The outbreak of the new Coronavirus disease, COVID-19, has been involved in 77,262 cases in China as well as in 27 other countries as of February 24, 2020. Because the virus is novel to human beings, ...and there is no vaccine yet available, every individual is susceptible and can become infected. Healthcare workers are at high risk, and unfortunately, more than 3,000 healthcare workers in China have been infected. Anesthesiologists are among healthcare workers who are at an even higher risk of becoming infected because of their close contact with infected patients and high potential of exposure to respiratory droplets or aerosol from their patients’ airways. In order to provide healthcare workers with updated recommendations on the management of patients in the perioperative setting as well as for emergency airway management outside of the operating room, the two largest anesthesia societies, the Chinese Society of Anesthesiology (CSA) and the Chinese Association of Anesthesiologists (CAA) have formed a task force to produce the recommendations. The task force hopes to help healthcare workers, particularly anesthesiologists, optimize the care of their patients and protect patients, healthcare workers, and the public from becoming infected. The recommendations were created mainly based on the practice and experience of anesthesiologists who provide care to patients in China. Therefore, adoption of these recommendations outside of China must be done with caution, and the local environment, culture, uniqueness of the healthcare system, and patients’ needs should be considered. The task force will continuously update the recommendations and incorporate new information in future versions.
Growing evidence underlines the pivotal role of infant gut colonization in the development of the immune system. The possibility to modify gut colonization through probiotic supplementation in ...childhood might prevent atopic diseases. The aim of the present systematic review and meta‐analysis was to evaluate the effect of probiotic supplementation during pregnancy and early infancy in preventing atopic diseases. PubMed, Embase and Cochrane Library were searched for randomized controlled trials evaluating the use of probiotics during pregnancy or early infancy for prevention of allergic diseases. Fixed‐effect models were used, and random‐effects models where significant heterogeneity was present. Results were expressed as risk ratio (RR) with 95% confidence interval (CI). Seventeen studies, reporting data from 4755 children (2381 in the probiotic group and 2374 in the control group), were included in the meta‐analysis. Infants treated with probiotics had a significantly lower RR for eczema compared to controls (RR 0.78 95% CI: 0.69–0.89, P = 0.0003), especially those supplemented with a mixture of probiotics (RR 0.54 95% CI: 0.43–0.68, P < 0.00001). No significant difference in terms of prevention of asthma (RR 0.99 95% CI: 0.77–1.27, P = 0.95), wheezing (RR 1.02 95% CI: 0.89–1.17, P = 0.76) or rhinoconjunctivitis (RR 0.91 95% CI: 0.67–1.23, P = 0.53) was documented. The results of the present meta‐analysis show that probiotic supplementation prevents infantile eczema, thus suggesting a new potential indication for probiotic use in pregnancy and infancy.
Coronary artery disease is a major cause of morbidity and mortality worldwide, and is a consequence of acute thrombotic events involving activation of platelets and coagulation proteins. Factor Xa ...inhibitors and aspirin each reduce thrombotic events but have not yet been tested in combination or against each other in patients with stable coronary artery disease.
In this multicentre, double-blind, randomised, placebo-controlled, outpatient trial, patients with stable coronary artery disease or peripheral artery disease were recruited at 602 hospitals, clinics, or community centres in 33 countries. This paper reports on patients with coronary artery disease. Eligible patients with coronary artery disease had to have had a myocardial infarction in the past 20 years, multi-vessel coronary artery disease, history of stable or unstable angina, previous multi-vessel percutaneous coronary intervention, or previous multi-vessel coronary artery bypass graft surgery. After a 30-day run in period, patients were randomly assigned (1:1:1) to receive rivaroxaban (2·5 mg orally twice a day) plus aspirin (100 mg once a day), rivaroxaban alone (5 mg orally twice a day), or aspirin alone (100 mg orally once a day). Randomisation was computer generated. Each treatment group was double dummy, and the patients, investigators, and central study staff were masked to treatment allocation. The primary outcome of the COMPASS trial was the occurrence of myocardial infarction, stroke, or cardiovascular death. This trial is registered with ClinicalTrials.gov, number NCT01776424, and is closed to new participants.
Between March 12, 2013, and May 10, 2016, 27 395 patients were enrolled to the COMPASS trial, of whom 24 824 patients had stable coronary artery disease from 558 centres. The combination of rivaroxaban plus aspirin reduced the primary outcome more than aspirin alone (347 4% of 8313 vs 460 6% of 8261; hazard ratio HR 0·74, 95% CI 0·65–0·86, p<0·0001). By comparison, treatment with rivaroxaban alone did not significantly improve the primary outcome when compared with treatment with aspirin alone (411 5% of 8250 vs 460 6% of 8261; HR 0·89, 95% CI 0·78–1·02, p=0·094). Combined rivaroxaban plus aspirin treatment resulted in more major bleeds than treatment with aspirin alone (263 3% of 8313 vs 158 2% of 8261; HR 1·66, 95% CI 1·37–2·03, p<0·0001), and similarly, more bleeds were seen in the rivaroxaban alone group than in the aspirin alone group (236 3% of 8250 vs 158 2% of 8261; HR 1·51, 95% CI 1·23–1·84, p<0·0001). The most common site of major bleeding was gastrointestinal, occurring in 130 2% patients who received combined rivaroxaban plus aspirin, in 84 1% patients who received rivaroxaban alone, and in 61 1% patients who received aspirin alone. Rivaroxaban plus aspirin reduced mortality when compared with aspirin alone (262 3% of 8313 vs 339 4% of 8261; HR 0·77, 95% CI 0·65–0·90, p=0·0012).
In patients with stable coronary artery disease, addition of rivaroxaban to aspirin lowered major vascular events, but increased major bleeding. There was no significant increase in intracranial bleeding or other critical organ bleeding. There was also a significant net benefit in favour of rivaroxaban plus aspirin and deaths were reduced by 23%. Thus, addition of rivaroxaban to aspirin has the potential to substantially reduce morbidity and mortality from coronary artery disease worldwide.
Bayer AG.
IMPORTANCE: The efficacy of factor XIa inhibition for thromboprophylaxis is unknown. Osocimab is a long-acting, fully human monoclonal antibody that inhibits factor XIa. OBJECTIVE: To compare ...different doses of osocimab with enoxaparin and apixaban for thromboprophylaxis in patients who have undergone knee arthroplasty. DESIGN, SETTING, AND PARTICIPANTS: Randomized, open-label, adjudicator-blinded, phase 2 noninferiority trial with observer blinding for osocimab doses, conducted at 54 hospitals in 13 countries. Adult patients undergoing unilateral knee arthroplasty were randomized from October 2017 through August 2018 and followed up until January 2019. INTERVENTIONS: Single intravenous osocimab postoperative doses of 0.3 mg/kg (n = 107), 0.6 mg/kg (n = 65), 1.2 mg/kg (n = 108), or 1.8 mg/kg (n = 106); preoperative doses of 0.3 mg/kg (n = 109) or 1.8 mg/kg (n = 108); or 40 mg of subcutaneous enoxaparin once daily (n = 105) or 2.5 mg of oral apixaban twice daily (n = 105) for at least 10 days or until venography. MAIN OUTCOMES AND MEASURES: The primary outcome was venous thromboembolism incidence between 10 and 13 days postoperatively (assessed by mandatory bilateral venography performed 10 to 13 days after surgery or confirmed symptomatic deep vein thrombosis or pulmonary embolism). A 5% noninferiority margin compared with enoxaparin was chosen. The primary safety outcome of major or clinically relevant nonmajor bleeding was assessed until 10 to 13 days postoperatively. RESULTS: Of 813 randomized participants (mean SD age, 66.5 years 8.2 years; body mass index, 32.7 5.7; and 74.2% women), 600 were included in the per-protocol population used for the primary analysis. The primary outcome occurred in 18 patients (23.7%) receiving 0.3 mg/kg, 8 (15.7%) receiving 0.6 mg/kg, 13 (16.5%) receiving 1.2 mg/kg, and 14 (17.9%) receiving 1.8 mg/kg of osocimab postoperatively; 23 (29.9%) receiving 0.3 mg/kg and 9 (11.3%) receiving 1.8 mg/kg of osocimab preoperatively; 20 (26.3%) receiving enoxaparin; and 12 (14.5%) receiving apixaban. Osocimab given postoperatively met criteria for noninferiority compared with enoxaparin with risk differences (1-sided 95% CIs) of 10.6% (95% CI, –1.2% to ∞) at the 0.6-mg/kg dose; 9.9% (95% CI, –0.9% to ∞) at the 1.2-mg/kg dose, and 8.4% (95% CI, –2.6 to ∞) at the 1.8-mg/kg dose. The preoperative dose of 1.8 mg/kg of osocimab met criteria for superiority compared with enoxaparin with a risk difference of 15.1%; 2-sided 90% CI, 4.9% to 25.2%). Postoperative and preoperative doses of 0.3 mg/kg of osocimab did not meet the prespecified criteria for noninferiority, with risk differences (1-sided 95% CIs) of 2.6% (95% CI, –8.9% to ∞) and –3.6% (95% CI, –15.5% to ∞), respectively. Major or clinically relevant nonmajor bleeding was observed in up to 4.7% of those receiving osocimab, 5.9% receiving enoxaparin, and 2% receiving apixaban. CONCLUSIONS AND RELEVANCE: Among patients undergoing knee arthroplasty, postoperative osocimab 0.6 mg/kg, 1.2 mg/kg, and 1.8 mg/kg met criteria for noninferiority compared with enoxaparin, and the preoperative 1.8-mg/kg dose of osocimab met criteria for superiority compared with enoxaparin for the primary outcome of incidence of venous thromboembolism at 10 to 13 days postoperatively. Further studies are needed to establish efficacy and safety of osocimab relative to standard thromboprophylaxis. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT03276143
Cities across China implemented stringent social distancing measures in early 2020 to curb coronavirus disease outbreaks. We estimated the speed with which these measures contained transmission in ...cities. A 1-day delay in implementing social distancing resulted in a containment delay of 2.41 (95% CI 0.97-3.86) days.
In December, 2019, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), a novel coronavirus, emerged in Wuhan, China. Since then, the city of Wuhan has taken unprecedented measures in ...response to the outbreak, including extended school and workplace closures. We aimed to estimate the effects of physical distancing measures on the progression of the COVID-19 epidemic, hoping to provide some insights for the rest of the world.
To examine how changes in population mixing have affected outbreak progression in Wuhan, we used synthetic location-specific contact patterns in Wuhan and adapted these in the presence of school closures, extended workplace closures, and a reduction in mixing in the general community. Using these matrices and the latest estimates of the epidemiological parameters of the Wuhan outbreak, we simulated the ongoing trajectory of an outbreak in Wuhan using an age-structured susceptible-exposed-infected-removed (SEIR) model for several physical distancing measures. We fitted the latest estimates of epidemic parameters from a transmission model to data on local and internationally exported cases from Wuhan in an age-structured epidemic framework and investigated the age distribution of cases. We also simulated lifting of the control measures by allowing people to return to work in a phased-in way and looked at the effects of returning to work at different stages of the underlying outbreak (at the beginning of March or April).
Our projections show that physical distancing measures were most effective if the staggered return to work was at the beginning of April; this reduced the median number of infections by more than 92% (IQR 66–97) and 24% (13–90) in mid-2020 and end-2020, respectively. There are benefits to sustaining these measures until April in terms of delaying and reducing the height of the peak, median epidemic size at end-2020, and affording health-care systems more time to expand and respond. However, the modelled effects of physical distancing measures vary by the duration of infectiousness and the role school children have in the epidemic.
Restrictions on activities in Wuhan, if maintained until April, would probably help to delay the epidemic peak. Our projections suggest that premature and sudden lifting of interventions could lead to an earlier secondary peak, which could be flattened by relaxing the interventions gradually. However, there are limitations to our analysis, including large uncertainties around estimates of R0 and the duration of infectiousness.
Bill & Melinda Gates Foundation, National Institute for Health Research, Wellcome Trust, and Health Data Research UK.
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Andrographis paniculata has long been part of the traditional herbal medicine system in Asia and in Scandinavia. Andrographolide was isolated as a major bioactive constituent of A. ...paniculata in 1951, and since 1984, andrographolide and its analogs have been scrutinized with modern drug discovery approach for anti-inflammatory properties. With this accumulated wealth of pre-clinical data, it is imperative to review and consolidate different sources of information, to decipher the major anti-inflammatory mechanisms of action in inflammatory diseases, and to provide direction for future studies. Andrographolide and its analogs have been shown to provide anti-inflammatory benefits in a variety of inflammatory disease models. Among the diverse signaling pathways investigated, inhibition of NF-κB activity is the prevailing anti-inflammatory mechanism elicited by andrographolide. There is also increasing evidence supporting endogenous antioxidant defense enhancement by andrographolide through Nrf2 activation. However, the exact pathway leading to NF-κB and Nrf2 activation by andrographolide has yet to be elucidated. Validation and consensus on the major mechanistic actions of andrographolide in different inflammatory conditions are required before translating current findings into clinical settings. There are a few clinical trials conducted using andrographolide in fixed combination formulation which have shown anti-inflammatory benefits and good safety profile. A concerted effort is definitely needed to identify potent andrographolide lead compounds with improved pharmacokinetics and toxicological properties. Taken together, andrographolide and its analogs have great potential to be the next new class of anti-inflammatory agents, and more andrographolide molecules are likely moving towards clinical study stage in the near future.
Summary
Environmental mastitis is the most common and costly form of mastitis in modern dairy herds where contagious transmission of intramammary pathogens is controlled through implementation of ...standard mastitis prevention programmes. Environmental mastitis can be caused by a wide range of bacterial species, and binary classification of species as contagious or environmental is misleading, particularly for Staphylococcus aureus, Streptococcus uberis and other streptococcal species, including Streptococcus agalactiae. Bovine faeces, the indoor environment and used pasture are major sources of mastitis pathogens, including Escherichia coli and S. uberis. A faeco‐oral transmission cycle may perpetuate and amplify the presence of such pathogens, including Klebsiella pneumoniae and S. agalactiae. Because of societal pressure to reduce reliance on antimicrobials as tools for mastitis control, management of environmental mastitis will increasingly need to be based on prevention. This requires a reduction in environmental exposure through bedding, pasture and pre‐milking management and enhancement of the host response to bacterial challenge. Efficacious vaccines are available to reduce the impact of coliform mastitis, but vaccine development for gram‐positive mastitis has not progressed beyond the “promising” stage for decades. Improved diagnostic tools to identify causative agents and transmission patterns may contribute to targeted use of antimicrobials and intervention measures. The most important tool for improved uptake of known mastitis prevention measures is communication. Development of better technical or biological tools for management of environmental mastitis must be accompanied by development of appropriate incentives and communication strategies for farmers and veterinarians, who may be confronted with government‐mandated antimicrobial use targets if voluntary reduction is not implemented.
•Subsyndromal mental health concerns are a common response to the COVID-19 outbreak.•These responses affect both the general public and healthcare workers.•Depressive and anxiety symptoms have been ...reported in 16–28% of subjects screened.•Novel methods of consultation, such as online services, can be helpful for these patients.•There is a need for further long-term research in this area, especially from other countries
The COVID-19 pandemic is a major health crisis affecting several nations, with over 720,000 cases and 33,000 confirmed deaths reported to date. Such widespread outbreaks are associated with adverse mental health consequences. Keeping this in mind, existing literature on the COVID-19 outbreak pertinent to mental health was retrieved via a literature search of the PubMed database. Published articles were classified according to their overall themes and summarized. Preliminary evidence suggests that symptoms of anxiety and depression (16–28%) and self-reported stress (8%) are common psychological reactions to the COVID-19 pandemic, and may be associated with disturbed sleep. A number of individual and structural variables moderate this risk. In planning services for such populations, both the needs of the concerned people and the necessary preventive guidelines must be taken into account. The available literature has emerged from only a few of the affected countries, and may not reflect the experience of persons living in other parts of the world. In conclusion, subsyndromal mental health problems are a common response to the COVID-19 pandemic. There is a need for more representative research from other affected countries, particularly in vulnerable populations.
Depression and anxiety (internalizing disorders) are the largest contributors to the non-fatal health burden among young people. This is the first meta-analysis to examine the joint efficacy of ...universal, selective, and indicated preventive interventions upon both depression and anxiety among children and adolescents (5-18 years) while accounting for their co-morbidity. We conducted a systematic review of reviews in Medline, PsycINFO and the Cochrane Library of Systematic Reviews, from 1980 to August 2014. Multivariate meta-analysis examined the efficacy of preventive interventions on depression and anxiety outcomes separately, and the joint efficacy on both disorders combined. Meta-regressions examined heterogeneity of effect according to a range of study variables. Outcomes were relative risks (RR) for disorder, and standardized mean differences (Cohen's d) for symptoms. One hundred and forty-six randomized controlled trials (46 072 participants) evaluated universal (children with no identified risk, n = 54) selective (population subgroups of children who have an increased risk of developing internalizing disorders due to shared risk factors, n = 45) and indicated prevention (children with minimal but detectable symptoms of an internalizing disorder, n = 47), mostly using psychological-only strategies (n = 105). Reductions in internalizing disorder onset occurred up to 9 months post-intervention, whether universal RR 0.47, 95% confidence interval (CI) 0.37-0.60, selective (RR 0.61, 95% CI 0.43-0.85) or indicated (RR 0.48, 95% CI 0.29-0.78). Reductions in internalizing symptoms occurred up to 12 months post-intervention for universal prevention; however, reductions only occurred in the shorter term for selective and indicated prevention. Universal, selective and indicated prevention interventions are efficacious in reducing internalizing disorders and symptoms in the short term. They might be considered as repeated exposures in school settings across childhood and adolescence. (PROSPERO registration: CRD42014013990.).
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