• Association between cardiovascular drugs and colon cancer

      Deshpande, Gaurav; Weiss-Smith, Sheila (2013)
      The objective of the study was to determine (1) if cardiovascular drugs (CV) are associated with increased risk of colon cancer (CC), (2) if the risk for any individual agent differs from the risk of the therapeutically class overall, and (3) if the risk differs for patients with CC on right side based on inhibition properties of some CV drugs for bile acid uptake. A population-based case control study was conducted using the HealthCore Integrated Research Database (HIRDSM), a US commercial insurance claims database. Incident cases of CC were patients aged 18 years or older at diagnosis, with first CC diagnostic claim between Jan 1, 2001 to Jan 30, 2011. Each case was matched to one eligible control based on: no diagnosis of CC during study period, actively enrolled at index date of the case, and matched to cases by length of pre-index enrollment (same or greater), sex, and age. Exposure to a CV drug was defined as at least one claim during the risk period. Conditional logistic regression was used to calculate adjusted Odds Ratios (OR). 36,736 cases of CC were identified and successfully matched to controls. Sensitivity analysis were conducted by using alternate case definition, varying lag time between last prescription and CC diagnosis, and setting a required minimum CV drug exposure (12 months).The mean age was 60 years (about 30% were 50-60 years old). Enalapril, labetalol, cholestyramin, diltiazem and furosemide (ORs range:1.07-2.05) were positively associated with CC while atorvastatin, pravastatin and simvastatin (ORs range:0.68-0.94) were negatively associated with CC. In the sensitivity analyses, positive associations remained for just cholestyramine and diltiazem, whereas the negative associations remained for atorvastatin and simvastatin. These results are consistent with beneficial impact of statins on CC risk. Drugs identified as inhibitors of bile acid uptake were not associated with CC on right side. However, the association of individual drugs was not consistent with that therapeutic class as a whole. This suggests that risk may vary by individual agent. Grouping drugs into therapeutic classes for studies of cancer risk may introduce a bias driven by the predominant agents used in a particular population.
    • Breast cancer patients' preferences for local and systemic therapy and willingness to participate in clinical trials

      Cooke, Jesse Lee, Jr.; Weiss-Smith, Sheila (2005)
      Objectives. To determine the effect of stage and health locus of control (HLC) on willingness to accept local and systemic therapy and willingness to participate in clinical trials. Methodology. This was a cross-sectional survey of female breast cancer patients at the Greenebaum Cancer Center. Respondents had the option of completing the questionnaire using a computer or a paper version. Willingness to accept therapy was determined by the minimum number of cancer-free years respondents required to accept therapy. Clinical data were abstracted from the respondents' medical records; stage was classified as either "early" (stages 0--2) or late (stages 3 and 4). HLC was assessed using the Multidimensional Health Locus of Control, Form C. Tobit models were used to determine the association between stage and HLC on willingness to accept therapy and to participate in clinical trials. Results. Among 79 respondents, the mean age was 56.0 years (SD +/- 9.43); 58.2% identified themselves as white; 75.6% had early stage cancer. Respondents required the most cancer-free years, a median of 4.0, to accept mastectomy, 3.5 to participate in a clinical trial, and 1.0 to accept breast conserving therapy, chemotherapy, or tamoxifen RTM. Late stage patients were more willing to participate in clinical trials than early stage patients. Late stage patients were less willing to take tamoxifen; late stage patients in good physical health were less willing to have mastectomies. Patients with a higher internal locus of control (IHLC) were more willing to accept mastectomy or chemotherapy, and more willing to participate in clinical trials. Respondents with less education, those with a higher chance health locus of control (CHLC) were more willing to participate in clinical trials. Conclusions. Late stage patients were less willing to accept therapy which may be perceived as a less aggressive or effective form of therapy such as tamoxifen, but are more willing to accept experimental therapy. Patients with a higher IHLC appear to prefer the therapies that are shorter in course and require less follow-up. Respondents with a higher CHLC accept therapies that "leave nothing to chance" and appear to have a greater understanding of the concept of randomization.
    • Gastroenterologists prescribing of infliximab for Crohn's disease: A national survey

      St. Charles, Meaghan Elizabeth; Weiss-Smith, Sheila (2007)
      Objective. We surveyed a national sample of gastroenterologists (GIs) to determine whether they are utilizing immunomodulators (IM) prior to infliximab (IFX) and prescribing maintenance IFX when treating Crohn's Disease (CD), as recommended by gastroenterology society guidelines and the package insert. Methods. An 18-item questionnaire was developed and validated by four experts in the field. The survey was emailed to 4,515 GIs who are members of the American Gastroenterology Association (AGA). Selected GIs were randomly assigned to each of three study arms. Two of the three study arms received an incentive. Each study arm received a total of six email blasts of the survey. Bivariate and multivariate analyses were performed on the outcomes of interest and important covariates. Results. A total of 305 out of 4,515 (6.7%) eligible GI's responded to the survey. The majority (82.6%) of respondents reported using IFX. 69.5% of respondents would use an IM prior to IFX, 85.6% would prescribe maintenance IFX, and 62.3% reported both ("on-label" use of IFX). GIs with a volume of CD patients >6%, practicing in an academic setting, and prescribing IFX a few times per year were significantly more likely to report the use of IM prior to IFX (OR=1.96, 5.11 and 3.46, respectively). GIs residing in the Midwest and infusing IFX in their office were significantly more likely to report the use of maintenance IFX (OR=11.70 and 4.55, respectively). GIs practicing in an academic setting, residing in the Midwest, and prescribing IFX a few times per year were significantly more likely to report the "on-label" use of IFX (both use of IM prior to IFX and maintenance IFX), (OR=4.56, 2.18 and 2.25, respectively). The use of an incentive significantly improved response rates (p=0.03; absolute difference=39%). Conclusion. The majority of GIs reported utilizing an IM prior to IFX and prescribing maintenance IFX. However, 38% of respondents failed to report both use of an IM prior to IFX and use of IFX maintenance therapy. GIs practicing outside of the Midwest and outside of an academic setting may need additional training regarding proper prescribing of IFX to improve outcomes in patients with CD
    • Impact of Erythropoiesis Stimulating Agents on Survival and Risk of Venous Thromboembolism Among Patients with Colorectal Cancer Receiving Chemotherapy

      Sato, Masayo; Weiss-Smith, Sheila (2012)
      Objectives: To describe utilization of erythropoiesis stimulating agents (ESAs) over time in the VA; to compare characteristics of ESA users with non-users among solid tumor patients receiving chemotherapy; and to evaluate the effect of ESA use on survival and risk of venous thromboembolism among colorectal cancer patients undergoing chemotherapy. Methods: This study is a nonconcurrent prospective cohort study using the 2006 - 2008 Veterans Health Administration administrative data. There were two components to the study sample; 28,868 solid tumor patientseceiving chemotherapy to describe ESA utilization over time and 2,462 colorectal cancer patients receiving chemotherapy to estimate the effect of ESA on mortality and time to venous thromboembolism. A conventional multivariate adjusted and propensity score weighted Cox proportional hazard regressions were performed. Results: Overall, 10% of solid tumor patients receiving chemotherapy in the cohort used ESAs at some time during the follow-up period. The proportion of ESA users among solid tumor patients decreased by half during the 2-year period. Use of ESA's during chemotherapy treatment was associated with a 2-fold increase in mortality. The estimated hazard ratios of ESA use for mortality among colorectal cancer patients receiving chemotherapy were 1.957 (95% CI = 1.522 - 2.517) in a conventional multivariate model and 2.045 (95% CI = 1.799 -2.326) in a propensity score weighted model. Conclusion: This population-based observational study demonstrated that the use of ESAs declined over time in the VA healthcare system between July 2006 and August 2008 and showed survival was decreased with the combination use of chemotherapy plus ESAs compared with chemotherapy alone. While gaps in the available data elements, particularly cancer staging, and other potential biases inherent in observational studies must be considered when interpreting these results, the study's findings are consistent with the clinical trials at other cancer sites and the meta-analyses which combined cancer sites suggesting that the decreases in survival are not site dependent. This provides important insight regarding a fair balance of risks and benefits for the management of anemia by the combination use of chemotherapy and ESAs in colorectal cancer population.
    • Use of Insulin and Risk of Cancer among Patients with Diabetes Mellitus: A Nonconcurrent Prospective Study

      Lu, Zhiqiang; Weiss-Smith, Sheila (2011-01)
      Objectives: There have been a number of studies showing an association between diabetes and cancer risk and a growing concern that this risk maybe linked to insulin therapy. This study aimed to (1) to assess the effect of insulin exposure on the risk of developing solid cancer among patients with diabetes mellitus; and (2) to explore the role of HbA1c value in modifying the risk. Methods: The study used the General Practice Research Database (GPRD), a large UK-based research database of patient electronic health records from general practitioners, to explore the use of insulin on the risk of cancer. Cox's Proportional hazards models were used to estimate the hazard ratio of solid tumors, all sites and selected individual sites, by types of antidiabetic therapy. The potential modifying role of diabetes control as measured by hemoglobin A1c (HbA1c) was also explored. Results: The study cohort contained a total of 230,330 patients with claims for antidiabetic therapy. The study found that use of insulin alone or in combination with other oral agents was associated with an increased risk of cancer. Insulin use was strongly associated with pancreatic cancer risk (HR=1.875, 95% CI 1.261, 2.787 for insulin alone and HR=2.330, 95% CI 2.007, 2.705 for insulin with oral agents). Moreover, HbA1c appears to be a risk factor for pancreatic cancer (HR=1.385, 95% CI 1.324, 1.450). The risk of pancreatic cancer was similarly increased for premixed and intermediate-acting insulin when compared with short-acting insulins. Role of HbA1c value in modifying the risk of cancer among patients with diabetes varies across different cancer types. Conclusion: Use of insulin, alone or in combination with oral agents, may pose a strong risk for pancreatic cancer and overall cancer. Use of insulin alone was also associated with an increased risk of colorectal cancer. These data suggest that there may be more than one mechanism by which insulin therapy impacts the risk of cancer among diabetics. Glucose control appears to impact the risk of pancreatic cancer, though it may be an independent factor for some common tumors. Caution should be used when prescribing insulin to patients for diabetes management.