Impact of HIV-specialized pharmacies on adherence to medications for comorbid conditions.

OBJECTIVE: To determine if patients using human immunodeficiency virus (HIV)-specialized pharmacies have greater adherence to drugs used to treat comorbid conditions and HIV compared with patients who use traditional pharmacies. DESIGN: Retrospective cohort study, with patients' propensity matched based on pharmacy use: HIV-specialized versus traditional. SETTING: Nationwide pharmacy chain. PARTICIPANTS: Adult patients who filled at least two prescriptions for an antiretroviral therapy (ART). Patients also needed to have at least two prescriptions for an angiotensin-converting enzyme (ACE) inhibitor/angiotensin receptor blocker (ARB) or a statin for analyses examining comorbid conditions. MAIN OUTCOME MEASURE: Proportion of days covered (PDC). RESULTS: The adherence analyses for ART, ACE inhibitors/ARBs, and statins included 14,278, 1,484, and 1,372 pairs, respectively. The mean PDC for ART patients using HIV-specialized pharmacies was higher than that for patients using traditional pharmacies (86.20% vs. 81.87%; P <0.0001). Patients taking ACE inhibitors/ARBs in the specialized group also had a higher mean PDC compared with patients in the traditional group (82.61 vs. 79.66; P = 0.0002), as did specialized pharmacy users in the statin group (83.77 vs. 81.29; P = 0.0009). CONCLUSION: HIV patients managed by an HIV-specialized pharmacy have significantly higher adherence to medication for comorbid conditions compared with patients using traditional pharmacies. Patients of HIV-specialized pharmacies also have significantly higher adherence to ART compared with peers using traditional pharmacies.

The prevalence of traditional herbal medicine use among hypertensives living in South African communities.

BACKGROUND: In South Africa, over 6 million people are hypertensive and the burden of disease shows that cardiovascular diseases (CVDs) are the leading cause of death among adults. Although treatments exist, few people comply or adhere to recommended treatment due to side effects or costs of the drugs, hence the reliance on alternative forms of treatment. Traditional herbal medicines (THM) are used for the management of hypertension but the prevalence of its use among hypertensive patients living in South African communities is not sufficiently known. METHODS: This was a cross-sectional descriptive study to determine the prevalence of THM use for hypertension, among 135 purposefully selected South African participants of the Prospective Urban and Rural Epidemiological (PURE) study, who are THM users. Data on THM use were collected by way of face to face interviews using structured questionnaires administered by trained field workers. Standard descriptive measures were used to characterize the study sample and responses to the questionnaire. Chi-square test was used when making comparisons between groups. RESULTS: There were 135 THM users, 21% of whom used THM to treat hypertension. Majority (82.1%) of the hypertensive THM users were females, only 29% were married or co-habitating, virtually all (96%) were unemployed and 86% were Christians. More than half (56%) of the respondents were aged between 55 and 64 years. THM was occasionally used (51.9%) as a combination of tea and other mixtures (63%) and prescribed by family/ friends/self-administered. There was a significant difference in the age, marital and employment status, as well as the form and frequency of THM use of hypertensive THM users compared to other THM users. CONCLUSIONS: The study gives an insight into the prevalence of THM use by hypertensive patients in selected South African communities. The practice of self-medication was also observed which raises concern regarding the safety of medications taken by the participants. Health care providers should however be more aware of THM use and counsel patients regarding the combination of prescribed treatment regimen and herbal medicines and the potential of herb-drug interactions.

Ground beetles suppress slugs in corn and soybean under conservation agriculture.

Conservation agriculture practices such as eliminating tillage and planting high residue cover crops are becoming increasingly important in field crop systems in the US Mid-Atlantic. However, these practices have sometimes been associated with an increase in moderate to severe damage to field crops by slugs. Conserving natural enemy populations is a desirable way to manage slug infestations because remedial control measures are limited. Here, we tested the effects of conservation practices, weather, and natural enemies on slug activity-density measured by tile traps placed among 41 corn and soybean fields during the spring of 2018 and 2019 in the Northern Shenandoah Valley, Virginia, USA. We found that a positive effect of cover crops on slug activity-density was reduced by tillage and that slug activity-density declined with increasing ground beetle activity-density. Slug activity-density also declined with decreasing rainfall and increasing average temperature. Weather was the only significant predictor of ground beetle activity-density, which was reduced in sites and weeks that were relatively hot and dry or that were cool and wet. However, we also found a marginally significant negative effect of pre-plant insecticides on ground beetles. We suggest that the observed interacting effects of cover crops and tillage reflect favorable conditions for slugs provided by increased small grain crop residue that can be mitigated to some extent by even low levels of tillage. More broadly, our study suggests that implementation of practices known to promote recruitment of ground beetles in crop fields can improve natural suppression of slugs in corn and soybean that are being increasingly cultivated according to conservation agriculture practices.

Cost of Traditional Herbal Medicines for Noncommunicable Diseases in Rural and Urban Communities in South Africa.

OBJECTIVES: This study assessed traditional herbal medicine (THM) and conventional medicine (CM) utilization among participants with noncommunicable disease in South Africa. METHODS: A cross-sectional study of the Prospective Urban and Rural Epidemiological study collected data through face-to-face interviews using structured questionnaires in 2014. Descriptive, bivariate, and multivariate logistic regression were used to determine the effect of sociodemographic and economic factors on THM and CM use. All statistical analyses were conducted using the statistical computing and graphics language "R." RESULTS: Of the total 417 randomly selected participants in this study, 85% were females, 95% with no health insurance, and 81% with monthly incomes of <2000 rand (R) ($137 equivalent) per month. Moreover, 73% spend 5% of their income on THM, and 10% say they are willing to pay >R500 per year on THM to feel better. Age was significantly associated with different spending patterns after controlling for other demographic factors, given that older adults were 82% (odds ratio 0.18; 95% confidence interval 0.02-0.93) less likely to pay >R100 for THM whereas younger adults were 59% (odds ratio 0.41; 95% confidence interval 0.17-0.97) less likely to pay for CM. CONCLUSIONS: The cost of using THM and CM largely differed by age. The economic insight into this study reveals individuals more willing to pay for THM to payors, which can ultimately clue payors into areas for medication optimization from potential drug-drug interactions and adverse events and, therefore, reduce healthcare costs.

Phase II trial of FOLFOX6, bevacizumab, and cetuximab in the first-line treatment of metastatic colorectal cancer.

PURPOSE: To examine FOLFOX/bevacizumab/cetuximab in the first-line treatment of metastatic colorectal cancer (mCRC). DESIGN: Randomized phase II trial aimed at achieving a 60% objective response rate (ORR). Due to frequent cetuximab-related hypersensitivity reactions the trial was amended to a single-arm design. Eligibility: Previously untreated mCRC, measurable disease, Eastern Cooperative Oncology Group performance status (ECOG-PS) 0-1. TREATMENT: Modified FOLFOX6 (oxaliplatin 85 mg/m², leucovorin 350 mg, and 5-fluorouracil 400 mg/m² bolus; 2.4 g/m² infusion, 46 h) day 1; bevacizumab 5 mg/kg on day 1; cetuximab 400 mg/m² on day 1, then 250 mg/m² on days 1 and 8, every 14 days (1 cycle) until progressive disease (PD); restaging occurred every 4 cycles. RESULTS: With emerging negative progression-free survival (PFS) data from a similarly designed trial, this trial closed early. Enrollment (N=31) was from August 2005-June 2008. PATIENT CHARACTERISTICS: Median age was 55 years (29-78); 58% were male; 71% were ECOG-PS 0. Ten cycles (median) were completed (range 2-62). The ORR was 55% (95% confidence interval [CI], 36-73%); 11 patients (35%) had stable disease; 1 patient (3%) had PD; 2 patients (6%) were unevaluable. Median PFS was 9 months (95% CI, 8.3-15.2 months); median overall survival was 25.7 months (95% CI, 15.4-27.6 months). Grade 3/4 toxicities (>1 patient) included neutropenia (25%), rash (23%; grade 2 events, 45%), diarrhea (19%), fatigue (16%), pain (16%), anemia (13%), sensory neuropathy (13%), deep-vein thrombosis (10%), nausea (10%), pulmonary embolism (7%), anorexia (6%), and vomiting (6%). CONCLUSION: In this limited trial, it is unclear whether cetuximab contributed to FOLFOX/bevacizumab efficacy, although the response rate, PFS, and overall survival were high. The regimen was generally well-tolerated, with expected skin effects; thromboembolic rates should be assessed in larger analyses. Cetuximab's role in first-line mCRC treatment is likely best guided by K-RAS testing in future clinical trials.

Demographics and outcomes at American Society for Metabolic and Bariatric Surgery Centers of Excellence.

INTRODUCTION: Surgery is currently an effective long-term therapy for morbid obesity and its complications. A variety of surgical procedures can now offer durable and safe weight control as well as previously unrealized full remission of costly comorbidities. This is a preliminary investigation of patient characteristics and outcomes at Bariatric Surgery Centers of Excellence) (BSCOE) hospitals. METHODS AND PROCEDURES: Data were analyzed from 235 American Society for Metabolic and Bariatric Surgery (ASMBS) BSCOE hospitals receiving Full Approval status from August 2005 to May 2007. Metrics for the 66,339 bariatric surgeries performed at these hospitals included type, volume and distribution of various bariatric surgical procedures performed at each hospital, patient demographics, payer information, and adverse outcomes. RESULTS: Data from these analyses demonstrate significant differences in terms of surgical procedure selection (laparoscopic gastric bypass 61%), patient demographics (females 83%, White 60%, mean age 43 years) and type of payer (private insurance 78%), and adverse outcomes (readmission 5%, re-operation 2%, mortality 0.36%). CONCLUSIONS: The collective performance of ASMBS BSCOE hospitals in bariatric outcomes of readmissions, re-operations, and mortality are equivalent to, or more favorable, than currently reported outcomes. However, risk assessment and risk adjustment of the patients and each of the bariatric procedures will be necessary to appropriately evaluate these rates.

The Impact of a Worksite-Based Diabetes Prevention Intervention: A Pilot Study.

The purpose of this study was to assess the impact of a program to prevent the development of type 2 diabetes among participants with prediabetes. The program focused on a healthy eating style, behavior modification, daily physical activity, and achieving a healthy weight. This was a retrospective observational analysis of a pilot program designed to prevent diabetes among employees with prediabetes. This intervention involved 12-16 weeks of nutrition counseling with the registered dietitian and participation in physical activity of at least 150 min/week. The primary outcome for this study was the prevention of type 2 diabetes. Secondary outcome measures included changes in the following biometrics: body mass index (BMI), systolic blood pressure (SBP), diastolic blood press (DBP), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), total cholesterol, waist circumference, and triglyceride levels. The diabetes prevention intervention was associated with significant improvements in glucose (-6.6%), A1c (-2.9%), weight (-5.5%), BMI (-5.5%), SBP (-4.9%), DBP (-3.9%), total cholesterol (-5.0%), LDL-C (-7.0%), and triglycerides (-13.9%). After the 12-16-week intervention, the prevalence of prediabetes was reduced by 31% by fasting blood glucose or A1c levels. Baseline A1c, baseline glucose level, age, and number of sessions attended were all significant predictors of the odds of transitioning out of the prediabetes stage, controlling for all other covariates in the model. This pilot study suggests that the implementation of a worksite diabetes prevention intervention can help employees transition from a prediabetes status to no risk of diabetes.

Relation of aortic valve sclerosis to risk of coronary heart disease in African-Americans.

To assess the relation between aortic valve sclerosis (AVS) and subsequent occurrence of coronary heart disease (CHD) events, we analyzed echocardiographic data obtained from 2,279 middle-aged African-Americans enrolled in the Jackson Mississippi Atherosclerosis Risk in Communities study cohort who were free of known CHD at the time of the examination. Cox regression analyses demonstrated a hazard ratio of 3.8 for incident first myocardial infarction or fatal CHD after adjusted for multiple risk factors, including markers of inflammation. An amplification of CHD risk in the AVS subgroup with high levels of serum inflammatory markers (the highest quartile of fibrinogen and von Willebrand Factor levels) demonstrated greater than fivefold higher risk of CHD associated with AVS than risk in the lowest quartile.

Walgreens connected care: impact of managed therapy on adherence to medications used to treat multiple sclerosis and related comorbid conditions.

BACKGROUND: The Walgreens Connected Care Multiple Sclerosis (CCMS) treatment management program provides enhanced levels of monitoring, oversight, and care for patients taking MS disease-modifying agents. This study compared rates of adherence to MS medications for patients participating in the CCMS program for at least 6 months with those for patients participating for less than 6 months. For a subsample of patients, we also examined the relationship between adherence and the presence of fatigue or depression. METHODS: This was a retrospective study of patients new to the CCMS program and followed up for 1 year of participation. Adherence to MS medications was measured as the proportion of days covered, with propensity scores used to match the CCMS intervention group to the less-managed comparison group. The impact of program participation on the relationship between depression or fatigue and adherence over time was a separate analysis. RESULTS: Mean proportion of days covered rates improved significantly in the group managed for at least 6 months compared with those who were less managed. Positive screenings for fatigue and depression reduced adherence in the less-managed group but not in patients with longer participation in the program. CONCLUSIONS: Overall, the CCMS program significantly increased adherence to MS medications. This improved adherence was not negatively impacted by positive screenings for fatigue and depression.

Which modifiable health risks are associated with changes in productivity costs?

The purpose of this retrospective, longitudinal study was to assess longitudinal associations between modifiable health risks and workplace absenteeism and presenteeism and to estimate lost productivity costs. Across the 4-year study period (2007-2010), 17,089 unique employees from a large US computer manufacturer with a highly technical workforce completed at least 1 health risk assessment. Generalized estimating equation models were used to estimate the mean population-level absenteeism and presenteeism for 11 modifiable health risks and adjust for 9 sociodemographic and employment-related factors. Because patient age was highly correlated with several other variables, the analysis was stratified by age (<45 vs. ≥45 years). For all ages, poor emotional health, inadequate exercise, tobacco use, and having a body mass index (BMI) greater than 35 (all P<.05) were consistently associated with both absenteeism and presenteeism. Having a BMI over 35 and poor emotional health were associated with the largest impact in absenteeism (0.46 days) and presenteeism (4.03 days), respectively. Younger and older workers had similar associations between health risks and presenteeism; however, hypertension, blood sugar, inadequate exercise, and alcohol were associated (P⋜.01) with greater absenteeism among older but not younger workers. The results suggest that productivity loss is strongly related to emotional health and obesity-related health risks (eg, BMI, exercise) but differs by age. These findings could help prioritize preventive health programs offered by employers at their worksite health centers. Given the aging of the US workforce, keeping older workers healthy and productive will be crucial to remaining competitive in the global economy. (Population Health Management 2015;18:30-38).

Neighbourhood characteristics and mortality in the Atherosclerosis Risk in Communities Study.

BACKGROUND: This study investigates the relationship between neighbourhood characteristics and mortality (all-cause, cardiovascular disease [CVD], and cancer) in the Atherosclerosis Risk in Communities Study (ARIC). METHODS: Analysis was limited to African-American and white participants 45-64 years of age at baseline whose records were linked to census data. Deaths ascertained through 31 December 1999 were included in the analysis. Individual-level characteristics were obtained from the baseline interview. A composite index was used to characterize the neighbourhood socioeconomic environment. Proportional hazards regression was used to estimate the effect of neighbourhood socioeconomic status (SES) index and family income on the survival time. RESULTS: The rate of mortality adjusted for age and gender was highest among those who lived in disadvantaged neighbourhoods and were of lower SES. In general, all-cause and CVD mortality rates decreased with increasing neighbourhood SES advantage and family income in all race-gender groups. Although this pattern generally persisted after adjustment for individual socioeconomic factors, statistically significant associations persisted for CVD mortality in whites only (hazard ratio = 1.4, 95% CI: 1.0, 2.0) for most disadvantaged versus most advantaged tertile). When compared with the most affluent participants living in the most advantaged neighbourhoods, the increased risk of all-cause and CVD mortality associated with being poor and living in the most disadvantaged neighbourhoods was equivalent to being 11 and 13 years older at baseline for whites and African Americans, respectively. CONCLUSION: Our findings indicate that neighbourhood socioeconomic characteristics are associated with modest increases in CVD mortality in white adults. The lack of neighbourhood effects in African Americans needs to be interpreted with caution due to the limited range in the characteristics of the neighbourhood from which these participants were drawn.

From 1960s Evans County Georgia to present-day Jackson, Mississippi: an exploration of the evolution of cardiovascular disease in African Americans.

Cardiovascular disease (CVD) is the No. 1 cause of mortality in the United States and it disproportionately affects African Americans. However, there are earlier reports that African Americans had significantly less CVD than whites. This racial discrepancy in CVD rates was noticed primarily for coronary heart disease (CHD). This issue was examined in the Evans County (Georgia) Cardiovascular Disease Study conducted in the 1960s. It showed that African American men had significantly lower rates of CHD than white men. Over the last couple of decades, the rates of CVD have been declining. However, the rate of decline of CVD in African Americans has not been equal to that seen in whites, such that African Americans now have a disproportionate share of CVD in the United States. In the 1990s, the Jackson Heart Study was designed to explore the reasons for the current racial discrepancy. This articles reviews the findings of the Evans County Study and explores various hypotheses for why CVD in African Americans has evolved from a disease from which African Americans may have been "protected" to one in which they shoulder a disproportionate burden.

Obesity, physical inactivity, and risk for cardiovascular disease.

Despite considerable progress in understanding disease mechanisms and risk factors, improved treatments, and public education efforts, cardiovascular disease (CVD) remains the leading cause of death in the United States. Obesity and physical inactivity, 2 important lifestyle-related risk factors for CVD, are prevalent in the southeastern United States and are becoming more prevalent in all racial groups and areas of the country. In reviewing these risk factors, we explored topics including prevalence and trends in population data; associated psychosocial and environmental factors; and some of the mechanisms through which these risk factors are thought to contribute to CVD. We identified significant, but as yet poorly understood, racial disparities in prevalence of obesity, low levels of physical activity, and correlates of these risk factors and examined important differences in the complex relationship between obesity, diabetes, and cardiovascular disease risk between African American and European American women. The Jackson Heart Study will provide important and unique information relevant to many unanswered questions about obesity, physical inactivity, and obesity in African Americans.

The impact of a worksite weight management program on obesity: a retrospective analysis.

The objective of this study was to examine the efficacy of a worksite weight management program on the reduction of weight and lipid levels in employees and their dependents. This retrospective study examined the impact of a one-on-one worksite weight management program. Patients with a body mass index (BMI)>30, or a BMI>25 and 2 or more risk factors were eligible for inclusion. Laboratory and biometric readings at study end were compared to those at baseline. In addition, the percentage change of patients reaching recommended guideline levels was reported. Of the 310 employees enrolled, 157 completed the program (50.6%) with an average weight loss of 5.6%. Improvement was realized for pre-post weight (-6.0 lbs.; P≤.0001), BMI (-0.9; P≤.0001), blood pressure (systolic: -2.6; P≤.0001; diastolic: -1.9; P≤.0001), total cholesterol (-5.9; P=.0485), low-density lipoprotein cholesterol (LDL; -4.7; P=.0004), and triglycerides (-7.6; P=.0060). The proportion moving to within guideline levels increased for the following metrics: normal BMI category (2.6%; P=.0060),<30 BMI (10%; P≤.0001), systolic and diastolic blood pressure readings (7.7%; P=.0011 and 6.1; P=.0056, respectively), total cholesterol (6.5%; P=.0020), LDL (3.9%; P=.0396), and triglycerides (4.8; P=.0137). Retention in the worksite program was almost twice that seen in some commercial weight loss programs and significant improvements in laboratory and biometric readings were achieved. This study suggests that employer worksite-based programs may have an important role in improving the health of an employee population, which is of particular interest given the high prevalence of obesity and its attendant costs.

The 340B discount program: outpatient prescription dispensing patterns through contract pharmacies in 2012.

Section 340B of the Public Health Service Act provides qualified organizations serving vulnerable populations with deep discounts for some outpatient medications. A 2010 regulatory change widely expanded the 340B program's reach, allowing these organizations to contract with retail pharmacies to dispense medications for eligible patients. Little is known about which medications are dispensed by contract pharmacies under the expanded program. We provide the first comparison of 340B prescriptions and all prescriptions dispensed in contract pharmacies. We used 2012 data from Walgreens, the national leader in 340B contract pharmacies. Medications used to treat chronic conditions such as diabetes, high cholesterol levels, asthma, and depression accounted for an overwhelming majority of all prescriptions dispensed at Walgreens as part of the 340B program. A higher percentage of antiretrovirals used to treat HIV/AIDS were dispensed through 340B prescriptions than through all prescriptions dispensed at Walgreens. The majority of 340B prescriptions dispensed at Walgreens originated at tuberculosis clinics, consolidated health centers, disproportionate-share hospitals, and Ryan White clinics. Our results suggest that 340B contract pharmacies dispense medications used to treat Americans' chronic disease burden and disproportionately dispense medications used by key vulnerable populations targeted by the program.

The effect of a collaborative pharmacist-hospital care transition program on the likelihood of 30-day readmission.

PURPOSE: The effect of a collaborative pharmacist-hospital care transition program on the likelihood of 30-day readmission was evaluated. METHODS: This retrospective cohort study was conducted in two acute care hospitals within the same hospital system in the southeastern United States. One hospital initiated a care transition program in January 2011; the other hospital did not have such a program. All patients who were discharged from either hospital to home from January 1, 2010, through December 31, 2011, were included in the study. The two key program components included bedside delivery of postdischarge medications and follow-up telephone calls two to three days after discharge. The likelihood of readmission was assessed using multiple logistic regression. RESULTS: Over the 2-year study period, 19,659 unique patients had 26,781 qualifying index admissions, 2,523 of which resulted in a readmission within 30 days of discharge. After adjusting for various demographic and clinical characteristics, the usual care group (i.e., patients who did not participate in the program) had nearly twice the odds of readmission within 30 days (odds ratio [OR], 1.90; 95% confidence interval [CI], 1.35-2.67), compared with the intervention group (i.e., program participants). For patients age 65 years or older, those in the usual care group had a sixfold increase in the odds of a 30-day readmission (OR, 6.05; 95% CI, 1.92-19.00) relative to those in the intervention group. CONCLUSION: A care transition program was associated with a lower likelihood of readmission and had a greater effect on older patients.

Evaluation of increased adherence and cost savings of an employer value-based benefits program targeting generic antihyperlipidemic and antidiabetic medications.

BACKGROUND: A major employer implemented a change to its employee health benefits program to allow beneficiaries with diabetes or high cholesterol to obtain preselected generic antidiabetic or generic antihyperlipidemic medications with a zero dollar copayment. To receive this benefit, plan beneficiaries were required to participate in a contracted vendor's case management and/or wellness program.  OBJECTIVE: To assess changes in medication adherence and the costs for generic antidiabetic and generic antihyperlipidemic medications resulting from participation in a zero copay (ZCP) program.   METHODS: This was a retrospective pre-post comparison group study, evaluating adherence and cost. Participants using an antihyperlipidemic and/or antidiabetic medication during the study identification period and post-implementation period for the program were considered eligible for the study. Eligible beneficiaries who enrolled in the ZCP program during the post-implementation period were considered participants, while those who did not enroll during this period were considered nonparticipants. ZCP program participants and nonparticipants were matched via a 1-to-1 propensity scoring method using age, gender, comorbidity count, medication type (antihyperlipidemic, antidiabetic, or both), and baseline adherence as matching criteria. The proportion of days covered (PDC) metric expressed as a mean percentage was used to assess adherence to medication therapy, while payer cost was examined using prescription drug utilization expressed as per member per year (PMPY) and cost change per 30 days of medication expressed in dollars.   RESULTS: Among participants who were users of antidiabetic medications, the mean adherence rate was sustained from pre- to post-implementation (81.8% vs. 81.9%); however, it decreased in the matched nonparticipant group (81.9% vs. 73.1%). This difference in mean adherence over time between the participants and nonparticipants was statistically significant (0.1% vs. -8.8%, P less than 0.001). Similar results were found among users of antihyperlipidemics. The mean adherence rate was sustained over time for participants (77.7% vs. 78.3%) but declined over time for nonparticipants (77.6% vs. 70.8%). The difference in mean change over time was statistically significant between participants and nonparticipants (0.6% vs. -6,8%, P less than 0.001). Average prescription costs PMPY increased for participants of the ZCP program during the post-implementation period; however, the increase was not larger than the cost increase among nonparticipants ($581 vs. $584, P = 0.95). Furthermore, among antihyperlipidemics the cost increase post-implementation was actually significantly less for participants than nonparticipants ($51 vs. $143, P less than 0.001).  CONCLUSIONS: Plan sponsors are increasingly evaluating the use of value-based benefit design (VBBD) to change member behavior. This ZCP program used a reduction in cost sharing to incentivize members to use more generic drugs and to enroll in a care management coaching program. The study also demonstrated that a VBBD program can have a positive impact on adherence and cost outcomes among those who participate compared with nonparticipants. 

Hormonal therapy plus bevacizumab in postmenopausal patients who have hormone receptor-positive metastatic breast cancer: a phase II Trial of the Sarah Cannon Oncology Research Consortium.

PURPOSE: Preclinical models suggest that addition of anti-vascular endothelial growth factor therapy may improve the efficacy of anti-estrogens in hormone-sensitive breast cancer. This phase II trial evaluated the feasibility and efficacy of bevacizumab added to either anastrozole or fulvestrant in the first-line treatment of patients who have hormone receptor-positive metastatic breast cancer. METHODS: Women who had newly diagnosed metastatic hormone receptor-positive breast cancer were eligible. Patients who had relapsed while receiving, or ≤ 12 months after receiving, adjuvant aromatase inhibitor therapy were treated with bevacizumab (10 mg/kg intravenously every 2 weeks) and fulvestrant (loading dose 500 mg intramuscularly [IM], then 250 mg IM 2 weeks later, then 250 mg IM every 4 weeks). All other patients received fulvestrant/bevacizumab or anastrozole (1 mg orally daily)/bevacizumab. Patients who were HER2-positive could also receive trastuzumab (8 mg/kg loading dose, then 6 mg/kg every 3 weeks). Patients were reevaluated after 8 weeks of therapy; responding or stable patients continued treatment until disease progression or unacceptable toxicity. RESULTS: Seventy-nine patients were enrolled (38 were administered anastrozole 41 fulvestrant). Median treatment duration was 8 months in the anastrozole group and 5.5 months in the fulvestrant group. Both regimens were efficacious: overall response rate and median progression-free survival for the entire group were 28% and 13.5 months, respectively. Both regimens were well-tolerated; toxicity was consistent with the known toxicity profiles of each single agent. CONCLUSION: Bevacizumab combined with either anastrozole or fulvestrant was feasible and active in the first-line treatment of patients who have hormone receptor-positive metastatic breast cancer. Phase III trials evaluating the efficacy of bevacizumab added to endocrine therapy are in progress.

A phase II study of higher dose weekly topotecan in relapsed small-cell lung cancer.

BACKGROUND: Five-day topotecan is approved by the US Federal Drug Administration (FDA) for sensitive relapsed small-cell lung cancer (SCLC). We previously found that 4 mg/m(2) intravenous (I.V.) weekly dosing resulted in low-grade 3/4 toxicity but an overall response rate (ORR) < 10%. We hypothesized that higher topotecan dosing could improve ORR without significantly increasing toxicity. PATIENTS AND METHODS: This multicenter phase II trial sought a 25% ORR (α = 0.04; ß = 0.20). Eligible patients (sensitive or refractory relapsed SCLC; Eastern Cooperative Oncology Group [ECOG] performance status [PS] 0-1; measurable disease) received weekly topotecan (6 mg/m(2) I.V. for 6 weeks) and were restaged every 8 weeks. RESULTS: Baseline characteristics were N = 38, enrolled 5/2006-10/2007; median age 64 years (range, 35-82), 47% female, 74% ECOG PS 1, 50% refractory relapsed SCLC. The median follow-up was 15 months (range, 12-24 months). No patients received all planned therapy; only 1 patient was able to receive all planned treatment in cycle 1 because of hematologic toxicity and progressive disease (PD). Among all patients, ORR was 8% (95% confidence interval [CI], 2%-21%), 24% had stable disease, and disease in 47% progressed. Among sensitive relapsed patients ORR was 16% (95% CI, 3%-40%) with no complete responses; median response duration was 3.3 months. Five (26%) patients had stable disease; 8 (42%) patients had PD. Among sensitive relapsed patients, the median time to progression (TTP) and overall survival (OS) was 2.5 months and 8.6 months, respectively. Among refractory relapsed patients there were no ORRs, and median TTP and OS were 1.5 months and 3.7 months, respectively. Grade 3/4 toxicities (> 10%) included neutropenia (53%), leukopenia (42%), thrombocytopenia (37%), anemia (13%), fatigue (13%), and pain (13%). There were no treatment-related deaths. CONCLUSION: Weekly topotecan (6 mg/m(2) I.V.) is not feasible because of hematologic toxicity and does not improve efficacy in patients with relapsed SCLC.

Phase II trial of vinflunine in relapsed small cell lung cancer.

BACKGROUND: Vinflunine is a new microtubule inhibitor with preclinical activity in small cell lung cancer (SCLC). In this phase II trial, we evaluated vinflunine in patients with relapse-sensitive and refractory SCLC. METHODS: This trial aimed to achieve a 20% objective response rate (ORR) in platinum-sensitive patients. Patients with Eastern Cooperative Oncology Group performance status 0 to 2 and measurable disease received vinflunine (320 mg/m(2) IV) every 21 days (< or =6 cycles; response evaluation every 6 weeks). RESULTS: Patient characteristics (N = 51): median age 63 years (range, 37-85 years); male, 55%; Eastern Cooperative Oncology Group performance status 2, 16%; relapse-sensitive SCLC, 53%. The overall ORR was 19.6% (95% confidence interval [CI] 10-33%). Twelve (23.5%) patients had stable disease; 18 (35.3%) patients had progressive disease. Among relapse-sensitive patients, ORR was 22.2% (95% CI 9-42%). Among relapse-refractory patients, ORR was 16.7% (95% CI 5-37%). Median follow-up was 15 months (range, 12-18 months); median progression-free survival (PFS) was 1.6 months (95% CI 1.3-3.9 months); median overall survival (OS) was 4.9 months (95% CI 3.2- 6.5 months). Among relapse-sensitive patients, PFS and OS were 1.6 and 4.9 months, respectively. Among relapsed-refractory patients, PFS and OS were 1.4 and 4.0 months, respectively. In general, vinflunine was well tolerated, although neutropenia was a notable toxicity. Grade 3/4 toxicities (>5%): neutropenia (32%), arthralgia/myalgia (16%), fatigue (16%), hyponatremia (12%), leukopenia (12%), nausea/vomiting (12%), constipation (6%), and thrombocytopenia (6%). The rates of toxicities were relatively well balanced among relapse-sensitive and refractory patients; one patient died of sepsis that was possibly treatment related. CONCLUSIONS: Vinflunine has activity in relapsed SCLC, including refractory relapsed patients. Neutropenia was common but associated with rare febrile episodes. Additional study in relapse-refractory SCLC is indicated.