In this section, we highlight the key high-impact studies, updates, and analyses published in medicine during the past week.
Proportein convertase subtilisin-kexin type 9 (PCSK9) plays an important role in the recycling and regulation of low-density lipoprotein (LDL) receptors. Monoclonal antibodies to PCSK9 have been show to lower LDL cholesterol by up to 70% in phase I and phase II clinical trials. Trials evaluating the efficacy of evolocumab and alirocumab have been in development and plan to enroll more than 40,000 patients with coronary artery disease, risk factors, or familial hypercholesterolemia. In the OSLER-1 and OSLER-2 trial, 4465 patients were randomized to various doses of evolocumab or standard therapy. At one year, there was a statistically significant difference in the rate of cardiovascular events (0.95% in the evolocumab arm vs. 2.18% in the control arm, HR 0.47, p = 0.003). In the ODYSSEY LONG TERM trial, 2341 patients were randomized to either alirocumab or standard therapy. At 78 weeks, there was a statistically significant difference in cardiovascular events (1.7% in the alirocumab arm vs. 3.3% in the control arm, HR 0.52, p = 0.02). Both trials showed statistically significant decreases in LDL cholesterol compared to standard therapy with statins. These clinical trials will continue to collect long term follow-up data to determine the long term effects of PCSK9 inhibitors.
Tissue pathology is the foundation of prognosis and treatment decisions in cancer, however its accuracy in routine clinical practice is unknown. In this study, 115 pathologists independently interpreted slides from 240 breast biopsies previously interpreted by a panel of experts in concordance with reference diagnoses. The overall concordance of diagnostic interpretations was 75.3%, with 96% concordance in cases of invasive carcinoma however only 48% concordance in cases of atypia. 17% of interpretations were deemed overinterpreted and 35% were underinterpreted. There was more disagreement with the reference diagnosis in samples from women with higher density breasts (73% higher-density vs. 77% lower-density, p < 0.001) and among pathologists with lower case volume, worked in smaller practices, or in nonacademic settings. With early detection and accurate diagnosis of breast cancer relying on accurate interpretation of breast biopsies, there is significant importance in the accurate interpretation of biopsy specimens.
New antiviral therapies are extremely effective for the treatment of Hepatitis C virus (HCV) genotype 2 or 3 in patients with concomitant HIV co-infection. In this multinational open-label study, 275 adult patients with stable HIV and HCV co-infection were given sofosbuvir and ribavirin for 12 or 24 weeks and followed for sustained virological response (SVR). SVR was achieved in 85% of patients with HCV genotype 1, 88% of patients with HCV genotype 2, 89% of patients with HCV genotype 3, and 84% of patients with HCV genotype 4. There was no statistically significant difference in response in patients with or without prior treatment for HCV. Four patients (1%) of patients had severe adverse events and four other patients (1%) were founded to have transient elevations in HIV viral load. This study suggests that sofosbuvir and ribavirin is effective in the treatment of HCV in patients with HIV co-infection without significant adverse effects.
Skin and soft tissue infections in community settings often require coverage of methicillin-resistant Staph aureus (MRSA), however the optimal oral antibiotic treatment of MRSA soft tissue infections is uncertain. In this American multicenter, randomized trial, 524 patients with cellulitis and/or abscesses greater than 5 centimeters were randomized to clindamycin or trimethoprim–sulfamethoxazole (TMP-SMX). Staph aureus was identified in 41.4% of patient isolates, of which 77.0% were methicillin resistant. There was no statistically significant difference in the proportion of patients cured (80.3% with clindamycin and 77.7% with TMP-SMX (p = 0.52)), and this lack of difference was consistent across multiple subgroups.
Novel antiretroviral therapies for Hepatitis C are effective and well tolerated, however also significantly more expensive than prior therapies. In this discrete-event simulation model, investigators examined the cost and relative quality-adjusted life year (QALY) benefit in the use of sofosbuvir, simeprevir, daclatasivir, and ledipasvir. For genotype 1, for which the novel therapies are most effective, the investigators found that sofosuvir-leipasivr cost $12,825 more per QALY. For genotype 2, sofosbuvir–ribavirin and sofosbuvir–daclatasvir cost $110,000 and $691,000 per QALY. This study concluded that sofosbuvir-ledipasvir was the superior option for genotype 1 HCV and there was net cost-savings if sofosbuvir cost less than $5,500 per week.
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