Positive Changes in Safety Perception Among Blacks with HIV and Comorbidities: Assessment of Social Determinants of Health During COVID-19.

PURPOSE: This study aimed to examine the impact of the COVID-19 lockdown on social determinants of health (SDOH) among Blacks with HIV and a comorbid diagnosis of hypertension or type 2 diabetes mellitus (T2DM). METHODS: This was a longitudinal survey study. The inclusion criteria were adults ≥ 18 years and the presence of hypertension and/or diabetes, along with a positive HIV diagnosis. This study enrolled patients in the HIV clinics and chain specialty pharmacies in the Dallas-Fort Worth (DFW) area. A survey of ten questions examining SDOH was conducted before, during, and after the lockdown. A proportional odds mixed effects logistic regression model was applied to assess differences between time points. RESULTS: A total of 27 participants were included. Respondents felt significantly safer in their living place post-lockdown than in the pre-lockdown period (odds ratio = 6.39, 95% CI [1.08-37.73]). No other statistically significant differences in the responses were found over the study timeframe. However, borderline p values indicated better SDOH status post-lockdown as compared to pre-lockdown. CONCLUSION: Study participants feel safer one year after lockdown compared to pre-lockdown. The CARES Act and the moratorium on rent and mortgage are among the factors that may explain this increase. Future research should include designing and evaluating interventions for social equity enhancement.

Prognostic peripheral blood biomarkers at ICU admission predict COVID-19 clinical outcomes.

The COVID-19 pandemic continues to challenge the capacities of hospital ICUs which currently lack the ability to identify prospectively those patients who may require extended management. In this study of 90 ICU COVID-19 patients, we evaluated serum levels of four cytokines (IL-1ß, IL-6, IL-10 and TNFα) as well as standard clinical and laboratory measurements. On 42 of these patients (binned into Initial and Replication Cohorts), we further performed CyTOF-based deep immunophenotyping of peripheral blood mononuclear cells with a panel of 38 antibodies. All measurements and patient samples were taken at time of ICU admission and retrospectively linked to patient clinical outcomes through statistical approaches. These analyses resulted in the definition of a new measure of patient clinical outcome: patients who will recover after short ICU stays (< 6 days) and those who will subsequently die or recover after long ICU stays (≥6 days). Based on these clinical outcome categories, we identified blood prognostic biomarkers that, at time of ICU admission, prospectively distinguish, with 91% sensitivity and 91% specificity (positive likelihood ratio 10.1), patients in the two clinical outcome groups. This is achieved through a tiered evaluation of serum IL-10 and targeted immunophenotyping of monocyte subsets, specifically, CD11clow classical monocytes. Both immune biomarkers were consistently elevated ( ≥15 pg/ml and ≥2.7 x107/L for serum IL-10 and CD11clow classical monocytes, respectively) in those patients who will subsequently die or recover after long ICU stays. This highly sensitive and specific prognostic test could prove useful in guiding clinical resource allocation.

In need of what? Section 17 Provision under the Children Act 1989

This article considers Section 17 'child in need' provision under the Children Act 1989, the main legislation governing Children's Services in England. Arguably, Section 17 has never been given the same priority as other statutory requirements under the Act. The intention was to create a broad umbrella provision for children living with their families, but children assessed as 'in need' are not entitled to receive such services unless they are disabled. This exploration is timely given the current Independent Review of Children's Social Care in England, ongoing austerity measures, high rates of child poverty and COVID‐19. Consideration is given to the development of Section 17 and what the future may hold.

The Utility of Blood Based Biomarkers in Detecting Neurological Complications of COVID‐19 in Critically Ill Patients

Background Neurological and neuropsychiatric complications have been documented in patients with COVID‐19. This study aims to investigate the utility of two neurological blood‐based biomarkers to predict neurological complications and mortality due to COVID‐19 in the intensive care unit (ICU). Neurofilament light (NF‐L) is a marker of axonal damage and glial fibrillary acidic protein (GFAP) is a marker of astrocytic activation. Methods Patients with respiratory failure were prospectively enrolled from the ICU at Vancouver General Hospital. COVID‐19 patients were excluded if the diagnosis was an incidental secondary finding upon ICU admission or if their enrollment was >10 days after ICU admission. Control patients were excluded if their enrollment was >4 days after ICU admission or if their primary diagnosis was non‐respiratory. Plasma samples were collected upon admission study enrollment, with additional samples collected on day 7 and day 14 from COVID‐19 patients. Plasma NF‐L and GFAP were quantified using the Quanterix Simoa HD‐X analyzer. Group comparisons were performed using a Mann‐Whitney test. Trajectory analysis was performed using a Wilcoxon test or Friedman one‐way ANOVA. Area under receiver operating curve (AUROC) analysis was calculated to predict neurological complications and mortality during ICU stay. Results Of the 242 patients enrolled, 209 were confirmed positive for SARS‐CoV‐2 while 33 served as ICU controls. Median age was 61 years for the COVID‐19 group, 64 years for controls. Upon ICU admission, NF‐L was 32% lower and GFAP was 24% lower in those with COVID‐19 compared to controls after correcting for age. NF‐L concentrations increase by doubling each week of ICU stay, while GFAP remained stable. Over the course of their ICU stay, 16% COVID‐19 patients were diagnosed with a neurological complication and 17% died. Plasma NF‐L and GFAP demonstrated a moderate to strong ability to predict neurological complications (AUROC: NF‐L=0.702;GFAP=0.722) and mortality (AUROC: NF‐L=0.815;GFAP=0.809) during ICU stay. Conclusions Upon ICU admission, NF‐L and GFAP were lower in patients with COVID‐19 compared to controls. NF‐L, but not GFAP, increased over the course of ICU stay in patients with COVID‐19. Both markers were able to predict neurological complication or ICU mortality with moderate to strong accuracy.

Prognostic peripheral blood biomarkers at ICU admission predict COVID-19 clinical outcomes

The COVID-19 pandemic continues to challenge the capacities of hospital ICUs which currently lack the ability to identify prospectively those patients who may require extended management. In this study of 90 ICU COVID-19 patients, we evaluated serum levels of four cytokines (IL-1β, IL-6, IL-10 and TNFα) as well as standard clinical and laboratory measurements. On 42 of these patients (binned into Initial and Replication Cohorts), we further performed CyTOF-based deep immunophenotyping of peripheral blood mononuclear cells with a panel of 38 antibodies. All measurements and patient samples were taken at time of ICU admission and retrospectively linked to patient clinical outcomes through statistical approaches. These analyses resulted in the definition of a new measure of patient clinical outcome: patients who will recover after short ICU stays (< 6 days) and those who will subsequently die or recover after long ICU stays (≥6 days). Based on these clinical outcome categories, we identified blood prognostic biomarkers that, at time of ICU admission, prospectively distinguish, with 91% sensitivity and 91% specificity (positive likelihood ratio 10.1), patients in the two clinical outcome groups. This is achieved through a tiered evaluation of serum IL-10 and targeted immunophenotyping of monocyte subsets, specifically, CD11clow classical monocytes. Both immune biomarkers were consistently elevated ( ≥15 pg/ml and ≥2.7 x107/L for serum IL-10 and CD11clow classical monocytes, respectively) in those patients who will subsequently die or recover after long ICU stays. This highly sensitive and specific prognostic test could prove useful in guiding clinical resource allocation.

Association of COVID-19 With Major Arterial and Venous Thrombotic Diseases: A Population-Wide Cohort Study of 48 Million Adults in England and Wales.

BACKGROUND: Infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) induces a prothrombotic state, but long-term effects of COVID-19 on incidence of vascular diseases are unclear. METHODS: We studied vascular diseases after COVID-19 diagnosis in population-wide anonymized linked English and Welsh electronic health records from January 1 to December 7, 2020. We estimated adjusted hazard ratios comparing the incidence of arterial thromboses and venous thromboembolic events (VTEs) after diagnosis of COVID-19 with the incidence in people without a COVID-19 diagnosis. We conducted subgroup analyses by COVID-19 severity, demographic characteristics, and previous history. RESULTS: Among 48 million adults, 125 985 were hospitalized and 1 319 789 were not hospitalized within 28 days of COVID-19 diagnosis. In England, there were 260 279 first arterial thromboses and 59 421 first VTEs during 41.6 million person-years of follow-up. Adjusted hazard ratios for first arterial thrombosis after COVID-19 diagnosis compared with no COVID-19 diagnosis declined from 21.7 (95% CI, 21.0-22.4) in week 1 after COVID-19 diagnosis to 1.34 (95% CI, 1.21-1.48) during weeks 27 to 49. Adjusted hazard ratios for first VTE after COVID-19 diagnosis declined from 33.2 (95% CI, 31.3-35.2) in week 1 to 1.80 (95% CI, 1.50-2.17) during weeks 27 to 49. Adjusted hazard ratios were higher, for longer after diagnosis, after hospitalized versus nonhospitalized COVID-19, among Black or Asian versus White people, and among people without versus with a previous event. The estimated whole-population increases in risk of arterial thromboses and VTEs 49 weeks after COVID-19 diagnosis were 0.5% and 0.25%, respectively, corresponding to 7200 and 3500 additional events, respectively, after 1.4 million COVID-19 diagnoses. CONCLUSIONS: High relative incidence of vascular events soon after COVID-19 diagnosis declines more rapidly for arterial thromboses than VTEs. However, incidence remains elevated up to 49 weeks after COVID-19 diagnosis. These results support policies to prevent severe COVID-19 by means of COVID-19 vaccines, early review after discharge, risk factor control, and use of secondary preventive agents in high-risk patients.

Enumeration of Public Health Nurses in the United States: Limits of Current Standards.

Recent national initiatives in nursing and public health have emphasized the need for a robust public health nursing (PHN) workforce. In this article, we analyze the extent to which recent national enumeration surveys base their counts of this workforce on the definitions, scope, and standards for practice and practice competencies of the PHN nursing specialty. By and large, enumeration surveys continue to rely on practice setting to define the PHN workforce, which is an insufficient approach for meeting the goals of major nursing and public health initiatives. We make recommendations for the development of new standards for PHN enumeration to strengthen the broader public health infrastructure and evaluate PHN contributions to population-level outcomes. (Am J Public Health. 2022;112(S3):S292-S297. https://doi.org/10.2105/AJPH.2022.306782).

COVID-19 trajectories among 57 million adults in England: a cohort study using electronic health records.

BACKGROUND: Updatable estimates of COVID-19 onset, progression, and trajectories underpin pandemic mitigation efforts. To identify and characterise disease trajectories, we aimed to define and validate ten COVID-19 phenotypes from nationwide linked electronic health records (EHR) using an extensible framework. METHODS: In this cohort study, we used eight linked National Health Service (NHS) datasets for people in England alive on Jan 23, 2020. Data on COVID-19 testing, vaccination, primary and secondary care records, and death registrations were collected until Nov 30, 2021. We defined ten COVID-19 phenotypes reflecting clinically relevant stages of disease severity and encompassing five categories: positive SARS-CoV-2 test, primary care diagnosis, hospital admission, ventilation modality (four phenotypes), and death (three phenotypes). We constructed patient trajectories illustrating transition frequency and duration between phenotypes. Analyses were stratified by pandemic waves and vaccination status. FINDINGS: Among 57 032 174 individuals included in the cohort, 13 990 423 COVID-19 events were identified in 7 244 925 individuals, equating to an infection rate of 12·7% during the study period. Of 7 244 925 individuals, 460 737 (6·4%) were admitted to hospital and 158 020 (2·2%) died. Of 460 737 individuals who were admitted to hospital, 48 847 (10·6%) were admitted to the intensive care unit (ICU), 69 090 (15·0%) received non-invasive ventilation, and 25 928 (5·6%) received invasive ventilation. Among 384 135 patients who were admitted to hospital but did not require ventilation, mortality was higher in wave 1 (23 485 [30·4%] of 77 202 patients) than wave 2 (44 220 [23·1%] of 191 528 patients), but remained unchanged for patients admitted to the ICU. Mortality was highest among patients who received ventilatory support outside of the ICU in wave 1 (2569 [50·7%] of 5063 patients). 15 486 (9·8%) of 158 020 COVID-19-related deaths occurred within 28 days of the first COVID-19 event without a COVID-19 diagnoses on the death certificate. 10 884 (6·9%) of 158 020 deaths were identified exclusively from mortality data with no previous COVID-19 phenotype recorded. We observed longer patient trajectories in wave 2 than wave 1. INTERPRETATION: Our analyses illustrate the wide spectrum of disease trajectories as shown by differences in incidence, survival, and clinical pathways. We have provided a modular analytical framework that can be used to monitor the impact of the pandemic and generate evidence of clinical and policy relevance using multiple EHR sources. FUNDING: British Heart Foundation Data Science Centre, led by Health Data Research UK.

Child Opportunity Index and Changes in Pediatric Acute Care Utilization in the COVID-19 Pandemic.

BACKGROUND: Pediatric acute care utilization decreased dramatically during the coronavirus disease 2019 (COVID-19) pandemic. This study examined the association between the Child Opportunity Index (COI), a multidimensional neighborhood measure of childhood opportunity, and changes in acute care utilization at US pediatric hospitals during the COVID-19 pandemic compared with the previous 3 years. METHODS: This observational study used administrative data across 41 US-based pediatric hospitals. Children aged 0 to 17 years with emergency department (ED) encounters during the study period were included. The COVID-19 pandemic time period (March 15, 2020-March 14, 2021) was the primary exposure. The primary outcome was the relative volume drop in ED encounters and observation/inpatient admissions through the ED by COI quintile. RESULTS: Of 12 138 750 encounters, 3 705 320 (30.5%) were among the very low COI quintile. Overall, there was a 46.8% relative volume reduction in the pandemic period compared with the prepandmic period. This drop in volume occurred disproportionately among the very low COI quintile (51.1%) compared with the very high COI quintile (42.8%). The majority of clinical diagnosis groups demonstrated larger relative volume drops among the very low COI quintile. CONCLUSIONS: Acute care utilization decreased the most among children from very low COI neighborhoods, narrowing previously described acute care utilization disparities. Additional study of patient perspectives on health care needs and access during this period is required to understand these changes.

Association of COVID-19 vaccines ChAdOx1 and BNT162b2 with major venous, arterial, or thrombocytopenic events: A population-based cohort study of 46 million adults in England.

BACKGROUND: Thromboses in unusual locations after the Coronavirus Disease 2019 (COVID-19) vaccine ChAdOx1-S have been reported, although their frequency with vaccines of different types is uncertain at a population level. The aim of this study was to estimate the population-level risks of hospitalised thrombocytopenia and major arterial and venous thromboses after COVID-19 vaccination. METHODS AND FINDINGS: In this whole-population cohort study, we analysed linked electronic health records from adults living in England, from 8 December 2020 to 18 March 2021. We estimated incidence rates and hazard ratios (HRs) for major arterial, venous, and thrombocytopenic outcomes 1 to 28 and >28 days after first vaccination dose for ChAdOx1-S and BNT162b2 vaccines. Analyses were performed separately for ages <70 and ≥70 years and adjusted for age, age2, sex, ethnicity, and deprivation. We also prespecified adjustment for anticoagulant medication, combined oral contraceptive medication, hormone replacement therapy medication, history of pulmonary embolism or deep vein thrombosis, and history of coronavirus infection in analyses of venous thrombosis; and diabetes, hypertension, smoking, antiplatelet medication, blood pressure lowering medication, lipid lowering medication, anticoagulant medication, history of stroke, and history of myocardial infarction in analyses of arterial thromboses. We selected further covariates with backward selection. Of 46 million adults, 23 million (51%) were women; 39 million (84%) were <70; and 3.7 million (8.1%) Asian or Asian British, 1.6 million (3.5%) Black or Black British, 36 million (79%) White, 0.7 million (1.5%) mixed ethnicity, and 1.5 million (3.2%) were of another ethnicity. Approximately 21 million (46%) adults had their first vaccination between 8 December 2020 and 18 March 2021. The crude incidence rates (per 100,000 person-years) of all venous events were as follows: prevaccination, 140 [95% confidence interval (CI): 138 to 142]; ≤28 days post-ChAdOx1-S, 294 (281 to 307); >28 days post-ChAdOx1-S, 359 (338 to 382), ≤28 days post-BNT162b2-S, 241 (229 to 253); >28 days post-BNT162b2-S 277 (263 to 291). The crude incidence rates (per 100,000 person-years) of all arterial events were as follows: prevaccination, 546 (95% CI: 541 to 555); ≤28 days post-ChAdOx1-S, 1,211 (1,185 to 1,237); >28 days post-ChAdOx1-S, 1678 (1,630 to 1,726), ≤28 days post-BNT162b2-S, 1,242 (1,214 to 1,269); >28 days post-BNT162b2-S, 1,539 (1,507 to 1,572). Adjusted HRs (aHRs) 1 to 28 days after ChAdOx1-S, compared with unvaccinated rates, at ages <70 and ≥70 years, respectively, were 0.97 (95% CI: 0.90 to 1.05) and 0.58 (0.53 to 0.63) for venous thromboses, and 0.90 (0.86 to 0.95) and 0.76 (0.73 to 0.79) for arterial thromboses. Corresponding aHRs for BNT162b2 were 0.81 (0.74 to 0.88) and 0.57 (0.53 to 0.62) for venous thromboses, and 0.94 (0.90 to 0.99) and 0.72 (0.70 to 0.75) for arterial thromboses. aHRs for thrombotic events were higher at younger ages for venous thromboses after ChAdOx1-S, and for arterial thromboses after both vaccines. Rates of intracranial venous thrombosis (ICVT) and of thrombocytopenia in adults aged <70 years were higher 1 to 28 days after ChAdOx1-S (aHRs 2.27, 95% CI: 1.33 to 3.88 and 1.71, 1.35 to 2.16, respectively), but not after BNT162b2 (0.59, 0.24 to 1.45 and 1.00, 0.75 to 1.34) compared with unvaccinated. The corresponding absolute excess risks of ICVT 1 to 28 days after ChAdOx1-S were 0.9 to 3 per million, varying by age and sex. The main limitations of the study are as follows: (i) it relies on the accuracy of coded healthcare data to identify exposures, covariates, and outcomes; (ii) the use of primary reason for hospital admission to measure outcome, which improves the positive predictive value but may lead to an underestimation of incidence; and (iii) potential unmeasured confounding. CONCLUSIONS: In this study, we observed increases in rates of ICVT and thrombocytopenia after ChAdOx1-S vaccination in adults aged <70 years that were small compared with its effect in reducing COVID-19 morbidity and mortality, although more precise estimates for adults aged <40 years are needed. For people aged ≥70 years, rates of arterial or venous thrombotic events were generally lower after either vaccine compared with unvaccinated, suggesting that either vaccine is suitable in this age group.

Persistently elevated complement alternative pathway biomarkers in COVID-19 correlate with hypoxemia and predict in-hospital mortality.

Mechanisms underlying the SARS-CoV-2-triggered hyperacute thrombo-inflammatory response that causes multi-organ damage in coronavirus disease 2019 (COVID-19) are poorly understood. Several lines of evidence implicate overactivation of complement. To delineate the involvement of complement in COVID-19, we prospectively studied 25 ICU-hospitalized patients for up to 21 days. Complement biomarkers in patient sera and healthy controls were quantified by enzyme-linked immunosorbent assays. Correlations with respiratory function and mortality were analyzed. Activation of complement via the classical/lectin pathways was variably increased. Strikingly, all patients had increased activation of the alternative pathway (AP) with elevated levels of activation fragments, Ba and Bb. This was associated with a reduction of the AP negative regulator, factor (F) H. Correspondingly, terminal pathway biomarkers of complement activation, C5a and sC5b-9, were significantly elevated in all COVID-19 patient sera. C5a and AP constituents Ba and Bb, were significantly associated with hypoxemia. Ba and FD at the time of ICU admission were strong independent predictors of mortality in the following 30 days. Levels of all complement activation markers were sustained throughout the patients' ICU stays, contrasting with the varying serum levels of IL-6, C-reactive protein, and ferritin. Severely ill COVID-19 patients have increased and persistent activation of complement, mediated strongly via the AP. Complement activation biomarkers may be valuable measures of severity of lung disease and the risk of mortality. Large-scale studies will reveal the relevance of these findings to thrombo-inflammation in acute and post-acute COVID-19.

In need of what? Section 17 Provision under the Children Act 1989

This article considers Section 17 ‘child in need’ provision under the Children Act 1989, the main legislation governing Children's Services in England. Arguably, Section 17 has never been given the same priority as other statutory requirements under the Act. The intention was to create a broad umbrella provision for children living with their families, but children assessed as ‘in need’ are not entitled to receive such services unless they are disabled. This exploration is timely given the current Independent Review of Children's Social Care in England, ongoing austerity measures, high rates of child poverty and COVID‐19. Consideration is given to the development of Section 17 and what the future may hold. [ABSTRACT FROM AUTHOR] Copyright of Children & Society is the property of Wiley-Blackwell and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Recognizing the Benefit of Telemedicine Before and After COVID-19: A Survey of Pediatric Surgery Providers.

BACKGROUND: Prior to the COVID-19 pandemic, the use of telemedicine to evaluate pediatric surgery patients was uncommon. Due in part to restrictions imposed to mitigate the spread of the virus, the use of telemedicine within pediatric surgery has significantly expanded. METHODS: Prior to the use of telemedicine within surgery divisions at our institution, pediatric surgeons were surveyed to determine their perspectives on the use of telemedicine. Following the expanded use of telemedicine in response to the COVID-19 pandemic, a follow up survey was distributed to determine the impact of telemedicine and the perceived benefits and barriers of continuing its use going forward. RESULTS: The pre-COVID survey was completed by 37 surgeons and the post-COVID survey by 36 surgeons and advanced practice providers across 10 pediatric surgical divisions. General surgeons were the most represented division for both the pre- (25%) and post-COVID (33.3%) survey. Less than 25% of providers reported use of telemedicine at any point in their career prior to COVID-19; but following the expanded use of telemedicine 95% of respondents reported interest in continuing its use. After expansion, 25% of respondents were concerned with the possibility of inaccurate diagnoses when using telemedicine compared to nearly 50% prior to expanded use. CONCLUSION: Following the expanded use of telemedicine within pediatric surgery, there was a decrease in the concern for inaccurate diagnoses and a near uniform desire to continue its use. Going forward, it will be imperative for pediatric surgeons to take an active role in creating a process for implementing telemedicine that best fits their needs and the needs of their patients and patients' families.

Nonsteroidal Antiinflammatory Drugs and Susceptibility to COVID-19.

OBJECTIVE: To identify whether active use of nonsteroidal antiinflammatory drugs (NSAIDs) increases susceptibility to developing suspected or confirmed coronavirus disease 2019 (COVID-19) compared to the use of other common analgesics. METHODS: We performed a propensity score-matched cohort study with active comparators, using a large UK primary care data set. The cohort consisted of adult patients age ≥18 years with osteoarthritis (OA) who were followed up from January 30 to July 31, 2020. Patients prescribed an NSAID (excluding topical preparations) were compared to those prescribed either co-codamol (paracetamol and codeine) or co-dydramol (paracetamol and dihydrocodeine). A total of 13,202 patients prescribed NSAIDs were identified, compared to 12,457 patients prescribed the comparator drugs. The primary outcome measure was the documentation of suspected or confirmed COVID-19, and the secondary outcome measure was all-cause mortality. RESULTS: During follow-up, the incidence rates of suspected/confirmed COVID-19 were 15.4 and 19.9 per 1,000 person-years in the NSAID-exposed group and comparator group, respectively. Adjusted hazard ratios for suspected or confirmed COVID-19 among the unmatched and propensity score-matched OA cohorts, using data from clinical consultations in primary care settings, were 0.82 (95% confidence interval [95% CI] 0.62-1.10) and 0.79 (95% CI 0.57-1.11), respectively, and adjusted hazard ratios for the risk of all-cause mortality were 0.97 (95% CI 0.75-1.27) and 0.85 (95% CI 0.61-1.20), respectively. There was no effect modification by age or sex. CONCLUSION: No increase in the risk of suspected or confirmed COVID-19 or mortality was observed among patients with OA in a primary care setting who were prescribed NSAIDs as compared to those who received comparator drugs. These results are reassuring and suggest that in the absence of acute illness, NSAIDs can be safely prescribed during the ongoing pandemic.

Linked electronic health records for research on a nationwide cohort of more than 54 million people in England: data resource.

OBJECTIVE: To describe a novel England-wide electronic health record (EHR) resource enabling whole population research on covid-19 and cardiovascular disease while ensuring data security and privacy and maintaining public trust. DESIGN: Data resource comprising linked person level records from national healthcare settings for the English population, accessible within NHS Digital's new trusted research environment. SETTING: EHRs from primary care, hospital episodes, death registry, covid-19 laboratory test results, and community dispensing data, with further enrichment planned from specialist intensive care, cardiovascular, and covid-19 vaccination data. PARTICIPANTS: 54.4 million people alive on 1 January 2020 and registered with an NHS general practitioner in England. MAIN MEASURES OF INTEREST: Confirmed and suspected covid-19 diagnoses, exemplar cardiovascular conditions (incident stroke or transient ischaemic attack and incident myocardial infarction) and all cause mortality between 1 January and 31 October 2020. RESULTS: The linked cohort includes more than 96% of the English population. By combining person level data across national healthcare settings, data on age, sex, and ethnicity are complete for around 95% of the population. Among 53.3 million people with no previous diagnosis of stroke or transient ischaemic attack, 98 721 had a first ever incident stroke or transient ischaemic attack between 1 January and 31 October 2020, of which 30% were recorded only in primary care and 4% only in death registry records. Among 53.2 million people with no previous diagnosis of myocardial infarction, 62 966 had an incident myocardial infarction during follow-up, of which 8% were recorded only in primary care and 12% only in death registry records. A total of 959 470 people had a confirmed or suspected covid-19 diagnosis (714 162 in primary care data, 126 349 in hospital admission records, 776 503 in covid-19 laboratory test data, and 50 504 in death registry records). Although 58% of these were recorded in both primary care and covid-19 laboratory test data, 15% and 18%, respectively, were recorded in only one. CONCLUSIONS: This population-wide resource shows the importance of linking person level data across health settings to maximise completeness of key characteristics and to ascertain cardiovascular events and covid-19 diagnoses. Although this resource was initially established to support research on covid-19 and cardiovascular disease to benefit clinical care and public health and to inform healthcare policy, it can broaden further to enable a wide range of research.

Renin-angiotensin system inhibitors and susceptibility to COVID-19 in patients with hypertension: a propensity score-matched cohort study in primary care.

INTRODUCTION: Renin-angiotensin system (RAS) inhibitors have been postulated to influence susceptibility to Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2). This study investigated whether there is an association between their prescription and the incidence of COVID-19 and all-cause mortality. METHODS: We conducted a propensity-score matched cohort study comparing the incidence of COVID-19 among patients with hypertension prescribed angiotensin-converting enzyme I (ACE) inhibitors or angiotensin II type-1 receptor blockers (ARBs) to those treated with calcium channel blockers (CCBs) in a large UK-based primary care database (The Health Improvement Network). We estimated crude incidence rates for confirmed/suspected COVID-19 in each drug exposure group. We used Cox proportional hazards models to produce adjusted hazard ratios for COVID-19. We assessed all-cause mortality as a secondary outcome. RESULTS: The incidence rate of COVID-19 among users of ACE inhibitors and CCBs was 9.3 per 1000 person-years (83 of 18,895 users [0.44%]) and 9.5 per 1000 person-years (85 of 18,895 [0.45%]), respectively. The adjusted hazard ratio was 0.92 (95% CI 0.68 to 1.26). The incidence rate among users of ARBs was 15.8 per 1000 person-years (79 out of 10,623 users [0.74%]). The adjusted hazard ratio was 1.38 (95% CI 0.98 to 1.95). There were no significant associations between use of RAS inhibitors and all-cause mortality. CONCLUSION: Use of ACE inhibitors was not associated with the risk of COVID-19 whereas use of ARBs was associated with a statistically non-significant increase compared to the use of CCBs. However, no significant associations were observed between prescription of either ACE inhibitors or ARBs and all-cause mortality.

The value of telemedicine for the pediatric surgery patient in the time of COVID-19 and beyond.

BACKGROUND: Prior to COVID-19, the use of telemedicine within pediatric surgery was uncommon. To curb the spread of the virus many institutions restricted non-emergent clinic appointments, resulting in an increase in telemedicine use. We examined the value of telemedicine for patients presenting to a pediatric surgery clinic before and after COVID-19 METHODS: Perspectives and the potential value of telemedicine were assessed by surveying patients or caregivers of patients being evaluated by a general pediatric surgeon in-person prior to COVID-19 and by patients or caregivers of patients who completed a telemedicine appointment with a pediatric surgical provider during the COVID-19 period. RESULTS: The pre-COVID survey was completed by 57 respondents and the post-COVID survey by 123. Most respondents were white and were caregivers 31-40 years of age. Prior to COVID-19, only 26% were familiar with telemedicine, 25% reported traveling more than 100 miles and >50% traveled more than 40 miles for their appointment. More than 25% estimated additional travel costs of at least $30 and in 43% of households, at least one adult had to miss time from work. Following a telemedicine appointment during the COVID-19 period, 76% reported the care received as excellent, 86% were very satisfied with their care, 87% reported the appointment was less stressful for their child than an in-person appointment, and 57% would choose a telemedicine appointment in the future. CONCLUSION: For families seeking an alternative to the in-person encounter, telemedicine can provide added value over the traditional in-person encounter by reducing the burden of travel without compromising the quality of care. Telemedicine should be viewed as a viable option for pediatric surgery patients and future research directed toward optimizing the experience for patients and providers. LEVEL OF EVIDENCE: III.

Association of Metformin with Susceptibility to COVID-19 in People with Type 2 Diabetes.

OBJECTIVE: Diabetes has emerged as an important risk factor for mortality from COVID-19. Metformin, the most commonly prescribed glucose-lowering agent, has been proposed to influence susceptibility to and outcomes of COVID-19 via multiple mechanisms. We investigated whether, in patients with diabetes, metformin is associated with susceptibility to COVID-19 and its outcomes. RESEARCH DESIGN AND METHODS: We performed a propensity score-matched cohort study with active comparators using a large UK primary care dataset. Adults with type 2 diabetes patients and a current prescription for metformin and other glucose-lowering agents (MF+) were compared to those with a current prescription for glucose-lowering agents that did not include metformin (MF-). Outcomes were confirmed COVID-19, suspected/confirmed COVID-19, and associated mortality. A negative control outcome analysis (back pain) was also performed. RESULTS: There were 29 558 and 10 271 patients in the MF+ and MF- groups, respectively, who met the inclusion criteria. In the propensity score-matched analysis, the adjusted hazard ratios for suspected/confirmed COVID-19, confirmed COVID-19, and COVID-19-related mortality were 0.85 (95% CI 0.67, 1.08), 0.80 (95% CI 0.49, 1.30), and 0.87 (95% CI 0.34, 2.20) respectively. The negative outcome control analysis did not suggest unobserved confounding. CONCLUSION: Current prescription of metformin was not associated with the risk of COVID-19 or COVID-19-related mortality. It is safe to continue prescribing metformin to improve glycemic control in patients with.

Rapid translation of clinical guidelines into executable knowledge: A case study of COVID-19 and online demonstration.

Introduction: We report a pathfinder study of AI/knowledge engineering methods to rapidly formalise COVID-19 guidelines into an executable model of decision making and care pathways. The knowledge source for the study was material published by BMJ Best Practice in March 2020. Methods: The PROforma guideline modelling language and OpenClinical.net authoring and publishing platform were used to create a data model for care of COVID-19 patients together with executable models of rules, decisions and plans that interpret patient data and give personalised care advice. Results: PROforma and OpenClinical.net proved to be an effective combination for rapidly creating the COVID-19 model; the Pathfinder 1 demonstrator is available for assessment at https://www.openclinical.net/index.php?id=746. Conclusions: This is believed to be the first use of AI/knowledge engineering methods for disseminating best-practice in COVID-19 care. It demonstrates a novel and promising approach to the rapid translation of clinical guidelines into point of care services, and a foundation for rapid learning systems in many areas of healthcare.