Blinatumomab vs historical standard therapy of adult relapsed/refractory acute lymphoblastic leukemia.

We compared outcomes from a single-arm study of blinatumomab in adult patients with B-precursor Ph-negative relapsed/refractory acute lymphoblastic leukemia (R/R ALL) with a historical data set from Europe and the United States. Estimates of complete remission (CR) and overall survival (OS) were weighted by the frequency distribution of prognostic factors in the blinatumomab trial. Outcomes were also compared between the trial and historical data using propensity score methods.

International reference analysis of outcomes in adults with B-precursor Ph-negative relapsed/refractory acute lymphoblastic leukemia.

Adults with relapsed/refractory acute lymphoblastic leukemia have an unfavourable prognosis, which is influenced by disease and patient characteristics. To further evaluate these characteristics, a retrospective analysis of 1,706 adult patients with Ph-negative relapsed/refractory B-precursor acute lymphoblastic leukemia diagnosed between 1990-2013 was conducted using data reflecting the standard of care from 11 study groups and large centers in Europe and the United States. Outcomes included complete remission, overall survival, and realization of stem cell transplantation after salvage treatment.

A large observational study of patients with primary immune thrombocytopenia receiving romiplostim in European clinical practice.

Objective: Romiplostim has maintained long-term platelet counts in patients with immune thrombocytopenia (ITP) for up to 5 yr in clinical studies. This prospective observational study aimed to describe romiplostim utilisation and outcomes in European clinical practice.

Methods: Adults with primary ITP who received romiplostim in routine care were eligible.

Design and methods for a Scandinavian pharmacovigilance study of osteonecrosis of the jaw and serious infections among cancer patients treated with antiresorptive agents for the prevention of skeletal-related events.

Objective: Osteonecrosis of the jaw (ONJ) is a recognized complication of potent antiresorptive therapies, especially at the doses indicated to prevent skeletal complications for cancer patients with bone metastases. This paper describes the rationale and methods for a prospective, post-authorization safety study of cancer patients treated with antiresorptive therapies.

Methods: As part of a comprehensive pharmacovigilance plan, developed with regulators' input, the study will estimate incidence of ONJ and of serious infections among adult cancer patients with bone metastases treated with denosumab (120 mg subcutaneously) or zoledronic acid (4 mg intravenously, adjusted for renal function).

Algorithms to Identify Statin Intolerance in Medicare Administrative Claim Data.

Purpose: To compare characteristics of patients with possible statin intolerance identified using different claims-based algorithms versus patients with high adherence to statins.

Methods: We analyzed 134,863 Medicare beneficiaries initiating statins between 2007 and 2011. Statin intolerance and discontinuation, and high adherence to statins, defined by proportion of days covered ≥80 %, were assessed during the 365 days following statin initiation.

Rate of bleeding-related episodes in adult patients with primary immune thrombocytopenia: a retrospective cohort study using a large administrative medical claims database in the US.

Background: Immune thrombocytopenia (ITP) is a rare disorder characterized by low platelet counts and an increased tendency to bleed. The goal of ITP therapy is to treat or prevent bleeding. Actual rates of bleeding are unknown.

Prognostic impact of tumor MET expression among patients with stage IV gastric cancer: a Danish cohort study.

Purpose: We aimed to investigate the prevalence and prognostic impact of tumor mesenchymal epithelial transition factor (MET) expression in stage IV gastric cancers in a real-world clinical setting because existing evidence is sparse.

Methods: The study included archived cancer specimens from 103 stage IV gastric cancer patients (2003-2010). We analyzed MET-protein expression by immunohistochemistry (MET-positive if ≥25% of tumor cells showed MET expression).

Relationship between severity and duration of chemotherapy-induced neutropenia and risk of infection among patients with nonmyeloid malignancies.

Purpose: Chemotherapy-induced neutropenia (CIN) may increase infection risk for cancer patients; however, there is limited understanding on the quantitative relationships between severity and duration of CIN and infection risk.

Methods: This study combined individual data from adult cancer patients receiving no granulocyte colony-stimulating factor during the first chemotherapy cycle in six trials. We used area over the curve (AOC) of absolute neutrophil count (ANC) time-response curve (below different thresholds) to measure the combined effect of severity and duration of CIN.

Geovariation in Fracture Risk among Patients Receiving Hemodialysis.

Background And Objectives: Fractures are a major source of morbidity and mortality in patients receiving dialysis. We sought to determine whether rates of fractures and tendon ruptures vary geographically.

Design, Setting, Participants, & Measurements: Data from the US Renal Data System were used to create four yearly cohorts, 2007-2010, including all eligible prevalent patients on hemodialysis in the United States on January 1 of each year.

Comparison of Length of Stay, 30-Day Mortality, and 30-Day Readmission Rates in Medicare Patients With Heart Failure and With Reduced Versus Preserved Ejection Fraction.

Length of stay (LOS), 30-day mortality, and 30-day readmission rates have not been compared between Medicare beneficiaries with heart failure (HF) with reduced ejection fraction (HFrEF) and beneficiaries with heart failure with preserved ejection fraction (HFpEF), although HFpEF is common in patients with HF. To determine whether type of HF (HFrEF or HFpEF) was associated with LOS, 30-day mortality, and 30-day readmission, we used a cohort of 19,477 Medicare beneficiaries admitted to the hospital and discharged alive with a primary discharge diagnosis of HF between 2007 and 2011. Gamma regression, Poisson regression, and Cox proportional hazards with a competing risk for death were used to model LOS, 30-day mortality, and 30-day readmission rate, respectively.

Mapping adipose and muscle tissue expression quantitative trait loci in African Americans to identify genes for type 2 diabetes and obesity.

Relative to European Americans, type 2 diabetes (T2D) is more prevalent in African Americans (AAs). Genetic variation may modulate transcript abundance in insulin-responsive tissues and contribute to risk; yet, published studies identifying expression quantitative trait loci (eQTLs) in African ancestry populations are restricted to blood cells. This study aims to develop a map of genetically regulated transcripts expressed in tissues important for glucose homeostasis in AAs, critical for identifying the genetic etiology of T2D and related traits.

Incidence of anemia in patients diagnosed with solid tumors receiving chemotherapy, 2010-2013.

Purpose: The purpose of this study was to evaluate and characterize the risk of anemia during the course of chemotherapy among patients with five common types of solid tumors.

Patients And Methods: Patients diagnosed with incident cancers of breast, lung, colon/rectum, stomach, and ovary who received chemotherapy were identified from Kaiser Permanente Southern California Health Plan (2010-2012). All clinical data were collected from the health plan's electronic medical records.

The effect of chemotherapy-induced anemia on dose reduction and dose delay.

Purpose: To evaluate moderate (grade 2, hemoglobin <10 g/dl) and severe (grade 3+, hemoglobin <8 g/dl) anemia as potential risk factors for DDR in the first line course of chemotherapy. While chemotherapy-induced neutropenia has been shown to be associated with dose delay/reduction (DDR) in several studies, the effect of anemia is less well studied.

Methods: We identified 3955 Kaiser Permanente patients diagnosed with incident non-Hodgkin's lymphoma (n = 574), breast (n = 2043), lung (n = 463), gastric (n = 113), ovarian (n = 204), or colorectal cancers (n = 558) between 2010 and 2012.

Development and validation of cardiovascular risk scores for haemodialysis patients.

Background: A simple clinical tool to predict cardiovascular disease risk does not exist for haemodialysis patients. The long-term coronary risk Framingham Heart Study Risk score (FRS), although used in this population, may be inadequate. Therefore, we developed separate risk-scores for cardiovascular mortality (CVM) and cardiovascular morbidity & mortality (CVMM) in a Fresenius Medical Care-based haemodialysis patient cohort (AROii).

The incidence of bone metastasis after early-stage breast cancer in Canada.

Current information on the incidence and prevalence of bone metastases in women with breast cancer is scarce. This study examined the occurrence and predictors of bone metastases, as well as post-metastasis survival in a prospective cohort of Canadian women with breast cancer. We included women treated for early-stage (stage I, II, or III) breast cancer at the Henrietta Banting Breast Centre (HBBC) in Toronto, Canada between 1987 and 2000.

Effects of Epoetin Alfa Titration Practices, Implemented After Changes to Product Labeling, on Hemoglobin Levels, Transfusion Use, and Hospitalization Rates.

Background: Little is known about epoetin alfa (EPO) dosing at dialysis centers after implementation of the US Medicare prospective payment system and revision of the EPO label in 2011.

Study Design: Retrospective cohort study.

Setting & Participants: Approximately 412,000 adult hemodialysis patients with Medicare Parts A and B as primary payer in 2009 to 2012 to describe EPO dosing and hemoglobin patterns; of these, about 70,000 patients clustered in about 1,300 dialysis facilities to evaluate facility-level EPO titration practices and patient-level outcomes in 2012.

Epoetin Alfa and Outcomes in Dialysis amid Regulatory and Payment Reform.

Erythropoiesis-stimulating agents (ESAs) are commonly used to treat anemia in patients with CKD, including those receiving dialysis, although clinical trials have identified risks associated with ESA use. We evaluated the effects of changes in dialysis payment policies and product labeling instituted in 2011 on mortality and major cardiovascular events across the United States dialysis population in an open cohort study of patients on dialysis from January 1, 2005, through December 31, 2012, with Medicare as primary payer. We compared observed rates of death and major cardiovascular events in 2011 and 2012 with expected rates calculated on the basis of rates in 2005-2010, accounting for differences in patient characteristics and influenza virulence.

Trajectory of absolute neutrophil counts in patients treated with pegfilgrastim on the day of chemotherapy versus the day after chemotherapy.

Purpose: Risk of infection increases with severity and duration of chemotherapy-induced neutropenia (CIN). Pegfilgrastim is approved for use on the day after chemotherapy to reduce incidence of infection, as manifested by febrile neutropenia (FN), in patients receiving myelosuppressive chemotherapy. In this study, we compared severity and duration of absolute neutrophil count (ANC) suppression in patients who received pegfilgrastim on the same day as chemotherapy versus the next day.

Trends in anemia treatment among patients with five non-myeloid malignancies treated with chemotherapy in a large integrated health care delivery system in California, 2000-2013.

Purpose: The aim of this study is to examine treatment patterns for chemotherapy-induced anemia (CIA) between calendar periods when the changes in the US prescribing information, for erythropoiesis-stimulating agents (ESAs) took place.

Methods: Patients diagnosed with breast, lung, colorectal, ovarian, or gastric cancer (2000-2012) who developed grade 2+ CIA (hemoglobin (Hb) <10 g/dl) were identified from Kaiser Permanente Southern California Health Plan. We estimated the proportions of CIA episodes with ESA use, red blood cell (RBC) transfusion, or prescription nutritional supplements in three calendar periods: January 1, 2000-December 31, 2006 (P1), January 1, 2007-March 24, 2010 (P2), and March 25, 2010-June 30, 2013 (P3).

Anti-parathyroid treatment effectiveness and persistence in incident haemodialysis patients with secondary hyperparathyroidism.

Background: Anti-parathyroid treatment initiation and discontinuation are important decisions in chronic haemodialysis (HD) patients, where pill burden is often excessive. The present study aimed to describe secondary hyperparathyroidism (sHPT) drug therapy changes in HD patients.

Methods: Retrospective observational cohort study of incident European HD patients with sHPT who were prescribed calcitriol or alfacalcidol (alpha calcitriol), paricalcitol or cinacalcet.

Validation of International Classification of Diseases coding for bone metastases in electronic health records using technology-enabled abstraction.

Objective: The accuracy of bone metastases diagnostic coding based on International Classification of Diseases, ninth revision (ICD-9) is unknown for most large databases used for epidemiologic research in the US. Electronic health records (EHR) are the preferred source of data, but often clinically relevant data occur only as unstructured free text. We examined the validity of bone metastases ICD-9 coding in structured EHR and administrative claims relative to the complete (structured and unstructured) patient chart obtained through technology-enabled chart abstraction.

Controlling confounding of treatment effects in administrative data in the presence of time-varying baseline confounders.

Purpose: Confounding, a concern in nonexperimental research using administrative claims, is nearly ubiquitous in claims-based pharmacoepidemiology studies. A fixed-length look-back window for assessing comorbidity from claims is common, but it may be advantageous to use all historical claims. We assessed how the strength of association between a baseline-identified condition and subsequent mortality varied by when the condition was measured and investigated methods to control for confounding.

Cross-sectional study on comorbidities and adverse events in patients with advanced and recurrent ovarian cancer in France.

Purpose: The purpose of this study was to evaluate the prevalence of comorbidities and adverse events (AEs), and determine the treatment patterns according to platinum-sensitivity status in patients with advanced (stage IIIB-IV) or recurrent epithelial ovarian cancer (EOC).

Methods: A cross-sectional study was carried out in France with patients over 18 years, diagnosed with advanced (stage IIIB-IV) or recurrent EOC between 2009 and 2012. A total of 23 physicians (oncologists and gynecologists) participated, contributing 127 patients.

Inflammation Modifies the Paradoxical Association between Body Mass Index and Mortality in Hemodialysis Patients.

High body mass index (BMI) is paradoxically associated with better outcome in hemodialysis (HD) patients. Persistent inflammation commonly features in clinical conditions where the obesity paradox is described. We examined the relationship between BMI and mortality in HD patients, accounting for inflammation, in a historic cohort study of 5904 incident HD patients enrolled in 2007-2009 (312 facilities; 15 European countries) with ≥3 months of follow-up.

Assessment of off-label use of denosumab 60 mg injection during the early postmarketing period using health insurance claims data.

Unlabelled: Off-label use of denosumab 60 milligram (mg) injection was assessed within an administrative claims database. The completeness of claims to assess off-label use was investigated with medical record review. Potential denosumab 60 mg off-label use was observed based on claims, but many had evidence of on-label indications based on medical record review.