by Jordan Bellis, Lydia Monk, Ritika Jhawar, Galia Pollock, Angela Liu, Charleen Jacobs-McFarlane, Brittany McCrary, Jeffrey Glassberg, Susanna Curtis
Sickle Cell Disease (SCD) is a hemoglobinopathy affecting millions of people globally. Pain, both acute and chronic, affects over half of those living with SCD, but treatment of chronic pain is an ongoing challenge. While opioid treatments are widely used for chronic pain, it’s efficacy is limited, so alternatives must be explored. This protocol outlines a procedure for investigation of dronabinol, an FDA-approved synthetic tetrahydrocannabinol (THC), for the treatment of pain in patients living with SCD and chronic pain. The study is an 8-week, randomized, double-blind placebo-controlled study which aims to assess both the efficacy and safety of this opioid alternative to pain treatment. The study will also track biomarkers of inflammation as THC has demonstrated anti-inflammatory properties, and inflammation is a driver of SCD pain and disease severity. Results from this study have the potential to further clinical understanding of cannabinoids for pain management in Sickle Cell Disease treatment and spark new questions for research.To explore community nurses' experiences of changes to their roles in palliative and end-of-life care.
An e-survey was followed by focus groups.
Fifty-one community nurses with recent experience of delivering end-of-life care in the United Kingdom completed a survey about changes to their roles. A purposive sample of 35 respondents participated in focus groups exploring these changes in more depth; thematic analysis was used with constant comparison.
As well as two new roles—prescribing and verifying death—many participants talked about a broader expansion of their role, increasing their leadership in making complex end-of-life care decisions with patients and families. Most nurses expressed pride in their new knowledge and skills, and satisfaction with the care they were providing. Yet many also expressed distress that heavy workloads impaired their capacity both to provide good clinical care and to train junior colleagues. The importance of General Practitioner support with complex cases was often highlighted, but accessing such support was sometimes difficult.
While welcoming the opportunity to extend their palliative care roles, many participants indicated experiencing moral distress.
Excessive workloads and patchy medical support threaten the retention of the experienced nurses upon whom community palliative care depends.
Our findings suggest that new and extended palliative care roles are viewed positively by nurses. To be sustainable, these changes require better workload management and consistent medical back-up.
We adhered to relevant EQUATOR guidelines, using the SRQR checklist.
Our Public and Clinician Advisory Group helped shape questions and commented on findings.
Immunotherapy with anti-programmed cell death protein 1 (anti-PD-1) inhibitors has revolutionised the treatment of many solid tumours, however, only 30–40% of patients will have a lasting clinical response. Tumour-derived extracellular vesicles (EVs) have been implicated in the spread of solid tumours and resistance to these agents. A lectin-affinity plasmapheresis device called the Hemopurifier (HP) has been developed and shown to remove EVs in vitro and in patients. We hypothesise that the treatment of patients who are not improving on a regimen that includes an anti-PD-1 agent will be safe, decrease EV concentrations and improve antitumour T cell activity.
This safety, feasibility and dose-finding study is designed in a 3+3 safety study design with three treatment cohorts. Participants who are determined not to be responding to a regimen that includes an anti-PD-1 agent will be assigned to receive either one, two or three (HP) treatments over a 1-week period prior to their next scheduled dose of anti-PD-1 antibody. Advancement from one cohort to the next will be determined by a Data and Safety Monitoring Board. Data collection will include adverse events, safety labs, EV concentrations and T cell measurements, repeat imaging and survival status.
The primary outcome of the study will be the safety of the HP in this population, with additional endpoints to include the kinetics of EV removal and rebound following HP treatment, in addition to the effects on T cell numbers and activity.
The clinical protocol and amendment to the study protocol have been approved by the Central Adelaide Local Health Network Human Research Ethics Committee for Royal Adelaide Hospital (reference number 2024/HRE00031) and the Bellberry Human Research Ethics Committee for Pindara Private Hospital and Genesis Care/Royal North Shore Hospital (reference number 2024-06-724-A-6). The Therapeutic Goods Administration has been notified. The clinical trial is listed on the Australian New Zealand Clinical Trials Registry. Informed Consent is obtained from all participants prior to any protocol procedures being performed. Results of the main trial and each of the secondary endpoints will be submitted for publication in a peer-reviewed journal.
Australia New Zealand registration number ACTRN12624000732583.
Scoping reviews, mapping reviews and evidence and gap maps (collectively known as ‘big picture reviews’) in health continue to gain popularity within the evidence ecosystem. These big-picture reviews are beneficial for policy-makers, guideline developers and researchers within the field of health for understanding the available evidence, characteristics, concepts and research gaps, which are often needed to support the development of policies, guidelines and practice. However, these reviews often face criticism related to poor and inconsistent methodological conduct and reporting. There is a need to understand which areas of these reviews require further methodological clarification and exploration. The aim of this project is to develop a research agenda for scoping reviews, mapping reviews and evidence and gap maps in health by identifying and prioritising specific research questions related to methodological uncertainties.
A modified e-Delphi process will be adopted. Participants (anticipated N=100) will include patients, clinicians, the public, researchers and others invested in creating a strategic research agenda for these reviews. This Delphi will be completed in four consecutive stages, including a survey collecting the methodological uncertainties for each of the big picture reviews, the development of research questions based on that survey and two further surveys and four workshops to prioritise the research questions.
This study was approved by the University of Adelaide Human Research Ethics Committee (H-2024-188). The results will be communicated through open-access peer-reviewed publications and conferences. Videos and infographics will be developed and placed on the JBI (previously Joanna Briggs Institute) Scoping Review Network webpage.