Statin use and risk of multiple myeloma: An analysis from the cancer research network.

Animal and human data suggest statins may be protective against developing multiple myeloma; however, findings may be biased by the interrelationship with lipid levels. We investigated the association between statin use and risk of multiple myeloma in a large US population, with an emphasis on accounting for this potential bias. We conducted a case-control study nested within 6 US integrated healthcare systems participating in the National Cancer Institute-funded Cancer Research Network. Adults aged ≥40 years who were diagnosed with multiple myeloma from 1998-2008 were identified through cancer registries (N = 2,532). For each case, five controls were matched on age, sex, health plan, and membership duration prior to diagnosis/index date. Statin prescriptions were ascertained from electronic pharmacy records. To address potential biases related to lipid levels and medication prescribing practices, multivariable marginal structural models were used to model statin use (≥6 cumulative months) and risk of multiple myeloma, with examination of multiple latency periods. Statin use 48-72 months prior to diagnosis/index date was associated with a suggestive 20-28% reduced risk of developing multiple myeloma, compared to non-users. Recent initiation of statins was not associated with myeloma risk (risk ratio range 0.90-0.99 with 0-36 months latency). Older patients had more consistent protective associations across all latency periods (risk ratio range 0.67-0.87). Our results suggest that the association between statin use and multiple myeloma risk may vary by exposure window and age. Future research is warranted to investigate the timing of statin use in relation to myeloma diagnosis.

Use of androgen deprivation therapy as salvage treatment after primary therapy for clinically localized prostate cancer.

PURPOSE: The optimal use of androgen deprivation therapy as salvage treatment (sADT) for men after initial prostatectomy or radiotherapy for clinically localized prostate cancer is undefined. We describe patterns of sADT use and investigate clinical and sociodemographic characteristics of insured men who received sADT versus surveillance in managed care settings. METHODS: Using comprehensive electronic health records and cancer registry data from three integrated health plans, we identified all men with newly diagnosed clinically localized prostate cancer between 1995 and 2009 who received either prostatectomy (n = 16,445) or radiotherapy (n = 19,531) as their primary therapy. We defined sADT based on the timing of ADT following primary therapy and stage of cancer. We fit Cox proportional hazard models to identify sociodemographic characteristics and clinical factors associated with sADT. RESULTS: With a median follow-up of 6 years (range 2-15 years), 13 % of men who underwent primary prostatectomy or radiotherapy received sADT. After adjusting for selected covariates, sADT was more likely to be used in men who were older (e.g., HR 1.70, 95 % CI 1.48-1.96 or HR 1.33, 95 % CI 1.17-1.52 for age 70+ relative to age 35-59 for primary prostatectomy or radiotherapy, respectively), were African-American, had a short PSA doubling time, had a higher pre-treatment risk of progression, had more comorbidities, and received adjuvant ADT for initial disease. CONCLUSIONS: In men with localized prostate cancer in community practice initially treated with prostatectomy or radiotherapy, sADT after primary treatment was more frequent for men at greater risk of death from prostate cancer, consistent with practice guidelines.

Risk of diabetes among patients receiving primary androgen deprivation therapy for clinically localized prostate cancer.

PURPOSE: Androgen deprivation therapy may increase diabetes risk. As the benefits of primary androgen deprivation therapy for localized prostate cancer are controversial, and most prostate cancer survivors are of advanced age with comorbidities, it is important to determine if primary androgen deprivation therapy increases the risk of diabetes and to determine the susceptibility factors. MATERIALS AND METHODS: We conducted a retrospective cohort study of 12,191 men diagnosed with incident localized prostate cancer during 1995 to 2008, age 35 to 100 years, and without diabetes or receipt of prostatectomy or radiation 1 year after diagnosis. Patients were enrolled in 1 of 3 managed health plans and followed through 2010. Primary androgen deprivation therapy was defined as androgen deprivation therapy within 1 year after diagnosis. Incident diabetes was ascertained using inpatient and outpatient diagnosis codes, diabetes medications and hemoglobin A1c values. We estimated primary androgen deprivation therapy associated diabetes risk using Cox proportional hazard models in conventional and propensity score analyses. RESULTS: Diabetes developed in 1,203 (9.9%) patients during followup (median 4.8 years) with incidence rates of 2.5 and 1.6 events per 100 person-years in the primary androgen deprivation therapy and nonprimary androgen deprivation therapy groups, respectively. Primary androgen deprivation therapy was associated with a 1.61-fold increased diabetes risk (95% CI 1.38-1.88). The number needed to harm was 29. The association was stronger in men age 70 or younger than in older men (HR 2.25 vs 1.40, p value for interaction=0.008). CONCLUSIONS: Primary androgen deprivation therapy may increase diabetes risk by 60% and should be used with caution when managing localized prostate cancer. Because of the consistent association between androgen deprivation therapy and greater diabetes risk across disease states, we recommend routine screening and lifestyle interventions to reduce the risk of diabetes in men receiving androgen deprivation therapy.

Incidence of liver injury among cancer patients receiving chemotherapy in an integrated health system.

PURPOSE: Using liver laboratory tests (LLTs), Hy's law is a method used to identify drug-induced liver injury (DILI), after excluding other causes. Elevated LLTs in chemotherapy-exposed patients may result from tumor effects or comorbidities. This study evaluated incidence of Hy's law in chemotherapy-treated cancer patients. METHODS: We identified breast, colorectal, and lung cancer patients diagnosed in 1 January 2000 to 31 December 2007 at a Midwestern health system. Using automated data, potential Hy's law (PHL) cases were defined by patterns of elevated LLTs suggestive of DILI. Among those treated with chemotherapy, we excluded PHL patients with pre-existing conditions that could cause liver injury, producing a cohort meeting Hy's law criteria, according to automated data. Medical record review, conducted among these automated data-derived Hy's law patients, further excluded those with causes of liver injury other than chemotherapy. RESULTS: Using automated data, among chemotherapy-exposed patients (N = 2788), 91 (3.3%) met PHL criteria using LLTs and 64 (2.3%) met Hy's law after excluding underlying liver injury using the International Classification of Diseases, 9th Revision codes. After a medical record review, 62 of 64 patients qualifying as Hy's law through automated data had other potential causes, leaving two patients (0.07%; 95%CI: 0.01-0.24%) with chemotherapy as a likely alternative cause of liver injury. CONCLUSIONS: Abnormal LLTs are common in chemotherapy-treated patients. Medical record review showed that the incidence of Hy's law events is rare. These data provide context for evaluating DILI in clinical trials and postmarketing surveillance of anticancer therapies, understanding that automated data alone may substantially overestimate the number of Hy's law cases.

Racial disparities in treatment patterns and clinical outcomes in patients with HER2-positive metastatic breast cancer.

Data characterizing demographics, treatment patterns, and clinical outcomes in black patients with human epidermal growth factor receptor 2 (HER2)-positive metastatic breast cancer (MBC) are limited. registHER is a large, observational cohort study of patients (n = 1,001) with HER2-positive MBC diagnosed ≤6 months of enrollment and followed until death, disenrollment, or June 2009 (median follow-up of 27 months). Demographics, treatment patterns, and clinical outcomes were described for black (n = 126) and white patients (n = 793). Progression-free survival (PFS) following first-line therapy and overall survival (OS) were examined. Multivariate analyses adjusted for baseline and treatment factors. Black patients were more likely than white patients to be obese (body mass index ≥30), to have diabetes, and to have a history of cardiovascular disease; they were also less likely to have estrogen receptor or progesterone receptor positive disease. In patients treated with trastuzumab, the incidence of cardiac safety events (grade ≥3) was higher in black patients (10.9 %) than in white patients (7.9 %). Unadjusted median OS and PFS (months) were significantly lower in black patients than in white patients (OS: black: 27.1, 95 % confidence interval [CI] 21.3-32.1; white: 37.3, 95 % CI 34.6-41.1; PFS: black: 7.0, 95 % CI 5.7-8.2; white: 10.2, 95 % CI 9.3-11.2). The adjusted OS hazard ratio (HR) for black patients compared with white patients was 1.29 (95 % CI 1.00-1.65); adjusted PFS HR was 1.29 (95 % CI 1.05-1.59). This real-world evaluation of a large cohort of patients with HER2-positive MBC shows poorer prognostic factors and independently worse clinical outcomes in black versus white patients. Further research is needed to identify potential biologic differences that could have predictive impact for black patients or that could explain these differences.

Association between second-generation antipsychotics and newly diagnosed treated diabetes mellitus: does the effect differ by dose?

BACKGROUND: The benefits of some second-generation antipsychotics (SGAs) must be weighed against the increased risk for diabetes mellitus. This study examines whether the association between SGAs and diabetes differs by dose. METHODS: Patients were ≥18 years of age from three US healthcare systems and exposed to an SGA for ≥45 days between November 1, 2002 and March 31, 2005. Patients had no evidence of diabetes before index date and no previous antipsychotic prescription filled within 3 months before index date.49,946 patients were exposed to SGAs during the study period. Person-time exposed to antipsychotic dose (categorized by tertiles for each drug) was calculated. Newly treated diabetes was identified using pharmacy data to determine patients exposed to anti-diabetic therapies. Adjusted hazard ratios for diabetes across dose tertiles of SGA were calculated using the lowest dose tertile as reference. RESULTS: Olanzapine exhibited a dose-dependent relationship for risk for diabetes, with elevated and progressive risk across intermediate (diabetes rate per 100 person-years = 1.9; adjusted Hazard Ratio (HR), 1.7, 95% confidence interval (CI), 1.0-3.1) and top tertile doses (diabetes rate per 100 person-years = 2.7; adjusted HR, 2.5, 95% CI, 1.4-4.5). Quetiapine and risperidone exhibited elevated risk at top dose tertile with no evidence of increased risk at intermediate dose tertile. Unlike olanzapine, quetiapine, and risperidone, neither aripiprazole nor ziprasidone were associated with risk of diabetes at any dose tertile. CONCLUSIONS: In this large multi-site epidemiologic study, within each drug-specific stratum, the risk of diabetes for persons exposed to olanzapine, risperidone, and quetiapine was dose-dependent and elevated at therapeutic doses. In contrast, in aripiprazole-specific and ziprasidone-specific stratum, these newer agents were not associated with an increased risk of diabetes and dose-dependent relationships were not apparent. Although, these estimates should be interpreted with caution as they are imprecise due to small numbers.

Epidemiologic study of aripiprazole use and the incidence of suicide events.

PURPOSE: Because second generation antipsychotics (SGA) might affect the risk of suicide, systematic assessment of suicide risk associated with SGA in the postmarketing setting is important and of interest to regulatory authorities. To fulfill a postmarketing request, our objective was to determine suicide event (attempted or completed) incidence in patients with schizophrenia or bipolar disorder, prescribed aripiprazole. METHODS: Using administrative data from three US sources, we assessed study endpoints of suicide attempts and death by suicide in patients aged ≥18 enrolled continuously for ≥3 months in their health plans before receiving their first ever antipsychotic (November 2002-December 2005). RESULTS: Among 20 489 antipsychotic users (8985 patient-years), unadjusted suicide event rates (per 1000 patient-years) were: 20.69 (aripiprazole); 23.99 (olanzapine); 32.33 (quetiapine); 19.69 (risperidone); 48.52 (ziprasidone). Compared with current users of other SGA combined, aripiprazole users did not have an increased risk of suicide events (crude hazard ratio (HR) = 0.79, 95%CI: 0.48-1.30; adjusted HR = 0.69, 95%CI: 0.42-1.14-(controlling for study site, age, sex, index prescription year, antipsychotic use history, other pharmacotherapy exposure, comorbidity presence, schizophrenia/bipolar disorder, suicide attempts, number inpatient/outpatient encounters). CONCLUSIONS: In this large, multi-site study, compared with other SGA combined, aripiprazole is not associated with an increased risk of suicide events in an inception cohort of patients with ICD-9/ICD-10 codes indicative of schizophrenia or bipolar disorder.

Impact of bipolar disorder: results from a screening study.

OBJECTIVE: To characterize the extent and impact of bipolar I and II disorders and rapid cycling in a managed care population using both coded diagnostic claims and clinical screening. METHOD: The Mood Disorder Questionnaire (MDQ) was used to identify bipolar disorder among patients attending the psychiatry service of a large Midwestern health system. Suicidal ideation screening questions were also asked, along with a brief set of relevant history and medication questions. Patients scoring positive on the MDQ or identified as bipolar-positive according to DSM-IV criteria by the screening clinician were administered the Work and Social Adjustment Scale and an Employment questionnaire. Descriptive statistics were used to summarize results. The study was conducted from July 2004 to November 2004. RESULTS: Seventy (6.4%) of 1087 patients had bipolar disorder, 59 of whom completed the entire study. For these patients, the mean time with bipolar disorder was 9.3 (SD 10.2) years. The mean length of the current episode was 10.4 (SD 14.4) weeks, with 22% of patients experiencing a mixed episode, 5% manic-predominant, 12% hypomanic-predominant, and 46% a depressive-predominant episode. Twenty-four percent of patients with bipolar disorder were rapid cycling at the time of their visit; for 5 of these patients, rapid cycling was thought to be related to antidepressant use. Sixty-one percent of patients with bipolar disorder were taking an antidepressant; 69.5% were taking a mood stabilizer. Of these patients with bipolar disorder, 19% were evaluated as high suicidality risk, while 47% were considered moderate risk. Bipolar disorder patients reported problems with employment/employability and social adjustment. About one quarter of these patients ranked problems with family and relationships as marked or severe. Fifty percent of these bipolar disorder patients reported missing at least 1 week of work during the past month; 41% reported fearing the loss of their current job due to their emotional state; and 20% reported being fired/laid off during the past 5 years due to their emotional state. CONCLUSIONS: This research documents some of the clinical features and social and labor-force impact of bipolar disorder in a managed care population and adds several dimensions to data published to date. Fully two thirds of our study subjects with bipolar disorder were found to be at substantial risk of suicide, and bipolar disorder patients in this study reported substantial problems with employment/employability and social functioning.

Late-stage breast cancer among women with recent negative screening mammography: do clinical encounters offer opportunity for earlier detection?

BACKGROUND: Opportunities to prevent late-stage breast cancer within the course of usual care are needed. We evaluate whether clinical encounters offer such opportunities. METHODS: Within seven health care plans, we identified 1298 women aged more than 50 years with early (<3 cm), late-stage (> or = 3 cm), or metastatic invasive breast cancer diagnosed during 1995-1999, whose first screening mammogram 13-36 months prior to the diagnosis (index) was negative. We audited all care occurring in the health plans up to 36 months prior to the cancer diagnoses. Ordinal logistic regression compared the frequency of events by disease category. We hypothesized that during the 13-36 months prior to diagnosis, women with late-stage or metastatic breast cancer would have more symptoms and be more likely to have breast-related clinical visits but have less breast screening (clinical breast examination [CBE] or mammography) than women with early-stage disease, thereby indicating clinical opportunities for earlier detection. RESULTS: We found no differences in demographic characteristics across breast cancer stage among the 1298 women. Both before and after the negative index mammogram but during the 13-36 months prior to diagnosis, few women had breast symptoms (5% before index, 8% after), but many sought breast care (86% before index, 90% after) and screening CBE (62% before index, 43% after). Only the occurrence of screening CBE (odds ratio [OR] = 0.73, 95% confidence interval [CI] = 0.56 to 0.95) or screening mammograms (OR = 0.74, 95% CI = 0.57 to 0.97) after the negative index mammogram reduced odds of more severe disease at diagnosis. CONCLUSION: Although the mortality benefit of CBE, or one compared to two year mammography has not been established, we found that women with late-stage breast cancers undetected by screening mammography did not experience opportunities for earlier detection except through CBE or additional screening mammography.

Breast and cervical cancer screening: clinicians' views on health plan guidelines and implementation efforts.

BACKGROUND: Optimizing breast and cervical cancer screening rates within health plans requires clinician support for screening guidelines, an awareness of whether there are tools available and functioning to aid screening implementation, and a perception of collegial and leadership support for quality screening services. This study investigated clinicians' perceptions of guidelines, reminders for screening, and plan and practice commitment in order to assess where opportunities exist to improve the screening process. METHODS: A stratified sample of 761 primary care clinicians from three comprehensive health plans were surveyed to assess awareness of and agreement with guideline elements, perception of guidelines' usefulness, awareness of plan strategies to promote guideline adherence, perception of support for high-quality screening services, and ratings of plan efforts to maximize members' access. RESULTS: Clinician awareness of and agreement with guideline elements was high (98% breast, 94% cervical). Across guideline elements, agreement was lower for mammography than cervical screening, notably for upper age limit recommendations (58% breast, 79% cervical). Knowledge of systems that cue patients and clinicians that screening is due varied by cancer test, and clinician report and plan report data about the existence of systems were, at times, not congruent. Views about consistent operation of systems differed by test (mammograms, 74%-92%; Pap, 66%-84%). Clinicians rated local colleagues and local and plan medical leadership as very committed to high-quality screening, albeit with somewhat lower ratings for cervical testing. Although the majority rated overall plan efforts to maximize screening as very good or excellent, perceived consistency of systems to cue a woman that she is due for testing and perception of collegial support were independently and significantly related to ratings of plan efforts. CONCLUSIONS: Improvements in knowledge of systems that support guideline implementation varied, and action to ensure accurate perception of reminders, as well as consistent implementation of systems, may be important for improving screening rates and outcomes. Plan efforts and clinician efforts at the practice level are closely linked and need to be aligned to maximize screening rates. This requires plan and practice-level analyses of structures and processes that could be improved.

Racial and age differences in colon examination surveillance following a diagnosis of colorectal cancer.

PURPOSE: The purpose of this analysis is to describe factors associated with colorectal surveillance following diagnosis and treatment of nonmetastatic colorectal cancer. METHODS: Subjects were identified as part of the HMO Cancer Research Network's study of colorectal cancer survivors. To be eligible for the main study, patients had to be part of the staff model components of health maintenance organizations in southeastern Michigan and Minnesota. Using computerized databases, individuals were identified who were 40 years or older with incident nonmetastatic colorectal cancer diagnosed between January 1, 1990, and December 31, 2000. Using data current through 2002, we analyzed the cohort using chi-square test statistics, life tables, and Cox proportional hazards models to understand variations in posttreatment surveillance practices. Subjects were followed up from date of diagnosis to date of recurrence, death, disenrollment from the health plan, or loss to follow-up, which ever came first. We assessed factors associated with colorectal surveillance at 1, 3, and 5 years after treatment. We also included an analysis comparing those who received an exam and those who didn't regardless of exam timing. RESULTS: A total of 908 patients were eligible for the main study. Of these, we excluded subjects who were not white or African American (n = 27), resulting in an analytic sample of 881 (97% of the eligible cohort). Twenty-five percent of subjects were African American, 43% were female, and 48% were aged 70 years or older. The proportion who received an exam at 1 year was 18%, at 3 years was 60%, and at 5 years was 67%. Chi-square tests showed that African Americans were statistically significantly less likely than whites to receive an exam at all three time points. The Cox proportional hazards model for examinations regardless of timing and adjusted for confounders showed that African Americans were still less likely than whites to receive an exam (hazard ratio = 0.62; 95% confidence interval [CI] = 0.51 to 0.75). The same trend in undersurveillance was also observed for those 80 years of age or older at diagnosis, with an adjusted hazard ratio of 0.39 (95% CI = 0.26 to 0.57). CONCLUSION: Our data indicate that colorectal cancer survivors who are African American or aged 80 years or more at diagnosis are less likely to receive posttreatment colorectal surveillance. Whether these differences are due to system or patient level barriers needs further study.

Effectiveness of primary androgen-deprivation therapy for clinically localized prostate cancer.

PURPOSE: Primary androgen-deprivation therapy (PADT) is often used to treat clinically localized prostate cancer, but its effects on cause-specific and overall mortality have not been established. Given the widespread use of PADT and the potential risks of serious adverse effects, accurate mortality data are needed to inform treatment decisions. METHODS: We conducted a retrospective cohort study using comprehensive utilization and cancer registry data from three integrated health plans. All men were newly diagnosed with clinically localized prostate cancer. Men who were diagnosed between 1995 and 2008, were not treated with curative intent therapy, and received follow-up through December 2010 were included in the study (n = 15,170). We examined all-cause and prostate cancer-specific mortality as our main outcomes. We used Cox proportional hazards models with and without propensity score analysis. RESULTS: Overall, PADT was associated with neither a risk of all-cause mortality (hazard ratio [HR], 1.04; 95% CI, 0.97 to 1.11) nor prostate-cancer-specific mortality (HR, 1.03; 95% CI, 0.89 to 1.19) after adjusting for all sociodemographic and clinical characteristics. PADT was associated with decreased risk of all-cause mortality but not prostate-cancer-specific mortality. PADT was associated with decreased risk of all-cause mortality only among the subgroup of men with a high risk of cancer progression (HR, 0.88; 95% CI, 0.78 to 0.97). CONCLUSION: We found no mortality benefit from PADT compared with no PADT for most men with clinically localized prostate cancer who did not receive curative intent therapy. Men with higher-risk disease may derive a small clinical benefit from PADT. Our study provides the best available contemporary evidence on the lack of survival benefit from PADT for most men with clinically localized prostate cancer.

Administrative data algorithms to identify second breast cancer events following early-stage invasive breast cancer.

BACKGROUND: Studies of breast cancer outcomes rely on the identification of second breast cancer events (recurrences and second breast primary tumors). Cancer registries often do not capture recurrences, and chart abstraction can be infeasible or expensive. An alternative is using administrative health-care data to identify second breast cancer events; however, these algorithms must be validated against a gold standard. METHODS: We developed algorithms using data from 3152 women in an integrated health-care system who were diagnosed with stage I or II breast cancer in 1993-2006. Medical record review served as the gold standard for second breast cancer events. Administrative data used in algorithm development included procedures, diagnoses, prescription fills, and cancer registry records. We randomly divided the cohort into training and testing samples and used a classification and regression tree analysis to build algorithms for classifying women as having or not having a second breast cancer event. We created several algorithms for researchers to use based on the relative importance of sensitivity, specificity, and positive predictive value (PPV) in future studies. RESULTS: The algorithm with high specificity and PPV had 89% sensitivity (95% confidence interval [CI] = 84% to 92%), 99% specificity (95% CI = 98% to 99%), and 90% PPV (95% CI = 86% to 94%); the high-sensitivity algorithm had 96% sensitivity (95% CI = 93% to 98%), 95% specificity (95% CI = 94% to 96%), and 74% PPV (95% CI = 68% to 78%). CONCLUSIONS: Algorithms based on administrative data can identify second breast cancer events with high sensitivity, specificity, and PPV. The algorithms presented here promote efficient outcomes research, allowing researchers to prioritize sensitivity, specificity, or PPV in identifying second breast cancer events.

Age, comorbidity, and breast cancer severity: impact on receipt of definitive local therapy and rate of recurrence among older women with early-stage breast cancer.

BACKGROUND: The definitive local therapy options for early-stage breast cancer are mastectomy and breast-conserving surgery followed by radiation therapy. Older women and those with comorbidities frequently receive breast-conserving surgery alone. The interaction of age and comorbidity with breast cancer severity and their impact on receipt of definitive therapy have not been well-studied. STUDY DESIGN: In a cohort of 1,837 women aged 65 years and older receiving treatment for early-stage breast cancer in 6 integrated health care delivery systems in 1990-1994 and followed for 10 years, we examined predictors of receiving nondefinitive local therapy and assessed the impact on breast cancer recurrence within levels of severity, defined as level of risk for recurrence. RESULTS: Age and comorbidity were associated with receipt of nondefinitive therapy. Compared with those at low risk, women at the highest risk were less likely to receive nondefinitive therapy (odds ratio = 0.32; 95% CI, 0.22-0.47), and women at moderate risk were about half as likely (odds ratio = 0.54; 95% CI, 0.35-0.84). Nondefinitive local therapy was associated with higher rates of recurrence among women at moderate (hazard ratio = 5.1; 95% CI, 1.9-13.5) and low risk (hazard ratio = 3.2; 95% CI, 1.1-8.9). The association among women at high risk was weak (hazard ratio = 1.3; 95% CI, 0.75-2.1). CONCLUSIONS: Among these older women with early-stage breast cancer, decisions about therapy partially balanced breast cancer severity against age and comorbidity. However, even among women at low risk, omitting definitive local therapy was associated with increased recurrence.

Sustained hyperglycemia among patients with diabetes: what matters when action is needed?

OBJECTIVE To estimate prevalence of, and factors associated with, sustained periods of hyperglycemia among patients with diabetes and factors associated with receipt of appropriate care once A1C values are persistently elevated. RESEARCH DESIGN AND METHODS Among patients initiating oral monotherapy (n = 5,070), Kaplan-Meier and Cox proportional hazards methods were used to estimate time to, and factors associated with, sustained hyperglycemia (defined by two A1cs >8% and no recent medication intensification), and among those experiencing sustained hyperglycemia, time to, and factors associated with, appropriate receipt of care (i.e., medication intensification or achieving A1C < or =7%). RESULTS Within 1 year, 8% experienced sustained hyperglycemia, with the proportion rising to 38% within 5 years. Patients using sulfonylurea had greater risk of hyperglycemia (hazard ratio [HR] 1.47 [95% CI 1.30-1.66]) compared with those initiating metformin. Risk increased with age (1.89 [1.27-2.83]), was greater for African Americans (1.19 [1.05-1.36]), and increased with A1C levels >7%. Among individuals with sustained hyperglycemia (n = 1,386), mean time to appropriate care was 9.7 months, with 25% not receiving appropriate care within 1 year. Shorter delays to appropriate care receipt were associated with increasing income (1.03 [1.00-1.07]), A1C >9% (1.38 [1.06-1.79]) and >11% (1.65 [1.25-2.18]), increasing medication adherence (1.03 [1.01-1.04]), and visits to primary care (4.22 [3.65-4.88]) or endocrinology (3.89 [2.26-6.70]). Longer delays were associated with increasing drug copayments (0.96 [0.93-0.98]). CONCLUSIONS Patients incurring sustained hyperglycemia are at risk of further delays in appropriate management. Barriers to appropriate care include prescription drug copayments, few physician contacts, and other factors that are likely amenable to intervention.

Barriers to the initiation of, and persistence with, insulin therapy.

OBJECTIVES: Many patients with Type 2 diabetes mellitus (DM) delay and/or discontinue the use of insulin. This study determined patient-perceived barriers to the initiation of, and persistence with, insulin therapy. RESEARCH DESIGN AND METHODS: Patients > or = 18 years with Type 2 DM and > or = 1 elevated HbA(1c) test result (> or = 9%) were identified from computerized laboratory test results within a single healthcare system, a study limitation. Insulin use patterns were characterized by automated pharmacy claims data, and patients were classified into those who discontinued insulin use (discontinuers) or those who did not initiate insulin use (non-initiators). Telephone interviews were conducted to determine the barriers to initiation of, and persistence with, insulin therapy. RESULTS: Response rates were 80.0% (73/91) for discontinuers and 82.0% (129/157) for non-initiators. Pharmacy claims data indicated that discontinuers stopped filling prescriptions for insulin; 46.6% of patients self-reported discontinuing insulin. The average time between first and last prescription for insulin among discontinuers was 4.9 years (SD = 4.4). The most common reasons for discontinuation were related to insulin injection (74.0%) and a doctor's advice not to use insulin (47.1%). In the non-initiator group, 86.1% were never advised by a healthcare provider to take insulin. CONCLUSIONS: These findings suggest that issues related to insulin injection are the primary reason patients with Type 2 DM discontinue insulin therapy. Understanding these patterns is important to develop interventions to overcome barriers to treatment and improve the medical outcomes of patients with Type 2 DM.

Incidence of non-Hodgkin's lymphoma among individuals with chronic hepatitis B virus infection.

UNLABELLED: Although hepatitis C virus (HCV) infection has been shown to be associated with development of non-Hodgkin's lymphoma (NHL), few studies have investigated the association between chronic HBV infection and NHL. The purpose of this study was to compare the incidence of NHL between patients with and without chronic hepatitis B virus (HBV) infection. Using automated laboratory result and clinical data from two United States health systems, we identified individuals with chronic HBV infection from January 1, 1995 through December 31, 2001. Using each health system's population-based tumor registry, we identified all cases of NHL diagnosed through December 31, 2002. We excluded any individual with a history of NHL or human immunodeficiency virus (HIV). We fit Cox proportional hazards models to calculate hazard ratios comparing the incidence of NHL between chronic HBV-infected patients (N = 3,888) and patients without HBV (N = 205,203) drawn from the source populations. We identified 8 NHL cases in the chronic HBV infection cohort and 111 cases in the comparison cohort. Patients with chronic HBV infection were 2.8 times more likely to develop NHL than matched comparison patients (adjusted hazard ratio = 2.80, 95% confidence interval = 1.16-6.75), after controlling for age, race, sex, income, Charlson comorbidity index, study site, and HCV infection. CONCLUSION: chronic HBV-infected patients were nearly 3 times more likely to develop NHL than comparison patients.

Recurrences and second primary breast cancers in older women with initial early-stage disease.

BACKGROUND: The association between common breast cancer therapies and recurrences and second primary breast cancers in older women is unclear, although older women are less likely to receive common therapies. METHODS: Women aged >or=65 years who were diagnosed with stage I or II breast cancer and who underwent mastectomy or breast-conserving surgery (BCS) from 1990 to 1994 were identified from automated data from 6 healthcare systems and then were followed for 10 years or until breast cancer recurrence, disenrollment, or death. Trained abstractors reviewed medical records to obtain recurrence, tumor, treatment and demographic data. The authors used proportional hazards models to examine predictors of recurrent and second primary breast cancers adjusted for demographic and tumor factors. RESULTS: Of 1837 eligible women, 34% were ages 65 to 69 years, 46% were ages 70 to 79 years, and 20% were aged >or=80 years. In multivariable models that used mastectomy as the reference group, BCS without radiation therapy was associated with an increased risk of any recurrent and second primary breast cancer (hazard ratio [HR], 1.6; 95% confidence interval [CI], 1.1-2.3), particularly with the subgroup of women with local and regional recurrence (HR, 3.5; 95% CI, 2.0-6.0). Tamoxifen use for <1 year versus >or=5 years exhibited a borderline association with any recurrent or second primary breast cancer (HR, 1.9; 95% CI, 0.9-4.2). CONCLUSIONS: Radiation therapy after BCS and 5 years of tamoxifen use were beneficial in reducing recurrences and second primary breast cancers in older women, regardless of their age or comorbidity burden.

Patterns and predictors of mammography utilization among breast cancer survivors.

BACKGROUND: Improvements in cancer detection and treatment have resulted in increasing numbers of breast cancer survivors. Information regarding the use of mammography by breast cancer survivors is limited. METHODS: The use of surveillance mammography was examined over a 5-year period in a retrospective cohort of women age>or=55 years who were diagnosed with incident primary breast cancer (1996-1997) while enrolled in 1 of 4 geographically diverse integrated health systems. RESULTS: Of the 797 women included in the study, 80% (n=636) underwent mammograms during the first year after treatment for breast cancer. The percentage of women having mammograms during each yearly period decreased significantly over time. In multivariable analyses, older women with comorbid illnesses or those with late-stage disease were less likely to undergo mammograms, whereas those who underwent breast-conserving therapy (adjusted odds ratio [OR] of 1.38 [95% confidence interval (95% CI), 1.09-1.75]) were more likely to have mammograms. Women who had outpatient visits with a gynecologist (adjusted OR of 3.49 [95% CI, 2.55-4.79]), or a primary care physician (adjusted OR of 2.21 [95% CI, 1.73-2.82]) during the year were more likely to undergo mammograms in that year. CONCLUSIONS: The use of mammography among breast cancer survivors declines over time. Efforts are needed to increase awareness among healthcare providers and breast cancer survivors of the value of follow-up mammography. The current findings highlight the importance of maintaining ongoing contact with primary care physicians and gynecologists.

The incidence and cost of hospitalization for 5-FU toxicity among Medicare beneficiaries with metastatic colorectal cancer.

OBJECTIVE: To estimate the incidence and associated cost of hospitalizations for toxicities associated with 5-fluorouracil (5-FU) among patients with metastatic colorectal cancer. METHODS: Using the 1994 Medicare 5% sample, we identified all patients with metastatic colorectal cancer who had undergone colorectal surgery. We then stratified them into those who received 5-FU therapy within 90 days of their surgery (5-FU group) and those who did not receive chemotherapy (no-chemotherapy group); patients who received chemotherapeutic agents other than 5-FU were excluded from the sample. Using techniques of survival analysis, we then compared the incidence and associated cost of all hospital admissions with listed International Classification of Disease, Ninth Revision, Clinical Modification (ICD-9-CM) diagnostic codes (primary or secondary) for conditions possibly related to 5-FU toxicity (e.g., volume depletion, stomatitis, nausea, and vomiting). RESULTS: A total of 441 patients met all study entry criteria, including 192 who received 5-FU and 249 who did not receive chemotherapy following surgery. Patients in the 5-FU group were younger than those in the no-chemotherapy group (p < .001). Mean (+/- SD) follow-up time was slightly longer in the 5-FU group (137 +/- 96 days vs. 117 +/- 88 days for no chemotherapy). The incidence of toxicity-related hospitalizations at 10.5 months (principally volume depletion, agranulocytosis, gastroenteritis, and nausea and vomiting) was 31% among patients who received 5-FU and 8% among those who did not receive chemotherapy. The cost of inpatient care at 10.5 months was $2716 higher among 5-FU patients. CONCLUSIONS: Hospitalization for toxicity of Medicare patients with metastatic colorectal cancer receiving 5-FU is frequent and costly.