Recent Submissions

  • Immune responses against SARS-CoV-2 variants after two and three doses of vaccine in B-cell malignancies: UK PROSECO study

    Ahearne, Matthew (2022-05)
    Patients with hematological malignancies are at increased risk of severe COVID-19 outcomes due to compromised immune responses, but the insights of these studies have been compromised due to intrinsic limitations in study design. Here we present the PROSECO prospective observational study ( NCT04858568 ) on 457 patients with lymphoma that received two or three COVID-19 vaccine doses. We show undetectable humoral responses following two vaccine doses in 52% of patients undergoing active anticancer treatment. Moreover, 60% of patients on anti-CD20 therapy had undetectable antibodies following full vaccination within 12 months of receiving their anticancer therapy. However, 70% of individuals with indolent B-cell lymphoma displayed improved antibody responses following booster vaccination. Notably, 63% of all patients displayed antigen-specific T-cell responses, which increased after a third dose irrespective of their cancer treatment status. Our results emphasize the urgency of careful monitoring of COVID-19-specific immune responses to guide vaccination schemes in these vulnerable populations.
  • Normative wrist-worn accelerometer values for self-paced walking and running: a walk in the park

    Davies, Melanie (2022-01)
    This study aimed to a) determine whether wrist acceleration varies by accelerometer brand, wear location, and age for self-paced "slow", "normal" and "brisk" walking; b) develop normative acceleration values for self-paced walking and running for adults. One-hundred-and-three adults (40-79 years) completed self-paced "slow", "normal" and "brisk" walks, while wearing three accelerometers (GENEActiv, Axivity, ActiGraph) on each wrist. A sub-sample (n = 22) completed a self-paced run. Generalized estimating equations established differences by accelerometer brand, wrist, and age-group (walking only, 40-49, 50-59, 60-69, 70-79 years) for self-paced walking and running. Brand*wrist interactions showed ActiGraph dominant wrist values were ~10% lower than GENEActiv/Axivity values for walking and running, and non-dominant ActiGraph values were ~5% lower for running only (p < 0.001). Acceleration during brisk walking was lower in those aged 70-79 (p < 0.05). Normative acceleration values (non-dominant wrist, all brands; dominant wrist GENEActiv/Axivity) for slow and normal walking were 140 mg and 210 mg. Brisk walking, values were 350 mg in those aged 40-69 years, but 270 mg in those aged 70-79 years. Accelerations >600 mg approximated running. These values facilitate user-friendly interpretation of accelerometer-determined physical activity in large cohort and epidemiological datasets.
  • 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; Simpson, Sandra
    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; Simpson, Sandra
    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.
  • 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.
  • 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 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.
  • Healing of ExcisionAl wounds on Lower legs by Secondary intention (HEALS) Cohort: Feasibility data from a multi-centre prospective observational cohort study to inform a future Randomised Controlled Trial (RCT)

    Veitch, David (2022-06-03)
    Background: Compression therapy is considered beneficial for lower limb post-surgical wounds healing by secondary intention, however there is a lack of supportive evidence. To plan a randomised controlled trial suitable data is needed. Objectives: Determine feasibility of recruitment and estimate recruitment rate Understand the standard post-operative wound management pathway Determine uptake of optional additional clinic visit for healing confirmation Explore patient acceptability of compression bandaging and a future RCT METHODS: Participant recruitment over 22 months from secondary care Dermatology clinics. Eligibility criteria: INCLUSION: over 18 years; planned excision of keratinocyte cancer on lower leg with healing by secondary intention; ankle-brachial pressure index ≥ 0.8 EXCLUSION: planned primary closure/graft or flap; unable to receive/comply/tolerate high compression; planned compression; suspected melanoma Followed up weekly (maximum 6 months) in secondary care clinics and/or by telephone. Information collected on healthcare resource use, unplanned compression, wound healing, optional clinic visit to confirm healing. Results: 58 patients recruited from 9 secondary care dermatology clinics in 22 months. Mean recruitment/centre/month was 0.8 (range 0.1-2.3). Four centres had dedicated Research Nurse support. The analysis population (n=53) attended weekly follow-up assessments. Standard care clinical contacts were: GP visits 7(1.2%), Community Nurse visits 169(28.5%), Practice nurse visits 189(31.8%), and Dermatology clinic visits 138(23.2%). Participants whose wounds healed, 34/45(75.6%) attended an optional clinic visit. Conclusions: Data were obtained to inform a future RCT. Recruitment rates are higher in centres with dedicated research support. People would be willing to take part in a trial and attend a confirmation of healing visit.
  • Healing of ExcisionAl wounds on Lower legs by Secondary intention (HEALS) Cohort Study: A multi-centre prospective observational cohort study in patients without planned compression

    Veitch, David
    Background: There is no agreed treatment pathway following excision of keratinocyte cancers. Compression therapy is considered beneficial for secondary intention healing on the lower limb, however there is a lack of supportive evidence. To plan a randomised controlled trial suitable data is needed. This paper reports a multi-centre prospective observational cohort study in this patient population, to inform a future trial design. Objectives: 1. To estimate the time to healing in wounds healing by secondary intention without planned post-operative compression, following excision of keratinocyte cancers on the lower leg 2. To characterise the patient population including factors affecting healing 3. To assess the incidence of complications METHODS: INCLUSION CRITERIA: People over 18 years; planned excision of keratinocyte cancer on lower leg with healing by secondary intention; ankle-brachial pressure index (ABPI) greater than or equal to 0.8; written informed consent EXCLUSION CRITERIA: Planned: primary closure, skin graft or flap; compression therapy for another indication; unable to receive, comply or tolerate high compression; planned compression; suspected diagnosis other than keratinocyte cancer. Results: This study recruited 58 patients from 9 secondary care dermatology clinics. In the analysis population (n=53): mean age was 81 (range 25-97) years; median time to healing was 81(95% Confidence Interval:73-92) days and at 6-month 45 patients (84.9%) had healed. Healing prognostic factors were wound parameters, and ABPI. Wound infections occurred in 16 participants(30.2%) and 4(7.5%) were admitted to hospital. Conclusions: Data collected has informed the RCT preparation. A relatively high (7.5-15%) proportion of wounds not healed, incidence of infection and hospital admissions demonstrated the need for clearly establishing potentially effective treatments and improve outcomes for this population.
  • Use of perioperative prophylactic antibiotics following excision of ulcerated skin lesions in the UK: a national, multispeciality survey of clinicians

    Wernham, Aaron (2022-05)
    Skin cancer is the most common malignancy in the UK, and up to a third of lesions are ulcerated at the time of excision. Ulceration has been shown to increase the risk of developing surgical site infection following excision, with some studies finding infection rates of 33%. However, no specific guidelines for the use of antibiotic prophylaxis in such cases exist. We surveyed 129 clinicians (covering Dermatology, Plastic Surgery, Ear, Nose and Throat Surgery, and Oral and Maxillofacial Surgery) who all excise skin lesions on a regular basis. There was significant variability in their practice with regard to antibiotic prophylaxis, with 9% always prescribing them and 19% never prescribing them. Variation exists both among and between specialities. This variation increases the risk of antimicrobial resistance and shows a paucity of good clinical evidence, indicating that a well-designed clinical trial is needed to guide future practice.

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