Statin use has increased dramatically in the U.S. in the past decade. Animal and mechanistic studies suggested that statins may have an inhibitory effect on cancer proliferation, including breast ...carcinoma. However, statins have been found to be carcinogenic in rodents and one clinical trial found an excess of breast carcinoma cases in the treatment group.
The current study assessed whether the use of statins altered the risk of breast carcinoma in older women. The population-based, case-control study comprised female residents from three western Washington State counties. Cases included 975 women identified from the Cancer Surveillance System who were diagnosed with primary invasive breast carcinoma between 1997-1999, whose names appeared on a list of Social Security recipients provided by the Centers for Medicare and Medicaid Services. The cases were ages 65-79 years at the time of diagnosis. The comparison group was comprised of 1007 women without breast carcinoma who were randomly selected from the same list of Social Security recipients. Information pertaining to statin use, medical history, and health behaviors was ascertained through an in-person interview.
Compared with nonusers, women who were currently using statins or had ever used statins were not found to be at an increased risk for breast carcinoma (odds ratios OR = 0.9; 95% confidence interval 95% CI, 0.7-1.2). There was some indication that long-term statin use (> 5 years) was related to a slight decrease in breast carcinoma risk (OR = 0.7; 95% CI, 0.4-1.0).
The results of the current study provided some degree of reassurance to the increasing numbers of women using statins that such use is not associated with an increased risk of breast carcinoma. Although the data gave some support to a reduced risk of breast carcinoma among long-term users of statins, further research is needed to confirm this association.
Purpose
We surveyed prostate cancer patients about complementary and alternative medicine (CAM) use and evaluated patient factors that correlated with CAM use 6 months following diagnosis.
Methods
...The Prostate CAncer Therapy Selection study was a prospective, observational multi-site study of men’s treatment decision-making process after a diagnosis of local stage prostate cancer. Recruitment occurred in community urology practices in Washington State, hospital-based urology clinics affiliated with the University of Southern California, and Kaiser Permanente in Northern California. Eligible study participants included men over age 21 diagnosed with local stage prostate cancer between May 1, 2005 and December 31, 2006.
Results
Fifty-two percent of survey respondents (379) reported using one or more types of CAM. Of the patients, 51% used one CAM method, 26% used two methods, and 23% used three or more methods. The most commonly reported category was mind–body therapies (65%). Only 43% of patients discussed their CAM use with a health professional; of those, 20% informed their primary care physician and 30% told the doctor managing their prostate cancer care. Less than half thought the CAM they used was “very helpful”, but a majority thought it was somewhat helpful for their condition.
Conclusions
Further research is needed to characterize the goals prostate cancer patients have for CAM, whether the treatments met those goals, and how this translates into the perceived helpfulness of these therapies. The implications of patients not discussing CAM use with health professionals at the time of prostate cancer treatment need further studies.
To examine the impact of a medication copayment increase on adherence to diabetes, hypertension, and hyperlipidemic medications.
Retrospective pre-post observational study.
This study compared ...medication adherence at 4 Veterans Affairs medical centers between veterans who were exempt from copayments and propensity-matched veterans who were not exempt. The diabetes sample included 1069 exempt veterans and 1069 nonexempt veterans, the hypertension sample included 3545 exempt veterans and 3545 nonexempt veterans, and the sample of veterans taking statins included 2029 exempt veterans and 2029 nonexempt veterans. The main outcome measure was medication adherence 12 months before and 23 months after the copayment increase. Adherence differences were assessed in a difference-in-difference approach by using generalized estimating equations that controlled for time, copayment exemption, an interaction between time and copayment exemption, and patient demographics, site, and other factors.
Adherence to all medications increased in the short term for all veterans, but then declined in the longer term (February-December 2003). The change in adherence between the preperiod and the postperiod was significantly different for exempt and nonexempt veterans in all 3 cohorts, and nonadherence increased over time for veterans required to pay copayments. The impact of the copayment increase was particularly adverse for veterans with diabetes who were required to pay copayments.
A $5 copayment increase (from $2 to $7) adversely impacted medication adherence for veterans subject to copayments taking oral hypoglycemic agents, antihypertensive medications, or statins.
Purpose: Fludarabine monophosphate (fludarabine) is frequently administered to patients receiving a reduced-intensity conditioning
regimen for allogeneic hematopoietic cell transplant (HCT) in an ...ambulatory care setting. These patients experience significant
interpatient variability in clinical outcomes, potentially due to pharmacokinetic variability in 2-fluoroadenine (F-ara-A)
plasma concentrations. To test such hypotheses, patient compliance with the blood sampling should be optimized by the development
of a minimally intrusive limited sampling schedule (LSS) to characterize F-ara-A pharmacokinetics. To this end, we sought
to create the first F-ara-A population pharmacokinetic model and subsequently a LSS.
Experimental Design: A retrospective evaluation of F-ara-A pharmacokinetics was conducted after one or more doses of daily i.v. fludarabine in
42 adult HCT recipients. NONMEM software was used to estimate the population pharmacokinetic parameters and compute the area
under the concentration-time curve.
Results: A two-compartment model best fits the data. A LSS was constructed using a simulation approach, seeking to minimize the scaled
mean squared error for the area under the concentration-time curve for each simulated individual. The LSS times chosen were
0.583, 1.5, 6.5, and 24 hours after the start of the 30-minute fludarabine infusion.
Discussion: The pharmacokinetics of F-ara-A in an individual HCT patient can be accurately estimated by obtaining four blood samples
(using the LSS) and maximum a posteriori Bayesian estimation.
Conclusion: These are essential tools for prospective pharmacodynamic studies seeking to determine if clinical outcomes are related to
F-ara-A pharmacokinetics in patients receiving i.v. fludarabine in the ambulatory clinic. (Clin Cancer Res 2009;15(16):5280â7)
Therapeutic drug monitoring of daily intravenous (IV) busulfan currently requires hospital admission. Population pharmacokinetic modeling and determination of an optimal pharmacokinetic sampling ...schedule over 6 hours could allow for personalizing these busulfan doses in the outpatient clinic. A retrospective evaluation of daily IV busulfan pharmacokinetics was conducted in 37 adults. SPK and NONMEM software were used to estimate the population pharmacokinetic parameters. Subsequent to model building, the area under the concentration‐time curve (AUC) was computed using NONMEM. A 1‐compartment model best fit the data. The optimal 6‐hour outpatient sampling schedule was constructed using a simulation approach that sought to minimize scaled mean squared error for the clearance and volume parameters for each simulated individual. The best sampling times were 2.75, 3, 3.25, 5.5, 5.75, and 6 hours from the start of a 3‐hour infusion. With these sampling times, the maximum a posteriori (MAP) Bayesian estimation was superior to maximum likelihood estimation with more samples. An individual patient's busulfan AUC and pharmacokinetic parameters may be accurately estimated with an outpatient sampling schedule that is used in conjunction with MAP Bayesian estimation, with a parameter prior based on population pharmacokinetic modeling. Prospective validation of this approach is needed.
A validation study evaluated the accuracy of self-reported use of commonly used medications among older women. Within a case-control study of breast cancer, drug information was ascertained by ...interview. Pharmacy records from 1990 to 1999 were obtained from a Washington State health maintenance organization (66% of subjects) and retail pharmacies (34% of subjects) on a sample of subjects (212 cases, 191 controls) and used as the “gold standard.” Recall accuracy was assessed for 6-month, 2-year, and 8-year time windows. Sensitivity of antihypertensive use was 92% (95% confidence interval (CI): 85, 96) for cases and controls in the 6-month period and slightly lower for the 2-year (90% (95% CI: 82, 94) and 87% (95% CI: 78, 92)) and 8-year (80% (95% CI: 69, 88) and 79% (95% CI: 68, 88)) periods. For statins, sensitivity was 83% (95% CI: 64, 93) for cases and 93% (95% CI: 69, 99) for controls in the 6-month period, 75% (95% CI: 55, 88) and 86% (95% CI: 60, 96) in the 2-year period, and 67% (95% CI: 42, 85) and 75% (95% CI: 41, 93) in the 8-year period. For self-report of antidepressants, sensitivities ranged from 66% (95% CI: 47, 80) in the 6-month period to 44% (95% CI: 30, 60) in the 8-year period. Specificity was high among all drug classes, ranging from 91% to 100%. Recall did not differ by case-control status. Trivial changes in estimates were observed when health maintenance organization records alone were used as the gold standard. Self-reported use of antihypertensives and statins appears to be relatively accurate among older women.
Background: Prior research found that in the Veterans Affairs health care system (VA), the proportion of patients adherent to oral hypoglycemic agents varies from 50% to 80% across primary care ...clinics. This study examined whether variation in patient and facility characteristics determined those differences. Methods: Retrospective cohort study of 444,418 VA primary care patients with diabetes treated in 559 clinics in fiscal year (FY) 2006-2007. Patients' adherence to each oral hypoglycemic agent was computed for the first 3 months of FY2007, and averaged across agents to produce an adherence score for the patient's overall regimen. Patients with an adherence score over 0.8 were defined as adherent. Risk adjustment used hierarchical logistic regression accounting for patient factors and facility effects by clustering patients within clinics and clinics within parent VA medical centers. We then assessed the influence of risk adjustment using observed-to-expected (O/E) ratios computed for each clinic. Results: The mean unadjusted proportion of adherent patients in clinics was 0.715 (interdecile range 0.559-0.826). The percent variation in patient's likelihood of being adherent explained at the patient, clinic, and parent VA medical center levels was 2.94%, 0.27%, and 0.76%, respectively. The mean clinic-level observed-to-expected ratio was 1.001 (interdecile range 0.975-1.027). Conclusions: The variation in the proportion of patients adherent across clinics remained large after risk adjustment. As patient and facility effects explained only 4% of the variance in adherence, comparing clinics based on unadjusted scores is a reasonable starting point unless more predictive patient, provider, and facility factors are identified.
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