) indicated a preference for a continuity model of inpatient consultant psychiatric care. There was a trend for those who reported a past experience of inpatient hospitalisation to indicate a preference for the continuity model (76% v. 61%, respectively, χ2 3.67, p=0.056). CONCLUSIONS: Patients indicate a preference for a continuity model of inpatient psychiatric care and this is important to consider in service planning. More research is needed to evaluate if any model of consultant care is associated with better patient outcomes.

Military psychologists and cultural competence: exploring implications for the manifestation and treatment of psychological trauma in the British armed forces.

This paper considers the manifestation and treatment of psychological trauma in the military. The article describes how military psychologists conceptualise psychological trauma within the culture of the Armed Forces (AF), which is reflected in the process of acquiring what has been referred to as cultural competency. Psychologists in this context acquire an understanding of the manner in which the psychological and organisational systems and culture of the military affect the presentation of psychological trauma, including post-traumatic stress disorder (PTSD). The paper outlines core psychological features of military life, including some of the ways in which the AF functions effectively as an adaptable fighting force. This highlights, for example, the potential for stigma within and between military personnel who experience mental health difficulties. The article proceeds to examine aspects of help-seeking in military mental healthcare, how symptoms can present at different stages in a deployment process, and the consequences that such problems can cause for military conduct and performance. Psychological care in the military is structured within an occupational mental health ethos, in which psychologists fulfil a range of clinical, organisational and leadership roles. These dynamics are explored with examples of care pathways and clarity on evidence-based interventions for trauma and PTSD in those experiencing military-related psychological injuries. Two vignettes are then offered to illustrate how some of these interventions can be used psychotherapeutically in addressing symptoms pertaining to hyperarousal, hypervigilance, guilt and shame.

Male psychosexual therapy in the UK military.

Military personnel can experience psychosexual difficulties for a variety of reasons. Problems can arise because of psychological trauma, physical injury, consequences arising from pharmacological and surgical complications and social or emotional concerns relating to intrapersonal and interpersonal relationship dynamics. Such individuals might seek to minimise or avoid resolving their pertinent difficulties, while others can experience cultural, personal or organisational barriers to accessing professional help. This paper offers an overview of the development of a national specialist psychosexual therapy service (PST), commenting specifically on the service delivery for male military personnel. It will also consider factors which may support progress in treatment and reflect upon the importance of considering psychosexual functioning in relationships as part of the broader service-life context, which is especially relevant to military personnel.

Military psychological trauma and therapy: a review of EMDR treatment and supervision in the UK Ministry of Defence.

Psychological injury has been associated with military service, and this can result in a variety of mental health symptoms and disorders. A range of barriers to help-seeking have been identified in the military and mental health services have sought to address such factors through effective and efficient care and consultation. The use of eye movement desensitisation and reprocessing forms part of a repertoire of trauma-focused therapies within the UK's Armed Forces. This article will outline the application of this approach within the British military, along with the role of specialist clinical supervision in treating those affected by operational trauma.

Defence Clinical Psychology Service: an overview of clinical psychology in the UK Ministry of Defence.

The Defence Clinical Psychology Service (DCPS) is the professional clinical psychology service and community of clinical psychology practice within UK Ministry of Defence (MoD). The DCPS provides professional clinical care, consultation and research in support of the UK Armed Forces. Regulated by the Health and Care Professions Council, DCPS psychologists are employed as Crown (Civil) Servants within the MoD. Serving as assets of Joint Forces Command within the Defence Primary Healthcare organisation, the professional leadership for such personnel is provided by the office of the Defence Consultant Advisor (DCA) for clinical psychology. The following paper offers an overview of the history, service context, training and mission of the DCPS. Areas for future development are also considered.

History of military psychology.

Military psychology is a specialist discipline within applied psychology. It entails the application of psychological science to military operations, systems and personnel. The specialty was formally founded during World War I in the UK and the USA, and it was integral to many early concepts and interventions for psychological and neuropsychological trauma. It also established a fundamental basis for the psychological assessment and selection of military personnel. During and after World War II, military psychology continued to make significant contributions to aviation psychology, cognitive testing, rehabilitation psychology and many models of psychotherapy. Military psychology now consists of several subspecialties, including clinical, research and occupational psychology, with the latter often referred to in the USA as industrial/organisational psychology. This article will provide an overview of the origins, history and current composition of military psychology in the UK, with select international illustrations also being offered.

Neuropsychology and clinical health psychology in the UK Ministry of Defence.

Neuropsychological testing has been used in a wide range of applications across military settings, including the selection of personnel to engage in covert operations, battlefield assessment and rehabilitation following blast exposure, traumatic brain injury, other neurological conditions and assessment of malingering. Over recent decades, military psychologists have helped to shape the advances in assessing and remediating the psychological sequela that is associated with operationally related neurological and other physical injuries. This paper will present an overview of some of the neuropsychological and related services within the UK Armed Forces, which are provided to service personnel with traumatic brain and other physical injuries.

A new paradigm for predicting risk of Torsades de Pointes during drug development: Commentary on: "Improved prediction of drug-induced Torsades de Pointes through simulations of dynamics and machine learning algorithms".

Drug-induced long QT syndrome (diLQTS) is a clinical entity in which administration of a drug produces marked prolongation of the QT interval on the ECG. DiLQTS places a patient at risk of developing Torsades de Pointes (TdP), a malignant polymorphic ventricular tachycardia associated with arrhythmic sudden cardiac death (SCD). In addition to diLQTS, other clinical risk factors for TdP include female gender, bradycardia, electrolyte disturbances, recent conversion to normal (sinus) rhythm, and congenital LQTS.