Pamela K. Green

Persistent Racial and Ethnic Disparities in Up-to-Date Colorectal Cancer Testing in Medicare Enrollees

OBJECTIVES: To assess whether greater colonoscopy use among white as compared with nonwhite Medicare enrollees since Medicare established coverage for colorectal cancer (CRC) screening has been associated with a widening in white versus nonwhite disparities in up‐to‐date CRC testing status.

Adrenalectomy Increases Sensitivity to Central Insulin

When infused into the third ventricle of rats, insulin dose-dependently reduces food intake and body weight, with doses of 1 mU/day and lower being ineffective. Because corticosterone functionally antagonizes many of insulins peripheral actions, and because corticosterone acts in the brain to enable hyperphagia under some conditions, a subthreshold dose of insulin (1 mU/day), or its saline vehicle, was infused into the third ventricle of adrenalectomized (ADX) and sham-ADX male Long-Evans rats. Sham-ADX rats that received insulin or saline had no significant change of food intake or body weight over a 2-week interval. Likewise, saline-infused ADX were unaffected. In contrast, ADX rats receiving insulin had a significant reduction of food intake and body weight. These results suggest that the absence of circulating glucocorticoids increases the brains sensitivity to insulin, and that insulin in the brain acts to lower food intake and body weight via a glucocorticoid-sensitive mechanism.

Effects of fat content on fat hedonics: cognition or taste?

Understanding and perhaps overriding preferences for fat is important, given the relationship between higher dietary fat consumption and poorer health. We have examined the roles of potential mechanisms for differences in fat preference: actual fat content and expected fat content. The subjects were women (n=192, ages=50-69) recruited to a study of low-fat dietary change. Subjects were randomized to one of the four cells: participants received either a high- or low-fat milkshake at baseline, and half of each group was told that their milkshake was low in fat and the other half high in fat. Women who received a high-fat milkshake consumed more grams than women who received a low-fat milkshake. Women who expected low-fat shakes reported liking them more than those who expected high-fat milkshakes. These data indicate that both physiology and cognition play a role in determining consumption of high- and low-fat foods.

Effect of diet-induced obesity and experimental hyperinsulinemia on insulin uptake into CSF of the rat

We examined the hypothesis that the uptake of plasma insulin into cerebrospinal fluid (CSF) is saturable in two rat models. Dietary obese and control female Osborne Mendel rats received 24-h infusions of vehicle or insulin. CSF insulin levels in cafeteria- and chow-fed rats were comparable at all levels of plasma insulin (4.5 +/- 2.8, 7.6 +/- 2.4, and 23.9 +/- 6.4 microU/ml in cafeteria diet vs. 4.5 +/- 0.9, 6.8 +/- 1.1, and 17.0 +/- 4.0 microU/ml in chow rats). CSF insulin uptake as a percentage of plasma insulin decreased with increased plasma insulin in both groups. A similar relationship was observed in Wistar rats receiving 6-day infusions of vehicle or insulin (plasma insulin = 55 +/- 12 vs. 365 +/- 98 microU/ml; CSF/plasma insulin ratio = 0.022 +/- .007 vs. 0.013 +/- .006, respectively). Hyperinsulinemic Wistar rats did not demonstrate decreased brain capillary insulin binding vs. vehicle-infused controls. The results suggest that a saturable transport process contributes insulin transport into CSF in normal rats and that this process is not altered by moderate diet-induced obesity or hyperinsulinemia per se.

Similar Effectiveness of Boceprevir and Telaprevir Treatment Regimens for Hepatitis C Virus Infection on the Basis of a Nationwide Study of Veterans

BACKGROUND & AIMS We investigated the real-world effectiveness of triple therapy regimens against hepatitis C virus (HCV) and compared rates of sustained virologic response (SVR) between telaprevir-based and boceprevir-based regimens in a population-based study. METHODS We analyzed data on all patients in the Veterans Administration healthcare system who were infected with HCV genotype 1 and began treatment with pegylated interferon, ribavirin, and either boceprevir (n = 3696, 83%) or telaprevir (n = 759, 17%) from June 2011 to February 2013. RESULTS Patients treated with telaprevir were more likely to have baseline characteristics associated with not achieving SVR than patients treated with boceprevir. Fewer than half of patients eligible for short-duration regimens (28 weeks for boceprevir, 24 weeks for telaprevir) successfully completed treatment (37% for boceprevir, 27.5% for telaprevir); ∼25% discontinued early, and the remaining patients were treated for longer durations. Of the patients who were supposed to complete 48-week regimens, only 35% of boceprevir-treated and 34% of telaprevir-treated patients completed >44 weeks. The rate of SVR was 51.5% overall, 42.7% among patients with cirrhosis, 56.8% among treatment-naive patients, 64.2% among prior relapsers, 31.7% among prior partial responders, and 29.8% among prior null responders. There were no significant differences in rate of SVR between patients given boceprevir or telaprevir in the entire population or among subgroups. The most important predictors of failure to achieve SVR were IL28B genotype, high viral load, black race, diabetes, high aspartate aminotransferase to platelet ratio index or FIB-4 scores, low platelet counts, or low levels of low-density lipoprotein cholesterol. Erythropoietin use was not associated with SVR. CONCLUSIONS In a nationwide analysis of veterans with HCV genotype 1 infection, rates of SVR were similar for those treated with boceprevir vs telaprevir. However, rates of treatment completion and SVR in real clinical practice were substantially lower than those in clinical trials.

Trends in Colorectal Cancer Testing Among Medicare Subpopulations

BACKGROUND In 1998, Medicare initiated universal coverage for colorectal cancer (CRC) screening via fecal occult blood testing (FOBT) and sigmoidoscopy. In mid-2001, universal coverage was advanced to screening colonoscopy. This study sought to determine whether trends in CRC testing differed among racial/ethnic, age, or gender subgroups of the Medicare population. METHODS In 2006, claims from 1995 to 2003 were analyzed for annual 5% random samples of fee-for-service Medicare enrollees living in Surveillance, Epidemiology, and End Results (SEER) regions to calculate the annual, age-standardized percentages of subjects who received FOBT, sigmoidoscopy, or colonoscopy. Logistic regression then modeled trends in annual test use within racial/ethnic, age, and gender subgroups across three Medicare coverage periods (precoverage [1995-1997]; limited coverage [1998-mid-2001]; and full coverage [mid-2001-2003]). RESULTS The annual use of FOBT and sigmoidoscopy declined from 1995 to 2003 in all racial/ethnic groups, but the relative decline in sigmoidoscopy use was greater among whites compared to nonwhites. In contrast, colonoscopy use increased substantially in all racial/ethnic groups. However, relative to the precoverage period among whites, the full-coverage period was associated with significantly greater colonoscopy use among whites (OR=2.14; 95% CI=2.09, 2.19) than blacks (OR=1.86; 95% CI=1.75, 1.96); Asian/Pacific Islanders (OR=1.73; 95% CI=1.62, 1.86); or Hispanics (OR=1.65; 95% CI=1.49, 1.81). The use of colonoscopy during the full-coverage period was also differentially greater among enrollees aged <80 years. CRC testing trends were similar among male and female enrollees. CONCLUSIONS Colonoscopy is supplanting sigmoidoscopy as a CRC test among Medicare enrollees, while FOBT use is in decline. The transition from sigmoidoscopy to colonoscopy has occurred more quickly among white than nonwhite Medicare enrollees.

HCV eradication induced by direct-acting antiviral agents reduces the risk of hepatocellular carcinoma

BACKGROUND & AIMS It is unclear whether direct-acting antiviral (DAA) treatment-induced sustained virologic response (SVR) reduces the risk of hepatocellular carcinoma (HCC) in patients with HCV infection. Therefore, in the current study, our aim was to determine the impact of DAA-induced SVR on HCC risk. METHODS We identified 62,354 patients who initiated antiviral treatment in the Veterans Affairs (VA) national healthcare system from 1 January 1999 to 31 December 2015, including 35,871 (58%) interferon (IFN)-only regimens, 4,535 (7.2%) DAA + IFN regimens, and 21,948 (35%) DAA-only regimens. We retrospectively followed patients until 15 June 2017 to identify incident cases of HCC. We used Cox proportional hazards regression to determine the association between SVR and HCC risk or between type of antiviral regimen (DAA-only vs. DAA + IFN vs. IFN-only) and HCC risk. RESULTS We identified 3,271 incident cases of HCC diagnosed at least 180 days after initiation of antiviral treatment during a mean follow-up of 6.1 years. The incidence of HCC was highest in patients with cirrhosis and treatment failure (3.25 per 100 patient-years), followed by cirrhosis and SVR (1.97), no cirrhosis and treatment failure (0.87), and no cirrhosis and SVR (0.24). SVR was associated with a significantly decreased risk of HCC in multivariable models irrespective of whether the antiviral treatment was DAA-only (adjusted hazard ratio [AHR] 0.29; 95% CI 0.23-0.37), DAA + IFN (AHR 0.48; 95% CI 0.32-0.73) or IFN-only (AHR 0.32; 95% CI 0.28-0.37). Receipt of a DAA-only or DAA + IFN regimen was not associated with increased HCC risk compared with receipt of an IFN-only regimen. CONCLUSIONS DAA-induced SVR is associated with a 71% reduction in HCC risk. Treatment with DAAs is not associated with increased HCC risk compared with treatment with IFN. LAY SUMMARY It was unclear whether direct-acting antiviral treatment-induced sustained virologic response reduces the risk of liver cancer in patients with HCV infection. We demonstrated that eradication of HCV infection with direct-acting antiviral agents reduces the risk of liver cancer by 71%.

Risk of endometrial cancer following cessation of menopausal hormone use (Washington, United States)

While there are a number of benefits to the health of postmenopausal women from use of unopposed estrogens, the increased risk of endometrial cancer related to these hormones has led many women to use combined estrogen-progestogen therapy instead, or not to use hormones at all. Most women who take hormones do so only in the early portion of their postmenopausal years, so the risk of endometrial cancer following cessation of use might bear heavily on the overal risk/benefit evaluation. We analyzed data from a case-control study of women in western Washington (United States) to assess the magnitude of excess risk of endometrial cancer following discontinuation of estrogen use. Cases (n=661) consisted of women aged 45 to 74 diagnosed between 1985 and 1991 who resided in one of three counties in Washington State. Controls (n=865) were identified by random-digit dialing. Subjects were interviewed in-person to ascertain current and prior hormone use. The analysis was restricted to women who had not received combined estrogen-progestin therapy. Among women who had used unopposed estrogens at some time, risk of endometrial cancer declined as time since last use increased. Nonetheless, even among women who used these hormones for just a few years, the risk remained elevated by 30 to 70 percent almost a decade after cessation. These results, combined with those of most (but not all) other studies of this issue, suggest that a woman who has discontinued unopposed estrogen therapy may retain a small increased risk of endometrial cancer for a long period of time.

Geographic variation of racial/ethnic disparities in colorectal cancer testing among medicare enrollees

The Medicare population has documented racial/ethnic disparities in colorectal cancer (CRC) screening, but it is unknown whether these disparities differ across geographic regions.

Regional Variation in Anesthesia Assistance During Outpatient Colonoscopy Is Not Associated With Differences in Polyp Detection or Complication Rates

BACKGROUND & AIMS We investigated the rate and predictors of anesthesia assistance during outpatient colonoscopy and whether anesthesia assistance is associated with colonoscopy interventions and outcomes. METHODS We performed a retrospective cohort study using a 20% sample of Medicare administrative claims submitted during the 2003 calendar year. We analyzed data from 328,177 adults, 66 years old or older, who underwent outpatient colonoscopy examinations. RESULTS Overall, 8.7% of outpatient colonoscopies were performed with anesthesia assistance. In multivariate analysis, independent predictors of anesthesia assistance included black race, female sex, and a nonscreening indication; anesthesia assistance increased with median income and comorbidities. General and colorectal surgeons, fewer years in their practice, and nonhospital site of service were also significantly associated with anesthesia assistance. The strongest predictor of anesthesia assistance was the Medicare carrier, with odds ratios ranging from 0.22 (95% confidence interval: 0.12-0.43) for the Arkansas carrier (crude rate 0.9%) to 9.90 (95% confidence interval: 7.92-12.39) for the Empire carrier in New York area (crude rate 35.3%) compared with the Wisconsin carrier (crude rate 4.3%). There was also considerable variation among endoscopists; 75% of providers had no colonoscopies with anesthesia assistance recorded in their dataset, and 4.5% of providers had anesthesia assistance in at least three quarters of their examinations. Anesthesia assistance was not associated with the diagnosis of polyps, the performance of biopsy or polypectomy, or complications in multivariate analyses. CONCLUSIONS There are significant variations among regions and sites of service in anesthesia assistance during outpatient colonoscopies of Medicare beneficiaries. Although this variation has considerable economic implications, it was not associated with measures of patient risk or outcomes, such as polyp detection or procedure-related complications.