Informed consent in palliative care clinical trials: challenging but possible

Obtaining informed consent is a key protection that should be afforded universally to people using health services and the basis around which any participation in clinical trials is built. Randomized controlled effectiveness studies are necessary to answer key questions in hospice and palliative care, in order to help systematically improve the quality of care. In order to be properly generalizable, such trials need to have broad inclusion criteria to reflect the population most likely to be affected by the condition. The inclusion of patients who are seriously ill, and therefore potentially vulnerable, requires careful exploration of ethical and legal principles that underpin informed consent. Specific challenges in obtaining informed consent for randomised clinical trials (RCTs) in clinically unstable populations such as hospice and palliative care include higher rates of people with impaired cognitive capacity as well as interventional studies in clinical situations which may present as a sudden change in condition. None of these challenges is unique to hospice and palliative care research, but the combination and frequency with which they are encountered require systematic and considered solutions. This article outlines five different ethically valid consent approaches and discusses their applicability to hospice and palliative care research trials. These include: consent by the patient (at the time of enrolment, in advance of the study, or delayed until after the study has commenced); a proxy (or legally authorised representative); or a consent waiver. Increased use of the less traditional modes of informed consent may lead to greater participation rates in hospice and palliative care trials, thereby improving the evidence base more rapidly in part by better reflecting the population served and hence improving generalizability

Epilogue: Reflections from International Mentors of the Quality Improvement Training Programme in India

The article collates the narratives of experiences of the international faculty who mentored the quality improvement teams from India since 2017

An Uncertain Dominion: Irish Psychiatry, Methadone, and the Treatment of Opiate Abuse

This paper investigates some productive ambiguities around the medical administration of methadone in the Republic of Ireland. The tensions surrounding methadone maintenance therapy (MMT) are outlined, as well as the sociohistorical context in which a serious heroin addiction problem in Ireland developed. Irish psychiatry intervened in this situation, during a time of institutional change, debates concerning the nature of addiction, moral panics concerning heroin addiction in Irish society and the recent boom in the Irish economy, known popularly as the Celtic Tiger. A particular history of this sort illuminates how technologies like MMT become cosmopolitan, settling into, while changing, local contexts

Molecular imaging of drug transit through the blood-brain barrier with MALDI mass spectrometry imaging

Drug transit through the blood-brain barrier (BBB) is essential for therapeutic responses in malignant glioma. Conventional methods for assessment of BBB penetrance require synthesis of isotopically labeled drug derivatives. Here, we report a new methodology using matrix assisted laser desorption ionization mass spectrometry imaging (MALDI MSI) to visualize drug penetration in brain tissue without molecular labeling. In studies summarized here, we first validate heme as a simple and robust MALDI MSI marker for the lumen of blood vessels in the brain. We go on to provide three examples of how MALDI MSI can provide chemical and biological insights into BBB penetrance and metabolism of small molecule signal transduction inhibitors in the brain – insights that would be difficult or impossible to extract by use of radiolabeled compounds

Mothers with Mental Health Disorders: Mental Health Promotion in the Context of Parenting

Parenting is a meaningful role for the majority of American women, including those with mental health disorders. Success in this role, particularly for women with mental health disorders, would seem to be intimately related to mental health promotion, the recovery process, and successful functioning in other major life domains (e.g., employment, community living, and personal health and well-being). The achievement of maximum social participation for women with mental health disorders may hinge on addressing the challenges they face as parents

High-risk sexual offenders: an examination of sexual fantasy, sexual paraphilia, psychopathy, and offence characteristics

High-risk sexual offenders are a complex and heterogeneous group of offenders about whom researchers, clinicians, and law enforcement agencies still know relatively little. In response to the paucity of information that is specifically applicable to high-risk offenders, the present study investigated the potential influence of sexual fantasy, sexual paraphilia, and psychopathy on the offending behaviour of 139 of the highest risk sexual offenders in one province of Canada. The sample included 41 child molesters, 42 rapists, 18 rapist/ molesters, 30 mixed offenders, and 6 "other" sexual offenders. Two offenders could not be categorized by type due to insufficient file information. Data analyses revealed significant differences between offender types for a number of criminal history variables including past sexual and nonsexual convictions, number of victims, weapon use, and age of offending onset. Further, there were significant differences between offender types for sexual fantasy themes, paraphilia diagnoses, and levels of psychopathy. For example, results revealed that offenders' sexual fantasies were significantly more likely to correspond with the specific type of index sexual offence that they had committed. Further, offenders scoring high in psychopathy were significantly more likely to have a sadistic paraphilia than offenders with either low or moderate psychopathy scores. Results from the current study provide a refined and informed understanding of sexual offending behaviour with important implications for future research, assessment, and treatment, as well as law enforcement practices when working with high-risk sexual offenders

RVD: A Handheld Device-Based Fundus Video Dataset for Retinal Vessel Segmentation

Retinal vessel segmentation is generally grounded in image-based datasets collected with bench-top devices. The static images naturally lose the dynamic characteristics of retina fluctuation, resulting in diminished dataset richness, and the usage of bench-top devices further restricts dataset scalability due to its limited accessibility. Considering these limitations, we introduce the first video-based retinal dataset by employing handheld devices for data acquisition. The dataset comprises 635 smartphone-based fundus videos collected from four different clinics, involving 415 patients from 50 to 75 years old. It delivers comprehensive and precise annotations of retinal structures in both spatial and temporal dimensions, aiming to advance the landscape of vasculature segmentation. Specifically, the dataset provides three levels of spatial annotations: binary vessel masks for overall retinal structure delineation, general vein-artery masks for distinguishing the vein and artery, and fine-grained vein-artery masks for further characterizing the granularities of each artery and vein. In addition, the dataset offers temporal annotations that capture the vessel pulsation characteristics, assisting in detecting ocular diseases that require fine-grained recognition of hemodynamic fluctuation. In application, our dataset exhibits a significant domain shift with respect to data captured by bench-top devices, thus posing great challenges to existing methods. In the experiments, we provide evaluation metrics and benchmark results on our dataset, reflecting both the potential and challenges it offers for vessel segmentation tasks. We hope this challenging dataset would significantly contribute to the development of eye disease diagnosis and early prevention

Europa's FUV auroral tail on Jupiter

peer reviewedaudience: researcher, professional, studentUltraviolet images of Jupiter's northern aurora obtained in 2005 confirm the existence of an electromagnetic interaction between Europa and the Jovian ionosphere. The auroral signature shows a two-component structure: a quasi-circular Europa spot, followed by a previously undetected faint tail emission trailing in the direction of corotation flow. The characteristic brightness for the auroral spot is similar to 14 +/- 1 kR above background, and approximately 7 +/- 1 kR for the tail. The spot's size is similar to 1100 km, magnetically mapping to an interaction region <= 15 Europa diameters. The auroral tail extends over similar to 5000 km, which maps along a region of at least 70 Europa diameters. The ultraviolet power emitted by both components varies from a fraction to several GW. The present study suggests auroral interaction at Europa similar to that at Io, but scaled-down by an order of magnitude, including a sub-corotating plasma plume in the geometrical wake of Europa

Phase II, double blind, placebo controlled, multi-site study to evaluate the safety, feasibility and desirability of conducting a phase III study of anamorelin for anorexia in people with small cell lung cancer: a study protocol (LUANA trial)

AbstractAnorexia is experienced by most people with lung cancer during the course of their disease and treatment. Anorexia reduces response to chemotherapy and the ability of patients to cope with, and complete their treatment leading to greater morbidity, poorer prognosis and outcomes. Despite the significant importance of cancer-related anorexia, current therapies are limited, have marginal benefits and unwarranted side effects. In this multi-site, randomised, double blind, placebo controlled, phase II trial, participants will be randomly assigned (1:1) to receive once-daily oral dosing of 100mg of anamorelin HCl or matched placebo for 12 weeks. Participants can then opt into an extension phase to receive blinded intervention for another 12 weeks (weeks 13-24) at the same dose and frequency. Adults (≥18 years) with small cell lung cancer (SCLC); newly diagnosed with planned systemic therapy OR with first recurrence of disease following a documented disease-free interval ≥6 months, AND with anorexia (i.e., ≤ 37 points on the 12-item Functional Assessment of Anorexia Cachexia Treatment (FAACT A/CS) scale) will be invited to participate. Primary outcomes are safety, desirability and feasibility outcomes related to participant recruitment, adherence to interventions, and completion of study tools to inform the design of a robust Phase III effectiveness trial. Secondary outcomes are the effects of study interventions on body weight and composition, functional status, nutritional intake, biochemistry, fatigue, harms, survival and quality of life. Primary and secondary efficacy analysis will be conducted at 12 weeks. Additional exploratory efficacy and safety analyses will also be conducted at 24 weeks to collect data over longer treatment duration. The feasibility of economic evaluations in Phase III trial will be assessed, including the indicative costs and benefits of anamorelin for SCLC to the healthcare system and society, the choice of methods for data collection and the future evaluation design. The trial has been registered with the Australian New Zealand Clinical Trials Registry [ACTRN12622000129785] and approved by the South Western Sydney Local Health District Human Research Ethics Committee [2021/ETH11339]