Understanding barriers and facilitators to palliative and end-of-life care research: a mixed method study of generalist and specialist health, social care, and research professionals

Background: Palliative care provision should be driven by high quality research evidence. However, there are barriers to conducting research. Most research attention focuses on potential patient barriers; staff and organisational issues that affect research involvement are underexplored. The aim of this research is to understand professional and organisational facilitators and barriers to conducting palliative care research. Methods: A mixed methods study, using an open cross-sectional online survey, followed by working groups using nominal group techniques. Participants were professionals interested in palliative care research, working as generalist/specialist palliative care providers, or palliative care research staff across areas of North West England. Recruitment was via local health organisations, personal networks, and social media in 2022. Data were examined using descriptive statistics and content analysis. Results: Participants (survey n = 293, working groups n = 20) were mainly from clinical settings (71%) with 45% nurses and 45% working more than 10 years in palliative care. 75% were not active in research but 73% indicated a desire to increase research involvement. Key barriers included lack of organisational research culture and capacity (including prioritisation and available time); research knowledge (including skills/expertise and funding opportunities); research infrastructure (including collaborative opportunities across multiple organisations and governance challenges); and patient and public perceptions of research (including vulnerabilities and burdens). Key facilitators included dedicated research staff, and active research groups, collaborations, and networking opportunities. Conclusions: Professionals working in palliative care are keen to be research active, but lack time, skills, and support to build research capabilities and collaborations. A shift in organisational culture is needed to enhance palliative care research capacity and collaborative opportunities across clinical and research settings.NIH

Understanding barriers and facilitators to palliative and end-of-life care research: a mixed method study of generalist and specialist health, social care, and research professionals

Background: Palliative care provision should be driven by high quality research evidence. However, there are barriers to conducting research. Most research attention focuses on potential patient barriers; staff and organisational issues that affect research involvement are underexplored. The aim of this research is to understand professional and organisational facilitators and barriers to conducting palliative care research. Methods: A mixed methods study, using an open cross-sectional online survey, followed by working groups using nominal group techniques. Participants were professionals interested in palliative care research, working as generalist/specialist palliative care providers, or palliative care research staff across areas of North West England. Recruitment was via local health organisations, personal networks, and social media in 2022. Data were examined using descriptive statistics and content analysis. Results: Participants (survey n = 293, working groups n = 20) were mainly from clinical settings (71%) with 45% nurses and 45% working more than 10 years in palliative care. 75% were not active in research but 73% indicated a desire to increase research involvement. Key barriers included lack of organisational research culture and capacity (including prioritisation and available time); research knowledge (including skills/expertise and funding opportunities); research infrastructure (including collaborative opportunities across multiple organisations and governance challenges); and patient and public perceptions of research (including vulnerabilities and burdens). Key facilitators included dedicated research staff, and active research groups, collaborations, and networking opportunities. Conclusions: Professionals working in palliative care are keen to be research active, but lack time, skills, and support to build research capabilities and collaborations. A shift in organisational culture is needed to enhance palliative care research capacity and collaborative opportunities across clinical and research settings

Multiorgan MRI findings after hospitalisation with COVID-19 in the UK (C-MORE): a prospective, multicentre, observational cohort study

Introduction: The multiorgan impact of moderate to severe coronavirus infections in the post-acute phase is still poorly understood. We aimed to evaluate the excess burden of multiorgan abnormalities after hospitalisation with COVID-19, evaluate their determinants, and explore associations with patient-related outcome measures. Methods: In a prospective, UK-wide, multicentre MRI follow-up study (C-MORE), adults (aged ≥18 years) discharged from hospital following COVID-19 who were included in Tier 2 of the Post-hospitalisation COVID-19 study (PHOSP-COVID) and contemporary controls with no evidence of previous COVID-19 (SARS-CoV-2 nucleocapsid antibody negative) underwent multiorgan MRI (lungs, heart, brain, liver, and kidneys) with quantitative and qualitative assessment of images and clinical adjudication when relevant. Individuals with end-stage renal failure or contraindications to MRI were excluded. Participants also underwent detailed recording of symptoms, and physiological and biochemical tests. The primary outcome was the excess burden of multiorgan abnormalities (two or more organs) relative to controls, with further adjustments for potential confounders. The C-MORE study is ongoing and is registered with ClinicalTrials.gov, NCT04510025. Findings: Of 2710 participants in Tier 2 of PHOSP-COVID, 531 were recruited across 13 UK-wide C-MORE sites. After exclusions, 259 C-MORE patients (mean age 57 years [SD 12]; 158 [61%] male and 101 [39%] female) who were discharged from hospital with PCR-confirmed or clinically diagnosed COVID-19 between March 1, 2020, and Nov 1, 2021, and 52 non-COVID-19 controls from the community (mean age 49 years [SD 14]; 30 [58%] male and 22 [42%] female) were included in the analysis. Patients were assessed at a median of 5·0 months (IQR 4·2–6·3) after hospital discharge. Compared with non-COVID-19 controls, patients were older, living with more obesity, and had more comorbidities. Multiorgan abnormalities on MRI were more frequent in patients than in controls (157 [61%] of 259 vs 14 [27%] of 52; p<0·0001) and independently associated with COVID-19 status (odds ratio [OR] 2·9 [95% CI 1·5–5·8]; padjusted=0·0023) after adjusting for relevant confounders. Compared with controls, patients were more likely to have MRI evidence of lung abnormalities (p=0·0001; parenchymal abnormalities), brain abnormalities (p<0·0001; more white matter hyperintensities and regional brain volume reduction), and kidney abnormalities (p=0·014; lower medullary T1 and loss of corticomedullary differentiation), whereas cardiac and liver MRI abnormalities were similar between patients and controls. Patients with multiorgan abnormalities were older (difference in mean age 7 years [95% CI 4–10]; mean age of 59·8 years [SD 11·7] with multiorgan abnormalities vs mean age of 52·8 years [11·9] without multiorgan abnormalities; p<0·0001), more likely to have three or more comorbidities (OR 2·47 [1·32–4·82]; padjusted=0·0059), and more likely to have a more severe acute infection (acute CRP >5mg/L, OR 3·55 [1·23–11·88]; padjusted=0·025) than those without multiorgan abnormalities. Presence of lung MRI abnormalities was associated with a two-fold higher risk of chest tightness, and multiorgan MRI abnormalities were associated with severe and very severe persistent physical and mental health impairment (PHOSP-COVID symptom clusters) after hospitalisation. Interpretation: After hospitalisation for COVID-19, people are at risk of multiorgan abnormalities in the medium term. Our findings emphasise the need for proactive multidisciplinary care pathways, with the potential for imaging to guide surveillance frequency and therapeutic stratification

The Efficacy of Passive Valve Antimicrobial Swab Caps Against Existing Clabsi Prevention Bundle in an Adult Hematology Inpatient Population: A Quality Improvement Initiative

Background: Central line associated blood stream infections (CLABSI) have been the costliest of all healthcare associated infections. The average CLABSI cost is approximately 46,000 (Haddadin & Regunath, 2019). Most cases may be preventable with utilization of aseptic techniques, surveillance, and management through local protocols. The majority of CLABSI occur more than five days after central vascular access (CVA); therefore, there has been a growing focus on central line handling and maintenance techniques. CLABSI prevention data has been largely focused on the intensive care unit (ICU) patient population where an average of about half of patients have CVA. There have been few studies exploring the rates of CLABSI in the adult hematology population, a population with unique risk factors due to their immunosuppressing treatments and prolonged immunocompromised states. There has been emerging data that suggests the use of new technology in addition to existing central line maintenance recommendations by the Center for Disease Control may further reduce the rate of CLABSI occurrences in high-risk patient populations. Aim: To determine the efficacy of passive valve antimicrobial swab caps on the reduction of CLABSI in an inpatient hematology patient population when compared to current existing local practices. Outcomes of reported incidents of CLABSI have been evaluated against pre-interventional data for this setting. Methods: Retrospective analysis of medical records from January 2016 - September 2019 identified the existing rate of CLABSI occurrence among inpatient hematology patients at a single institution. We utilized the intervention of antimicrobial swab caps for 10 months and tracked the rate of CLABSI during this time. The nursing staff were educated on the quality improvement project, the use of the new equipment, and expectations that existing standard practices per local policy for CLABSI prevention bundles would be adhered to prior to the start of the intervention. To evaluate the impact of the antimicrobial swab caps on the rate of CLABSI we compared the number of infections pre- and post-intervention. Randomized audits, including chart reviews for compliance with existing standard CLABSI bundle practices were performed during the initial 3 months of the intervention. Results: Prior to the introduction of the passive valve antimicrobial swab cap to the existing CLABSI prevention protocol, CLABSI rates on the hematology unit exceeded the standardized infection ratio 75th percentile on 9 of the previous 15 calendar quarters. The intervention was observed for 6,674 central line days. The CLABSI rate during the intervention was 0.4495 per 1,000 central line days. The CLABSIs identified were due to nosocomial opportunistic infection in setting of immunosuppressed status (66%) and gastrointestinal translocation (33%). The common diagnosis in setting of CLABSI was refractory/relapse diffuse large B-cell lymphoma (66%) and active acute myeloid leukemia (33%). The two patients who were diagnosed with CLABSI were neutropenic with an absolute neutrophil count of 0 at time of CLABSI diagnosis. The organisms identified at time of CLABSI diagnosis were Clostridium ramosom, Enterococcus faecium, Staphylococcus epidermisis, and Candida parapsilosis. When considering the cost of a CLABSI to be about 46,000 per event and the annual cost for the inpatient hematology unit\u27s use of the caps of approximately $19,710, the implementation of the antimicrobial swab cap reduced the cost associated with CLASBI in the hematology unit by approximately$26,290 annually. Conclusions: The introduction of the passive valve antimicrobial swab caps appears to demonstrate potential for reduced costs due to CLABSI when implemented into current CLABSI prevention bundles. This resulted in a 25% reduction in rates of CLABSI in the adult hematology patient population when compared to the previous year. The prevention of CLABSI in hematology patients with central vascular access remains challenging, however, standardized protocols for CLABSI prevention and use of antimicrobial swab caps may help further reduce the rate of CLABSI in hematology patients

Initial Efficacy and Safety of Acalabrutinib Plus RICE in Transplant Eligible Patients with Relapsed/Refractory Diffuse Large B-Cell Lymphoma

Background: Patients (pts) with relapsed/refractory (R/R) diffuse large B-cell lymphoma (DLBCL) undergoing second-line chemoimmunotherapy (2L CIT) often have a poor prognosis with a minority achieving curative outcomes. Achievement of CR with 2L CIT is associated with favorable long-term outcomes in patients consolidated with autologous stem cell transplant (ASCT). Unfortunately, only 25-35% of patients achieve complete response (CR/CR unconfirmed) with RICE CIT (Gisselbrecht 2010). Addition of novel targeted agents such as Bruton Tyrosine Kinase inhibitors (BTKi) to 2L CIT may offer improved treatment responses given the importance of B-cell receptor (BCR) signaling in DLBCL. Here we report the feasibility and efficacy of combining acalabrutinib (acala) 100mg BID with RICE (A-RICE) chemotherapy in ASCT eligible pts with R/R DLBCL. Study Design and Methods: In a single-center, open-label, phase 2 trial (NCT03736616) we evaluate the feasibility, efficacy, and tolerability of combining acala with RICE as 2L CIT in R/R DLBCL pts. There are two study cohorts. Cohort A is open to R/R DLBCL pts who are eligible for 2L CIT followed by ASCT consolidation. Cohort B is open to R/R DLBCL pts considered medically ineligible for ASCT. The primary objective for cohort A is to estimate the confirmed CR rate (RECIL 2017 criteria) of A-RICE prior to HCT. Primary endpoint for cohort A is met if \u3e10 of maximum 24 enrolled patients achieve CR, which allows rejection of the null hypothesis that confirmed CR rate is ≤ 25% if true CR rate is 50% (one-sided α =0.05, power = 85%). The primary endpoint for cohort B is the estimate of one-year progression-free survival in patients undergoing 2L CIT followed by maintenance acala for up to 12 months. Secondary endpoints include overall response rate (ORR), incidence of Grade 3/4 adverse events (AEs), and incidence of serious AEs in both cohorts. Pts in cohort A received 2 cycles of A-RICE in a 21 day cycle. After 2 cycles A-RICE, response assessment via PET-CT (PET2) was completed with responding patients receiving a 3rd cycle of A-RICE followed by stem cell mobilization and collection. PET-CT was performed 14-21 days after day 1 of cycle 3 (PET3) to assess response to 2L CIT. Those patients with CR or partial response (PR) after PET3 proceeded to BEAM conditioned ASCT within 28-42 days of PET3. After hematopoietic recovery, patients may continue acalabrutinib 100mg BID as maintenance therapy for 12 months post ASCT. Minimal residual disease (MRD) is assessed using ctDNA (clonoseq) at time points pre-ASCT, post-ASCT, and during maintenance A. Results: Primary endpoint for Cohort A has been met and is reported here, while Cohort B has not yet met pre-specified enrollment or follow up maturity for efficacy analyses. Safety for both cohorts to date is reported. Twenty-six pts have been enrolled (19 cohort A, 7 cohort B). In Cohort A, 5 pts had refractory DLBCL, 7 pts were GCB, 10 non-GCB. Median age of Cohort A was 58, and median of Cohort B was 75 (Table 1). 19 Cohort A pts received at least 1 cycle of A-RICE, with 16 pts completing 3 cycles. One patient (4%) stopped A-RICE due to AE, 3 patients (13%) discontinued due to progressive disease (PD). All 19 pts in cohort A were considered response evaluable following initiation A-RICE: ORR was 74% (14 pts), with 53% CR (10 pts), 21% PR (4 pts). Thirteen pts (68%) underwent planned consolidative ASCT. See Figure 1 for response data. Safety data for all 26 cohort A and B patients who received at least 1 cycle A-RICE was assessed for the first three cycles of A-RICE. The most common treatment-related AEs were thrombocytopenia (All 50%, Gr 3/4 46%) and neutropenia (Gr 3/4 30%). SAEs were reported in 5 pts with 1 therapy related SAE of neutropenic fever, and 4 treatment unrelated SAEs. Of the 19 efficacy evaluable pts in cohort A, 10 pts interrupted 1 or more doses of acalabrutinib during a A-RICE cycle either due to patient error or protocol specified dose hold related to AE. Conclusions: A-RICE in ASCT eligible pts w/ R/R DLBCL demonstrated CR in 53% of response evaluable patients. Further, we observed a high ORR (74%) and high proportion of pts completing planned ASCT (68%). AEs with A-RICE were consistent with those expected for CIT. A-RICE warrants further investigation in pts w/ R/R DLBCL eligible for 2L CIT with intention to undergo ASCT. Further analyses of cohort A, including ctDNA based MRD dynamics, PFS, and OS are ongoing and will be updated at meeting