Risk of diabetes complications among those with diabetes receiving androgen deprivation therapy for localized prostate cancer.

PURPOSE: Androgen deprivation therapy (ADT), used increasingly in the treatment of localized prostate cancer, is associated with substantial long-term adverse consequences, including incident diabetes. While previous studies have suggested that ADT negatively influences glycemic control in existing diabetes, its association with diabetes complications has not been investigated. In this study, we examined the association between ADT use and diabetes complications in prostate cancer patients. METHODS: A retrospective cohort study was conducted among men with newly diagnosed localized prostate cancer between 1995 and 2008, enrolled in three integrated health care systems. Men had radical prostatectomy or radiotherapy (curative intent therapy), existing type II diabetes mellitus (T2DM), and were followed through December 2010 (n = 5,336). Cox proportional hazards models were used to examine associations between ADT use and diabetes complications (any complication), and individual complications (diabetic neuropathy, diabetic retinopathy, diabetic amputation or diabetic cataract) after prostate cancer diagnosis. RESULTS: ADT use was associated with an increased risk of any diabetes complication after prostate cancer diagnosis (adjusted hazard ratio, AHR, 1.12, 95% CI 1.03-1.23) as well as an increased risk of each individual complication compared to non-use. CONCLUSION: ADT use in men with T2DM, who received curative intent therapy for prostate cancer, was associated with an increased risk of diabetes complications. These findings support those of previous studies, which showed that ADT worsened diabetes control. Additional, larger studies are required to confirm these findings and to potentially inform the development of a risk-benefit assessment for men with existing T2DM, before initiating ADT.

Serum cholesterol trajectories in the 10 years prior to lymphoma diagnosis.

PURPOSE: Many studies suggest a role for cholesterol in cancer development. Serum cholesterol levels have been observed to be low in newly diagnosed lymphoma cases. The objective of these analyses was to examine the time-varying relationship of cholesterol with lymphomagenesis in the 10 years prior to diagnosis by lymphoma subtype. METHODS: Participants were selected from the combined membership of six National Cancer Institute-funded Cancer Research Network health plans from 1998 to 2008, excluding members with human immunodeficiency virus, cancer (except lymphoma), or organ transplants. Incident lymphoma cases within this population were ascertained and matched with up to five controls. Total serum cholesterol, high-density lipoprotein, and low-density lipoprotein were collected from plan databases. Multilevel, multivariable longitudinal models were fit after choosing the best polynomial order by deviance statistics for selected lymphoma histotypes to examine pre-diagnosis cholesterol trajectories: Hodgkin lymphoma (n = 519) and all non-Hodgkin lymphomas combined (n = 12,635) as well as six subtypes of the latter. RESULTS: For all categories, lymphoma cases had statistically significantly lower estimated total serum cholesterol, high-density lipoprotein, and low-density lipoprotein levels than controls in the years prior to diagnosis/index date. Between-group differences were most pronounced 3-4 years prior to diagnosis, when cases' cholesterol levels declined steeply. CONCLUSIONS: This analysis is the first to examine changes in serum cholesterol for a decade prior to lymphoma diagnosis. A drop in cholesterol levels was evident several years before diagnosis. Our results suggest that cholesterol-related pathways have an important relationship with lymphomagenesis and low cholesterol could be a preclinical lymphoma marker.

Mortality and Androgen Deprivation Therapy as Salvage Treatment for Biochemical Recurrence after Primary Therapy for Clinically Localized Prostate Cancer.

PURPOSE: Androgen deprivation therapy is often used as salvage treatment in men with rising prostate specific antigen after initial radical prostatectomy or radiotherapy for clinically localized prostate cancer. Given the lack of evidence from general practice, we examined the association of salvage androgen deprivation therapy with mortality in an observational cohort study. MATERIALS AND METHODS: From 3 managed care organizations we assembled a retrospective cohort of all 5,804 men with newly diagnosed localized prostate cancer from 1995 to 2009 who had a prostate specific antigen increase (biochemical recurrence) after primary radical prostatectomy or radiotherapy. The main outcomes were all-cause and prostate cancer specific mortality. We used Cox proportional hazards models to estimate mortality with salvage androgen deprivation therapy as a time dependent predictor. RESULTS: Overall salvage androgen deprivation therapy was not associated with all-cause or prostate cancer specific mortality in the prostatectomy cohort (HR 0.97, 95% CI 0.70-1.35 or HR 1.18, 95% CI 0.68-2.07) or in the radiotherapy cohort (HR 0.84, 95% CI 0.70-1.01 or HR 1.06, 95% CI 0.80-1.40, respectively). Among men with prostate specific antigen doubling time less than 9 months after the prostate specific antigen rise, salvage androgen deprivation therapy was statistically significantly associated with a decreased risk of all-cause and prostate cancer specific mortality in the prostatectomy cohort (HR 0.35, 95% CI 0.20-0.63 and HR 0.43, 95% CI 0.21-0.91) and in the radiotherapy cohort (HR 0.62, 95% CI 0.48-0.80 and HR 0.65, 95% CI 0.47-0.90, respectively). CONCLUSIONS: We found no association of salvage androgen deprivation therapy with all-cause or cause specific mortality in most men with biochemical recurrence after primary radical prostatectomy or radiotherapy for clinically localized prostate cancer. Men with quickly progressed disease may derive a clinical benefit from salvage androgen deprivation therapy.

Treatment patterns and clinical outcomes for patients with de novo versus recurrent HER2-positive metastatic breast cancer.

Improvements in screening and adjuvant therapy for breast cancer are associated with decreased recurrence, which may have the effect of increasing the proportion of patients presenting with first-line de novo versus recurrent metastatic breast cancer (MBC). Here, we describe and compare patients with de novo versus recurrent human epidermal growth factor 2 (HER2)-positive MBC. registHER was a prospective observational cohort study (late 2003-early 2006) of 1,023 patients with HER2-positive MBC. Baseline characteristics, treatment patterns, and clinical outcomes were examined in patients with newly diagnosed de novo (n = 327) compared with recurrent HER2-positive MBC after prior treatment for early-stage disease (n = 674). Patients with de novo HER2-positive MBC were less likely to have lung metastases, more likely to have lymph node, bone, and/or liver metastases and >4 sites of metastases and more likely to receive combined or concurrent chemotherapy and hormonal therapy with or without trastuzumab than those with recurrent HER2-positive MBC. Median follow-up was 29 months. Median progression-free survival was 12.1 versus 9.3 months [hazard ratio = 0.716 (95 % confidence interval (CI) 0.617-0.831)], and overall survival was 41.7 versus 32.8 months [hazard ratio = 0.766 (95 % CI 0.633-0.928)] for patients with de novo versus recurrent HER2-positive MBC, respectively. Patients with recurrent HER2-positive MBC had similar outcomes regardless of whether they received prior adjuvant therapy, excluding hormonal therapy. Despite presenting with more advanced-stage disease and higher tumor burdens, patients with de novo HER2-positive MBC have more favorable clinical outcomes than those with recurrent HER2-positive MBC. These differences may be due to effects of prior drug exposure and could have implications for designing and interpreting clinical trials.

Comprehensive evaluation of the incidence of late effects in 5-year survivors of breast cancer.

Late effects of breast cancer affect the quality of survivorship. Using administrative data, we compared the occurrence of almost all ICD9 codes among older breast cancer survivors to that among a matched comparison cohort to generate new hypotheses. Breast cancer patients 65 years or older diagnosed 1990-1994 in 6 integrated care settings and who survived at least 5 years were matched with a cohort of women without a history of breast cancer on care setting, age, and calendar time. We collected data on the occurrence of incident ICD9 codes beginning 6 years after the breast cancer diagnosis date and continuing to year 15, and comparable data for the matched woman. We calculated hazard ratios (HRs) and 95 % confidence intervals associating breast cancer survivorship with incidence of each ICD9 code. We used semi-Bayes methods to address multiple comparisons. Older breast cancer survivors had about the same occurrence of diseases and conditions 6-15 years after breast cancer diagnosis as comparable women. The median of 564 adjusted HRs equaled 1.06, with interquartile range 0.92-1.3. The distribution of HRs pertaining to cancer-related ICD codes was shifted toward positive associations, and the distribution pertaining to cardiovascular-related ICD codes was shifted toward negative associations. In this hypothesis-scanning study, we observed little difference in the occurrence of non-breast cancer-related diseases and conditions among older, long-term breast cancer survivors, and comparable women without a history of breast cancer.

Incident comorbidities and all-cause mortality among 5-year survivors of Stage I and II breast cancer diagnosed at age 65 or older: a prospective-matched cohort study.

Five-year breast cancer survivors, diagnosed after 65 years of age, may develop more incident comorbidities than similar populations free of cancer. We investigated whether older breast cancer survivors have a similar comorbidity burden 6-15 years after cancer diagnosis to matched women free of breast cancer at start of follow-up and whether incident comorbidities are associated with all-cause mortality. In this prospective cohort study, 1,361 older 5-year early-stage breast cancer survivors diagnosed between 1990 and 1994 and 1,361 age- and health system-matched women were followed for 10 years. Adjudicated medical record review captured prevalent and incident comorbidities during follow-up or until death as collected from the National Death Index. Older 5-year breast cancer survivors did not acquire incident comorbidities more often than matched women free of breast cancer in the subsequent 10 years [hazard ratio (HR) 1.0, 95 % confidence interval (95 % CI) 0.93, 1.1]. Adjusted for cohort membership, women with incident comorbidities had a higher mortality rate than those without incident comorbidities (HR 4.8, 95 % CI 4.1, 5.6). A breast cancer history continued to be a hazard for mortality 6-15 years after diagnosis (HR 1.3, 95 % CI 1.1, 1.4). We found that older breast cancer survivors who developed comorbidities had an increased all-cause mortality rate even after adjusting for age and prevalent comorbidity burden. Additionally, survivors acquire comorbidities at a rate similar to older women free of breast cancer. These results highlight the association between comorbidity burden and long-term mortality risk among older breast cancer survivors and their need for appropriate oncology and primary care follow-up.

Performance of claims-based algorithms for identifying heart failure and cardiomyopathy among patients diagnosed with breast cancer.

BACKGROUND: Cardiotoxicity is a known complication of certain breast cancer therapies, but rates come from clinical trials with design features that limit external validity. The ability to accurately identify cardiotoxicity from administrative data would enhance safety information. OBJECTIVE: To characterize the performance of clinical coding algorithms for identification of cardiac dysfunction in a cancer population. RESEARCH DESIGN: We sampled 400 charts among 6460 women diagnosed with incident breast cancer, tumor size ≥ 2 cm or node positivity, treated within 8 US health care systems between 1999 and 2007. We abstracted medical records for clinical diagnoses of heart failure (HF) and cardiomyopathy (CM) or evidence of reduced left ventricular ejection fraction. We then assessed the performance of 3 different International Classification of Diseases, 9th Edition (ICD-9)-based algorithms. RESULTS: The HF/CM coding algorithm designed a priori to balance performance characteristics provided a sensitivity of 62% (95% confidence interval, 40%-80%), specificity of 99% (range, 97% to 99%), positive predictive value (PPV) of 69% (range, 45% to 85%), and negative predictive value (NPV) of 98% (range, 96% to 99%). When applied only to incident HF/CM (ICD-9 codes and gold standard diagnosis both occurring after breast cancer diagnosis) in patients exposed to anthracycline and/or trastuzumab therapy, the PPV was 42% (range, 14% to 76%). CONCLUSIONS: Claims-based algorithms have moderate sensitivity and high specificity for identifying HF/CM among patients with invasive breast cancer. As the prevalence of HF/CM among the breast cancer population is low, ICD-9 codes have high NPV but only moderate PPV. These findings suggest a significant degree of misclassification due to HF/CM overcoding versus incomplete clinical documentation of HF/CM in the medical record.

First-line treatment patterns and clinical outcomes in patients with HER2-positive and hormone receptor-positive metastatic breast cancer from registHER.

BACKGROUND: Limited data are available describing the natural history of patients with HER2-positive and hormone receptor (HR)-positive metastatic breast cancer (MBC). We examined first-line treatment patterns and clinical outcomes in patients with HER2-positive, HR-positive MBC in a real-world setting. METHODS: registHER is a prospective, observational cohort of 1,023 patients with HER2-positive MBC diagnosed within 6 months of enrollment and followed until death, disenrollment, or June 2009 (median follow-up time: 27 months). Demographics, first-line treatment patterns, and clinical outcomes were examined for 530 HER2-positive, HR-positive patients. Progression-free survival (PFS) and overall survival (OS) times were examined. Multivariate analyses adjusted for baseline demographic and prognostic factors. RESULTS: HER2-positive, HR-positive patients receiving first-line trastuzumab plus hormonal therapy had significantly longer PFS times than patients who received hormonal therapy only (13.8 vs. 4.8 months; adjusted hazard ratio [HR]: 0.37, 95% confidence interval [CI]: 0.22-0.60); a nonsignificant reduction in OS time was observed (adjusted HR: 0.55, 95% CI: 0.27-1.14). Compared with patients who received first-line trastuzumab plus chemotherapy, patients who received first-line trastuzumab plus chemotherapy and hormonal therapy had longer median PFS times (20.4 months vs. 9.5 months; adjusted HR: 0.53, 95% CI: 0.42-0.68); a statistically significant reduction in risk of death was observed (adjusted HR: 0.50, 95% CI: 0.36-0.70). Sequential use of chemotherapy and hormonal therapy was associated with improved OS times when compared with concurrent use (adjusted PFS HR: 0.81, 95% CI: 0.54-1.21; adjusted OS HR: 0.48, 95% CI: 0.26-0.89). CONCLUSIONS: These real-world data in patients with HER2-positive/HR-positive MBC provide evidence that, with or without chemotherapy, dual targeting of HRs and HER2 receptors is associated with significantly prolonged PFS and OS times.

Long-term surveillance mammography and mortality in older women with a history of early stage invasive breast cancer.

Annual surveillance mammograms in older long-term breast cancer survivors are recommended, but this recommendation is based on little evidence and with no guidelines on when to stop. Surveillance mammograms should decrease breast cancer mortality by detecting second breast cancer events at an earlier stage. We examined the association between surveillance mammography beyond 5 years after diagnosis on breast cancer-specific mortality in a cohort of women aged ≥ 65 years diagnosed 1990-1994 with early stage breast cancer. Our cohort included women who survived disease free for ≥ 5 years (N = 1,235) and were followed from year 6 through death, disenrollment, or 15 years after diagnosis. Asymptomatic surveillance mammograms were ascertained through medical record review. We used Cox proportional hazards regression stratified by follow-up year to calculate the association between time-varying surveillance mammography and breast cancer-specific and other-than-breast mortality adjusting for site, stage, primary surgery type, age and time-varying Charlson Comorbidity Index. The majority (85 %) of the 1,235 5-year breast cancer survivors received ≥ 1 surveillance mammogram in years 5-9 (yearly proportions ranged from 48 to 58 %); 82 % of women received ≥ 1 surveillance mammogram in years 10-14. A total of 120 women died of breast cancer and 393 women died from other causes (average follow-up 7.3 years). Multivariable models and lasagna plots suggested a modest reduction in breast cancer-specific mortality with surveillance mammogram receipt in the preceding year (IRR 0.82, 95 % CI 0.56-1.19, p = 0.29); the association with other-cause mortality was 0.95 (95 % CI 0.78-1.17, p = 0.64). Among older breast cancer survivors, surveillance mammography may reduce breast cancer-specific mortality even after 5 years of disease-free survival. Continuing surveillance mammography in older breast cancer survivors likely requires physician-patient discussions similar to those recommended for screening, taking into account comorbid conditions and life-expectancy.

Treatment patterns and clinical outcomes in elderly patients with HER2-positive metastatic breast cancer from the registHER observational study.

Limited data exist regarding treatment patterns and outcomes in elderly patients with HER2-positive metastatic breast cancer (MBC). registHER is an observational study of patients (N = 1,001) with HER2-positive MBC diagnosed within 6 months of enrollment and followed until death, disenrollment, or June 2009 (median follow-up 27 months). Outcomes were analyzed by age at MBC diagnosis: younger (<65 years), older (65-74 years), elderly (≥75 years). For progression-free survival (PFS) and overall survival (OS) analyses of first-line trastuzumab versus nontrastuzumab, older and elderly patients were combined. Cox regression analyses were adjusted for baseline characteristics and treatments. Estrogen receptor/progesterone receptor status was similar across age groups. Underlying cardiovascular disease was most common in elderly patients. In patients receiving trastuzumab-based first-line treatment, elderly patients were less likely to receive chemotherapy. In trastuzumab-treated patients, incidence of left ventricular dysfunction (LVD) and congestive heart failure (CHF) (grades ≥ 3) were highest in elderly patients (LVD: elderly 4.8 %, younger 2.8 %, older 1.5 %; CHF: elderly 3.2 %, younger 1.9 %, older 1.5 %). Unadjusted median PFS (months) was significantly higher in patients treated with first-line trastuzumab than those who were not (<65 years: 11.0 vs. 3.4, respectively; ≥65 years: 11.7 vs. 4.8, respectively). In patients <65 years, unadjusted median OS (months) was significantly higher in trastuzumab-treated patients; in patients ≥65 years, median OS was similar (<65 years: 40.4 vs. 25.9; ≥65 years: 31.2 vs. 28.5). In multivariate analyses, first-line trastuzumab use was associated with significant improvement in PFS across age. For OS, significant improvement was observed for patients <65 years and nonsignificant improvement for patients ≥65 years. Elderly patients with HER2-positive MBC had higher rates of underlying cardiovascular disease than their younger counterparts and received less aggressive treatment, including less first-line trastuzumab. These real-world data suggest improved PFS across all age groups and similar trends for OS.

Cardiovascular outcomes in women with advanced breast cancer exposed to chemotherapy.

PURPOSE: To quantify incidence of cardiovascular outcomes in patients with advanced breast cancer receiving cardiotoxic and non-cardiotoxic chemotherapy. METHODS: This study identified all women at a Midwestern health system with initial diagnosis of American Joint Commission on Cancer Stage III/IV breast cancer (1995-2003) and random sample of 50 women initially diagnosed with Stage I/II who progressed to Stage III/IV. The rate of new cardiovascular outcomes (heart failure, dysrhythmia, and ischemia events) for cardiotoxic (anthracycline or trastuzumab) and non-cardiotoxic agents was calculated. RESULTS: Of 315 patients, 90.5% (n = 285) received systemic cancer therapy; 67.7% (n = 193) received cardiotoxic drugs. Older patients were less likely to receive cardiotoxic agents (86.4%, ≤59 years vs. 31.9%, 70+ years). Adjusting for age, race, stage, surgery/radiation, estrogen receptor/progesterone receptor status, and diagnosis year, rate of new cardiac events was higher in patients exposed to cardiotoxic drugs compared with those exposed to non-cardiotoxic drugs (adjusted hazard ratio = 2.5, 95%CI = 0.9-7.2). Patients with cardiac event history (relative risk = 3.2, 95%CI = 2.0-5.1) and those with heart failure history (relative risk = 5.9, 95%CI = 2.4-14.6) were more likely to receive non-cardiotoxic treatment. Heart failure events occurred steadily over time; after 3 years of follow-up, 16% exposed to cardiotoxic drugs experienced an event, and 8% of those exposed to non-cardiotoxic drugs experienced an event. CONCLUSIONS: Patients with cardiac comorbidity are less likely to receive cardiotoxic agents. Use of cardiotoxic agents is common; treatment is related to patient and tumor characteristics and is associated with substantial risk of cardiotoxicity that persists during patients' remaining lifespan.

Risks of congenital malformations and perinatal events among infants exposed to calcium channel and beta-blockers during pregnancy.

PURPOSE: Calcium channel blockers and beta-blockers (BBs) are widely used during pregnancy, but data on their safety for the developing infant are scarce. We used population-based data from 5 HMOs to study risks for perinatal complications and congenital defects among infants exposed in-utero. METHODS: We studied women older than 15 years delivering an infant between 1/1/96 and 12/31/00, who had been continuously enrolled with prescription drug coverage for ≥ 1 year prior to delivery. Information on prescription drug dispensings, inpatient, and outpatient diagnoses and procedures was obtained from automated databases at each HMO. RESULTS: There were 584 full-term infants exposed during pregnancy to BBs and 804 full-term infants exposed to calcium-channel blockers, and over 75,000 unexposed mother-infant pairs with ≥ 30 days follow-up. Infants exposed to BBs in the third trimester of pregnancy had over threefold increased risk for hypoglycemia (RR 3.1; 95% CI 2.2, 4.2) and an approximately twofold increased risk for feeding problems (RR 1.8; 95% CI 1.3, 2.5). Infants exposed to calcium-channel blockers in the third trimester had an increased risk for seizures (RR 3.6 95% CI 1.3, 10.4). Chart review confirmed the majority of the exposed seizure and hypoglycemia cases. There were no increased risks for congenital anomalies among either group of infants, except for the category of upper alimentary tract anomalies; this increased risk was based on only two exposed cases. CONCLUSIONS: Infants whose mothers receive BBs are at increased risk for neonatal hypoglycemia, while those whose mothers take calcium-channel blockers are at increased risk for neonatal seizures.

Incident cardiovascular disease in patients diagnosed with multiple sclerosis: A multi-database study.

BACKGROUND: Recent data on rates of cardiovascular disease (CVD) in patients after MS diagnosis are sparse. OBJECTIVE: To describe incident CVD in MS patients after diagnosis compared with a matched non-MS population. METHODS: We conducted a matched cohort study in two separate electronic medical databases, the United States Department of Defense military health care system and the United Kingdom's Clinical Practice Research Datalink GOLD. The study population included all patients with a first recorded diagnosis of MS and no history of CVD or selected measurable comorbidities associated with CVD and matched non-MS patients who were also free of CVD and the CVD associated comorbidities. We identified incident CVD outcomes first recorded after the MS diagnosis / matched date and calculated incidence rates and incidence rate ratios by type of CVD. RESULTS: Rates of venous thromboembolism and peripheral vascular disease were 2-fold higher among MS than non-MS patients in both databases and the risk of myocardial infarction was 2.5 times higher among female MS patients compared with non-MS females in both databases. Other CVD outcomes were not consistent between databases. CONCLUSION: MS patients in the UK and the US have increased risk of venous thromboembolism and peripheral vascular disease. The risk of myocardial infarction is increased among female MS patients.

Clinical outcomes associated with bevacizumab-containing treatment of metastatic colorectal cancer: the BRiTE observational cohort study.

BACKGROUND: The Bevacizumab Regimens' Investigation of Treatment Effects (BRiTE) study is a prospective, observational cohort study designed to elucidate safety and effectiveness outcomes associated with bevacizumab combined with chemotherapy as used in clinical practice for first-line treatment of metastatic colorectal cancer (mCRC). PATIENTS AND METHODS: Baseline characteristics, prespecified bevacizumab-related adverse events, and effectiveness data were collected from 1,953 mCRC patients who were receiving first-line treatment including bevacizumab at 248 U.S. sites. RESULTS: At database lock, the median follow-up was 20.1 months. At baseline, 46% of patients were aged >or=65 years and 49% had an Eastern Cooperative Oncology Group performance status score >or=1. Fluorouracil, leucovorin, and oxaliplatin was the most common first-line chemotherapy regimen (56%). Overall rates of bevacizumab-related adverse events in the BRiTE study, such as gastrointestinal perforation (1.9%), arterial thromboembolic events (2%), grade 3-4 bleeding (2.2%), and de novo hypertension requiring medication (22%), were consistent with those reported in randomized clinical trials (RCTs) of bevacizumab in first-line mCRC treatment. The median progression-free survival (PFS) and overall survival (OS) times were 9.9 (95% confidence interval [CI], 9.5-10.3) months and 22.9 (95% CI, 21.9-24.4) months, respectively. CONCLUSION: The median PFS and OS durations and safety profile of bevacizumab in the BRiTE study were similar to those in RCTs of bevacizumab plus chemotherapy in first-line mCRC patients. The observations from the BRiTE study complement and expand upon RCT data, providing clinical information in a large cohort of bevacizumab-treated patients and subgroups such as the elderly.

The incidence of diabetes in atypical antipsychotic users differs according to agent--results from a multisite epidemiologic study.

PURPOSE: The purpose of this study was to examine the association between atypical antipsychotics, including the newer agents, aripiprazole and ziprasidone, and newly treated diabetes, using the largest post-marketing cohort of patients exposed to these newer treatments that has been studied to date. METHODS: Identified two overlapping cohorts-a simple cohort (all antipsychotic users) and an inception cohort (new users of antipsychotics)-using automated data from three United States sites (60.4 million covered lives). Patients exposed to antipsychotics > or = 45 days were identified and followed for incident diagnoses of treated diabetes. Data analysis accounted for drug switching and non-consistent drug use. RESULTS: In the 55 287-member inception cohort, 357 cases of newly treated diabetes were identified. Compared with current use of typical antipsychotics, current users of aripiprazole (adjusted hazard ratio (aHR) 0.93, 95% confidence interval (CI) 0.50-1.76), quetiapine (aHR 1.04, 95%CI, 0.67-1.62), risperidone (aHR 0.85, 95%CI, 0.54-1.36) and ziprasidone (aHR 1.05, 95%CI, 0.54-2.08) had similar low risk of diabetes. Patients exposed to olanzapine had an increased risk of diabetes (aHR 1.71, 95%CI, 1.12-2.61), and although the effect estimate is imprecise, clozapine-exposed patients had a trend towards an elevated hazard ratio (aHR 2.58, 95%CI, 0.76-8.80). Results for the simple cohort were similar. CONCLUSIONS: Relative to typical antipsychotics, aripiprazole, ziprasidone, risperidone and quetiapine were not associated with an increased risk of diabetes; olanzapine and clozapine were associated with an increased risk. This analysis constitutes the largest post-marketing pharmacoepidemiologic study to date that includes the newer agents.

Multi-database study of multiple sclerosis: identification, validation and description of MS patients in two countries.

OBJECTIVE: To describe the resources and methods used to identify and validate multiple sclerosis (MS) and match non-MS patients in each of the two databases, and to characterize their demographics, comorbidities and concomitant medications. METHODS: This study was conducted in two separate electronic medical databases, the United States Department of Defense (DOD) military health care system and the United Kingdom's Clinical Practice Research Datalink (CPRD) GOLD. We identified patients with a first recorded diagnosis of MS in 2001-2016 (CPRD) or 2004-2017 (DOD) and matched non-MS patients using algorithms appropriate to each database. We describe patient symptoms, comorbidities, and medication use at the time of the MS diagnosis and compared them to the non-MS cohort. RESULTS: We identified 8695 patients with MS and 86,934 matched non-MS patients in the DOD database and 6932 patients with MS and 68,526 matched non-MS patients in CPRD GOLD. Most MS patients were female (around 70%) and were diagnosed before age 60 (88%). MS patients had higher prevalence of depression and other psychiatric conditions at MS diagnosis compared to non-MS patients. Epilepsy, fractures and infections were also more common. MS patients had many expected symptoms and treatments documented in their records prior to the MS diagnosis. CONCLUSION: These results are consistent between the two databases, as well as with previous studies of MS. Future analyses of these patients' experience after MS diagnosis will provide valuable insights into disease and treatment patterns in relation to risk of chronic diseases and mortality.

Administrative data used to identify patients with irritable bowel syndrome.

OBJECTIVE: To assess the usefulness of health plan administrative data for identifying patients with irritable bowel syndrome (IBS). STUDY DESIGN AND SETTING: In this retrospective study of 442 medical records of patients in nine U.S. health plans, five sets of criteria that used administrative data were used to identify potential IBS patients. Physician reviewers provided an assessment of the likelihood of the diagnosis of IBS being present. IBS was considered to be present if the physician reviewer categorized the case as definite, probable, or possible based on medical record review. Analyses were also performed with cases categorized as possible placed in an "IBS not present" category. RESULTS: The positive predictive value (PPV) for the five sets of criteria ranged from 63% to 83% with the highest PPV found with one of the most restrictive criteria. When cases characterized as possible were included in the "IBS not present" category, the PPV for each of the five sets of criteria decreased substantially, ranging from 33% to 63%. CONCLUSION: The PPV of different criteria used to identify patients with IBS from administrative data varies substantially based on the criteria that are used. Use of criteria with a higher PPV may come at the expense of generalizability.

Under utilization of surveillance mammography among older breast cancer survivors.

BACKGROUND: Annual surveillance mammography is recommended for follow-up of women with a history of breast cancer. We examined surveillance mammography among breast cancer survivors who were enrolled in integrated healthcare systems. METHODS: Women in this study were 65 or older when diagnosed with early stage invasive breast cancer (N = 1,762). We assessed mammography use during 4 years of follow-up, using generalized estimating equations to account for repeated measurements. RESULTS: Eighty-two percent had mammograms during the first year after treatment; the percentage declined to 68.5% in the fourth year of follow-up. Controlling for age and comorbidity, women who were at higher risk of recurrence by being diagnosed at stage II or receiving breast-conserving surgery (BCS) without radiation therapy were less likely to have yearly mammograms (compared to stage I, odds ratio [OR] for stage IIA 0.72, confidence interval [CI] 0.59, 0.87, OR for stage IIB 0.75, CI 0.57, 1.0; compared to BCS with radiation, OR 0.58, CI 0.43, 0.77). Women with visits to a breast cancer surgeon or oncologist were more likely to receive mammograms (OR for breast cancer surgeon 6.0, CI 4.9, 7.4, OR for oncologist 7.4, CI 6.1, 9.0). CONCLUSIONS: Breast cancer survivors who are at greater risk of recurrence are less likely to receive surveillance mammograms. Women without a visit to an oncologist or breast cancer surgeon during a year have particularly low rates of mammography. Improvements to surveillance care for breast cancer survivors may require active participation by primary care physicians and improvements in cancer survivorship programs by healthcare systems.

Use of anti-inflammatory drugs and lower esophageal sphincter-relaxing drugs and risk of esophageal and gastric cancers.

BACKGROUND & AIMS: The incidence of esophageal and gastric cardia adenocarcinoma has increased in Western countries in recent decades for largely unknown reasons. We investigated whether use of LES-relaxing drugs was related to an increased risk of esophageal and gastric cardia adenocarcinoma, and whether use of NSAIDs was related to a reduced risk of esophageal and gastric cancers. METHODS: We examined these associations by using administrative databases in a case-control study in 2 integrated health care delivery systems. Cases were incident esophageal adenocarcinomas (n = 163) and squamous cell carcinomas (n = 114) and gastric cardia (n = 176) and non-cardia adenocarcinomas (n = 320), diagnosed between 1980-2002 in one health system and between 1993-2002 in the other. Matched controls (n = 3996) were selected. Complete prescription information was available for the study period. RESULTS: Prescription of corticosteroids was associated with a decreased risk of esophageal adenocarcinoma (odds ratio [OR], 0.6; 95% confidence interval [CI], 0.4-0.9), esophageal squamous cell carcinoma (OR, 0.4; 95% CI, 0.2-0.6), and gastric non-cardia carcinoma (OR, 0.4, 95% CI, 0.3-0.6). Ever use of pharmacy-purchased aspirin was associated with 30%-60% decreased risks of the studied cancers. As a group, LES-relaxing drugs showed little evidence of association with increased risk of any esophageal or gastric cancer. CONCLUSIONS: Corticosteroid and aspirin use were associated with significantly decreased risks of esophageal and gastric cancer. LES-relaxing drugs as a group did not affect these risks, although we had limited power to assess individual drugs. The possibility that corticosteroids and aspirin might reduce esophageal cancer risk warrants further consideration.

What do medical records tell us about potentially harmful co-prescribing?

BACKGROUND: Previous efforts document drug-drug interactions in ambulatory care. Yet little is known about medical record documentation or clinical management when interacting medications are received. METHODS: The study population was identified from the HMO Research Network's Centers for Education and Research on Therapeutics (n = 2,020,037). A random subsample of patients > or = 18 years of age with drug coverage in 2000 initiating a co-dispensing for (1) warfarin with a nonsteroidal anti-inflammatory drug (n = 97), (2) digoxin with verapamil or diltiazem (n = 100), or (3) lovastatin/simvastatin with diltiazem or verapamil (n = 89) was identified. RESULTS: The majority (63%-74%) of patients had documentation indicating receipt of both drugs during a single office visit. Documentation of risks and patient education was less common (< or = 14%, with all corresponding upper bounds of the 95% CIs < 23%). Clinical management changes were more frequently documented, ranging from 64% (95% CI: 47-81%) for lovastatin/simvastatin patients to 79% (95% CI: 60-99%) for warfarin patients. CONCLUSIONS: The findings, although indicating that clinicians are likely aware of concomitant receipt of interacting medications, call into question the adequacy of medical record documentation as well as clinical management when interacting drugs are co-prescribed in the ambulatory setting.