Effects of sodium selenite and selenium-enriched yeast on cardiometabolic indices of patients with atherosclerosis: A double-blind randomized clinical trial study

Introduction: Atherosclerosis and related cardiovascular diseases (CVDs) are the major causes of mortality worldwide. The available reports regarding the effects of selenium (Se) supplementation in the realm of atherosclerosis have been equivocal. The present investigation is aimed to assess the effects of sodium selenite and Se-enriched yeast supplementation on metabolic parameters among atherosclerotic patients. Methods: In this double-blind placebo-controlled randomized clinical trial, 60 patients diagnosed with atherosclerosis were randomly allocated into either 200 μg/day selenite, yeast, or placebo groups for eight consecutive weeks. Serum levels of lipid profile and glycemic indices were measured at the baseline and end of the intervention. Results: There were no significant within-or between-group changes in levels of total cholesterol, triglycerides, high-density lipoprotein cholesterol (HDL-c), fasting blood sugar, insulin, and homeostatic model assessment for IR throughout the study (P≥0.05). Only the low density lipoprotein cholesterol (LDL-c) levels were significantly lower in the yeast group in comparison with the placebo group (P= 0.015). Conclusion: The administration of Se-enriched yeast is significantly effective in decreasing LDL-c levels in patients with atherosclerosis. Additional clinical trial studies investigating the effect of Se administration on glucose homeostasis parameters and lipid profiles in atherosclerotic patients are suggested for a more definitive conclusion.

720. Efficacy of Nifurtimox + Eflornithine in the Treatment of African Trypanosomiasis. Systematic Review

Background Sleeping sickness is an infectious disease transmitted mainly by the Trypanosoma Brucei, with the tsetse fly as a vector. The condition has two stages: The hemolymphatic and the meningo-encephalitic stage. The second stage is caused mainly by the Trypanosoma Brucei Gambiense. The treatment of the second stage has changed from melarsoprol, eflornithine, to now nifurtimox-eflornithine (NECT). This systematic review will focus on the efficacy and the toxicity of the medication. Methods We use PRISMA and MOOSE protocol for this review. On figure 1, we detail the methodology used for the extraction of information from the systematic review. To assess the study's bias, we used Cochrane Collaboration’s tool for risk assessment of the clinical trials and the Robins I tool for the observational studies. Results We collected four clinical trials and two observational studies after an extensive search. Three clinical trials showed that NECT was non-inferior to eflornithine with the following cure rates (NECT VS eflornithine): 1) 96.3% vs. 94.1% ; 2) 90.9% vs. 88.9%; 3) 91.6% vs. 96.5%. An additional clinical trial revealed that the proportion of patient discharge from the hospital was 98.4% (619/629); 95% CI [97.1%; 99.1%]). The two observational studies discussed the pharmacovigilance of the drug and toxicity related to NECT. In one study, patients treated with NECT, 589 (86%) experienced at least one adverse effect (AE) during treatment, and 70 (10.2%) experience serious AE. On average, children experienced fewer AEs than adults. In the other study at least one AE was described in 1043 patients (60.1%), and Serious AE was reported in 19 patients (1.1% of treated), leading to nine deaths (case fatality rate of 0.5%). The major limitations of the studies were the lack of blinding because most of them were open-label. Also, there was heterogenicity in the definition of the outcomes in the observational studies. PRISMA Flow Chart Conclusion NECT is not inferior to eflornithine, and the proportion of patients discharged from the hospital alive showed favorable results. The observational studies revealed a high frequency of AE. However, NECT is more convenient and safe than Eflornithine and Melarsoprol. Disclosures All Authors: No reported disclosures

Precision medicine, genetics and genomics in a community cancer clinic.

e13511 Background: With advances in technology and the decreasing cost of next generation sequencing (NGS) to identify both germline and somatic pathogenic variants, there is a critical need for curation and interpretation of these results. Clinicians often order the tests simultaneously. Our objective was to analyze results of NGS testing in a community cancer care clinic setting with a coordinated precision medicine program. Methods: In a retrospective review, we analyzed the germline NGS results from patients who were seen by the Hereditary Cancer Program (HCP) at Hoag Family Cancer Institute since 2001. Additionally, we compared those who had both positive genetic testing results and had tumor molecular profiling. Results: A total of 8,239 patients were seen by HCP, 6,100 had germline testing done, approximately 50% had multi gene panel testing (MGPT). 15% of the patients with germline testing had a pathogenic or likely pathogenic mutation. Of those with the positive results, 71% were breast and ovarian cancer and 29% were other cancer types. We also analyzed NGS results for 713 tumors tested through a commercial laboratory in one year. All cases were subjected to our secondary annotation, resulting in additional recommendations in 40% of cases, beyond what was in the commercial report and additional clinical trial options in 30%. Based on a new initiative in the past year, we examined tumor profiling results for indications of possible germline mutations. By analyzing those results, we made recommendations for genetic counseling in 91 (12.8%) cases. Conclusions: The data show the importance of genetic counseling and MGPT in a community setting in patients with personal and/or family history of cancer. Adoption of somatic and germline testing is increasing at our cancer center due to demonstrated benefit to patients and increased physician understanding of the clinical utility of molecular testing.

A Review of the First Long-term Implantable Continuous Glucose Monitoring System Available in the United States

Background: Although real-time continuous glucose monitoring (rtCGM) has been shown to improve glycemic control in patients with type 1 diabetes mellitus and type 2 diabetes mellitus treated with insulin, rates of adoption have been low. A novel approach, with the use of a long-term implantable continuous glucose monitoring (LTI CGM) has the potential to overcome barriers to rtCGM. The purpose of this review is to provide a background on the first LTI CGM technology to be approved, along with a review of contraindications, interference, safety, accuracy, and efficacy. Considerations for patient selection are discussed based on the available evidence. Methods: PubMed, EMBASE, and Cochrane Library were searched for keywords and subject headings to identify studies assessing LTI CGM. Results: Seven studies were identified which assessed LTI CGM. Mean absolute relative difference is similar to available CGM devices. Rates of adverse events were low. Change in hemoglobin A1c with LTI CGM may be comparable to rtCGM. Conclusions: Based on the available evidence, LTI CGM appears to be safe and accurate. Additional clinical trial investigation is warranted to evaluate the glycemic efficacy of LTI CGM.

End points for sickle cell disease clinical trials: patient-reported outcomes, pain, and the brain

To address the global burden of sickle cell disease (SCD) and the need for novel therapies, the American Society of Hematology partnered with the US Food and Drug Administration to engage the work of 7 panels of clinicians, investigators, and patients to develop consensus recommendations for clinical trial end points. The panels conducted their work through literature reviews, assessment of available evidence, and expert judgment focusing on end points related to: patient-reported outcomes (PROs), pain (non-PROs), the brain, end-organ considerations, biomarkers, measurement of cure, and low-resource settings. This article presents the findings and recommendations of the PROs, pain, and brain panels, as well as relevant findings and recommendations from the biomarkers panel. The panels identify end points, where there were supporting data, to use in clinical trials of SCD. In addition, the panels discuss where further research is needed to support the development and validation of additional clinical trial end points.

Denosumab in Osteoporosis and Oncology

Objective: To review the pharmacology, pharmacokinetics, pharmacodynamics, safety, efficacy, and use of denosumab in osteoporosis, breast cancer, prostate cancer, and multiple myeloma. Data Sources: Studies and abstracts were identified through MEDLINE and International Pharmaceutical Abstracts (1966–July 2009). Key search terms include denosumab, AMG-162, and receptor activator of nuclear factor-κB ligand system. Information available in abstract form was retrieved from major oncology and bone metabolism meetings. Additional data were obtained from the manufacturer. Study Selection and Data Extraction: All available studies in humans were included except for studies in rheumatoid arthritis and giant cell tumor of the bone. Data Synthesis: In patients with osteoporosis, denosumab significantly reduces bone resorption and fractures. Studies of denosumab in the prevention and treatment of osteoporosis have demonstrated significantly increased bone mineral density and reduced bone turnover markers. Studies of denosumab versus placebo in the treatment of osteoporosis have demonstrated reductions in vertebral, hip, and nonvertebral fractures. In oncology, positive results from clinical trials in patients receiving endocrine therapy for breast and prostate cancer demonstrated decreases in bone loss and skeletal-related events. Denosumab seems to be at least as effective in reducing bone turnover markers as intravenous bisphosphonates in the oncology setting. The most common adverse effects in patients with osteoporosis were arthralgia, nasopharyngitis, back pain, and headache. The most common adverse effects in patients with cancer were infection, pain in the extremities, arthralgia, bone pain, fatigue, and pain. Serious adverse effects include infections requiring hospitalization. Conclusions: Denosumab has documented efficacy and safety in patients with osteoporosis, breast cancer, and prostate cancer. Additional clinical trial data are needed to more completely establish the effectiveness of denosumab in the treatment of osteoporosis and neoplastic disease as well as its cost-effectiveness and long-term safety.

Update on Abatacept: A Selective Costimulation Modulator for Rheumatoid Arthritis

Objective: To review and update the pharmacology, pharmacokinetics, safety, precautions, efficacy, and use of abatacept for rheumatoid arthritis (RA). Data Sources: Studies and abstracts were identified through MEDLINE, International Pharmaceutical Abstracts, Cochrane databases, and Science Citation Index (1990–April 2007). Key search terms included abatacept, CTLA4–Ig, and BMS 1888667. Information available only in abstract form was retrieved from national and international rheumatology associations. Additional data were obtained from the manufacturer. Study Selection and Data Extraction: All available animal and human studies describing the pharmacology of abatacept and human studies describing the pharmacokinetics, pharmacodynamics, efficacy, safety, adverse events, and precautions of abatacept were included. Data Synthesis: Abatacept significantly improves the signs and symptoms of moderate-to-severe RA in patients who experienced an Inadequate response to methotrexate or antitumor necrosis factor-α inhibitors. By month 12, approximately 50% of patients achieved remission (defined as a disease activity score <2.6) that was maintained until at least 24 months of therapy. The most common adverse events include headache, upper respiratory tract infections, nausea, and nasopharyngitis. Rare but serious adverse events include serious infections and malignancy. Conclusions: Abatacept has documented efficacy and safety in patients with inadequate responses to methotrexate and antitumor necrosis factor agents in both short- and long-term studies. Additional clinical trial and postmarketing evidence is necessary to understand the long-term safety, efficacy, economics, and rote of abatacept in clinical practice.