2 Minute Medicine Rewind May 8, 2017

Bystander efforts and 1-year outcomes in out-of-hospital cardiac arrest

The effect of bystander CPR on long-term outcomes in cases of out-of-hospital cardiac arrest is currently unknown. This investigation aimed to examine the relationship between bystander CPR and long-term outcomes, including 1-year risks of anoxic brain damage and nursing home admission, and all-cause mortality. In this retrospective study, 2,855 patients in Denmark who had out-of-hospital cardiac arrest and survived 30 days afterwards were followed-up. Researchers found that bystander CPR resulted in a lower rate of nursing home admission and anoxic brain injury (HR 0.62, 95% CI 0.47 to 0.82), as compared to patients who did not receive bystander intervention. Bystander CPR also resulted in lower mortality rates (HR 0.70, 95% CI 0.50 to 0.99), and a lower risk of any of the three primary outcomes studied (HR 0.67, 95 % CI 0.53 to 0.84). Defibrillation performed by bystanders was also associated with a significantly reduced risk of brain damage or nursing home admission (HR 0.45, 95% CI 0.24 to 0.84) and mortality (HR 0.22, 95% CI 0.07 to 0.73). This study therefore shows that, in patients that experience out-of-hospital cardiac arrest, bystander intervention with CPR and/or defibrillation may significantly lower the 1-year risk of anoxic brain damage, nursing home admission, and death.

Long-term management of moderate-to-severe atopic dermatitis with dupilumab and concomitant topical corticosteroids

Signs and symptoms of moderate-to-severe atopic dermatitis have previously been shown to improve with dupilumab, a monoclonal antibody directed at the interleukin-4-receptor. However, the long-term safety and efficacy of this drug is unknown. In this randomized, double-blinded, placebo-controlled trial, 740 patients were randomized to receive dupilumab and topical corticosteroids or topical corticosteroids alone to study the long-term efficacy of dupilumab. Patients receiving dupilumab were administered 300 mg of dupilumab once weekly for a year, or 300 mg of dupilumab every 2 weeks. Primary endpoints, measured at week 16 and week 52, included achieving Investigator’s Global Assessment (IGA) scores of 0 or 1. A 75% improvement from baseline on the Eczema Area and Severity Index (EASI) was also evaluated as an outcome. Researchers found that, at 16 weeks of follow-up, 39% of patients who received dupilumab every week and 39% of those who received dupilumab every 2 weeks reached the primary end point of an IGA score of 0 or 1, as compared to 12% who received placebo (p<0.0001). Dupilumab also resulted in a higher rate of patients achieving the EASI endpoint (p<0.0001). These findings persisted at 52 weeks. Overall adverse event rates were comparable between the three groups, with 83% of those who received dupilumab every week reporting an adverse event, as compared to 88% of those who received dupilumab every 2 weeks, and 84% of patients who received placebo. This study therefore shows that the use of dupilumab in addition to topical corticosteroids is associated with improvement in atopic dermatitis with an acceptable safety profile.

Long-term gluten consumption in adults without celiac disease and risk of coronary heart disease

Gluten-free diets have been previously shown to lower the incidence of coronary heart disease in those with celiac disease. In this prospective cohort study, 64,714 women and 45,903 men who had completed food frequency surveys every 4 years from 1986 to 2010 were followed up to investigate the effects of consumption of gluten on the incidence of coronary heart disease in adults without celiac disease. Upon adjusting for known risk factors, researchers found that those in the highest fifth percentile of gluten intake did not have a significantly increased risk of developing coronary heart disease (HR 0.95, 95% CI 0.88 to 1.02). In addition, after adjusting the results for intake of refined grains, those in the highest fifth percentile of gluten intake had a lower risk for coronary heart disease, with a hazard ratio of 0.85 (95% CI 0.77 to 0.93). As such, the investigators concluded that intake of gluten was not associated with a higher risk of coronary heart disease, but may result in less consumption of whole grains known to decrease cardiovascular risk.

Evolocumab and clinical outcomes in patients with cardiovascular disease

Evolocumab is a monoclonal antibody directed against proprotein convertase subtilisin-kexin type 9 (PCSK9). It has been shown to lower levels of low-density lipoprotein (LDL), however, its effects on cardiovascular outcomes have not yet been investigated. In this randomized, double-blind, placebo-controlled study, 27,654 patients with atherosclerotic cardiovascular disease on statin therapy with LDL levels of 70 mg/dL or higher were randomized to receive two 140 mg doses of evolocumab every 2 weeks, one 420 mg dose of evolocumab monthly, or placebo injections in order to investigate the relationship between evolocumab treatment and cardiovascular outcomes. The investigators used a composite measurement that included cardiovascular death, stroke, coronary revascularization, myocardial infarction, and hospitalization for unstable angina. After a median follow-up of 2.2 years, researchers found that treatment with evolocumab resulted in a median LDL reduction from 92 mg/dL to 30 mg/dL. Treatment also resulted in a significantly reduced risk of the composite cardiovascular end point  (HR 0.85, 95% CI 0.79 to 0.92, p<0.001). Evolocumab was associated with a higher risk for injection-site reactions, but no other adverse events. As such, the investigators concluded that, in the setting of current statin use, PSCK9 inhibitors are able to lower cardiovascular risk by further lowering LDL levels below current targets.

Efficacy and safety of adalimumab every other week versus methotrexate once weekly in children and adolescents with severe chronic plaque psoriasis

Psoriasis is a chronic inflammatory skin disease frequently diagnosed before the age of 20. Adalimumab, a tumor necrosis factor inhibitor, is currently in use for moderate to severe psoriasis in adults, however its effects in younger patients have not been well studied. In this randomized, double-blind trial, 114 children aged 4-18 were randomly assigned to receive 16 weeks of either a 0.8 mg/kg subcutaneous injection of adalimumab every other week, a 0.4 mg/kg subcutaneous injection of adalimumab every other week, or 0.1 to 0.4 mg/kg oral methotrexate once weekly to investigate the safety and efficacy of adalimumab in children and adolescents. Primary end points included a 75% improvement from baseline on the Psoriasis Area and Severity Index (PASI) and a score of minimal or clear on the physician global assessment (PGA). Results showed that the higher dose of adalimumab was associated with a 58% achievement of the PASI outcome, as compared to 32% of patients in the methotrexate group (p=0.027). Additionally, 61% of patients in the high dose adalimumab group achieved the PGA primary end point, relative to 41% in the methotrexate group, however this finding was not statistically significant (p=0.083). The rate of the most common adverse event, infection, was higher in the methotrexate group (57%) than the high dose adalimumab group (45%). Therefore, it was concluded that compared to oral methotrexate, the use of adalimumab is associated with a significant improvement in moderate to severe psoriasis in children and adolescents. However, the use of adalimumab does not result in a significant increase in the proportion of patients that achieve clear or minimal PGA as compared to methotrexate.

Image: PD

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