Telencephalic eversion in embryos and early larvae of four teleost species.

The telencephalon of ray-finned fishes undergoes eversion, which is very different to the evagination that occurs in most other vertebrates. Ventricle morphogenesis is key to build an everted telencephalon. Thus, here we use the apical marker zona occludens 1 to understand ventricle morphology, extension of the tela choroidea and the eversion process during early telencephalon development of four teleost species: giant danio (Devario aequipinnatus), blind cavefish (Astyanax mexicanus), medaka (Oryzias latipes), and paradise fish (Macroposus opercularis). In addition, by using immunohistochemistry against tubulin and calcium-binding proteins, we analyze the general morphology of the telencephalon, showing changes in the location and extension of the olfactory bulb and other telencephalic regions from 2 to 5 days of development. We also analyze the impact of abnormal eye and telencephalon morphogenesis on eversion, showing that cyclops mutants do undergo eversion despite very dramatic abnormal eye morphology. We discuss how the formation of the telencephalic ventricle in teleost fish, with its characteristic shape, is a crucial event during eversion.

p-tau Ser356 is associated with Alzheimer's disease pathology and is lowered in brain slice cultures using the NUAK inhibitor WZ4003.

Tau hyperphosphorylation and aggregation is a common feature of many dementia-causing neurodegenerative diseases. Tau can be phosphorylated at up to 85 different sites, and there is increasing interest in whether tau phosphorylation at specific epitopes, by specific kinases, plays an important role in disease progression. The AMP-activated protein kinase (AMPK)-related enzyme NUAK1 has been identified as a potential mediator of tau pathology, whereby NUAK1-mediated phosphorylation of tau at Ser356 prevents the degradation of tau by the proteasome, further exacerbating tau hyperphosphorylation and accumulation. This study provides a detailed characterisation of the association of p-tau Ser356 with progression of Alzheimer's disease pathology, identifying a Braak stage-dependent increase in p-tau Ser356 protein levels and an almost ubiquitous presence in neurofibrillary tangles. We also demonstrate, using sub-diffraction-limit resolution array tomography imaging, that p-tau Ser356 co-localises with synapses in AD postmortem brain tissue, increasing evidence that this form of tau may play important roles in AD progression. To assess the potential impacts of pharmacological NUAK inhibition in an ex vivo system that retains multiple cell types and brain-relevant neuronal architecture, we treated postnatal mouse organotypic brain slice cultures from wildtype or APP/PS1 littermates with the commercially available NUAK1/2 inhibitor WZ4003. Whilst there were no genotype-specific effects, we found that WZ4003 results in a culture-phase-dependent loss of total tau and p-tau Ser356, which corresponds with a reduction in neuronal and synaptic proteins. By contrast, application of WZ4003 to live human brain slice cultures results in a specific lowering of p-tau Ser356, alongside increased neuronal tubulin protein. This work identifies differential responses of postnatal mouse organotypic brain slice cultures and adult human brain slice cultures to NUAK1 inhibition that will be important to consider in future work developing tau-targeting therapeutics for human disease.

Microtubules are not required to generate a nascent axon in embryonic spinal neurons in vivo.

Our understanding of the cell behaviours and cytoskeletal requirements of axon formation is largely derived from in vitro models but how these relate to axon formation in vivo is not clear. In vitro, neurons progress through a well-defined multineurite stage to form an axon and both actin and microtubules cooperate to drive the first steps in neurite and axon morphogenesis. However, these steps are not recapitulated in vivo, and it is not clear whether the underlying cell biological mechanisms may differ also. Here, we investigate the mechanisms that regulate axon formation in embryonic zebrafish spinal neurons in vivo. We find microtubule organising centres are located distant from the site of axon initiation, and microtubule plus-ends are not enriched in the axon during axon initiation. Focal F-actin accumulation precedes axon formation, and we find that nocodazole-treated neurons with no detectable microtubules are still able to form nascent axonal protrusions that are approximately 10-µm long, dilated and relatively long-lived. We suggest spinal axon formation in vivo is fundamentally different from axon formation in in vitro models.

May Measurement Month 2021: an analysis of blood pressure screening results from Paraguay.

The aim of this study was to highlight the importance of measuring blood pressure (BP) to identify new, known, and treated individuals with hypertension and to raise awareness in the general population about the importance of good BP control. In Paraguay, 3663 individuals aged ≥18 years of both sexes were recruited from May to November 2021 as part of the May Measurement Month (MMM) campaign, which was initiated by the International Society of Hypertension in 2017. Volunteers of 18 regional health teams applied the questionnaire provided by the MMM 2021 organization throughout the country. Due to COVID-19 constraints, the majority of the questionnaires (52.2%) were administered in health centres of the Ministry of Health and concluded with three BP and pulse readings using OMRON-automated BP measurement devices. Hypertension was defined as a systolic BP ≥ 140 mmHg or as a diastolic BP ≥ 90 mmHg or taking antihypertensive medication. We found that 57.4% of screenees were hypertensive and 72.9% of these (82.3% of women and 59.4% of men) had known hypertension. Of patients with hypertension, 70.1% were on antihypertensive medication, and 40.9% had controlled BP (<140/90 mmHg). Among hypertensives detected, 79.7% of women were on antihypertensive medication and 44.1% had controlled BP, while 56.4% of men were on treatment and 34.3% had controlled BP. In summary, we found high levels of hypertension with high rates of awareness and treatment particularly among women, although control rates were low particularly among men. This may be because most screening was conducted predominately in hospital settings.

May Measurement Month 2021: an analysis of blood pressure screening results from Thailand.

Blood pressure (BP) measurement is the mainstay for diagnosing and treating hypertension. Blood pressure screening in the May Measurement Month (MMM) project is helpful for the early detection of hypertension, which is usually asymptomatic. This study aimed to investigate the epidemiology of hypertension from data in the MMM21 project in Thailand. A cross-sectional study was conducted according to the MMM clinical study protocol for MMM21 in all regions of Thailand from August to November 2021. We included adults aged ≥18 years. Baseline characteristics, history of hypertension diagnosis, and treatment were collected through the questionnaires followed by three standardized BP measurements, 1 min apart. We included 10 940 participants with a mean age of 41.3 (SD ± 13.5) years. Only 6% never had their BP measured before. Of all participants, 30.2% had hypertension, and among this hypertensive population, 50.3% were aware, and 46.2% were taking antihypertensive medications. Of participants with hypertension, 31.6% had controlled BP (<140/90 mmHg), and BP control was 68.5% among those taking antihypertensive medication. The proportion of participants who had diabetes, were on aspirin, and were on statin were 6, 7.2, and 11.4%, respectively. Almost all participants (93.7%) had received at least one COVID-19 vaccination, and 8.0% reported a previous COVID-19 positive test. Most of the participants (97.4%) received hypertension care at no cost. Hypertension awareness and overall BP control rate were relatively low, while most subjects had previously had their BP checked. The widespread use of BP measurement may improve the diagnosis and treatment of hypertension to improve the care of those with hypertension in Thailand.

May Measurement Month 2021: an analysis of blood pressure screening results from Nepal.

Despite the well-recognized importance of prevention and early treatment of hypertension, the majority of adults in Nepal are not aware of their high blood pressure (BP) and are left untreated. In this paper, we report the result of the May Measure Month 2021 campaign in Nepal: a nationwide community-based hypertension screening campaign. An opportunistic cross-sectional survey was conducted in 15 districts between September 2021 and December 2021. An individual was included if aged 18 years or more and provided informed consent. Structured questionnaires were administered, and BP was measured three times in a sitting position by trained volunteers. A total of 5172 participants were included. The median age (interquartile range) was 37 (25-51), and 49.9% were female. The mean (SD) of the systolic and diastolic BP was 123.9 (14.9) and 80.2 (9.3) mmHg, respectively. A total of 1066 participants (20.6%) were identified as hypertensive (systolic BP ≥ 140 mmHg or diastolic BP ≥ 90 mmHg or on antihypertensive medication), of whom 399 (39.5%) and 298 (29.5%) were aware of their BP status and treated with at least one antihypertensive medicine, respectively. Blood pressure control (<140/90 mmHg) was achieved in 15.6% of all hypertensives and in 56.0% of treated individuals. Multivariate logistic regression showed an association between hypertension and the following variables: every 1-year increase of age [odds ratio (OR) = 1.13 (1.11-1.15) if age < 40 and OR = 1.05 (1.04-1.06) if age ≥ 40], male [OR = 1.57 (1.33-1.89)], regular alcohol use [OR = 1.59 (1.30-1.93)], and diabetes [OR = 2.63 (1.93-3.58)]. Hypertension awareness, treatment, and control were suboptimal in Nepal. This study supports a strong need to scale up community-based hypertension programmes in Nepal and raises the possibility of task sharing with community health workers.

May Measurement Month 2021: an analysis of blood pressure screening results from Australia.

May Measurement Month (MMM) is a global and national blood pressure (BP) screening campaign initiated by the International Society of Hypertension to improve awareness of BP worldwide. This study reports on the findings of the MMM21 campaign in Australia. Adult participants (≥18 years) were screened through opportunistic sampling across Australia between 1 May and 30 November 2021. Trained volunteers recorded standardized BP measurements from community volunteer participants along with demographic data, lifestyle factors, comorbidities, and history of COVID-19 infection and vaccination. Hypertension was defined as systolic BP ≥ 140 mmHg and/or diastolic BP ≥ 90 mmHg and/or taking antihypertensive medication. Data were collated and analysed centrally using the current MMM protocol and presented after the imputation of missing BP readings. A total of 1307 participants were screened in 2021, comprising 652 (49.9%) females and 654 (50.0%) males with a mean age of 48 years (SD 20.1). Of all 1307 participants, 524 (40.1%) had hypertension. Of participants with hypertension, 65.4% were aware and 59.3% were on antihypertensive medication. Of 311 participants on antihypertensive medication, 54.7% had controlled BP. Of all 524 participants with hypertension, 32.5% had controlled BP. The current 2021 data may indicate some progress in creating BP awareness; however, consecutive Australian data obtained since 2017 demonstrated stagnating treatment, and control rates compared with global rates and those in other high-income countries. Concerted efforts from all stakeholders will be required to further improve BP awareness, treatment, and control rates in Australia.

May Measurement Month 2021: an analysis of blood pressure screening campaign results from India.

Raised blood pressure (BP) is the leading preventable risk factor for cardiovascular diseases that makes a major impact on early mortality and morbidity. Recognizing hypertension in the community, educating people about routine BP monitoring, and improving medication compliance are all important steps in detecting, controlling, and managing hypertension. During the course of 5 months, members of the Indian Society of Hypertension organized unique medical indoor and outdoor camps at 100 screening locations around India for the May Measurement Month (MMM) 2021 study. At every location, BP was measured three times, and a questionnaire was completed. Participants known to have hypertension before the study whether taking or not taking treatment were not included (not a normal pre-requisite for exclusion in MMM). The analysis included 15 045 participants in total. After calculating the average of the second and third BP measurements, 16.4% of participants were found to have hypertension based on ≥140/90 mmHg thresholds (2461 out of 15 045). 14.0% of females and 16.4% of males had hypertension. 16.4% of participants had undiagnosed hypertension and were not receiving treatment. The MMM screening campaign has the potential for identifying large numbers of people with undiagnosed hypertension and raising awareness of the importance of raised BP among the general public, medical professionals, policymakers, the government, and the media. Future BP screening campaigns should be larger in scope and involve follow-ups with past participants.

May Measurement Month 2021: an analysis of blood pressure screening results from the Philippines.

The Philippine Society of Hypertension (PSH) took part again in the annual May Measurement Month 2021 (MMM21) blood pressure (BP) campaign to raise awareness of hypertension. The MMM standard protocol designed by the MMM coordinating centre was used during screening. These included the collection of basic data on demography, lifestyle, and environmental factors. Standardized sitting BP measurements were taken three times, using automated BP apparatus and were either entered via MMM21 app, MMM@Home, and Google Forms or recorded on paper and transferred to Excel spreadsheets by PSH encoders. Hypertension was defined either as systolic BP ≥ 140 mmHg or diastolic BP ≥ 90 mmHg or on antihypertensive medication. A total of 59 655 participated through opportunistic convenience sampling. After multiple imputation, a total of 26 813 (44.9%) participants were identified as having hypertension. Of these, 14 449 (53.9%) were aware and 12 978 (48.4%) were on antihypertensive medication. Of those who were treated, 5644 (43.5%) had controlled BP (<140/90 mmHg) and 7334 (56.5%) were uncontrolled. These latest local data showed that BP awareness is still low with BP control achieved in less than half of treated patients. Continued collaboration is needed to improve BP screening programmes in the country.

Coordinated assembly and release of adhesions builds apical junctional belts during de novo polarisation of an epithelial tube.

Using the zebrafish neural tube as a model, we uncover the in vivo mechanisms allowing the generation of two opposing apical epithelial surfaces within the centre of an initially unpolarised, solid organ. We show that Mpp5a and Rab11a play a dual role in coordinating the generation of ipsilateral junctional belts whilst simultaneously releasing contralateral adhesions across the centre of the tissue. We show that Mpp5a- and Rab11a-mediated resolution of cell-cell adhesions are both necessary for midline lumen opening and contribute to later maintenance of epithelial organisation. We propose that these roles for both Mpp5a and Rab11a operate through the transmembrane protein Crumbs. In light of a recent conflicting publication, we also clarify that the junction-remodelling role of Mpp5a is not specific to dividing cells.

Home oxygen monitoring and therapy: learning from the pandemic.

PURPOSE OF REVIEW: Home oxygen monitoring and therapy have been increasingly used in the management of patients with chronic diseases. The COVID-19 pandemic has prompted the rapid uptake of remote monitoring programmes to support people with COVID-19 at home. This review discusses the recent evidence and learning in home oxygen monitoring and therapy from the pandemic. RECENT FINDINGS: Many home oxygen monitoring programmes were established around the world during the pandemic, mostly in high-income countries to support early detection of hypoxaemia and/or early hospital discharge. The characteristics of these programmes vary widely in the type of monitoring (self-monitoring or clinician-monitoring) and the patient risk groups targeted. There is a lack of evidence for benefits on clinical outcomes, including mortality, and on reductions in healthcare utilisation or cost-effectiveness, but programmes are viewed positively by patients. Recent studies have highlighted the potential bias in pulse oximetry in people with darker skin. SUMMARY: Recent evidence indicates that home oxygen monitoring therapy programmes are feasible in acute disease, but further research is needed to establish whether they improve patient outcomes, are cost-effective and to understand their equity impact.

Back to basics: A mediation analysis approach to addressing the fundamental questions of integrated care evaluations.

Health systems around the world are aiming to improve the integration of health and social care services to deliver better care for patients. Existing evaluations have focused exclusively on the impact of care integration on health outcomes and found little effect. That suggests the need to take a step back and ask whether integrated care programmes actually lead to greater clinical integration of care and indeed whether greater integration is associated with improved health outcomes. We propose a mediation analysis approach to address these two fundamental questions when evaluating integrated care programmes. We illustrate our approach by re-examining the impact of an English integrated care program on clinical integration and assessing whether greater integration is causally associated with fewer admissions for ambulatory care sensitive conditions. We measure clinical integration using a concentration index of outpatient referrals at the general practice level. While we find that the scheme increased integration of primary and secondary care, clinical integration did not mediate a decrease in unplanned hospital admissions. Our analysis emphasizes the need to better understand the hypothesized causal impact of integration on health outcomes and demonstrates how mediation analysis can inform future evaluations and program design.

PI(5)P regulates autophagosome biogenesis.

Phosphatidylinositol 3-phosphate (PI(3)P), the product of class III PI3K VPS34, recruits specific autophagic effectors, like WIPI2, during the initial steps of autophagosome biogenesis and thereby regulates canonical autophagy. However, mammalian cells can produce autophagosomes through enigmatic noncanonical VPS34-independent pathways. Here we show that PI(5)P can regulate autophagy via PI(3)P effectors and thereby identify a mechanistic explanation for forms of noncanonical autophagy. PI(5)P synthesis by the phosphatidylinositol 5-kinase PIKfyve was required for autophagosome biogenesis, and it increased levels of PI(5)P, stimulated autophagy, and reduced the levels of autophagic substrates. Inactivation of VPS34 impaired recruitment of WIPI2 and DFCP1 to autophagic precursors, reduced ATG5-ATG12 conjugation, and compromised autophagosome formation. However, these phenotypes were rescued by PI(5)P in VPS34-inactivated cells. These findings provide a mechanistic framework for alternative VPS34-independent autophagy-initiating pathways, like glucose starvation, and unravel a cytoplasmic function for PI(5)P, which previously has been linked predominantly to nuclear roles.

Perceptions of chief clinical information officers on the state of electronic health records systems interoperability in NHS England: a qualitative interview study.

BACKGROUND: In the era of electronic health records (EHR), the ability to share clinical data is a key facilitator of healthcare delivery. Since the introduction of EHRs, this aspect has been extensively studied from the perspective of healthcare providers. Less often explored are the day-to-day challenges surrounding the procurement, deployment, maintenance, and use of interoperable EHR systems, from the perspective of healthcare administrators, such as chief clinical information officers (CCIOs). OBJECTIVE: Our study aims to capture the perceptions of CCIOs on the current state of EHR interoperability in the NHS, its impact on patient safety, the perceived facilitators and barriers to improving EHR interoperability, and what the future of EHR development in the NHS may entail. METHODS: Semi-structured interviews were conducted between November 2020 - October 2021. Convenience sampling was employed to recruit NHS England CCIOs. Interviews were digitally recorded and transcribed verbatim. A thematic analysis was performed by two independent researchers to identify emerging themes. RESULTS: Fifteen CCIOs participated in the study. Participants reported that limited EHR interoperability contributed to the inability to easily access and transfer data into a unified source, thus resulting in data fragmentation. The resulting lack of clarity on patients' health status negatively impacts patient safety through suboptimal care coordination, duplication of efforts, and more defensive practice. Facilitators to improving interoperability included the recognition of the need by clinicians, patient expectations, and the inherent centralised nature of the NHS. Barriers included systems usability difficulties, and institutional, data management, and financial-related challenges. Looking ahead, participants acknowledged that realising that vision across the NHS would require a renewed focus on mandating data standards, user-centred design, greater patient involvement, and encouraging inter-organisational collaboration. CONCLUSION: Tackling poor interoperability will require solutions both at the technical level and in the wider policy context. This will involve demanding interoperability functionalities from the outset in procurement contracts, fostering greater inter-organisation cooperation on implementation strategies, and encouraging systems vendors to prioritise interoperability in their products. Only by comprehensively addressing these challenges would the full potential promised by the use of fully interoperable EHRs be realised.

Evaluating the impact of a pulse oximetry remote monitoring programme on mortality and healthcare utilisation in patients with COVID-19 assessed in emergency departments in England: a retrospective matched cohort study.

BACKGROUND: To identify the impact of enrolment onto a national pulse oximetry remote monitoring programme for COVID-19 (COVID-19 Oximetry @home; CO@h) on health service use and mortality in patients attending Emergency Departments (EDs). METHODS: We conducted a retrospective matched cohort study of patients enrolled onto the CO@h pathway from EDs in England. We included all patients with a positive COVID-19 test from 1 October 2020 to 3 May 2021 who attended ED from 3 days before to 10 days after the date of the test. All patients who were admitted or died on the same or following day to the first ED attendance within the time window were excluded. In the primary analysis, participants enrolled onto CO@h were matched using demographic and clinical criteria to participants who were not enrolled. Five outcome measures were examined within 28 days of first ED attendance: (1) Death from any cause; (2) Any subsequent ED attendance; (3) Any emergency hospital admission; (4) Critical care admission; and (5) Length of stay. RESULTS: 15 621 participants were included in the primary analysis, of whom 639 were enrolled onto CO@h and 14 982 were controls. Odds of death were 52% lower in those enrolled (95% CI 7% to 75%) compared with those not enrolled onto CO@h. Odds of any ED attendance or admission were 37% (95% CI 16% to 63%) and 59% (95% CI 32% to 91%) higher, respectively, in those enrolled. Of those admitted, those enrolled had 53% (95% CI 7% to 76%) lower odds of critical care admission. There was no significant impact on length of stay. CONCLUSIONS: These findings indicate that for patients assessed in ED, pulse oximetry remote monitoring may be a clinically effective and safe model for early detection of hypoxia and escalation. However, possible selection biases might limit the generalisability to other populations.

The use of clinical photography to aid in the triage of ENT patient referrals.

Waiting lists for Ear, Nose and Throat (ENT) outpatient appointments are currently the longest that they have ever been. The Aneurin Bevan University Health Board has adopted a unique Clinical Photography ENT triage service to tackle this. General Practitioner referrals are triaged by ENT consultants, to identify those patients in whom otoscopic imaging could be used to detect a serious otological condition or to enable virtual management. They are triaged to Clinical Photography, to undergo digital imaging which is reviewed in a virtual clinic alongside the initial referral. 72 patients have completed the pathway, with 51.3% discharged without requirement for face-to-face consultant appointment. 9.7% were upgraded to urgent or 2 week waits. This intervention is predicted to help identify patients on the waiting list with potentially serious disease so that they do not wait excessively, and to reduce waiting times for outpatient appointments in ENT.

A picture of health: determining the core population served by an urban NHS hospital trust and understanding the key health needs.

BACKGROUND: NHS hospitals do not have clearly defined geographic populations to whom they provide care, with patients able to attend any hospital. Identifying a core population for a hospital trust, particularly those in urban areas where there are multiple providers and high population churn, is essential to understanding local key health needs especially given the move to integrated care systems. This can enable effective planning and delivery of preventive interventions and community engagement, rather than simply treating those presenting to services. In this article we describe a practical method for identifying a hospital's catchment population based on where potential patients are most likely to reside, and describe that population's size, demographic and social profile, and the key health needs. METHODS: A 30% proportional flow method was used to identify a catchment population using an acute hospital trust in West London as an example. Records of all hospital attendances between 1st April 2017 and 31st March 2018 were analysed using Hospital Episode Statistics. Any Lower Layer Super Output Areas where 30% or more of residents who attended any hospital for care did so at the example trust were assigned to the catchment area. Publicly available local and national datasets were then applied to identify and describe the population's key health needs. RESULTS: A catchment comprising 617,709 people, of an equal gender-split (50.4% male) and predominantly working age (15 to 64 years) population was identified. Thirty nine point six percent of residents identified as being from Black and Minority Ethnic (BAME) groups, a similar proportion that reported being born abroad, with over 85 languages spoken. Health indicators were estimated, including: a healthy life expectancy difference of over twenty years; bowel cancer screening coverage of 48.8%; chlamydia diagnosis rates of 2,136 per 100,000; prevalence of visible dental decay among five-year-olds of 27.9%. CONCLUSIONS: We define a blueprint by which a catchment can be defined for a hospital trust and demonstrate the value a hospital-view of the local population could provide in understanding local health needs and enabling population-level health improvement interventions. While an individual approach allows tailoring to local context and need, there could be an efficiency saving were such public health information made routinely and regularly available for every NHS hospital.

The Impact of Electronic Health Record Interoperability on Safety and Quality of Care in High-Income Countries: Systematic Review.

BACKGROUND: Electronic health records (EHRs) and poor system interoperability are well-known issues in the use of health information technologies in most high-income countries worldwide. Despite the abundance of literature exploring their relationship, their practical implications on patient safety and quality of care remain unclear. OBJECTIVE: This study aimed to examine how EHR interoperability affects patient safety, or other dimensions of care quality, in high-income health care settings. METHODS: A systematic search was conducted using 4 web-based medical journal repositories and grey literature sources. The publications included were published in English between 2010 and 2022, pertaining to EHR use, interoperability, and patient safety or care quality in high-income settings. Screening was completed by 3 researchers in accordance with the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines. Risk of bias assessments were performed using the Risk of Bias in Non-randomized Studies of Interventions and the Cochrane Risk of Bias 2 tools. The findings were presented as a narrative synthesis and mapped based on the Institute of Medicine's framework for health care quality. RESULTS: A total of 12 studies met the inclusion criteria to be included in our review. The findings were categorized into 6 common outcome measure categories: patient safety events, medication safety, data accuracy and errors, care effectiveness, productivity, and cost savings. EHR interoperability positively influenced medication safety, reduced patient safety events, and reduced costs. Improvements in time saving and clinical workflow are mixed. However, true measures of effect are difficult to determine with certainty because of the heterogeneity in the outcome measures used and notable variation in study quality. CONCLUSIONS: The benefits of EHR interoperability on the quality and safety of care remain unclear and reflect extensive heterogeneity in the interventions, designs, and outcome measures used. The establishment of common health information technology research outcome measures would support higher-quality research on the topic. Future research efforts should focus on both the positive and negative impacts of interoperable EHR interventions and explore patient perspectives, given the growing trend for patient involvement and stewardship over their own electronic clinical data. TRIAL REGISTRATION: PROSPERO CRD42020209285; https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=209285. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): RR2-10.1136/bmjopen-2020-044941.

Population-level impact of a pulse oximetry remote monitoring programme on mortality and healthcare utilisation in the people with COVID-19 in England: a national analysis using a stepped wedge design.

BACKGROUND: To identify the population-level impact of a national pulse oximetry remote monitoring programme for COVID-19 (COVID Oximetry @home (CO@h)) in England on mortality and health service use. METHODS: We conducted a retrospective cohort study using a stepped wedge pre-implementation and post-implementation design, including all 106 Clinical Commissioning Groups (CCGs) in England implementing a local CO@h programme. All symptomatic people with a positive COVID-19 PCR test result from 1 October 2020 to 3 May 2021, and who were aged ≥65 years or identified as clinically extremely vulnerable were included. Care home residents were excluded. A pre-intervention period before implementation of the CO@h programme in each CCG was compared with a post-intervention period after implementation. Five outcome measures within 28 days of a positive COVID-19 test: (i) death from any cause; (ii) any ED attendance; (iii) any emergency hospital admission; (iv) critical care admission and (v) total length of hospital stay. RESULTS: 217 650 people were eligible and included in the analysis. Total enrolment onto the programme was low, with enrolment data received for only 5527 (2.5%) of the eligible population. The period of implementation of the programme was not associated with mortality or length of hospital stay. The period of implementation was associated with increased health service utilisation with a 12% increase in the odds of ED attendance (95% CI: 6% to 18%) and emergency hospital admission (95% CI: 5% to 20%) and a 24% increase in the odds of critical care admission in those admitted (95% CI: 5% to 47%). In a secondary analysis of CO@h sites with at least 10% or 20% of eligible people enrolled, there was no significant association with any outcome measure. CONCLUSION: At a population level, there was no association with mortality before and after the implementation period of the CO@h programme, and small increases in health service utilisation were observed. However, lower than expected enrolment is likely to have diluted the effects of the programme at a population level.

Impact of the COVID-19 Pandemic on Emergency Adult Surgical Patients and Surgical Services: An International Multi-center Cohort Study and Department Survey.

OBJECTIVES: The PREDICT study aimed to determine how the COVID-19 pandemic affected surgical services and surgical patients and to identify predictors of outcomes in this cohort. BACKGROUND: High mortality rates were reported for surgical patients with COVID-19 in the early stages of the pandemic. However, the indirect impact of the pandemic on this cohort is not understood, and risk predictors are yet to be identified. METHODS: PREDICT is an international longitudinal cohort study comprising surgical patients presenting to hospital between March and August 2020, conducted alongside a survey of staff redeployment and departmental restructuring. A subgroup analysis of 3176 adult emergency patients, recruited by 55 teams across 18 countries is presented. RESULTS: Among adult emergency surgical patients, all-cause in-hospital mortality (IHM) was 3.6%, compared to 15.5% for those with COVID-19. However, only 14.1% received a COVID-19 test on admission in March, increasing to 76.5% by July.Higher Clinical Frailty Scale scores (CFS >7 aOR 18.87), ASA grade above 2 (aOR 4.29), and COVID-19 infection (aOR 5.12) were independently associated with significantly increased IHM.The peak months of the first wave were independently associated with significantly higher IHM (March aOR 4.34; April aOR 4.25; May aOR 3.97), compared to non-peak months.During the study, UK operating theatre capacity decreased by a mean of 63.6% with a concomitant 27.3% reduction in surgical staffing. CONCLUSION: The first wave of the COVID-19 pandemic significantly impacted surgical patients, both directly through co-morbid infection and indirectly as shown by increasing mortality in peak months, irrespective of COVID-19 status.Higher CFS scores and ASA grades strongly predict outcomes in surgical patients and are an important risk assessment tool during the pandemic.