关键词： COVID-19   MIS-C   pediatric   ROTEM   SARS-CoV-2   thrombosis  

摘要： Background Adults infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have had high rates of thrombosis. A novel condition in children infected with SARS-CoV-2, multisystem inflammatory syndrome in children (MIS-C), has limited data on their prothrombotic state or need for thromboprophylaxis. Objectives We aimed to analyze the prothrombotic state using coagulation profiles, rotational thromboelastometry (ROTEM) parameters and clinical outcomes, to determine if this could aid in risk stratification for thromboprophylaxis. Methods This analysis included patients (<21 years of age) with a diagnosis of MIS-C (n = 40) and controls (presenting with suspicion of MIS-C but later ruled out;n = 26). Results MIS-C patients had higher levels of inflammatory markers including D-dimer (p < .0001), compared with controls, along with evidence of hypercoagulability on ROTEM with elevated evaluation of fibrinogen activity (FIBTEM) maximum clot firmness (MCF) (p < .05). For MIS-C patients with D-dimers >1000 ng/ml, there was a significant correlation of FIBTEM MCF (p < .0001) with a mean value of 37.4 (standard deviation 5.1). D-dimer >2144 ng/ml was predictive of intensive care unit admission (area under the curve [AUC] 0.80;95% confidence interval, 0.60-0.99;p < .01;sensitivity: 82%, specificity: 75%), and elevated FIBTEM MCF (AUC 1 for >2500 ng/ml). MIS-C patients (50%) received enoxaparin thromboprophylaxis (in addition to aspirin) with significant improvement in their inflammatory and ROTEM parameters upon outpatient follow-up;none developed symptomatic thrombosis. Conclusions Despite an observed prothrombotic state, none of the MIS-C patients (on aspirin alone or in combination with enoxaparin) developed symptomatic thrombosis. ROTEM, in addition to coagulation profiles, may be helpful to tailor thromboprophylaxis in critically ill MIS-C patients.

摘要： BACKGROUND Previous studies have suggested that healthcare professionals may be susceptible to substance use disorders, and among the medical specialties, anaesthesia providers appear to be overrepresented. OBJECTIVE We aimed to compare the prevalence of substance use-related mortality and suicides between anaesthesia and nonanaesthesia professionals. DESIGN Systematic review of observational studies with meta-analyses. We defined anaesthesia providers as any healthcare professionals belonging to the specialty, regardless of age and duration of employment. Other healthcare professionals served as the control group. DATA SOURCES Ovid Medline, EMBASE, Web of Science, Scopus, Scielo, LILACS and ProQuest databases up to March 2020. RESULTS Thirty-nine studies were included, 31 cross-sectional studies involving 13 819 participants and eight cohorts with a total 129 811 participants proved eligible. Results suggested a higher rate of drug-related mortality with odds ratio (OR) 2.69 [95% confidence interval (CI), 1.80 to 4.00;P I-2 = 0%, P = 0.55;high-certainty evidence] and suicide (OR 2.18, 95% CI, 1.33 to 3.58;P = 0.002;I-2 = 0%, P = 0.68;moderate-certainty evidence) for anaesthesia providers compared with other healthcare professionals. CONCLUSION High-to-moderate-certainty evidence shows that there is more than a two-fold increased rate of substance use-related mortality and suicide among anaesthesia providers compared with other healthcare professionals. Investigations examining substance abuse between healthcare professionals, with particular attention to working conditions and exposure are essential to further develop preventive strategies.

关键词： CAM   Complementary and alternative medicine   Adverse events   Surveillance study  

摘要： Pediatric use of complementary and alternative medicine (CAM) in the Netherlands is highly prevalent. The risks of pediatric CAM use are, however, largely unknown. Therefore, a 3-year survey was carried out at the Dutch Pediatric Surveillance Unit. Pediatricians were asked to register cases of adverse events associated with pediatric CAM usage. In 3 years, 32 unique adverse events were registered. Twenty-two of these adverse events were indirect and not related to the specific CAM therapy but due to delaying, changing, or stopping of regular treatment, a deficient or very restrictive diet or an incorrect diagnosis by a CAM therapist. These events were associated with many different CAM therapies. Nine events were deemed direct adverse events like bodily harm or toxicity and one-third of them occurred in infants. Only supplements, manual therapies, and (Chinese) herbs were involved in these nine events. In one case, there was a risk of a serious adverse event but harm had not yet occurred. Conclusion: Relatively few cases of adverse events associated with pediatric CAM usage were found, mostly due to delaying or stopping conventional treatment. Nevertheless, parents, pediatricians and CAM providers should be vigilant for both direct and indirect adverse events in children using CAM, especially in infants.

摘要： The COVID-19 pandemic has disrupted medical research, pushing mentors and mentees to decide if COVID-19 research would be germane to the early career investigator's developing research portfolio. With COVID-19 halting hundreds of federal trials involving non-COVID-19 research, mentors and mentees must also consider the broader moral calling of contributing to COVID-19 research. At the time of writing, the National Institutes of Health had responded to the pandemic with significant funding for COVID-19 research. However, because this pandemic is a new phenomenon, few mentors have expertise in the disease and relevant established resources. As a result, many mentors are unable to provide insight on COVID-19 research to early career investigators considering a pivot toward research related to this disease. The authors suggest 4 ways for mentees and mentors to respond to the changes the pandemic has brought to research funding and opportunities: (1) include COVID-19 research in existing portfolios to diversify intellectual opportunities and reduce funding risks;(2) negotiate the mentor-mentee relationship and roles and expectations early in project discussions-considering, as relevant, the disproportionate burden of home responsibilities often borne by early career faculty members who are women and/or from a minority group;(3) address any mentor limitations in content expertise;and (4) if the decision is to pivot to COVID-19 research, select projects with implications generalizable beyond this pandemic to other infectious outbreaks or to the redesign of health care delivery. Mentors and mentees must weigh the relevance of COVID-19 research projects to the postpandemic world and the amount of available funding against the developing interests of early career investigators. Academic medical centers nationwide must enable seasoned and early career researchers to contribute meaningfully to COVID-19 and non-COVID-19 research.

关键词： Carbon accounting   Land use   Scenario planning   LANDIS-II   PnET  

摘要： The extent to which forest carbon sequestration can help mitigate climate change will be determined in large part by future land use. Here we quantify the impacts of five divergent future land-use scenarios on aboveground forest carbon stocks and fluxes throughout New England. These scenarios, four co-designed with stakeholders from throughout the region and the fifth a continuation of recent trends in land use, were simulated by coupling a land-cover change model with a mechanistic forest growth model to produce estimates of aboveground carbon over 50 years. We tracked the fate of forest carbon removed through harvesting and development using a standard carbon accounting methodology, modified to fit our modeling framework. Of the simulated changes in land use, changes in harvesting had the most profound and immediate impacts on carbon stocks and fluxes. In one land-use scenario that included a rapid expansion of harvesting for biomass energy, New England's forests stopped serving as a net carbon sink and became a net carbon source by 2060. In an alternative scenario, relatively small reductions in harvest intensities (i.e., similar to 10% less biomass removed), coupled with an increased percent of wood going into longer-term storage, led to substantial reductions in net carbon emissions (909 MMtCO(2)eq) as compared to a continuation of recent trends in land use. However, these projected gains in carbon storage and reduction in emissions from less intense harvesting regimes can only be realized if they are paired with a reduction in the consumption of the timber products, and their replacements, that otherwise would result in additional emissions from leakage and substitution.

摘要： To establish a research and development agenda for Entrustable Professional Activities (EPAs) for the coming decade, the authors, all active in this area of investigation, reviewed recent research papers, seeking recommendations for future research. They pooled their knowledge and experience to identify 3 levels of potential research and development: the micro level of learning and teaching;the meso level of institutions, programs, and specialty domains;and the macro level of regional, national, and international dynamics. Within these levels, the authors categorized their recommendations for research and *** authors identified 14 discrete themes, each including multiple questions or issues for potential exploration, that range from foundational and conceptual to *** research to date has focused on a variety of issues regarding development and early implementation of EPAs. Future research should focus on large-scale implementation of EPAs to support competency-based medical education (CBME) and on its consequences at the 3 levels. In addition, emerging from the implementation phase, the authors call for rigorous studies focusing on conceptual issues. These issues include the nature of entrustment decisions and their relationship with education and learner progress and the use of EPAs across boundaries of training phases, disciplines and professions, including continuing professional development. International studies evaluating the value of EPAs across countries are another important consideration. Future studies should also remain alert for unintended consequences of the use of *** were conceptualized to support CBME in its endeavor to improve outcomes of education and patient care, prompting creation of this agenda.

关键词： Agglutinin-like sequence protein 3   azole derivatives   Terminalia chebula   vulvovaginal candidiasis  

摘要： Chebulinic acid, a chemotaxonamic marker of Terminalia chebula has been described in Ayurveda, Unani and Homeopathy traditional medicinal system for the treatment of various fungal diseases. Almost 70-80 % of women are currently affected from vulvovaginal candidiasis and the overgrowth of Candida albicans is the major reason behind it. The aim of the present study was to determine the efficacy of chebulinic acid in inhibiting adhesion as well as growth of Candida albicans inside the host in comparison with currently available azole derivatives in the market. The inhibitory effect of chebulinic acid was determined by spectrophotometric growth curve analysis reflecting 10 % lower minimum inhibitory concentration value of fluconazole, ketaconazole, itraconazole and chebulinic acid. Virtual docking study was carried out at catalytic domain of agglutinin-like sequence protein 3 chain A and B respectively, to determine the binding affinity and its active binding sites. Chebulinic acid exhibited high sensitivity against Candida albicans with minimum inhibitory concentration of (0.025 mu g/ml) followed by ketaconazole (0.05), itraconazole (0.048) and fluconazole (1.5). An extended lag phase and a decline in overall growth were observed in Candida albicans when compared to control when grown in presence of chebulinic acid. At ASN22, TYR23, TRP224, ASP169, TYR166, ASP162, ASN225 GLY297, ARG294 and ASP162, ASN160, ASP169, THR168, TYR166, TYR226, chebulinic acid binds with agglutinin-like sequence protein 3 chain A and B respectively with binding affinity of -10.4 and -9.8 kcal/mol. Our present study strengthens the evidences which stand in support of the fact that chebulinic acid can be used as potent inhibitor of Candida albicans than other commercially available synthetic anti-fungal drugs.