A simplified G-CSF-free procedure allows for in vivo HSC gene therapy of sickle cell disease in a mouse model.

ABSTRACT: We have reported the direct repair of the sickle cell mutation in vivo in a disease model using vectorized prime editors after hematopoietic stem cell (HSC) mobilization with granulocyte colony-stimulating factor (G-CSF)/AMD3100. The use of G-CSF for HSC mobilization is a hurdle for the clinical translation of this approach. Here, we tested a G-CSF-free mobilization regimen using WU-106, an inhibitor of integrin α4ß1, plus AMD3100 for in vivo HSC prime editing in sickle cell disease (SCD) mice. Mobilization with WU-106 + AMD3100 in SCD mice was rapid and efficient. In contrast to the G-CSF/AMD3100 approach, mobilization of activated granulocytes and elevation of the key proinflammatory cytokine interleukin-6 in the serum were minimal. The combination of WU-106 + AMD3100 mobilization and IV injection of the prime editing vector together with in vivo selection resulted in ∼23% correction of the SCD mutation in the bone marrow and peripheral blood cells of SCD mice. The treated mice demonstrated phenotypic correction, as reflected by normalized blood parameters and spleen size. Editing frequencies were significantly increased (29%) in secondary recipients, indicating the preferential mobilization/transduction of long-term repopulating HSCs. Using this approach, we found <1% undesired insertions/deletions and no detectable off-target editing at the top-scored potential sites. Our study shows that in vivo transduction to treat SCD can now be done within 2 hours involving only simple IV injections with a good safety profile. The same-day mobilization regimen makes in vivo HSC gene therapy more attractive for resource-poor settings, where SCD does the most damage.

A rapid systematic review of breakthrough pain definitions and descriptions.

Background: Breakthrough pain is common in life-limiting conditions and at end-of-life. Despite over 30 years of study, there is little consensus regarding the definition and characteristics of breakthrough pain. Objective: This study aims to update and expand a 2010 systematic review by Haugen and colleagues to identify (1) all definitions of breakthrough pain and (2) all descriptions and classifications of breakthrough pain reported by patients, caregivers, clinicians, and experts. Design: This rapid systematic review followed the Cochrane Rapid Review Methods Group guidelines. A protocol is published on PROSPERO (CRD42019155583). Data sources: CINAHL, MEDLINE, PsycINFO, and the Web of Science were searched for breakthrough pain terms from the inception dates of each database to 26th August 2022. Results: We identified 65 studies that included data on breakthrough pain definitions, descriptions, or classifications from patients (n = 30), clinicians (n = 6), and experts (n = 29), but none with data from caregivers. Most experts proposed that breakthrough pain was a sudden, severe, brief pain occurring in patients with adequately controlled mild-moderate background pain. However, definitions varied and there was no consensus. Pain characteristics were broadly similar across studies though temporal factors varied widely. Experts classified breakthrough pain into nociceptive, neuropathic, visceral, somatic, or mixed types. Patients with breakthrough pain commonly experienced depression, anxiety, and interference with daily life. Conclusions: Despite ongoing efforts, there is still no consensus on the definition of breakthrough pain. A compromise is needed on breakthrough pain nomenclature to collect reliable incidence and prevalence data and to inform further refinement of the construct.

Assessing the Cost-Effectiveness of Next-Generation Sequencing as a Biomarker Testing Approach in Oncology and Policy Implications: A Literature Review.

OBJECTIVE: A key hurdle in broader next-generation sequencing (NGS) biomarker testing access in oncology is the ongoing debate on NGS's cost-effectiveness. We conducted a systematic review of existing evidence of the costs of NGS as a biomarker testing strategy in oncology and developed policy suggestions. METHODS: We searched multiple databases for studies reporting cost comparisons and cost-effectiveness of NGS across oncology indications and geographies between 2017 and 2022, inclusive. Inclusion criteria were established based on indication and type of cost-effectiveness analysis provided. We validated analyses and policy recommendations with 5 payer/policy maker interviews in the United States, Europe, and United Kingdom. RESULTS: Of the 634 identified studies, 29 met inclusion criteria, spanning 12 countries and 6 indications. Cost comparisons of NGS were evaluated using 3 methodologies: (1) comparison of direct testing costs, (2) comparison of holistic testing costs, and (3) comparison of long-term patient outcomes and costs. Targeted panel testing (2-52 genes) was considered cost-effective when 4+ genes were assessed, and larger panels (hundreds of genes) were generally not cost-effective. Holistic analysis demonstrated that NGS reduces turnaround time, healthcare staff requirements, number of hospital visits, and hospital costs. Finally, studies evaluating NGS testing including the cost of targeted therapies generally found the incremental cost-effectiveness ratio to be above common thresholds but highlighted valuable patient benefits. CONCLUSIONS: Current literature supports NGS's cost-effectiveness as an oncology biomarker testing strategy under specific conditions. These findings underscore the need to develop policies to support holistic assessment of NGS to ensure appropriate reimbursement and access.

Definition and Assessment of Paediatric Breakthrough Pain: A Qualitative Interview Study.

Infants, children and young people with life-limiting or life-threatening conditions often experience acute, transient pain episodes known as breakthrough pain. There is currently no established way to assess breakthrough pain in paediatric palliative care. Anecdotal evidence suggests that it is frequently underdiagnosed and undertreated, resulting in reduced quality of life. The development of a standardised paediatric breakthrough pain assessment, based on healthcare professionals' insights, could improve patient outcomes. This study aimed to explore how healthcare professionals define and assess breakthrough pain in paediatric palliative care and their attitudes towards a validated paediatric breakthrough pain assessment. This was a descriptive qualitative interview study. Semi-structured interviews were conducted with 29 healthcare professionals working in paediatric palliative care across the UK. An inductive thematic analysis was conducted on the data. Five themes were generated: 'the elusive nature of breakthrough pain', 'breakthrough pain assessment', 'positive attitudes towards', 'reservations towards' and 'features to include in' a paediatric breakthrough pain assessment. The definition and assessment of breakthrough pain is inconsistent in paediatric palliative care. There is a clear need for a validated assessment questionnaire to improve assessment, diagnosis and management of breakthrough pain followed by increased healthcare professional education on the concept.

Clinical consensus recommendations for the non-surgical treatment of children with Perthes' disease in the UK.

Aims: The aim of this study was to produce clinical consensus recommendations about the non-surgical treatment of children with Perthes' disease. The recommendations are intended to support clinical practice in a condition for which there is no robust evidence to guide optimal care. Methods: A two-round, modified Delphi study was conducted online. An advisory group of children's orthopaedic specialists consisting of physiotherapists, surgeons, and clinical nurse specialists designed a survey. In the first round, participants also had the opportunity to suggest new statements. The survey included statements related to 'Exercises', 'Physical activity', 'Education/information sharing', 'Input from other services', and 'Monitoring assessments'. The survey was shared with clinicians who regularly treat children with Perthes' disease in the UK using clinically relevant specialist groups and social media. A predetermined threshold of ≥ 75% for consensus was used for recommendation, with a threshold of between 70% and 75% being considered as 'points to consider'. Results: A total of 40 participants took part in the first round, of whom 31 completed the second round. A total of 87 statements were generated by the advisory group and included in the first round, at the end of which 31 achieved consensus and were removed from the survey, and an additional four statements were generated. A total of 60 statements were included in the second round and 45 achieved the threshold for consensus from both rounds, with three achieving the threshold for 'points to consider'. The recommendations predominantly included self-management, particularly relating to advice about exercise and education for children with Perthes' disease and their families. Conclusion: Children's orthopaedic specialists have reached consensus on recommendations for non-surgical treatment in Perthes' disease. These statements will support decisions made in clinical practice and act as a foundation to support clinicians in the absence of robust evidence. The dissemination of these findings and the best way of delivering this care needs careful consideration, which we will continue to explore.

Impact of COVID-19 on patients undergoing scheduled procedures for chronic venous disease.

OBJECTIVE: The COVID-19 pandemic has drastically altered the medical landscape. Various strategies have been employed to preserve hospital beds, personal protective equipment, and other resources to accommodate the surges of COVID-19 positive patients, hospital overcapacities, and staffing shortages. This has had a dramatic effect on vascular surgical practice. The objective of this study is to analyze the impact of the COVID-19 pandemic on surgical delays and adverse outcomes for patients with chronic venous disease scheduled to undergo elective operations. METHODS: The Vascular Surgery COVID-19 Collaborative (VASCC) was founded in March 2020 to evaluate the outcomes of patients with vascular disease whose operations were delayed. Modules were developed by vascular surgeon working groups and tested before implementation. A data analysis of outcomes of patients with chronic venous disease whose surgeries were postponed during the COVID-19 pandemic from March 2020 through February 2021 was performed for this study. RESULTS: A total of 150 patients from 12 institutions in the United States were included in the study. Indications for venous intervention were: 85.3% varicose veins, 10.7% varicose veins with venous ulceration, and 4.0% lipodermatosclerosis. One hundred two surgeries had successfully been completed at the time of data entry. The average length of the delay was 91 days, with a median of 78 days. Delays for venous ulceration procedures ranged from 38 to 208 days. No patients required an emergent intervention due to their venous disease, and no patients experienced major adverse events following their delayed surgeries. CONCLUSIONS: Interventions may be safely delayed for patients with venous disease requiring elective surgical intervention during the COVID-19 pandemic. This finding supports the American College of Surgeons' recommendations for the management of elective vascular surgical procedures. Office-based labs may be safe locations for continued treatment when resources are limited. Although the interventions can be safely postponed, the negative impact on quality of life warrants further investigation.

Development of an International Virtual Multidisciplinary Tumor Board for Breast Cancer in Mongolia.

INTRODUCTION: Breast cancer is the most diagnosed cancer among Mongolian women and mortality rates are high. We describe a virtual multi-institutional and multidisciplinary tumor board (MTB) for breast cancer created to assist the National Cancer Center of Mongolia. MATERIALS AND METHODS: A virtual MTB for breast cancer was conducted with participation of two United States and 1 Mongolian cancer centers. A standardized template for presentations was developed. Recommendations were summarized and shared with participants. Collected data included patient demographics, tumor characteristics, stage, imaging and treatments performed, and recommendations. Questions were categorized as treatment, diagnosis, or palliative questions. RESULTS: Fifteen patients were evaluated. Median age was 39 y. 86.7% of breast cancers were invasive ductal cancers and 13.3% were metaplastic carcinomas. 53.3% were estrogen and progesterone receptor positive (ER+/PR+), 60% were HER2+, 13.3% were triple negative, and 26.7% were recurrent. 40% of patients were evaluated with mammography. 6% received positron emission tomography scans for metastatic evaluation. 66.7% of surgical patients received neoadjuvant chemotherapy. Herceptin was administered to 55.6% of patients with Her2+ cancers. Modified radical mastectomy was most commonly performed and reconstruction was rare. Sentinel lymph node biopsy was not performed. 66.7% of ER+/PR+ patients received endocrine therapy. 6.7% of patients received radiation. 75% of MTB questions pertained to treatment. Recommendations were related to systemic therapy (40%), surgical management (33.3%), pathology (13.3%), and imaging (13.3%). CONCLUSIONS: This study illustrates the development of an international, virtual, multi-institutional breast cancer MTB and provides insight into challenges and potential interventions to improve breast cancer care in Mongolia.

Supporting patients to prepare for total knee replacement: Evidence-, theory- and person-based development of a 'Virtual Knee School' digital intervention.

INTRODUCTION: Digital delivery of pre-operative total knee replacement (TKR) education and prehabilitation could improve patient outcomes pre- and post-operatively. Rigorously developing digital interventions is vital to help ensure they achieve their intended outcomes whilst mitigating their potential drawbacks. OBJECTIVE: To develop a pre-operative TKR education and prehabilitation digital intervention, the 'Virtual Knee School' (VKS). METHODS: The VKS was developed using an evidence-, theory- and person-based approach. This involved a mixed methods design with four phases. The first three focused on planning the VKS. The final phase involved creating a VKS prototype and iteratively refining it through concurrent think-aloud interviews with nine patients who were awaiting/had undergone TKR. Meta-inferences were generated by integrating findings from all the phases. ISRCTN registration of the overall project was obtained on 24 April 2020 (ISRCTN11759773). RESULTS: Most participants found the VKS prototype acceptable overall and considered it a valuable resource. Conversely, a minority of participants felt the prototype's digital format or content did not meet their individual needs. Participants' feedback was used to refine the prototype's information architecture, design and content. Two meta-inferences were generated and recommend: 1. Comprehensive pre-operative TKR education and prehabilitation support should be rapidly accessible in digital and non-digital formats. 2. Pre-operative TKR digital interventions should employ computer- and self-tailoring to account for patients' individual needs and preferences. CONCLUSIONS: Integrating evidence, theory and stakeholders' perspectives enabled the development of a promising VKS digital intervention for patients awaiting TKR. The findings suggest future research evaluating the VKS is warranted and provide recommendations for optimising pre-operative TKR care. PATIENT OR PUBLIC CONTRIBUTION: Patient and Public Involvement (PPI) was central throughout the project. For example, PPI representatives contributed to the project planning, were valued members of the Project Advisory Group, had key roles in developing the VKS prototype and helped disseminate the project findings.

Stable HIV decoy receptor expression after in vivo HSC transduction in mice and NHPs: Safety and efficacy in protection from SHIV.

We aim to develop an in vivo hematopoietic stem cell (HSC) gene therapy approach for persistent control/protection of HIV-1 infection based on the stable expression of a secreted decoy protein for HIV receptors CD4 and CCR5 (eCD4-Ig) from blood cells. HSCs in mice and a rhesus macaque were mobilized from the bone marrow and transduced by an intravenous injection of HSC-tropic, integrating HDAd5/35++ vectors expressing rhesus eCD4-Ig. In vivo HSC transduction/selection resulted in stable serum eCD4-Ig levels of ∼100 µg/mL (mice) and >20 µg/mL (rhesus) with half maximal inhibitory concentrations (IC50s) of 1 µg/mL measured by an HIV neutralization assay. After simian-human-immunodeficiency virus D (SHIV.D) challenge of rhesus macaques injected with HDAd-eCD4-Ig or a control HDAd5/35++ vector, peak plasma viral load levels were ∼50-fold lower in the eCD4-Ig-expressing animal. Furthermore, the viral load was lower in tissues with the highest eCD4-Ig expression, specifically the spleen and lymph nodes. SHIV.D challenge triggered a selective expansion of transduced CD4+CCR5+ cells, thereby increasing serum eCD4-Ig levels. The latter, however, broke immune tolerance and triggered anti-eCD4-Ig antibody responses, which could have contributed to the inability to eliminate SHIV.D. Our data will guide us in the improvement of the in vivo approach. Clearly, our conclusions need to be validated in larger animal cohorts.

In vivo HSC prime editing rescues sickle cell disease in a mouse model.

Sickle cell disease (SCD) is a monogenic disease caused by a nucleotide mutation in the ß-globin gene. Current gene therapy studies are mainly focused on lentiviral vector-mediated gene addition or CRISPR/Cas9-mediated fetal globin reactivation, leaving the root cause unfixed. We developed a vectorized prime editing system that can directly repair the SCD mutation in hematopoietic stem cells (HSCs) in vivo in a SCD mouse model (CD46/Townes mice). Our approach involved a single intravenous injection of a nonintegrating, prime editor-expressing viral vector into mobilized CD46/Townes mice and low-dose drug selection in vivo. This procedure resulted in the correction of ∼40% of ßS alleles in HSCs. On average, 43% of sickle hemoglobin was replaced by adult hemoglobin, thereby greatly mitigating the SCD phenotypes. Transplantation in secondary recipients demonstrated that long-term repopulating HSCs were edited. Highly efficient target site editing was achieved with minimal generation of insertions and deletions and no detectable off-target editing. Because of its simplicity and portability, our in vivo prime editing approach has the potential for application in resource-poor countries where SCD is prevalent.

"I could have a proper ankle" - a qualitative study of patients' perceptions of total ankle replacement and ankle fusion surgery.

BACKGROUND: End-stage ankle osteoarthritis typically causes severe pain and impaired function. Surgical treatment involves total ankle replacement (TAR) or ankle fusion. Definitive evidence about which procedure is optimal is lacking. No previous studies have thoroughly explored patients' experiences across the entire TAR/ankle fusion pathway. This study aimed to address this gap by exploring perceptions of surgery, education, rehabilitation and outcomes among patients who had undergone TAR or ankle fusion. METHODS: Seven participants were purposively selected from an orthopaedic centre in northern England (3 females, 4 males). Participants had undergone primary TAR without revision (n = 2), TAR requiring revision (n = 3) or ankle fusion (n = 2). Each participant completed a single semi-structured interview. Interviews were digitally recorded, transcribed verbatim and analysed thematically. RESULTS: Three themes, each with two subthemes, were identified: decision-making (seeking help; surgical options), perceptions of support (information/education; clinical support) and impact on the individual (personal circumstances and beliefs; post-operative outcomes). Pain affecting participants' valued activities was key to their decision to seek help. Participants' decision between TAR and ankle fusion was influenced by multiple factors. Concerns regarding the lack of joint flexibility following fusion were highlighted, with some participants perceiving TAR as a "proper ankle" that would enable them to avoid limping. Participants obtained information from various sources, with most feeling that the education from their care team was inadequate. Participants' individual circumstances and beliefs influenced their decision-making and perceptions of their post-operative outcomes. Finally, whilst most participants were pleased with their outcomes, some experienced substantial ongoing problems such as difficulty walking and chronic pain. CONCLUSIONS: This study demonstrates the importance of providing adequate education about TAR and ankle fusion to enable patients to make informed decisions. Most participants felt that the education and clinical support they received did not fully meet their needs. Participants' personal circumstances and beliefs had a strong influence on their decision-making and perceptions of their post-operative outcomes, highlighting the need to personally tailor education and clinical support. Future work with a larger sample of patients and other key stakeholders is required to develop consensus-based guidelines on pre- and post-operative support for patients undergoing TAR/ankle fusion.

Content and delivery of pre-operative interventions for patients undergoing total knee replacement: a rapid review.

BACKGROUND: Total knee replacement (TKR) is a common operation typically performed for end-stage knee osteoarthritis. Patients awaiting TKR often have poor health-related quality of life. Approximately 20% of patients experience persistent pain post-TKR. Pre-operative TKR interventions could improve pre- and post-operative outcomes, but future research is required to inform their design. This review aimed to identify and synthesize recent literature on the content and delivery of pre-operative TKR interventions to help guide future research and clinical practice. METHODS: This rapid review included randomized trials of pre-operative TKR interventions ("outcomes studies") and primary studies exploring patients' and/or health professionals' views of pre-operative TKR interventions ("views studies"). Medline, Embase, PsycINFO, CINAHL and the Cochrane Central Register of Controlled Trials were searched for English language studies published between January 2009 and December 2020. Eligible studies' reference lists were screened. Studies were appraised using the Mixed Methods Appraisal Tool. The findings were narratively synthesized using a convergent segregated approach. RESULTS: From 3263 records identified, 52 studies were included (29 outcomes studies, 21 views studies, two outcomes/views studies). The studies' methodological quality varied but was generally highest in qualitative studies. The outcomes studies investigated education (n=5), exercise (n=20), psychological (n=2), lifestyle (n=1), and/or other interventions (n=5). The views studies addressed education (n=20), exercise (n=3), psychological (n=1), lifestyle (n=4), and/or other interventions (n=1). Only three outcomes studies (two randomized controlled trials (RCTs) and a pilot study) compared the effectiveness of intervention components/delivery approaches. The two RCTs' results suggest that pre-operative TKR exercise interventions are equally effective regardless of whether they include strength or strength plus balance training and whether they are hospital- or home-based. Personal tailoring and using more than one delivery format were associated with improved outcomes and/or perceived as beneficial for multiple intervention types. CONCLUSIONS: Definitive evidence on the optimal design of pre-operative TKR interventions is lacking. Personal tailoring and employing multiple delivery formats appear to be valuable design elements. Preliminary evidence suggests that including balance training and hospital versus home delivery may not be critical design elements for pre-operative TKR exercise interventions. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42019143248 FUNDER: National Institute for Health and Care Research (ICA-CDRF-2018-04-ST2-006).

In vivo base editing by a single i.v. vector injection for treatment of hemoglobinopathies.

Individuals with ß-thalassemia or sickle cell disease and hereditary persistence of fetal hemoglobin (HPFH) possessing 30% fetal hemoglobin (HbF) appear to be symptom free. Here, we used a nonintegrating HDAd5/35++ vector expressing a highly efficient and accurate version of an adenine base editor (ABE8e) to install, in vivo, a -113 A>G HPFH mutation in the γ-globin promoters in healthy CD46/ß-YAC mice carrying the human ß-globin locus. Our in vivo hematopoietic stem cell (HSC) editing/selection strategy involves only s.c. and i.v. injections and does not require myeloablation and HSC transplantation. In vivo HSC base editing in CD46/ß-YAC mice resulted in > 60% -113 A>G conversion, with 30% γ-globin of ß-globin expressed in 70% of erythrocytes. Importantly, no off-target editing at sites predicted by CIRCLE-Seq or in silico was detected. Furthermore, no critical alterations in the transcriptome of in vivo edited mice were found by RNA-Seq. In vitro, in HSCs from ß-thalassemia and patients with sickle cell disease, transduction with the base editor vector mediated efficient -113 A>G conversion and reactivation of γ-globin expression with subsequent phenotypic correction of erythroid cells. Because our in vivo base editing strategy is safe and technically simple, it has the potential for clinical application in developing countries where hemoglobinopathies are prevalent.

Effect of Glucocorticoid and 11ß-Hydroxysteroid-Dehydrogenase Type 1 (11ß-HSD1) in Neurological and Psychiatric Disorders.

11ß-hydroxysteroid dehydrogenase type 1 (11ß-HSD1) activity is implicated as a moderator of the progression of multiple diseases and disorders in medicine and is actively subject to investigation as a therapeutic target. Here we summarize the mechanisms of the enzyme and detail the novel agents under investigation. Such agents modulate peripheral cortisol and cortisone levels in hypertension, type 2 diabetes, metabolic disorders, and Alzheimer's disease models, but there is mixed evidence for transduction into symptom management. There is inchoate evidence that 11ß-HSD1 modulators may be useful pharmacotherapies for clinical improvement in psychiatry and neurology; however, more research is required.

Independent External Validation of Artificial Intelligence Algorithms for Automated Interpretation of Screening Mammography: A Systematic Review.

PURPOSE: The aim of this study was to describe the current state of science regarding independent external validation of artificial intelligence (AI) technologies for screening mammography. METHODS: A systematic review was performed across five databases (Embase, PubMed, IEEE Explore, Engineer Village, and arXiv) through December 10, 2020. Studies that used screening examinations from real-world settings to externally validate AI algorithms for mammographic cancer detection were included. The main outcome was diagnostic accuracy, defined by area under the receiver operating characteristic curve (AUC). Performance was also compared between radiologists and either stand-alone AI or combined radiologist and AI interpretation. Study quality was assessed using the Quality Assessment of Diagnostic Accuracy Studies 2 tool. RESULTS: After data extraction, 13 studies met the inclusion criteria (148,361 total patients). Most studies (77% [n = 10]) evaluated commercially available AI algorithms. Studies included retrospective reader studies (46% [n = 6]), retrospective simulation studies (38% [n = 5]), or both (15% [n = 2]). Across 5 studies comparing stand-alone AI with radiologists, 60% (n = 3) demonstrated improved accuracy with AI (AUC improvement range, 0.02-0.13). All 5 studies comparing combined radiologist and AI interpretation with radiologists alone demonstrated improved accuracy with AI (AUC improvement range, 0.028-0.115). Most studies had risk for bias or applicability concerns for patient selection (69% [n = 9]) and the reference standard (69% [n = 9]). Only two studies obtained ground-truth cancer outcomes through regional cancer registry linkage. CONCLUSIONS: To date, external validation efforts for AI screening mammographic technologies suggest small potential diagnostic accuracy improvements but have been retrospective in nature and suffer from risk for bias and applicability concerns.

Medical Student Perspectives on Choosing a Career in Vascular Surgery.

BACKGROUND: Vascular surgery is facing an impending workforce shortage as the population ages and the demand for vascular surgical services increases. The integrated vascular surgery residency (0+5) paradigm is well-established and provides a mechanism to increase the number of board-certified vascular surgeons. Recruitment of medical students to these programs has proven challenging with unfilled positions in each of the past 2 years. The aim of this study is to explore factors that influence medical students' interest in vascular surgery and their decision to ultimately pursue a career in the field. METHODS: Medical students listed on the Society for Vascular Surgery "Find a VSIG (Vascular Surgery Interest Group)" webpage were contacted via email to participate in the study. A snowball sampling technique was employed to recruit additional participants, including recent medical school graduates who had matched into a 0+5 program. Fifteen students participated in 5 focus groups. Directed content analysis was employed to qualitatively analyze focus group transcripts. RESULTS: Five domains were identified as influencing students' decision to pursue vascular surgery. Experiential learning facilitated early exploration of the field. The intellectuality of the specialty was a feature that attracted students to vascular surgery. In addition, the professional identify of vascular surgeons as comprehensive care providers was appealing. Students identified with their mentors' relationships as observed during clinical encounters. Long-term mentorship was important in sustaining students' interest. CONCLUSION: Medical students pursue a career in vascular surgery based on early exposure to the specialty, experiential learning through hands-on VSIG events, clinical experiences, and longitudinal faculty mentorship. The unique aspects of the specialty, including professional identity and intellectuality, should be highlighted to both attract and maintain students' interest in the field. These findings can be used by national vascular surgery leaders, practicing vascular surgeons, and faculty and student leadership of VSIGs to optimize recruitment programs and increase the vascular surgery workforce.

Understanding peer mentorship in supporting self-management of hip and knee osteoarthritis: A qualitative study of mentees' perspectives.

BACKGROUND: Hip and knee osteoarthritis (OA) are common musculoskeletal conditions. Treatment is usually conservative, making self-management a priority. We developed and trialled an OA peer mentorship intervention to support self-management in older people. Our objectives were to gain understanding of the perceived challenges of living with OA and explore how a peer mentorship intervention can support tackling these challenges; and to explore mentees' experiences of receiving the intervention to understand how this affected their OA self-management. METHODS: Qualitative semi-structured interviews focussing on acceptability and feasibility of being in the study were conducted with mentees. Transcribed interviews were double coded and subject to framework analysis. To address the objectives of this paper, three main themes were subject to focused analysis: mentees' experiences of OA, experience of peer mentorship support and factors influencing self-management. RESULTS: Seventeen mentees participated in an interview following completion of the peer support intervention. Themes emerging from focused analysis were the following: tackling the challenges of living with OA pre- and post-intervention; and the interplay of the peer mentorship intervention and self-management. Key elements of the latter theme are enabling factors provided by peer mentorship, and mentees' readiness to self-manage. CONCLUSION: To effectively support OA self-management, peer mentorship interventions should include core educational components and focus on strategies that enhance key enablers of self-management. Paying attention to the mentor-mentee relationship and timing of intervention engagement can maximise opportunities for older people to adjust and transition from supported to independent self-management.