Publications

OBJECTIVE

Taxane containing chemotherapy extends survival for breast cancer patients. However, taxane-induced peripheral neuropathy (TIPN) cannot be predicted, prevented or effectively treated. Using genome-wide analyses, we sought to identify common risk variants for TIPN.

PATIENTS AND METHODS

Women with high-risk breast cancer enrolled in SWOG 0221 were genotyped using the Illumina 1M chip. Genome-wide analyses were performed in relation to ≥grade 3 Common Terminology Criteria for Adverse Events (CTCAE) neuropathy in European and African Americans. Data were meta-analyzed with GW associations of CTCAE ≥grade 3 versus

RESULTS

The percentage of ≥grade 3 TIPN in 1269 European Americans and 139 African Americans in S0221, was 11.6 and 22.3%, respectively. CALGB 40101 ≥grade 3 TOPN was 7.2%. The most significant association with ≥grade 3 TIPN was the G allele of rs1858826 in GNGT1 (Pmeta=1.1×10), which showed a decrease in risk of ≥grade 3 TIPN (odds ratio=0.29, 95% confidence interval: 0.18-0.46).

CONCLUSION

The genetic variants associated with ≥grade 3 TIPN are hypothesized to have biochemical functions and reside in and near genes involved in diabetes and diabetic neuropathy. This finding is consistent with results from CALGB 40101 pathway analyses. Larger homogeneous trials with similar dosing and criteria for defining neuropathy are needed to properly assess the relationship of genomics with the neuropathy spectrum.

BACKGROUND

Insulin resistance (IR) is associated with hepatitis C virus (HCV), and Latinos are both at risk of IR and are disproportionately affected by HCV. Moderate alcohol consumption improves insulin sensitivity and may modify HCV-associated IR. We investigated the impact of moderate alcohol discontinuation on insulin sensitivity and secretion in Latinos using direct measurements.

METHODS

Twenty-five nondiabetic, noncirrhotic Latino adults without (n = 17) or with (n = 8) HCV underwent 3-day metabolic assessment before and after prescription of 6 weeks of moderate alcohol discontinuation. Peripheral IR was measured via steady-state plasma glucose (SSPG) and hepatic IR using endogenous glucose production during a 2-step 240-minute insulin suppression test. Insulin secretion was measured using graded glucose infusion test.

RESULTS

Baseline mean age was 46 ± 11 years, 63% male, 29% had HCV, and mean body mass index was 27 ± 4 kg/m . Compared to non-HCV, HCV patients had a higher median SSPG (132 vs. 98.8 mg/dl, p = 1.0), hepatic IR (13.5 vs. 11.3, p = 0.24), and insulin secretion rate (ISR-AUC, 1,290 vs. 1,250 pmol/min, p = 0.98). After confirmed alcohol discontinuation, hepatic IR was the only parameter that changed significantly (increased, mean change 2.6 ± 4.8, p = 0.02). Higher baseline alanine aminotransferase (ALT) was also associated with a greater change in hepatic IR (average 4.0 points/ALT doubling, p = 0.004), and HCV was associated with a lesser change (average -7.3 points, p = 0.002), independent of ALT.

CONCLUSIONS

Short-term moderate alcohol discontinuation adversely impacted hepatic IR in Latinos which was influenced by level of ALT at baseline independent of etiology. Although reduction in ALT through weight loss and HCV eradication remains a priority in improving IR, the observed nonharmful effect of moderate alcohol use represents a potentially confounding variable that warrants further study.

OBJECTIVE

Increased out-of-pocket health-care expenditures may exert budget pressure on low-income households that leads to food insecurity. The objective of the present study was to examine whether older adults with higher chronic disease burden are at increased risk of food insecurity.

DESIGN

Secondary analysis of the 2013 Health and Retirement Study (HRS) Health Care and Nutrition Study (HCNS) linked to the 2012 nationally representative HRS.

SETTING

USA.

SUBJECTS

Respondents of the 2013 HRS HCNS with household incomes <300 % of the federal poverty line (n 3552). Chronic disease burden was categorized by number of concurrent chronic conditions (0-1, 2-4, ≥5 conditions), with multiple chronic conditions (MCC) defined as ≥2 conditions.

RESULTS

The prevalence of food insecurity was 27·8 %. Compared with those having 0-1 conditions, respondents with MCC were significantly more likely to report food insecurity, with the adjusted odds ratio for those with 2-4 conditions being 2·12 (95 % CI 1·45, 3·09) and for those with ≥5 conditions being 3·64 (95 % CI 2·47, 5·37).

CONCLUSIONS

A heavy chronic disease burden likely exerts substantial pressure on the household budgets of older adults, creating an increased risk for food insecurity. Given the high prevalence of food insecurity among older adults, screening those with MCC for food insecurity in the clinical setting may be warranted in order to refer to community food resources.

OBJECTIVE

The aim of this study was to establish high-quality, valid standards to improve surgical care of the older adult.

BACKGROUND

The aging population increases demand for high-quality surgical care. Building upon prior guidelines, quality indicators, and pilot projects, the Coalition for Quality in Geriatric Surgery (CQGS) includes 58 diverse stakeholder organizations committed to improving geriatric surgery.

METHODS

Using a modified RAND-UCLA Appropriateness Methodology, 44 of 58 CQGS Stakeholders twice rated validity (primary outcome) and feasibility for 308 standards, ranging from goals and decision-making, pre-operative assessment and optimization, perioperative and postoperative care, to transitions of care beyond the acute care hospital.

RESULTS

Three hundred six of 308 (99%) standards were rated as valid to improve quality of geriatric surgery. There were 4 sections. Section 1 included 157 (57%) standards and focused on goals and decision-making, preoperative optimization, and transitions into and out of the hospital. Section 2 included 84 (27.3%) standards focused on in-hospital care, across the immediate preoperative, intraoperative, and postoperative phases. Section 3 included 59 (19.1%) standards about program management, including personnel and committee structure, credentialing, and education. Section 4 included 8 (2.6%) standards establishing overarching concepts for data collection and patient follow-up. Two hundred ninety of 308 standards (94.2%) were rated as feasible; 18 (5.8%) were rated as uncertain in feasibility.

CONCLUSIONS

CQGS Stakeholders rated the vast majority of standards of care as highly valid (99%) and feasible (94%) for improving the quality of surgical care provided to older adults. Future work will focus on a pilot phase to better understand and address challenges to implementation of the standards.