Clinical Mortality in a Large COVID-19 Cohort: Observational Study.

BACKGROUND: Northwell Health, an integrated health system in New York, has treated more than 15,000 inpatients with COVID-19 at the US epicenter of the SARS-CoV-2 pandemic. OBJECTIVE: We describe the demographic characteristics of patients who died of COVID-19, observation of frequent rapid response team/cardiac arrest (RRT/CA) calls for non-intensive care unit (ICU) patients, and factors that contributed to RRT/CA calls. METHODS: A team of registered nurses reviewed the medical records of inpatients who tested positive for SARS-CoV-2 via polymerase chain reaction before or on admission and who died between March 13 (first Northwell Health inpatient expiration) and April 30, 2020, at 15 Northwell Health hospitals. The findings for these patients were abstracted into a database and statistically analyzed. RESULTS: Of 2634 patients who died of COVID-19, 1478 (56.1%) had oxygen saturation levels ≥90% on presentation and required no respiratory support. At least one RRT/CA was called on 1112/2634 patients (42.2%) at a non-ICU level of care. Before the RRT/CA call, the most recent oxygen saturation levels for 852/1112 (76.6%) of these non-ICU patients were at least 90%. At the time the RRT/CA was called, 479/1112 patients (43.1%) had an oxygen saturation of \u3c80%. CONCLUSIONS: This study represents one of the largest reviewed cohorts of mortality that also captures data in nonstructured fields. Approximately 50% of deaths occurred at a non-ICU level of care despite admission to the appropriate care setting with normal staffing. The data imply a sudden, unexpected deterioration in respiratory status requiring RRT/CA in a large number of non-ICU patients. Patients admitted at a non-ICU level of care suffered rapid clinical deterioration, often with a sudden decrease in oxygen saturation. These patients could benefit from additional monitoring (eg, continuous central oxygenation saturation), although this approach warrants further study

Fifteen minute consultation: Managing neonatal and childhood herpes encephalitis

Herpes simplex encephalitis (HSE) is the most common single cause of viral encephalitis in infants and children. Treated or untreated, it can be associated with considerable morbidity and mortality, and its presentation is usually insidious and non-specific. Prompt and careful investigation is important in order to establish the diagnosis so that treatment can be optimised. We address some common questions arising when diagnosing and treating presumed HSE throughout childhood

A One Health Framework for the Evaluation of Rabies Control Programmes: A Case Study from Colombo City, Sri Lanka

<div><p>Background</p><p>One Health addresses complex challenges to promote the health of all species and the environment by integrating relevant sciences at systems level. Its application to zoonotic diseases is recommended, but few coherent frameworks exist that combine approaches from multiple disciplines. Rabies requires an interdisciplinary approach for effective and efficient management.</p><p>Methodology/Principal Findings</p><p>A framework is proposed to assess the value of rabies interventions holistically. The economic assessment compares additional monetary and non-monetary costs and benefits of an intervention taking into account epidemiological, animal welfare, societal impact and cost data. It is complemented by an ethical assessment. The framework is applied to Colombo City, Sri Lanka, where modified dog rabies intervention measures were implemented in 2007. The two options included for analysis were the control measures in place until 2006 (“baseline scenario”) and the new comprehensive intervention measures (“intervention”) for a four-year duration. Differences in control cost; monetary human health costs after exposure; Disability-Adjusted Life Years (DALYs) lost due to human rabies deaths and the psychological burden following a bite; negative impact on animal welfare; epidemiological indicators; social acceptance of dogs; and ethical considerations were estimated using a mixed method approach including primary and secondary data. Over the four years analysed, the intervention cost US $1.03 million more than the baseline scenario in 2011 prices (adjusted for inflation) and caused a reduction in dog rabies cases; 738 DALYs averted; an increase in acceptability among non-dog owners; a perception of positive changes in society including a decrease in the number of roaming dogs; and a net reduction in the impact on animal welfare from intermediate-high to low-intermediate.</p><p>Conclusions</p><p>The findings illustrate the multiple outcomes relevant to stakeholders and allow greater understanding of the value of the implemented rabies control measures, thereby providing a solid foundation for informed decision-making and sustainable control.</p></div

Using a simple point-prevalence survey to define appropriate antibiotic prescribing in hospitalised children across the UK.

BACKGROUND: The National Health Service England, Commissioning for Quality and Innovation for Antimicrobial Resistance (CQUIN AMR) aims to reduce the total antibiotic consumption and the use of certain broad-spectrum antibiotics in secondary care. However, robust baseline antibiotic use data are lacking for hospitalised children. In this study, we aim to describe, compare and explain the prescription patterns of antibiotics within and between paediatric units in the UK and to provide a baseline for antibiotic prescribing for future improvement using CQUIN AMR guidance. METHODS: We conducted a cross-sectional study using a point prevalence survey (PPS) in 61 paediatric units across the UK. The standardised study protocol from the Antibiotic Resistance and Prescribing in European Children (ARPEC) project was used. All inpatients under 18 years of age present in the participating hospital on the day of the study were included except neonates. RESULTS: A total of 1247 (40.9%) of 3047 children hospitalised on the day of the PPS were on antibiotics. The proportion of children receiving antibiotics showed a wide variation between both district general and tertiary hospitals, with 36.4% ( 95% CI 33.4% to 39.4%) and 43.0% (95% CI 40.9% to 45.1%) of children prescribed antibiotics, respectively. About a quarter of children on antibiotic therapy received either a medical or surgical prophylaxis with parenteral administration being the main prescribed route for antibiotics (>60% of the prescriptions for both types of hospitals). General paediatrics units were surprisingly high prescribers of critical broad-spectrum antibiotics, that is, carbapenems and piperacillin-tazobactam. CONCLUSIONS: We provide a robust baseline for antibiotic prescribing in hospitalised children in relation to current national stewardship efforts in the UK. Repeated PPS with further linkage to resistance data needs to be part of the antibiotic stewardship strategy to tackle the issue of suboptimal antibiotic use in hospitalised children

Novel genome-wide associations for anhedonia, genetic correlation with psychiatric disorders, and polygenic association with brain structure

Funder: DJS acknowledges the support of a Lister Prize Fellowship (173096) and the MRC Mental Health Data Pathfinder Award (MC_PC_17217).Funder: JW is supported by the JMAS Sim Fellowship for depression research from the Royal College of Physicians of Edinburgh (173558).Funder: RAIB is supported by a British Academy Post-Doctoral Fellowship.Funder: RJS is supported by a UKRI Innovation- HDR-UK Fellowship (MR/S003061/1).Abstract: Anhedonia is a core symptom of several psychiatric disorders but its biological underpinnings are poorly understood. We performed a genome-wide association study of state anhedonia in 375,275 UK Biobank participants and assessed for genetic correlation between anhedonia and neuropsychiatric conditions (major depressive disorder, schizophrenia, bipolar disorder, obsessive compulsive disorder and Parkinson’s Disease). We then used a polygenic risk score approach to test for association between genetic loading for anhedonia and both brain structure and brain function. This included: magnetic resonance imaging (MRI) assessments of total grey matter volume, white matter volume, cerebrospinal fluid volume, and 15 cortical/subcortical regions of interest; diffusion tensor imaging (DTI) measures of white matter tract integrity; and functional MRI activity during an emotion processing task. We identified 11 novel loci associated at genome-wide significance with anhedonia, with a SNP heritability estimate (h2SNP) of 5.6%. Strong positive genetic correlations were found between anhedonia and major depressive disorder, schizophrenia and bipolar disorder; but not with obsessive compulsive disorder or Parkinson’s Disease. Polygenic risk for anhedonia was associated with poorer brain white matter integrity, smaller total grey matter volume, and smaller volumes of brain regions linked to reward and pleasure processing, including orbito-frontal cortex. In summary, the identification of novel anhedonia-associated loci substantially expands our current understanding of the biological basis of state anhedonia and genetic correlations with several psychiatric disorders confirm the utility of this phenotype as a transdiagnostic marker of vulnerability to mental illness. We also provide the first evidence that genetic risk for state anhedonia influences brain structure, including in regions associated with reward and pleasure processing

Screening history of women with cervical cancer: a 6-year study in Aarhus, Denmark

To identify possible weaknesses in cervical screening in Aarhus County, 10 years after the programme was introduced, screening histories were examined. A major problem for the screening programme was that 31% of women were never screened and 61% under-screened, the latter group being significantly dominated by older women and high-stage tumours

Effect of moderate walnut consumption on lipid profile, arterial stiffness and platelet activation in humans

BACKGROUND/OBJECTIVES: A large intake of walnuts may improve lipid profile and endothelial function. The effect of moderate walnut consumption is not known. We investigated whether a moderate intake of walnuts would affect lipid profile, arterial stiffness and platelet activation in healthy volunteers. SUBJECTS/METHODS: Thirty healthy males were recruited into a single-blind randomised controlled crossover trial of 4 weeks dietary walnut supplementation (15 g/day) and 4 weeks control (no walnuts). Arterial stiffness was assessed using pulse waveform analysis to determine the augmentation index and augmented pressure. Platelet activation was determined using flow cytometry to measure circulating platelet-monocyte aggregates. RESULTS: There were no differences in lipid profile after 4 weeks of walnut supplementation compared with control. Dietary intake of alpha-linolenic acid was increased during the walnut diet (2.1±0.4 g/day versus 0.7±0.4 g/day, P<0.0001). There were no differences in augmentation index or augmented pressure during walnut supplementation. Walnut supplementation did not affect platelet-monocyte aggregation . CONCLUSIONS: Dietary intervention with a moderate intake of walnuts does not affect lipid profile, arterial stiffness or platelet activation in man. Our results suggest that the potentially beneficial cardiac effects of walnuts may not be apparent at lower and more practical levels of consumption

Rising powers, UN Security Council reform, and the failure of rhetorical coercion

Despite repeated calls for reform, the UN Security Council has as yet resisted to satisfy the demands of a group of rising powers – Brazil, Germany, India, and Japan (G4) – for a permanent seat. We focus on one strategy of institutional adaptation to power shifts mentioned in the introductory article to this special issue and examine why the G4’s rhetorical coercion strategy has failed to resonate with the Council’s permanent members and the wider UN membership. Looking at the key debate on Security Council reform in the General Assembly in 2005, we examine the justifications the G4 have offered to support their proposal and whether these have been accepted as legitimate by UN member states. We show that the G4’s rhetorical coercion strategy has failed to resonate with the targeted audience because the G4 have justified their demand strongly in terms of how their material contributions would enhance the UN’s performance. In contrast, the G4’s opponents provided justifications predominantly based on fair and democratic procedures, generating higher levels of expressed support. The importance of procedural fairness is consistent with findings in social psychology and challenges the prominent argument that performance is the main path to legitimacy for international institutions

Antenatal nutritional supplementation and autism spectrum disorders in the Stockholm youth cohort:population based cohort study

Abstract Objective To determine whether nutritional supplementation during pregnancy is associated with a reduced risk of autism spectrum disorder (ASD) with and without intellectual disability in offspring. Design Observational prospective cohort study using multivariable logistic regression, sibling controls, and propensity score matching. Setting Stockholm County, Sweden. Participants 273 107 mother-child pairs identified through population registers. The study sample was restricted to children who were aged 4 to 15 years by the end of follow-up on 31 December 2011 and were born between 1996 and 2007. Exposures Multivitamin, iron, and folic acid supplement use was reported at the first antenatal visit. Main outcome measure Diagnosis of ASD with and without intellectual disability in children determined from register data up to 31 December 2011. Results Prevalence of ASD with intellectual disability was 0.26% (158 cases in 61 934) in the maternal multivitamin use group and 0.48% (430 cases in 90 480) in the no nutritional supplementation use group. Maternal multivitamin use with or without additional iron or folic acid, or both was associated with lower odds of ASD with intellectual disability in the child compared with mothers who did not use multivitamins, iron, and folic acid (odds ratio 0.69, 95% confidence interval 0.57 to 0.84). Similar estimates were found in propensity score matched (0.68, 0.54 to 0.86) and sibling control (0.77, 0.52 to 1.15) matched analyses, though the confidence interval for the latter association included 1.0 and was therefore not statistically significant. There was no consistent evidence that either iron or folic acid use were inversely associated with ASD prevalence. Conclusions Maternal multivitamin supplementation during pregnancy may be inversely associated with ASD with intellectual disability in offspring. Further scrutiny of maternal nutrition and its role in the cause of autism is recommended. </jats:sec

Validation of the brain health index in the European Prevention of Alzheimer's Dementia cohort

Background Brain Health Index (BHI) assimilates various MRI sequences, giving a quantitative measure of brain health. To date, BHI validation has been cross-sectional and limited to selected populations. Further large-scale validation and assessment of temporal change is required to understand its clinical utility. Aim Assess 1) relationships between variables associated with cognitive decline and BHI 2) associations between BHI and measures of cognition and 3) longitudinal changes in BHI and relationship with cognitive function. Methods BHI computation involved Gaussian mixture-model cluster analysis of T1, T2, T2*, and T2 FLAIR MRI data from participants within the European Prevention of Alzheimer's Dementia (EPAD) cohort. Group differences (gender- and health-based) were evaluated using independent samples Welch's t-tests. Relationships between BHI, age and cognitive tests used linear regression. Longitudinal analysis (12/24 months) utilised mixed linear regression models to examine BHI changes, and paired BHI/cognition associations. Results Data from N = 1496 predominantly Caucasian participants (50–88 years old, 43.32% male) were used. BHI scores were lower in those with diabetes (p &lt; 0.001, d = 0.419), hypertension (p &lt; 0.001, d = 0.375), hypercholesterolemia (p &lt; 0.001, d = 0.193) and stroke (p &lt; 0.05, d = 0.512). APOE was not significantly related to BHI scores. After correction for age, cross-sectional BHI scores were significantly associated with all measures of cognitive function in males, but only the Four Mountains Test (4MT) in females. Longitudinal change in BHI and cognition were not consistently related. Conclusions BHI is a valid marker of cognitive decline and relatively stable over 1-2 year follow-up periods. Further work should assess temporal changes over a longer duration and determine relationships between BHI and cognition in more diverse populations