Outcomes using direct-acting antiviral hepatitis-C treatment in older versus younger Veterans.

BACKGROUND: Historically, older adults have been excluded from trials evaluating hepatitis C virus (HCV) treatment, in part, due to the adverse effects associated with previous regimens. Veterans are at high risk of HCV infection. Ledipasvir/sofosbuvir (LED/SOF) is a once daily antiviral regimen with demonstrated efficacy and tolerability among the younger population. We examined the tolerability and effectiveness of LED/SOF in Veterans age ≥65 years versus those <65 years who were treated at the Atlanta VA Health Care System (AVAHCS). METHODS: Using the VA Clinical Case Registry, all persons who filled a LED/SOF prescription at the AVAHCS from January 1, 2015, through March 31, 2016, were identified. The electronic medical records were reviewed to identify basic demographic information: comorbidities; polypharmacy; and outcomes. Sustained virologic response (SVR) was defined as an undetectable HCV RNA, at least 12 weeks after completing treatment. Descriptive statistics were employed using SAS v9.2. RESULTS: We identified 345 Veterans who filled LED/SOF during the study period; 94 were excluded due to exposure to ribavirin and IFN containing regimens; 97 (38.6%) were ≥65 years. Veterans were predominantly black (57%) and male (97%). Cancer was more prevalent among older Veterans (p = 0.047) as was polypharmacy (p = 0.001). Treatment completion rates between older and younger Veterans were not significantly different (99 vs. 95%, respectively; p = 0.16), but significantly more older Veterans achieved SVR (98 vs. 91%; p = 0.03). CONCLUSIONS: LED/SOF was a well-tolerated and effective regimen in an older Veteran population despite their multiple comorbidities and polypharmacy presence.

Inflammation Modulation by Vitamin D and Calcium in the Morphologically Normal Colorectal Mucosa of Patients with Colorectal Adenoma in a Clinical Trial.

Increased COX-2 and decreased 15-hydroxyprostaglandin dehydrogenase (15-HPGD) expression promote prostaglandin-mediated inflammation and colorectal carcinogenesis. Experimental studies suggest that vitamin D and calcium may inhibit these pathways, but their effects on colorectal tissue COX-2 and 15-HPGD expression in humans are unknown. We tested the effects of supplemental vitamin D (1,000 IU/day) and/or calcium (1,200 mg/day) on COX-2 and 15-HPGD expression in the morphologically normal rectal mucosa from 62 paients with colorectal adenoma in a placebo-controlled chemoprevention trial. We measured biomarker expression using automated IHC and quantitative image analysis at baseline and 1-year follow-up, and assessed treatment effects using mixed linear models. The primary outcome was the COX-2/15-HPGD expression ratio, because these enzymes function as physiologic antagonists. After 1 year of treatment, the mean COX-2/15-HPGD expression ratio in full-length crypts proportionately decreased 47% in the vitamin D group (P = 0.001), 46% in the calcium group (P = 0.002), and 34% in the calcium + vitamin D group (P = 0.03), relative to the placebo group. Among individuals with the functional vitamin D-binding protein isoform DBP2 (GC rs4588*A), the COX-2/15-HPDG ratio decreased 70% (P = 0.0006), 75% (P = 0.0002), and 60% (P = 0.006) in the vitamin D, calcium, and combined supplementation groups, respectively, relative to placebo. These results show that vitamin D and calcium favorably modulate the balance of expression of COX-2 and 15-HPGD-biomarkers of inflammation that are strongly linked to colorectal carcinogenesis-in the normal-appearing colorectal mucosa of patients with colorectal adenoma (perhaps especially those with the DBP2 isoform). PREVENTION RELEVANCE: Supplemental calcium and vitamin D reduce indicators of cancer-promoting inflammation in normal colorectal tissue in humans, thus furthering our understanding of how they may help prevent colorectal cancer.

A Severe Episode of Hemolytic Anemia After Amoxicillin Exposure in A G6PD Deficient Patient.

Glucose-6-phosphate dehydrogenase (G6PD) deficiency is the most common enzyme deficiency worldwide, with genetic variants resulting in a range of phenotypes that vary from asymptomatic to severe hemolysis. We report a case of severe hemolytic anemia in a G6PD deficient patient whose only known exposure was amoxicillin two weeks prior to his episode of severe hemolysis, for which he presented to our hospital. An extensive infectious and hematologic workup resulted negative with the exception of a positive G6PD deficiency result. Although rare, we suggest that the patient's severe hemolytic anemia is possibly related to amoxicillin exposure.