Royal College of Physicians

Background: There is sparse normative data on clitoral-vestibular bulb anatomy and how it changes with aging, despite growing evidence of the latter playing a notable role in female sexual function and other pelvic symptoms. Objective: To identify age differences in clitoral-vestibular bulb anatomy (dimensions, position, shape) among women across the adult lifespan. Study Design: This was a retrospective study of pelvic magnetic resonance images of women (≥18 years) without pelvic floor disorder/dysfunction symptom indications (pelvic organ prolapse, urinary incontinence/pain, fecal incontinence/pain, dyspareunia) and with normal pelvic anatomy (radiographically normal reproductive, genitourinary, or gastrointestinal systems). Participants were categorized into the following age groups: Young Adult (18-34 years), Early Midlife (35-49 years), and Older Adult (≥50 years). Axial images of participants in the supine position at rest were acquired for medical indications. The clitoral-vestibular bulb complex, vagina, and urethra were manually segmented to construct 3-dimensional anatomical models. Computational methods quantified clitoral-vestibular bulb dimensions, position, vaginal-urethral distances, and shape (given by principal component scores obtained from a statistical shape model). Age differences in clitoral-vestibular bulb measures were evaluated using Bonferroni-corrected one-way multivariate and univariate analyses of covariance, with adjustments for body mass index and parity. Age-related correlations were assessed using Spearman’s rank correlation. Results: A total of 134 women were analyzed (median [range] age, 39 [19-80] years): 47 Young Adult, 46 Early Midlife, and 41 Older Adult women. All Young Adult and Early Midlife women were premenopausal, whereas 27 (71%) of Older Adult women were postmenopausal. Older Adult women had a shorter clitoral body length than Early Midlife women (24.1 mm vs 27.9 mm; P=.006). Overall, smaller vestibular bulb volume was associated with increasing age (P=.04). Older Adult women had a more inferiorly positioned clitoral-vestibular bulb complex (lower in the pelvis) than Early Midlife women (-21.0 mm vs -17.6 mm; P<.001) and Young Adult women (-21.0 mm vs -17.9 mm; P<.001). Across the entire cohort, increasing age correlated with a shorter clitoral body length (ρ=-0.21; P=.01) and vestibular bulb volume (ρ=-0.20; P=.02), and a more posteriorly (ρ=-0.22; P=.01) and inferiorly (ρ=-0.43; P<.001) positioned clitoral-vestibular bulb complex, whereas clitoral volume remained unchanged (ρ=-0.03; P=.73). The shape analysis revealed that age predominantly affected the vestibular bulbs, which became more medially positioned (closer together) (ρ=-0.28; P=.001) and proportionally smaller relative to the clitoris (ρ=-0.28; P=.001) with advancing age. Conclusions: Older age was associated with reduced size and posterior-inferior descent of the clitoral-vestibular bulb complex, with aging primarily affecting the vestibular bulbs compared to the clitoris. Findings demonstrate age-related atrophy and descent of clitoral-vestibular bulb anatomy, which may contribute to sexual function and other pelvic symptoms.

Lichen planus (LP) is a rare, chronic inflammatory disorder affecting both skin and mucous membranes. LP has been associated with autoimmune conditions, glucose intolerance, dyslipidemia, and cardiovascular disorders; however, comprehensive data on these associations is limited. This study utilized data from the TrinetX Linked Network, comprising over 112 million patients, to assess the risk of comorbidities in LP patients from July 1, 2016, to December 9, 2024. LP patients were identified using International Classification of Diseases, 10th Revision, Clinical Modification codes, and propensity score matching was applied to compare comorbidity risks with a control cohort. The analysis revealed a significant association between LP and autoimmune dermatologic and rheumatologic conditions, including localized scleroderma, alopecia areata, vitiligo, psoriasis, lupus erythematous, Sjögren syndrome, autoimmune hepatitis, and autoimmune thyroiditis. Additionally, a lower risk was observed for hepatitis C and B infections in LP patients. The study highlights the stronger association between LP and autoimmune comorbidities, which could be linked to the higher prevalence of autoimmune diseases in women, explaining LP’s female predilection. These findings emphasize the need for heightened awareness of LP’s autoimmune nature. Limitations include diagnostic misclassification and potential geographic biases in the dataset.

Abstract Background Severe COVID-19 results in substantial economic burden and impacts quality of life. Assessing how non-hospitalized COVID-19 impacts health utilities during acute infection and long term is important to estimate the full economic impact of SARS-CoV-2 infection. Methods We analyzed EQ-5D-3L survey data from SARS-CoV-2 infected adults (aged ≥16 years) and children (aged 8-15 years) from three community and household cohorts in the United States (2020-2022). EQ-5D-3L scores were analyzed at three time points after symptom onset or first positive SARS-CoV-2 test result and converted to health utilities on a scale of 0-1 (1=perfect health). Among adults, regression models were used to compare differences in health utility by demographic/clinical characteristics. Results Among 538 SARS-CoV-2 non-hospitalized asymptomatic/symptomatic infections from 575 adults with EQ-5D-3L surveys, mean utilities were near 1 throughout the observation period. During 0-14 days, vaccinated participants had higher health utilities (Beta:0.57, 95% CI:0.07,1.07). Seeking medical care and having gastrointestinal symptoms (vs. none), were associated with lower health utilities (Beta, 95% CI:-0.96, −1.60, −0.31; and −0.76, −1.30, −0.21 respectively). During 15-30 days, unemployment was associated with lower health utility (Beta:-0.64, 95% CI:-1.15,-0.14). During 31-90 days, underlying conditions were associated with lower health utilities (Beta:-0.32, 95% CI:-0.54, −0.09). Results for children were similar to adults. Conclusion Non-hospitalized COVID-19 may have minimal overall impact on quality of life; however, health utilities differed by vaccination status, presence of gastrointestinal symptoms, employment status, and presence of underlying conditions. Vaccination may play an important role in minimizing illness impact from SARS-CoV-2 infection. Key points Severe COVID-19 illness causes substantial economic burden and impacts on quality of life; however, the incidence of non-hospitalized COVID-19 is far greater. Assessing how non-hospitalized COVID-19 impacts health during acute infection and long term is important to understand the full impact of SARS-CoV-2 infection. This study utilizes the EQ-5D-3L, a standardized generic preference-based instrument used in population health studies, to estimate health utilities at multiple time points following SARS-CoV-2 infection. The study also examines demographic/medical characteristics that are associated with health utility over time. While mean health utilities were high for all infection periods regardless of age, health utility was lower at varying time points post-infection among adults who sought medical care, reported gastrointestinal symptoms, were unemployed, and with underlying conditions. Vaccinated adults (vs. unvaccinated) had higher health utility and were less likely to report reduced health. Findings can be used as inputs for economic evaluation and assessing impact of interventions for non-hospitalized SARS-CoV-2 illness, such as vaccination.

Aberrant WNT/β-catenin signaling drives tumorigenesis and metastasis in cancer. Although enzymatic inhibitors of tankyrase (TNKS) effectively block AXIN degradation and stabilize the β-catenin destruction complex (DC), they have demonstrated limited efficacy in various cancer models. Here we demonstrate that, unexpectedly, the induction of AXIN puncta represents a major barrier to achieving therapeutic efficacy. Mechanistically, catalytic inhibition of TNKS prevents TNKS turnover and drives its accumulation in the DC, wherein the scaffolding function of TNKS induces AXIN puncta formation, rigidifies the DC, and impedes β-catenin turnover. Chemically induced degradation of TNKS overcomes this limitation by stabilizing AXIN without puncta formation, providing a deeper suppression of the WNT/β-catenin pathway activity and the proliferation of colorectal cancer cells harboring dysfunctional APC mutations. Collectively, these findings provide an explanation for the unsatisfactory outcomes of drugging the WNT/β-catenin signaling pathway by TNKS inhibitors and highlight TNKS degradation as a promising approach to treat WNT/β-catenin-driven cancers.

<h3>Background</h3> The Pulmonary Rehabilitation Services Accreditation Scheme (PRSAS), hosted by the Royal College of Physicians (RCP), was launched in April 2018 to improve the quality of UK pulmonary rehabilitation services. Participating services work to an accreditation pathway which involves self-assessment and quality improvement against the standards. Accredited services submit evidence annually to demonstrate maintenance to the standards and have a 5-yearly on-site assessment. The aim of this analysis was to explore the experiences of accredited services. <h3>Methods</h3> A mixed method survey was sent to current accredited services (2024) to record experiences of the service accreditation journey and to explore impact, barriers and facilitators to completing the accreditation process. A descriptive analysis was undertaken with content analysis for qualitative content. <h3>Results</h3> At the time of the survey 160 services were participating in PRSAS, of which 21 were accredited, 18(86%) returned the service annual survey. Most of the services (77.8% 14/18) reported measurable changes since starting and achieving accreditation, these included improvements to the exercise delivery programme (21.4% 3/14), reduced waiting times (28.6% 4/14) and improved patient outcome measures tools/data collection (42.8% 6/14). Similar numbers (77.8% 14/18) reported positive opportunities post-accreditation, including better clinical links, awareness of PR services within their organisation and/or externally (64.3% 9/14) and increased staffing (retention/recruitment/promotion, 42.8% 6/14). 88.9% (16/18) had implemented recommendations (i.e. embedding operational plans and processes [50.0% 8/16], exercise programme changes [37.5% 6/16]). Feedback from participants highlighted a lack of standardised templates and the need for more information resources to support the process. Variation in assessor requests and as well as additional hurdles with trust requirements for data presentation were also highlighted. Several participants highlighted that the accreditation process can be ’overwhelming’ and ‘tricky’ to coordinate alongside running clinical services. However, after completion of the process many would consider being an accreditation champion (66.7% 12/18), the numbers participating in and completing the process successfully are increasing. <h3>Conclusions</h3> These findings suggest that accreditation provides measurable impact on service Key Performance Indicators and patient outcomes.

<h3>Background</h3> Despite established standards for ward and ED discharge letters, the quality of paediatric asthma discharge letters remains variable, and information can lack salient details, including management and follow-up. There is a need for a consensus on the information and structure required for discharge letters to ensure safe and effective handover of care to the primary care clinician, child’s school or parent/carer. <h3>Aim</h3> To establish agreed core elements for standardised paediatric asthma discharge letter template. <h3>Method</h3> The National Respiratory Audit Programme (NRAP) Children and Young People Asthma Team used the Delphi method, comprising of multiple survey rounds, to secure a consensus from subject experts. We recruited clinicians from all healthcare settings involved in paediatric asthma care directly and via national groups: British Paediatric Respiratory Society, British Thoracic Society, Association of Respiratory Nurses, Primary Care Respiratory Society, School and Public Health Nurses Association, National Paediatric Respiratory and Allergy Nurses Group, and teams participating in the National Respiratory Audit Program audit. For Patients and Public Involvement and Engagement, we consulted the RCPCH. <h3>Initial Results</h3> 55 participants, including clinicians (general practitioners, general and respiratory paediatric consultants, nurses, pharmacists), and parents/carers were asked to identify the top 3 discharge elements out of a list of 25, which were established during initial open consultation with stakeholders. Each choice was then graded by the level of importance on a scale of 1–5. 71% of participants identified red flags (e.g. previous hospitalisation, high salbutamol use), as the most important element, followed by treatment plan (31%), record of previous exacerbations/hospitalisations (31%), inhaler technique check and provision of asthma action plan (27%), hospital treatment (27%), clear diagnosis (22%), and instructions for GP (24%). The remaining elements were scored as of lower relevance, with less than 20% of participants voting for them. <h3>Conclusions</h3> This initial DELPHI round to develop best practice standards for CYP with Asthma identified patient red flags as the most important core element of the discharge letter; further rounds are required to reach consensus on the other elements, which will inform the outline of the discharge letter template.

BackgroundCoaching is increasingly recognized as a valuable tool to amplify learning in undergraduate medical education (UME), yet national data on its implementation, particularly in the context of clinical skills education, remain limited. Previous survey studies on coaching in medical education have focused on select institutions with established coaching programs, leaving a gap in understanding the broader landscape of coaching in UME. This study aims to address three critical gaps: current descriptions of coaching programs across U.S. medical schools, the nature of support provided to faculty coaches in these programs, and understanding how coaching is integrated into clinical skills development.MethodsA national survey was distributed to members of the Directors of Clinical Skills (DOCS) organization, targeting clinical skills educators at U.S. allopathic medical schools. The 29-item survey included multiple-choice, ranked, and open-ended questions. Responses were analyzed using both qualitative and quantitative approaches, combining descriptive statistics with content and thematic analysis to explore coaching program structure, goals, clinical skills impact, evaluation practices, and faculty development.ResultsOf the 44 respondents, 38 completed the majority of the survey. Nearly half (47%) reported having an active coaching program, with an additional 14% planning to implement a program. Coaching commonly begins in the pre-clerkship phase (93%) and emphasizes longitudinal relationships (87%). Key priorities included professional identity formation and clinical skills development, with history-taking, presentation skills, and clinical reasoning identified as skills most amenable to coaching. Respondents highlighted coaching’s role in fostering constructive learning environments, promoting skill development, and increasing student confidence. However, variations persist in program structure, oversight, and evaluation practices between institutions. Faculty development is widely implemented, with 94% of programs offering ongoing training and 79% compensating their coaches. Communication skills were ranked as the most critical competency for coach development. Evaluation practices were varied, with most programs relying on student satisfaction surveys (69%) and formative feedback (73%).ConclusionThis study provides a current national snapshot of coaching in UME through the lens of clinical skills educators. It underscores the growing recognition of coaching’s value in clinical skills development and professional identity formation. While coaching programs are increasingly supported by faculty development and compensation, variability in structure, oversight, and evaluation remains.Supplementary InformationThe online version contains supplementary material available at 10.1186/s12909-025-08115-5.

ABCA7 (ATP-binding cassette sub-family A member 7) encodes a lipid transporter linked to Alzheimers disease (AD). While common variants confer modest risk in Europeans, a 44-base pair deletion (rs142076058; p.Arg578Alafs) is a strong risk factor in African Americans (AA). Despite this, the biological consequences of this ancestry-specific variant are not well understood. We expressed the truncated ABCA7 protein in HEK and HepG2 cells to assess localization and lipid metabolism. Additionally, induced pluripotent stem cell (iPSC)-derived neurons carrying the deletion were compared with isogenic controls. The truncated ABCA7 localized to the plasma membrane similarly to wild type but induced significant lipid droplet accumulation in HepG2 cells and iPSC-derived neurons. These findings show that the AA-specific ABCA7 deletion disrupts lipid regulation despite normal localization, suggesting a mechanistic link between impaired lipid homeostasis and increased AD risk. This work underscores the importance of ancestry-specific studies in AD research.

In transference-focused psychotherapy (TFP), an evidence-based treatment for patients with borderline personality disorder (BPD), the attention paid to establishing and tracking goals is both organizing and distinctive. The objective of this article is to describe TFP's unusual emphasis on first elucidating and then focusing on a patient's concrete, measurable personal goals. We review the critical distinction between the patient's goals and the therapist's goals. We also provide pertinent examples of material related to goals in TFP. The examination of the role of goals in the treatment of patients with BPD has significant salience given accumulating data that suggests that symptom remission does not reliably lead to enhanced functioning (sustained work/study performance, stable relations with a partner or parents) in this patient population.

Reflex syncope is a common cause of transient loss of consciousness, often leading to injuries and a reduced quality of life. Despite the benign nature of isolated episodes, recurrent syncope poses significant clinical challenges. Cardiac pacing has been investigated as a treatment modality, particularly in patients with cardioinhibitory phenotypes, yet prior studies have shown heterogeneous outcomes. A systematic review and meta-analysis were conducted to evaluate the efficacy of permanent cardiac pacing in preventing recurrent reflex syncope. Comprehensive searches of PubMed and the Cochrane Library were performed up to September 2024 using the terms "reflex syncope" and "cardiac pacing." Eligible studies included randomised controlled trials (RCTs) involving adult patients with recurrent reflex syncope undergoing permanent pacemaker implantation. Systematic reviews, narrative reviews, case reports or series, editorials, and conference abstracts were excluded from the review. Two independent reviewers screened studies and extracted data using Covidence, with discrepancies resolved by consensus. A meta-analytical synthesis was performed using odds ratios (ORs) for recurrent syncope, employing a random- and fixed-effects model. Heterogeneity was assessed using Cochran's Q, I² statistic, and τ². Seven RCTs were included, comprising a total of 458 patients. The primary outcomes showed a pooled analysis indicating a significant protective effect of pacing in reducing syncope recurrence compared to controls (OR 0.37; 95% CI: 0.22-0.62; p = 0.009), supporting the efficacy of permanent cardiac pacing in this population. Heterogeneity was low (Q = 6.60, p = 0.36; I² = 38%; τ² = 0.051), supporting the use of a fixed-effects model, which showed a similar outcome (Log(OR) 0.378 (95% CI, 0.229-0.624; p < 0.001)). The included trials varied in pacing modality (dual-chamber pacing (DDD), closed-loop stimulation (CLS), rate-drop response (RDR)), patient selection criteria, and diagnostic approaches. Secondary outcomes included reductions in pre-syncopal symptoms and delayed recurrence of syncope with pacing, along with a low incidence of device-related adverse events. However, inconsistent reporting limited the comprehensive meta-analysis of these endpoints. Permanent pacing reduces the risk of recurrent syncope in selected patients with reflex syncope, particularly those with documented asystole or cardioinhibitory phenotypes. CLS and RDR pacing algorithms may provide enhanced protection compared to conventional DDD pacing; however, variability in patient selection and device programming across studies limits the generalisability of these findings. Larger, standardised RCTs are needed to refine patient selection criteria and optimise pacing strategies for reflex syncope.