Phenotypic clustering of bipolar disorder supports stratification by lithium responsiveness over diagnostic subtypes.

INTRODUCTION: The aim of this study was to determine whether the clinical profiles of bipolar disorder (BD) patients could be differentiated more clearly using the existing classification by diagnostic subtype or by lithium treatment responsiveness. METHODS: We included adult patients with BD-I or II (N = 477 across four sites) who were treated with lithium as their principal mood stabilizer for at least 1 year. Treatment responsiveness was defined using the dichotomized Alda score. We performed hierarchical clustering on phenotypes defined by 40 features, covering demographics, clinical course, family history, suicide behaviour, and comorbid conditions. We then measured the amount of information that inferred clusters carried about (A) BD subtype and (B) lithium responsiveness using adjusted mutual information (AMI) scores. Detailed phenotypic profiles across clusters were then evaluated with univariate comparisons. RESULTS: Two clusters were identified (n = 56 and n = 421), which captured significantly more information about lithium responsiveness (AMI range: 0.033 to 0.133) than BD subtype (AMI: 0.004 to 0.011). The smaller cluster had disproportionately more lithium responders (n = 47 [83.8%]) when compared to the larger cluster (103 [24.4%]; p = 0.006). CONCLUSIONS: Phenotypes derived from detailed clinical data may carry more information about lithium responsiveness than the current classification of diagnostic subtype. These findings support lithium responsiveness as a valid approach to stratification in clinical samples.

GP trainees as teachers: a rapid review of the barriers, facilitators and outcomes.

BACKGROUND: There is a workforce crisis in General Practice (GP) within the United Kingdom (UK). High-quality clinical placement experiences in GP influence medical students' interest and likelihood to enter this speciality. GP trainees often express a desire to teach, yet teaching does not feature significantly within their current practice. This study aims to explore outcomes, barriers, and facilitators of GP trainees teaching medical students through a rapid review of published literature. METHODS: MEDLINE, EMBASE, PsychINFO, Web of Science were searched for articles relating to GP trainees teaching. Studies conducted in the UK and Australia, between January 2000 and October 2022 were included. The Medical Education Research Study Quality Index and the Critical Appraisal Skills Programme checklist were used to assess quality. RESULTS: Twenty-seven publications, 11 qualitative, six quantitative, three mixed-methods and seven opinion pieces, were identified. Many studies have methodological limitations. Empirical studies show that there are benefits of near-peer teaching, but these are limited by trainees' capacity and capability to teach, and GPs' confidence in trainees' teaching. The culture within the practice influenced whether trainees were seen solely as learners or also as teachers for students. DISCUSSION: When GP trainees teach there are positive outcomes for medical students and trainees. Teaching was considered an activity that trainees did in 'addition to' rather than 'part' of' their training. Appropriate teaching opportunities, and relevant training, were key to trainees' competence and confidence in teaching. Resources and recognition and a strong teaching culture are needed to support GP trainees to teach.

Direct decarboxylative Giese amidations: photocatalytic vs. metal- and light-free.

A direct intermolecular decarboxylative Giese amidation reaction from bench stable, non-toxic and environmentally benign oxamic acids has been developed, which allows for easy access to 1,4-difunctionalised compounds which are not otherwise readily accessible. Crucially, a more general acceptor substrate scope is now possible, which renders the Giese amidation applicable to more complex substrates such as natural products and chiral building blocks. Two different photocatalytic methods (one via oxidative and the other via reductive quenching cycles) and one metal- and light-free method were developed and the flexibility provided by different conditions proved to be crucial for enabling a more general substrate scope.

Differential characteristics of bipolar I and II disorders: a retrospective, cross-sectional evaluation of clinical features, illness course, and response to treatment.

BACKGROUND: The distinction between bipolar I and bipolar II disorder and its treatment implications have been a matter of ongoing debate. The aim of this study was to examine differences between patients with bipolar I and II disorders with particular emphasis on the early phases of the disorders. METHODS: 808 subjects diagnosed with bipolar I (N = 587) or bipolar II disorder (N = 221) according to DSM-IV criteria were recruited between April 1994 and March 2022 from tertiary-level mood disorder clinics. Sociodemographic and clinical variables concerning psychiatric and medical comorbidities, family history, illness course, suicidal behavior, and response to treatment were compared between the bipolar disorder types. RESULTS: Bipolar II disorder patients were more frequently women, older, married or widowed. Bipolar II disorder was associated with later "bipolar" presentation, higher age at first (hypo)mania and treatment, less frequent referral after a single episode, and more episodes before lithium treatment. A higher proportion of first-degree relatives of bipolar II patients were affected by major depression and anxiety disorders. The course of bipolar II disorder was typically characterized by depressive onset, early depressive episodes, multiple depressive recurrences, and depressive predominant polarity; less often by (hypo)mania or (hypo)mania-depression cycles at onset or during the early course. The lifetime clinical course was more frequently rated as chronic fluctuating than episodic. More patients with bipolar II disorder had a history of rapid cycling and/or high number of episodes. Mood stabilizers and antipsychotics were prescribed less frequently during the early course of bipolar II disorder, while antidepressants were more common. We found no differences in global functioning, lifetime suicide attempts, family history of suicide, age at onset of mood disorders and depressive episodes, and lithium response. CONCLUSIONS: Differences between bipolar I and II disorders are not limited to the severity of (hypo)manic syndromes but include patterns of clinical course and family history. Caution in the use of potentially mood-destabilizing agents is warranted during the early course of bipolar II disorder.

Familial traits of bipolar disorder: A systematic review and meta-analysis.

BACKGROUND: Genetic studies of bipolar disorder (BD) have shown varied results, which is in part because of the heterogeneity of the disorder. Identifying clinical phenotypes of BD could reduce variability and benefit research. Since BD has a robust genetic component, studies can investigate clinical traits that cluster in families to identify phenotypes with a probable genetic basis. METHODS: We conducted a systematic review of the current literature on familial clinical traits of BD. Text screening and data extraction were performed independently by two reviewers, and random effects meta-analysis was used. RESULTS: Of 1117 unique records, 16 studies met inclusion criteria. These studies indicated 14 potentially familial traits of BD: age of onset (OR: 4.50; 95% CI: [3.25, 6.22]), bipolar type (OR: 2.05 [1.50, 2.79]), lithium response (OR: 3.71 [1.28, 10.82]), polarity at onset (OR: 1.17 [1.03, 1.34]), psychotic features (OR: 2.20 [1.51, 3.20]), mood-incongruent psychosis (OR: 2.52 [1.66, 3.83]), puerperal psychosis (OR: 6.54 [2.55, 16.77]), rapid cycling (OR: 4.95 [0.96, 25.40]), suicide attempt (OR: 1.04 [0.65, 1.67]), alcoholism (OR: 1.53 [1.09, 2.16]), obsessive-compulsive disorder (OR: 3.10 [1.31; 7.09]), panic disorder (OR: 2.69 [1.12; 6.48]), social anxiety disorder (OR: 1.00 [0.39, 2.55]), and specific phobia (OR: 1.94 [0.95; 3.96]). For most traits, tests of heterogeneity were significant and publication bias was likely. CONCLUSION: The results of our review and meta-analysis highlight the lack of studies investigating familial clinical traits of BD, despite the need to address heterogeneity. The large degree of variability between studies must be reduced for future research.

High fat diet improves metabolic flexibility during progressive exercise to exhaustion (VO2max testing) and during 5 km running time trials.

Recently we reported similar performances in both progressive tests to exhaustion (VO2max) and 5km running time trials (5KTT) after consuming low-carbohydrate, high-fat (LCHF) or high-carbohydrate, low-fat (HCLF) diets. Accordingly, we tested the null hypothesis that the metabolic responses during both tests would be similar across diets. In a randomized, counterbalanced, cross-over design, seven male athletes (VO2max: 61.9 ± 6.1 mL/kg/min; age: 35.6 ± 8.4 years; height: 178.7 ± 4.1 cm; mass: 68.6 ± 1.6 kg; body fat: 5.0 ± 1.3%) completed six weeks of LCHF (6/69/25% energy carbohydrate/fat/protein) and HCLF (57/28/15% energy carbohydrate/fat/protein) diets, separated by a two-week washout. Substrate utilization and energy expenditure were measured during VO2max tests and 5KTTs. The LCHF diet markedly increased fat oxidation and reduced carbohydrate oxidation, with no associated impairment in either the VO2max tests or the 5KTTs. Following the LCHF diet, athletes generated 50% or more of their energy requirements from fat at exercise intensities up to 90% VO2max and reached the crossover point for substrate utilization at ~85% VO2max. In contrast, following the HCLF diet, carbohydrate provided more than 50% of the total energy consumption at all exercise intensities. During the 5KTT, ~56% of energy was derived from fat following the LCHF diet whereas more than 93% of the energy came from carbohydrate following the HCLF diet. This study provides evidence of greater metabolic flexibility following LCHF eating and challenges the popular doctrines of "carbohydrate dependence" for high intensity exercise and the role dietary macronutrients play in human performance.

Recommendations for Medical Discharge Documentation and Academic Supports for University Students Recovering From Concussion.

OBJECTIVE: This study sought to (1) collate the experiences of university students with concussion history and academic stakeholders through interviews and (2) develop concussion management recommendations for institutions of higher learning using a multidisciplinary Delphi procedure. SETTING: Remote semistructured interviews and online surveys. PARTICIPANTS: The first aim of this study included undergraduate university students with concussion history who did not participate in varsity athletics ( n = 21; 57.1% female), as well as academic faculty/staff with experience assisting university students with their postconcussion academic needs ( n = 7; 71.4% female). The second aim enrolled 22 participants (54.5% female) to serve on the Delphi panel including 9 clinicians, 8 researchers, and 5 academic faculty/staff. DESIGN: An exploratory-sequential mixed-methods approach. MAIN MEASURES: Semistructured interviews were conducted to unveil barriers regarding the return-to-learn (RTL) process after concussion, with emergent themes serving as a general framework for the Delphi procedure. Panelists participated in 3 stages of a modified Delphi process beginning with a series of open-ended questions regarding postconcussion management in higher education. The second stage included anonymous ratings of the recommendations, followed by an opportunity to review and/or modify responses based on the group's consensus. RESULTS: The results from the semistructured interviews indicated students felt supported by their instructors; however, academic faculty/staff lacked information on appropriate academic supports and/or pathways to facilitate the RTL process. Of the original 67 statements, 39 achieved consensus (58.2%) upon cessation of the Delphi procedure across 3 main categories: recommendations for discharge documentation (21 statements), guidelines to facilitate a multidisciplinary RTL approach (10 statements), and processes to obtain academic supports for students who require them after concussion (8 statements). CONCLUSIONS: These findings serve as a basis for future policy in higher education to standardize RTL processes for students who may need academic supports following concussion.

Achieving Consensus Through a Modified Delphi Technique to Create the Post-concussion Collegiate Return-to-Learn Protocol.

BACKGROUND: Sport-related concussions (SRCs) affect millions of adolescents and young adults annually in the USA; however, current SRC consensus statements provide limited guidance on academic support for students within higher education. OBJECTIVE: To generate consensus on appropriate academic recommendations for clinicians, students, and academic stakeholders to support university students during their recovery. METHODS: Panelists participated in three stages of a modified Delphi procedure: the first stage included a series of open-ended questions after reviewing a literature review on post-SRC return-to-learn (RTL) in higher education; the second stage asked panelists to anonymously rate the recommendations developed through the first Delphi stage using a 9-point scale; and the final stage offered panelists the opportunity to change their responses and/or provide feedback based on the group's overall ratings. RESULTS: Twenty-two panelists including clinicians, concussion researchers, and academic stakeholders (54.5% female) from 15 institutions and/or healthcare systems participated in a modified Delphi procedure. A total of 42 statements were developed after round one. Following the next two rounds, 27 statements achieved consensus amongst the panel resulting in the four-stage Post-Concussion Collegiate RTL Protocol. CONCLUSION: There are several unique challenges when assisting university students back to the classroom after SRC. Explicit guidelines on when to seek additional medical care (e.g., if they are experiencing worsening or persistent symptoms) and how to approach their instructor(s) regarding academic support may help the student self-advocate. Findings from the present study address barriers and provide a framework for universities to facilitate a multidisciplinary approach amongst medical and academic stakeholders.

"Having Pain is Normal": How Talk about Chronic Pelvic and Genital Pain Reflects Messages from Menarche.

Chronic pelvic and genital pain conditions (CPGPCs) often go undiagnosed and untreated in women for years after symptom onset. This is due, in part, to communication challenges experienced by patients such as difficulties describing pain and the stigmatized nature of CPGPCs. However, studies have yet to explore how early messages about menstruation, a context similar in its stigmatized and painful nature, may contribute to undertreatment and diagnostic delays for adult women experiencing CPGPCs by normalizing pelvic and genital pain when they are young girls. Guided by critical feminist theorizing (CFT) and sensitized by an existing typology of negative messages communicated by mothers to daughters about menstruation, this study analyzes interviews with 17 women with CPGPCs to explore how features of negative messages about menstruation (i.e., information restriction and omission) appear and recur in women's descriptions of their later CPGP experiences. Findings suggest that early life talk about menstruation forms a communicative precedent for young girls which later constrains how they talk about CPGP in adulthood. Findings also problematize early-life communication about menstruation, which normalizes women's pain, and suggest connections to outcomes (e.g., diagnostic delays) for women with CPGPCs. Theoretical and practical implications are offered. Limitations and future directions are described.

The impact of Covid-19 on professional identity formation: an international qualitative study of medical students' reflective entries in a Global Creative Competition.

INTRODUCTION: The Covid-19 pandemic, which affected medical students globally, could be viewed as a disorientating dilemma with the potential to offer opportunities for transformative learning. In 2021 the Medical Education Innovation and Research Centre at Imperial College London launched a Global Creative Competition as a platform for medical students to reflect on their experiences during the pandemic. METHODS: Six hundred forty-eight creative pieces with written reflections were submitted by medical students from 52 countries. 155 students from 28 countries consented for their entries to be included in this study. The reflections were analysed thematically and independently by three reviewers to explore how the pandemic impacted students' professional identity formation (PIF). RESULTS: The pandemic increased students' awareness of the social and global role of doctors in addressing health inequities. Students felt part of a wider healthcare community and showed greater appreciation towards person-centred care. Students also became more aware of their personal needs, priorities, and the importance of self-care. DISCUSSION: In agreement with Mezirow's theory of transformative learning (2003), the pandemic led students to re-examine pre-existing epistemic and sociocultural assumptions concerning the role of doctors and explore new perspectives of what it means to be a doctor. In accordance with Cheng's theory of coping flexibility (2021), students developed both emotion-focused coping strategies (e.g., arts engagement) and problem-solving strategies (e.g., volunteering), suggesting they were able to adjust psychologically and develop agency. However, students experienced tension between their sense of duty and sense of wellbeing, highlighting the need for medical educators to design into programmes formal support systems where medical students have the space and time they need to reflect on their emergent identities as a doctor. CONCLUSION: Medical educators should encourage students to reflect on their identity formation while encountering disorientating dilemmas. The inclusion of arts and humanities within the medical curriculum is strongly recommended to provide an avenue for students to access and express complex emotions and experiences.

The Effects of Carbohydrate versus Fat Restriction on Lipid Profiles in Highly Trained, Recreational Distance Runners: A Randomized, Cross-Over Trial.

A growing number of endurance athletes have considered switching from a traditional high-carbohydrate/low-fat (HCLF) to a low-carbohydrate/high-fat (LCHF) eating pattern for health and performance reasons. However, few studies have examined how LCHF diets affect blood lipid profiles in highly-trained runners. In a randomized and counterbalanced, cross-over design, athletes (n = 7 men; VO2max: 61.9 ± 6.1 mL/kg/min) completed six weeks of two, ad libitum, LCHF (6/69/25% en carbohydrate/fat/protein) and HCLF (57/28/15% en carbohydrate/fat/protein) diets, separated by a two-week washout. Plasma was collected on days 4, 14, 28, and 42 during each condition and analyzed for: triglycerides (TG), LDL-C, HDL-C, total cholesterol (TC), VLDL, fasting glucose, and glycated hemoglobin (HbA1c). Capillary blood beta-hydroxybutyrate (BHB) was monitored during LCHF as a measure of ketosis. LCHF lowered plasma TG, VLDL, and TG/HDL-C (all p < 0.01). LCHF increased plasma TC, LDL-C, HDL-C, and TC/HDL-C (all p < 0.05). Plasma glucose and HbA1c were unaffected. Capillary BHB was modestly elevated throughout the LCHF condition (0.5 ± 0.05 mmol/L). Healthy, well-trained, normocholesterolemic runners consuming a LCHF diet demonstrated elevated circulating LDL-C and HDL-C concentrations, while concomitantly decreasing TG, VLDL, and TG/HDL-C ratio. The underlying mechanisms and implications of these adaptive responses in cholesterol should be explored.

Public health for paediatricians: 15-minute guide to identify and address food insecurity.

Food insecurity is a major problem in the UK. It has been both highlighted and exacerbated by the COVID-19 pandemic, and particularly affects children and young people (CYP). The effects of inadequate nutrition manifest themselves in all stages of child development and adversely affect health and educational outcomes. Healthcare professionals working with CYP can address food insecurity at individual, local community, organisational and national levels. The government plays an important role in monitoring and responding to food insecurity, supporting CYP most in need.This paper summarises how food insecurity can be identified and approached by healthcare professionals in clinical consultations, including the use of screening tools and awareness of risk factors that signpost family food insecurity. Examples of services and clinician-assisted referrals to support vulnerable patients are provided, alongside suggested methods to implement further education for the multidisciplinary healthcare team.

WATCCH: a multiprofessional approach to widening participation in healthcare careers.

BACKGROUND: Students from lower socioeconomic backgrounds are underrepresented in higher education and healthcare careers. Whilst most healthcare-related widening participation schemes focus on one healthcare profession, the Widening Access to Careers in Community Healthcare (WATCCH) programme at Imperial College London supports participation in a range of community healthcare careers. We aim to evaluate the impact of WATCCH on students' perceptions and aspirations towards community healthcare careers. METHOD: WATCCH provides educational and application support to 16-18 year-old students interested in a variety of community healthcare careers via work experience, educational workshops and mentoring. The programme was evaluated by focus groups using semi-structured questions to explore the impact of WATCCH on students' healthcare career perceptions and aspirations. RESULTS: Five themes were identified from the focus groups: increased awareness and understanding of a range of community healthcare careers; improved insight into the realities of healthcare careers enabling reflection on career aspirations; altered perceptions of healthcare professionals and acquisition of new role models; increased confidence in achieving a career in healthcare; and valued access to previously inaccessible work experience. DISCUSSION: WATCCH is a multi-professional widening participation programme that has supported students from lower socioeconomic backgrounds interested in entering healthcare careers by increasing insights into varied healthcare careers, provision of role models, and increasing students' confidence of ability to enter healthcare careers. Similar programmes in other institutions could support large numbers of aspiring students to enter varied community healthcare careers in the future.

The experiences of therapists providing psychological treatment for adults with depression and intellectual disabilities as part of a randomised controlled trial.

BACKGROUND: Health professionals were trained to deliver adapted psychological interventions for depression to people with learning disabilities and depression alongside a supporter. Exploring the delivery of psychological interventions can help increase access to therapy. METHOD: Twenty-seven participants took part in six focus groups, and the data were subject to a Framework Analysis. RESULTS: The structure and focus of the manualised therapies, and the use of specific techniques were perceived as key to service-user engagement. Supporters' involvement was valued by therapists if they had a good relationship and regular contact with the individual they supported. Regular clinical supervision was regarded as vital in understanding their role, assessing progress and delivering the interventions. CONCLUSIONS: The findings highlight that health professionals can embrace a focussed therapeutic role and increase access to psychological therapies for people with intellectual disabilities.

Communication Work About Chronic Unexplained Pain.

This essay draws upon Donovan's conceptualization of "communication as work" to explicate types of communicative work undertaken by the authors - two patients with vulvodynia, a poorly understood chronic genital pain condition - during patient-provider interactions prior to diagnosis. Uniquely positioned as patients-turned-scholars, we extend the rich construct of "communication work" by narrating the types of communicative work undertaken ourselves as patients communicating within a stigmatized health context for which a clear diagnosis is often ambiguous or unable to be reached. Donovan notes that conditions with a high degree of uncertainty and ambiguity have the capacity to shift the nature of talk. This brief essay illustrates the ways in which the nature of patient-provider communication work is shifted by the ambiguity of this health context. Theoretical and practical implications are briefly offered.

The Use of B-Cell Polysome Profiling to Validate Novel RPL5 (uL18) and RPL26 (uL24) Variants in Diamond-Blackfan Anemia.

Diamond-Blackfan anemia (DBA) is a rare bone marrow failure syndrome usually caused by heterozygous variants in ribosomal proteins (RP) and which leads to severe anemia. Genetic studies in DBA rely primarily on multigene panels that often result in variants of unknown significance. Our objective was to optimize polysome profiling to functionally validate new large subunit RP variants. We determined the optimal experimental conditions for B-cell polysome profiles then performed this analysis on 2 children with DBA and novel missense RPL5 (uL18) and RPL26 (uL24) variants of unknown significance. Both patients had reduced 60S and 80S fractions when compared with an unaffected parent consistent with a large ribosomal subunit defect. Polysome profiling using primary B-cells is an adjunctive tool that can assist in validation of large subunit RP variants of uncertain significance. Further studies are necessary to validate this method in patients with known DBA mutations, small RP subunit variants, and silent carriers.

Treatment challenges and support needs of underserved Hispanic patients diagnosed with lung cancer and head-and-neck cancer.

Purpose: We explored the treatment challenges and support needs that Hispanic underserved lung cancer and head-and-neck cancer patients face while undergoing cancer treatment.Design: Qualitative design - ethnography.Sample: Using a sample of 29 participants, we conducted semi-structured interviews with nine lung cancer and head-and-neck cancer survivors and seven health care providers and focus group interviews with six caregivers and seven patient navigators.Method: Relevant themes were extracted with Ethnographic content analysis.Findings: Participants reported treatment challenges and support needs in four areas: medical, financial, socio-cultural, and mental health. Health care providers and navigators primarily identified medical and financial challenges that impact treatment adherence, while patients and caregivers expressed the need for support for mental health problems (i.e., depression, anxiety).Implications for psychosocial providers: Understanding the experiences of underserved Hispanic cancer survivors can aid in creating psychosocial interventions that successfully target treatment-related challenges and provide them with the support they need.

High Rates of Fat Oxidation Induced by a Low-Carbohydrate, High-Fat Diet, Do Not Impair 5-km Running Performance in Competitive Recreational Athletes.

A common belief is that high intensity exercise (>60%VO2max) is best sustained by high rates of carbohydrate oxidation. The belief is based, in part, on an idea developed by Krogh and Lindhard in 1920. In the 100 years since, few studies have tested its validity. We tested the null hypothesis that performance in competitive recreational athletes exercising at >80% VO2max, during simulated 5-km running time trials (5KTT) would be impaired during a 6-week period of adaption to a low-carbohydrate, high-fat (LCHF) diet, compared to their performances when they ate a diet higher in carbohydrate and lower in fat (HCLF). Seven male athletes (age 35.6 ± 8.4 years, height 178.7 ± 4.1 cm, weight 68.6 ± 1.6 kg) completed two maximal exercise (VO2max) tests (Day 1 and 39) and four 5KTT (Day 4, 14, 28, and 42) in a fasted state during two 6-week periods when they ate either a HCLF or a LCHF diet, in a randomized counterbalanced, crossover design. Exercise performance during the VO2max tests was unchanged on either diet (p = 0.251). Performance in the initial 5KTT was significantly slower on the LCHF diet (p = 0.011). There were no diet-related performance differences in the remaining three 5KTT (p > 0.22). Subjects exercised at ~82%VO2max. Carbohydrate oxidation provided 94% of energy on the HCLF diet, but only 65% on the LCHF diet. 5KTT performance at ~82%VO2max was independent of the runners' habitual diet. The HCLF diet offered no advantage over a diet with a high-fat content. Since these athletes run faster than 88% of recreational distance runners in the United States (U.S.), this finding may have wide general application.