Patient portal registration and healthcare utilisation in general practices in England: a longitudinal cohort study.

BACKGROUND: Patient portals introduced in most of England's general practices since 2015 have the potential to improve healthcare efficiency. There is a paucity of information on the use of patient portals within the NHS general practices and the potential impact on healthcare utilisation. AIM: To investigate the association between patient portal registration and care utilisation (measured by the number of general practice consultations) among general practice patients. DESIGN & SETTING: A longitudinal analysis using electronic health record data from the Clinical Practice Research Datalink (CPRD). METHOD: We analysed patients registered for patient portals (n = 284 666), aggregating their consultations 1 year before and 1 year after registration. We ran a multilevel negative binomial regression model to examine patient portal registration's association with face-to-face and remote consultations. RESULTS: Patients who registered to the portal had a small decrease in the total number of face-to-face consultations after registering to the patient portal (incidence rate ratio = 0.93, 95% confidence interval [CI] = 0.93 to 0.94). Patients who registered to the portal had an increase in the total number of remote consultations after registering to the portal (incidence rate ratio = 1.16, 95% CI = 1.15 to 1.18). CONCLUSION: The study found minor changes in consultation numbers post-patient portal registration, notably with an increase in remote consultations. While causality between portal registration and consultation number remains unclear, the potential link between patient portal use and healthcare utilisation warrants further investigation, especially within the NHS, where portal impacts are not well-studied. Detailed portal utilisation data could clarify this relationship.

Cross-sectional analyses of online appointment booking and repeat prescription ordering user characteristics in general practices of England in the years 2018-2020.

OBJECTIVES: To explore the characteristics of the General Practice Patient Survey (GPPS) respondents using the different functionalities of the online services in the context of England's National Health Service General Practices. We hypothesised that respondents who are older, with lower socioeconomic status and non-white ethnicity would be less likely to use online services, while long-term conditions might increase their usage. DESIGN: Cross-sectional study using respondent-level data from the GPPS in England of the years 2018, 2019 and 2020. We assessed the association between online services use and respondent characteristics using two-level mixed-effects logistic regression. PARTICIPANTS: Survey respondents of the GPPS 2018-2020. PRIMARY OUTCOME MEASURES: Online appointment booking and online repeat prescription ordering. RESULTS: 1 807 049 survey respondents were included in this study. 15% (n=263 938) used online appointment booking in the previous 12 months, and 19% (n=339 449) had ordered a repeat prescription in the previous 12 months. Respondents with a long-term condition, on regular multiple medications, who have deafness or hearing loss and who are from the lowest deprivation quintile were more likely to have used online services. Male respondents (compared with females) and respondents with black and other ethnicity compared with white ethnicity were less likely to use online services. Respondents over 85 years old were less likely to use online appointment booking and online repeat prescription ordering compared with the younger age groups. CONCLUSIONS: Specific groups of respondents were more likely to use online services such as patients with long-term conditions or those with deafness or hearing loss. While online services could provide efficiency to patients and practices it is essential that alternatives continue to be provided to those that cannot use or choose not to use online services. Understanding the different patients' needs could inform solutions to increase the uptake and use of the services.

Prevalence of electronic screening for sepsis in National Health Service acute hospitals in England.

Sepsis is a worldwide public health problem. Rapid identification is associated with improved patient outcomes-if followed by timely appropriate treatment. OBJECTIVES: Describe digital sepsis alerts (DSAs) in use in English National Health Service (NHS) acute hospitals. METHODS: A Freedom of Information request surveyed acute NHS Trusts on their adoption of electronic patient records (EPRs) and DSAs. RESULTS: Of the 99 Trusts that responded, 84 had an EPR. Over 20 different EPR system providers were identified as operational in England. The most common providers were Cerner (21%). System C, Dedalus and Allscripts Sunrise were also relatively common (13%, 10% and 7%, respectively). 70% of NHS Trusts with an EPR responded that they had a DSA; most of these use the National Early Warning Score (NEWS2). There was evidence that the EPR provider was related to the DSA algorithm. We found no evidence that Trusts were using EPRs to introduce data driven algorithms or DSAs able to include, for example, pre-existing conditions that may be known to increase risk.Not all Trusts were willing or able to provide details of their EPR or the underlying algorithm. DISCUSSION: The majority of NHS Trusts use an EPR of some kind; many use a NEWS2-based DSA in keeping with national guidelines. CONCLUSION: Many English NHS Trusts use DSAs; even those using similar triggers vary and many recreate paper systems. Despite the proliferation of machine learning algorithms being developed to support early detection of sepsis, there is little evidence that these are being used to improve personalised sepsis detection.

Comparing the longer-term effectiveness of a single dose of the Pfizer-BioNTech and Oxford-AstraZeneca COVID-19 vaccines across the age spectrum.

Background: A single dose strategy may be adequate to confer population level immunity and protection against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, especially in low- and middle-income countries where vaccine supply remains limited. We compared the effectiveness of a single dose strategy of the Oxford-AstraZeneca or Pfizer-BioNTech vaccines against SARS-CoV-2 infection across all age groups and over an extended follow-up period. Methods: Individuals vaccinated in North-West London, UK, with either the first dose of the Oxford-AstraZeneca or Pfizer-BioNTech vaccines between January 12, 2021 and March 09, 2021, were matched to each other by demographic and clinical characteristics. Each vaccinated individual was additionally matched to an unvaccinated control. Study outcomes included SARS-CoV-2 infection of any severity, COVID-19 hospitalisation, COVID-19 death, and all-cause mortality. Findings: Amongst matched individuals, 63,608 were in each of the vaccine groups and 127,216 were unvaccinated. Between 14 and 84 days of follow-up after matching, there were 534 SARS-CoV-2 infections, 65 COVID-19 hospitalisations, and 190 deaths, of which 29 were categorized as due to COVID-19. The incidence rate ratio (IRR) for SARS-CoV-2 infection was 0.85 (95% confidence interval [CI], 0.69 to 1.05) for Oxford-Astra-Zeneca, and 0.69 (0.55 to 0.86) for Pfizer-BioNTech. The IRR for both vaccines was the same at 0.25 (0.09 to 0.55) and 0.14 (0.02 to 0.58) for reducing COVID-19 hospitalization and COVID-19 mortality, respectively. The IRR for all-cause mortality was 0.25 (0.15 to 0.39) and 0.18 (0.10 to 0.30) for the Oxford-Astra-Zeneca and Pfizer-BioNTech vaccines, respectively. Age was an effect modifier of the association between vaccination and SARS-CoV-2 infection of any severity; lower hazard ratios for increasing age. Interpretation: A single dose strategy, for both vaccines, was effective at reducing COVID-19 mortality and hospitalization rates. The magnitude of vaccine effectiveness was comparatively lower for SARS-CoV-2 infection, although this was variable across the age range, with higher effectiveness seen with older adults. Our results have important implications for health system planning -especially in low resource settings where vaccine supply remains constrained.

Variation in global COVID-19 symptoms by geography and by chronic disease: A global survey using the COVID-19 Symptom Mapper.

Background: COVID-19 is typically characterised by a triad of symptoms: cough, fever and loss of taste and smell, however, this varies globally. This study examines variations in COVID-19 symptom profiles based on underlying chronic disease and geographical location. Methods: Using a global online symptom survey of 78,299 responders in 190 countries between 09/04/2020 and 22/09/2020, we conducted an exploratory study to examine symptom profiles associated with a positive COVID-19 test result by country and underlying chronic disease (single, co- or multi-morbidities) using statistical and machine learning methods. Findings: From the results of 7980 COVID-19 tested positive responders, we find that symptom patterns differ by country. For example, India reported a lower proportion of headache (22.8% vs 47.8%, p<1e-13) and itchy eyes (7.3% vs. 16.5%, p=2e-8) than other countries. As with geographic location, we find people differed in their reported symptoms if they suffered from specific chronic diseases. For example, COVID-19 positive responders with asthma (25.3% vs. 13.7%, p=7e-6) were more likely to report shortness of breath compared to those with no underlying chronic disease. Interpretation: We have identified variation in COVID-19 symptom profiles depending on geographic location and underlying chronic disease. Failure to reflect this symptom variation in public health messaging may contribute to asymptomatic COVID-19 spread and put patients with chronic diseases at a greater risk of infection. Future work should focus on symptom profile variation in the emerging variants of the SARS-CoV-2 virus. This is crucial to speed up clinical diagnosis, predict prognostic outcomes and target treatment. Funding: We acknowledge funding to AAF by a UKRI Turing AI Fellowship and to CEC by a personal NIHR Career Development Fellowship (grant number NIHR-2016-090-015). JKQ has received grants from The Health Foundation, MRC, GSK, Bayer, BI, Asthma UK-British Lung Foundation, IQVIA, Chiesi AZ, and Insmed. This work is supported by BREATHE - The Health Data Research Hub for Respiratory Health [MC_PC_19004]. BREATHE is funded through the UK Research and Innovation Industrial Strategy Challenge Fund and delivered through Health Data Research UK. Imperial College London is grateful for the support from the Northwest London NIHR Applied Research Collaboration. The views expressed in this publication are those of the authors and not necessarily those of the NIHR or the Department of Health and Social Care.

Bacterial genotypic and patient risk factors for adverse outcomes in Escherichia coli bloodstream infections: a prospective molecular epidemiological study.

OBJECTIVES: Escherichia coli bloodstream infections have shown a sustained increase in England, for reasons that are unknown. Furthermore, the contribution of MDR lineages such as ST131 to overall E. coli disease burden and outcome is undetermined. METHODS: We genome-sequenced E. coli blood isolates from all patients with E. coli bacteraemia in north-west London from July 2015 to August 2016 and assigned MLST genotypes, virulence factors and AMR genes to all isolates. Isolate STs were then linked to phenotypic antimicrobial susceptibility, patient demographics and clinical outcome data to explore relationships between the E. coli STs, patient factors and outcomes. RESULTS: A total of 551 E. coli genomes were analysed. Four STs (ST131, 21.2%; ST73, 14.5%; ST69, 9.3%; and ST95, 8.2%) accounted for over half of cases. E. coli genotype ST131-C2 was associated with phenotypic non-susceptibility to quinolones, third-generation cephalosporins, amoxicillin, amoxicillin/clavulanic acid, gentamicin and trimethoprim. Among 300 patients from whom outcome was known, an association between the ST131-C2 lineage and longer length of stay was detected, although multivariable regression modelling did not demonstrate an association between E. coli ST and mortality. Several unexpected associations were identified between gentamicin non-susceptibility, ethnicity, sex and adverse outcomes, requiring further research. CONCLUSIONS: Although E. coli ST was associated with defined antimicrobial non-susceptibility patterns and prolonged length of stay, E. coli ST was not associated with increased mortality. ST131 has outcompeted other lineages in north-west London. Where ST131 is prevalent, caution is required when devising empiric regimens for suspected Gram-negative sepsis, in particular the pairing of ß-lactam agents with gentamicin.

Identifying local authority need for, and uptake of, school-based physical activity promotion in England-a cluster analysis.

BACKGROUND: School-based physical activity interventions such as The Daily Mile (TDM) are widely promoted in children's physical activity guidance. However, targeting such interventions to areas of greatest need is challenging since determinants vary across geographical areas. Our study aimed to identify local authorities in England with the greatest need to increase children's physical activity and assess whether TDM reaches school populations in areas with the highest need. METHODS: This was a cross-sectional study using routinely collected data from Public Health England. Datasets on health, census and the built environment were linked. We conducted a hierarchical cluster analysis to group local authorities by 'need' and estimated the association between 'need' and registration to TDM. RESULTS: We identified three clusters of high, medium and low need for physical activity interventions in 123 local authorities. Schools in high-need areas were more likely to be registered with TDM (incidence rate ratio 1.25, 95% confidence interval: 1.12-1.39) compared with low-need areas. CONCLUSIONS: Determinants of children's physical activity cluster geographically across local authorities in England. TDM appears to be an equitable intervention reaching schools in local authorities with the highest needs. Health policy should account for clustering of health determinants to match interventions with populations most in need.

Global health systems' data science approach for precision diagnosis of sepsis in early life.

Neonates and children in low-income and middle-income countries (LMICs) contribute to the highest number of sepsis-associated deaths globally. Interventions to prevent sepsis mortality are hampered by a lack of comprehensive epidemiological data and pathophysiological understanding of biological pathways. In this review, we discuss the challenges faced by LMICs in diagnosing sepsis in these age groups. We highlight a role for multi-omics and health care data to improve diagnostic accuracy of clinical algorithms, arguing that health-care systems urgently need precision medicine to avoid the pitfalls of missed diagnoses, misdiagnoses, and overdiagnoses, and associated antimicrobial resistance. We discuss ethical, regulatory, and systemic barriers related to the collection and use of big data in LMICs. Technologies such as cloud computing, artificial intelligence, and medical tricorders might help, but they require collaboration with local communities. Co-partnering (joint equal development of technology between producer and end-users) could facilitate integration of these technologies as part of future care-delivery systems, offering a chance to transform the global management and prevention of sepsis for neonates and children.

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.

Changes in Emergency Department Activity and the First COVID-19 Lockdown: A Cross-sectional Study.

INTRODUCTION: Emergency department (ED) attendances fell across the UK after the 'lockdown' introduced on 23rd March 2020 to limit the spread of coronavirus disease 2019 (COVID-19). We hypothesised that reductions would vary by patient age and disease type. We examined pre- and in-lockdown ED attendances for two COVID-19 unrelated diagnoses: one likely to be affected by lockdown measures (gastroenteritis), and one likely to be unaffected (appendicitis). METHODS: We conducted a retrospective cross-sectional study across two EDs in one London hospital Trust. We compared all adult and paediatric ED attendances, before (January 2020) and during lockdown (March/April 2020). Key patient demographics, method of arrival, and discharge location were compared. We used Systemised Nomenclature of Medicine codes to define attendances for gastroenteritis and appendicitis. RESULTS: ED attendances fell from 1129 per day before lockdown to 584 in lockdown, 51.7% of pre-lockdown rates. In-lockdown attendances were lowest for under-18s (16.0% of pre-lockdown). The proportion of patients admitted to hospital increased from 17.3% to 24.0%, and the proportion admitted to intensive care increased fourfold. Attendances for gastroenteritis fell from 511 to 103, 20.2% of pre-lockdown rates. Attendances for appendicitis also decreased, from 144 to 41, 28.5% of pre-lockdown rates. CONCLUSION: ED attendances fell substantially following lockdown implementation. The biggest reduction was for under-18s. We observed reductions in attendances for gastroenteritis and appendicitis. This may reflect lower rates of infectious disease transmission, although the fall in appendicitis-related attendances suggests that behavioural factors were also important. Larger studies are urgently needed to understand changing patterns of ED use and access to emergency care during the coronavirus 2019 pandemic.

Association between intrahospital transfer and hospital-acquired infection in the elderly: a retrospective case-control study in a UK hospital network.

BACKGROUND: Intrahospital transfers have become more common as hospital staff balance patient needs with bed availability. However, this may leave patients more vulnerable to potential pathogen transmission routes via increased exposure to contaminated surfaces and contacts with individuals. OBJECTIVE: This study aimed to quantify the association between the number of intrahospital transfers undergone during a hospital spell and the development of a hospital-acquired infection (HAI). METHODS: A retrospective case-control study was conducted using data extracted from electronic health records and microbiology cultures of non-elective, medical admissions to a large urban hospital network which consists of three hospital sites between 2015 and 2018 (n=24 240). As elderly patients comprise a large proportion of hospital users and are a high-risk population for HAIs, the analysis focused on those aged 65 years or over. Logistic regression was conducted to obtain the OR for developing an HAI as a function of intrahospital transfers until onset of HAI for cases, or hospital discharge for controls, while controlling for age, gender, time at risk, Elixhauser comorbidities, hospital site of admission, specialty of the dominant healthcare professional providing care, intensive care admission, total number of procedures and discharge destination. RESULTS: Of the 24 240 spells, 2877 cases were included in the analysis. 72.2% of spells contained at least one intrahospital transfer. On multivariable analysis, each additional intrahospital transfer increased the odds of acquiring an HAI by 9% (OR=1.09; 95% CI 1.05 to 1.13). CONCLUSION: Intrahospital transfers are associated with increased odds of developing an HAI. Strategies for minimising intrahospital transfers should be considered, and further research is needed to identify unnecessary transfers. Their reduction may diminish spread of contagious pathogens in the hospital environment.

Sociodemographic profiles, educational attainment and physical activity associated with The Daily Mile™ registration in primary schools in England: a national cross-sectional linkage study.

OBJECTIVE: To examine primary school and local authority characteristics associated with registration for The Daily Mile (TDM), an active mile initiative aimed at increasing physical activity in children. DESIGN: A cross-sectional linkage study using routinely collected data. SETTING: All state-funded primary schools in England from 2012 to 2018 (n=15,815). RESULTS: 3,502 of all 15,815 (22.1%) state-funded primary schools in England were registered to do TDM, ranging from 16% in the East Midlands region to 31% in Inner London. Primary schools registered for TDM had larger mean pupil numbers compared with schools that had not registered (300 vs 269, respectively). There was a higher proportion of TDM-registered schools in urban areas compared with non-urban areas. There was local authority variation in the likelihood of school registration (intraclass correlation coefficient: 0.094). After adjusting for school and local authority characteristics, schools located in a major urban conurbation (OR 1.46 (95% CI 1.24 to 1.71) urban vs rural) and schools with a higher proportion of disadvantaged pupils had higher odds of being registered for TDM (OR 1.16 (95% CI 1.02 to 1.33)). Area-based physical activity and schools' educational attainment were not significantly associated with registration to TDM. CONCLUSION: One in five primary schools in England has registered for TDM since 2012. TDM appears to be a wide-reaching school-based physical activity intervention that is reaching more disadvantaged primary school populations in urban areas where obesity prevalence is highest. TDM-registered schools include those with both high and low educational attainment and are in areas with high and low physical activity.

Health Professions Digital Education on Antibiotic Management: Systematic Review and Meta-Analysis by the Digital Health Education Collaboration.

BACKGROUND: Inappropriate antibiotic prescription is one of the key contributors to antibiotic resistance, which is managed with a range of interventions including education. OBJECTIVE: We aimed to summarize evidence on the effectiveness of digital education of antibiotic management compared to traditional education for improving health care professionals' knowledge, skills, attitudes, and clinical practice. METHODS: Seven electronic databases and two trial registries were searched for randomized controlled trials (RCTs) and cluster RCTs published between January 1, 1990, and September 20, 2018. There were no language restrictions. We also searched the International Clinical Trials Registry Platform Search Portal and metaRegister of Controlled Trials to identify unpublished trials and checked the reference lists of included studies and relevant systematic reviews for study eligibility. We followed Cochrane methods to select studies, extract data, and appraise and synthesize eligible studies. We used random-effect models for the pooled analysis and assessed statistical heterogeneity by visual inspection of a forest plot and calculation of the I2 statistic. RESULTS: Six cluster RCTs and two RCTs with 655 primary care practices, 1392 primary care physicians, and 485,632 patients were included. The interventions included personal digital assistants; short text messages; online digital education including emails and websites; and online blended education, which used a combination of online digital education and traditional education materials. The control groups received traditional education. Six studies assessed postintervention change in clinical practice. The majority of the studies (4/6) reported greater reduction in antibiotic prescription or dispensing rate with digital education than with traditional education. Two studies showed significant differences in postintervention knowledge scores in favor of mobile education over traditional education (standardized mean difference=1.09, 95% CI 0.90-1.28; I2=0%; large effect size; 491 participants [2 studies]). The findings for health care professionals' attitudes and patient-related outcomes were mixed or inconclusive. Three studies found digital education to be more cost-effective than traditional education. None of the included studies reported on skills, satisfaction, or potential adverse effects. CONCLUSIONS: Findings from studies deploying mobile or online modalities of digital education on antibiotic management were complementary and found to be more cost-effective than traditional education in improving clinical practice and postintervention knowledge, particularly in postregistration settings. There is a lack of evidence on the effectiveness of other digital education modalities such as virtual reality or serious games. Future studies should also include health care professionals working in settings other than primary care and low- and middle-income countries. CLINICAL TRIAL: PROSPERO CRD42018109742; https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=109742.

How big should the pilot study for my cluster randomised trial be?

There is currently a lot of interest in pilot studies conducted in preparation for randomised controlled trials. This paper focuses on sample size requirements for external pilot studies for cluster randomised trials. We consider how large an external pilot study needs to be to assess key parameters for input to the main trial sample size calculation when the primary outcome is continuous, and to estimate rates, for example recruitment rates, with reasonable precision. We used simulation to provide the distribution of the expected number of clusters for the main trial under different assumptions about the natural cluster size, intra-cluster correlation, eventual cluster size in the main trial, and various decisions made at the piloting stage. We chose intra-cluster correlation values and pilot study size to reflect those commonly reported in the literature. Our results show that estimates of sample size required for the main trial are likely to be biased downwards and very imprecise unless the pilot study includes large numbers of clusters and individual participants. We conclude that pilot studies will usually be too small to estimate parameters required for estimating a sample size for a main cluster randomised trial (e.g. the intra-cluster correlation coefficient) with sufficient precision and too small to provide reliable estimates of rates for process measures such as recruitment or follow-up rates.

IL-4 attenuates the neuroinflammation induced by amyloid-beta in vivo and in vitro.

It has been shown that Abeta inhibits long-term potentiation (LTP) in the rat hippocampus and this is accompanied by an increase in hippocampal concentration of IL-1beta. Abeta also increases microglial activation, which is the likely cell source of IL-1beta. Because IL-4 attenuates the effects of IL-1beta in hippocampus, and microglial activation is inhibited by minocycline, we assessed the ability of both IL-4 and minocycline to modulate the effects of Abeta on LTP and IL-1beta concentration. Following treatment with Abeta, IL-4 or minocycline, rats were assessed for their ability to sustain LTP in perforant path-granule cell synapses. We report that the Abeta-induced inhibition of LTP was associated with increases in expression of MHCII, JNK phosphorylation and IL-1beta concentration, and that these changes were attenuated by treatment of rats with IL-4 and minocycline. We also report that Abeta-induced increases in expression of MHCII and IL-1beta were similarly attenuated by IL-4 and minocycline in glial cultures prepared from neonatal rats. These data suggest that glial cell activation and the consequent increase in IL-1beta concentration mediate the inhibitory effect of Abeta on LTP and indicate that IL-4, by down-regulating glial cell activation, antagonizes the effects of Abeta.