Search

Routinely collected health data (RCD) including electronic health records, disease registries, health administrative data and wearables data are not specifically collected for research purposes. Analysis of these data poses unique methodological challenges that must be addressed when conducting research, particularly as availability and use increase. This scoping review aimed to identify methodological challenges in research using RCD from existing literature (registered protocol: https://doi.org/10.17605/OSF.IO/EBM4D). We searched 6 electronic databases, including medical, health economics, nursing and psychology research databases, between Jan 2015 and Jan 2023, combining multiple “RCD” and “research” search terms (e.g., epidemiologic, informatics, pharmaceutical research). After screening abstracts and full-texts, we doubly extracted methodological themes, categorizing them into different study stages. We screened more than 23,000 records and included 430 papers. Bias and confounding were the most common methodological issues identified, discussed in relation to both study design and data analysis. Data quality, including data accuracy, validation, completeness, timeliness and cleaning, also posed substantial challenges, particularly during data processing stage. Record linkage and conducting analyses using distributed health networks also pose unique methodological challenges. Heterogeneity, incorporating social determinants of health and statistical models that address methodological challenges are also described in the literature. External validity and reporting are important considerations for RCD research. Our review identified several methodological challenges facing researchers using RCD. These issues should be addressed to ensure methodologically sound research. These findings will inform the development of a standardized protocol template and accompanying educational platform aimed at enhancing methodological quality and transparency when conducting research using RCD.

Some antihypertensive medications are photosensitizing. The implications for skin cancer risk remain unclear because results from prior studies are inconsistent and as new evidence is published. We performed a systematic review and meta-analysis to evaluate the association between antihypertensives and common skin cancers (cutaneous squamous cell carcinoma, basal cell carcinoma, and melanoma) and to evaluate dose–response relationships. Forty-four articles met inclusion criteria, and 42 could be meta analyzed. Increased risks were seen for basal cell carcinoma with calcium channel blockers (relative risk [RR] = 1.17, 95% confidence interval [CI] = 1.11–1.22), diuretics (RR = 1.06, 95% CI = 1.03–1.10), and thiazides (RR = 1.10, 95% CI = 1.04–1.16); for squamous cell carcinoma with calcium channel blockers (RR = 1.08, 95% CI = 1.01–1.14), diuretics (RR = 1.29, 95% CI = 1.17–1.43), and thiazides (RR = 1.36, 95% CI = 1.15–1.61); and for melanoma in angiotensin-converting enzyme inhibitors (RR = 1.09, 95% CI = 1.03–1.14), calcium channel blockers (RR = 1.08, 95% CI = 1.03–1.12), and thiazides (RR = 1.09, 95% CI = 1.02–1.17). The quality of evidence was low or very low. We observed evidence for dose–response for thiazides with basal cell carcinoma; angiotensin-converting enzyme inhibitors, diuretics, and thiazides with squamous cell carcinoma; and angiotensin-converting enzyme inhibitors, diuretics, and thiazides with melanoma. Our meta-analysis supports a potential causal association between some antihypertensives, particularly diuretics, and skin cancer risk.

Abstract Background Evidence demonstrates that individuals with atopic eczema (eczema) have increased depression and anxiety; however, the role of ethnicity in these associations is poorly understood. We aimed to investigate whether associations between eczema and depression or anxiety differed between adults from white and minority ethnic groups in the UK. Methods We used UK Clinical Practice Research Datalink GOLD to conduct matched cohort studies of adults (≥18 years) with ethnicity recorded in primary care electronic health records (April 2006‐January 2020). We matched (age, sex, practice) adults with eczema to up to five adults without. We used stratified Cox regression with an interaction between eczema and ethnicity, to estimate hazard ratios (HRs) for associations between eczema and incident depression and anxiety in individuals from white ethnic groups and a pooled minority ethnic group (adults from Black, South Asian, Mixed and Other groups). Results We identified separate cohorts for depression (215,073 with eczema matched to 646,539 without) and anxiety (242,598 with eczema matched to 774,113 without). After adjusting for matching variables and potential confounders (age, sex, practice, deprivation, calendar period), we found strong evidence (p

Anatoxin-a and its analogues are potent neurotoxins produced by several genera of cyanobacteria. Due in part to its high toxicity and potential presence in drinking water, these toxins pose threats to public health, companion animals and the environment. It primarily exerts toxicity as a cholinergic agonist, with high affinity at neuromuscular junctions, but molecular mechanisms by which it elicits toxicological responses are not fully understood. To advance understanding of this cyanobacteria, proteomic characterization (DIA shotgun proteomics) of two common fish models (zebrafish and fathead minnow) was performed following (±) anatoxin-a exposure. Specifically, proteome changes were identified and quantified in larval fish exposed for 96 h (0.01–3 mg/L (±) anatoxin-a and caffeine (a methodological positive control) with environmentally relevant treatment levels examined based on environmental exposure distributions of surface water data. Proteomic concentration - response relationships revealed 48 and 29 proteins with concentration - response relationships curves for zebrafish and fathead minnow, respectively. In contrast, the highest number of differentially expressed proteins (DEPs) varied between zebrafish (n = 145) and fathead minnow (n = 300), with only fatheads displaying DEPs at all treatment levels. For both species, genes associated with reproduction were significantly downregulated, with pathways analysis that broadly clustered genes into groups associated with DNA repair mechanisms. Importantly, significant differences in proteome response between the species was also observed, consistent with prior observations of differences in response using both behavioral assays and gene expression, adding further support to model specific differences in organismal sensitivity and/or response. When DEPs were read across from humans to zebrafish, disease ontology enrichment identified diseases associated with cognition and muscle weakness consistent with the prior literature. Our observations highlight limited knowledge of how (±) anatoxin-a, a commonly used synthetic racemate surrogate, elicits responses at a molecular level and advances its toxicological understanding.

[This corrects the article DOI: 10.1371/journal.pgph.0002601.].

Abstract Background Psoriasis and atopic eczema are common inflammatory skin diseases. Existing research has identified increased risks of common mental disorders (anxiety, depression) in people with eczema and psoriasis; however, explanations for the associations remain unclear. We aimed to establish the risk factors for mental illness in those with eczema or psoriasis and identify the population groups most at risk. Methods We used routinely collected data from the UK Clinical Practice Research Datalink (CPRD) GOLD. Adults registered with a general practice in CPRD (1997–2019) were eligible for inclusion. Individuals with eczema/psoriasis were matched (age, sex, practice) to up to five adults without eczema/psoriasis. We used Cox regression to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for hazards of anxiety or depression in people with eczema/psoriasis compared to people without. We adjusted for known confounders (deprivation, asthma [eczema], psoriatic arthritis [psoriasis], Charlson comorbidity index, calendar period) and potential mediators (harmful alcohol use, body mass index [BMI], smoking status, and, in eczema only, sleep quality [insomnia diagnoses, specific sleep problem medications] and high-dose oral glucocorticoids). Results We identified two cohorts with and without eczema (1,032,782, matched to 4,990,125 without), and with and without psoriasis (366,884, matched to 1,834,330 without). Sleep quality was imbalanced in the eczema cohorts, twice as many people with eczema had evidence of poor sleep at baseline than those without eczema, including over 20% of those with severe eczema. After adjusting for potential confounders and mediators, eczema and psoriasis were associated with anxiety (adjusted HR [95% CI]: eczema 1.14 [1.13–1.16], psoriasis 1.17 [1.15–1.19]) and depression (adjusted HR [95% CI]: eczema 1.11 [1.1–1.12], psoriasis 1.21 [1.19–1.22]). However, we found evidence that these increased hazards are unlikely to be constant over time and were especially high 1-year after study entry. Conclusions Atopic eczema and psoriasis are associated with increased incidence of anxiety and depression in adults. These associations may be mediated through known modifiable risk factors, especially sleep quality in people with eczema. Our findings highlight potential opportunities for the prevention of anxiety and depression in people with eczema/psoriasis through treatment of modifiable risk factors and enhanced eczema/psoriasis management.

Abstract Background Topical corticosteroids (TCS) are a first‐line treatment for eczema, but there are concerns about their safety when used long‐term. Objectives To systematically review adverse effects associated with longer‐term use of TCS for eczema. Methods Randomised controlled trials (RCTs), cohort and case‐control studies reporting adverse effects of TCS (comparators: no TCS treatment, other topicals) in patients with eczema were identified. Included studies had greater than one year of follow‐up, minimum cohort size of 50 participants, or minimum 50 per arm for RCTs. Evidence was GRADE‐assessed. Prospero registration CRD42021286413. Results We found seven studies (two randomised, five observational); two RCTs (n = 2570, including 1288 receiving TCS), two cohort (all received TCS n = 148) and three case‐control studies (cases n = 10 322, controls n = 12 201). Evidence from two RCTS (n = 2570, children, three and five years' duration) comparing TCS to topical calcineurin inhibitors found intermittent TCS use probably results in little to no difference in risk of growth abnormalities, non‐skin infections, impaired vaccine response and lymphoma/non lymphoma malignancies. The five‐year RCT reported only one episode of skin atrophy (n = 1213 TCS arm; mild/moderate potency), suggesting TCS use probably results in little to no difference in skin thinning when used intermittently to treat flares. No cases of clinical adrenal insufficiency were reported in 75 patients using mild/moderate TCS in the three‐year RCT. Small associations between TCS and type‐2 diabetes and lymphoma were identified in two case‐control studies compared to no TCS, but the evidence is very uncertain. No long‐term studies concerning topical steroid withdrawal or eye problems were identified. Conclusion This review provides some reassuring data on growth and skin thinning when TCS are used intermittently for up to 5 years, but many knowledge gaps remain.

Objectives: Investigate risk factors for SARS-CoV-2 infections in school students and staff. Methods: In the 2020/2021 school year, we administered polymerase chain reaction, antibody tests, and questionnaires to a sample of primary and secondary school students and staff, with data linkage to COVID-19 surveillance. We fitted logistic regression models to identify the factors associated with infection. Results: We included 6799 students and 5090 staff in the autumn and 11,952 students and 4569 staff in the spring/summer terms. Infections in students in autumn 2020 were related to the percentage of students eligible for free school meals. We found no statistical association between infection risk in primary and secondary schools and reported contact patterns between students and staff in either period in our study. Using public transports was associated with increased risk in autumn in students (adjusted odds ratio = 1.72; 95% confidence interval 1.31-2.25) and staff. One or more infections in the same household during either period was the strongest risk factor for infection in students and more so among staff. Conclusion: Deprivation, community, and household factors were more strongly associated with infection than contacts patterns at school; this suggests that the additional school-based mitigation measures in England in 2020/2021 likely helped reduce transmission risk in schools.

Summary: Background: The COVID-19 pandemic disrupted healthcare and may have impacted ethnic inequalities in healthcare. We aimed to describe the impact of pandemic-related disruption on ethnic differences in clinical monitoring and hospital admissions for non-COVID conditions in England. Methods: In this population-based, observational cohort study we used primary care electronic health record data with linkage to hospital episode statistics data and mortality data within OpenSAFELY, a data analytics platform created, with approval of NHS England, to address urgent COVID-19 research questions. We included adults aged 18 years and over registered with a TPP practice between March 1, 2018, and April 30, 2022. We excluded those with missing age, sex, geographic region, or Index of Multiple Deprivation. We grouped ethnicity (exposure), into five categories: White, Asian, Black, Other, and Mixed. We used interrupted time-series regression to estimate ethnic differences in clinical monitoring frequency (blood pressure and Hba1c measurements, chronic obstructive pulmonary disease and asthma annual reviews) before and after March 23, 2020. We used multivariable Cox regression to quantify ethnic differences in hospitalisations related to diabetes, cardiovascular disease, respiratory disease, and mental health before and after March 23, 2020. Findings: Of 33,510,937 registered with a GP as of 1st January 2020, 19,064,019 were adults, alive and registered for at least 3 months, 3,010,751 met the exclusion criteria and 1,122,912 were missing ethnicity. This resulted in 14,930,356 adults with known ethnicity (92% of sample): 86.6% were White, 7.3% Asian, 2.6% Black, 1.4% Mixed ethnicity, and 2.2% Other ethnicities. Clinical monitoring did not return to pre-pandemic levels for any ethnic group. Ethnic differences were apparent pre-pandemic, except for diabetes monitoring, and remained unchanged, except for blood pressure monitoring in those with mental health conditions where differences narrowed during the pandemic. For those of Black ethnicity, there were seven additional admissions for diabetic ketoacidosis per month during the pandemic, and relative ethnic differences narrowed during the pandemic compared to the White ethnic group (Pre-pandemic hazard ratio (HR): 0.50, 95% confidence interval (CI) 0.41, 0.60, Pandemic HR: 0.75, 95% CI: 0.65, 0.87). There was increased admissions for heart failure during the pandemic for all ethnic groups, though highest in those of White ethnicity (heart failure risk difference: 5.4). Relatively, ethnic differences narrowed for heart failure admission in those of Asian (Pre-pandemic HR 1.56, 95% CI 1.49, 1.64, Pandemic HR 1.24, 95% CI 1.19, 1.29) and Black ethnicity (Pre-pandemic HR 1.41, 95% CI: 1.30, 1.53, Pandemic HR: 1.16, 95% CI 1.09, 1.25) compared with White ethnicity. For other outcomes the pandemic had minimal impact on ethnic differences. Interpretation: Our study suggests that ethnic differences in clinical monitoring and hospitalisations remained largely unchanged during the pandemic for most conditions. Key exceptions were hospitalisations for diabetic ketoacidosis and heart failure, which warrant further investigation to understand the causes. Funding: LSHTM COVID-19 Response Grant (DONAT15912).

Abstract Eczema and asthma are allergic diseases and two of the commonest chronic conditions in high-income countries. Their co-existence with other allergic conditions is common, but little research exists on wider multimorbidity with these conditions. We set out to identify and compare clusters of multimorbidity in people with eczema or asthma and people without. Using routinely-collected primary care data from the U.K. Clinical Research Practice Datalink GOLD, we identified adults ever having eczema (or asthma), and comparison groups never having eczema (or asthma). We derived clusters of multimorbidity from hierarchical cluster analysis of Jaccard distances between pairs of diagnostic categories estimated from mixed-effects logistic regressions. We analysed 434,422 individuals with eczema (58% female, median age 47 years) and 1,333,281 individuals without (55% female, 47 years), and 517,712 individuals with asthma (53% female, 44 years) and 1,601,210 individuals without (53% female, 45 years). Age at first morbidity, sex and having eczema/asthma affected the scope of multimorbidity, with women, older age and eczema/asthma being associated with larger morbidity clusters. Injuries, digestive, nervous system and mental health disorders were more commonly seen in eczema and asthma than control clusters. People with eczema and asthma of all ages and both sexes may experience greater multimorbidity than people without eczema and asthma, including conditions not previously recognised as contributing to their disease burden. This work highlights areas where there is a critical need for research addressing the burden and drivers of multimorbidity in order to inform strategies to reduce poor health outcomes.

Eczema is a common chronic disease that affects both children and adults, and may have an adverse impact on school performance, as it is characteristically pruritic, and hence may lead to poor concentration and inadequate sleep. The aim of this study was to elucidate the relationship between eczema and self-reported difficulties keeping up with school education. The study was based on cross-sectional questionnaire data collected in schools among all 9th graders (15–16 years old) within a Swedish county. Logistic regression analyses were used to assess the association between having eczema and self-reported difficulties keeping up with school education. A total of 2,620 pupils participated (50.1% female). An increased odds ratio (OR) of self-reported difficulties keeping up with school education was found in adolescents with eczema compared with those without eczema after adjustment for sex and family residence (OR 2.13, 95% confidence interval (95% CI) 1.32–3.44), and with additional adjustment for sleeping problems, attention-deficit hyperactivity disorder, allergy, rhinitis, asthma, and alcohol consumption (adjusted OR 1.78, CI 1.05–3.00). Eczema may be a relevant risk factor for difficulty keeping up with school education in adolescents. However, studies that can assess temporality, based in different settings with objective reports of both eczema and self-reported difficulties at school, are needed to confirm these findings.

Implementation studies rarely examine how health interventions are delivered in emergencies. Informed by May's general theory of implementation (GTI), we undertook qualitative longitudinal research to investigate how schools in England implemented Covid-19-prevention measures and how this evolved over the 2020–2021 school year in a rapidly changing epidemiological and policy context. We conducted 74 semi-structured interviews over two time-points with headteachers, teachers, parents and students across eight primary and secondary schools. School leaders rapidly made sense of government guidance despite many challenges. They developed and disseminated prevention plans to staff, parents and students. As defined by GTI, ‘cognitive participation’ and ‘collective action’ to enact handwashing, one-way systems within schools and enhanced cleaning were sustained over time. However, measures such as physical distancing and placing students in separated groups were perceived to conflict with schools' mission to promote student education and wellbeing. Commitment to implement these was initially high during the emergency phase but later fluctuated dependant on perceived risk and local disease epidemiology. They were not considered sustainable in the long term. Adherence to some measures, such as wearing face-coverings, initially considered unworkable, improved as they were routinised. Implementing home-based asymptomatic testing was considered feasible. Formal and informal processes of ‘reflexive monitoring’ by staff informed improvements in intervention workability and implementation. Leaders also developed skills and confidence, deciding on locally appropriate actions, some of which deviated from official guidance. However, over time, accumulating staff burnout and absence eroded school capacity to collectively enact implementation. Qualitative longitudinal research allowed us to understand how implementation in an emergency involved the above emergent processes. GTI was useful in understanding school implementation processes in a pandemic context but may need adaptation to take into account the changing and sometimes contradictory objectives, time-varying factors and feedback loops that can characterise implementation of health interventions in emergencies.

The COVID-19 pandemic has brought about valuable insights regarding models, data, and experiments. In this narrative review, we summarised the existing literature on these three themes, exploring the challenges of providing forecasts, the requirement for real-time linkage of health-related datasets, and the role of 'experimentation' in evaluating interventions. This literature review encourages us to broaden our perspective for the future, acknowledging the significance of investing in models, data, and experimentation, but also to invest in areas that are conceptually more abstract: the value of 'team science', the need for public trust in science, and in establishing processes for using science in policy. Policy-makers rely on model forecasts early in a pandemic when there is little data, and it is vital to communicate the assumptions, limitations, and uncertainties (theme 1). Linked routine data can provide critical information, for example, in establishing risk factors for adverse outcomes but are often not available quickly enough to make a real-time impact. The interoperability of data resources internationally is required to facilitate sharing across jurisdictions (theme 2). Randomised controlled trials (RCTs) provided timely evidence on the efficacy and safety of vaccinations and pharmaceuticals but were largely conducted in higher income countries, restricting generalisability to low- and middle-income countries (LMIC). Trials for non-pharmaceutical interventions (NPIs) were almost non-existent which was a missed opportunity (theme 3). Building on these themes from the narrative review, we underscore the importance of three other areas that need investment for effective evidence-driven policy-making. The COVID-19 response relied on strong multidisciplinary research infrastructures, but funders and academic institutions need to do more to incentivise team science (4). To enhance public trust in the use of scientific evidence for policy, researchers and policy-makers must work together to clearly communicate uncertainties in current evidence and any need to change policy as evidence evolves (5). Timely policy decisions require an established two-way process between scientists and policy makers to make the best use of evidence (6). For effective preparedness against future pandemics, it is essential to establish models, data, and experiments as fundamental pillars, complemented by efforts in planning and investment towards team science, public trust, and evidence-based policy-making across international communities. The paper concludes with a 'call to actions' for both policy-makers and researchers.

The Victorian Specialist Immunization Services (VicSIS) was established in Victoria, Australia, in February 2021, aiming to enhance vaccine safety services for Coronavirus disease (COVID-19) vaccines. VicSIS supports practitioners and patients with complex vaccine safety questions, including those who experience adverse events following immunization (AEFI) after COVID-19 vaccines. VicSIS provides individual vaccination recommendations, allergy testing, vaccine challenges, and vaccination under supervision. VicSIS initially comprised of eight adult COVID-19 specialist vaccination clinics, subsequently, expanding to better support pediatric patients as the Australian vaccine roll-out extended to adolescents and children. Since their establishment to September 2021, the inaugural VicSIS clinics received a total of 26,401 referrals and reviewed 6,079 patients. Consults were initially predominantly for pre-vaccination reviews, later predominantly becoming post-vaccination AEFI reviews as the program progressed. Regardless of the type of consult, the most common consult outcome was a recommendation for routine vaccination (73% and 55% of consult outcomes respectively). VicSIS is an integral component of the COVID-19 vaccination program and supports confidence in COVID-19 vaccine safety by providing consistent advice across the state. VicSIS aims to strengthen the health system through the pandemic, bolstering specialist immunization services beyond COVID-19 vaccines, including training the next generation of vaccinology experts.

BackgroundOne of the most debated questions in the COVID-19 pandemic has been the role of schools in SARS-CoV-2 transmission. The COVID-19 Schools Infection Survey (SIS) aims to provide much-needed evidence addressing this issue. ObjectiveWe present the study protocol and participation profile for the SIS study, aimed at assessing the role of schools in SARS-CoV-2 infection and transmission within school settings, and investigating how transmission within and from schools could be mitigated through the implementation of school COVID-19 control measures. MethodsSIS was a multisite, prospective, observational cohort study conducted in a stratified random sample of primary and secondary schools in selected local authorities in England. A total of 6 biobehavioral surveys were planned among participating students and staff during the 2020-2021 academic year, between November 2020 and July 2021. Key measurements were SARS-CoV-2 virus prevalence, assessed by nasal swab polymerase chain reaction; anti-SARS-CoV-2 (nucleocapsid protein) antibody prevalence and conversion, assessed in finger-prick blood for staff and oral fluid for students; student and staff school attendance rates; feasibility and acceptability of school-level implementation of SARS-CoV-2 control measures; and investigation of selected school outbreaks. The study was approved by the United Kingdom Health Security Agency Research Support and Governance Office (NR0237) and London School of Hygiene & Tropical Medicine Ethics Review Committee (reference 22657). ResultsData collection and laboratory analyses were completed by September 2021. A total of 22,585 individuals—1891 staff and 4654 students from 59 primary schools and 5852 staff and 10,188 students from 97 secondary schools—participated in at least one survey. Across all survey rounds, staff and student participation rates were 45.2% and 16.4%, respectively, in primary schools and 30% and 15.2%, respectively, in secondary schools. Although primary student participation increased over time, and secondary student participation remained reasonably consistent, staff participation declined across rounds, especially for secondary school staff (3165/7583, 41.7% in round 1 and 2290/10,374, 22.1% in round 6). Although staff participation overall was generally reflective of the eligible staff population, student participation was higher in schools with low absenteeism, a lower proportion of students eligible for free school meals, and from schools in the least deprived locations (in primary schools, 446/4654, 9.6% of participating students were from schools in the least deprived quintile compared with 1262/22,225, 5.7% of eligible students). ConclusionsWe outline the study design, methods, and participation, and reflect on the strengths of the SIS study as well as the practical challenges encountered and the strategies implemented to address these challenges. The SIS study, by measuring current and incident infection over time, alongside the implementation of control measures in schools across a range of settings in England, aims to inform national guidance and public health policy for educational settings. International Registered Report Identifier (IRRID)RR1-10.2196/34075

Summary: Background: There remains uncertainty about the epidemiology of SARS-CoV-2 among school students and staff and the extent to which non-pharmaceutical-interventions reduce the risk of school settings. Methods: We conducted an open cohort study in a sample of 59 primary and 97 secondary schools in 15 English local authority areas that were implementing government guidance to schools open during the pandemic. We estimated SARS-CoV-2 infection prevalence among those attending school, antibody prevalence, and antibody negative to positive conversion rates in staff and students over the school year (November 2020–July 2021). Findings: 22,585 staff and students participated. SARS-CoV-2 infection prevalence among those attending school was highest during the first two rounds of testing in the autumn term, ranging from 0.7% (95% CI 0.2, 1.2) among primary staff in November 2020 to 1.6% (95% CI 0.9, 2.3) among secondary staff in December 2020. Antibody conversion rates were highest in the autumn term. Infection patterns were similar between staff and students, and between primary and secondary schools. The prevalence of nucleoprotein antibodies increased over the year and was lower among students than staff. SARS-CoV-2 infection prevalence in the North-West region was lower among secondary students attending school on normal school days than the regional estimate for secondary school-age children. Interpretation: SARS-CoV-2 infection prevalence in staff and students attending school varied with local community infection rates. Non-pharmaceutical interventions intended to prevent infected individuals attending school may have partially reduced the prevalence of infection among those on the school site. Funding: UK Department of Health and Social Care.

Objective To assess implementation and ease of implementation of control measures in schools as reported by staff and parents.Design A descriptive cross-sectional survey.Setting Staff and parents/guardians of the 132 primary schools and 19 secondary schools participating in COVID-19 surveillance in school kids (sKIDs and sKIDsPLUS Studies).Main outcome measure Prevalence of control measures implemented in schools in autumn 2020, parental and staff perception of ease of implementation.Results In total, 56 of 151 (37%) schools participated in this study, with 1953 parents and 986 staff members completing the questionnaire. Most common measures implemented by schools included regular hand cleaning for students (52 of 56, 93%) and staff (70 of 73, 96%), as reported by parents and staff, respectively, and was among the easiest to implement at all times for students (57%) and even more so, for staff (78%). Maintaining 2-metre distancing was less commonly reported for students (24%–51%) as it was for staff (81%–84%), but was one of the most difficult to follow at all times for students (25%) and staff (16%) alike. Some measures were more commonly reported by primary school compared to secondary school parents, including keeping students within the same small groups (28 of 41, 68% vs 8 of 15, 53%), ensuring the same teacher for classes (29 of 41, 71% vs 6 of 15, 40%). On the other hand, wearing a face covering while at school was reported by three-quarters of secondary school parents compared with only parents of 4 of 41 (10%) primary schools. Other measures such as student temperature checks (5%–13%) and advising staff work from home if otherwise healthy (7%–15%) were rarely reported.Conclusions Variable implementation of infection control measures was reported, with some easier to implement (hand hygiene) than others (physical distancing).

Abstract Background Trials of novel agents are required to improve the care of patients with rare diseases, but trial feasibility may be uncertain due to concerns over insufficient patient numbers. We aimed to determine the size of the pool of potential participants in England 2015–2017 for trials in the autoimmune blistering skin disease bullous pemphigoid. Methods The size of the pool of potential participants was estimated using routinely collected healthcare data from linked primary care (Clinical Practice Research Datalink; CPRD) and secondary care (Hospital Episode Statistics; HES) databases. Thirteen consultant dermatologists were surveyed to determine the likelihood that a patient would be eligible for a trial based on the presence of cautions or contra-indications to prednisolone use. These criteria were applied to determine how they influenced the potential pool of participants. Results Extrapolated to the population of England, we would expect approximately 10,800 (point estimate 10,747; 95% CI 7191 to 17,239) new cases of bullous pemphigoid to be identified in a three-year period. For a future trial involving oral prednisolone (standard care), the application of cautions to its use as exclusion criteria would result in approximately 365 potential participants unlikely to be recruited, a further 5332 could be recruited with caution, and 5104 in whom recruitment is still possible. 11–17% of potential participants may have pre-existing dementia and require an alternative consent process. Conclusions Routinely collected electronic health records can be used to inform the feasibility of clinical trials in rare diseases, such as whether recruitment is feasible nationally and how long recruitment might take to meet recruitment targets. Future trials of bullous pemphigoid in England may use the data presented to inform trial design, including eligibility criteria and consent processes for enrolling people with dementia.

Background Recent studies indicate that vitamin D supplementation may decrease respiratory tract infections, but the association between vitamin D and COVID-19 is still unclear. Objective To explore the association between vitamin D status and infections, hospitalisation, and mortality due to COVID-19. Methods We used UK Biobank, a nationwide cohort of 500,000 individuals aged between 40 and 69 years at recruitment between 2006 and 2010. We included people with at least one serum vitamin D test, living in England with linked primary care and inpatient records. The primary exposure was serum vitamin D status measured at recruitment, defined as deficiency at Results We included 307,512 participants (54.9% female, 55.9% over 70 years old) in our analysis. During summertime months, weak evidence existed that the vitamin D deficiency group had a lower hazard of being diagnosed with COVID-19 (hazard ratio [HR] = 0.86, 95% confidence interval [CI] = 0.77–0.95). During non-summertime, the vitamin D deficiency group had a higher hazard of COVID-19 compared with the vitamin D sufficient group (HR = 1.14, 95% CI = 1.01–1.30). No evidence was found that vitamin D deficiency or insufficiency was associated with either hospitalisation or mortality due to COVID-19 in any time strata. Conclusion We found no evidence of an association between historical vitamin D status and hospitalisation or mortality due to COVID-19, along with inconsistent results for any association between vitamin D and diagnosis of COVID-19. However, studies using more recent vitamin D measurements and systematic COVID-19 testing are needed.

BackgroundFollowing the full re-opening of schools in England and emergence of the SARS-CoV-2 Alpha variant, we investigated the risk of SARS-CoV-2 infection in students and staff who were contacts of a confirmed case in a school bubble (school groupings with limited interactions), along with their household members.MethodsPrimary and secondary school bubbles were recruited into sKIDsBUBBLE after being sent home to self-isolate following a confirmed case of COVID-19 in the bubble. Bubble participants and their household members were sent home-testing kits comprising nasal swabs for RT-PCR testing and whole genome sequencing, and oral fluid swabs for SARS-CoV-2 antibodies.ResultsDuring November-December 2020, 14 bubbles were recruited from 7 schools, including 269 bubble contacts (248 students, 21 staff) and 823 household contacts (524 adults, 299 children). The secondary attack rate was 10.0% (6/60) in primary and 3.9% (4/102) in secondary school students, compared to 6.3% (1/16) and 0% (0/1) among staff, respectively. The incidence rate for household contacts of primary school students was 6.6% (12/183) and 3.7% (1/27) for household contacts of primary school staff. In secondary schools, this was 3.5% (11/317) and 0% (0/1), respectively. Household contacts were more likely to test positive if their bubble contact tested positive although there were new infections among household contacts of uninfected bubble contacts.InterpretationCompared to other institutional settings, the overall risk of secondary infection in school bubbles and their household contacts was low. Our findings are important for developing evidence-based infection prevention guidelines for educational settings.

Abstract Introduction The most common cancers in the UK are keratinocyte cancers (KCs): the combined term for basal cell carcinomas (BCCs) and cutaneous squamous cell carcinomas (cSCCs). Registration of KC is challenging due to high numbers and multiplicity of tumours per person. Methods We provide an updated report on the descriptive epidemiology of trends in KC incidence for the resident populations of UK countries (England, Northern Ireland, Scotland and Wales) using population‐based cancer registry and pathology report data, 2013–18. Results Substantial increases in cSCC incidence in England, Scotland and Northern Ireland can be detected for the period of 2013–18, and the incidence of cSCC also increased in Wales from 2016 to 2018. In contrast, however, the pattern of annual change in the incidence of BCC across the nations differs. In England, the incidence of BCC declined slightly from 2016 to 2018, however, the overall trend across 2013–18 is not statistically significant. In Scotland, the incidence of BCC shows some variability, declining in 2017 before increasing in 2018, and the overall trend across 2013–18 was also not statistically significant. In Northern Ireland, the incidence of BCC increased significantly over the study period, and in Wales, the incidence of BCC increased from 2016 to 2018. One in five people will develop non‐melanoma skin cancers (NMSC) in their lifetime in England. This estimate is much higher than the lifetime risk of melanoma (1 in 36 males and 1 in 47 females born after 1960 in the UK), which further highlights the burden of the disease and importance of early prevention strategies. Conclusions We highlight how common these tumours are by publishing the first ever lifetime incidence of NMSC. Additionally, the first time reporting of the age standardised incidence of KC in Wales further confirms the scale of the disease burden posed by these cancers in the UK. With approximately one in five people developing NMSC in their lifetime, optimisation of skin cancer prevention, management and research are essential.

Background: At the outset of the COVID-19 pandemic, there was no routine comprehensive hospital medicines data from the UK available to researchers. These records can be important for many analyses including the effect of certain medicines on the risk of severe COVID-19 outcomes. With the approval of NHS England, we set out to obtain data on one specific group of medicines, “high-cost drugs” (HCD) which are typically specialist medicines for the management of long-term conditions, prescribed by hospitals to patients. Additionally, we aimed to make these data available to all approved researchers in OpenSAFELY-TPP. This report is intended to support all studies carried out in OpenSAFELY-TPP, and those elsewhere, working with this dataset or similar data. Methods: Working with the North East Commissioning Support Unit and NHS Digital, we arranged for collation of a single national HCD dataset to help inform responses to the COVID-19 pandemic. The dataset was developed from payment submissions from hospitals to commissioners. Results: In the financial year (FY) 2018/19 there were 2.8 million submissions for 1.1 million unique patient IDs recorded in the HCD. The average number of submissions per patient over the year was 2.6. In FY 2019/20 there were 4.0 million submissions for 1.3 million unique patient IDs. The average number of submissions per patient over the year was 3.1. Of the 21 variables in the dataset, three are now available for analysis in OpenSafely-TPP: Financial year and month of drug being dispensed; drug name; and a description of the drug dispensed. Conclusions: We have described the process for sourcing a national HCD dataset, making these data available for COVID-19-related analysis through OpenSAFELY-TPP and provided information on the variables included in the dataset, data coverage and an initial descriptive analysis.

Objective An umbrella review summarising all safety data from systematic reviews of topical corticosteroids (TCS) in adults and children with atopic eczema.Methods Embase, MEDLINE, PubMed, Cochrane Database of Systematic Reviews and the Centre of Evidence Based Dermatology map of eczema systematic reviews were searched until 7 November 2018 and Epistemonikos until 2 March 2021. Reviews were included if they assessed the safety of TCS in atopic eczema and searched >1 database using a reproducible search strategy. Review quality was assessed using version 2 of 'A MeaSurement Tool to Assess systematic Reviews' (AMSTAR 2 tool).Results 38 systematic reviews included, 34 low/critically low quality. Treatment and follow-up were usually short (2–4 weeks).Key findings TCS versus emollient/vehicle: No meta-analyses identified for skin-thinning. Two 2-week randomised controlled trials (RCTs) found no significant increased risk with very potent TCS (0/196 TCS vs 0/33 vehicle in children and 6/109 TCS vs 2/50 vehicle, age unknown). Biochemical adrenal suppression (cortisol) was 3.8% (95% CI 2.4% to 5.8%) in a meta-analysis of 11 uncontrolled observational studies (any potency TCS, 522 children). Effects reversed when treatment ceased.TCS versus topical calcineurin inhibitors: Meta-analysis showed higher relative risk of skin thinning with TCS (4.86, 95% CI 1.06 to 22.28, n=4128, four RCTs, including one 5-year RCT). Eight cases in 2068 participants, 7 using potent TCS. No evidence of growth suppression.Once daily versus more frequent TCS: No meta-analyses identified. No skin-thinning in one RCT (3 weeks potent TCS, n=94) or biochemical adrenal suppression in two RCTs (up to 2 weeks very potent/moderate TCS, n=129).TCS twice/week to prevent flares (‘weekend therapy’) versus vehicle: No meta-analyses identified. No evidence of skin thinning in five RCTs. One RCT found biochemical adrenal suppression (2/44 children, potent TCS).Conclusions We found no evidence of harm when TCS were used intermittently ‘as required’ to treat flares or ‘weekend therapy’ to prevent flares. However, long-term safety data were limited.PROSPERO registration number CRD42018079409.

Background: Protocols are an essential document for conducting randomised controlled trials (RCTs). However, the completeness of the information provided is often inadequate. To help improve the content of trial protocols, an international group of stakeholders published the Standard Protocol Items: Recommendations for Interventional Trials (SPIRIT) Initiative in 2013. Presently, there is increasing use of cohorts and routinely collected data (RCD) for RCTs because these data have the potential to improve efficiencies by facilitating recruitment, simplifying, and reducing the cost of data collection. Reporting guidelines have been shown to improve the quality of reporting, but there is currently no specific SPIRIT guidance on protocols for trials conducted using cohorts and RCD. This protocol outlines steps for developing SPIRIT-ROUTINE, which aims to address this gap by extending the SPIRIT guidance to protocols for trials conducted using cohorts and RCD. Methods: The development of the SPIRIT-ROUTINE extension comprises five stages. Stage 1 consists of a project launch and a meeting to finalise the membership of the steering group and scope of the extension. In Stage 2, a rapid review will be performed to identify possible modifications to the original SPIRIT 2013 checklist. Other key reporting guidelines will be reviewed to identify areas where additional items may be needed, such as the Consolidated Standards of Reporting Trials (CONSORT) extension for trials conducted using cohorts and RCD (CONSORT-ROUTINE). Stage 3 will involve an online Delphi exercise, consisting of two rounds and involving key international stakeholders to gather feedback on the preliminary checklist items. In Stage 4, a consensus meeting of the SPIRIT-ROUTINE steering group will finalise the items to include in the extension. Stage 5 will involve the publication preparation and dissemination of the final checklist. Conclusion: The SPIRIT-ROUTINE extension will contribute to improving design of trials using cohorts and RCD and transparency of reporting.

Background: Antimicrobial resistance (AMR) is a global health priority. Acne vulgaris is a common skin condition for which antibiotic use ranges from a few months to years of daily exposure. Aim: To systemically search for and synthesise evidence on the risk of treatment-resistant infections, and other evidence of AMR, following long-term oral antibiotic use for acne. Design & setting: In this systematic review, a literature search was carried out using the databases Embase, MEDLINE, Cochrane, and Web of Science. They were searched using MeSH, Emtree, or other relevant terms, and followed a pre-registered protocol. Method: Search strategies were developed with a librarian and undertaken in July 2019. All searches date from database inception. The primary outcome was antibiotic treatment failure or infection caused by a resistant organism. Secondary outcomes included detection of resistant organisms without an infection, rate of infection, or changes to flora. Results: A total of 6996 records were identified. Seventy-three full-text articles were shortlisted for full review, of which five were included. Two investigated rates of infection, and three resistance or changes to microbial flora. Three studies had 35 or fewer participants (range 20–118 496). Three studies had a serious or high risk of bias, one moderate, and one a low risk of bias. Weak evidence was found for an association between antibiotic use for acne and subsequent increased rates of upper respiratory tract infections and pharyngitis. Conclusion: There is a lack of high quality evidence on the relationship between oral antibiotics for acne treatment and subsequent AMR sequelae. This needs to be urgently addressed with rigorously conducted studies.

Abstract Background Randomized controlled trials (RCTs) are often complex and expensive to perform. Less than one third achieve planned recruitment targets, follow-up can be labor-intensive, and many have limited real-world generalizability. Designs for RCTs conducted using cohorts and routinely collected health data, including registries, electronic health records, and administrative databases, have been proposed to address these challenges and are being rapidly adopted. These designs, however, are relatively recent innovations, and published RCT reports often do not describe important aspects of their methodology in a standardized way. Our objective is to extend the Consolidated Standards of Reporting Trials (CONSORT) statement with a consensus-driven reporting guideline for RCTs using cohorts and routinely collected health data. Methods The development of this CONSORT extension will consist of five phases. Phase 1 (completed) consisted of the project launch, including fundraising, the establishment of a research team, and development of a conceptual framework. In phase 2, a systematic review will be performed to identify publications (1) that describe methods or reporting considerations for RCTs conducted using cohorts and routinely collected health data or (2) that are protocols or report results from such RCTs. An initial “long list” of possible modifications to CONSORT checklist items and possible new items for the reporting guideline will be generated based on the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) and The REporting of studies Conducted using Observational Routinely-collected health Data (RECORD) statements. Additional possible modifications and new items will be identified based on the results of the systematic review. Phase 3 will consist of a three-round Delphi exercise with methods and content experts to evaluate the “long list” and generate a “short list” of key items. In phase 4, these items will serve as the basis for an in-person consensus meeting to finalize a core set of items to be included in the reporting guideline and checklist. Phase 5 will involve drafting the checklist and elaboration-explanation documents, and dissemination and implementation of the guideline. Discussion Development of this CONSORT extension will contribute to more transparent reporting of RCTs conducted using cohorts and routinely collected health data.

BackgroundAtopic dermatitis is known to be common among children, but there are few studies examining the epidemiology across the life course. In particular, there is a paucity of data on atopic dermatitis among older adults.ObjectiveTo evaluate participant characteristics, patterns of disease activity and severity, and calendar trends in older adult atopic dermatitis in comparison to other age groups in a large population-based cohort.MethodsThis was a cohort study of 9,154,936 individuals aged 0-99 years registered in The Health Improvement Network, a database comprised of electronic health records from general practices in the United Kingdom between 1994 and 2013. Atopic dermatitis was defined by a previously validated algorithm using a combination of at least one recorded atopic dermatitis diagnostic code in primary care and two atopic dermatitis therapies recorded on separate days. Cross-sectional analyses of disease prevalence were conducted at each age. Logistic mixed effect regression models were used to identify predictors of prevalent disease over time among children (0-17 years), adults (18-74 years), and older adults (75-99 years).ResultsPhysician-diagnosed atopic dermatitis was identified in 894,454 individuals with the following proportions in each age group: 18.3% of children, 7.7% of adults, and 11.6% of older adults. Additionally, atopic dermatitis prevalence increased across the 2-decade period (beta from linear regression test for trend in the change in proportion per year = 0.005, p = 0.044). In older adults, atopic dermatitis was 27% less common among females (adjusted OR 0.73, 95% CI 0.70-0.76) and was more likely to be active (59.7%, 95% CI 59.5-59.9%) and of higher severity (mean annual percentage with moderate and severe disease: 31.8% and 3.0%, respectively) than in other age groups.ConclusionIn a large population-based cohort, the prevalence of physician-diagnosed atopic dermatitis has increased throughout adulthood and was most common among males age 75 years and above. Compared to children ages 0-17 and adults ages 18-74, older adult atopic dermatitis was more active and severe. Because the prevalence of atopic dermatitis among older adults has increased over time, additional characterization of disease triggers and mechanisms and targeted treatment recommendations are needed for this population.

ObjectivesTo investigate whether partner bereavement is associated with adverse cardiovascular and kidney-related events in people with reduced kidney function.DesignTwo parallel matched cohort studies using linked routinely collected health data.SettingEngland (general practices and hospitals using linked Clinical Practice Research Datalink, Hospital Episode Statistics, and Office of National Statistics) and Denmark (hospitals and community pharmacies using the Danish National Patient, Prescription and Education Registries and the Civil Registration System).ParticipantsBereaved people with reduced kidney function (estimated glomerular filtration rate (eGFR) Main outcome measuresCardiovascular disease (CVD) or acute kidney injury (AKI) hospitalization, or death.ResultsIn people with reduced kidney function, we identified 19,820 (England) and 5,408 (Denmark) bereaved individuals and matched them with 134,828 (England) and 35,741 (Denmark) non-bereaved individuals. Among the bereaved, the rates of hospitalizations (per 1000 person-years) with CVD were 31.7 (95%-CI: 30.5-32.9) in England and 78.8 (95%-CI: 74.9-82.9) in Denmark; the rates of hospitalizations with AKI were 13.2 (95%-CI: 12.5-14.0) in England and 11.2 (95%-CI: 9.9-12.7) in Denmark; and the rates of death were 70.2 (95%-CI: 68.5-72.0) in England and 126.4 (95%-CI: 121.8-131.1) in Denmark. After adjusting for confounders, we found increased rates of CVD (England, HR 1.06 [95%-CI: 1.01-1.12]; Denmark, HR 1.10 [95%-CI: 1.04-1.17]), of AKI (England, HR 1.20 [95%-CI: 1.10-1.31]; Denmark HR 1.36 [95%-CI: 1.17-1.58]), and of death (England, HR 1.10 [95%-CI: 1.05-1.14]; Denmark HR 1.20 [95%-CI: 1.15-1.25]) in bereaved compared with non-bereaved people.ConclusionsPartner bereavement is associated with an increased rate of CVD and AKI hospitalization, and death in people with reduced kidney function. Additional supportive care for this at-risk population may help prevent serious adverse events.

The treatment of hallux abductovalgus continues to evolve as surgeons better understand first ray biomechanical pathology. Many authors have advocated the use of the 1st tarsometatarsal joint arthrodesis for correction of moderate to severe hallux abductovalgus deformities and those with hypermobility of the 1st ray. There continues to be debate over the best surgical technique, fixation construct, and post operative protocol for the 1st tarsometatarsal joint fusion. We describe a technique with a unique hardware construct that is reproducible and allows for excellent deformity correction and pain relief while minimizing associated complications with this procedure.

Category: Bunion; Midfoot/Forefoot; Other Introduction/Purpose: Potential shortening of the first ray is an important consideration when performing a first tarsometatarsal (TMTJ) fusion. However, no previous study has sought to directly quantify the resultant shortening after TMTJ fusion. The purpose of the present anatomic study was to directly assess and compare shortening of the first ray using two joint preparation techniques (curettage, planal resection) for first TMTJ fusion. Methods: Ten pairs of matched lower extremity cadaver specimens were divided into two groups. Preoperative length assessments were performed at the first TMTJ dorsally and plantarly using a digital caliper. In Group 1, joint preparation for first TMTJ fusion was performed with curettage, whereas specimens in Group 2 underwent planal resection. Post-operative length assessments were repeated. All data was analyzed using two-tailed Students t-tests. Results: Mean shortening of the first ray following curettage was 1.1 (range, 0.3 to 2.0) mm dorsally and 1.6 (range, 0.6 to 3.7) mm plantarly; while mean shortening following planal resection was 4.5 (range, 2.7 to 7.9) mm dorsally and 4.6 (range, 2.4 to 8.9) mm plantarly. The measured differences were statistically significant (p

Objectives The validity of bullous pemphigoid and pemphigus vulgaris recording in routinely collected healthcare data in the UK is unknown. We assessed the positive predictive value (PPV) for bullous pemphigoid and pemphigus vulgaris primary care Read codes in the Clinical Practice Research Datalink (CPRD) using linked inpatient data (Hospital Episode Statistics (HES)) as the diagnostic benchmark.Setting Adult participants with bullous pemphigoid or pemphigus vulgaris registered with HES-linked general practices in England between January 1998 and December 2017. Code-based algorithms were used to identify patients from the CPRD and extract their benchmark blistering disease diagnosis from HES.Primary outcome measure The PPVs of Read codes for bullous pemphigoid and pemphigus vulgaris.Results Of 2468 incident cases of bullous pemphigoid and 431 of pemphigus vulgaris, 797 (32.3%) and 85 (19.7%) patients, respectively, had a hospitalisation record for a blistering disease. The PPV for bullous pemphigoid Read codes was 93.2% (95% CI 91.3% to 94.8%). Of the bullous pemphigoid cases, 3.0% had an HES diagnosis of pemphigus vulgaris and 3.8% of another blistering disease. The PPV for pemphigus vulgaris Read codes was 58.5% (95% CI 48.0% to 68.9%). Of the pemphigus vulgaris cases, 24.7% had an HES diagnosis of bullous pemphigoid and 16.5% of another blistering disease.Conclusions The CPRD can be used to study bullous pemphigoid, but recording of pemphigus vulgaris needs to improve in primary care.

Category: Bunion Introduction/Purpose: The Lapidus procedure is common for the treatment of moderate to severe hallux abductovalgus deformity. Standard fixation consists of a combination of crossing screws and plates. Despite arthrodesis of the first tarsometatarsal joint, recurrence of the deformity remains a concern. A recently described construct adds an additional point of fixation from the plantar medial first metatarsal to the intermediate cuneiform. This construct is termed the cross screw intermediate cuneiform construct. The purpose of this study is to determine the long-term angular maintained correction of the 1st and 2nd intermetatarsal angle, hallux abductus angle, and tibial sesamoid position after undergoing a 1st tarsometatarsal joint arthrodesis utilizing the cross screw intermediate cuneiform construct to correct and maintain the hallux abductovalgus deformity. Methods: A retrospective, single-center chart and radiographic review was performed of all patients with HAV treated with a 1st tarsometatarsal joint arthrodesis with cross screw intermediate cuneiform construct fixation by the senior author. The study period was from June 1st, 2016 to June 1st, 2017. Patients who underwent 1st tarsometatarsal joint arthrodesis for a primary diagnosis of HAV were studied. Three observers independently reviewed radiographic data including preoperative weight bearing, 1st weight bearing, and final weight bearing plain films radiographs. Preoperative films were used if they were within 3 months of the surgery, and the radiographic time line for the post-operative intervals were at 12 ± 2 weeks, 18 ± 4 weeks, 26 ± 4 weeks, 52 ± 12 weeks, and the final follow-up visit. Radiographic data evaluated were initial improvement and long-term maintenance of intermetatarsal ankle, hallux abductus angle, and tibial sesamoid position. Results: Forty-five patients met inclusion criteria and were included in the study. Mean follow-up time was 9.76 months (SD ± 7.62). Bony union was achieved in 43 of 45 patients (95.6%). Two patients required revision bunionectomy as result of recurrence (4.4%). Other complications included symptomatic hardware in 2 patients requiring hardware removal and neuritis in 2 patients. Average preoperative IMA was 15.95º (±2.55), HAA was 31.14º (±6.19), and tibial sesamoid position was 4.36 (±1.07). Final average improvement of IMA was 6.26º (±2.9), HAA was 13.89º (±7.02), and tibial sesamoid position was 2.07 (±1.34) positions. Average loss of IMA correction was 1.70º (±1.64), HAA was 2.45º (±4.6), and tibial sesamoid position was 0.8 (±0.82) positions. Wilcoxon signed rank test showed statistical significance in all radiographic parameters both in initial improvements and loss of correction (p

Category: Hindfoot Introduction/Purpose: Autogenous bone graft remains the standard bone graft in foot and ankle surgery when filling a bone void or adding biology to an arthrodesis site. Harvesting autograft can have serious donor site morbidity with an average complication rate of 8% and reports as high as 25%. Complications range from persistent pain to severe infection. Most procedures in the foot and ankle require only a small volume of graft. Using a small reaming graft harvester, surgeons can harvest autograft from the ipsilateral calcaneus. This is done within the same surgical field and requires minimal additional operative time. The purpose of this article is to review a population of patients who underwent calcaneal autograft harvesting with a reaming graft harvester and evaluate the outcomes of the procedure. Methods: From August 2015 to February 2018, all patients who underwent calcaneal autograft harvesting by a single surgeon were identified and reviewed. Patients were included if they had autograft harvested from the calcaneus on the ipsilateral operative limb using a reamer bone graft harvester and if they had complete clinical follow up of at least 6 months. Patients were excluded if they had autograft from a site other than the ipsilateral calcaneus, had a previous harvest from the ipsilateral calcaneus, or if they did not have full follow up of at least 6 months. Outcomes of interest were major and minor complications, intra- operative complications, and long term radiographic findings. Patients required graft for numerous primary procedures including a variety of arthrodesis or filling of bone voids. Postoperative protocols and return to weightbearing times varied with the accepted protocols for the primary procedure. Results: 300 patients were identified and met inclusion criteria. Average follow up was 12.6 months. There was 1 major complication (0.3%) consisting of a calcaneal stress fracture that healed with a period of 4 weeks of non weightbearing followed by 4 weeks of protected weightbearing. There were 3 minor complications (1%) consisting of transient painful scar and medial heel pain that all resolved uneventfully. There were no intraoperative complications while performing the 300 procedures. There were no incidences of neurovascular damage. Of the patients with over 1 year radiographic follow up, all harvest sites were still visible on lateral plain film radiographs. Conclusion: Using a small reamer to harvest calcaneal autograft for foot and ankle surgeries that require a small to moderate amount of bone graft is safe and effective. Approximately 4 cc of graft can be harvested very quickly without needing to prepare another surgical site for harvesting. The complication rate for harvesting calcaneal autograft was found to be extremely low in this study, despite the harvest site remaining visible on radiographs past 1 year. The proposed technique can be extremely useful to the foot and ankle surgeon.

Category: Bunion Introduction/Purpose: Fusion of the first tarsometatarsal joint is common for the treatment of moderate to severe hallux abductovalgus deformity. Despite arthrodesis of the first tarsometatarsal joint, recurrence of the deformity remains a concern. The addition of a screw from the 1st metatarsal base to the 2nd metatarsal base allows for increased stability and can help create a “spot weld” between the metatarsal bases to prevent loss of deformity correction. The additional screw construct is termed the intermetatarsal screw in this study. The purpose of the current study is to determine the long-term maintenance of angular correction of the 1st and 2nd intermetatarsal angle, hallux abductus angle, and tibial sesamoid position after undergoing a 1st tarsometatarsal joint arthrodesis with the addition of the intermetatarsal screw. Methods: A retrospective, single-center chart and radiographic review was performed of 17 consecutive patients who underwent primary hallux abductovalgus correction with a 1st tarsometatarsal joint arthrodesis using the intermetatarsal screw fixation by the senior author. The study period was from January 1, 2017 to May 14, 2018. Three observers independently reviewed radiographic data including preoperative weight bearing, 1st weight bearing, and final weight bearing plain film radiographs. Preoperative films were used if they were within 3 months of the surgery and the radiographic time line for the post-operative intervals were at 12 ± 2 weeks, 18 ± 4 weeks, 26 ± 4 weeks, 52 ± 12 weeks, and the final follow-up visit. Radiographic data evaluated were initial improvement and long-term maintenance of intermetatarsal angle, hallux abductus angle, and tibial sesamoid position. Results: 17 consecutive patients were identified for review that met inclusion criterea. Mean follow up time was 8.12 months (SD ± 3.68). Bony union was achieved in all patients. There was 1 symptomatic recurrent bunion, 1 case of symptomatic hardware, and 1 case of transient neuritis. Average preoperative IMA was 16.05º (±2.34), HAA was 33.05º (±6.24), and tibial sesamoid position was 5.77 (±0.9). Average IMA improvement was 8.38º (±2.21), HAA improvement was 17.25º (±8.21), and TSP improvement was 3.29 (±1.36) positions. Average loss of IMA was 1.03º (±1.24), HAA was 4.14º (±5.34), and tibial sesamoid position was 0.65 (±0.86) positions. Wilcoxon signed rank test showed statistical significance in all radiographic parameters; both in initial improvements and loss of correction (p

Compared to two-dimensional (2D) cell culture, cellular aggregates or spheroids (3D) offer a more appropriate alternative in vitro system where individual cell-cell communication and micro-environment more closely represent the in vivo organ; yet we understand little of the physiological conditions at this scale. The relationship between spheroid size and oxygen microenvironment, an important factor influencing the metabolic capacity of cells, was first established using the fish intestine derived RTgutGC cell line. Subsequently, pharmaceutical metabolism (Propranolol), as determined by high performance liquid chromatography, in this intestinal model was examined as a function of spheroid size. Co-efficient of variation between spheroid size was below 12% using the gyratory platform method, with the least variation observed in the highest cell seeding density. The viable, high oxygen micro-environment of the outer rim of the spheroid, as determined by electron paramagnetic resonance (EPR) oximetry, decreased over time, and the hypoxic zone increased as a function of spheroid size. Despite a trend of higher metabolism in smaller spheroids, the formation of micro-environments (quiescent, hypoxic or anoxic) did not significantly affect metabolism or function of an environmentally relevant pharmaceutical in this spheroid model.

A novel method for the establishment and long-term maintenance of ex vivo cultures from intestinal regions of the rainbow trout, Oncorhynchus mykiss (Walbaum), is reported. Adherence of cells was observed within hours, epithelial island formation recorded at 48 h and rapid proliferation with confluence achieved between 9-14 days. In addition to metabolic characterisation, basic morphology of growing cells was characterised using histology, immunofluorescence, transmission electron microscopy (TEM) and transepithelial electrical resistance (TEER). Regional differences in intestinal ethoxyresorufin-O-deethylase (EROD) and 7-ethoxycoumarin-O-deethylation (ECOD) activities in these primary grown enterocytes were compared following exposure to model inducers [i.e. α-NF, β-NF, B(a)P] which demonstrated significant differences. Regional differences in dietary uptake and metabolism of contaminants can therefore be studied in this in vitro system to increase our understanding of fundamental processes, while concurrently providing a means to reduce the number of fish required for biological studies in line with the principles of the 3Rs (Reduce, Refine and Replace). This article has an associated First Person interview with the first author of the paper.

ObjectiveTo quantify inequalities in zoster vaccine uptake by determining its association with socio-demographic factors: age, gender, ethnicity, immigration status, deprivation (at Lower-layer Super Output Area-level), care home residence and living arrangements.MethodThis population-based cohort study utilised anonymised primary care electronic health records from England (Clinical Practice Research Datalink) linked to deprivation and hospitalisation data. Data from 35,333 individuals from 277 general practices in England and eligible for zoster vaccination during the two-year period (2013-2015) after vaccine introduction were analysed. Logistic regression was used to obtain adjusted odds ratios (aOR) for the association of socio-demographic factors with zoster vaccine uptake for adults aged 70 years (main target group) and adults aged 79 years (catch-up group).ResultsAmongst those eligible for vaccination, 52.4% (n = 18,499) received the vaccine. Socio-demographic factors independently associated with lower zoster vaccine uptake in multivariable analyses were: being older (catch-up group: aged 79 years) aOR = 0.89 (95% confidence interval (CI):0.85-0.93), care home residence (aOR = 0.64 (95%CI: 0.57-0.73)) and living alone (aOR = 0.85 (95%CI: 0.81-0.90)). Uptake decreased with increasing levels of deprivation (p-value for trendConclusionsInequalities in zoster vaccine uptake exist in England; with lower uptake among those of non-White ethnicities, and among those living alone, in a care home and in more deprived areas. Tailored interventions to increase uptake in these social groups should assist in realising the aim of mitigating vaccination inequalities. As care home residents are also at higher risk of zoster, improving the uptake of zoster vaccination in this group will also mitigate inequalities in zoster burden.