Previous data has shown that interferon and ribavirin use in the treatment of chronic hepatitis C virus (HCV) infection in kidney transplant recipients is limited because of the increased risk for interferon-mediated graft rejection and low efficacy. The purpose of this study was to evaluate the safety and efficacy of interferon and ribavirin free ledipasvir-sofosbuvir regimen in kidney transplant recipients with chronic genotype 1 or 4 HCV infection. This was a randomized phase 2, open label study conducted in 5 sites in Europe involving 114 patients with treatment-naïve or treatment-experienced kidney transplant recipients with chronic genotype HCV 1 or 4 infection with or without compensated cirrhosis who were randomly assigned 1:1 to receive ledipasvir (90mg) and sofosbuvir (400mg) for 12 or 24 weeks. The authors found that 57 out of 57 patients (100%) treated for 24 weeks (95% CI: 94% to 100%) and 57 out of 57 (100%) treated for 12 weeks (95% C: 94% to 100%) achieved HCV RNA less than the lower limit of quantification. Serious adverse events were reported in 13 patients (11%). The most frequent adverse events overall were headache (n=22 (19%)), asthma (n=16 (14%)), and fatigue (n=11 (10%)). The authors concluded that ledipasvir-sofosbuvir appeared to be an effective treatment with an acceptable safety profile.
Pembrolizumab is a monoclonal antibody against programmed death ligand 1 (PD-L1) and because a substantial proportion of patients with non-small-cell lung cancer (NSCLC) have high levels of PD-L1 expression, several studies have sought to investigate the utility of pembrolizumab in the primary treatment of NSCLC. This is an open label phase 3 trial where 305 patients with previously untreated NSCLC with PD-L1 expression on at least 50% of tumor cells were randomly assigned in a 1:1 ratio to the pembrolizumab group (n=154) or chemotherapy group (n=151) with a median duration of follow-up of 11.2 months. The primary endpoint, progression-free survival, was assessed by means of blinded, independent, central radiologic review. The authors found that the median progression-free survival in the pembrolizumab group was 10.3 months (95% CI: 6.7 to not reached) versus 6 months (95% CI: 4.2 to 6.2) in the chemotherapy group (hazard ratio for disease progression or death, 0.50; 95% CI: 0.37 to 0.68; P<0.001). For overall survival at 6 months, this was found to be 80.2% (95%CI: 72.9 to 85.7%) in the pembrolizumab group and 72.4% (95%CI: 64.5 to 78.9%) in the chemotherapy group (HR 0.60; 95%CI: 0.41 to 0.89; p = 0.005). The response rate was higher in the pembrolizumab group than in the chemotherapy group (44.8% vs 27.8%). The authors concluded that in advanced NSCLC and PD-L1 expression on at least 50% of tumor cells, pembrolizumab was associated with significantly longer progression-free and overall survival with fever adverse events than platinum based chemotherapy.
While in adult out-of hospital cardiac arrest can be managed by compression-only CPR as opposed to conventional CPR with rescue breaths without worsened outcomes, in the pediatric population, the same may not be true as most of the arrests in this population are caused by asphyxiation where CPR rescue breaths may be efficacious. The purpose of this study was to evaluate the outcome and prevalence of bystander cardiopulmonary resuscitation (BCPR) in children 18 years and younger. The outcome of interest was the overall survival and neurologically favorable survival defined as the Cerebral Performance Category score of 1 or 2 at the time of hospital discharge. This was a retrospective cohort study which used data from the Cardiac Arrest Registry to Enhance Survival (CARES) database that collected details of cardiac arrests for 37 states from 2013 to 2015. Of the 3,900 out-of hospital cardiac arrests during the study period, 59% occurred in infants <1 year of age with 83.7% occurring at a home/residence and 3595 (92.2%) having non-shockable rhythms (asystole). BCPR was performed in 1814 children (46.5%) and was more common for white children (687 of 1221 [56.3%]) compared to African American children (447 of 1134 [39.4%]). BCPR was associated with improved survival to hospital discharge (aOR 1.57; 95%CI: 1.25-1.96) and favorable neurologic outcome (aOR 1.54; 95% CI: 1.21-1.98). Conventional CPR was linked to improved survival (aOR 2.23, 95% CI: 1.69-2.95) and neurologic outcomes (aOR 2.06, 95%CI: 1.51-2.79), whereas compression-only CPR was only associated with improved survival (aOR 1.14, 95%CI: 1.05-1.97) and not improved neurologic outcomes. The authors concluded that BCPR is associated with improved outcomes in pediatric out-of-hospital cardiac arrests and that increasing the use of conventional CPR may improve outcomes for these children.
Although patient-centered medical homes have been incorporated into primary care practice, the evidence supporting their effect on health care outcomes has primarily come from integrated health systems. The purpose of this study was to evaluate the relationship between patient-centered medical homes and medication adherence for certain chronic conditions. This was a retrospective cohort study which used Aetna administrative claims data to identify patients who began using an oral hypoglycemic, antihypertensive, or cholesterol-lowering statin medication between 2011 to 2013. A total of 18,611 patients met both study criteria and received care from a medical home. Mean rates of medication adherence was 64% among medical home patients and 59% among control patients. Among 4660 matched control and medical home practices, medication adherence was significantly higher in medical homes (2.2% [95% CI: 1.5% to 2.9%]) and adherence increased in all three disease states studied. The authors concluded that receipt of care in a patient-centered medical home is associated with better adherence, a vital measure of health care quality, among patients undergoing treatment for common chronic conditions.
While it is well established that high levels (>885 mg/dL) of triglycerides is associated with acute pancreatitis, it is unclear if the increased risk exists with mild-to-moderate elevation (177-885mg/dL) as well. The purpose of this study was to determine if non-fasting mild-to-moderate hypertriglyceridemia was associated with acute pancreatitis. This was a prospective cohort study which gathered data from the Copenhagen General Population study and the Copenhagen City Heart Study with median follow-up of 6.7 years. A total of 116,550 individuals included in the study and the outcome of interests were acute pancreatitis and myocardial infarction. Compared to individuals with serum triglyceride levels of <1 mmol/L, the multivariable adjusted hazard ratios (HRs) for acute pancreatitis were as follows: 1.6 (95% CI: 1.0 to 2.6) for levels of 1.00 to 1.99 mmol/L, 2.3 (95% CI: 1.3 to 4.0) for 2.00 to 2.99 mmol/L, 2.9 (95% CI: 1.4 to 5.9) for 3.00 to 3.99 mmol/L, 3.9 (95% CI: 1.5 to 10.0) for 4.00 to 4.99 mmol/L, 8.7 (95%CI: 3.7 to 20.0) for ≥5.00 mmol/L. The corresponding HRs for myocardial infarction were 1.6 (95% CI: 1.4 to1.9), 2.2 (95%CI: 1.9 to 2.7), 3.2 (95% CI: 2.6 to 4.1), 2.8 (95% CI: 2.0 to 3.9) and 3.4 (95% CI: 2.4 to 4.7), respectively. The authors concluded that nonfasting mild-to-moderate hypertriglyceridemia from 177mg/dL and above is associated with high risk of acute pancreatitis with HR estimates higher than for myocardial infarction.
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