The performance of COBRA, a decision rule to predict the need for intensive care interventions in intentional drug overdose

BACKGROUND: COBRA was developed as a decision rule to predict which patients visiting the emergency department (ED) following intentional drug overdose will not require intensive care unit (ICU) interventions. COBRA uses parameters from five vital systems (cardiac conduction, oxygenation, blood pressure, respiration, and awareness) that are readily available in the ED. COBRA recommends against ICU admission when all these parameters are normal. OBJECTIVE: The primary aim of this study was to determine the negative predictive value (NPV) of COBRA in predicting ICU interventions. Secondary outcomes were the sensitivity, specificity and positive predictive value (PPV), and the observation time required for a reliable prediction. DESIGN: Observational cohort study. SETTINGS AND PARTICIPANTS: Patients with a reported intentional overdose with drugs having potential acute effects on neurological, circulatory or ventilatory function were included, and data necessary to complete the decision rule was collected. The attending physician in the ED made the actual admission decision, on the basis of clinical judgement. COBRA was measured 0, 3 and 6 h after arrival at the ED. OUTCOME MEASURES: Need for ICU interventions (treatment of convulsion; defibrillation; mechanical or noninvasive ventilation; intravenous administration of vasopressive agents, antiarrhythmics, atropine, calcium, magnesium or sedation; continuous hemofiltration or administration of antagonist/antidote and fluid resuscitation). MAIN RESULTS: Of 230 new cases (144 unique patients), 59 were immediately referred to the psychiatric services and/or sent home by the attending physician, 27 went to a regular ward, and 144 were admitted to the ICU. Of these 144 cases, 40 required one or more ICU interventions. By the time the first parameters were collected, the NPV of COBRA was 95.6%. After 3 h of observation, NPV was 100%, while sensitivity, specificity and PPV were 100, 61.1 and 35.1%, respectively. None of these values improved by prolonging the observation time to 6 h. CONCLUSION: In patients with a reported intentional overdose with drugs having potential acute effects on neurological, circulatory or ventilatory function, the COBRA decision rule showed good performances in predicting the need for intensive care interventions, with a NPV of 100% after 3 h of observation

Sex and Gender-Related Differences in COVID-19 Diagnoses and SARS-CoV-2 Testing Practices During the First Wave of the Pandemic:The Dutch Lifelines COVID-19 Cohort Study

Background: Although sex differences are described in Coronavirus Disease 2019 (COVID-19) diagnoses and testing, many studies neglect possible gender-related influences. Additionally, research is often performed in clinical populations, while most COVID-19 patients are not hospitalized. Therefore, we investigated associations between sex and gender-related variables, and COVID-19 diagnoses and testing practices in a large general population cohort during the first wave of the pandemic when testing capacity was limited. Methods: We used data from the Lifelines COVID-19 Cohort (N = 74,722; 60.8% female). We applied bivariate and multiple logistic regression analyses. The outcomes were a COVID-19 diagnosis (confirmed by SARS-CoV-2 PCR testing or physician's clinical diagnosis) and PCR testing. Independent variables included among others participants' sex, age, somatic comorbidities, occupation, and smoking status. Sex-by-comorbidity and sex-by-occupation interaction terms were included to investigate sex differences in associations between the presence of comorbidities or an occupation with COVID-19 diagnoses or testing practices. Results: In bivariate analyses female sex was significantly associated with COVID-19 diagnoses and testing, but significance did not persist in multiple logistic regression analyses. However, a gender-related variable, being a health care worker, was significantly associated with COVID-19 diagnoses (OR = 1.68; 95%CI = 1.30-2.17) and testing (OR = 12.5; 95%CI = 8.55-18.3). Female health care workers were less often diagnosed and tested than male health care workers (ORinteraction = 0.54; 95%CI = 0.32-0.92, ORinteraction = 0.53; 95%CI = 0.29-0.97, respectively). Conclusions: We found no sex differences in COVID-19 diagnoses and testing in the general population. Among health care workers, a male preponderance in COVID-19 diagnoses and testing was observed. This could be explained by more pronounced COVID-19 symptoms in males or by gender inequities

Genomic Dissection of Bipolar Disorder and Schizophrenia, Including 28 Subphenotypes

publisher: Elsevier articletitle: Genomic Dissection of Bipolar Disorder and Schizophrenia, Including 28 Subphenotypes journaltitle: Cell articlelink: https://doi.org/10.1016/j.cell.2018.05.046 content_type: article copyright: © 2018 Elsevier Inc

The Wadden Sea Region: Towards a science for sustainable development

The Wadden Sea is one of the largest intertidal areas in the world and has been designated as a UNESCO World Heritage Site in recognition of its unique natural features. Major changes in the morphology and ecology of the Wadden Sea over the past millennium resulted from increasing anthropogenic influences such as coastal protection, land claim from the sea and drainage of wetland for agriculture, exploitation of natural resources from hunting and fishing to the extraction of groundwater, gas and oil, industrialisation at port locations and tourism at the islands. A sustainable future can only be achieved if policy and management are backed by solid science. Many of the anticipated changes result from the upscaling of pressures on the Wadden Sea system. Economic globalization leads to upscaling of fisheries, tourism and industrial activities, and thus to changed pressures on space and nature. Climate change will lead to changes in hydrographic patterns, species distribution and possibly tourism; through sea-level rise it will put pressure on coastal protection and the extent of intertidal areas. Invasions of exotic species will transform the ecosystem. There are three major related challenges to management: 1. Nature conservation in a changing system requires a focus on preservation of the values and not the state of the system; 2. The adaptation of the management structure to the scale increase of the pressures, so that local and regional management becomes better nested in transregional and transnational governance structures; 3. Finally, the management approach needs to deal with increasing uncertainty in external forcing of the system, as well as with nonlinearities in system dynamics when it is pushed outside its normal range of operation. Based on these pressures and management challenges, we advocate an integrated social-ecological systems approach for the scientific study and the science-based management of the Wadden Sea Region. The essential characteristics of this approach are strong interdisciplinarity and a focus on aspects of scale and cumulative processes

Mutations in PPCS, Encoding Phosphopantothenoylcysteine Synthetase, Cause Autosomal-Recessive Dilated Cardiomyopathy

Coenzyme A (CoA) is an essential metabolic cofactor used by around 4% of cellular enzymes. Its role is to carry and transfer acetyl and acyl groups to other molecules. Cells can synthesize CoA de novo from vitamin B5 (pantothenate) through five consecutive enzymatic steps. Phosphopantothenoylcysteine synthetase (PPCS) catalyzes the second step of the pathway during which phosphopantothenate reacts with ATP and cysteine to form phosphopantothenoylcysteine. Inborn errors of CoA biosynthesis have been implicated in neurodegeneration with brain iron accumulation (NBIA), a group of rare neurological disorders characterized by accumulation of iron in the basal ganglia and progressive neurodegeneration. Exome sequencing in five individuals from two unrelated families presenting with dilated cardiomyopathy revealed biallelic mutations in PPCS, linking CoA synthesis with a cardiac phenotype. Studies in yeast and fruit flies confirmed the pathogenicity of identified mutations. Biochemical analysis revealed a decrease in CoA levels in fibroblasts of all affected individuals. CoA biosynthesis can occur with pantethine as a source independent from PPCS, suggesting pantethine as targeted treatment for the affected individuals still alive