Palliative care and Parkinson's disease : meeting summary and recommendations for clinical research

Introduction: Palliative care is an approach to caring for patients and families affected by serious illnesses that focuses on the relief of suffering through the management of medical symptoms, psychosocial issues, advance care planning and spiritual wellbeing. Over the past decade there has been an emerging clinical and research interest in the application of palliative care approaches to Parkinson’s disease (PD) and outpatient palliative care services are now offered by several movement disorders centers. Methods: An International Working Group Meeting on PD and Palliative Care supported by the Parkinson’s Disease Foundation was held in October 2015 to review the current state of the evidence and to make recommendations for clinical research and practice. Results: Topics included: 1) Defining palliative care for PD; 2) Lessons from palliative care for heart failure and other chronic illnesses; 3) Patient and caregiver Needs; 4) Needs assessment tools; 5) Intervention strategies; 6) Predicting prognosis and hospice referrals; 7) Choice of appropriate outcome measures; 8) Implementation, dissemination and education research; and 9) Need for research collaborations. We provide an overview of these discussions, summarize current evidence and practices, highlight gaps in our knowledge and make recommendations for future research. Conclusions: Palliative Care for PD is a rapidly growing area which holds great promise for improving outcomes for PD patients and their caregivers. While clinical research in this area can build from lessons learned in other diseases, there is a need for observational, methodological and interventional research to address the unique needs of PD patients and caregivers

Can variability in the effect of opioids on refractory breathlessness be explained by genetic factors?

© 2015, BMJ Publishing Group. All rights reserved. Objectives: Opioids modulate the perception of breathlessness with a considerable variation in response, with poor correlation between the required opioid dose and symptom severity. The objective of this hypothesis-generating, secondary analysis was to identify candidate single nucleotide polymorphisms (SNP) from those associated with opioid receptors, signalling or pain modulation to identify any related to intensity of breathlessness while on opioids. This can help to inform prospective studies and potentially lead to better tailoring of opioid therapy for refractory breathlessness. Setting: 17 hospice/palliative care services (tertiary services) in 11 European countries. Participants: 2294 people over 18 years of age on regular opioids for pain related to cancer or its treatment. Primary outcome measures: The relationship between morphine dose, breathlessness intensity (European Organisation for Research and Treatment of Cancer Core Quality of Life Questionnaire; EORTCQLQC30 question 8) and 112 candidate SNPs from 25 genes (n=588). Secondary outcome measures: The same measures for people on oxycodone (n=402) or fentanyl (n=429). Results: SNPs not in Hardy-Weinberg equilibrium or with allele frequencies ( < 5%) were removed. Univariate associations between each SNP and breathlessness intensity were determined with Benjamini-Hochberg false discovery rate set at 20%. Multivariable ordinal logistic regression, clustering over country and adjusting for available confounders, was conducted with remaining SNPs. For univariate morphine associations, 1 variant on the 5-hydroxytryptamine type 3B (HTR3B) gene, and 4 on the β-2-arrestin gene (ARRB2) were associated with more intense breathlessness. 1 SNP remained significant in the multivariable model: people with rs7103572 SNP (HTR3B gene; present in 8.4% of the population) were three times more likely to have more intense breathlessness (OR 2.86; 95% CIs 1.46 to 5.62; p=0.002). No associations were seen with fentanyl nor with oxycodone. Conclusions: This large, exploratory study identified 1 biologically plausible SNP that warrants further study in the response of breathlessness to morphine therapy

Specific modulation of airway epithelial tight junctions by apical application of an occludin peptide

Tight junctions are directly involved in regulating the passage of ions and macromolecules (gate functions) in epithelial and endothelial cells. The modulation of these gate functions to transiently regulate the paracellular permeability of large solutes and ions could increase the delivery of pharmacological agents or gene transfer vectors. To reduce the inflammatory responses caused by tight junction-regulating agents, alternative strategies directly targeting specific tight junction proteins could prove to be less toxic to airway epithelia. The apical delivery of peptides corresponding to the first extracellular loop of occludin to transiently modulate apical paracellular flux has been demonstrated in intestinal epithelia. We hypothesized that apical application of these occludin peptides could similarly modulate tight junction permeability in airway epithelia. Thus, we investigated the effects of apically applied occludin peptide on the paracellular permeability of molecular tracers and viral vectors in well differentiated human airway epithelial cells. The effects of occludin peptide on cellular toxicity, tight junction protein expression and localization, and membrane integrity were also assessed. Our data showed that apically applied occludin peptide significantly reduced transepithelial resistance in airway epithelia and altered tight junction permeability in a concentration-dependent manner. These alterations enhanced the paracellular flux of dextrans as well as gene transfer vectors. The occludin peptide redistributed occludin but did not alter the expression or distribution of ZO-1, claudin-1, or claudin-4. These data suggest that specific targeting of occludin could be a better-suited alternative strategy for tight junction modulation in airway epithelial cells compared with current agents that modulate tight junctions

Livestreaming Technology and Online Child Sexual Exploitation and Abuse: A Scoping Review

Livestreaming of child sexual abuse (LSCSA) is an established form of online child sexual exploitation and abuse (OCSEA). However, only a limited body of research has examined this issue. The Covid-19 pandemic has accelerated internet use and user knowledge of livestreaming services emphasizing the importance of understanding this crime. In this scoping review, existing literature was brought together through an iterative search of eight databases containing peer-reviewed journal articles, as well as grey literature. Records were eligible for inclusion if the primary focus was on livestream technology and OCSEA, the child being defined as eighteen years or younger. Fourteen of the 2,218 records were selected. The data were charted and divided into four categories: victims, offenders, legislation, and technology. Limited research, differences in terminology, study design, and population inclusion criteria present a challenge to drawing general conclusions on the current state of LSCSA. The records show that victims are predominantly female. The average livestream offender was found to be older than the average online child sexual abuse offender. Therefore, it is unclear whether the findings are representative of the global population of livestream offenders. Furthermore, there appears to be a gap in what the records show on platforms and payment services used and current digital trends. The lack of a legal definition and privacy considerations pose a challenge to investigation, detection, and prosecution. The available data allow some insights into a potentially much larger issue

Palliative care needs in patients hospitalized with heart failure (PCHF) study: rationale and design

Abstract Aims The primary aim of this study is to provide data to inform the design of a randomized controlled clinical trial (RCT) of a palliative care (PC) intervention in heart failure (HF). We will identify an appropriate study population with a high prevalence of PC needs defined using quantifiable measures. We will also identify which components a specific and targeted PC intervention in HF should include and attempt to define the most relevant trial outcomes. Methods An unselected, prospective, near-consecutive, cohort of patients admitted to hospital with acute decompensated HF will be enrolled over a 2-year period. All potential participants will be screened using B-type natriuretic peptide and echocardiography, and all those enrolled will be extensively characterized in terms of their HF status, comorbidity, and PC needs. Quantitative assessment of PC needs will include evaluation of general and disease-specific quality of life, mood, symptom burden, caregiver burden, and end of life care. Inpatient assessments will be performed and after discharge outpatient assessments will be carried out every 4 months for up to 2.5 years. Participants will be followed up for a minimum of 1 year for hospital admissions, and place and cause of death. Methods for identifying patients with HF with PC needs will be evaluated, and estimates of healthcare utilisation performed. Conclusion By assessing the prevalence of these needs, describing how these needs change over time, and evaluating how best PC needs can be identified, we will provide the foundation for designing an RCT of a PC intervention in HF

Psychiatric symptoms in COVID-19-positive individuals in the general population: Trajectories of depression, anxiety, and insomnia

The present study investigates differences in the trajectories of anxiety, depression, and sleep problems among infected versus non-infected case-controlled individuals. Patients who tested positive for COVID-19 were selected from a representative sample in Norway (N > 10,000). In total, 126 of these individuals were infected during the project period, and this group was analyzed at T5 (May 2021). Of these positive cases, those who had completed both PHQ-9 and GAD-7 at all three measurement points were selected for longitudinal analysis using multilevel modeling. There was a significant difference at T5 between those who had tested positive for COVID-19 and matched controls. Anxiety and depression were reduced among those who tested positive, but there were no differences in trajectory when compared to matched controls. Limitations include the use of self-report measures and the assessment of symptoms at a time when strict virus mitigation protocols were in place. The present findings indicate that individuals who test positive for COVID-19 exhibit higher levels of depressive symptoms after restrictions are lifted. However, comparison of anxiety and depression symptom trajectories with matched controls reveals that both groups exhibited stable or slightly decreased symptoms.publishedVersio

Radio studies of novae: a current status report and highlights of new results

Novae, which are the sudden visual brightening triggered by runaway thermonuclear burning on the surface of an accreting white dwarf, are fairly common and bright events. Despite their astronomical significance as nearby laboratories for the study of nuclear burning and accretion phenomena, many aspects of these common stellar explosions are observationally not well-constrained and remain poorly understood. Radio observations, modeling and interpretation can potentially play a crucial role in addressing some of these puzzling issues. In this review on radio studies of novae, we focus on the possibility of testing and improving the nova models with radio observations, and present a current status report on the progress in both the observational front and theoretical developments. We specifically address the issues of accurate estimation of ejecta mass, multi-phase and complex ejection phenomena, and the effect of a dense environment around novae. With highlights of new observational results, we illustrate how radio observations can shed light on some of these long-standing puzzles.Comment: 19 pages, 4 figures. Review article published in the Bulletin of the Astronomical Society of India (BASI) special issue on nova

The longitudinal pattern of response when morphine is used to treat chronic refractory dyspnea

Background: While evidence supports using sustained release morphine for chronic refractory breathlessness, little is known about the longitudinal pattern of breathlessness intensity as people achieve symptomatic benefit. The aim of this study is to describe this pattern. Methods: This secondary analysis used breathlessness intensity scores (100mm visual analogue scale (VAS)) from a prospective, dose increment study of once daily (morning) sustained release morphine for chronic refractory breathlessness. Participants who achieved < 10% improvement over their own baseline at one week (10 mg) were titrated to 20mg and if no response, another week later to 30mg for one week. Time was standardized at the first day of the week in which participants responded generating twice daily data one week either side of symptomatic benefit. Analysis used random effect mixed modeling. Results: Of the 83 participants, 17/52 responders required > 10 mg: 13 participants (20 mg) and 4 (30 mg), contributing 634 VAS observations. In the week leading to a response, average VAS scores worsened by 0.3mm/ day ( p = 0.16); the average improvement in the first 24 hours of response was 10.9mm (7.0 to 14.7; p < 0.0001), with continued improvement of 2.2 mm/day ( p < 0.001) for six more days. Conclusion: When treating chronic refractory breathlessness with once daily sustained release morphine, titrate to effect, since inadequate dose may generate no response; and following an initial response, further dose increases should not occur for at least one week. Whether further benefit would be derived beyond day six on the dose to which people respond, and what net effect a further dose increase would have are questions yet to be answered

The rise of the citizen author: Writing within social media

The concept of the citizen author is defined and explored within the publishing industry. In order to understand what positions the citizen author currently, and potentially could, hold it begins with a historical view of their rise, including concepts of their eighteenth century antecedents. But the focus of this research is on their growth alongside that of social media platforms. This allows for drawing out relationships between genre fiction, publishers, and the citizen author, which provides a more full understanding of the power dynamics involved when publishers, social media, and the citizen authors mix in the current industry climate.N/