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Among patients with heart failure and a reduced ejection fraction, those who received the cardiac myosin activator omecamtiv mecarbil had a lower incidence of a composite of heart-failure events or cardiovascular death at a median of 22 months than those who received placebo.

In two randomized trials, evolocumab, a monoclonal antibody that inhibits proprotein convertase subtilisin–kexin type 9 (PCSK9), reduced LDL cholesterol levels by 61%. In an exploratory analysis, the incidence of cardiovascular events was reduced in the evolocumab group. Reduction in low-density lipoprotein (LDL) cholesterol levels has proved to be highly effective in reducing rates of major cardiovascular events in numerous large outcome trials. 1 – 3 For this reason, LDL cholesterol reduction has been incorporated into practice guidelines as a fundamental means of reducing cardiovascular morbidity and mortality. 4 – 7 During the past 3 years, monoclonal antibodies that inhibit proprotein convertase subtilisin–kexin type 9 (PCSK9) have emerged as a new class of drugs that very effectively lower LDL cholesterol levels. 8 One of the members of this class is evolocumab, a fully human monoclonal antibody that typically achieves approximately a 60% reduction . . .

Replication procedures have proven useful for variance estimation for large scale complex surveys. As an extension of bootstrap procedures to rejective samples, we define a bootstrap sample that is a rejective, unequal probability, replacement sample selected from the original sample. A modification of the bootstrap with improved performance is suggested for stratified samples with small stratum sizes. Simulations for Poisson and stratified rejective samples support the use of replicates in estimating the variance of the regression estimator for rejective samples.

Background Healthcare claims databases have been used in several studies to characterize the risk and burden of chemotherapy-induced febrile neutropenia (FN) and effectiveness of colony-stimulating factors against FN. The accuracy of methods previously used to identify FN in such databases has not been formally evaluated. Methods Data comprised linked electronic medical records from Geisinger Health System and healthcare claims data from Geisinger Health Plan. Subjects were classified into subgroups based on whether or not they were hospitalized for FN per the presumptive “gold standard” (ANC <1.0×10 9 /L, and body temperature ≥38.3°C or receipt of antibiotics) and claims-based definition (diagnosis codes for neutropenia, fever, and/or infection). Accuracy was evaluated principally based on positive predictive value (PPV) and sensitivity. Results Among 357 study subjects, 82 (23%) met the gold standard for hospitalized FN. For the claims-based definition including diagnosis codes for neutropenia plus fever in any position (n=28), PPV was 100% and sensitivity was 34% (95% CI: 24–45). For the definition including neutropenia in the primary position (n=54), PPV was 87% (78–95) and sensitivity was 57% (46–68). For the definition including neutropenia in any position (n=71), PPV was 77% (68–87) and sensitivity was 67% (56–77). Conclusions Patients hospitalized for chemotherapy-induced FN can be identified in healthcare claims databases--with an acceptable level of mis-classification--using diagnosis codes for neutropenia, or neutropenia plus fever.

This study evaluated the correlation between the risk of febrile neutropenia (FN) estimated by physicians and the risk of severe neutropenia or FN predicted by a validated multivariate model in patients with nonmyeloid malignancies receiving chemotherapy. Before patient enrollment, physician and site characteristics were recorded, and physicians self‐reported the FN risk at which they would typically consider granulocyte colony‐stimulating factor (G‐CSF) primary prophylaxis (FN risk intervention threshold). For each patient, physicians electronically recorded their estimated FN risk, orders for G‐CSF primary prophylaxis (yes/no), and patient characteristics for model predictions. Correlations between physician‐assessed FN risk and model‐predicted risk (primary endpoints) and between physician‐assessed FN risk and G‐CSF orders were calculated. Overall, 124 community‐based oncologists registered; 944 patients initiating chemotherapy with intermediate FN risk enrolled. Median physician‐assessed FN risk over all chemotherapy cycles was 20.0%, and median model‐predicted risk was 17.9%; the correlation was 0.249 (95% CI, 0.179−0.316). The correlation between physician‐assessed FN risk and subsequent orders for G‐CSF primary prophylaxis (n = 634) was 0.313 (95% CI, 0.135−0.472). Among patients with a physician‐assessed FN risk ≥20%, 14% did not receive G‐CSF orders. G‐CSF was not ordered for 16% of patients at or above their physician's self‐reported FN risk intervention threshold (median, 20.0%) and was ordered for 21% below the threshold. Physician‐assessed FN risk and model‐predicted risk correlated weakly; however, there was moderate correlation between physician‐assessed FN risk and orders for G‐CSF primary prophylaxis. Further research and education on FN risk factors and appropriate G‐CSF use are needed. This prospective study evaluated the correlation between physician‐assessed risk of febrile neutropenia and model‐predicted risk of severe or febrile neutropenia in patients with nonmyeloid malignancies receiving chemotherapy. Physician‐assessed FN risk and model‐predicted risk correlated weakly; however, there was moderate correlation between physician‐assessed FN risk and orders for G‐CSF primary prophylaxis..

Romiplostim increases platelet counts and reduces the risk of bleeding in patients with immune thrombocytopenia (ITP). This post hoc analysis compared the effect of romiplostim versus medical standard of care (SOC) on clinically relevant bleeding-related episodes (BREs) in a 52-week open-label study of patients with ITP. BREs were defined as actual bleeding events and/or use of rescue medication. Nonsplenectomized adult patients with ITP were randomized to receive weekly subcutaneous injections of romiplostim ( n  = 157) or SOC ( n  = 77). The rate of all BREs (per 100 patient-weeks) was lower in patients treated with romiplostim (3.1) than in those treated with SOC (9.4); the relative rate (romiplostim/SOC) was 0.33 (95 % CI 0.27–0.40). The rate of BREs associated with immunoglobulin (Ig) rescue medication was also lower for romiplostim (0.2) than SOC (4.8); the relative rate (romiplostim/SOC) was 0.05 (95 % CI 0.03–0.08). BRE rates were lower in patients with platelet counts ≥50 × 10 9 /L, and patients treated with romiplostim spent more time with platelet counts ≥50 × 10 9 /L than did patients treated with SOC. Bleeding-related hospitalizations were rare in both groups. Thus, romiplostim treatment provided greater reductions in all BREs, as well as BREs involving Ig rescue medications, than did SOC.

Electronic medical records (EMRs) are used increasingly for research in clinical oncology, epidemiology, and comparative effectiveness research (CER). To assess the utility of using EMR data in population-based cancer research by comparing a database of EMRs from community oncology clinics against Surveillance Epidemiology and End Results (SEER) cancer registry data and two claims databases (Medicare and commercial claims). DEMOGRAPHIC, CLINICAL, AND TREATMENT PATTERNS IN THE EMR, SEER, MEDICARE, AND COMMERCIAL CLAIMS DATA WERE COMPARED USING SIX TUMOR SITES: breast, lung/bronchus, head/neck, colorectal, prostate, and non-Hodgkin's lymphoma (NHL). We identified various challenges in data standardization and selection of appropriate statistical procedures. We describe the patient and clinic inclusion criteria, treatment definitions, and consideration of the administrative and clinical purposes of the EMR, registry, and claims data to address these challenges. Sex and 10-year age distributions of patient populations for each tumor site were generally similar across the data sets. We observed several differences in racial composition and treatment patterns, and modest differences in distribution of tumor site. Our experience with an oncology EMR database identified several factors that must be considered when using EMRs for research purposes or generalizing results to the US cancer population. These factors were related primarily to evaluation of treatment patterns, including evaluation of stage, geographic location, race, and specialization of the medical facilities. While many specialty EMRs may not provide the breadth of data on medical care, as found in comprehensive claims databases and EMR systems, they can provide detailed clinical data not found in claims that are extremely important in conducting epidemiologic and outcomes research.

Background : Granulocyte-colony stimulating factor (G-CSF) reduces the risk of severe neutropenia associated with chemotherapy, but its cost implications following chemotherapy are unknown. Objective : Our objective was to examine associations between G-CSF use and medical costs after initial adjuvant chemotherapy in early-stage (stage I–III) breast cancer (ESBC). Methods : Women diagnosed with ESBC from 1999 to 2005, who had an initial course of chemotherapy beginning within 180 days of diagnosis and including ≥1 highly myelosuppressive agent, were identified from the Surveillance, Epidemiology, and End Results (SEER)-Medicare database. Medicare claims were used to describe the initial chemotherapy regimen according to the classes of agents used: anthracycline ([A]: doxorubicin or epirubicin); cyclophosphamide (C); taxane ([T]: paclitaxel or docetaxel); and fluorouracil (F). Patients were classified into four study groups according to their G-CSF use: (i) primary prophylaxis, if the first G-CSF claim was within 5 days of the start of the first chemotherapy cycle; (ii) secondary prophylaxis, if the first claim was within 5 days of the start of the second or subsequent cycles; (iii)G-CSF treatment, if the first claim occurred outside of prophylactic use; and (iv) no G-CSF. Patients were described by age, race, year of diagnosis, stage, grade, estrogen (ER) and progesterone (PR) receptor status, National Cancer Institute (NCI) Co-morbidity Index, chemotherapy regimen and G-CSF use. Total direct medical costs ($US, year 2009 values) to Medicare were estimated from 4 weeks after the last chemotherapy administration up to 48 months. Medical costs included those for ESBC treatment and all other medical services received after chemotherapy. Least squares regression, using inverse probability weighting (IPW) to account for censoring within the cohort, was used to evaluate adjusted associations between G-CSF use and costs. Results: A total of 7026 patients were identified, with an average age of 72 years, of which 63% had stage II disease, and 59% were ER and/or PR positive. Compared with no G-CSF, those receiving G-CSF primary prophylaxis were more likely to have stage III disease (30% vs 16%; p < 0.0001), to be diagnosed in 2003–5 (87% vs 26%; p < 0.0001), and to receive dose-dense AC-T (26% vs 1%; p < 0.0001), while they were less likely to receive an F-based regimen (12% vs 42%; p < 0.0001). Overall, the estimated average direct medical cost over 48months after initial chemotherapy was $US42 628. In multivariate analysis, stage II or III diagnosis (compared with stage I),NCI Co-morbidity Index score 1 or ≥2 (compared with 0), or FAC or standard AC-T (each compared with AC) were associated with significantly higher IPW 48-month costs. Adjusting for patient demographic and clinical factors, costs in the G-CSF primary prophylaxis group were not significantly different from those not receiving primary prophylaxis (the other three study groups combined). In an analysis that included four separate study groups, G-CSF treatment was associated with significantly greater costs (incremental cost = $US2938; 95% CI 285, 5590) than no G-CSF. Conclusions : Direct medical costs after initial chemotherapy were not statistically different between those receiving G-CSF primary prophylaxis and those receiving no G-CSF, after adjusting for potential confounders.

The National Resources Inventory (NRI) is a large-scale longitudinal survey conducted to assess trends and conditions of nonfederal land. A key NRI estimate is year-to-year change in acres of developed land, where developed land includes roads and urban areas. In 2003, a digital data collection procedure was implemented replacing a map overlay. Data from an NRI calibration experiment are used to estimate the relationship between data collected under the old and new protocols. A measurement error model is postulated for the relationship, where duplicate measurements are used to estimate the error variance of the new procedure. If any significant discrepancy is detected between new and old measures, some parameters that govern the algorithm for the new protocol can be changed to alter the relationship. Parameters were initially calibrated so overall averages nearly match for the new and old protocols. Analyses on the data after initial parameter calibration suggest that a line with an intercept of 0 and a slope of 1 is an acceptable representation for the relationship between the two determinations. Estimation of the measurement error variances as functions of the proportion of developed land are also given.

Replication procedures have proven useful for variance estimation for large scale complex surveys. As an extension of bootstrap procedures to rejective samples, we define a bootstrap sample that is a rejective, unequal probability, replacement sample selected from the original sample. A modification of the bootstrap with improved performance is suggested for stratified samples with small stratum sizes. Simulations for Poisson and stratified rejective samples support the use of replicates in estimating the variance of the regression estimator for rejective samples.