The COVID-19 pandemic has led to more than 760,000 deaths worldwide (correct as of 16th August 2020). Studies suggest a hyperinflammatory response is a major cause of disease severity and death. ...Identitfying COVID-19 patients with hyperinflammation may identify subgroups who could benefit from targeted immunomodulatory treatments. Analysis of cytokine levels at the point of diagnosis of SARS-CoV-2 infection can identify patients at risk of deterioration.
We used a multiplex cytokine assay to measure serum IL-6, IL-8, TNF, IL-1β, GM-CSF, IL-10, IL-33 and IFN-γ in 100 hospitalised patients with confirmed COVID-19 at admission to University Hospital Southampton (UK). Demographic, clinical and outcome data were collected for analysis.
Age > 70 years was the strongest predictor of death (OR 28, 95% CI 5.94, 139.45). IL-6, IL-8, TNF, IL-1β and IL-33 were significantly associated with adverse outcome. Clinical parameters were predictive of poor outcome (AUROC 0.71), addition of a combined cytokine panel significantly improved the predictability (AUROC 0.85). In those ≤70 years, IL-33 and TNF were predictive of poor outcome (AUROC 0.83 and 0.84), addition of a combined cytokine panel demonstrated greater predictability of poor outcome than clinical parameters alone (AUROC 0.92 vs 0.77).
A combined cytokine panel improves the accuracy of the predictive value for adverse outcome beyond standard clinical data alone. Identification of specific cytokines may help to stratify patients towards trials of specific immunomodulatory treatments to improve outcomes in COVID-19.
Hunting by humans played a major role in extirpating terrestrial megafauna on several continents and megafaunal loss continues today in both terrestrial and marine ecosystems. Recent declines of ...large marine vertebrates that are of little or no commercial value, such as sea turtles, seabirds and marine mammals, have focused attention on the ecological impacts of incidental take, or bycatch, in global fisheries. In spite of the recognition of the problem of bycatch, few comprehensive assessments of its effects have been conducted. Many vulnerable species live in pelagic habitats, making surveys logistically complex and expensive. Bycatch data are sparse and our understanding of the demography of the affected populations is often rudimentary. These factors, combined with the large spatial scales that pelagic vertebrates and fishing fleets cover, make accurate and timely bycatch assessments difficult. Here, we review the current research that addresses these challenging questions in the face of uncertainty, analytical limitations and mounting conservation crises.
There is tremendous interpatient variability in the response to analgesic therapy (even for efficacious treatments), which can be the source of great frustration in clinical practice. This has led to ...calls for "precision medicine" or personalized pain therapeutics (ie, empirically based algorithms that determine the optimal treatments, or treatment combinations, for individual patients) that would presumably improve both the clinical care of patients with pain and the success rates for putative analgesic drugs in phase 2 and 3 clinical trials. However, before implementing this approach, the characteristics of individual patients or subgroups of patients that increase or decrease the response to a specific treatment need to be identified. The challenge is to identify the measurable phenotypic characteristics of patients that are most predictive of individual variation in analgesic treatment outcomes, and the measurement tools that are best suited to evaluate these characteristics. In this article, we present evidence on the most promising of these phenotypic characteristics for use in future research, including psychosocial factors, symptom characteristics, sleep patterns, responses to noxious stimulation, endogenous pain-modulatory processes, and response to pharmacologic challenge. We provide evidence-based recommendations for core phenotyping domains and recommend measures of each domain.
Systematic reviews of observational studies can be affected by biases that lead to under- or over-estimates of true intervention effects. Several tools have been reported in the literature that ...attempt to characterize potential bias. Our objective in this study was to determine the extent to which study-specific bias may have influenced intervention impacts on total costs of care (TCOC) in round 1 of the Health Care Innovation Awards.
We reviewed 82 statistical evaluations of innovation impacts on Medicare TCOC. We developed five risk-of-bias measures and assessed their influence on TCOC impacts using meta-regression.
The majority of evaluations used propensity score matching to create their comparison groups. One third of the non-randomized interventions were judged to have some risk of biased effects due largely to the way they recruited their treatment groups, and 35% had some degree of covariate imbalance remaining after propensity score adjustments. However, in the multivariable analysis of TCOC effects, none of the bias threats we examined (comparison group construction method, risk of bias, or degree of covariate imbalance) had a major impact on the magnitude of HCIA1 innovation effects. Evaluations using propensity score weighting produced larger but imprecise savings effects compared to propensity score matching.
Our results suggest that it is unlikely that HCIA1 TCOC effect sizes were systematically affected by the types of bias we considered. Assessing the risk of bias based on specific study design features is likely to be more useful for identifying problematic characteristics than the subjective quality ratings used by existing risk tools.
A new damage-healing model for self-healing cementitious materials is described. The model is formulated using results from a discrete ligament model and guided by the findings of a linked ...experimental study. Healing is simulated using the interaction of curing fronts propagating from opposing crack faces within a body of healing-agent. This approach accounts for the dependency of the healing response on the crack opening displacement (COD) and its rate. The new damage-healing cohesive-zone model is applied to an element with an embedded strong-discontinuity within a coupled finite-element code, which simulates healing-agent transport and mechanical behaviour. The model is validated using data from tests with different CODs and COD rates. The validations show that the coupled model represents the mechanical and flow behaviour of an autonomic self-healing system with good accuracy for a range of cracking configurations and load paths.
Summary
The effectiveness of bariatric surgery has been well‐studied. However, complications after bariatric surgery have been understudied. This review assesses <30‐d major complications associated ...with bariatric procedures, including anastomotic leak, myocardial infarction and pulmonary embolism. This review included 71 studies conducted in the USA between 2003 and 2014 and 107,874 patients undergoing either gastric bypass, adjustable gastric banding or sleeve gastrectomy, with mean age of 44 years and pre‐surgery body mass index of 46.5 kg m−2. Less than 30‐d anastomotic leak rate was 1.15%; myocardial infarction rate was 0.37%; pulmonary embolism rate was 1.17%. Among all patients, mortality rate following anastomotic leak, myocardial infarction and pulmonary embolism was 0.12%, 0.37% and 0.18%, respectively. Among surgical procedures, <30‐d after surgery, sleeve gastrectomy (1.21% 95% confidence interval, 0.23–2.19%) had higher anastomotic leak rate than gastric bypass (1.14% 95% confidence interval, 0.84–1.43%); gastric bypass had higher rates of myocardial infarction and pulmonary embolism than adjustable gastric banding or sleeve gastrectomy. During the review, we found that the quality of complication reporting is lower than the reporting of other outcomes. In summary, <30‐d rates of the three major complications after either one of the procedures range from 0% to 1.55%. Mortality following these complications ranges from 0% to 0.64%. Future studies reporting complications after bariatric surgery should improve their reporting quality.
Precision medicine is a promising framework for generating evidence to improve health and health care. Yet, a gap persists between the ever-growing number of statistical precision medicine strategies ...for evidence generation and implementation in real-world clinical settings, and the strategies for closing this gap will likely be context-dependent. In this paper, we consider the specific context of partial compliance to wound management among patients with peripheral artery disease. Using a Gaussian process surrogate for the value function, we show the feasibility of using Bayesian optimization to learn optimal individualized treatment rules. Further, we expand beyond the common precision medicine task of learning an optimal individualized treatment rule to the characterization of classes of individualized treatment rules and show how those findings can be translated into clinical contexts.
While the effects of social stratification by gender, race, class, and ethnicity on health inequalities are well‐documented, our understanding of the intersecting consequences of these social ...dimensions on diagnosis remains limited. This is particularly the case in studies of mental health, where “paradoxical” patterns of stratification have been identified. Using a Bayesian multi‐level random‐effects Poisson model and a nationally representative random sample of 138,009 households from the National Survey of Children's Health, this study updates and extends the literature on mental health inequalities through an intersectional investigation of one of the most commonly diagnosed psychiatric conditions of childhood/adolescence: attention‐deficit hyperactivity disorder (ADHD). Findings indicate that gender, race, class, and ethnicity combine in mutually constitutive ways to explain between‐group variation in ADHD diagnosis. Observed effects underscore the importance and feasibility of an intersectional, multi‐level modelling approach and data mapping technique to advance our understanding of social subgroups more/less likely to be diagnosed with mental health conditions.
The depletion of fish stocks from global fisheries has been a long‐standing concern. More recently, incidental catch of non‐target (termed bycatch) vertebrates also has been proposed as a serious ...conservation issue. Here we present a bycatch assessment for loggerhead and leatherback sea turtles that are incidentally caught by global pelagic longlines. We integrate catch data from over 40 nations and bycatch data from 13 international observer programmes. Despite infrequent rates of encounter, our analyses show that more than 200 000 loggerheads and 50 000 leatherbacks were likely taken as pelagic longline bycatch in 2000. Our analyses suggest that thousands of these turtles die each year from longline gear in the Pacific Ocean alone. Given 80–95% declines for Pacific loggerhead and leatherback populations over the last 20 years, this bycatch level is not sustainable. Adopting a large‐scale, synthetic approach is critical to accurately characterize the influence of global fisheries bycatch on globally distributed and imperilled pelagic vertebrates.
During geomagnetically disturbed conditions the midlatitude ionosphere is subject to intense poleward directed electric fields in the dusk‐midnight sector. These electric fields lead to the ...generation of a latitudinally narrow westward directed flow channel in the subauroral region called a subauroral polarization stream (SAPS). If the magnetic field lines are treated as equipotentials, electrodynamic events such as SAPS are expected to occur simultaneously at magnetically conjugate locations with similar features. In this paper we present simultaneous observations of a SAPS event in both hemispheres made by midlatitude SuperDARN radars with conjugate fields‐of‐view. We analyze the relation between the geomagnetic conditions and the characteristics of the channels such as latitudinal location, electric field, total potential variations across the channels, and Pedersen current. The results suggest a strong correlation between the strength of the ring current and the latitudinal location of the channel. An inter‐hemispheric comparison of the characteristics of the channel indicates that the potential variations across the channels are similar while the electric fields, Pedersen currents and latitudinal widths of the channel exhibit differences that are consistent with equal potential variations. We attribute these differences to seasonal differences in ionospheric conductivity between the hemispheres and magnetic distortion effects in the inner magnetosphere.
Key Points
Study the characteristics of SAPS observed in both hemispheres
Investigate the extent of inter‐hemispheric conjugacy exhibited during SAPS
Analyze the influence of geomagnetic conditions on SAPS
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