Atrial fibrillation inpatient management patterns and clinical outcomes during the conflict in Syria: An observational cohort study.

BACKGROUND: Atrial fibrillation (AF) is the most common sustained arrhythmia worldwide. However, there is no data on AF inpatient management strategies and clinical outcomes in Syria. OBJECTIVES: The study aims were to review the inpatient management of patients with AF and assess cardiovascular (CV) mortality in a tertiary cardiology centre in Latakia, Syria. METHODS: A single-centre retrospective observational cohort study was conducted at Tishreen's University Hospital, Latakia, Syria, from June 2021 to June 2023. Patients ≥16 years of age presenting and being treated for AF as the primary diagnosis with or without a thromboembolic event were included. Medical records were examined for patients' demographics, laboratory results, treatment plans and inpatient details. Studied outcomes include inpatient all-cause and CV mortality, ischemic and bleeding events, and conversion to sinus rhythm (SR). RESULTS: The study included 596 patients. The median age was 58, and 61% were males. 121 patients (20.3%) were known to have AF. A rhythm control strategy was pursued in 39% of patients. Ischemic and bleeding events occurred in 62 (11%) and 12 (2%), respectively. CV and all-cause mortality occurred in 28 (4.7%) and 31 patients (5%), respectively. The presence of valvular heart disease (VHD) (adjusted odds ratio (aOR) = 9.1, 95% confidence interval (CI): 1.7 to 55.1, p < .001), thyroid disease (aOR: 9.7, 95% CI = 1.2 to 91.6, p < .001) and chronic obstructive pulmonary disease (COPD) (aOR: 82, 95% CI: 12.7 to 71, p < .001) were independent risk factors of increased CV inpatient mortality. CONCLUSION: Syrian inpatients admitted with AF in Latakia are relatively younger than those in other countries. Active thyroid disease, COPD and VHD were independent risk factors of inpatient CV mortality with AF.

Artificial intelligence for ventricular arrhythmia capability using ambulatory electrocardiograms.

Aims: European and American clinical guidelines for implantable cardioverter defibrillators are insufficiently accurate for ventricular arrhythmia (VA) risk stratification, leading to significant morbidity and mortality. Artificial intelligence offers a novel risk stratification lens through which VA capability can be determined from the electrocardiogram (ECG) in normal cardiac rhythm. The aim of this study was to develop and test a deep neural network for VA risk stratification using routinely collected ambulatory ECGs. Methods and results: A multicentre case-control study was undertaken to assess VA-ResNet-50, our open source ResNet-50-based deep neural network. VA-ResNet-50 was designed to read pyramid samples of three-lead 24 h ambulatory ECGs to decide whether a heart is capable of VA based on the ECG alone. Consecutive adults with VA from East Midlands, UK, who had ambulatory ECGs as part of their NHS care between 2014 and 2022 were recruited and compared with all comer ambulatory electrograms without VA. Of 270 patients, 159 heterogeneous patients had a composite VA outcome. The mean time difference between the ECG and VA was 1.6 years (⅓ ambulatory ECG before VA). The deep neural network was able to classify ECGs for VA capability with an accuracy of 0.76 (95% confidence interval 0.66-0.87), F1 score of 0.79 (0.67-0.90), area under the receiver operator curve of 0.8 (0.67-0.91), and relative risk of 2.87 (1.41-5.81). Conclusion: Ambulatory ECGs confer risk signals for VA risk stratification when analysed using VA-ResNet-50. Pyramid sampling from the ambulatory ECGs is hypothesized to capture autonomic activity. We encourage groups to build on this open-source model. Question: Can artificial intelligence (AI) be used to predict whether a person is at risk of a lethal heart rhythm, based solely on an electrocardiogram (an electrical heart tracing)? Findings: In a study of 270 adults (of which 159 had lethal arrhythmias), the AI was correct in 4 out of every 5 cases. If the AI said a person was at risk, the risk of lethal event was three times higher than normal adults. Meaning: In this study, the AI performed better than current medical guidelines. The AI was able to accurately determine the risk of lethal arrhythmia from standard heart tracings for 80% of cases over a year away-a conceptual shift in what an AI model can see and predict. This method shows promise in better allocating implantable shock box pacemakers (implantable cardioverter defibrillators) that save lives.

ECGVEDNET: A Variational Encoder-Decoder Network for ECG Delineation in Morphology Variant ECGs.

Electrocardiogram (ECG) delineation to identify the fiducial points of ECG segments, plays an important role in cardiovascular diagnosis and care. Whilst deep delineation frameworks have been deployed within the literature, several factors still hinder their development: (a) data availability: the capacity of deep learning models to generalise is limited by the amount of available data; (b) morphology variations: ECG complexes vary, even within the same person, which degrades the performance of conventional deep learning models. To address these concerns, we present a large-scale 12-leads ECG dataset, ICDIRS, to train and evaluate a novel deep delineation model-ECGVEDNET. ICDIRS is a large-scale ECG dataset with 156,145 QRS onset annotations and 156,145 T peak annotations. ECGVEDNET is a novel variational encoder-decoder network designed to address morphology variations. In ECGVEDNET, we construct a well-regularized latent space, in which the latent features of ECG follow a regular distribution and present smaller morphology variations than in the raw data space. Finally, a transfer learning framework is proposed to transfer the knowledge learned on ICDIRS to smaller datasets. On ICDIRS, ECGVEDNET achieves accuracy of 86.28%/88.31% within 5/10 ms tolerance for QRS onset and accuracy of 89.94%/91.16% within 5/10 ms tolerance for T peak. On QTDB, the average time errors computed for QRS onset and T peak are -1.86 ± 8.02 ms and -0.50 ± 12.96 ms, respectively, achieving state-of-the-art performances on both large and small-scale datasets. We will release the source code and the pre-trained model on ICDIRS once accepted.

Can clinician's risk assessments distinguish those who disclose suicidal ideation from those who attempt suicide?

Participants were 85 individuals who made suicide attempts within two years of their Improving Access to Psychological Therapies (IAPT) assessment, identified using record linkage. Two comparison groups, non-suicidal controls (n = 1416) and (ideators, n = 743) were compared on variables extracted from the standardized IAPT risk assessment interview. Disclosure of a historical suicide attempt or non-suicidal self-injury (NSSI) distinguished those making an attempt from those with suicidal ideation only, but suicidal intent did not. A third of the participants concealed a historical suicide attempt. The IAPT Phobia Scale classified 49.30% of attempters with 100% specificity. The IAPT Phobia Scale may have clinical value in assessing risk but requires validation. Past suicide attempt and NSSI have better clinical risk assessment utility than current suicidal ideation intensity. Risk assessment relying on disclosure is likely to be flawed and risks support being withheld from those assumed to be at lower risk.

Digitally enabled acute care for atrial fibrillation: conception, feasibility and early outcomes of an AF virtual ward.

BACKGROUND: Atrial fibrillation (AF) represents a growing healthcare challenge, mainly driven by acute hospitalisations. Virtual wards could be the way forward to manage acute AF patients through remote monitoring, especially with the rise in global access to digital telecommunication and the growing acceptance of telemedicine post-COVID-19. METHODS: An AF virtual ward was implemented as a proof-of-concept care model. Patients presenting acutely with AF or atrial flutter and rapid ventricular response to the hospital were onboarded to the virtual ward and managed at home through remote ECG-monitoring and 'virtual' ward rounds, after being given access to a single-lead ECG device, a blood pressure monitor and pulse oximeter with instructions to record daily ECGs, blood pressure, oxygen saturations and to complete an online AF symptom questionnaire. Data were uploaded to a digital platform for daily review by the clinical team. Primary outcomes included admission avoidance, readmission avoidance and patient satisfaction. Safety outcomes included unplanned discharge from the virtual ward, cardiovascular mortality and all-cause mortality. RESULTS: There were 50 admissions to the virtual ward between January and August 2022. Twenty-four of them avoided initial hospital admission as patients were directly enrolled to the virtual ward from outpatient settings. A further 25 readmissions were appropriately prevented during virtual surveillance. Patient satisfaction questionnaires yielded 100% positive responses among participants. There were three unplanned discharges from the virtual ward requiring hospitalisation. Mean heart rate on admission to the virtual ward and discharge was 122±26 and 82±27 bpm respectively. A rhythm control strategy was pursued in 82% (n=41) and 20% (n=10) required 3 or more remote pharmacological interventions. CONCLUSION: This is a first real-world experience of an AF virtual ward that heralds a potential means for reducing AF hospitalisations and the associated financial burden, without compromising on patients' care or safety.

Endovascular revascularization strategies for aortoiliac and femoropopliteal artery disease: a meta-analysis.

AIMS: Optimal endovascular management of intermittent claudication (IC) remains disputed. This systematic review and meta-analysis compares efficacy and safety outcomes for balloon angioplasty (BA), bare-metal stents (BMS), drug-coated balloons (DCB), drug-eluting stents (DES), covered stents, and atherectomy. METHODS AND RESULTS: Electronic databases were searched for randomized, controlled trials (RCT) from inception through November 2021. Efficacy outcomes were primary patency, target-lesion revascularization (TLR), and quality-of-life (QoL). Safety endpoints were all-cause mortality and major amputation. Outcomes were evaluated at short-term (<1 year), mid-term (1-2 years), and long-term (≥2 years) follow-up. The study was registered on PROSPERO (CRD42021292639). Fifty-one RCTs enrolling 8430 patients/lesions were included. In femoropopliteal disease of low-to-intermediate complexity, DCBs were associated with higher likelihood of primary patency [short-term: odds ratio (OR) 3.21, 95% confidence interval (CI) 2.44-4.24; long-term: OR 2.47, 95% CI 1.93-3.16], lower TLR (short-term: OR 0.33, 95% CI 0.22-0.49; long-term: OR 0.42, 95% CI 0.29-0.60) and similar all-cause mortality risk, compared with BA. Primary stenting using BMS was associated with improved short-to-mid-term patency and TLR, but similar long-term efficacy compared with provisional stenting. Mid-term patency (OR 1.64, 95% CI 0.89-3.03) and TLR (OR 0.50, 95% CI 0.22-1.11) estimates were comparable for DES vs. BMS. Atherectomy, used independently or adjunctively, was not associated with efficacy benefits compared with drug-coated and uncoated angioplasty, or stenting approaches. Paucity and heterogeneity of data precluded pooled analysis for aortoiliac disease and QoL endpoints. CONCLUSION: Certain devices may provide benefits in femoropopliteal disease, but comparative data in aortoiliac arteries is lacking. Gaps in evidence quantity and quality impede identification of the optimal endovascular approach to IC.

The importance of the interface for picosecond spin pumping in antiferromagnet-heavy metal heterostructures.

Interfaces in heavy metal (HM) - antiferromagnetic insulator (AFI) heterostructures have recently become highly investigated and debated systems in the effort to create spintronic devices that function at terahertz frequencies. Such heterostructures have great technological potential because AFIs can generate sub-picosecond spin currents which the HMs can convert into charge signals. In this work we demonstrate an optically induced picosecond spin transfer at the interface between AFIs and Pt using time-domain THz emission spectroscopy. We select two antiferromagnets in the same family of fluoride cubic perovskites, KCoF3 and KNiF3, whose magnon frequencies at the centre of the Brillouin zone differ by an order of magnitude. By studying their behaviour with temperature, we correlate changes in the spin transfer efficiency across the interface to the opening of a gap in the magnon density of states below the Néel temperature. Our observations are reproduced in a model based on the spin exchange between the localized electrons in the antiferromagnet and the free electrons in Pt. Through this comparative study of selected materials, we are able to shine light on the microscopy of spin transfer at picosecond timescales between antiferromagnets and heavy metals and identify a key figure of merit for its efficiency: the magnon gap. Our results are important for progressing in the fundamental understanding of the highly discussed physics of the HM/AFI interfaces, which is the necessary cornerstone for the designing of femtosecond antiferromagnetic spintronics devices with optimized characteristics.

COVID-19 inpatient treatments and outcomes during the conflict in Syria: an observational cohort study.

Background: During the COVID-19 pandemic, countries undergoing conflict have faced difficulties in mounting an effective health response. This observational cohort study describes the treatments and outcomes for inpatients with COVID-19 in the Syrian city of Latakia. Design and methods: A single-centre observational cohort study was conducted at Tishreen University Hospital, involving all patients over 18 admitted between October 1 and December 31, 2021 with a positive RT-PCR test for SARS-CoV-2. Clinical features, investigations, treatments, and outcomes were reported. Results: In total, 149 patients fitted the study criteria. Only one patient was double vaccinated against COVID-19. Oxygen supplementation was required in 87% (n = 130) of participants. Invasive mechanical ventilation was required in 4% (n = 5). Therapeutic anticoagulation was administered in 97.3% (n = 144). Intravenous dexamethasone was received by 97.3% (n = 145) of participants. All patients received empiric antibiotic treatment. In-hospital mortality was 48.4% (n = 72), while only 40.9% (n = 61) were discharged during the study period. Conclusion: The pandemic has placed a compromised Syrian healthcare system under more significant strain. This requires urgent international relief efforts from health agencies in order to aid the pandemic response.

Uptake and effect of universal test-and-treat on twelve months retention and initial virologic suppression in routine HIV program in Kenya.

Early combination antiretroviral therapy (cART), as recommended in WHO's universal test-and-treat (UTT) policy, is associated with improved linkage to care, retention, and virologic suppression in controlled studies. We aimed to describe UTT uptake and effect on twelve-month non-retention and initial virologic non-suppression (VnS) among HIV infected adults starting cART in routine HIV program in Kenya. Individual-level HIV service delivery data from 38 health facilities, each representing 38 of the 47 counties in Kenya were analysed. Adults (>15 years) initiating cART between the second-half of 2015 (2015HY2) and the first-half of 2018 (2018HY1) were followed up for twelve months. UTT was defined based on time from an HIV diagnosis to cART initiation and was categorized as same-day, 1-14 days, 15-90 days, and 91+ days. Non-retention was defined as individuals lost-to-follow-up or reported dead by the end of the follow up period. Initial VnS was defined based on the first available viral load test with >400 copies/ml. Hierarchical mixed-effects survival and generalised linear regression models were used to assess the effect of UTT on non-retention and VnS, respectively. Of 8592 individuals analysed, majority (n = 5864 [68.2%]) were female. Same-day HIV diagnosis and cART initiation increased from 15.3% (2015HY2) to 52.2% (2018HY1). The overall non-retention rate was 2.8 (95% CI: 2.6-2.9) per 100 person-months. When compared to individuals initiated cART 91+ days after a HIV diagnosis, those initiated cART on the same day of a HIV diagnosis had the highest rate of non-retention (same-day vs. 91+ days; aHR, 1.7 [95% CI: 1.5-2.0], p<0.001). Of those included in the analysis, 5986 (69.6%) had a first viral load test done at a median of 6.3 (IQR, 5.6-7.6) months after cART initiation. Of these, 835 (13.9%) had VnS. There was no association between UTT and VnS (same-day vs. 91+ days; aRR, 1.0 [95% CI: 0.9-1.2], p = 0.664). Our findings demonstrate substantial uptake of the UTT policy but poor twelve-month retention and lack of an association with initial VnS from routine HIV settings in Kenya. These findings warrant consideration for multi-pronged program interventions alongside UTT policy for maximum intended benefits in Kenya.

Machine learning in sudden cardiac death risk prediction: a systematic review.

AIMS: Most patients who receive implantable cardioverter defibrillators (ICDs) for primary prevention do not receive therapy during the lifespan of the ICD, whilst up to 50% of sudden cardiac death (SCD) occur in individuals who are considered low risk by conventional criteria. Machine learning offers a novel approach to risk stratification for ICD assignment. METHODS AND RESULTS: Systematic search was performed in MEDLINE, Embase, Emcare, CINAHL, Cochrane Library, OpenGrey, MedrXiv, arXiv, Scopus, and Web of Science. Studies modelling SCD risk prediction within days to years using machine learning were eligible for inclusion. Transparency and quality of reporting (TRIPOD) and risk of bias (PROBAST) were assessed. A total of 4356 studies were screened with 11 meeting the inclusion criteria with heterogeneous populations, methods, and outcome measures preventing meta-analysis. The study size ranged from 122 to 124 097 participants. Input data sources included demographic, clinical, electrocardiogram, electrophysiological, imaging, and genetic data ranging from 4 to 72 variables per model. The most common outcome metric reported was the area under the receiver operator characteristic (n = 7) ranging between 0.71 and 0.96. In six studies comparing machine learning models and regression, machine learning improved performance in five. No studies adhered to a reporting standard. Five of the papers were at high risk of bias. CONCLUSION: Machine learning for SCD prediction has been under-applied and incorrectly implemented but is ripe for future investigation. It may have some incremental utility in predicting SCD over traditional models. The development of reporting standards for machine learning is required to improve the quality of evidence reporting in the field.

What distinguishes high and low-lethality suicide attempts in older adults? A systematic review and meta-analysis.

Those making suicide attempts with highly lethal medical consequences are arguably the best proxy for those who die by suicide and represent a qualitatively different population from those making lower lethality attempts. Different factors influence the likelihood of a suicide attempt occurring and the lethality of that attempt. Both are important dimensions of risk. Older adults represent a distinct group in suicide research with unique risk factors that influence the lethality of their suicide attempts. This systematic review and meta-analysis summarises factors distinguishing those making high and low-lethality suicide attempts in older adulthood. Databases PsycINFO, PubMed (MEDLINE), Embase and CINAHL were systematically searched with seven of 1182 unique records included. Random effects meta-analyses were conducted on 18 variables in addition to a narrative synthesis regarding executive function. Only increased suicidal intent and planning meaningfully distinguished high from low-lethality attempters in meta-analyses. A large effect size was additionally observed for white ethnicity. Diminished alcohol use disorder prevalence and depression severity, and greater cognitive impairment, may be associated with high lethality attempters but further research is needed. Age and gender were not associated with lethality, contrary to adult populations. A narrative synthesis of studies exploring differences in executive functioning suggested high-lethality attempters were less likely to impulsively act on suicidal urges, allowing them to better plan suicide attempts that are more lethal, and are less likely to alter suicidal plans. Key limitations were that meta-analyses were underpowered to detect small effect sizes, and samples were largely white and limited to the USA.

Effect of serial awake prone positioning on oxygenation in patients admitted to intensive care with COVID-19.

INTRODUCTION: Awake prone positioning (APP) might benefit patients with COVID-19 by improving oxygenation, but it is unknown whether this improvement can be sustained with serial proning episodes. METHODS: We conducted a retrospective review of adults with COVID-19 admitted to one intensive care unit, in those who underwent APP and controls. Patients in both groups had type 1 respiratory failure requiring oxygen (but not initially intubated), confirmed SARS-CoV-2 PCR by nasopharyngeal swab and findings of multifocal ground-glass opacities on imaging. For the APP group, serial SpO2/FiO2 measurements were recorded after each proning episode. RESULTS: Of 77 patients admitted, 50 (65%) were excluded because they had already been intubated. Another 7 (9%) had undergone APP prior to admission. Of the remaining 20, 10 underwent APP and 10 were controls. Patients in both groups had similar demographics, subsequent intubation and survival. Of those who underwent APP, SpO2/FiO2 was most likely to increase after the first episode (before median: 152, IQR 135-185; after: median 192, IQR 156-234, p=0.04). Half of participants (5) in the APP group were unable to tolerate more than two APP episodes. CONCLUSIONS: Most patients with COVID-19 admitted to the intensive care are not suitable for APP. Of those who are, many cannot tolerate more than two episodes. Improvements in SpO2/FiO2 secondary to APP are transient and most likely in the first episode. Our findings may explain why other studies have failed to show improvements in mortality from APP despite improvements in oxygenation.

Treatment-adjusted prevalence to assess HIV testing programmes.

Scale-up of human immunodeficiency virus (HIV) testing and antiretroviral therapy (ART) for people living with HIV has been increasing in sub-Saharan Africa. As a result, areas with high HIV prevalence are finding a declining proportion of people testing positive in their national testing programmes. In eastern and southern Africa, where there are settings with adult HIV prevalence of 12% and above, the positivity from national HIV testing services has dropped to below 5%. Identifying those in need of ART is therefore becoming more costly for national HIV programmes. Annual target-setting assumes that national testing positivity rates approximate that of population prevalence. This assumption has generated an increased focus on testing approaches which achieve higher rates of HIV positivity. This trend is a departure from the provider-initiated testing and counselling strategy used early in the global HIV response. We discuss a new indicator, treatment-adjusted prevalence, that countries can use as a practical benchmark for estimating the expected adult positivity in a testing programme when accounting for both national HIV prevalence and ART coverage. The indicator is calculated by removing those people receiving ART from the numerator and denominator of HIV prevalence. Treatment-adjusted prevalence can be readily estimated from existing programme data and population estimates, and in 2019, was added to the World Health Organization guidelines for HIV testing and strategic information. Using country examples from Kenya, Malawi, South Sudan and Zimbabwe we illustrate how to apply this indicator and we discuss the potential public health implications of its use from the national to facility level.

Le dépistage du virus de l'immunodéficience humaine (VIH) et le traitement antirétroviral (TAR) pour les personnes vivant avec le VIH ont connu un véritable essor en Afrique subsaharienne. Par conséquent, les régions touchées par une forte prévalence du VIH détectent un pourcentage moins élevé de personnes testées positives dans leurs programmes de dépistage nationaux. En Afrique orientale et australe, là où certains endroits affichent une prévalence du VIH chez l'adulte égale ou supérieure à 12%, le taux de positivité des services de dépistage nationaux est passé sous la barre des 5%. Identifier les personnes nécessitant un TAR devient donc plus coûteux pour les programmes nationaux consacrés au VIH. Pour définir les objectifs annuels, on part du principe que les taux de positivité nationaux se rapprochent du taux de prévalence au sein de la population. Cette supposition a orienté les démarches vers des méthodes de dépistage permettant d'obtenir des taux de positivité plus élevés; une tendance qui s'écarte de la stratégie des services de dépistage et de conseil à l'initiative des prestataires, utilisée à l'aube de la lutte mondiale contre le VIH. Dans le présent document, nous nous intéressons à un nouvel indicateur, la prévalence ajustée sur le traitement. Cet indicateur peut servir de référence concrète pour les pays qui souhaitent évaluer le taux de positivité attendu chez l'adulte dans un programme de dépistage, en tenant compte de la prévalence du VIH au niveau national ainsi que de la portée du TAR. Le calcul consiste à enlever les personnes recevant un TAR du numérateur et du dénominateur de la prévalence du VIH. La prévalence ajustée sur le traitement peut aisément être déterminée en fonction des données de programme et estimations de population existantes. En 2019, elle a également été ajoutée aux lignes directrices de l'Organisation mondiale de la Santé pour l'information stratégique et le dépistage du VIH. En nous inspirant d'exemples issus du Kenya, du Malawi, du Soudan du Sud et du Zimbabwe, nous expliquons comment employer cet indicateur et abordons les potentielles implications liées à son utilisation en matière de santé publique, en partant du niveau national jusqu'aux établissements.

La ampliación de las pruebas de detección del virus de la inmunodeficiencia humana (VIH) y del tratamiento antirretrovírico (TAR) para las personas infectadas por el VIH ha aumentado en el África subsahariana. En consecuencia, el porcentaje de personas que dan positivo en las pruebas de detección del VIH en los programas nacionales está disminuyendo en las zonas con alta prevalencia del virus. En África meridional y oriental, donde hay entornos con una prevalencia del VIH en adultos del 12 % o superior, la tasa de positividad de los servicios nacionales de pruebas de detección del VIH ha descendido a menos del 5 %. Por lo tanto, la identificación de las personas que necesitan TAR es cada vez más costosa para los programas nacionales de VIH. El establecimiento de objetivos anuales supone que las tasas de positividad de las pruebas nacionales se aproximan a las de la prevalencia de la población. Esta suposición ha generado una mayor atención a los enfoques de las pruebas que logran tasas más altas de positividad del VIH. Esta tendencia se aleja de la estrategia del asesoramiento y las pruebas que iniciaron los proveedores y que se utilizó al principio de la respuesta mundial al VIH. Se analiza un nuevo indicador, la prevalencia ajustada según el tratamiento, que los países pueden emplear como punto de referencia práctico para estimar la tasa de positividad esperada en adultos en un programa de pruebas de detección cuando se tiene en cuenta tanto la prevalencia nacional del VIH como la cobertura del TAR. El indicador se calcula eliminando del numerador y el denominador de la prevalencia del VIH a las personas que reciben TAR. La prevalencia ajustada según el tratamiento se puede estimar con facilidad a partir de los datos de los programas existentes y de las estimaciones de población, además, en 2019, se incluyó en las directrices de la Organización Mundial de la Salud para las pruebas de detección del VIH y en la información estratégica. A través de ejemplos de países como Kenia, Malaui, Sudán meridional y Zimbabue, se demuestra cómo aplicar este indicador y se discuten las posibles implicaciones para la salud pública de su uso desde el nivel nacional hasta el de los centros.

Accelerating the Evolution of Severe Acute Respiratory Syndrome Coronavirus 2: A Risk of Combining Dexamethasone and Tocilizumab for Severe Coronavirus Disease 2019.

Emerging data from open-label randomized trials without placebo controls suggest potential mortality benefits for combining corticosteroids with the interleukin 6 receptor antagonist tocilizumab in severe coronavirus disease 2019. Conversely, dual immunomodulation may weaken antiviral responses and delay viral clearance, allowing severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) to expand its population and accrue genetic diversity within individual hosts. Generating a pool of hosts with genetically diverse viral populations while introducing new selective pressures in the form of vaccination-induced immunity could accelerate the process of antigenic drift in SARS-CoV-2. However, clinical trials to date have largely disregarded viral outcomes, and data on viral kinetics in response to immunomodulation are scarce. Coadministration of antiviral agents with immunomodulation could serve as a potential strategy to aid viral clearance and reduce the risk of genetic diversification.

Electronic alerts for acute kidney injury across primary and secondary care.

PROBLEM: In 2009 the National Confidential Enquiry into Patient Outcome and Death suggested only 50% of patients with acute kidney injury (AKI) receive good standards of care. In response National Health Service (NHS) England mandated the use of electronic AKI alerts within secondary care. However, we recognised AKI is not just a secondary care problem, where primary care has a crucial role to play in prevention, early detection and management as well as post-AKI care. METHODS: AKI alerts were implemented in primary and secondary care services for a population of 480 000. Comparisons were made in AKI incidence, peak creatinine following AKI and renal recovery in the years before and after using Byar's approximation (95% CI). INTERVENTION: A complex quality improvement initiative was implemented based on the design and integration of an AKI alerting system within laboratory information management systems for primary and secondary care, with an affixed URL for clinicians to access a care bundle of AKI guidelines on safe prescribing, patient advice and early contact with nephrology. RESULTS: The intervention was associated with an 8% increase in creatinine testing (n=32 563). Hospital acquired AKI detection increased by 6%, while community acquired AKI detection increased by 3% and AKI stage 3 detected in primary care fell by 14%. The intervention overall had no effect on AKI severity but did improve follow-up testing and renal recovery. Importantly hospital AKI 3 recoveries improved by 22%. In a small number of AKI cases, the algorithm did not produce an alert resulting in a reduction in follow-up testing compared with preintervention levels. CONCLUSION: The introduction of AKI alerts in primary and secondary care, in conjunction with access to an AKI care bundle, was associated with higher rates of repeat blood sampling, AKI detection and renal recovery. Validating accuracy of alerts is required to avoid patient harm.

The new UK SARS-CoV-2 variant and lockdown - causes and consequences.

The new variant of concern (VOC), B.1.1.7, has a distinct set of mutations in nucleotides encoding the spike (S) protein on the surface of SARS-CoV-2. SARS-CoV-2 previously accumulated mutations at a much slower rate, of 1-2 per month; the sudden appearance of a large cluster of mutations was thought to be unusual. We now suspect that VOC may have arisen from immunosuppressed individuals who shed virus for longer periods. Epidemiological analyses estimate VOC to be more infectious; this is of most concern because these estimates were calculated during periods where many regions of the UK were in high social distancing restrictions. Therefore, the previous 'tiered' system implemented in the UK was ineffective at containing VOC. The most likely reason for this is that previous restrictions, no matter how strict, still allowed for gatherings in certain places. VOC also has implications for the national vaccination programme - a higher proportion of people will need to be vaccinated with a more infectious virus. Prolongation of the second dose of vaccines to increase vaccine uptake has understandably caused concern, but is based on sound immunological principles. There is now an urgent need to monitor the effect of new variants on vaccine efficacy - marking a new chapter in the global fight against COVID-19.

Enhanced Spin-Orbit Coupling in Heavy Metals via Molecular Coupling.

5d metals are used in electronics because of their high spin-orbit coupling (SOC) leading to efficient spin-electric conversion. When C60 is grown on a metal, the electronic structure is altered due to hybridization and charge transfer. In this work, we measure the spin Hall magnetoresistance for Pt/C60 and Ta/C60, finding that they are up to a factor of 6 higher than those for pristine metals, indicating a 20-60% increase in the spin Hall angle. At low fields of 1-30 mT, the presence of C60 increased the anisotropic magnetoresistance by up to 700%. Our measurements are supported by noncollinear density functional theory calculations, which predict a significant SOC enhancement by C60 that penetrates through the Pt layer, concomitant with trends in the magnetic moment of transport electrons acquired via SOC and symmetry breaking. The charge transfer and hybridization between the metal and C60 can be controlled by gating, so our results indicate the possibility of dynamically modifying the SOC of thin metals using molecular layers. This could be exploited in spin-transfer torque memories and pure spin current circuits.

The need for improved discharge criteria for hospitalised patients with COVID-19-implications for patients in long-term care facilities.

In the COVID-19 pandemic, patients who are older and residents of long-term care facilities (LTCF) are at greatest risk of worse clinical outcomes. We reviewed discharge criteria for hospitalised COVID-19 patients from 10 countries with the highest incidence of COVID-19 cases as of 26 July 2020. Five countries (Brazil, Mexico, Peru, Chile and Iran) had no discharge criteria; the remaining five (USA, India, Russia, South Africa and the UK) had discharge guidelines with large inter-country variability. India and Russia recommend discharge for a clinically recovered patient with two negative reverse transcription polymerase chain reaction (RT-PCR) tests 24 h apart; the USA offers either a symptom based strategy-clinical recovery and 10 days after symptom onset, or the same test-based strategy. The UK suggests that patients can be discharged when patients have clinically recovered; South Africa recommends discharge 14 days after symptom onset if clinically stable. We recommend a unified, simpler discharge criteria, based on current studies which suggest that most SARS-CoV-2 loses its infectivity by 10 days post-symptom onset. In asymptomatic cases, this can be taken as 10 days after the first positive PCR result. Additional days of isolation beyond this should be left to the discretion of individual clinician. This represents a practical compromise between unnecessarily prolonged admissions and returning highly infectious patients back to their care facilities, and is of particular importance in older patients discharged to LTCFs, residents of which may be at greatest risk of transmission and worse clinical outcomes.