Management of Dyslipidemia for Cardiovascular Disease Risk Reduction: Synopsis of the 2020 Updated U.S. Department of Veterans Affairs and U.S. Department of Defense Clinical Practice Guideline.

DESCRIPTION: In June 2020, the U.S. Department of Veterans Affairs (VA) and U.S. Department of Defense (DoD) released a joint update of their clinical practice guideline for managing dyslipidemia to reduce cardiovascular disease risk in adults. This synopsis describes the major recommendations. METHODS: On 6 August to 9 August 2019, the VA/DoD Evidence-Based Practice Work Group (EBPWG) convened a joint VA/DoD guideline development effort that included clinical stakeholders and conformed to the Institute of Medicine's tenets for trustworthy clinical practice guidelines. The guideline panel developed key questions, systematically searched and evaluated the literature (English-language publications from 1 December 2013 to 16 May 2019), and developed 27 recommendations and a simple 1-page algorithm. The recommendations were graded by using the GRADE (Grading of Recommendations Assessment, Development and Evaluation) system. RECOMMENDATIONS: This synopsis summarizes key features of the guideline in 7 crucial areas: targeting of statin dose (not low-density lipoprotein cholesterol goals), additional tests for risk prediction, primary and secondary prevention, laboratory testing, physical activity, and nutrition.

Randomized placebo-controlled pilot trial of omega 3 fatty acids for prevention of aromatase inhibitor-induced musculoskeletal pain.

PURPOSE: Aromatase inhibitor (AI)-induced joint symptoms negatively impact drug adherence and quality of life in breast cancer survivors. Mechanisms underlying symptoms may include inflammation. It is hypothesized that n - 3 polyunsaturated fatty acids (PUFAs) have anti-inflammatory properties and may reduce symptoms. METHODS: We conducted a randomized, double-blind, placebo-controlled study comparing 4.3 g/day n - 3 PUFA supplements vs placebo for 24 weeks in postmenopausal breast cancer patients starting adjuvant AIs. Primary endpoints were adherence and tolerability; secondary outcomes included inflammatory cytokines and symptoms assessed by the Brief Pain Inventory short form (BPI-SF) and Functional Assessment of Cancer Treatment-Endocrine Symptoms (FACT-ES) at 0, 12, and 24 weeks. RESULTS: Forty-four women were randomized, of which 35 completed the study. Adherence was ≥ 88% based on these 35 patients with pill counts as well as change in red blood cell (RBC) n - 3 PUFAs. Common toxicities included grade 1 flatulence (55% of both groups) and belching (45% of n - 3 group). Mean pain severity scores (BPI-SF) did not change significantly by time or treatment arm. Quality of life, based on FACT-ES scores, significantly decreased within placebo (p = 0.04), but not the n - 3 group (p = 0.58), with a trend toward between-group differences (p = 0.06) at 12 weeks, but no significant differences at 24 weeks. RBC n - 3 levels were strongly positively correlated with FACT-ES at 12 weeks, but attenuated at 24 weeks. CONCLUSION: High-dose n - 3 PUFA supplementation is feasible and well tolerated when administered with AIs. Additional studies are needed to evaluate efficacy in prevention of joint symptoms.

Isothermal assay targeting class 1 integrase gene for environmental surveillance of antibiotic resistance markers.

Antimicrobial resistance genes (ARGs) present in the environment pose a risk to human health due to potential for transfer to human pathogens. Surveillance is an integral part of mitigating environmental dissemination. Quantification of the mobile genetic element class 1 integron-integrase gene (intI1) has been proposed as a surrogate to measuring multiple ARGs. Measurement of such indicator genes can be further simplified by adopting emerging nucleic acids methods such as loop mediated isothermal amplification (LAMP). In this study, LAMP assays were designed and tested for estimating relative abundance of the intI1 gene, which included design of a universal bacteria 16S rRNA gene assay. Following validation of sensitivity and specificity with known bacterial strains, the assays were tested using DNA extracted from river and lake samples. Results showed a significant Pearson correlation (R2 = 0.8) between the intI1 gene LAMP assay and ARG relative abundance (measured via qPCR). To demonstrate the ruggedness of the LAMP assays, experiments were also run in the hands of relatively "untrained" personnel by volunteer undergraduate students at a local community college using a hand-held real-time DNA analysis device - Gene-Z. Overall, results support use of the intI1 gene as an indicator of ARGs and the LAMP assays exhibit the opportunity for volunteers to monitor environmental samples for anthropogenic pollution outside of a specialized laboratory.

Plasma ascorbic acid concentrations in prevalent patients with end-stage renal disease on hemodialysis.

OBJECTIVE: To determine the prevalence of vitamin C (ascorbic acid [AA]) deficiency in patients with end-stage renal disease, the effect of supplemental AA on plasma AA concentrations, and the extrinsic and intrinsic factors that affect plasma AA concentrations in this patient population. DESIGN: In study 1, we compared the effect of hemodialysis (HD) on plasma AA concentrations between patients with low and high pre-HD AA concentrations. In study 2, we analyzed kinetic and nonkinetic factors for their association with increased plasma AA concentrations in patients on maintenance HD. Study 1 was performed in a single outpatient HD clinic in Cherry Hill, New Jersey. Study 2 was performed in 4 outpatient HD clinics in Southern New Jersey. SUBJECTS AND INTERVENTION: In study 1, we collected plasma samples from 8 adult patients on maintenance HD at various time points around their HD treatment and assayed them for AA concentration. In study 2, we enrolled 203 adult patients and measured pre-HD plasma AA concentrations. We ascertained supplemental AA use and assessed dietary AA intake. MAIN OUTCOME MEASURE: In study 1, plasma AA concentrations were compared during the intradialytic and interdialytic period. In study 2, pre-HD plasma AA concentrations were correlated with supplement use and demographic factors. RESULTS: Study 1 showed that over the course of a single HD treatment, the plasma AA concentration decreased by a mean (±standard deviation) of 60% (±6.6). In study 2, the median pre-HD plasma AA concentration was 15.7 µM (interquartile range, 8.7-66.8) in patients who did not take a supplement and 50.6 µM (interquartile range, 25.1-88.8) in patients who did take a supplement (P < .001). Supplement use, increasing age, and diabetes mellitus were associated with a pre-HD plasma AA concentration ≥30 µM. CONCLUSION: HD depletes plasma AA concentrations, and AA supplementation allows patients to achieve higher plasma AA concentrations.

Plasma oxalate levels in prevalent hemodialysis patients and potential implications for ascorbic acid supplementation.

OBJECTIVES: Ascorbic acid (AA) supplementation may increase hemoglobin levels and decrease erythropoiesis-stimulating agent dose requirement in patients with end stage renal disease (ESRD). While plasma AA levels >100µM may be supratherapeutic, levels of at least 30µM may be needed to improve wound healing and levels may need to reach 70µM to optimize erythropoiesis. Of concern, oxalate (Ox), an AA metabolite, can accumulate in ESRD. Historically, if plasma Ox levels remain ≥30µM, oxalosis was of concern. Contemporary hemodialysis (HD) efficiencies may decrease the risk of oxalosis by maintaining pre-HD Ox levels <30µM. This study focuses on the plasma Ox levels in HD patients. DESIGN AND METHODS: A prospective, observational study of 197 HD patients with pre-HD AA levels and pre-HD and post-HD Ox levels. RESULTS: Mean plasma Ox levels decreased 71% during the intradialytic period (22.3±11.1µM to 6.4±3.2µM, P<0.001). In regression analysis, pre-HD plasma AA levels ≤100µM were not associated with a pre-HD plasma Ox level≥30µM, even if ferritin levels were increased. Pre-HD plasma Ox levels ≥20 or ≥30µM were not associated with lower cumulative 4-year survival. CONCLUSIONS: Pre-HD plasma AA levels up to 100µM in HD patients do not appear to be associated with an increased risk of developing secondary oxalosis, as the corresponding pre-HD plasma Ox level appears to be maintained at tolerable levels.

Management of Dyslipidemia for cardiovascular disease risk Reduction: synopsis of the 2020 updated U.S. Department of Veterans Affairs and U.S. Department of Defense Clinical Practice Guideline

In June 2020, the U.S. Department of Veterans Affairs (VA) and U.S. Department of Defense (DoD) released a joint update of their clinical practice guideline for managing dyslipidemia to reduce cardiovascular disease risk in adults. This synopsis describes the major recommendations. The guideline panel developed key questions, systematically searched and evaluated the literature (English-language publications from 1 December 2013 to 16 May 2019), and developed 27 recommendations and a simple 1-page algorithm. The recommendations were graded by using the GRADE (Grading of Recommendations Assessment, Development and Evaluation) system. This synopsis summarizes key features of the guideline in 7 crucial areas: targeting of statin dose (not low-density lipoprotein cholesterol goals), additional tests for risk prediction, primary and secondary prevention, laboratory testing, physical activity, and nutrition.