Antiinflammatory Therapy with Canakinumab for Atherosclerotic Disease

Background: Experimental and clinical data suggest that reducing inflammation without affecting lipid levels may reduce the risk of cardiovascular disease. Yet, the inflammatory hypothesis of atherothrombosis has remained unproved. Methods: We conducted a randomized, double-blind trial of canakinumab, a therapeutic monoclonal antibody targeting interleukin-1β, involving 10,061 patients with previous myocardial infarction and a high-sensitivity C-reactive protein level of 2 mg or more per liter. The trial compared three doses of canakinumab (50 mg, 150 mg, and 300 mg, administered subcutaneously every 3 months) with placebo. The primary efficacy end point was nonfatal myocardial infarction, nonfatal stroke, or cardiovascular death. RESULTS: At 48 months, the median reduction from baseline in the high-sensitivity C-reactive protein level was 26 percentage points greater in the group that received the 50-mg dose of canakinumab, 37 percentage points greater in the 150-mg group, and 41 percentage points greater in the 300-mg group than in the placebo group. Canakinumab did not reduce lipid levels from baseline. At a median follow-up of 3.7 years, the incidence rate for the primary end point was 4.50 events per 100 person-years in the placebo group, 4.11 events per 100 person-years in the 50-mg group, 3.86 events per 100 person-years in the 150-mg group, and 3.90 events per 100 person-years in the 300-mg group. The hazard ratios as compared with placebo were as follows: in the 50-mg group, 0.93 (95% confidence interval [CI], 0.80 to 1.07; P = 0.30); in the 150-mg group, 0.85 (95% CI, 0.74 to 0.98; P = 0.021); and in the 300-mg group, 0.86 (95% CI, 0.75 to 0.99; P = 0.031). The 150-mg dose, but not the other doses, met the prespecified multiplicity-adjusted threshold for statistical significance for the primary end point and the secondary end point that additionally included hospitalization for unstable angina that led to urgent revascularization (hazard ratio vs. placebo, 0.83; 95% CI, 0.73 to 0.95; P = 0.005). Canakinumab was associated with a higher incidence of fatal infection than was placebo. There was no significant difference in all-cause mortality (hazard ratio for all canakinumab doses vs. placebo, 0.94; 95% CI, 0.83 to 1.06; P = 0.31). Conclusions: Antiinflammatory therapy targeting the interleukin-1β innate immunity pathway with canakinumab at a dose of 150 mg every 3 months led to a significantly lower rate of recurrent cardiovascular events than placebo, independent of lipid-level lowering. (Funded by Novartis; CANTOS ClinicalTrials.gov number, NCT01327846.

Multi-messenger observations of a binary neutron star merger

On 2017 August 17 a binary neutron star coalescence candidate (later designated GW170817) with merger time 12:41:04 UTC was observed through gravitational waves by the Advanced LIGO and Advanced Virgo detectors. The Fermi Gamma-ray Burst Monitor independently detected a gamma-ray burst (GRB 170817A) with a time delay of ~1.7 s with respect to the merger time. From the gravitational-wave signal, the source was initially localized to a sky region of 31 deg2 at a luminosity distance of 40+8-8 Mpc and with component masses consistent with neutron stars. The component masses were later measured to be in the range 0.86 to 2.26 Mo. An extensive observing campaign was launched across the electromagnetic spectrum leading to the discovery of a bright optical transient (SSS17a, now with the IAU identification of AT 2017gfo) in NGC 4993 (at ~40 Mpc) less than 11 hours after the merger by the One- Meter, Two Hemisphere (1M2H) team using the 1 m Swope Telescope. The optical transient was independently detected by multiple teams within an hour. Subsequent observations targeted the object and its environment. Early ultraviolet observations revealed a blue transient that faded within 48 hours. Optical and infrared observations showed a redward evolution over ~10 days. Following early non-detections, X-ray and radio emission were discovered at the transient’s position ~9 and ~16 days, respectively, after the merger. Both the X-ray and radio emission likely arise from a physical process that is distinct from the one that generates the UV/optical/near-infrared emission. No ultra-high-energy gamma-rays and no neutrino candidates consistent with the source were found in follow-up searches. These observations support the hypothesis that GW170817 was produced by the merger of two neutron stars in NGC4993 followed by a short gamma-ray burst (GRB 170817A) and a kilonova/macronova powered by the radioactive decay of r-process nuclei synthesized in the ejecta

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

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

The cross-sectional association of frailty with chronic past and current use of benzodiazepine drugs

Frailty, a clinical syndrome characterized by vulnerability to stressors resulting from multisystemic loss of physiological reserve. The use of benzodiazepines in older adults has been associated with confusion, sedation, and cognitive impairment, which in turn may lead to frailty. The purpose of this study was to determine the cross-sectional association between frailty and chronic past or current use of benzodiazepine drugs among older US Veterans. This is a cross-sectional study of community-dwelling older Veterans who had determinations of frailty. Benzodiazepine prescription data were obtained via EHR. A 31-item VA Frailty Index (VA-FI) was generated at the time of the assessment. We categorized Veterans into robust (FI ≤ 0.10), pre-frail (FI 0.10-0.21), and Frail (FI ≥ 0.21). After adjusting for sociodemographic characteristics, we calculated ORs and 95% CIs using a binomial logistic regression (BLR) model to assess the cross-sectional association between benzodiazepine use and frailty. Population sample consisted of 17,423 Veterans, mean age 75.53 (SD = 8.03) years, 70.80% Caucasian, 97.34% male, 14,545 (83.50%) patients were non-users of benzodiazepine drugs, 2408 (13.80%) had a past use, and 470 (2.70%) were current users. In BLR, individuals with past (OR 2.51, 95% CI 2.30-2.74, p < .001) or current (OR 2.36, 95% CI 1.96-2.83, p < .001) use showed a higher association with frailty as compared to individuals who were non-users. The use of benzodiazepine was cross-sectionally associated with frailty in older Veterans. These results suggest that screening for frailty in patients with past or current exposure to benzodiazepine medications may be necessary for proper management

Association between a Frailty Index from Common Laboratory Values and Vital Signs (FI-LAB) and Hospital and Post-Hospital Outcomes in Veterans with COVID-19 Infection

ObjectivesDetermine the association of higher FI-LAB scores, derived from common laboratory values and vital signs, with hospital and post-hospital outcomes in Veterans hospitalized with COVID-19 infection.Design, Setting, and ParticipantsA retrospective, multicenter, cohort study of 7 Veterans Health Administration (VHA) medical centers in Florida and Puerto Rico. Patients aged 18 years and older hospitalized with COVID-19 and followed for up to 1 year post discharge or until death.Clinical Frailty Measure: FI-LAB. Main Outcomes and MeasuresHospital and post-hospital outcomes.ResultsOf the 671 eligible patients, 615 (91.5%) patients were included (mean [SD] age, 66.1 [14.8] years; 577 men [93.8%]; median stay, 8 days [IQR:3-15]. There were sixty-one in-hospital deaths. Veterans in the moderate and high FI-LAB groups had a higher proportion of inpatient mortality (13.3% and 20.6%, respectively) than the low group (4.1%), p <0.001. Moderate and high FI-LAB scores were associated with greater inpatient mortality when compared to the low group, OR:3.22 (95%CI:1.59-6.54), p=.001 and 6.05 (95%CI:2.48-14.74), p<0.001, respectively. Compared with low FI-LAB scores, moderate and high scores were also associated with prolonged length of stay, intensive care unit (ICU) admission, and transfer.Conclusions and RelevanceIn this study of patients admitted to 7 VHA Hospitals during the first surge of the pandemic, higher FI-LAB scores were associated with higher in-hospital mortality and other in-hospital outcomes; FI-LAB can serve as a validated, rapid, feasible, and objective frailty tool in hospitalized adults with COVID-19 that can aid clinical care