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  • Safety, immunogenicity, and reactogenicity of BNT162b2 and mRNA-1273 COVID-19 vaccines given as fourth-dose boosters following two doses of ChAdOx1 nCoV-19 or BNT162b2 and a third dose of BNT162b2 (COV-BOOST): a multicentre, blinded, phase 2, randomised trial

    Palfreeman, Adrian; Pan, Daniel
    Background: Some high-income countries have deployed fourth doses of COVID-19 vaccines, but the clinical need, effectiveness, timing, and dose of a fourth dose remain uncertain. We aimed to investigate the safety, reactogenicity, and immunogenicity of fourth-dose boosters against COVID-19. Methods: The COV-BOOST trial is a multicentre, blinded, phase 2, randomised controlled trial of seven COVID-19 vaccines given as third-dose boosters at 18 sites in the UK. This sub-study enrolled participants who had received BNT162b2 (Pfizer-BioNTech) as their third dose in COV-BOOST and randomly assigned them (1:1) to receive a fourth dose of either BNT162b2 (30 μg in 0·30 mL; full dose) or mRNA-1273 (Moderna; 50 μg in 0·25 mL; half dose) via intramuscular injection into the upper arm. The computer-generated randomisation list was created by the study statisticians with random block sizes of two or four. Participants and all study staff not delivering the vaccines were masked to treatment allocation. The coprimary outcomes were safety and reactogenicity, and immunogenicity (anti-spike protein IgG titres by ELISA and cellular immune response by ELISpot). We compared immunogenicity at 28 days after the third dose versus 14 days after the fourth dose and at day 0 versus day 14 relative to the fourth dose. Safety and reactogenicity were assessed in the per-protocol population, which comprised all participants who received a fourth-dose booster regardless of their SARS-CoV-2 serostatus. Immunogenicity was primarily analysed in a modified intention-to-treat population comprising seronegative participants who had received a fourth-dose booster and had available endpoint data. This trial is registered with ISRCTN, 73765130, and is ongoing. Findings: Between Jan 11 and Jan 25, 2022, 166 participants were screened, randomly assigned, and received either full-dose BNT162b2 (n=83) or half-dose mRNA-1273 (n=83) as a fourth dose. The median age of these participants was 70·1 years (IQR 51·6-77·5) and 86 (52%) of 166 participants were female and 80 (48%) were male. The median interval between the third and fourth doses was 208·5 days (IQR 203·3-214·8). Pain was the most common local solicited adverse event and fatigue was the most common systemic solicited adverse event after BNT162b2 or mRNA-1273 booster doses. None of three serious adverse events reported after a fourth dose with BNT162b2 were related to the study vaccine. In the BNT162b2 group, geometric mean anti-spike protein IgG concentration at day 28 after the third dose was 23 325 ELISA laboratory units (ELU)/mL (95% CI 20 030-27 162), which increased to 37 460 ELU/mL (31 996-43 857) at day 14 after the fourth dose, representing a significant fold change (geometric mean 1·59, 95% CI 1·41-1·78). There was a significant increase in geometric mean anti-spike protein IgG concentration from 28 days after the third dose (25 317 ELU/mL, 95% CI 20 996-30 528) to 14 days after a fourth dose of mRNA-1273 (54 936 ELU/mL, 46 826-64 452), with a geometric mean fold change of 2·19 (1·90-2·52). The fold changes in anti-spike protein IgG titres from before (day 0) to after (day 14) the fourth dose were 12·19 (95% CI 10·37-14·32) and 15·90 (12·92-19·58) in the BNT162b2 and mRNA-1273 groups, respectively. T-cell responses were also boosted after the fourth dose (eg, the fold changes for the wild-type variant from before to after the fourth dose were 7·32 [95% CI 3·24-16·54] in the BNT162b2 group and 6·22 [3·90-9·92] in the mRNA-1273 group). Interpretation: Fourth-dose COVID-19 mRNA booster vaccines are well tolerated and boost cellular and humoral immunity. Peak responses after the fourth dose were similar to, and possibly better than, peak responses after the third dose.
  • Risk factors associated with SARS-CoV-2 infection in a multiethnic cohort of United Kingdom healthcare workers (UK-REACH): A cross-sectional analysis

    Martin, Christopher; Pan, Daniel; Carr, Sue; Nazareth, Joshua; Pareek, Manish
    Background: Healthcare workers (HCWs), particularly those from ethnic minority groups, have been shown to be at disproportionately higher risk of infection with Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) compared to the general population. However, there is insufficient evidence on how demographic and occupational factors influence infection risk among ethnic minority HCWs. Methods and findings: We conducted a cross-sectional analysis using data from the baseline questionnaire of the United Kingdom Research study into Ethnicity and Coronavirus Disease 2019 (COVID-19) Outcomes in Healthcare workers (UK-REACH) cohort study, administered between December 2020 and March 2021. We used logistic regression to examine associations of demographic, household, and occupational risk factors with SARS-CoV-2 infection (defined by polymerase chain reaction (PCR), serology, or suspected COVID-19) in a diverse group of HCWs. The primary exposure of interest was self-reported ethnicity. Among 10,772 HCWs who worked during the first UK national lockdown in March 2020, the median age was 45 (interquartile range [IQR] 35 to 54), 75.1% were female and 29.6% were from ethnic minority groups. A total of 2,496 (23.2%) reported previous SARS-CoV-2 infection. The fully adjusted model contained the following dependent variables: demographic factors (age, sex, ethnicity, migration status, deprivation, religiosity), household factors (living with key workers, shared spaces in accommodation, number of people in household), health factors (presence/absence of diabetes or immunosuppression, smoking history, shielding status, SARS-CoV-2 vaccination status), the extent of social mixing outside of the household, and occupational factors (job role, the area in which a participant worked, use of public transport to work, exposure to confirmed suspected COVID-19 patients, personal protective equipment [PPE] access, aerosol generating procedure exposure, night shift pattern, and the UK region of workplace). After adjustment, demographic and household factors associated with increased odds of infection included younger age, living with other key workers, and higher religiosity. Important occupational risk factors associated with increased odds of infection included attending to a higher number of COVID-19 positive patients (aOR 2.59, 95% CI 2.11 to 3.18 for ≥21 patients per week versus none), working in a nursing or midwifery role (1.30, 1.11 to 1.53, compared to doctors), reporting a lack of access to PPE (1.29, 1.17 to 1.43), and working in an ambulance (2.00, 1.56 to 2.58) or hospital inpatient setting (1.55, 1.38 to 1.75). Those who worked in intensive care units were less likely to have been infected (0.76, 0.64 to 0.92) than those who did not. Black HCWs were more likely to have been infected than their White colleagues, an effect which attenuated after adjustment for other known risk factors. This study is limited by self-selection bias and the cross sectional nature of the study means we cannot infer the direction of causality. Conclusions: We identified key sociodemographic and occupational risk factors associated with SARS-CoV-2 infection among UK HCWs, and have determined factors that might contribute to a disproportionate odds of infection in HCWs from Black ethnic groups. These findings demonstrate the importance of social and occupational factors in driving ethnic disparities in COVID-19 outcomes, and should inform policies, including targeted vaccination strategies and risk assessments aimed at protecting HCWs in future waves of the COVID-19 pandemic.
  • Persistence of immunogenicity after seven COVID-19 vaccines given as third dose boosters following two doses of ChAdOx1 nCov-19 or BNT162b2 in the UK: Three month analyses of the COV-BOOST trial

    Palfreeman, Adrian; Pan, Daniel (2022-06)
    Objectives: To evaluate the persistence of immunogenicity three months after third dose boosters. Methods: COV-BOOST is a multicentre, randomised, controlled, phase 2 trial of seven COVID-19 vaccines used as a third booster dose. The analysis was conducted using all randomised participants who were SARS-CoV-2 naïve during the study. Results: Amongst the 2883 participants randomised, there were 2422 SARS-CoV-2 naïve participants until D84 visit included in the analysis with median age of 70 (IQR: 30-94) years. In the participants who had two initial doses of ChAdOx1 nCov-19 (Oxford-AstraZeneca; hereafter referred to as ChAd), schedules using mRNA vaccines as third dose have the highest anti-spike IgG at D84 (e.g. geometric mean concentration of 8674 ELU/ml (95% CI: 7461-10,085) following ChAd/ChAd/BNT162b2 (Pfizer-BioNtech, hearafter referred to as BNT)). However, in people who had two initial doses of BNT there was no significant difference at D84 in people given ChAd versus BNT (geometric mean ratio (GMR) of 0.95 (95%CI: 0.78, 1.15). Also, people given Ad26.COV2.S (Janssen; hereafter referred to as Ad26) as a third dose had significantly higher anti-spike IgG at D84 than BNT (GMR of 1.20, 95%CI: 1.01,1.43). Responses at D84 between people who received BNT (15 μg) or BNT (30 μg) after ChAd/ChAd or BNT/BNT were similar, with anti-spike IgG GMRs of half-BNT (15 μg) versus BNT (30 μg) ranging between 0.74-0.86. The decay rate of cellular responses were similar between all the vaccine schedules and doses. Conclusions: 84 days after a third dose of COVID-19 vaccine the decay rates of humoral response were different between vaccines. Adenoviral vector vaccine anti-spike IgG concentrations at D84 following BNT/BNT initial doses were similar to or even higher than for a three dose (BNT/BNT/BNT) schedule. Half dose BNT immune responses were similar to full dose responses. While high antibody tires are desirable in situations of high transmission of new variants of concern, the maintenance of immune responses that confer long-lasting protection against severe disease or death is also of critical importance. Policymakers may also consider adenoviral vector, fractional dose of mRNA, or other non-mRNA vaccines as third doses.
  • Tuberculosis incidence in country of origin is a key determinant of the risk of active tuberculosis in people living with HIV: Data from a 30-year observational cohort study

    Dillon, Helen; White, Helena; Hefford, Phillip; Wiselka, Martin; Pareek, Manish
    Introduction: People living with HIV (PLWH) are at high risk of active tuberculosis (TB) but this risk in the era of antiretroviral treatment (ART) remains unclear. It is critical to identify the groups who should be prioritised for latent TB (LTBI) screening. In this study we identified the risk factors associated with developing incident TB disease, by analysing a 30-year observational cohort. Methods: We evaluated PLWH in Leicester, UK, between 1983 and 2017 to ascertain those who developed active TB and the timing of this in relation to HIV diagnosis; whether before, concurrently with, or more than 3 months after the diagnosis of HIV (incident TB). Predictors of incident TB were ascertained using Cox proportional hazards models. Results: In all, 325 out of 2158 (15.1%) PLWH under care had had active TB; 64/325 (19.7%) prior to HIV diagnosis, 161/325 (49.5%) concurrently with/within 3 months of HIV diagnosis and 100/325 (30.8%) had incident TB. Incident TB risk was 4.57/1000 person-years. Increased TB incidence in the country of birth was associated with an increased risk of developing incident TB [50-149/100 000 population, adjusted hazard ratio (AHR) = 3.10, 95% CI: 0.94-10.20; 150-249/100 000 population, AHR = 7.14, 95% CI: 3.46-14.74; 250-349/100 000 population, AHR = 5.90, 95% CI: 2.32-14.99; ≥ 350/100 000 population, AHR = 3.96, 95% CI: 1.39-11.26]. Conclusions: Tuberculosis risk remains high among PLWH and is related to TB incidence in the country of birth. Further work is required to determine whether specific groups of PLWH should be targeted for programmatic LTBI screening, and whether it will result in high uptake and completion of chemoprophylaxis and is cost-effective for widespread implementation.
  • Access to personal protective equipment in healthcare workers during the COVID-19 pandemic in the United Kingdom: results from a nationwide cohort study (UK-REACH)

    Martin, Christopher; Pan, Daniel; Nazareth, Joshua; Carr, Sue; Pareek, Manish
    Background: Healthcare workers (HCWs) are at high risk of SARS-CoV-2 infection. Effective use of personal protective equipment (PPE) reduces this risk. We sought to determine the prevalence and predictors of self-reported access to appropriate PPE (aPPE) for HCWs in the UK during the COVID-19 pandemic. Methods: We conducted cross sectional analyses using data from a nationwide questionnaire-based cohort study administered between December 2020-February 2021. The outcome was a binary measure of self-reported aPPE (access all of the time vs access most of the time or less frequently) at two timepoints: the first national lockdown in the UK in March 2020 (primary analysis) and at the time of questionnaire response (secondary analysis). Results: Ten thousand five hundred eight HCWs were included in the primary analysis, and 12,252 in the secondary analysis. 35.2% of HCWs reported aPPE at all times in the primary analysis; 83.9% reported aPPE at all times in the secondary analysis. In the primary analysis, after adjustment (for age, sex, ethnicity, migration status, occupation, aerosol generating procedure exposure, work sector and region, working hours, night shift frequency and trust in employing organisation), older HCWs and those working in Intensive Care Units were more likely to report aPPE at all times. Asian HCWs (aOR:0.77, 95%CI 0.67-0.89 [vs White]), those in allied health professional and dental roles (vs those in medical roles), and those who saw a higher number of COVID-19 patients compared to those who saw none (≥ 21 patients/week 0.74, 0.61-0.90) were less likely to report aPPE at all times. Those who trusted their employing organisation to deal with concerns about unsafe clinical practice, compared to those who did not, were twice as likely to report aPPE at all times. Significant predictors were largely unchanged in the secondary analysis. Conclusions: Only a third of HCWs in the UK reported aPPE at all times during the first lockdown and that aPPE had improved later in the pandemic. We also identified key determinants of aPPE during the first UK lockdown, which have mostly persisted since lockdown was eased. These findings have important implications for the safe delivery of healthcare during the pandemic.
  • Similar Benefits Seen After Radial Extracorporeal Shockwave Therapy or Autologous Blood Injection in Patients With Chronic Plantar Fasciitis-A Retrospective Cohort Study

    Wheeler, Patrick; Dudson, Chloe
    Objective: To compare the outcomes for patients with chronic plantar fasciitis after extracorporeal shockwave therapy (ESWT) or autologous blood injection (ABI). Design: Cohort study-retrospective analysis of prospectively collected data. Setting: Hospital-based Sports Medicine Outpatient Clinic. Patients: One hundred two consecutive patients with chronic plantar fasciitis, treated with either radial-ESWT (rESWT) (n = 54) or ABI (n = 48), with minimum 3-month follow-up and 96% (98/102) having 6-month follow-up. Mean age 49.5 years and mean duration of symptoms 37.5 months before treatment. Interventions: Patients received either 3 sessions of radial ESWT (one session per week for 3 weeks), or a single ultrasound-guided dry needling and ABI (3 mL whole autologous blood). All patients received standardized after-care, including progressive structured home exercise program of flexibility, strengthening, and proprioception exercises. Main outcome measures: 0 to 10 numerical rating scale (NRS) for self-reported "average pain" and "average stiffness" values. Secondary outcome measures included assessments of local foot function [including Manchester-Oxford Foot Questionnaire (MOXFQ), revised-Foot Function Index] as well as markers of mental health functioning (HAD), global health (EQ-5D-5L), and physical activity (International Physical Activity Questionnaire). Results: This study demonstrated statistically significant improvements in self-reported measures of pain and local foot function after either procedure at 6 weeks, 3 months, and 6 months, but no statistically significant differences were seen between groups at any time-period studied. At 6 months, the average pain using a 0 to 10 NRS was improved from 6.8 ± 1.8 to 4.0 ± 2.7 (P < 0.001) after ESWT and from 7.1 ± 1.6 to 3.8 ± 2.7 (P < 0.001) after ABI. At 6 months, significant improvements were seen following either group using a number of different validated patient-rated outcome measures assessing local foot pain and function, eg, the total score for MOXFQ improved from 56.1 ± 12.8 to 42.5 ± 16.6 (P < 0.001) after ESWT and from 58.8 ± 13.2 to 44.2 ± 19.2 (P < 0.001) after ABI. However, measures of physical activity or wider aspects of patient functioning did not consistently improve from baseline values to follow-up periods. Conclusions: Patients with chronic plantar fasciitis improved to statistically significant extent after either rESWT or ABI procedures, with no significant differences seen between groups. The lack of randomization in this pragmatic study is noted, which may have influenced the outcome seen. Potentially larger and more robust studies are required to investigate this treatment comparison further.
  • Three Sessions of Radial Extracorporeal Shockwave Therapy Gives No Additional Benefit Over "Minimal-Dose" Radial Extracorporeal Shockwave Therapy for Patients With Chronic Greater Trochanteric Pain Syndrome: A Double-Blinded, Randomized, Controlled Trial

    Wheeler, Patrick; Dudson, Chloe; Calver, Rachel; Goodall, Duncan; Gregory, Kim; Singh, Harjinder; Boyd, Kevin
    Objective: To investigate the outcomes following 3 weekly sessions of radial extracorporeal shockwave therapy (rESWT) in patients with chronic greater trochanteric pain syndrome (GTPS) presenting to an NHS Sports Medicine Clinic in the United Kingdom. Design: Double-blinded randomized controlled trial. Setting: A single NHS Sports Medicine Clinic, in the United Kingdom. Patients: One hundred twenty patients in an NHS Sports Medicine clinic presenting with symptoms of GTPS who had failed to improve with a minimum of 3 months of rehabilitation were enrolled in the study and randomized equally to the intervention and treatment groups. Mean age was 60.6 ± 11.5 years; 82% were female, and the mean duration of symptoms was 45.4 ± 33.4 months (range, 6 months to 30 years). Interventions: Participants were randomized to receive either 3 sessions of ESWT at either the "recommended"/"maximally comfortably tolerated" dose or at "minimal dose." All patients received a structured home exercise program involving flexibility, strength, and balance exercises. Main outcome measures: Follow-up was at 6 weeks, 3 months, and 6 months. Outcome measures included local hip pain, validated hip PROMs (Oxford hip score, non-arthritic hip score, Victorian Institute of Sport assessment questionnaire), and wider measures of function including sleep (Pittsburgh sleep quality index) and mood (hospital anxiety and depression scale). Results: Results were available for 98% of patients at the 6-month period. There were statistically significant within-group improvements in pain, local function, and sleep seen in both groups. However, fewer benefits were seen in other outcome measures, including activity or mood. Conclusion: There were no time × group interaction effects seen between the groups at any time point, indicating that in the 3 sessions, the "recommended-dose" rESWT had no measurable benefit compared with "minimal dose" rESWT in this group of patients with GTPS. The underlying reason remains unclear; it may be that rESWT is ineffective in the treatment of patients with chronic GTPS, that "minimal dose" rESWT is sufficient for a therapeutic effect, or that a greater number of treatment sessions are required for maximal benefit. These issues need to be considered in further research. Trial registration: ClinicalTrials.gov NCT02546128.
  • Autologous Blood Injection With Dry-Needling vs Dry-Needling Alone Treatment for Chronic Plantar Fasciitis: A Randomized Controlled Trial

    Wheeler, Patrick; Dudson, Chloe; Gregory, Kim; Singh, Harjinder; Boyd, Kevin
    Background: Autologous blood injection (ABI) for patients with chronic plantar fasciitis has been promoted as an approach to improve outcomes over standard dry-needling approaches. The purpose of this trial was to investigate if there are improved outcomes following an ultrasonography-guided ABI compared to dry needling alone for patients with chronic plantar fasciitis. Methods: A double-blinded (participant-blinded and observer-blinded) RCT within a single clinic enrolled 90 patients with symptoms of plantar fasciitis that had failed to improve with a minimum of 3 months of rehabilitation. The mean age was 49.5±8.9 years, 67% were female, and the mean symptom duration was 40.0±28.2 months (range: 8 months-10 years). Participants were randomized to receive ABI or an identical dry-needle fenestration-procedure without coadministration of autologous blood. All participants received identical structured rehabilitation and were followed up at 2, 6, 12, and 26 weeks. Outcome measures included local foot pain, validated foot patient-reported outcome measures (Foot Function Index-revised, Manchester-Oxford Foot Questionnaire, Foot and Ankle Ability Measure), measures of general function and "ability" (EuroQol [EQ]-5D-5L, Oswestry Disability Index), specific measures of activity (International Physical Activity Questionnaire), sleep (Pittsburgh Sleep Quality Index), and mood (Hospital Anxiety and Depression Scale). Results: There were no significant between-group differences seen at any time-point studied. There were a number of statistically significant within-group improvements for local foot pain and function in both groups comparing baseline/follow-up data. Overall, levels of pain improved by 25% by 6 weeks and by 50% at 6 months. There were improvements in some generalized function markers. Activity rates did not change, demonstrating that improvements in pain did not necessarily influence physical activity. Conclusion: Coadministration of 3 mL of autologous blood had no additional effect compared to a dry-needling procedure alone for patients with chronic plantar fasciitis.
  • BSACI 2021 guideline for the management of egg allergy

    Ball, Heidi
    This guideline advises on the management of patients with egg allergy. Most commonly egg allergy presents in infancy, with a prevalence of approximately 2% in children and 0.1% in adults. A clear clinical history will confirm the diagnosis in most cases. Investigation by measuring egg-specific IgE (by skin prick testing or specific IgE assay) is useful in moderate-severe cases or where there is diagnostic uncertainty. Following an acute allergic reaction, egg avoidance advice should be provided. Egg allergy usually resolves, and reintroduction can be achieved at home if reactions have been mild and there is no asthma. Patients with a history of severe reactions or asthma should have reintroduction guided by a specialist. All children with egg allergy should receive the MMR vaccine. Most adults and children with egg allergy can receive the influenza vaccine in primary care, unless they have had anaphylaxis to egg requiring intensive care support. Yellow Fever vaccines should only be considered in egg-allergic patients under the guidance of an allergy specialist. This guideline was prepared by the Standards of Care Committee (SOCC) of the British Society for Allergy and Clinical Immunology (BSACI) and is intended for allergists and others with a special interest in allergy. The recommendations are evidence based. Where evidence was lacking, consensus was reached by the panel of specialists on the committee. The document encompasses epidemiology, risk factors, diagnosis, treatment, prognosis and co-morbid associations.
  • No cases of asymptomatic SARS-CoV-2 infection among healthcare staff in a city under lockdown restrictions: lessons to inform 'Operation Moonshot'

    Martin, Christopher; Jenkins, David; Patel, Prashanth; Goss, Charles; Price, Arthur; Barton, Linda; Gupta, Pankaj; Zaccardi, Francesco; Brunskill, Nigel; Haldar, Pranab; et al.
    Background Leicester was the first city in the UK to have ‘local lockdown’ measures imposed in response to high community rates of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) transmission. As part of this response, a directive was issued by NHS England to offer testing of asymptomatic healthcare workers (HCWs) at University Hospitals of Leicester NHS Trust (UHL) for SARS-CoV-2 infection. Methods Between 20 July and 14 August 2020, we invited all HCWs at UHL to attend for SARS-CoV-2 testing by nucleic acid amplification (NAAT). We combined the result of this assay with demographic information from the electronic staff record. Results A total of 1150 staff (~8% of the workforce) volunteered. The median age was 46 years (IQR 34–55), 972 (84.5%) were female; 234 (20.4%) were of South Asian and 58 (5.0%) of Black ethnicity; 564 (49.0%) were nurses/healthcare assistants. We found no cases of asymptomatic infection. In comparison, average community test positivity rate in Leicester city was 2.6%. Conclusions Within the context of local lockdowns due to high community transmission rates, voluntary testing of asymptomatic staff has low uptake and low yield and thus its premise and cost-effectiveness should be re-considered.
  • Demographic and occupational determinants of anti-SARS-CoV-2 IgG seropositivity in hospital staff

    Martin, Christopher; Patel, Prashanth; Goss, Charles; Jenkins, David; Price, Arthur; Barton, Linda; Gupta, Pankaj; Zaccardi, Francesco; Jerina, Helen; Duraisingham, Sai; et al.
    Background Although evidence suggests that demographic characteristics including minority ethnicity increase the risk of infection with Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), it is unclear whether these characteristics, together with occupational factors, influence anti-SARS-CoV-2 IgG seroprevalence in hospital staff. Methods We conducted cross-sectional surveillance examining seroprevalence of anti-SARS-CoV-2 IgG amongst staff at University Hospitals of Leicester (UHL) NHS Trust. We quantified seroprevalence stratified by ethnicity, occupation and seniority of practitioner and used logistic regression to examine demographic and occupational factors associated with seropositivity. Results A total of 1148/10662 (10.8%) hospital staff members were seropositive. Compared to White staff (seroprevalence 9.1%), seroprevalence was higher in South Asian (12.3%) and Black (21.2%) staff. The occupations and department with the highest seroprevalence were nurses/healthcare assistants (13.7%) and the Emergency Department (ED)/Acute Medicine (17.5%), respectively. Seroprevalence decreased with seniority in medical/nursing practitioners. Minority ethnicity was associated with seropositivity on an adjusted analysis (South Asian: aOR 1.26; 95%CI: 1.07–1.49 and Black: 2.42; 1.90–3.09). Anaesthetics/ICU staff members were less likely to be seropositive than ED/Acute medicine staff (0.41; 0.27–0.61). Conclusions Ethnicity and occupational factors, including specialty and seniority, are associated with seropositivity for anti-SARS-Cov-2 IgG. These findings could be used to inform occupational risk assessments for front-line healthcare workers.
  • Effectiveness of a web-based virtual journal club to promote medical education (Web-Ed): protocol of a multicentre pragmatic randomised trial

    Murugesu, Nilaani (2022-06-16)
    Introduction A journal club (JC) is a commonly used medical educational tool. Videoconferencing technology can facilitate the delivery of JCs, however, there remains no evidence on the role of web-based virtual JCs in promoting the acquisition and retention of medical knowledge. The Web-Ed trial aims to evaluate the educational benefits, feasibility and acceptability of web-based virtual JCs compared with traditional face-to-face ones. Methods and analysis Web-Ed is a multicentre pragmatic parallel-group randomised trial across teaching hospitals within the UK National Health Service (NHS). We will enrol qualified doctors or medical students who are >18 years old, proficient in English and able to use online videoconferencing software. Block randomisation will be used to allocate participants in 1:1 ratio to either intervention group. Both groups will be presented with the same educational material and follow a standardised JC structure hosted by nominated moderators and medical faculty members. The primary outcome is the difference in participants’ knowledge acquisition and retention 7 days after the JCs evaluated using standardised multiple-choice questions. We will report secondarily on the feasibility and acceptability of the JCs using Likert scale questionnaires. Assuming a 30% drop-out rate, we aim to enrol 75 participants to detect a 20% improvement in knowledge acquisition at 80% power and 5% significance. We will report using mean difference or risk ratio with 95% CIs and assess significance using parametric/non-parametric testing. Where relevant, we will adjust for predetermined characteristics (age, grade of training and session duration) using multivariate regression analyses. Ethics and dissemination Web-Ed was designed by doctors in training to address their learning needs and evaluate the preferred mode of learning. The trial results will be published in peer-reviewed journals and presented at relevant scientific conferences. The trial has been approved by the NHS Health Regulation Authority (21/HRA/3361).
  • Live streaming to sustain clinical learning

    Grafton-Clarke, Ciaran; Uraiby, Hussain; Abraham, Shalin; Kirtley, Joanne; Xu, Gang; McCarthy, Mark
    Background The COVID-19 pandemic has necessitated the need to develop teaching innovations that provide safe, authentic clinical encounters which facilitate experiential learning. In tandem with the dissemination of teleconsultation and online teaching, this pilot study describes, evaluates and justifies a multi-camera live-streaming teaching session to medical students from the clinical environment. Approach Multiple audio and video inputs capturing an outpatient clinic setting were routed through Open Broadcast Software (OBS) to create a customised feed streamed to remote learners through a videoconferencing platform. Sessions were conducted between September 2020 and March 2021. Twelve students sequentially interacted with a patient who held an iPad. Higher quality Go-Pro cameras captured the scene, allowing students to view the consultation from the patient and doctor's perspective. A consultant then conducted a ‘gold standard’ patient consultation observed by students. A faculty member remotely facilitated the session, providing pre-clinic teaching and debriefing. The equipment required with costing for a standard and low-cost version is described, as well as a set-up schematic and overview of ideal conditions and barriers encountered during trials. Evaluation All students completed a post-participation questionnaire, rating the overall quality of the sessions as 9.7/10. The quality of online facilitation, utility of observing peers' and consultant interaction with the patient, opportunity for peer-to-peer learning and availability of multiple camera angles were particularly valued by students. Implications This innovation permits an authentic clinical interaction to be experienced by multiple students remotely, promoting equitable access to high-quality teaching, while maintaining the safety of students and patients.
  • Isolated tectal cavernomas: A comprehensive literature review with a case presentation

    Asfour, Hasan
    ntracranial cavernous angiomas or cavernomas (ICCs) are abnormal blood-filled vasculatures made of mono-endothelial layer and characterized by their bubble-like caverns. Brainstem cavernomas (BSCs) is a critical form of ICCs since slight changes in the lesion can result in devastating or life-threatening outcomes. We hereby present a rare case of BSC developed in the mesencephalic tectum with intraventricular bleeding and Parinaud's Syndrome. Our patient was managed by complete surgical resection of the lesion through an infra-tentorial supracerebellar approach. Additionally, we reviewed and analyzed the hitherto reported cases of isolated tectal cavernomas (TCs) in the literature, including our case, to elucidate the main factors associated with the management outcomes of TCs. There have been 25 cases of isolated TC reported until now. Most of the patients were adults between 18-77 y of age, except for two children (7 and 13 y). There was no sex predominance. Symptomatic patients presented with headache 56%, altered level of consciousness 24%, and/or double vision 20%. Most cases (64%) had hemorrhagic lesions at presentation, and 60% of all cases experienced recurrent hemorrhages. Parinaud's Syndrome was recorded in five cases, including the current one. All cases affected with Parinaud's were males. Lesion size was a determinant of the outcome as larger lesions were more likely to result in persistent deficits. Surgical resection of the lesion was an effective management modality with ∼79% (15/19) of patients who underwent surgery ended up with complete recovery.
  • Antiplatelets or anticoagulants? Secondary prevention in cervical artery dissection: an updated meta-analysis

    The, Ei Zune
    Background: Extracranial artery dissection involving either internal carotid artery or vertebral artery is a major cause of stroke in adults under 50 years of age. There is no conclusive evidence whether antiplatelets or anticoagulants are better suited in the treatment of extracranial artery dissection. Objectives: To determine whether antiplatelets or anticoagulants have advantage over the other in the treatment of extracranial artery dissection for secondary prevention of recurrent ischemic events or death. Methods: Present meta-analysis followed Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) 2020 statement. Database search was done in Medline, Cochrane Central Register of Controlled Trials (CENTRAL) and ClinicalTrials.gov from inception to May 2021 using pre-defined search strategy. Additional studies were identified from reference lists from included studies, reviews and previous meta-analyses. Outcome measures were ischaemic stroke, ischaemic stroke or transient ischaemic attack (TIA), and death. Results: Two RCTs and 64 observational studies were included in the meta-analysis. While the outcome measures of stroke, stroke or TIA and death were numerically higher with antiplatelet use, there were no statistically significant differences between antiplatelets and anticoagulants. Conclusion: We found no significant difference between antiplatelet and anticoagulation treatment after extracranial artery dissection. The choice of treatment should be tailored to individual cases. Keywords: Anticoagulants; Aspirin; Extracranial artery dissection; Internal carotid artery; Meta-analysis; Secondary prevention; Stroke; Vertebral artery.
  • A multicentre qualitative study of patient skin surgery experience during the COVID-19 pandemic in the UK

    Gnanappiragasam, Dushyanth; Veitch, David; Wernham, Aaron
    Understanding patient concerns regarding skin surgery during the COVID-19 pandemic is a vital way of learning from individual experiences. A shift towards using superficial absorbable sutures (AS) has been anecdotally observed. We explored patient attitudes to the use of AS, and their experiences and perceptions of attending for skin surgery during the pandemic. In total, 35 participants were interviewed (74% men, 100% white British; mean age 72.5 years, range 43-95 years). Participants reported that they were reassured by precautions taken to minimize exposure and risk from COVID-19. The majority (86%) did not feel that personal protective equipment worn by staff impaired their experience, and 29% reported that their experience of attending for skin surgery during the lockdown period was more efficient and organized than on prepandemic visits. The vast majority (94%) of participants would opt to have AS again or had no strong preference for either suture type. Based on their experiences, most participants would have no concerns about attending for further skin surgery during the pandemic and would opt to have AS.
  • Local anesthetics in dermatologic surgery: a review of adjuncts and pain reduction techniques

    Gnanappiragasam, Dushyanth; Veitch, David; Wernham, Aaron (2022-05-27)
    A variety of local anesthetic adjuncts exist for dermatological surgery. Similarly, many options to reduce the pain of local anesthesia exist. This review aims to summarise the evidence relating to local anesthetic adjuncts and methods to reduce the pain of local anesthesia. Adjuncts to local anesthetics can be an important consideration to optimise anesthetic effect. Current evidence suggests that buffering and warming local anesthetics, skin cooling, pinching, as well as administering vibrations to the skin are effective at reducing pain during administration. No significant difference was found between administering vibrations and skin cooling with regards to reducing pain. Studies demonstrate that overall, local anesthesia injection into distal sites is safe. However, there remains limited evidence specific to dermatologic surgery supporting ways to reduce pain during local anesthetic injection, and in determining the safety of local anesthetics for distal sites with confidence. Further high-quality research in the form of multi-centre randomised trials is required.
  • Translation into Spanish and Field-Testing of a New Score for Evaluating Psoriasis Severity: The Simplified Psoriasis Index (SPI)

    Helbling, Ingrid (2022-04)
    Background: The simplified psoriasis index (SPI) was developed in the United Kingdom to provide a simple summary measure for monitoring changes in psoriasis severity and associated psychosocial impact as well as for obtaining information about past disease behavior and treatment. Two complementary versions of the SPI allow for self-assessment by the patient or professional assessment by a doctor or nurse. Both versions have proven responsive to change, reliable, and interpretable, and to correlate well with assessment tools that are widely used in clinical trials - the Psoriasis Area and Severity Index and the Dermatology Quality of Life Index. The SPI has already been translated into several languages, including French, Brazilian Portuguese, Dutch, Arabic, and Thai. Objective: To translate the professional and self-assessment versions of the SPI to Spanish and to field test the translations. Method: A medically qualified native Spanish speaker translated both versions of the SPI into Spanish. The Spanish translations were discussed by comparing them to blinded back translations into English undertaken by native English speakers; the Spanish texts were then revised in an iterative process involving the translators, 4 dermatologists, and 20 patients. The patients scored their own experience of psoriasis with the self-assessment version and commented on it. The process involved checking the conceptual accuracy of the translation, language-related differences, and subtle gradations of meaning in a process involving all translators and a panel of both Spanish- and English-speaking dermatologists, including a coauthor of the SPI. Results: The final self-assessment and professional Spanish versions of the SPI are presented in this manuscript. Conclusions: Castilian Spanish translations of both versions of the SPI are now available for monitoring disease changes in Spanish-speaking patients with psoriasis under routine clinical care.

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