An Open-Label, Pragmatic, Randomized Controlled Clinical Trial to Evaluate the Comparative Effectiveness of Daptomycin Versus Vancomycin for the Treatment of Complicated Skin and Skin Structure Infection

Treatment of complicated skin and skin structure infection (cSSSI) places a tremendous burden on the health care system. Understanding relative resource utilization associated with different antimicrobials is important for decision making by patients, health care providers, and payers. Methods: The authors conducted an open-label, pragmatic, randomized (1:1) clinical study (N = 250) to compare the effectiveness of daptomycin with that of vancomycin for treatment of patients hospitalized with cSSSI caused by suspected or documented methicillin-resistant Staphylococcus aureus infection. The primary study end point was infection-related length of stay (IRLOS). Secondary end points included health care resource utilization, cost, clinical response, and patient-reported outcomes. Patient assessments were performed daily until the end of antibiotic therapy or until hospital discharge, and at 14 days and 30 days after discharge. Results: No difference was found for IRLOS, total LOS, and total inpatient cost between cohorts. Hospital LOS contributed 85.9 % to the total hospitalization cost, compared with 6.4 % for drug costs. Daptomycin showed a nonsignificant trend toward a higher clinical success rate, compared with vancomycin, at treatment days 2 and 3. In the multivariate analyses, vancomycin was associated with a lower likelihood of day 2 clinical success (odds ratio [OR] = 0.498, 95 % confidence interval [CI], 0.249-0.997; P < 0.05). Conclusion: This study did not provide conclusive evidence of the superiority of one treatment over the other in terms of clinical, economic, or patient outcomes. The data suggest that physician and patient preference, rather than drug acquisition cost, should be the primary driver of initial antibiotic selection for hospitalized patients with cSSSI.Merck & Co., Inc., Kenilworth, NJ USAKinesiology and Health Educatio

How many bird and mammal extinctions has recent conservation action prevented?

Aichi Target 12 of the Convention on Biological Diversity (CBD) aims to ‘prevent extinctions of known threatened species’. To measure its success, we used a Delphi expert elicitation method to estimate the number of bird and mammal species whose extinctions were prevented by conservation action in 1993 - 2020 (the lifetime of the CBD) and 2010 - 2020 (the timing of Aichi Target 12). We found that conservation prevented 21–32 bird and 7–16 mammal extinctions since 1993, and 9–18 bird and 2–7 mammal extinctions since 2010. Many remain highly threatened, and may still become extinct in the near future. Nonetheless, given that ten bird and five mammal species did go extinct (or are strongly suspected to) since 1993, extinction rates would have been 2.9–4.2 times greater without conservation action. While policy commitments have fostered significant conservation achievements, future biodiversity action needs to be scaled up to avert additional extinctions

The Chemokine CXCL16 and Its Receptor, CXCR6, as Markers and Promoters of Inflammation-Associated Cancers

Clinical observations and mouse models have suggested that inflammation can be pro-tumorigenic. Since chemokines are critical in leukocyte trafficking, we hypothesized that chemokines play essential roles in inflammation-associated cancers. Screening for 37 chemokines in prostate cancer cell lines and xenografts revealed CXCL16, the ligand for the receptor CXCR6, as the most consistently expressed chemokine. Immunohistochemistry and/or immunofluorescence and confocal imaging of 121 human prostate specimens showed that CXCL16 and CXCR6 were co-expressed, both on prostate cancer cells and adjacent T cells. Expression levels of CXCL16 and CXCR6 on cancer cells correlated with poor prognostic features including high-stage and high-grade, and expression also correlated with post-inflammatory changes in the cancer stroma as revealed by loss of alpha-smooth muscle actin. Moreover, CXCL16 enhanced the growth of CXCR6-expressing cancer and primary CD4 T cells. We studied expression of CXCL16 in an additional 461 specimens covering 12 tumor types, and found that CXCL16 was expressed in multiple human cancers associated with inflammation. Our study is the first to describe the expression of CXCL16/CXCR6 on both cancer cells and adjacent T cells in humans, and to demonstrate correlations between CXCL16 and CXCR6 vs. poor both prognostic features and reactive changes in cancer stoma. Taken together, our data suggest that CXCL16 and CXCR6 may mark cancers arising in an inflammatory milieu and mediate pro-tumorigenic effects of inflammation through direct effects on cancer cell growth and by inducing the migration and proliferation of tumor-associated leukocytes

ARIA digital anamorphosis : Digital transformation of health and care in airway diseases from research to practice

Digital anamorphosis is used to define a distorted image of health and care that may be viewed correctly using digital tools and strategies. MASK digital anamorphosis represents the process used by MASK to develop the digital transformation of health and care in rhinitis. It strengthens the ARIA change management strategy in the prevention and management of airway disease. The MASK strategy is based on validated digital tools. Using the MASK digital tool and the CARAT online enhanced clinical framework, solutions for practical steps of digital enhancement of care are proposed.Peer reviewe

How many bird and mammal extinctions has recent conservation action prevented?

Aichi Target 12 of the Convention on Biological Diversity (CBD) contains the aim to ‘prevent extinctions of known threatened species’. To measure the degree to which this was achieved, we used expert elicitation to estimate the number of bird and mammal species whose extinctions were prevented by conservation action in 1993–2020 (the lifetime of the CBD) and 2010–2020 (the timing of Aichi Target 12). We found that conservation action prevented 21–32 bird and 7–16 mammal extinctions since 1993, and 9–18 bird and two to seven mammal extinctions since 2010. Many remain highly threatened and may still become extinct. Considering that 10 bird and five mammal species did go extinct (or are strongly suspected to) since 1993, extinction rates would have been 2.9–4.2 times greater without conservation action. While policy commitments have fostered significant conservation achievements, future biodiversity action needs to be scaled up to avert additional extinctions.https://wileyonlinelibrary.com/journal/conlMammal Research Institut

Cabbage and fermented vegetables : From death rate heterogeneity in countries to candidates for mitigation strategies of severe COVID-19

Large differences in COVID-19 death rates exist between countries and between regions of the same country. Some very low death rate countries such as Eastern Asia, Central Europe, or the Balkans have a common feature of eating large quantities of fermented foods. Although biases exist when examining ecological studies, fermented vegetables or cabbage have been associated with low death rates in European countries. SARS-CoV-2 binds to its receptor, the angiotensin-converting enzyme 2 (ACE2). As a result of SARS-CoV-2 binding, ACE2 downregulation enhances the angiotensin II receptor type 1 (AT(1)R) axis associated with oxidative stress. This leads to insulin resistance as well as lung and endothelial damage, two severe outcomes of COVID-19. The nuclear factor (erythroid-derived 2)-like 2 (Nrf2) is the most potent antioxidant in humans and can block in particular the AT(1)R axis. Cabbage contains precursors of sulforaphane, the most active natural activator of Nrf2. Fermented vegetables contain many lactobacilli, which are also potent Nrf2 activators. Three examples are: kimchi in Korea, westernized foods, and the slum paradox. It is proposed that fermented cabbage is a proof-of-concept of dietary manipulations that may enhance Nrf2-associated antioxidant effects, helpful in mitigating COVID-19 severity.Peer reviewe

Nrf2-interacting nutrients and COVID-19 : time for research to develop adaptation strategies

There are large between- and within-country variations in COVID-19 death rates. Some very low death rate settings such as Eastern Asia, Central Europe, the Balkans and Africa have a common feature of eating large quantities of fermented foods whose intake is associated with the activation of the Nrf2 (Nuclear factor (erythroid-derived 2)-like 2) anti-oxidant transcription factor. There are many Nrf2-interacting nutrients (berberine, curcumin, epigallocatechin gallate, genistein, quercetin, resveratrol, sulforaphane) that all act similarly to reduce insulin resistance, endothelial damage, lung injury and cytokine storm. They also act on the same mechanisms (mTOR: Mammalian target of rapamycin, PPAR gamma:Peroxisome proliferator-activated receptor, NF kappa B: Nuclear factor kappa B, ERK: Extracellular signal-regulated kinases and eIF2 alpha:Elongation initiation factor 2 alpha). They may as a result be important in mitigating the severity of COVID-19, acting through the endoplasmic reticulum stress or ACE-Angiotensin-II-AT(1)R axis (AT(1)R) pathway. Many Nrf2-interacting nutrients are also interacting with TRPA1 and/or TRPV1. Interestingly, geographical areas with very low COVID-19 mortality are those with the lowest prevalence of obesity (Sub-Saharan Africa and Asia). It is tempting to propose that Nrf2-interacting foods and nutrients can re-balance insulin resistance and have a significant effect on COVID-19 severity. It is therefore possible that the intake of these foods may restore an optimal natural balance for the Nrf2 pathway and may be of interest in the mitigation of COVID-19 severity

ARIA digital anamorphosis: Digital transformation of health and care in airway diseases from research to practice

Digital anamorphosis is used to define a distorted image of health and care that may be viewed correctly using digital tools and strategies. MASK digital anamorphosis represents the process used by MASK to develop the digital transformation of health and care in rhinitis. It strengthens the ARIA change management strategy in the prevention and management of airway disease. The MASK strategy is based on validated digital tools. Using the MASK digital tool and the CARAT online enhanced clinical framework, solutions for practical steps of digital enhancement of care are proposed

Elite Motorcycle Racing: Crash Types and Injury Patterns in the MotoGP Class

Crashes are a small but regular feature of elite motorcycle racing. These crashes provide a novel opportunity to benchmark and analyze motorcycle crash mechanics, crash types, and associated injuries at high speeds in a cohort of riders who are well protected and in a controlled environment. The purpose was to benchmark the prevalence of injuries, categorize crash subtypes, and determine associated injury patterns. This was an institutional review board-approved, prospective observational cohort study of MotoGP riders for 1 racing season in 3 venues. Accident type was determined by race-marshal report and visual analysis of race footage for each crash. Accident types were defined as lowside (falling toward the inside of the turn), highside (falling over and toward the outside of the turn), and topside (going over the handlebars of the motorcycle). Specific injuries and hospital admission data were collected using a standardized data collection form. Basic descriptive statistics were performed on all categorical variables. We used the exact binomial test examine the association between accident type and retirement from race, transport to medical building, transport to hospital, and injuries sustained. Crash prevalence was 9.7 per hundred rider hours. There were 78 crashes: 58 lowsides, 13 highsides, 2 topsides, and 5 indeterminate. In the lowside group (n = 58), 19 (95% confidence interval [CI], 0.21-0.46) riders retired, 0 required emergent transportation to the track facility or to the hospital, and 1 (95% CI, <0.1-0.9) significant injury was noted. In the highside group (n = 13), 10 (95% CI, 0.46-0.95) retired, 9 (95% CI, 0.39-0.91) were transported to the track medical facility, and 3 (95% CI, 0.05-0.54) were admitted to the hospital. In the highside group, there were 7 (95% CI, 0.25-0.81) significant injuries. In the topside group, both riders were retired with 1 hospital admission. Lowside crashes had a lower rate of retirement from race, emergent transport, and significant injuries compared with highside crashes. Lowside crashes are lower risk than highside crashes. Most highside crashes are caused by oversteering to prevent an impending lowside crash. Strategies to reduce oversteering to prevent a lowside crash may reduce highside crashes, enhance the safety for riders in MotoGP racing, and be applicable to recreational motorcycle riding