Enhancing Equity in a Widening Participation Scheme for School Students.

OBJECTIVES: The Royal College of Surgeons (RCS) Diversity Review 2021 found that premedical school students from ethnic minority backgrounds were dissuaded from pursuing a surgical career. Gloucestershire is in the bottom 20% of disadvantaged counties; there is no widening participation (WP) scheme in the county. We implemented a fully inclusive WP scheme in Gloucester, with means of accessing virtual and face-to-face work experience, to enhance the equity of work experience. METHODS: A three-stage project was conducted. Stage 1; two separate virtual Q and A sessions, to allow students to ask questions about life as a doctor. Stage 2; conversation between student and patient held virtually, to gain insight into working as a doctor to help determine whether medicine is the career for them. Stage 3; face-to-face work experience. Distribution sent to all 58 schools (state and private) in the county, targeted at secondary school children. RESULTS: One hundred twenty-nine people attended the Q and A; 70 feedback responses received. Of the total, 86% female and 56% of ethnic minority background. 26% did not have an immediate family member that attended university, 10% had care-giving responsibilities. Eighty-one percent rated the session >8/10 for usefulness. Twenty-seven undertook the virtual conversation, feedback from 11; 91% female, 45% of ethnic minority background, and 27% did not have an immediate family member that attended university. All rated the session 10/10 for usefulness. 10 attended the face-to-face experience, 50% from an ethnic minority background. CONCLUSION: The RCS Report identified barriers to aspiring students from less-privileged backgrounds pursuing a medical career. More needs to be done with WP schemes to promote equity. Targeted distribution of WP schemes to all schools, utilization of a variety of means of offering work experience, and accessibility to any school-aged student were aspects of our WP to improve exposure to the medical profession.

Psychosocial interventions and strategies to support young people at mass gathering events: a scoping review.

OBJECTIVES: To improve health and safety outcomes at mass gathering events (MGEs) for young attendees, it is essential to understand the psychosocial factors that may influence behaviour so that the implementation of support strategies before, during and after MGEs can be developed to enhance outcomes. This review identifies the psychosocial outcomes that may occur at MGEs, including social connection, substance use, risky behaviours and psychological distress and examines what interventions have been implemented to target these outcomes. STUDY DESIGN: Scoping review. METHODS: This study examined MGE psychosocial interventions with predominantly youth attendees was conducted using the Preferred Reporting Items of Systematic reviews and Meta-Analysis extension for Scoping Reviews guidelines. Papers were collected from the databases CINAHL, MEDLINE, Embase and PsycINFO. Titles and abstracts were scanned for relevance, followed by a full-text screening. Information relevant to the research question was extracted from papers meeting the inclusion criteria. RESULTS: Twenty-six papers met the inclusion criteria. The psychosocial factors that were most studied included social influence, social interactions and psychological stressors, which lead to behaviours such as excessive alcohol consumption, drug taking, risky casual sex and risk taking amongst psychological factors of young attendees. Effective interventions implemented before or during MGEs, such as alcohol-free zones, antidrinking campaigns, psychoeducation and disapproval from parents with regard to drinking alcohol, showed promise in reducing harms. CONCLUSION: Psychosocial interventions have the potential to reduce harms and enhance well-being for young people attending MGEs. This review has identified gaps and opportunities in the current literature with regard to psychosocial interventions and strategies to support young people at MGEs and makes recommendations to support the development and refinement of evidence-based interventions aimed at young MGE attendees.

Mental health and well-being of anaesthetists during the COVID-19 pandemic: a scoping review.

The COVID-19 pandemic has imposed substantial burdens on clinicians and there is a need to better understand the impact on mental health and well-being. This scoping review investigates the prevalence of mental health concerns in anaesthetists, risk and protective factors for mental well-being, and anaesthetists' pandemic-related concerns and support. We searched online databases for articles published between January 2020 and May 2022, using search terms related to: anaesthesia; burnout, well-being, mental health or stress; and COVID-19. We identified 20 articles comprising 19 different populations of anaesthetists (n = 8680) from 14 countries. Studies identified the prevalence of the following condition in anaesthetists: burnout (14-59%); stress (50-71%); anxiety (11-74%); depression (12-67%); post-traumatic stress (17-25%); psychological distress (52%); and insomnia (17-61%). Significant risk factors for poorer mental health included: direct COVID-19-related issues (fear of self and family exposure to infection; requirement for quarantine); practitioner health factors (insomnia; comorbidities); psychosocial factors (loneliness; isolation; perceived lack of support at home and work); demographic factors (female gender; non-white ethnicity; LGBTQIA+); and workplace factors (redeployment outside area of clinical practice; increased work effort; personal protective equipment shortages). Protective factors identified included: job satisfaction; perceived organisational justice; older age; and male sex. Anaesthetists' self-reported concerns related to: personal protective equipment; resource allocation; fear of infection; fear of financial loss; increased workload; and effective communication of protocols for patient treatment. Support from family, colleagues and hospital management was identified as an important coping mechanism. Findings from this review may support the design of interventions to enhance anaesthetists' psychological health during pandemic conditions and beyond. Future research should include consistent psychological outcome measures and rigorous experimental design beyond cross-sectional studies.

Long-term, durable, absolute Psoriasis Area and Severity Index and health-related quality of life improvements with risankizumab treatment: a post hoc integrated analysis of patients with moderate-to-severe plaque psoriasis.

BACKGROUND: Risankizumab has demonstrated durable, high rates of efficacy in patients with moderate-to-severe plaque psoriasis as assessed by the achievement of relative Psoriasis Area and Severity Index (PASI) improvement and Dermatology Life Quality Index (DLQI) 0/1. OBJECTIVES: The aim of this post hoc analysis is to assess the achievement of absolute PASI thresholds and related improvements in health-related quality of life (HRQoL) in patients with moderate-to-severe plaque psoriasis treated with (i) risankizumab compared with ustekinumab, and (ii) long-term (>52 weeks to 172 weeks) risankizumab. METHODS: Data from patients randomised to 150 mg risankizumab or 45 or 90 mg ustekinumab in replicate randomised controlled trials UltIMMa-1 and UltIMMa-2 were analysed for the achievement of absolute PASI thresholds PASI ≤ 3, PASI ≤ 1, and PASI = 0, time to achieve these thresholds, and combined PASI and DLQI endpoints. Data from pat ients initially randomised to risankizumab who continued on risankizumab in the open-label extension study LIMMitless were analysed for the achievement of absolute PASI levels, mean DLQI scores, and DLQI 0/1. RESULTS: Significantly greater proportions of patients treated with risankizumab compared with ustekinumab achieved PASI ≤ 3, PASI ≤ 1, and PASI = 0, as well as combined endpoints for absolute PASI and DLQI [(PASI ≤ 3 and DLQI ≤ 5) or (PASI ≤ 1 and DLQI 0/1)]. The median time to first achieve PASI ≤ 3, PASI ≤ 1, and PASI = 0 was significantly lower for risankizumab-treated patients compared with ustekinumab-treated patients. Among patients treated with long-term risankizumab, more than 90% achieved PASI ≤ 3 though week 172 and more than 80% achieved DLQI 0/1. Low absolute PASI scores corresponded with low mean absolute DLQI scores through week 172 of continuous risankizumab treatment. CONCLUSIONS: Risankizumab treatment demonstrated high rates of rapid and durable efficacy as measured by absolute PASI thresholds and improvements in patient HRQoL.

A head-to-head comparison of ixekizumab vs. guselkumab in patients with moderate-to-severe plaque psoriasis: 12-week efficacy, safety and speed of response from a randomized, double-blinded trial.

BACKGROUND: Patients with psoriasis value rapid and complete skin clearance. No head-to-head studies have focused on early responses to interleukin (IL)-17 vs. IL-23 inhibitors. OBJECTIVES: To compare early and complete skin clearance by the IL-17A inhibitor ixekizumab vs. the IL-23p19 inhibitor guselkumab. METHODS: IXORA-R, a 24-week, randomized, double-blinded study, enrolled adults with moderate-to-severe plaque psoriasis [static Physician's Global Assessment of Disease (sPGA) score of ≥ 3, Psoriasis Area and Severity Index (PASI) ≥ 12, and ≥ 10% body surface area]. Patients were randomized (1 : 1) to receive the approved dose of subcutaneous ixekizumab or guselkumab. Primary end point was 100% improvement in PASI (PASI 100) at week 12. Major secondary end points included other levels of improved PASI and sPGA at different time points. Comparisons were made using the Cochran-Mantel-Haenszel test with a multiple testing strategy. Nonresponder imputation was used for missing data. After the completion of the study, the final secondary end point (PASI 100 at 24 weeks) and safety data through week 24 will be reported. RESULTS: In total, 1027 patients were randomized. The primary end point PASI 100 at week 12 was met [215/520 ixekizumab (41%); 126/507 guselkumab (25%); P < 0·001]. All major secondary end points measured up to week 12 were met, including PASI 50 at week 1 and PASI 75 at week 2. Serious adverse event frequency was 3% for each group; no new safety signals were identified. CONCLUSIONS: Ixekizumab was superior to guselkumab for rapidly improving signs and symptoms in patients with moderate-to-severe plaque psoriasis by week 12. Adverse events were similar to previous ixekizumab and guselkumab studies. Compared with the IL-23 inhibitor guselkumab, ixekizumab can offer complete skin clearance more rapidly to patients with moderate-to-severe plaque psoriasis. What's already known about this topic? Patients with plaque psoriasis desire both high levels of clearance and rapid onset of treatment effects. Ixekizumab, a high-affinity monoclonal antibody that selectively targets interleukin (IL)-17A, has demonstrated greater and faster skin clearance than etanercept and ustekinumab, with consistent long-term efficacy, safety and durability of response. Clinical trial data and systematic reviews have suggested that IL-17 inhibitors can improve a patient's psoriasis more rapidly than IL-23 inhibitors. What does this study add? The head-to-head study design directly compares the efficacy and speed of response of ixekizumab and the IL-23 inhibitor guselkumab in moderate-to-severe plaque psoriasis. The primary end point was met, showing superiority of ixekizumab over guselkumab for achieving complete skin clearance at week 12. The safety profile of ixekizumab was consistent with previous studies. Ixekizumab can deliver patients complete skin clearance and improved quality of life more rapidly than guselkumab.

A study of dysphagia symptoms and esophageal body function in children undergoing anti-reflux surgery.

BACKGROUND: The role of high-resolution esophageal impedance manometry (HRIM) for establishing risk for dysphagia after anti-reflux surgery is unclear. We conducted a prospective study of children with primary gastroesophageal reflux (GER) disease, for whom symptoms of dysphagia were determined pre-operatively and then post-operatively and we examined for features that may predict post-operative dysphagia. METHODS: Thirteen children (aged 6.8-15.5 years) undergoing work-up prior to 360o Nissen fundoplication were included in the study. A dysphagia score assessed symptoms at pre-operative study and post-operatively (mean 1.4 years). A HRIM procedure recorded 5-ml liquid, 5-ml viscous and 2-cm solid boluses. We assessed esophageal motility, esophago-gastric junction (EGJ) morphology, EGJ contractility and pressure-flow variables indicative of bolus distension pressures and bolus clearance pressures. A composite pressure-flow index score was also derived. RESULTS: Pre-operative pressure-flow index was positively correlated with post-operative dysphagia score (viscous bolus r = 0.771, p < 0.005). Of three variables that comprise the pressure-flow index, the ramp pressure measured during bolus clearance was the main driver of the effect seen (viscous bolus r = 0.819, p < 0.005). CONCLUSIONS: In order to mitigate symptoms in relation to anti-reflux surgery, dysphagia symptoms and esophageal function need to be pre-operatively assessed. In patients with normal motility, an elevated pressure-flow index may predict post-operative dysphagia.

Pathophysiology of swallowing following oropharyngeal surgery for obstructive sleep apnea syndrome.

BACKGROUND: Uvulopalatopharyngoplasty (UPPP) and coblation channeling of the tongue (CCT) are oropharyngeal surgeries used to treat obstructive sleep apnea syndrome. The extent to which UPPP and CCT affect pharyngeal swallow has not been determined. We therefore conducted a novel case series study employing high-resolution impedance manometry (HRIM) to quantify the swallowing-related biomechanics following UPPP and/or CCT surgery. METHODS: Twelve patients who underwent UPPP+CCT or CCT only were assessed an average 2.5 years postsurgery. Swallow function data were compared with ten healthy controls. All patients completed the Sydney swallow questionnaire (SSQ). Pharyngeal pressure-flow analysis of HRIM recordings captured key distension, contractility and pressure-flow timing swallow parameters testing 5, 10, and 20 mL volumes of thin and thick fluid consistencies. KEY RESULTS: Postoperative patients had more dysphagia symptoms with five returning abnormal SSQ scores. Swallowing was biomechanically altered compared to controls, consistent with diminished swallowing reserve, largely driven by elevated hypopharyngeal intrabolus pressure due to a reduced capacity to open the upper esophageal sphincter to accommodate larger volumes. CONCLUSIONS & INFERENCES: Patients who have undergone UPPP and/or CCT surgery appear to have a deficiency in normal modulation of the swallowing mechanism and a reduced swallowing functional reserve. We speculate that these changes may become relevant in later life with the onset of age-related stressors to the swallowing mechanism. This case series strikes a note of caution that further studies are needed to determine the role of preoperative swallow assessment in patients undergoing UPPP and/or CCT surgery.

Upper Gastrointestinal Function in Morbidly Obese Adolescents Before and 6 Months After Gastric Banding.

BACKGROUND: The effects of laparoscopic adjustable gastric band (LAGB) placement on upper gastrointestinal tract function in obese adolescents are unknown. Therefore, our aim was to determine the short-term effects of LAGB on esophageal motility, gastroesophageal reflux, gastric emptying, appetite-regulatory hormones, and perceptions of post-prandial hunger and fullness. METHODS: This study was part of a prospective cohort study (March 2009-December 2015) in one tertiary referral hospital. The study included obese adolescents (14-18 years) with a body mass index (BMI) > 40 (or ≥ 35 with comorbidities). Gastric emptying was assessed by 13C-octanoic acid breath test, pharyngeal, and esophageal motor function by high-resolution manometry with impedance (HRIM), and appetite and other perceptions using 100-mm visual analogue scales. Dysphagia symptoms were scored using a Dakkak questionnaire. Data were compared pre- and post-LAGB placement and at a 6-month follow-up. RESULTS: Based upon analysis of 15 adolescents, at the 6-month follow-up, LAGB placement: (i) led to a significant reduction in weight and BMI; (ii) increased fullness and decreased hunger post-meal; (iii) increased symptoms of dysphagia after solid food; and, despite these effects, (iv) caused little or no changes to appetite hormones, while (v) effects on gastric emptying, esophageal motility, esophageal bolus transport, and esophageal emptying were not significant. CONCLUSION: In adolescents, LAGB improved BMI and altered the sensitivity to nutrients without significant effects on upper gastrointestinal tract physiology at the 6-month follow-up.

Extension of ustekinumab maintenance dosing interval in moderate-to-severe psoriasis: results of a phase IIIb, randomized, double-blinded, active-controlled, multicentre study (PSTELLAR).

BACKGROUND: Phase III studies showed that some patients maintained response for ≥ 6 months following ustekinumab discontinuation. OBJECTIVES: To assess clinical responses with extended ustekinumab maintenance dosing intervals. METHODS: Adults with moderate-to-severe plaque psoriasis received ustekinumab at weeks 0, 4 and 16 during open-label treatment. Patients achieving a week-28 Physician's Global Assessment (PGA) score of cleared/minimal (PGA = 0/1) were randomized 1 : 4 to group 1 [approved every 12 weeks (q12 wk) maintenance] or group 2 (q12-24 wk; response-based dosing determined by time to loss of PGA = 0/1). Key end points included the number of visits with PGA = 0/1 (primary end point) and ≥ 75% improvement in Psoriasis Area and Severity Index (PASI 75) between weeks 88 and 112, and PGA/PASI responses between weeks 28 and 112. RESULTS: Overall, 378 patients achieved PGA = 0/1 at week 28 and were randomized to group 1 (n = 76) or group 2 (n = 302). Patients in group 1 had numerically greater mean numbers of visits with PGA = 0/1 than group 2 and also with PASI 75 from week 88 to 112. A higher proportion of patients in group 1 (55%) than group 2 (39%) had PGA = 0/1 at all seven visits from week 88 to 112. Maintenance of response was observed with dose-interval extension beyond q12 wk in a subset of patients. Extending the dosing interval did not affect antibody development or safety. CONCLUSIONS: Efficacy was better maintained among week-28 PGA responders randomized to continue q12 wk ustekinumab vs. extending maintenance dosing based on clinical response, although some patients maintained high levels of efficacy with up to q24 wk dosing.

Applying the Chicago Classification criteria of esophageal motility to a pediatric cohort: effects of patient age and size.

BACKGROUND: Applying the 2012 Chicago Classification (CC) of esophageal motility disorders to pediatric patients is problematic as it relies upon adult-derived criteria. As shorter esophageal length and smaller esophago-gastric junction (EGJ) diameter may influence CC metrics, we explored the potential for age- and size-adjustment of diagnostic criteria. METHODS: We evaluated 76 high-resolution solid state impedance-manometry recordings in children referred for manometry (32M; mean age 9 ± 1 years) and 25 recordings from healthy adult subjects (7M; mean age 36 ± 2 years). CC metrics; integrated relaxation pressure (IRP4s, mmHg), contractile front velocity (CFV, cm/s), distal contractile integral (DCI, mmHg cm/s), distal latency (DL, s), and peristaltic break size (BS, cm) were derived for 10 liquid swallows using CC analysis software. Effects of age and size were examined using regression analysis. KEY RESULTS: Younger patient age and shorter size correlated significantly with greater IRP4s (p < 0.05), shorter DL (p < 0.001) and smaller BS (p < 0.05). Standard diagnostic CC criteria were adjusted using the slope of the linear regression equation to define the age/size-related trend. Sixty-six percent of the pediatric cohort showed abnormal motility when applying standard CC criteria. Adjustment for age and size reduced this to 50% and 53% respectively, with the largest reduction being in the IRP4s- and DL-dependent disorders EGJ outflow obstruction and diffuse esophageal spasm (13% to 7% and 5% and 14% to 1 and 5%, respectively). CONCLUSIONS & INFERENCES: CC metrics, particularly IRP4s and DL, are age and size dependent, and therefore, require adjustment to improve accuracy of diagnosis of esophageal motility disorders in children.

Inter- and intra-rater reproducibility of automated and integrated pressure-flow analysis of esophageal pressure-impedance recordings.

BACKGROUND: Automated impedance manometry pressure-flow analysis (AIM analysis) determines pressure measurements relative to bolus flow and has to date shown subtle variations in esophageal motility in relation to dysphagia. In this study, we assessed intra- and inter-rater reproducibility of AIM metrics derived using purpose designed software. METHODS: Fifty patients referred for evaluation of gastro-esophageal reflux symptoms (33 men, age 52 ± 1.9 years) underwent combined high-resolution impedance manometry and completed a dysphagia questionnaire. From 10 liquid and 10 viscous swallows, a subset of four swallows (two saline and two viscous) was systematically selected from each patient for manual and AIMplot analysis, which was performed twice by five observers (two experts, three non-experts). Intra- and inter-rater agreement were determined using intraclass correlation coefficients. KEY RESULTS: AIMplot-based analysis showed high intra-rater and inter-rater reproducibility for all metrics (mean ICCs of 0.95 and 0.94, respectively). Reproducibility of metrics derived for liquid and viscous did not differ (ICCs of 0.96 and 0.91 for liquid and viscous, respectively). In addition, metrics derived by experts had an equivalent level of reproducibility compared to non-experts (ICCs of 0.96 and 0.94, respectively). Variables that could be derived with commercial software (ManoView™) correlated highly with variables from AIMplot-based analysis, such as 4-s integrated relaxation pressure (r = 0.85) and the 20-mmHg isobaric contour defect (r = 0.92). CONCLUSIONS & INFERENCES: Esophageal AIM analysis is highly reproducible, independent of an observer's level of experience in esophageal motility. Therefore, AIM analysis produces data that are reliable for clinical and research purposes.

Characteristics of fibrin formation and clot stability in individuals with congenital type IIb protein C deficiency.

Many studies have shown that unregulated or excessive thrombin formation is potentially a cause of thrombosis; however, studies examining processes that contribute to fibrin stabilization in individuals predisposed to thrombosis are limited. In this study, we investigate a family with familial thrombosis via type IIb protein C (PC) deficiency. Using contact pathway inhibited whole blood, thrombin generation, fibrin clot formation and factor (f)XIII activation were monitored over time in control (n=5) and PC deficient (n=4, 34 - 69% PC by activity) subjects. The dynamics of thrombin generation varied significantly with the time required to reach the maximal rate of thrombin-antithrombin formation being much shorter in PC deficiency (5.8 ± 0.4 minutes) than in controls (9.7 ± 0.4 minutes; p < 0.001). PC deficient clots were significantly heavier than control clots (p < 0.001) and this difference could not be contributed exclusively to differences in fibrinogen levels between groups. FXIII was consumed faster in PC deficient subjects (23.7 ± 2.0 nM/minute) than in controls (5.1 ± 1.5 nM/minute; p < 0.0001) suggesting increased fXIII activation and incorporation of fXIIIa substrates into the clot. In plasma, the clot lysis time was increased in PC deficiency by both TAFIa dependent and independent mechanisms. Since PC deficient clots are both denser and show a greater degree of resistance to fibrinolysis, these clots would likely resist fibrinolysis and potentiate fibrin deposition observed in thrombosis.

The influence of prophylactic factor VIII in severe haemophilia A.

Haemophilia A individuals displaying a similar genetic defect have heterogeneous clinical phenotypes. Our objective was to evaluate the underlying effect of exogenous factor (f)VIII on tissue factor (Tf)-initiated blood coagulation in severe haemophilia utilizing both empirical and computational models. We investigated twenty-five clinically severe haemophilia A patients. All individuals were on fVIII prophylaxis and had not received fVIII from 0.25 to 4 days prior to phlebotomy. Coagulation was initiated by the addition of Tf to contact-pathway inhibited whole blood ± an anti-fVIII antibody. Aliquots were quenched over 20 min and analyzed for thrombin generation and fibrin formation. Coagulation factor levels were obtained and used to computationally predict thrombin generation with fVIII set to either zero or its value at the time of the draw. As a result of prophylactic fVIII, at the time of the blood draw, the individuals had fVIII levels that ranged from <1% to 22%. Thrombin generation (maximum level and rate) in both empirical and computational systems increased as the level of fVIII increased. FXIII activation rates also increased as the fVIII level increased. Upon suppression of fVIII, thrombin generation became comparable in both systems. Plasma composition analysis showed a negative correlation between bleeding history and computational thrombin generation in the absence of fVIII. Residual prophylactic fVIII directly causes an increase in thrombin generation and fibrin cross-linking in individuals with clinically severe haemophilia A. The combination of each individual's coagulation factors (outside of fVIII) determine each individual's baseline thrombin potential and may affect bleeding risk.

Sharing research findings with research participants and communities.

In occupational and environmental health research, individual, group and community research participants have a unique and vested interest in the research findings. The ethical principles of autonomy, non-maleficence and beneficence are helpful in considering the ethical issues in the disclosure of research findings in occupational and environmental health research. Researchers need to include stakeholders, such as groups and communities, in these discussions and in planning for the dissemination of research findings. These discussions need to occur early in the research process.

The current and future role of the dietetic support worker.

BACKGROUND: The role of the dietetic support worker (DSW) was developed to provide cost-effective support to dietetic services in the National Health Service (NHS). However, there is little evidence about how the role is perceived or the impact of the introduction of Agenda for Change in 2004 (a guide to pay terms and conditions for NHS staff) on role definition. The present study aimed to gather evidence from DSWs and dietitians on the current role of the DSW to help inform the future development of the role. METHODS: A questionnaire survey was conducted on DSWs and dietitians in 10 trusts in the East of England. Issues included qualifications, experience, training, satisfaction with Agenda for Change, supervision and responsibility. Themes were further explored by semi-structured telephone interviews conducted on a subsample. RESULTS: Eighteen out of 24 DSWs and 62 out of 98 dietitians responded to the questionnaire. The role of the DSW is highly valued by dietitians. Over three-quarters of DSWs and over 90% of dietitians agree that the employment of DSWs improved the working lives of dietitians. Only 50% of DSWs were happy with their Agenda for Change banding, although this did not adversely affect their job satisfaction. Both groups saw the role of the DSW becoming more specialised, despite concerns about access to appropriate training and the lack of a structured career pathway. CONCLUSIONS: This study identified issues relating to the future development of the role of the DSW from the viewpoint of DSWs and dietetic assistants.