Self-reported MeasUrement of Physical and PsychosOcial Symptoms Response Tool (SUPPORT-dialysis): systematic symptom assessment and management in patients on in-centre haemodialysis - a parallel arm, non-randomised feasibility pilot study protocol.

INTRODUCTION: Patients with kidney failure experience symptoms that are often under-recognised and undermanaged. These symptoms negatively impact health-related quality of life and are associated with adverse clinical outcomes. Regular symptom assessment, using electronic patient reported outcomes measure (ePROMs) linked to systematic symptom management, could improve such outcomes. Clinical implementation of ePROMs have been successful in routine oncology care, but not used for patients on dialysis. In this study, we describe a pilot study of ePROM-based systematic symptom monitoring and management intervention in patients treated with in-centre haemodialysis. METHODS AND ANALYSIS: This is a parallel-arm, controlled pilot of adult patients receiving in-centre maintenance haemodialysis. Participants in the intervention arm will complete ePROMs once a month for 6 months. ePROMs will be scored real time and the results will be shared with participants and with the clinical team. Moderate-severe symptoms will be flagged using established cut-off scores. Referral options for those symptoms will be shared with the clinical team, and additional symptom management resources will also be provided for both participants and clinicians. Participants in the control arm will be recruited at a different dialysis unit, to prevent contamination. They will receive usual care, except that they will complete ePROMs without the presentation of results to participants of the clinical team. The primary objectives of the pilot are to assess (1) the feasibility of a larger, randomised clinical effectiveness trial and (2) the acceptability of the intervention. Interviews conducted with participants and staff will be assessed using a content analysis approach. ETHICS AND DISSEMINATION: Ethical approval for this study was obtained from the University Health Network (REB#21-5199) and the William Osler Health System (#23-0005). All study procedures will be conducted in accordance with the standards of University Health Network research ethics board and with the 1964 Helsinki declaration and its later amendments. Results of this study will be shared with participants, patients on dialysis and other stakeholders using lay language summaries, oral presentations to patients and nephrology professionals. We will also be publishing the results in a peer-reviewed journal and at scientific meetings. PROTOCOL VERSION: 4 (16 November 2022). TRIAL REGISTRATION NUMBER: NCT05515991.

The quality of death and dying of patients with advanced cancer in hospice care in Uganda and Kenya.

OBJECTIVES: Minimal information is available about the quality of dying and death in Uganda and Kenya, which are African leaders in palliative care. We investigated the quality of dying and death in patients with advanced cancer who had received hospice care in Uganda or Kenya. METHODS: Observational study with bereaved caregivers of decedents (Uganda: n = 202; Kenya: n = 127) with advanced cancer who had received care from participating hospices in Uganda or Kenya. Participants completed the Quality of Dying and Death questionnaire and a measure of family satisfaction with cancer care (FAMCARE). RESULTS: Quality of Dying and Death Preparation and Connectedness subscales were most frequently rated as good to almost perfect for patients in both countries (45.5% to 81.9%), while Symptom Control and Transcendence subscales were most frequently rated as intermediate (42.6% to 60.4%). However, 35.4% to 67.7% of caregivers rated overall quality of dying and overall quality of death as terrible to poor. Ugandan caregivers reported lower Preparation, Connectedness, and Transcendence (p < .001). Controlling for covariates, overall quality of dying was associated with better Symptom Control in both countries (p < .001) and Transcendence in Uganda (p = .010); overall quality of death, with greater Transcendence in Uganda (p = .004); and family satisfaction with care, with better Preparation in Uganda (p = .004). SIGNIFICANCE OF RESULTS: Findings indicate strengths in spiritual and social domains of the quality of dying and death in patients who received hospice care in Uganda and Kenya, but better symptom control is needed to improve this outcome in these countries.

Differences in Palliative Care Provision by Primary and Specialist Providers Supporting Patients With COVID-19: A Qualitative Study.

Objectives: To describe the delivery of palliative care by primary providers (PP) and specialist providers (SP) to hospitalized patients with COVID-19. Methods: PP and SP completed interviews about their experiences providing palliative care. Results were analyzed using thematic analysis. Results: Twenty-one physicians (11 SP, 10 PP) were interviewed. Six thematic categories emerged. Care provision: PP and SP described their support of care discussions, symptom management, managing end of life, and care withdrawal. Patients provided care: PP described patients at end of life, with comfort-focused goals; SP included patients seeking life-prolonging treatments. Approach to symptom management: SP described comfort, and PP discomfort in providing opioids with survival-focused goals. Goals of care: SP felt these conversations were code status-focused. Supporting family: both groups indicated difficulties engaging families due to visitor restrictions; SP also outlined challenges in managing family grief and need to advocate for family at the bedside. Care coordination: internist PP and SP described difficulties supporting those leaving the hospital. Conclusion: PP and SP may have a different approach to care, which may affect consistency and quality of care.

Quality of Dying and Death of Patients With Cancer in Hospice Care in Uganda.

PURPOSE: Despite advances in palliative care in Uganda, there has been relatively little recent patient-centered research investigating end-of-life outcomes in this region. We assessed the quality of dying and death of patients with cancer in hospice care in Uganda. METHODS: Bereaved caregivers of patients who received hospice care in Uganda and died 2-12 months earlier (N = 201) completed the Quality of Dying and Death Questionnaire, which includes 31 items and single-item ratings of overall quality of dying and moment of death, and the FAMCARE measure of family satisfaction with cancer care. RESULTS: Caregivers reported low-intermediate overall quality of dying (mean [M] standard deviation [SD], 3.25 [2.98]) and overall quality of moment of death (M [SD], 3.59 [3.51]), with 47.0% of the ratings of these two outcomes in the poor range, but the mean family satisfaction with care was high (M [SD], 77.75 [10.26]). Most Quality of Dying and Death Questionnaire items (74.2%) were rated within the intermediate range. Items rated within the good range were religious-spiritual, interpersonal, and personal facets; two items within the poor range reflected physical functioning. Overall quality of dying was most strongly correlated with pain control (Spearman's rho [rs] = 0.45, P < .001), and overall quality of moment of death with state of consciousness before death and being unafraid of dying (rs = 0.42, P < .001). The FAMCARE score was not correlated with overall quality of dying or moment of death (P = .576-.813). Only one FAMCARE item, information on managing patient's pain, was correlated with overall quality of moment of death (rs = -0.19, P = .008). CONCLUSION: End-of-life care in hospices in Uganda requires further improvement, particularly with regard to symptom control. Patient-centered data could bolster advocacy efforts to support quality improvement of palliative care in this and other countries.

Physician perceptions of restrictive visitor policies during the COVID-19 pandemic: a qualitative study.

BACKGROUND: Little is understood of the consequences of restrictive visitor policies that were implemented in hospitals to minimize risk of infection during the COVID-19 pandemic. The objective of this study was to describe physician experiences with these policies and reflections of their effects. METHODS: We conducted semistructured phone interviews from September 2020 to March 2021 with physicians practising in Ontario hospitals, recruited via professional networks and snowball sampling. We audio-recorded, transcribed and analyzed interviews to describe and interpret overarching themes by thematic analysis. RESULTS: We interviewed 21 physicians (5 intensivists, 5 internists, 11 specialists in palliative care). Four main thematic categories emerged, including provider, system, patient and caregiver effects. Provider-related factors included increased time and effort on communication with a need to establish limits; increased effort to develop rapport with caregivers; lack of caregiver input on patient care; the need to act as a caregiver surrogate; and the emotional toll of being a gatekeeper or advocate for visitors, exacerbated by lack of evidence for restrictions and inconsistent enforcement. System effects included the avoidance of hospital admission and decreased length of stay, leading to readmissions, increased deaths at home and avoidance of transfer to other facilities with similar policies. Patient-related factors included isolation and dying alone; lack of caregiver advocacy; and prioritization of visitor presence that, at times, resulted in a delay or withdrawal of aspects of care. Caregiver-related factors included inability to personally assess patient health, leading to poor understanding of patient status and challenging decision-making; perceived inadequate communication; difficulty accessing caregiver supports; and increased risk of complicated grief. Participants highlighted a disproportionate effect on older adults and people who did not speak English. INTERPRETATION: Our study highlights substantial negative consequences of restrictive visitor policies, with heightened effects on older adults and people who did not speak English. Research is required to identify whether the benefits of visitor restrictions on infection control outweigh the numerous deleterious consequences to patients, families and care providers.

Protocol for the development and multisite validation of the Quality of Dying and Death-Revised Global Version scale.

INTRODUCTION: Evaluating the quality of dying and death is essential to ensure high-quality end-of-life care. The Quality of Dying and Death (QODD) scale is the best-validated measure of the construct, but many items are not relevant to participants, particularly in low-resource settings. The aim of this multisite cross-sectional study is to develop and validate the QODD-Revised Global Version (QODD-RGV), to enhance ease of completion and relevance in higher-resource and lower-resource settings. METHODS AND ANALYSIS: This study will be a two-arm, multisite evaluation of the cultural relevance, reliability and validity of the QODD-RGV across four participating North American hospices and a palliative care site in Malawi, Africa. Bereaved caregivers and healthcare providers of patients who died at a participating North American hospice and bereaved caregivers of patients who died of cancer at the Malawian palliative care site will complete the QODD-RGV and validation measures. Cognitive interviews with subsets of North American and Malawian caregivers will assess the perceived relevance of the scale items. Psychometric evaluations will include internal consistency and convergent and concurrent validity. ETHICS AND DISSEMINATION: The North American arm received approval from the University Health Network Research Ethics Board (21-5143) and the University of North Carolina Institutional Review Board (21-1172). Ethics approval for the Malawi arm is being obtained from the University of North Carolina Institutional Review Board and the Malawian National Health Science Research Committee. Study findings will be disseminated through publication in peer-reviewed journals and conference presentations.

Identifying barriers and facilitators to palliative care integration in the management of hospitalized patients with COVID-19: A qualitative study.

BACKGROUND: Palliative care is well suited to support patients hospitalized with COVID-19, but integration into care has been variable and generally poor. AIM: To understand barriers and facilitators of palliative care integration for hospitalized patients with COVID-19. METHODS: Internists, Intensivists and palliative care physicians completed semi-structured interviews about their experiences providing care to patients with COVID-19. Results were analysed using thematic analysis. RESULTS: Twenty-three physicians (13 specialist palliative care, five intensivists, five general internists) were interviewed; mean ± SD age was 42 ± 11 years and 61% were female. Six thematic categories were described including: patient and family factors, palliative care knowledge, primary provider factors, COVID-19 specific factors, palliative care service factors, and leadership and culture factors. Patient and family factors included patient prognosis, characteristics that implied prognosis (i.e., age, etc.), and goals of care. Palliative care knowledge included confidence in primary palliative care skills, misperception that COVID-19 is not a 'palliative diagnosis', and the need to choose quantity or quality of life in COVID-19 management. Primary provider factors included available time, attitude, and reimbursement. COVID-19 specific factors were COVID-19 as an impetus to act, uncertain illness trajectory, treatments and outcomes, and infection control measures. Palliative care service factors were accessibility, adaptability, and previous successful relationships. Leadership and culture factors included government-mandated support, presence at COVID planning tables, and institutional and unit culture. CONCLUSION: The study findings highlight the need for leadership support for formal integrated models of palliative care for patients with COVID-19, a palliative care role in pandemic planning, and educational initiatives with primary palliative care providers.

ABO blood groups influence macrophage-mediated phagocytosis of Plasmodium falciparum-infected erythrocytes.

Erythrocyte polymorphisms associated with a survival advantage to Plasmodium falciparum infection have undergone positive selection. There is a predominance of blood group O in malaria-endemic regions, and several lines of evidence suggest that ABO blood groups may influence the outcome of P. falciparum infection. Based on the hypothesis that enhanced innate clearance of infected polymorphic erythrocytes is associated with protection from severe malaria, we investigated whether P. falciparum-infected O erythrocytes are more efficiently cleared by macrophages than infected A and B erythrocytes. We show that human macrophages in vitro and mouse monocytes in vivo phagocytose P. falciparum-infected O erythrocytes more avidly than infected A and B erythrocytes and that uptake is associated with increased hemichrome deposition and high molecular weight band 3 aggregates in infected O erythrocytes. Using infected A(1), A(2), and O erythrocytes, we demonstrate an inverse association of phagocytic capacity with the amount of A antigen on the surface of infected erythrocytes. Finally, we report that enzymatic conversion of B erythrocytes to type as O before infection significantly enhances their uptake by macrophages to observed level comparable to that with infected O wild-type erythrocytes. These data provide the first evidence that ABO blood group antigens influence macrophage clearance of P. falciparum-infected erythrocytes and suggest an additional mechanism by which blood group O may confer resistance to severe malaria.

Combinations of host biomarkers predict mortality among Ugandan children with severe malaria: a retrospective case-control study.

BACKGROUND: Severe malaria is a leading cause of childhood mortality in Africa. However, at presentation, it is difficult to predict which children with severe malaria are at greatest risk of death. Dysregulated host inflammatory responses and endothelial activation play central roles in severe malaria pathogenesis. We hypothesized that biomarkers of these processes would accurately predict outcome among children with severe malaria. METHODOLOGY/FINDINGS: Plasma was obtained from children with uncomplicated malaria (n = 53), cerebral malaria (n = 44) and severe malarial anemia (n = 59) at time of presentation to hospital in Kampala, Uganda. Levels of angiopoietin-2, von Willebrand Factor (vWF), vWF propeptide, soluble P-selectin, soluble intercellular adhesion molecule-1 (ICAM-1), soluble endoglin, soluble FMS-like tyrosine kinase-1 (Flt-1), soluble Tie-2, C-reactive protein, procalcitonin, 10 kDa interferon gamma-induced protein (IP-10), and soluble triggering receptor expressed on myeloid cells-1 (TREM-1) were determined by ELISA. Receiver operating characteristic (ROC) curve analysis was used to assess predictive accuracy of individual biomarkers. Six biomarkers (angiopoietin-2, soluble ICAM-1, soluble Flt-1, procalcitonin, IP-10, soluble TREM-1) discriminated well between children who survived severe malaria infection and those who subsequently died (area under ROC curve>0.7). Combinational approaches were applied in an attempt to improve accuracy. A biomarker score was developed based on dichotomization and summation of the six biomarkers, resulting in 95.7% (95% CI: 78.1-99.9) sensitivity and 88.8% (79.7-94.7) specificity for predicting death. Similar predictive accuracy was achieved with models comprised of 3 biomarkers. Classification tree analysis generated a 3-marker model with 100% sensitivity and 92.5% specificity (cross-validated misclassification rate: 15.4%, standard error 4.9%). CONCLUSIONS: We identified novel host biomarkers of pediatric severe and fatal malaria (soluble TREM-1 and soluble Flt-1) and generated simple biomarker combinations that accurately predicted death in an African pediatric population. While requiring validation in further studies, these results suggest the utility of combinatorial biomarker strategies as prognostic tests for severe malaria.