Representativeness of whole-genome sequencing approaches in England: the importance for understanding inequalities associated with SARS-CoV-2 infection.

Whole-genome sequencing (WGS) information has played a crucial role in the SARS-CoV-2 (COVID-19) pandemic by providing evidence about variants to inform public health policy. The purpose of this study was to assess the representativeness of sequenced cases compared with all COVID-19 cases in England, between March 2020 and August 2021, by demographic and socio-economic characteristics, to evaluate the representativeness and utility of these data in epidemiological analyses. To achieve this, polymerase chain reaction (PCR)-confirmed COVID-19 cases were extracted from the national laboratory system and linked with WGS data. During the study period, over 10% of COVID-19 cases in England had WGS data available for epidemiological analysis. With sequencing capacity increasing throughout the period, sequencing representativeness compared to all reported COVID-19 cases increased over time, allowing for valuable epidemiological analyses using demographic and socio-economic characteristics, particularly during periods with emerging novel SARS-CoV-2 variants. This study demonstrates the comprehensiveness of England's sequencing throughout the COVID-19 pandemic, rapidly detecting variants of concern, and enabling representative epidemiological analyses to inform policy.

Exploring temporal trends and risk factors for resistance in Escherichia coli-causing bacteraemia in England between 2013 and 2018: an ecological study.

BACKGROUND: Escherichia coli are Gram-negative bacteria associated with an increasing burden of antimicrobial resistance (AMR) in England. OBJECTIVES: To create a comprehensive epidemiological picture of E. coli bacteraemia resistance trends and risk factors in England by linking national microbiology data sources and performing a longitudinal analysis of rates. METHODS: A retrospective observational study was conducted on all national records for antimicrobial susceptibility testing on E. coli bacteraemia in England from 1 January 2013 to 31 December 2018 from the UK Health Security Agency (UKHSA) and the BSAC Resistance Surveillance Programme (BSAC-RSP). Trends in AMR and MDR were estimated using iterative sequential regression. Logistic regression analyses were performed on UKHSA data to estimate the relationship between risk factors and AMR or MDR in E. coli bacteraemia isolates. RESULTS: An increase in resistance rates was observed in community- and hospital-onset bacteraemia for third-generation cephalosporins, co-amoxiclav, gentamicin and ciprofloxacin. Among community-acquired cases, and after adjustment for other factors, patients aged >65 years were more likely to be infected by E. coli isolates resistant to at least one of 11 antibiotics than those aged 18-64 years (OR: 1.21, 95% CI: 1.18-1.25; P < 0.05). In hospital-onset cases, E. coli isolates from those aged 1-17 years were more likely to be resistant than those aged 18-64 years (OR: 1.33, 95% CI: 1.02-1.73; P < 0.05). CONCLUSIONS: Antibiotic resistance rates in E. coli-causing bacteraemia increased between 2013 and 2018 in England for key antimicrobial agents. Findings of this study have implications for guiding future policies on a prescribing of antimicrobial agents, for specific patient populations in particular.

An analysis of the global pharmacy workforce capacity.

BACKGROUND: The World Health Organization (WHO) estimates that there is a global healthcare workforce shortage of 7.2 million, which is predicted to grow to 12.9 million by 2035. Globally, people are living longer with multiple co-morbidities and require increased access and use of medicines. Pharmacists are a key component of the healthcare workforce, and in many countries, pharmacists are the most accessible healthcare profession. This paper identifies key issues and current trends affecting the global pharmacy workforce, in particular workforce distribution, country economic status, capacity, and workforce gender balance. METHODS: National professional pharmacy leadership bodies, together with other contacts for professional bodies, regulatory bodies, and universities, were approached to provide country-level data on pharmacy workforce. A descriptive and comparative analysis was conducted to assess each country's pharmacy workforce. RESULTS: A total of 89 countries and territories responded to the survey. To standardise the capacity measure, an analysis of the population density of pharmacists (per 10 000 population) was performed. The sample mean was 6 pharmacists per 10 000 population (n = 80). There is considerable variation between the surveyed countries/territories ranging from 0.02 (Somalia) to 25.07 (Malta) pharmacists per 10 000 population. African nations have significantly fewer pharmacists per capita. Pharmacist density correlates with gross national income (GNI) and health expenditure. The majority of pharmacists are employed in community settings, followed by hospital, industry-related, academia, and regulation. There is a greater proportion of females in the pharmacy workforce globally, with some WHO regions showing female representation of more than 65 % with an increasing trend trajectory. CONCLUSIONS: Pharmacy workforce capacity varies considerably between countries and regions and generally correlates with population- and country-level economic indicators. Those countries and territories with lower economic indicators tend to have fewer pharmacists and pharmacy technicians; this has implications for inequalities regarding access to medicines and medicine expertise.

Learning from Somaliland? Transferability of learning from volunteering to national health service practice in the UK.

BACKGROUND: Capacity building partnerships between healthcare institutions have the potential to benefit both partners particularly in staff development. Previous research suggests that volunteering can contribute to professional development but there is little evidence on how learning is acquired, the barriers and facilitators to learning in this context or the process of translation of learning to the home environment. RESULTS: Volunteers from a healthcare partnership between the UK and Somaliland reported learning in communication, interdisciplinary working, teaching, management, leadership and service development. This learning came from observing familiar practices in unfamiliar environments; alternative solutions to familiar problems; learning about Somali culture; opportunities to assume higher levels of responsibility and new professional relationships. There was variability in the extent of translation to NHS practice. Time and support available for reflection and mentoring were important facilitators of this process. CONCLUSIONS: The professional development outcomes documented in this study came directly from the experience of volunteering. Experiential learning theory suggests that this requires a complex process of critical reflection and new knowledge generation, testing and translation for use in new contexts. This process benefits from identification of learning as an important element of volunteering and support for reflection and the translation translation of learning to UK contexts. We suggest that missed opportunities for volunteer learning will remain until the volunteering process is overtly framed as part of continuing professional development.

Use of Sotrovimab in Pregnancy: Experiences from the COVID-19 International Drug Pregnancy Registry.

INTRODUCTION: Available data regarding the safety and efficacy of sotrovimab in pregnant patients remain limited due to their exclusion from clinical trials. METHODS: The COVID-19 International Drug Pregnancy Registry (COVID-PR) was established to gather comprehensive safety data from pregnant women who have received monoclonal antibody (mAb) or antiviral treatments for mild, moderate, or severe coronavirus disease 2019 (COVID-19) during pregnancy. Participants actively contributed self-reported data concerning their COVID-19 symptoms, in addition to sociodemographic and health-related characteristics. Obstetric, neonatal, and infant outcomes were also documented, with follow-up extending up to 12 months after childbirth. RESULTS: As of 30 November 2023, sotrovimab was administered to 39 participants enrolled in the COVID-PR. At the time of this report, 26 participants had given birth, with nine deliveries performed via cesarean section. The infants' birthweight ranged from 2381 g to 4762 g, with a mean of 3439.91 g. Twenty-five infants were born at ≥37 weeks. A total of 31 adverse events (AEs) were reported by 12 participants. The most frequently reported AE was gestational hypertension, observed in three participants. COVID-19 re-infection, fatigue, gestational diabetes, headache, and morning sickness were each reported by two participants. Of the reported AEs, eight (in five participants) were classified as serious, including four AEs (prolonged labor, pre-eclampsia, polyhydramnios, premature labor) that affected pregnancy. Seven of these eight serious AEs (SAEs) were found to be unrelated to sotrovimab, with one event (urinary retention) not assessable. A total of 44 AEs were reported in 19 delivered infants or in utero fetuses. The most common were COVID-19 (n = 6 events), ear infection (n = 5 events), neonatal dyspnea (n = 3 events), and respiratory syncytial virus infection (n = 3 events). Sixteen AEs (in 11 infants/fetuses) were classified as serious, including one report each of fetal cardiac disorder, congenital ankyloglossia, persistent right umbilical vein, and congenital hydronephrosis; the latter was considered a major congenital malformation. For all assessable SAEs, causality of sotrovimab treatment was ruled out based on lack of a temporal relationship alone or in combination with absence of a plausible mechanism. CONCLUSION: A sizable proportion of sotrovimab-treated participants in the COVID-PR had underlying medical conditions associated with an increased risk of severe COVID-19. None of the assessable SAEs were considered to be related to sotrovimab treatment.

Descriptive epidemiology of SARS-CoV-2 Beta (B.1.351) variant cases in England, December 2020 to June 2022.

The emergence of the SARS-CoV-2 Beta (B.1.351) variant in November 2020 raised concerns of increased transmissibility and severity. We describe the epidemiology of 949 confirmed SARS-CoV-2 Beta variant cases in England, identified between December 2020 and June 2022. Most cases were detected in the first 3 months. A total of 10 deaths (1.1%; 10/949) were identified among all cases and of those with travel information, 38 (4.9%; 38/781) cases with hospital admissions within 14 days of a positive test being detected. 52.9% (413/781) cases were imported. This study reinforces the importance of monitoring of travel-associated cases to inform public health response and reduce transmissibility of new variants.

Intra-cardiac pressure drop and flow distribution of bicuspid aortic valve disease in preserved ejection fraction.

Background: Bicuspid aortic valve (BAV) is more than a congenital defect since it is accompanied by several secondary complications that intensify induced impairments. Hence, BAV patients need lifelong evaluations to prevent severe clinical sequelae. We applied 4D-flow magnetic resonance imaging (MRI) for in detail visualization and quantification of in vivo blood flow to verify the reliability of the left ventricular (LV) flow components and pressure drops in the silent BAV subjects with mild regurgitation and preserved ejection fraction (pEF). Materials and methods: A total of 51 BAV patients with mild regurgitation and 24 healthy controls were recruited to undergo routine cardiac MRI followed by 4D-flow MRI using 3T MRI scanners. A dedicated 4D-flow module was utilized to pre-process and then analyze the LV flow components (direct flow, retained inflow, delayed ejection, and residual volume) and left-sided [left atrium (LA) and LV] local pressure drop. To elucidate significant diastolic dysfunction in our population, transmitral early and late diastolic 4D flow peak velocity (E-wave and A-wave, respectively), as well as E/A ratio variable, were acquired. Results: The significant means differences of each LV flow component (global measurement) were not observed between the two groups (p > 0.05). In terms of pressure analysis (local measurement), maximum and mean as well as pressure at E-wave and A-wave timepoints at the mitral valve (MV) plane were significantly different between BAV and control groups (p: 0.005, p: 0.02, and p: 0.04 and p: <0.001; respectively). Furthermore, maximum pressure and pressure difference at the A-wave timepoint at left ventricle mid and left ventricle apex planes were significant. Although we could not find any correlation between LV diastolic function and flow components, Low but statistically significant correlations were observed with local pressure at LA mid, MV and LV apex planes at E-wave timepoint (R: -0.324, p: 0.005, R: -0.327, p: 0.004, and R: -0.306, p: 0.008, respectively). Conclusion: In BAV patients with pEF, flow components analysis is not sensitive to differentiate BAV patients with mild regurgitation and healthy control because flow components and EF are global parameters. Inversely, pressure (local measurement) can be a more reliable biomarker to reveal the early stage of diastolic dysfunction.

Hospital admission and emergency care attendance risk for SARS-CoV-2 delta (B.1.617.2) compared with alpha (B.1.1.7) variants of concern: a cohort study.

BACKGROUND: The SARS-CoV-2 delta (B.1.617.2) variant was first detected in England in March, 2021. It has since rapidly become the predominant lineage, owing to high transmissibility. It is suspected that the delta variant is associated with more severe disease than the previously dominant alpha (B.1.1.7) variant. We aimed to characterise the severity of the delta variant compared with the alpha variant by determining the relative risk of hospital attendance outcomes. METHODS: This cohort study was done among all patients with COVID-19 in England between March 29 and May 23, 2021, who were identified as being infected with either the alpha or delta SARS-CoV-2 variant through whole-genome sequencing. Individual-level data on these patients were linked to routine health-care datasets on vaccination, emergency care attendance, hospital admission, and mortality (data from Public Health England's Second Generation Surveillance System and COVID-19-associated deaths dataset; the National Immunisation Management System; and NHS Digital Secondary Uses Services and Emergency Care Data Set). The risk for hospital admission and emergency care attendance were compared between patients with sequencing-confirmed delta and alpha variants for the whole cohort and by vaccination status subgroups. Stratified Cox regression was used to adjust for age, sex, ethnicity, deprivation, recent international travel, area of residence, calendar week, and vaccination status. FINDINGS: Individual-level data on 43 338 COVID-19-positive patients (8682 with the delta variant, 34 656 with the alpha variant; median age 31 years [IQR 17-43]) were included in our analysis. 196 (2·3%) patients with the delta variant versus 764 (2·2%) patients with the alpha variant were admitted to hospital within 14 days after the specimen was taken (adjusted hazard ratio [HR] 2·26 [95% CI 1·32-3·89]). 498 (5·7%) patients with the delta variant versus 1448 (4·2%) patients with the alpha variant were admitted to hospital or attended emergency care within 14 days (adjusted HR 1·45 [1·08-1·95]). Most patients were unvaccinated (32 078 [74·0%] across both groups). The HRs for vaccinated patients with the delta variant versus the alpha variant (adjusted HR for hospital admission 1·94 [95% CI 0·47-8·05] and for hospital admission or emergency care attendance 1·58 [0·69-3·61]) were similar to the HRs for unvaccinated patients (2·32 [1·29-4·16] and 1·43 [1·04-1·97]; p=0·82 for both) but the precision for the vaccinated subgroup was low. INTERPRETATION: This large national study found a higher hospital admission or emergency care attendance risk for patients with COVID-19 infected with the delta variant compared with the alpha variant. Results suggest that outbreaks of the delta variant in unvaccinated populations might lead to a greater burden on health-care services than the alpha variant. FUNDING: Medical Research Council; UK Research and Innovation; Department of Health and Social Care; and National Institute for Health Research.

The relationship between austerity and food insecurity in the UK: A systematic review.

BACKGROUND: In 2010, the UK government implemented austerity measures, involving reductions to public spending and welfare reform. We aimed to systematically review the relationship of austerity policies with food insecurity including foodbank use in the UK. METHODS: We undertook a narrative systematic review (CRD42020164508) and searched seven databases, grey literature, and reference lists through September 2020. Studies with austerity policies (including welfare reform) as exposure and food insecurity (including foodbank use as a proxy) as study outcome were included. We included quantitative longitudinal and cross-sectional studies. Two reviewers assessed eligibility, extracted data directly from studies, and undertook quality assessment. FINDINGS: Eight studies were included: two individual-level studies totalling 4129 participants and six ecological studies. All suggested a relationship between austerity and increased food insecurity. Two studies found that austerity policies were associated with increased food insecurity in European countries including the UK. Six studies found that the welfare reform aspect of UK austerity policies was associated with increased food insecurity and foodbank use. Sanctions involving delays to benefits as a response to a claimant not actively seeking work may increase food insecurity, with studies finding that increases of 100 sanctions per 100,000 people may have led to increases of between 2 and 36 food parcels per 100,000 population. INTERPRETATION: UK austerity policies were consistently linked to food insecurity and foodbank use. Policymakers should consider impacts of austerity on food insecurity when considering how to reduce budget deficits. FUNDING: NIHR School for Public Health Research.

Effect of antibiotic stewardship interventions in primary care on antimicrobial resistance of Escherichia coli bacteraemia in England (2013-18): a quasi-experimental, ecological, data linkage study.

BACKGROUND: Antimicrobial resistance is a major global health concern, driven by overuse of antibiotics. We aimed to assess the effectiveness of a national antimicrobial stewardship intervention, the National Health Service (NHS) England Quality Premium implemented in 2015-16, on broad-spectrum antibiotic prescribing and Escherichia coli bacteraemia resistance to broad-spectrum antibiotics in England. METHODS: In this quasi-experimental, ecological, data linkage study, we used longitudinal data on bacteraemia for patients registered with a general practitioner in the English National Health Service and patients with E coli bacteraemia notified to the national mandatory surveillance programme between Jan 1, 2013, and Dec 31, 2018. We linked these data to data on antimicrobial susceptibility testing of E coli from Public Health England's Second-Generation Surveillance System. We did an ecological analysis using interrupted time-series analyses and generalised estimating equations to estimate the change in broad-spectrum antibiotics prescribing over time and the change in the proportion of E coli bacteraemia cases for which the causative bacteria were resistant to each antibiotic individually or to at least one of five broad-spectrum antibiotics (co-amoxiclav, ciprofloxacin, levofloxacin, moxifloxacin, ofloxacin), after implementation of the NHS England Quality Premium intervention in April, 2015. FINDINGS: Before implementation of the Quality Premium, the rate of antibiotic prescribing for all five broad-spectrum antibiotics was increasing at rate of 0·2% per month (incidence rate ratio [IRR] 1·002 [95% CI 1·000-1·004], p=0·046). After implementation of the Quality Premium, an immediate reduction in total broad-spectrum antibiotic prescribing rate was observed (IRR 0·867 [95% CI 0·837-0·898], p<0·0001). This effect was sustained until the end of the study period; a 57% reduction in rate of antibiotic prescribing was observed compared with the counterfactual situation (ie, had the Quality Premium not been implemented). In the same period, the rate of resistance to at least one broad-spectrum antibiotic increased at rate of 0·1% per month (IRR 1·001 [95% CI 0·999-1·003], p=0·346). On implementation of the Quality Premium, an immediate reduction in resistance rate to at least one broad-spectrum antibiotic was observed (IRR 0·947 [95% CI 0·918-0·977], p=0·0007). Although this effect was also sustained until the end of the study period, with a 12·03% reduction in resistance rate compared with the counterfactual situation, the overall trend remained on an upward trajectory. On examination of the long-term effect following implementation of the Quality Premium, there was an increase in the number of isolates resistant to at least one of the five broad-spectrum antibiotics tested (IRR 1·002 [1·000-1·003]; p=0·047). INTERPRETATION: Although interventions targeting antibiotic use can result in changes in resistance over a short period, they might be insufficient alone to curtail antimicrobial resistance. FUNDING: National Institute for Health Research, Economic and Social Research Council, Rosetrees Trust, and The Stoneygate Trust.

Patient Portal Functionalities and Uptake: Systematic Review Protocol.

BACKGROUND: Patient portals are digital health tools adopted by health care organizations. The portals are generally connected to the electronic health record of the health care organization and offer patients functionalities such as access to the medical record, ability to order repeat prescriptions, make appointments, or message the health care provider. Patient portals may be beneficial for both patients and the health care system. Patient portals can widely differ from one context to another due to the differences in the portal functionalities and capabilities and it is anticipated that outcomes associated with the functionalities also differ. Current systematic reviews report outcomes associated with patient portal uptake but do not explicitly specify the patient portal functionalities. OBJECTIVE: The aim of this systematic review is to synthesize the evidence on health and health care quality outcomes associated with patient portal use among adult (18 years or older) patients. The review research questions are as follows: What kind of health outcomes do tethered patient portals and patient portal functionalities contribute to in adult patients (18 years or older)? and What kind of health care quality outcomes, including health care utilization outcomes, do tethered patient portals and patient portal functionalities contribute to in adult patients (18 years or older)? METHODS: The systematic review will be conducted by searching the MEDLINE, EMBASE, and Scopus databases for relevant literature. The review inclusion criteria will be studies about adult patients (18 years or older), studies only about tethered patient portals, and studies with or without a comparator. We will report patient portal-associated health and health care quality outcomes based on the patient portal functionalities. All quantitative primary study types will be included. Risk of bias of included studies will be assessed using the Cochrane Collaboration's tool for assessing risk of bias in randomized trials and the National Heart, Lung, and Blood Institute's quality assessment tools. Data will be synthesized using narrative synthesis and will be reported according to the patient portal functionalities, country, disease, and health care system model. RESULTS: Searches will be conducted in September 2019, and the review is anticipated to be completed by the end of June 2020. CONCLUSIONS: This systematic review will provide an overview of health and health care quality outcomes associated with patient portal use among adult patients, providing detailed information about the functionalities of the portals and their associations with the outcomes. The review could potentially help patient portal evaluation studies by providing insights into outcomes associated with the different functionalities of patient portals. TRIAL REGISTRATION: International Prospective Register of Systematic Reviews (PROSPERO) CRD42019141131; https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=141131. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): PRR1-10.2196/14975.