Comparing life cycle environmental impacts of food access and consumption pre- and during COVID 19 in New York State's Capital Region.

The COVID-19 pandemic has significantly influenced household food shopping, food consumption, and food waste generation. However, the dietary environmental impacts for different income groups during COVID-19 remain unknown. To analyze dietary environmental impacts for various income groups, a process-based life cycle assessment (LCA) was conducted based on two electronic food access surveys implemented in the New York State's Capital Region during the COVID-19 pandemic and public and proprietary databases. We found that life cycle global warming potential, cumulative energy demand, acidification potential, and water resource depletion of per capital food consumption in the studied area tended to be lower during COVID-19 than pre-COVID-19. In contrast, life cycle eutrophication during COVID-19 was slightly higher than pre-COVID-19. The environmental impacts occurring at the food production stage were higher than those at the local transportation and waste disposal stages. The lowest income group had the lowest dietary environmental impacts due to their lowest food consumption of all the food categories. The second-highest income group had the highest dietary environmental impacts, since they consumed the most red meat which has a high impact intensity. This is the first study to our knowledge to investigate the differences in dietary environmental impacts among income groups during COVID-19.

Optimising the use of colonoscopy to improve risk stratification for colorectal cancer in symptomatic patients: A decision-curve analysis.

OBJECTIVES: Pressured healthcare resources make risk stratification and patient prioritisation fundamental issues for the investigation of colorectal cancer (CRC) in symptomatic patients. The present study uses machine learning algorithms and decision strategies to improve the appropriate use of colonoscopy. DESIGN: All symptomatic patients in a single health board (2018-2021) proceeding to colonoscopy to investigate for CRC were included. Machine learning algorithms (NeuralNetwork, randomForest, Logistic regression, Naïve-Bayes and Adaboost) were used to risk-stratify patients for CRC using demographics, symptoms, quantitative faecal immunochemical test (qFIT) and haematological tests. Decision curve analyses were performed to determine the optimal decision strategies. RESULTS: 3776 patients were included (median age, 65; M:F,0.9:1.0) and CRC was identified in 217 patients (5.7%). qFIT > 400 µg Hb/g was the most important variable (%IncMSE = 78.5). RandomForrest had the highest area under curve (0.91) and accuracy (0.80) for CRC. When utilising decision curve analysis (DCA), 30%, 46% and 54% of colonoscopies were saved at accepted CRC probabilities of 1%, 2% and 3%, respectively. RandomForrest modelling had superior net clinical benefit compared to default colonoscopy strategies. CONCLUSIONS: MLA-derived decision strategies that account for patient and referrer risk preference reduce colonoscopy demand and carry net clinical benefit compared to default colonoscopy strategies.

Polygenic risk score adds to a clinical risk score in the prediction of cardiovascular disease in a clinical setting.

BACKGROUND AND AIMS: A cardiovascular disease polygenic risk score (CVD-PRS) can stratify individuals into different categories of cardiovascular risk, but whether the addition of a CVD-PRS to clinical risk scores improves the identification of individuals at increased risk in a real-world clinical setting is unknown. METHODS: The Genetics and the Vascular Health Check Study (GENVASC) was embedded within the UK National Health Service Health Check (NHSHC) programme which invites individuals between 40-74 years of age without known CVD to attend an assessment in a UK general practice where CVD risk factors are measured and a CVD risk score (QRISK2) is calculated. Between 2012-2020, 44,141 individuals (55.7% females, 15.8% non-white) who attended an NHSHC in 147 participating practices across two counties in England were recruited and followed. When 195 individuals (cases) had suffered a major CVD event (CVD death, myocardial infarction or acute coronary syndrome, coronary revascularisation, stroke), 396 propensity-matched controls with a similar risk profile were identified, and a nested case-control genetic study undertaken to see if the addition of a CVD-PRS to QRISK2 in the form of an integrated risk tool (IRT) combined with QRISK2 would have identified more individuals at the time of their NHSHC as at high risk (QRISK2 10-year CVD risk of ≥10%), compared with QRISK2 alone. RESULTS: The distribution of the standardised CVD-PRS was significantly different in cases compared with controls (cases mean score .32; controls, -.18, P = 8.28×10-9). QRISK2 identified 61.5% (95% confidence interval [CI]: 54.3%-68.4%) of individuals who subsequently developed a major CVD event as being at high risk at their NHSHC, while the combination of QRISK2 and IRT identified 68.7% (95% CI: 61.7%-75.2%), a relative increase of 11.7% (P = 1×10-4). The odds ratio (OR) of being up-classified was 2.41 (95% CI: 1.03-5.64, P = .031) for cases compared with controls. In individuals aged 40-54 years, QRISK2 identified 26.0% (95% CI: 16.5%-37.6%) of those who developed a major CVD event, while the combination of QRISK2 and IRT identified 38.4% (95% CI: 27.2%-50.5%), indicating a stronger relative increase of 47.7% in the younger age group (P = .001). The combination of QRISK2 and IRT increased the proportion of additional cases identified similarly in women as in men, and in non-white ethnicities compared with white ethnicity. The findings were similar when the CVD-PRS was added to the atherosclerotic cardiovascular disease pooled cohort equations (ASCVD-PCE) or SCORE2 clinical scores. CONCLUSIONS: In a clinical setting, the addition of genetic information to clinical risk assessment significantly improved the identification of individuals who went on to have a major CVD event as being at high risk, especially among younger individuals. The findings provide important real-world evidence of the potential value of implementing a CVD-PRS into health systems.

Managing well-being in paediatric critical care: a multiperspective qualitative study of nurses' and allied health professionals' experiences.

OBJECTIVES: It is well evidenced that healthcare professionals working in paediatric critical care experience high levels of burn-out, compassion fatigue and moral distress. This worsened during the COVID-19 pandemic. This work examines the nature of challenges to workplace well-being and explores what well-being means to staff. This evidence will inform the development of staff interventions to improve and maintain staff well-being. DESIGN: Qualitative study. SETTING: Paediatric critical care units in the UK. PARTICIPANTS: 30 nurses and allied health professionals took part in online interviews and were asked about well-being and challenges to well-being. Lived experiences of well-being were analysed using interpretative phenomenological analysis. RESULTS: Themes generated were as follows: perception of self and identity; relationships and team morale; importance of control and balance and consequences of COVID-19. They focused on the impact of poor well-being on participants' sense of self; the significance of how or whether they feel able to relate well with their team and senior colleagues; the challenges associated with switching off, feeling unable to separate work from home life and the idealised goal of being able to do just that; and lessons learnt from working through the pandemic, in particular associated with redeployment to adult intensive care. CONCLUSIONS: Our findings align closely with the self-determination theory which stipulates autonomy, belonging and competence are required for well-being. Participants' accounts supported existing literature demonstrating the importance of empowering individuals to become self-aware, to be skilled in self-reflection and to be proactive in managing one's own well-being. Change at the individual and staff group level may be possible with relatively low-intensity intervention, but significant change requires systemic shifts towards the genuine prioritisation of staff well-being as a prerequisite for high-quality patient care.

Adaptation and qualitative evaluation of the BETTER intervention for chronic disease prevention and screening by public health nurses in low income neighbourhoods: views of community residents.

BACKGROUND: The BETTER intervention is an effective comprehensive evidence-based program for chronic disease prevention and screening (CDPS) delivered by trained prevention practitioners (PPs), a new role in primary care. An adapted program, BETTER HEALTH, delivered by public health nurses as PPs for community residents in low income neighbourhoods, was recently shown to be effective in improving CDPS actions. To obtain a nuanced understanding about the CDPS needs of community residents and how the BETTER HEALTH intervention was perceived by residents, we studied how the intervention was adapted to a public health setting then conducted a post-visit qualitative evaluation by community residents through focus groups and interviews. METHODS: We first used the ADAPT-ITT model to adapt BETTER for a public health setting in Ontario, Canada. For the post-PP visit qualitative evaluation, we asked community residents who had received a PP visit, about steps they had taken to improve their physical and mental health and the BETTER HEALTH intervention. For both phases, we conducted focus groups and interviews; transcripts were analyzed using the constant comparative method. RESULTS: Thirty-eight community residents participated in either adaptation (n = 14, 64% female; average age 54 y) or evaluation (n = 24, 83% female; average age 60 y) phases. In both adaptation and evaluation, residents described significant challenges including poverty, social isolation, and daily stress, making chronic disease prevention a lower priority. Adaptation results indicated that residents valued learning about CDPS and would attend a confidential visit with a public health nurse who was viewed as trustworthy. Despite challenges, many recipients of BETTER HEALTH perceived they had achieved at least one personal CDPS goal post PP visit. Residents described key relational aspects of the visit including feeling valued, listened to and being understood by the PP. The PPs also provided practical suggestions to overcome barriers to meeting prevention goals. CONCLUSIONS: Residents living in low income neighbourhoods faced daily stress that reduced their capacity to make preventive lifestyle changes. Key adapted features of BETTER HEALTH such as public health nurses as PPs were highly supported by residents. The intervention was perceived valuable for the community by providing access to disease prevention. TRIAL REGISTRATION: #NCT03052959, 10/02/2017.

Mammographic surveillance after breast cancer.

Early detection of local recurrence has been shown to improve survival. What is unclear is how frequently mammography should be performed, how long surveillance should continue and how the answers to these questions vary with tumour pathology, patients age, and surgery type. Many of these questions are not directly answerable from the current literature. While some of these questions will be answered by the Mammo-50 study, evidence from local recurrence rates, tumour biology, and the lead time of mammography can be used to guide policy. Young age is the strongest predictor of local recurrence and given the short lead time of screening in women under 50, these women require annual mammography. Women over 50 with HER-2 positive and triple negative breast cancer have higher rates of local recurrence after breast conserving surgery than women with luminal cancers. Women with HER-2 positive and triple negative breast cancer also have a higher rate of recurrence in years 1-3 post surgery. Annual mammography in year 1-4 would appear justified. Women over 50 with luminal cancers have low rates of local recurrence and no early peak. Recurrence growth will be low due to tumour biology and hormone therapy. Biennial mammography after year 2 would seem appropriate. Women over 50 following mastectomy have no early peak in contralateral cancers so the frequency should be determined by the lead time of screening. This would suggest 2 yearly mammography for women aged 50-60 while 3 yearly mammography may suffice for women over 60.

A polygenic risk score added to a QRISK®2 cardiovascular disease risk calculator demonstrated robust clinical acceptance and clinical utility in the primary care setting.

AIMS: The aim of the study was to assess the real-world feasibility, acceptability, and impact of an integrated risk tool for cardiovascular disease (CVD IRT, combining the standard QRISK®2 risk algorithm with a polygenic risk score), implemented within routine primary practice in the UK National Health Service. METHODS AND RESULTS: The Healthcare Evaluation of Absolute Risk Testing Study (NCT05294419) evaluated participants undergoing primary care health checks. Both QRISK2 and CVD IRT scores were returned to the healthcare providers (HCPs), who then communicated the results to participants. The primary outcome of the study was feasibility of CVD IRT implementation. Secondary outcomes included changes in CVD risk (QRISK2 vs. CVD IRT) and impact of the CVD IRT on clinical decision-making. A total of 832 eligible participants (median age 55 years, 62% females, 97.5% White ethnicity) were enrolled across 12 UK primary care practices. Cardiovascular disease IRT scores were obtained on 100% of the blood samples. Healthcare providers stated that the CVD IRT could be incorporated into routine primary care in a straightforward manner in 90.7% of reports. Participants stated they were 'likely' or 'very likely' to recommend the use of this test to their family or friends in 86.9% of reports. Participants stated that the test was personally useful (98.8%) and that the results were easy to understand (94.6%). When CVD IRT exceeded QRISK2, HCPs planned changes in management for 108/388 (27.8%) of participants and 47% (62/132) of participants with absolute risk score changes of >2%. CONCLUSION: Amongst HCPs and participants who agreed to the trial of genetic data for refinement of clinical risk prediction in primary care, we observed that CVD IRT implementation was feasible and well accepted. The CVD IRT results were associated with planned changes in prevention strategies.

When a standard cardiovascular risk tool, as currently used in National Health Service Health Checks, was expanded to include genetic risk information, it was well accepted by both participants and healthcare providers and generated impactful changes in planned clinical decision-making.Most participants found the test useful and easy to understand, and healthcare providers found it straightforward to use in most cases.When risk was increased by the addition of genetic information, this influenced planned management decisions.

Meiotic DNA breaks drive multifaceted mutagenesis in the human germ line.

Meiotic recombination commences with hundreds of programmed DNA breaks; however, the degree to which they are accurately repaired remains poorly understood. We report that meiotic break repair is eightfold more mutagenic for single-base substitutions than was previously understood, leading to de novo mutation in one in four sperm and one in 12 eggs. Its impact on indels and structural variants is even higher, with 100- to 1300-fold increases in rates per break. We uncovered new mutational signatures and footprints relative to break sites, which implicate unexpected biochemical processes and error-prone DNA repair mechanisms, including translesion synthesis and end joining in meiotic break repair. We provide evidence that these mechanisms drive mutagenesis in human germ lines and lead to disruption of hundreds of genes genome wide.

Characterization of meiotic recombination intermediates through gene knockouts in founder hybrid mice.

Mammalian meiotic recombination proceeds via repair of hundreds of programmed DNA double-strand breaks, which requires choreographed binding of RPA, DMC1, and RAD51 to single-stranded DNA substrates. High-resolution in vivo binding maps of these proteins provide insights into the underlying molecular mechanisms. When assayed in F1-hybrid mice, these maps can distinguish the broken chromosome from the chromosome used as template for repair, revealing more mechanistic detail and enabling the structure of the recombination intermediates to be inferred. By applying CRISPR-Cas9 mutagenesis directly on F1-hybrid embryos, we have extended this approach to explore the molecular detail of recombination when a key component is knocked out. As a proof of concept, we have generated hybrid biallelic knockouts of Dmc1 and built maps of meiotic binding of RAD51 and RPA in them. DMC1 is essential for meiotic recombination, and comparison of these maps with those from wild-type mice is informative about the structure and timing of critical recombination intermediates. We observe redistribution of RAD51 binding and complete abrogation of D-loop recombination intermediates at a molecular level in Dmc1 mutants. These data provide insight on the configuration of RPA in D-loop intermediates and suggest that stable strand exchange proceeds via multiple rounds of strand invasion with template switching in mouse. Our methodology provides a high-throughput approach for characterization of gene function in meiotic recombination at low animal cost.

Characterisation of Ferritin-Lymphocyte Ratio in COVID-19.

Introduction: The ferritin-lymphocyte ratio (FLR) is a novel inflammatory biomarker for the assessment of acute COVID-19 patients. However, the prognostic value of FLR for predicting adverse clinical outcomes in COVID-19 remains unclear, which hinders its clinical translation. Methods: We characterised the prognostic value of FLR in COVID-19 patients, as compared to established inflammatory markers. Results: In 217 study patients (69 years [IQR: 55-82]; 60% males), FLR was weakly correlated with CRP (R = 0.108, p = 0.115) and white cell count (R = -0.144; p = 0.034). On ROC analysis, an FLR cut-off of 286 achieved a sensitivity of 86% and a specificity of 30% for predicting inpatient mortality (AUC 0.60, 95% CI: 0.53-0.67). The negative predictive values of FLR for ruling out mortality, non-invasive ventilation requirement and critical illness (intubation and/or ICU admission) were 86%, 85% and 93%, respectively. FLR performed similarly to CRP (AUC 0.60 vs. 0.64; p = 0.375) for predicting mortality, but worse than CRP for predicting non-fatal outcomes (all p < 0.05). On Kaplan-Meier analysis, COVID-19 patients with FLR values > 286 had worse inpatient survival than patients with FLR ≤ 286, p = 0.041. Conclusions: FLR has prognostic value in COVID-19 patients, and appears unrelated to other inflammatory markers such as CRP and WCC. FLR exhibits high sensitivity and negative predictive values for adverse clinical outcomes in COVID-19, and may be a good "rule-out" test. Further work is needed to improve the sensitivity of FLR and validate its role in prospective studies for guiding clinical management.

Low CRB-65 Scores Effectively Rule out Adverse Clinical Outcomes in COVID-19 Irrespective of Chest Radiographic Abnormalities.

Background: CRB-65 (Confusion; Respiratory rate ≥ 30/min; Blood pressure ≤ 90/60 mmHg; age ≥ 65 years) is a risk score for prognosticating patients with COVID-19 pneumonia. However, a significant proportion of COVID-19 patients have normal chest X-rays (CXRs). The influence of CXR abnormalities on the prognostic value of CRB-65 is unknown, limiting its wider applicability. Methods: We assessed the influence of CXR abnormalities on the prognostic value of CRB-65 in COVID-19. Results: In 589 study patients (71 years (IQR: 57-83); 57% males), 186 (32%) had normal CXRs. On ROC analysis, CRB-65 performed similarly in patients with normal vs. abnormal CXRs for predicting inpatient mortality (AUC 0.67 ± 0.05 vs. 0.69 ± 0.03). In patients with normal CXRs, a CRB-65 of 0 ruled out mortality, NIV requirement and critical illness (intubation and/or ICU admission) with negative predictive values (NPVs) of 94%, 98% and 99%, respectively. In patients with abnormal CXRs, a CRB-65 of 0 ruled out the same endpoints with NPVs of 91%, 83% and 86%, respectively. Patients with low CRB-65 scores had better inpatient survival than patients with high CRB-65 scores, irrespective of CXR abnormalities (all p < 0.05). Conclusions: CRB-65, CXR and CRP are independent predictors of mortality in COVID-19. Adding CXR findings (dichotomised to either normal or abnormal) to CRB-65 does not improve its prognostic accuracy. A low CRB-65 score of 0 may be a good rule-out test for adverse clinical outcomes in COVID-19 patients with normal or abnormal CXRs, which deserves prospective validation.

Genotyping and population characteristics of the China Kadoorie Biobank.

The China Kadoorie Biobank (CKB) is a population-based prospective cohort of >512,000 adults recruited from 2004 to 2008 from 10 geographically diverse regions across China. Detailed data from questionnaires and physical measurements were collected at baseline, with additional measurements at three resurveys involving ∼5% of surviving participants. Analyses of genome-wide genotyping, for >100,000 participants using custom-designed Axiom arrays, reveal extensive relatedness, recent consanguinity, and signatures reflecting large-scale population movements from recent Chinese history. Systematic genome-wide association studies of incident disease, captured through electronic linkage to death and disease registries and to the national health insurance system, replicate established disease loci and identify 14 novel disease associations. Together with studies of candidate drug targets and disease risk factors and contributions to international genetics consortia, these demonstrate the breadth, depth, and quality of the CKB data. Ongoing high-throughput omics assays of collected biosamples and planned whole-genome sequencing will further enhance the scientific value of this biobank.

Variation in Early Pediatric Intensive Care Management Strategies and Duration of Invasive Mechanical Ventilation for Acute Viral Bronchiolitis in the United Kingdom: A Retrospective Multicenter Cohort Study.

OBJECTIVES: Management of mechanically ventilated patients with bronchiolitis is not standardized and duration of mechanical ventilation has been shown to vary widely between centers. The aim of this study was to examine practice in a large number of U.K. PICUs with a view to identify if early management choices relating to fluid prescription, sedative agent use, and endotracheal tube (ETT) placement were associated with differences in duration of invasive mechanical ventilation (IMV). DESIGN: Retrospective multicenter cohort study. Primary outcome was duration of IMV. A hierarchical gamma generalized linear model was used to test for associations between practice variables (sedative and neuromuscular blocking agents, route of endotracheal intubation at 24 hr and fluid balance at 48 hr) and duration of IMV after adjustment for known confounders. SETTING: Thirteen U.K. PICUs. Duration of 2 months between November and December 2019. PATIENTS: Three hundred fifty infants receiving IMV for bronchiolitis. Excluded were patients receiving long-term ventilation, extracorporeal life support, or who died before separation from IMV. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: After adjustment for confounders, several variables were associated with an increase in the geometric mean duration of IMV (expressed as a percentage) including: nasal ETT use, 16% (95% CI, 1-32%); neuromuscular blockade use, 39% (95% CI, 21-61%); and fluid balance at 48 hr, 13% per 100 mL/kg positive fluid balance (95% CI, -1% to 28%). The association of sedative use varied with class of agent. The use of an alpha-2 agonist alone was associated with a reduction in duration of IMV by 19% in relation to no sedative agent (95% CI, -31 to -5%), whereas benzodiazepine uses alone or with alpha-2 agonist in combination were similar to using neither agent. CONCLUSIONS: Early management strategies for bronchiolitis were associated with the duration of IMV across U.K. centers after adjustment for confounders. Future work should prospectively assess the impact of fluid restriction, route of endotracheal intubation, and alpha-2 agonist use on duration of IMV in infants with bronchiolitis, with the aim of reducing seasonal bed pressure.

Comparison of Lymphocyte-CRP Ratio to Conventional Inflammatory Markers for Predicting Clinical Outcomes in COVID-19.

Background: In COVID-19 patients, lymphocyte-CRP ratio (LCR) is a promising biomarker for predicting adverse clinical outcomes. How well LCR performs compared to conventional inflammatory markers for prognosticating COVID-19 patients remains unclear, which hinders the clinical translation of this novel biomarker. Methods: In a cohort of COVID-19 inpatients, we characterised the clinical applicability of LCR by comparing its prognostic value against conventional inflammatory markers for predicting inpatient mortality and a composite of mortality, invasive/non-invasive ventilation and intensive care unit admissions. Results: Of the 413 COVID-19 patients, 100 (24%) patients suffered inpatient mortality. On Receiver Operating Characteristics analysis, LCR performed similarly to CRP for predicting mortality (AUC 0.74 vs. 0.71, p = 0.049) and the composite endpoint (AUC 0.76 vs. 0.76, p = 0.812). LCR outperformed lymphocyte counts (AUC 0.74 vs. 0.66, p = 0.002), platelet counts (AUC 0.74 vs. 0.61, p = 0.003) and white cell counts (AUC 0.74 vs. 0.54, p < 0.001) for predicting mortality. On Kaplan-Meier analysis, patients with a low LCR (below a 58 cut-off) had worse inpatient survival than patients with other LCR values (p < 0.001). Conclusion: LCR appears comparable to CRP, but outperformed other inflammatory markers, for prognosticating COVID-19 patients. Further studies are required to improve the diagnostic value of LCR to facilitate clinical translation.

Development of the HT&Me intervention to support women with breast cancer to adhere to adjuvant endocrine therapy and improve quality of life.

BACKGROUND: Breast cancer is the most common cancer in women worldwide. Approximately 80% of breast cancers are oestrogen receptor positive (ER+). Patients treated surgically are usually recommended adjuvant endocrine therapy (AET) for 5-10 years. AET significantly reduces recurrence, but up to 50% of women do not take it as prescribed. OBJECTIVE: To co-design and develop an intervention to support AET adherence and improve health-related quality-of-life (QoL) in women with breast cancer. METHODS: Design and development of the HT&Me intervention took a person-based approach and was guided by the Medical Research Council framework for complex interventions, based on evidence and underpinned by theory. Literature reviews, behavioural analysis, and extensive key stakeholder involvement informed 'guiding principles' and the intervention logic model. Using co-design principles, a prototype intervention was developed and refined. RESULTS: The blended tailored HT&Me intervention supports women to self-manage their AET. It comprises initial and follow-up consultations with a trained nurse, supported with an animation video, a web-app and ongoing motivational 'nudge' messages. It addresses perceptual (e.g. doubts about necessity, treatment concerns) and practical (e.g. forgetting) barriers to adherence and provides information, support and behaviour change techniques to improve QoL. Iterative patient feedback maximised feasibility, acceptability, and likelihood of maintaining adherence; health professional feedback maximised likelihood of scalability. CONCLUSIONS: HT&Me has been systematically and rigorously developed to promote AET adherence and improve QoL, and is complemented with a logic model documenting hypothesized mechanisms of action. An ongoing feasibility trial will inform a future randomised control trial of effectiveness and cost-effectiveness.

Development and validation of the C-SHADE scale for measuring perpetration of common sexually harassing and aggressive behaviors in drinking environments.

BACKGROUND: Sexual aggression (SA) is ubiquitous in drinking environments. Although such behavior is often seen as normal and acceptable, the targets of SA experience many negative consequences. This research aimed to develop a valid measure of common acts of SA in drinking settings for estimating prevalence and evaluating prevention initiatives. METHODS: We developed a questionnaire measure of common acts of sexual harassment and aggression in drinking environments (C-SHADE) based on descriptions of SA behavior from our own and others' research. The measure was validated in a cross-sectional survey of 335 men aged 19 to 25 using webpanels from an online survey company. Validation measures included: a modified version of the Sexual Experiences Survey (M-SES), measures of SA by peers in drinking environments, SA-related attitudes, expectancies about sexual effects of alcohol, and alcohol consumption. RESULTS: The C-SHADE showed high internal consistency (α = 0.96) and was significantly correlated with M-SES (r = 0.52), SA by peers (r = 0.61 to 0.70), SA-related attitudes/expectations (r = 0.38 to 0.55), and measures of alcohol consumption (r = 0.22 to 0.36). Overall, 71.9% of participants reported SA using the C-SHADE versus 24.7% with the M-SES. We compared the responses of participants who reported perpetration on both measures (N = 83), on only the C-SHADE (N = 141), and among nonperpetrators (N = 89; excluding four participants who reported perpetration only on the M-SES). The M-SES/C-SHADE perpetrators scored significantly higher than C-SHADE-only perpetrators and nonperpetrators on most SA-related and drinking measures, while C-SHADE-only perpetrators scored significantly higher than nonperpetrators on peer SA and two attitude measures. CONCLUSIONS: The C-SHADE is suitable for measuring prevalence and evaluating interventions in drinking settings. The C-SHADE confirmed a high prevalence of SA in drinking settings and identified an important group of C-SHADE-only perpetrators for whom interventions that focus on situational precipitators of SA in drinking settings may be especially useful.

Normal high-sensitivity cardiac troponin for ruling-out inpatient mortality in acute COVID-19.

INTRODUCTION: Assessment of inpatient mortality risk in COVID-19 patients is important for guiding clinical decision-making. High sensitivity cardiac troponin T (hs-cTnT) is a biomarker of cardiac injury associated with a worse prognosis in COVID-19. We explored how hs-cTnT could potentially be used in clinical practice for ruling in and ruling out mortality in COVID-19. METHOD: We tested the diagnostic value of hs-cTnT in laboratory-confirmed COVID-19 patients (≥18 years old) admitted to the Royal Berkshire Hospital (UK) between 1st March and 10th May 2020. A normal hs-cTnT was defined as a value within the 99th percentile of healthy individuals (≤14 ng/L), and an elevated hs-cTnT was defined as >14 ng/L. Adverse clinical outcome was defined as inpatient mortality related to COVID-19. RESULTS: A total of 191 COVID-19 patients (62% male; age 66±16 years) had hs-cTnT measured on admission. Of these patients, 124 (65%) had elevated hs-cTnT and 67 (35%) had normal hs-cTnT. On a group level, patients with elevated hs-cTnT had worse inpatient survival (p = 0.0014; Kaplan-Meier analysis) and higher risk of inpatient mortality (HR 5.84 [95% CI 1.29-26.4]; p = 0.02; Cox multivariate regression) compared to patients with normal hs-cTnT. On a per-patient level, a normal hs-cTnT had a negative predictive value of 94% (95% CI: 85-98%) for ruling out mortality, whilst an elevated hs-cTnT had a low positive predictive value of 38% (95% CI: 39-47%) for ruling in mortality. CONCLUSIONS: In this study cohort of COVID-19 patients, the potential clinical utility of hs-cTnT appears to rest in ruling out inpatient mortality. This finding, if prospectively validated in a larger study, may allow hs-cTnT to become an important biomarker to facilitate admission-avoidance and early safe discharge.

Effective prognostic and clinical risk stratification in COVID-19 using multimodality biomarkers.

In acute coronavirus disease 19 (COVID-19) patients, effective clinical risk stratification has important implications on treatment and therapeutic resource distribution. This article reviews the evidence behind a wide range of biomarkers with prognostic value in COVID-19. Patient characteristics and co-morbidities, such as cardiovascular and respiratory diseases, are associated with increased mortality risk. Peripheral oxygen saturation and arterial oxygenation are predictive of severe respiratory compromise, whereas risk scores such as the 4C-score enable multi-factorial prognostic risk estimation. Blood tests such as markers of inflammation, cardiac injury and d-dimer and abnormalities on electrocardiogram are linked to inpatient prognosis. Of the imaging modalities, lung ultrasound and echocardiography enable the bedside assessment of prognostic abnormalities in COVID-19. Chest radiograph (CXR) and computed tomography (CT) can inform about prognostic pulmonary pathologies, whereas cardiovascular CT detects high-risk features such as coronary artery and aortic calcification. Dynamic changes in biomarkers, such as blood tests, CXR, CT and electrocardiogram findings, can further inform about disease severity and prognosis. Despite the vast volumes of existing evidence, several gaps exist in our understanding of COVID-19 biomarkers. First, the pathophysiological basis on which these markers can foretell prognosis in COVID-19 remains poorly understood. Second, certain under-explored tests such as thoracic impedance assessment and cardiovascular magnetic resonance imaging deserve further investigation. Lastly, the prognostic values of most biomarkers in COVID-19 are derived from retrospective analyses. Prospective studies are required to validate these markers for guiding clinical decision-making and to facilitate their translation into clinical management pathways.

2022 William Allan Award.

This article is based on the address given by the author at the 2022 meeting of The American Society of Human Genetics (ASHG) in Los Angeles, CA. The video of the original address can be found at the ASHG website.