NatHER: protocol for systematic evaluation of trends in survival among patients with HER2-positive advanced breast cancer.

BACKGROUND: Human epidermal growth factor receptor 2 (HER2)-positive metastatic breast cancer (MBC) is an aggressive form of breast cancer and is historically associated with poor outcomes compared with HER2-negative MBC. Since 1998, four drugs have been globally approved for the targeted treatment of HER2-positive MBC. Additional advances in patient care-such as improved breast cancer screening, HER2 testing, and supportive care-have also occurred. The objective of this systematic review and meta-analysis is to determine whether there has been a cumulative change in survival over time in patients with HER2-positive advanced breast cancer based on results from interventional clinical trials (ICTs) and observational studies and to compare outcomes across these types of studies. METHODS/DESIGN: A systematic search of Medline, EMBASE, and the Cochrane Central Register of Controlled Trials will be performed. Two investigators will independently assess each abstract for inclusion. English language reports of ICTs and observational studies that include patients with HER2-positive advanced breast cancer from 1987 onwards will be considered. The primary outcome of interest is overall survival; secondary outcomes include progression-free survival and safety. Data on clinical outcomes, as well as on study design, study population, treatment/intervention, methodological quality, and outcomes, will be extracted using a structured codebook developed by the authors for this study. Standard and cumulative random effects meta-analysis will be performed to derive pooled risk estimates, both overall and by study design, controlling for covariates such as aggregate demographic and clinical characteristics of patients, treatment/intervention, and study characteristics. Heterogeneity of studies will be evaluated using the I(2) statistic. Differences in risk estimates by quality characteristics will be performed using meta-regression. DISCUSSION: This study will evaluate current and evolving trends in survival associated with HER2-positive advanced breast cancer over nearly 30 years and will build upon prior, less comprehensive, systematic analyses. This information is important to patients, healthcare providers, and researchers, particularly in the advanced disease setting, in which new therapies have been recently approved. Including observational studies allows us to evaluate real-world effectiveness; useful information will be gained by comparing findings from observational studies with those from ICTs. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42014014345.

Improving prescribing safety in patients with renal insufficiency in the ambulatory setting: the Drug Renal Alert Pharmacy (DRAP) program.

STUDY OBJECTIVE: To determine whether a computerized Drug Renal Alert Pharmacy (DRAP) program could decrease the rate of medication errors in drug selection or dosing for 15 target drugs in patients with renal insufficiency. DESIGN: Randomized, controlled, population-based effectiveness trial. SETTING: A large integrated health care delivery system. PATIENTS: A total of 32,917 health plan members who were at least 18 years old, had an estimated creatinine clearance of 50 ml/minute or lower, and were not receiving dialysis between December 1, 2003, and February 28, 2005, were randomly assigned to either the intervention group (16,577 patients) or usual care (control) group (16,340 patients). Of the 32,917 patients, 6125 patients (3025 in the intervention group and 3100 in the usual care group) were prescribed at least one target drug and were included in the analysis. INTERVENTION: A computerized tool--the DRAP program--was used to alert pharmacists at the time of dispensing to possible errors in target drug selection and dosing for patients with renal insufficiency. The 15 target drugs were previously identified based on frequency of use in our health care system and risk of serious adverse events. MEASUREMENTS AND MAIN RESULTS: The primary outcome was the proportion of medication errors, defined as target drugs that should be avoided or were dosed inappropriately, in the intervention and usual care groups. The Reach, Effectiveness, Adoption, Implementation, Maintenance (RE-AIM) framework was used to evaluate the intervention's potential for translation and generalizability. Among the 6125 patients who received a target drug, no significant differences were noted in age, sex, creatinine clearance, comorbid conditions, and number of target drugs between groups at baseline. Over the 15-month intervention period, the proportion of medication errors was significantly lower in the intervention group than the usual care group (33% vs 49%, p<0.001). After the study period, when the intervention was expanded to both groups, a 20% reduction in errors was sustained in the combined groups over the subsequent 7 months. CONCLUSION: The DRAP program was successful in reducing medication errors for patients with renal insufficiency in an ambulatory setting and was demonstrated to have sustainability after study completion.

Comorbidities, healthcare service utilization and costs for patients identified with painful DPN in a managed-care setting.

OBJECTIVE: This study examined the association of comorbidities, healthcare service use, and costs for diabetes patients with and without painful diabetic peripheral neuropathy (pDPN). METHODS: This was a retrospective, cohort analysis of data from members of a health maintenance organization. Patients with pDPN identified from a previously validated algorithm that was based on inclusion ICD-9 diagnosis codes consistent with signs and symptoms of peripheral neuropathy, as well as ICD-9 diagnosis codes to exclude non-diabetic etiologies. These subjects were matched 2 : 1 to patients without pDPN on age (+/-4 years), gender, and HbA(1c) stratum (<7%, 7-9%, and >9%) based on median HbA(1c) measured in 2002. Administrative data associated with outpatient and hospital-based care for the year 2003 were used to estimate healthcare service utilization and costs. Chi-square, univariate, and multivariate regression analyses were employed to estimate the variation in healthcare service utilization and costs. RESULTS: After applying inclusion and exclusion criteria, 1543 patients with pPDN were matched to 3069 patients without pDPN among prevalent diabetes cases. Patients with pDPN had significantly higher prevalence of comorbidities, including twice as many limb infections and nearly ten-fold greater limb amputations, and had consistently higher healthcare service utilization and costs across categories of care. The likelihood of any hospital admission for pDPN patients was more than 2.5-fold higher relative to patients without pDPN, and the excess cost associated with pDPN was estimated to be almost $6000 for the calendar year. CONCLUSIONS: The presence of pDPN in patients with diabetes was associated with significantly greater comorbidity, greater healthcare service utilization, and higher costs. While this study is limited to the direct medical care costs borne by the health plan, given the association of comorbidities and cost for patients with pDPN, further investigation is needed to determine if management approaches that are effective across chronic illnesses may prove to be beneficial for high cost diabetes patients.

Painful diabetic peripheral neuropathy in a managed care setting: patient identification, prevalence estimates, and pharmacy utilization patterns.

The objectives of this study were to validate an algorithm for identifying patients with painful diabetic peripheral neuropathy (pDPN) and demonstrate its practical applications. Using the Kaiser Permanente Colorado Diabetes Registry, an algorithm was developed with selected ICD-9 diagnosis codes combined with automated pharmacy data for medications prescribed for pDPN symptoms. Medical records were reviewed to confirm pDPN presence and to inform algorithm refinement. Prevalence was estimated with a numerator of members with diabetes who had inclusion but no exclusion codes in 2003 (Method 1) and with a numerator of diabetes patients with inclusion codes between 1998 and 2003 who had no subsequent exclusion codes and who remained members in 2003 (Method 2); the denominator was all members with diabetes in 2003. Medication utilization was compared between patients with and without pDPN. A total of 19,577 members with diabetes were identified; 2612 met initial inclusion criteria. Medical record review (n = 298) demonstrated sensitivity of 94%, specificity of 55%, and positive predictive value (PPV) of 64%. Inclusion criteria were modified and pharmacy data eliminated. The revised algorithm identified 1754 additional patients meeting inclusion criteria. Medical record review (n = 190) demonstrated sensitivity of 99%, specificity of 49%, and PPV of 79%. Using the validated algorithm, pDPN prevalence was 113 (Method 1) and 208 (Method 2) per 1000 persons with diabetes. Significant differences were observed in medication prescriptions between patients with and without pDPN. Estimated pDPN prevalence among persons with diabetes was 11%-21% and pDPN patients had greater utilization of selected medications than those without pDPN. Identifying patients with pDPN is a fundamental step for improving disease management and understanding the economic impact of pDPN.

Factors related to adherence to statin therapy.

BACKGROUND: Retrospective database analyses have revealed that 50% of patients receiving statins discontinue therapy after one year of treatment. Typically, these data do not focus on patient-specific reasons for discontinuation. OBJECTIVE: To examine the reasons that patients discontinue statins and compare the patient and clinical factors of those who do and do not discontinue therapy. METHODS: All patients with a new statin prescription between January 1, 2004, and March 31, 2004, were identified through pharmacy claims. Patients who had discontinued and continued statin therapy were identified. Medical records were reviewed to determine whether there were documented reasons for statin discontinuation. Subsequently, telephone surveys addressing statin knowledge, relationships, communication with healthcare providers, and general health status were conducted. RESULTS: At one year, 47.5% (n = 671) of patients had obtained fewer than 80% of the refills of their prescribed statin. We reviewed 435 medical records and conducted 255 patient surveys. A total of 29.9% of discontinuers had reasons documented in the medical record. Compared with continuers, fewer discontinuers had follow-up and/or laboratory visits with a provider within 6 months after the start of statin therapy. The surveys indicated that more continuers than discontinuers trusted their providers (p < 0.05) and felt that providers had adequate knowledge to answer their questions (p < 0.001). In contrast, more discontinuers felt the statin was of limited benefit/unsure of the benefit (p < 0.001) and believed that their providers were not interested in their input on their medical condition (p < 0.01). CONCLUSIONS: Utilizing pharmacy claims records alone to determine statin nonadherence may not only overestimate the percentage of patients who are nonadherent, but also prevent healthcare providers from understanding the reasons that patients discontinue or continue statin therapy. Statin adherence is complex and affected by several factors. Interventions to improve adherence should focus on patient communications, education, and follow-up.

Randomized trial to improve prescribing safety in ambulatory elderly patients.

OBJECTIVES: To determine whether a computerized tool that alerted pharmacists when patients aged 65 and older were newly prescribed potentially inappropriate medications was effective in decreasing the proportion of patients dispensed these medications. DESIGN: Prospective, randomized trial. SETTING: U.S. health maintenance organization. PARTICIPANTS: All 59,680 health plan members aged 65 and older were randomized to intervention (n=29,840) or usual care (n=29,840). Pharmacists received alerts on all patients randomized to intervention who were newly prescribed a targeted medication. INTERVENTION: Prescription and age information were linked to alert pharmacists when a patient aged 65 and older was newly prescribed one of 11 medications that are potentially inappropriate in older people. MEASUREMENTS: Physicians and pharmacists collaborated to develop the targeted medication list, indications for medication use for which an intervention should occur, intervention guidelines and scripts, and to implement the intervention. RESULTS: Over the 1-year study, 543 (1.8%) intervention group patients aged 65 and older were newly dispensed prescriptions for targeted medications, compared with 644 (2.2%) usual care group patients (P=.002). For medication use indications in which an intervention should occur, dispensings of amitriptyline (P<.001) and diazepam (P=.02) were reduced. CONCLUSIONS: This study demonstrated the effectiveness of a computerized pharmacy alert system plus collaboration between healthcare professionals in decreasing potentially inappropriate medication dispensings in elderly patients. Coupling data available from information systems with the knowledge and skills of physicians and pharmacists can improve prescribing safety in patients aged 65 and older.

Cultural competence in health care and its implications for pharmacy. Part 1. Overview of key concepts in multicultural health care.

Pharmacists are caring for more individuals of diverse age, gender, race, ethnicity, socioeconomic status, religion, sexual orientation, and health beliefs than in previous decades. Not all residents of the United States equally experience long life spans and good health. Health disparities in various cultures have been documented. One critical aspect of reducing health disparities is moving health care providers, staff, administrators, and practices toward increased cultural competence and proficiency. Effective delivery of culturally and linguistically appropriate service in cross-cultural settings is identified as cultural competence. Culture is a dynamic process, with people moving in and out of various cultures throughout their lives. The failure to understand and respect individuals and their cultures could impede pharmaceutical care. Incongruent beliefs and expectations between the patient and pharmacist could lead to misunderstandings, confusion, and ultimately to drug misadventures. Models and frameworks have been developed that provide descriptions of the process by which individuals, practice settings, and organizations can become culturally competent and proficient. This article, the first in a five-part series, presents an overview of issues related to cultural competence in health care with an emphasis on the pharmacy profession. Also provided are definitions for cultural competence and related terms, a brief overview of health disparities and challenges to the common morality, and a discussion of models and frameworks that describe pathways to cultural competence and proficiency.

Estimation of the period prevalence of inflammatory bowel disease among nine health plans using computerized diagnoses and outpatient pharmacy dispensings.

BACKGROUND: There are few contemporary estimates of prevalence rates for inflammatory bowel disease (IBD) in diverse North American communities. METHODS: We estimated the period prevalence of IBD for January 1, 1999, through June 30, 2001, among 1.8 million randomly sampled members of nine integrated healthcare organizations in the US using computerized diagnoses and outpatient pharmaceutical dispensing. We also assessed the positive predictive value (PPV) and sensitivities of 1) the case-finding algorithm, and 2) the 30-month sampling period using medical chart review and linkage to a 78-month dataset, respectively. RESULTS: The PPV of the case-finding algorithm was 81% (95% confidence interval [CI], 78-87) and 84% (95% CI, 79-89) in two different organizations. In both, the sensitivity of the optimal algorithm, compared with the most inclusive, exceeded 90%. The sensitivity of the 30-month sampling period compared with 78 months was 61% (95% CI, 57-64) in one organization. Applying a slightly more sensitive case-finding algorithm, the average period prevalence of IBD across the nine organizations, standardized to the age- and gender-distribution of the US population, 2000 census, was 388 cases (95% CI, 378-397) per 100,000 persons (range 209-784 per 100,000; average follow-up 26 months). The prevalence of Crohn's disease, ulcerative colitis, and unspecified IBD was 129, 191, and 69 per 100,000, respectively. CONCLUSIONS: The observed average prevalence was similar to prevalence proportions reported for other North American populations (369-408 per 100,000). Additional research is needed to understand differences in the occurrence of IBD among diverse populations as well as practice variation in diagnosis and treatment of IBD.

Racial differences in tumor stage and survival for colorectal cancer in an insured population.

BACKGROUND: Despite declining death rates from colorectal cancer (CRC), racial disparities have continued to increase. In this study, the authors examined disparities in a racially diverse group of insured patients. METHODS: This study was conducted among patients who were diagnosed with CRC from 1993 to 1998, when they were enrolled in integrated healthcare systems. Patients were identified from tumor registries and were linked to information in administrative databases. The sample was restricted to non-Hispanic whites (n = 10,585), non-Hispanic blacks (n = 1479), Hispanics (n = 985), and Asians/Pacific Islanders (n = 909). Differences in tumor stage and survival were analyzed by using polytomous and Cox regression models, respectively. RESULTS: In multivariable regression analyses, blacks were more likely than whites to have distant or unstaged tumors. In Cox models that were adjusted for nonmutable factors, blacks had a higher risk of death from CRC (hazard ratio [HR], 1.17; 95% confidence interval [95% CI], 1.06-1.30). Hispanics had a risk of death similar to whites (HR, 1.04; 95% CI, 0.92-1.18), whereas Asians/Pacific Islanders had a lower risk of death from CRC (HR, 0.89; 95% CI, 0.78-1.02). Adjustment for tumor stage decreased the HR to 1.11 for blacks, and the addition of receipt of surgical therapy to the model decreased the HR further to 1.06. The HR among Hispanics and Asians/Pacific Islanders was stable to adjustment for tumor stage and surgical therapy. CONCLUSIONS: The relation between race and survival from CRC was complex and appeared to be related to differences in tumor stage and therapy received, even in insured populations. Targeted interventions to improve the use of effective screening and treatment among vulnerable populations may be needed to eliminate disparities in CRC.

Disparities and survival among breast cancer patients.

BACKGROUND: Although rates of survival for women with breast cancer have improved, the survival disparity between African American and white women in the United States has increased. PURPOSE: To determine whether this survival disparity persists in an insured population with access to medical care. METHODS: In this retrospective cohort study, we extracted data from the tumor registries of six nonprofit, integrated health care delivery systems affiliated with the Cancer Research Network and assessed the survival of African American (n = 2276) and white (n = 18 879) female enrollees who were diagnosed with invasive breast cancer from January 1, 1993, through December 31, 1998. Cox proportional hazards regression was used to estimate the death rate among African American women relative to that of white women after adjustment for potential explanatory factors including stage at diagnosis, tumor characteristics, and treatment. RESULTS: Five-year survival was lower for African American women (73.8%) than for white women (81.6%). African American women were less likely to have tumor characteristics with good prognosis. Controlling for age at diagnosis, stage, grade, tumor size, and estrogen and progesterone receptor status, the adjusted hazard rate ratio for African American women was 1.34 (95% confidence interval = 1.22 to 1.46). Similar risks were found among women ages 20-49 and 50 and older. Controlling for treatment slightly lowered the hazard rate ratio to 1.31 (95% confidence interval = 1.20 to 1.43). CONCLUSIONS: Among women with invasive breast cancer, being insured and having access to medical care does not eliminate the survival disparity for African American women.

The power of collaboration: using internet-based tools to facilitate networking and benchmarking within a consortium of academic health centers.

The University HealthSystem Consortium (UHC) represents a strategic alliance of 169 academic health centers and associated institutions engaged in knowledge sharing and idea-generation. The use of the Internet as a tool in the delivery of UHC's products and services has increased dramatically over the past year and will continue to increase during the foreseeable future. This paper examines the current state of UHC-member institution driven tools and services that utilize the Web as a fundamental component in their delivery. The evolution of knowledge management at UHC, its management information and reporting tools, and expansion of e-commerce provide real world examples of Internet use in health care delivery and management. Health care workers are using these Web-based tools to help manage rising costs and optimize patient outcomes. Policy, technical, and organizational issues must be resolved to facilitate rapid adoption of Internet applications.