Multicentre service evaluation of injectable cabotegravir and rilpivirine delivery and outcomes across 12 UK clinics (SHARE LAI-net).

INTRODUCTION: Long-acting injectable cabotegravir + rilpivirine (CAB + RPV LAI) was approved for use in virally suppressed adults in the England and Wales national health service in November 2021. We describe a service evaluation of delivery processes and outcomes in 12 clinics. METHODS: Centres populated a database using information from local policies and clinical records. Services were asked to describe approval processes, clinic pathways, and adherence to national guidelines. Additional data were collected on reasons for regimen choice, treatment discontinuations, and management of viraemia. RESULTS: In total, 518 adults from 12 clinics were approved for CAB + RPV LAI between February 2022 and December 2023. Of the 518 people approved for CAB + RPV LAI, 423 received at least one injection. Median duration on CAB + RPV was 7.5 months (interquartile range 3.7-11.3). In total, 97% of injections were administered within the ±7-day window. Virological failure occurred in 0.7%, and 6% discontinued CAB + RPV. CONCLUSION: In this large UK-based cohort, robust approval processes and clinic protocols facilitated on-time injections and low rates of both discontinuation and virological failure.

Patient satisfaction from two studies of collaborative doctor-pharmacist prescribing in Australia.

BACKGROUND: Pharmacist prescribing has been introduced in several countries and is a possible future role for pharmacy in Australia. OBJECTIVE: To assess whether patient satisfaction with the pharmacist as a prescriber, and patient experiences in two settings of collaborative doctor-pharmacist prescribing may be barriers to implementation of pharmacist prescribing. DESIGN: Surveys containing closed questions, and Likert scale responses, were completed in both settings to investigate patient satisfaction after each consultation. A further survey investigating attitudes towards pharmacist prescribing, after multiple consultations, was completed in the sexual health clinic. SETTING AND PARTICIPANTS: A surgical pre-admission clinic (PAC) in a tertiary hospital and an outpatient sexual health clinic at a university hospital. Two hundred patients scheduled for elective surgery, and 17 patients diagnosed with HIV infection, respectively, recruited to the pharmacist prescribing arm of two collaborative doctor-pharmacist prescribing studies. RESULTS: Consultation satisfaction response rates in PAC and the sexual health clinic were 182/200 (91%) and 29/34 (85%), respectively. In the sexual health clinic, the attitudes towards pharmacist prescribing survey response rate were 14/17 (82%). Consultation satisfaction was high in both studies, most patients (98% and 97%, respectively) agreed they were satisfied with the consultation. In the sexual health clinic, all patients (14/14) agreed that they trusted the pharmacist's ability to prescribe, care was as good as usual care, and they would recommend seeing a pharmacist prescriber to friends. DISCUSSION AND CONCLUSION: Most of the patients had a high satisfaction with pharmacist prescriber consultations, and a positive outlook on the collaborative model of care in the sexual health clinic.

Tamoxifen for the treatment of myeloproliferative neoplasms: A Phase II clinical trial and exploratory analysis.

Current therapies for myeloproliferative neoplasms (MPNs) improve symptoms but have limited effect on tumor size. In preclinical studies, tamoxifen restored normal apoptosis in mutated hematopoietic stem/progenitor cells (HSPCs). TAMARIN Phase-II, multicenter, single-arm clinical trial assessed tamoxifen's safety and activity in patients with stable MPNs, no prior thrombotic events and mutated JAK2V617F, CALRins5 or CALRdel52 peripheral blood allele burden ≥20% (EudraCT 2015-005497-38). 38 patients were recruited over 112w and 32 completed 24w-treatment. The study's A'herns success criteria were met as the primary outcome ( ≥ 50% reduction in mutant allele burden at 24w) was observed in 3/38 patients. Secondary outcomes included ≥25% reduction at 24w (5/38), ≥50% reduction at 12w (0/38), thrombotic events (2/38), toxicities, hematological response, proportion of patients in each IWG-MRT response category and ELN response criteria. As exploratory outcomes, baseline analysis of HSPC transcriptome segregates responders and non-responders, suggesting a predictive signature. In responder HSPCs, longitudinal analysis shows high baseline expression of JAK-STAT signaling and oxidative phosphorylation genes, which are downregulated by tamoxifen. We further demonstrate in preclinical studies that in JAK2V617F+ cells, 4-hydroxytamoxifen inhibits mitochondrial complex-I, activates integrated stress response and decreases pathogenic JAK2-signaling. These results warrant further investigation of tamoxifen in MPN, with careful consideration of thrombotic risk.

Ruxolitinib Versus Best Available Therapy for Polycythemia Vera Intolerant or Resistant to Hydroxycarbamide in a Randomized Trial.

PURPOSE: Polycythemia vera (PV) is characterized by JAK/STAT activation, thrombotic/hemorrhagic events, systemic symptoms, and disease transformation. In high-risk PV, ruxolitinib controls blood counts and improves symptoms. PATIENTS AND METHODS: MAJIC-PV is a randomized phase II trial of ruxolitinib versus best available therapy (BAT) in patients resistant/intolerant to hydroxycarbamide (HC-INT/RES). Primary outcome was complete response (CR) within 1 year. Secondary outcomes included duration of response, event-free survival (EFS), symptom, and molecular response. RESULTS: One hundred eighty patients were randomly assigned. CR was achieved in 40 (43%) patients on ruxolitinib versus 23 (26%) on BAT (odds ratio, 2.12; 90% CI, 1.25 to 3.60; P = .02). Duration of CR was superior for ruxolitinib (hazard ratio [HR], 0.38; 95% CI, 0.24 to 0.61; P < .001). Symptom responses were better with ruxolitinib and durable. EFS (major thrombosis, hemorrhage, transformation, and death) was superior for patients attaining CR within 1 year (HR, 0.41; 95% CI, 0.21 to 0.78; P = .01); and those on ruxolitinib (HR, 0.58; 95% CI, 0.35 to 0.94; P = .03). Serial analysis of JAK2V617F variant allele fraction revealed molecular response was more frequent with ruxolitinib and was associated with improved outcomes (progression-free survival [PFS] P = .001, EFS P = .001, overall survival P = .01) and clearance of JAK2V617F stem/progenitor cells. ASXL1 mutations predicted for adverse EFS (HR, 3.02; 95% CI, 1.47 to 6.17; P = .003). The safety profile of ruxolitinib was as previously reported. CONCLUSION: The MAJIC-PV study demonstrates ruxolitinib treatment benefits HC-INT/RES PV patients with superior CR, and EFS as well as molecular response; importantly also demonstrating for the first time, to our knowledge, that molecular response is linked to EFS, PFS, and OS.

A web-based team-oriented medical error communication assessment tool: development, preliminary reliability, validity, and user ratings.

BACKGROUND: Multiple-choice exams are not well suited for assessing communication skills. Standardized patient assessments are costly and patient and peer assessments are often biased. Web-based assessment using video content offers the possibility of reliable, valid, and cost-efficient means for measuring complex communication skills, including interprofessional communication. DESCRIPTION: We report development of the Web-based Team-Oriented Medical Error Communication Assessment Tool, which uses videotaped cases for assessing skills in error disclosure and team communication. Steps in development included (a) defining communication behaviors, (b) creating scenarios, (c) developing scripts, (d) filming video with professional actors, and (e) writing assessment questions targeting team communication during planning and error disclosure. EVALUATION: Using valid data from 78 participants in the intervention group, coefficient alpha estimates of internal consistency were calculated based on the Likert-scale questions and ranged from α=.79 to α=.89 for each set of 7 Likert-type discussion/planning items and from α=.70 to α=.86 for each set of 8 Likert-type disclosure items. The preliminary test-retest Pearson correlation based on the scores of the intervention group was r=.59 for discussion/planning and r=.25 for error disclosure sections, respectively. Content validity was established through reliance on empirically driven published principles of effective disclosure as well as integration of expert views across all aspects of the development process. In addition, data from 122 medicine and surgical physicians and nurses showed high ratings for video quality (4.3 of 5.0), acting (4.3), and case content (4.5). CONCLUSIONS: Web assessment of communication skills appears promising. Physicians and nurses across specialties respond favorably to the tool.

Donor acquired visceral leishmaniasis following liver transplantation.

Patients who undergo solid organ transplantation are at risk of opportunistic infection associated with immunosuppression. We report a case of confirmed donor derived visceral leishmaniasis (VL), in a patient following liver transplantation causing fever and pancytopenia. The diagnosis was confirmed by bone marrow biopsy, with confirmed positive donor serology, with no other route of transmission. To our knowledge, this is the first case report in the United Kingdom and Europe, of confirmed organ donor transmission of VL. This case report highlights an important consideration of donor derived infections, in the context of solid organ transplantation.

CD8(+) T-cell immunity against cancer-testis antigens develops following allogeneic stem cell transplantation and reveals a potential mechanism for the graft-versus-leukemia effect.

BACKGROUND: Allogeneic stem cell transplantation is associated with a powerful 'graft-versus-leukemia' effect that is generally considered to result from an alloreactive T-cell immune response. However, disease remission can also be observed after syngeneic transplantation and we investigated whether a T-cell immune response to cancer-testis antigens can be detected in patients in the post-transplant period. DESIGN AND METHODS: The T-cell immune response against cancer-testis antigens was studied in a cohort of 41 patients who underwent allogeneic stem cell transplantation for the management of acute myeloid leukemia or multiple myeloma. The cytokine secretion assay was combined with magnetic selection to allow detection of an interferon-gamma-secreting T-cell response to a panel of cancer-testis antigen peptides. RESULTS: A cancer-testis antigen-specific CD8(+) T-cell immune response was observed in the peripheral blood of five patients with an average magnitude of 0.045% of the CD8(+) T-cell repertoire. Four of these patients had undergone reduced intensity conditioning transplantation with alemtuzumab for the treatment of acute myeloid leukemia and three remain in long-term remission. T-cell immunity was focused against peptides derived from MAGE proteins and was markedly increased within the bone marrow. CONCLUSIONS: Functional cancer-testis antigen-specific CD8(+) T-cell immune responses develop in the early period following reduced intensity allogeneic stem cell transplantation and are preferentially localized to bone marrow. These immune responses are likely to contribute to the cellular basis of the graft-versus-leukemia effect.

Factors predicting long-term survival after T-cell depleted reduced intensity allogeneic stem cell transplantation for acute myeloid leukemia.

BACKGROUND: Reduced intensity conditioning regimens permit the delivery of a potentially curative graft-versus-leukemia effect in older patients with acute myeloid leukemia. Although T-cell depletion is increasingly used to reduce the risk of graft-versus-host disease its impact on the graft-versus-leukemia effect and long-term outcome post-transplant is unknown. DESIGN AND METHODS: We have characterized pre- and post-transplant factors determining overall survival in 168 patients with acute myeloid leukemia transplanted using an alemtuzumab based reduced intensity conditioning regimen with a median duration of follow-up of 37 months. RESULTS: The 3-year overall survival for patients transplanted in CR1 or CR2/CR3 was 50% (95% CI, 38% to 62%) and 44% (95% CI, 31% to 56%), respectively compared to 15% (95% CI, 2% to 36%) for patients with relapsed/refractory disease. Multivariate analysis demonstrated that both survival and disease relapse were influenced by status at transplant (P=0.008) and presentation cytogenetics (P=0.01). Increased exposure to cyclosporine A (CsA) in the first 21 days post-transplant was associated with an increased relapse risk (P<0.0001) and decreased overall survival (P<0.0001). CONCLUSIONS: Disease stage, presentation karyotype and post-transplant CsA exposure are important predictors of outcome in patients undergoing a T-cell depleted reduced intensity conditioning allograft for acute myeloid leukemia. These data confirm the presence of a potent graft-versus-leukemia effect after a T-cell depleted reduced intensity conditioning allograft in acute myeloid leukemia and identify CsA exposure as a manipulable determinant of outcome in this setting.

Identifying the World Health Organization's fifth moment for hand hygiene: Infection prevention in the operating room.

BACKGROUND: The World Health Organization have designed the fifth of their '5 moments' for hand hygiene to account for microbial transfer from patients to equipment in a narrow area around that patient, known as the patient zone. The study was prompted by emerging local confusion about application of the patient zone in the operating room (OR). AIM/OBJECTIVES: In two phases, we aimed to create a '5 moments' style poster displaying an OR patient zone: phase 1, quantify equipment, in direct contact with the patient and, touched by non-scrubbed staff immediately after touching the patient; and phase 2, categorise equipment identified in phase 1 into patient zone and healthcare zone. An objective is to produce a '5 moments' poster for the OR. METHODS: The first phase used non-participant direct overt observation. In phase 2, phase 1 data were collaboratively assigned to patient zone or healthcare zone. Photography and graphic design were used to produce the OR '5 moments' poster. RESULTS: In 11 full-length surgeries, 20 pieces of equipment were in direct contact with the patient and 57 pieces of equipment were touched. In phase 2, a '5 moments' poster showing an OR patient zone was designed. DISCUSSION: Content of the patient zone was identified and displayed in a novel resource. Having shared understanding of the patient zone has potential to sustain hand hygiene compliance and equipment cleaning in the OR. CONCLUSION: Limitations in methods were balanced by collaboration with frontline staff. The study has been used as a teaching tool in the OR and similar settings.