Heart Failure Among Patients with Multiple Myeloma Treated with Carfilzomib-Based Versus Non-Carfilzomib-Based Regimens in the United States by Race.

BACKGROUND: Carfilzomib treatment for multiple myeloma (MM) can increase heart failure risk. Whether this risk differs by race is unknown. PATIENTS AND METHODS: We sought to estimate the incidence rates (IRs) of heart failure hospitalization among mostly 65-years-and-older US patients with MM by race treated with carfilzomib- and non-carfilzomib-based regimens in the real-world using Centers for Medicare & Medicaid Services Medicare Fee-for-Service data, Optum Clinformatics Data Mart, and Humana Research Database. The risk of heart failure hospitalization associated with a carfilzomib-based regimen was evaluated using propensity score matching among Black and White patients receiving second or later lines of therapy. RESULTS: Most patient-episodes (88%) were in persons 65 years or older for the 3 cohorts combined. The IR (95% CI) of heart failure hospitalization was higher for patient-episodes treated with a carfilzomib-based regimen than those with a non-carfilzomib-based regimen for both White (14.5 [12.2-17.0] vs. 10.7 [10.3-11.2] events per person-years) and Black patients (15.8 [10.1-23.5] vs. 12.1 [10.9-13.4] events per person-years) in the Medicare cohort. After propensity score matching, the hazard ratio (95% CI) of increased heart failure hospitalization comparing carfilzomib-based to non-carfilzomib-based regimens for White patients (1.6 [1.3-2.0]) was similar to that of Black patients (1.7 [1.0-2.9]) in the Medicare Database, and in the Humana Database (1.4 [0.8-2.6] and 1.2 [0.4-3.5], respectively). CONCLUSION: Although the IR of heart failure among patients with MM treated with a carfilzomib-based regimen was slightly higher, no evidence suggested the relative risk was different between White and Black patients with MM.

Prevalence of hypercalcemia of malignancy among pediatric cancer patients in the UK Clinical Practice Research Datalink database.

BACKGROUND: The reported proportion of cancer patients who experience hypercalcemia of malignancy (HCM) is low, particularly in the pediatric population, ranging between <1% and 5%. HCM can be observed with any type of tumor in children and occurs most commonly with leukemia. While HCM is a potentially fatal condition, the prevalence of HCM is not well understood in pediatric cancer patients. METHODS: Using the UK Clinical Practice Research Datalink, we identified pediatric cancer patients with recorded corrected serum calcium (CSC) from 2003 through 2014. Hypercalcemic patients (CSC ≥10.8 mg/dL) were classified into 4 CSC levels. We estimated the annual prevalence of HCM using Byar's method. RESULTS: Among 517 pediatric cancer patients, leukemia, lymphoma, and brain tumors were the most frequent cancer types. The prevalence of HCM overall (grade 1 or higher) ranged from 0.24% to 0.81% between 2003 and 2014. There were too few cases to compare prevalence by type of cancer. CONCLUSION: We provide the first systematic analysis using a UK population-based data source to estimate the number of pediatric cancer patients affected with HCM by grade. Our findings showed that the prevalence of pediatric HCM was very low (0.24%-0.81%) over the 12-year study period, which is consistent with previous study of adult cancer patients in the UK (0.20%-0.67%).

Prevalence of hypercalcemia among cancer patients in the United States.

Hypercalcemia of malignancy (HCM) is a serious metabolic complication whose population-based prevalence has not been quantified. Rates of HCM differ by tumor type, with highest rates reported in multiple myeloma and lowest among colorectal and prostate cancer patients. This analysis estimates HCM prevalence in the US. This retrospective study used the Oncology Services Comprehensive Electronic Records (OSCER) warehouse of electronic health records (EHR) including laboratory values from 569000 patients treated at 565 oncology outpatient sites. OSCER data were projected to the national level by linking EHR to claims data. Cancer patients included were ≥18 years, and had serum calcium (Ca) and albumin (for corrected serum Ca [CSC]) records. Period prevalence was estimated by HCM CTCAE grade, tumor type, and year (2009-2013). Estimates were adjusted to capture patients diagnosed with HCM outside oncology practices based on a subset of patients linkable to office and hospital data. The analysis included 68023 (2009) to 121482 (2013) cancer patients. In 2013, patients with HCM had a median of six Ca tests, 69.7% had chemotherapy, and 34% received bone modifying agents. HCM rates were highest for multiple myeloma patients (7.5% [2012]-10.2% [2010]), lowest for prostate cancer (1.4% [2012]-2.1% [2011]).The estimated adjusted annual prevalence of HCM from 2009 to 2013 was 95441, 96281, 89797, 70158, and 71744, respectively. HCM affected 2.0-2.8% of all cancer patients. EHR data from oncology clinics were critical for this study because these data contain results from laboratory studies (i.e., serum calcium values) that are routinely ordered in that setting. We estimated that the prevalence of HCM in the US in 2013 is 71744, affecting approximately 2% of cancer patients overall. This percentage differs by tumor type and appears to have decreased over the five-year study period.

Prevalence of hypercalcemia of malignancy among cancer patients in the UK: analysis of the Clinical Practice Research Datalink database.

BACKGROUND: The reported proportion of cancer patients who experience hypercalcemia of malignancy (HCM) ranges between 3% and 30%. HCM can be observed with any type of tumor and occurs most commonly in lung cancer, breast cancer and multiple myeloma. While HCM is a potentially fatal condition, the prevalence of HCM is not well defined. METHODS: Using the United Kingdom Clinical Practice Research Datalink, we identified adult cancer patients with recorded corrected serum calcium (CSC). Hypercalcemic patients (CSC ≥ 10.8 mg/dL) were classified into 4 CSC levels. We estimated annual prevalence of HCM overall, stratified by cancer type, and in patients with stage IV cancer. RESULTS: Among 37,442 cancer patients in 2003-2012 the prevalence of grade 1 HCM increased from 0.13% to 0.45% and the prevalence of HCM overall (grade 1 or higher) increased from 0.20% to 0.67% over the study period. Prevalence estimates varied across cancer type and were highest for lung cancer, multiple myeloma and patients with stage IV cancer. CONCLUSION: We provide the first systematic analysis using a UK population-based data source to estimate number of cancer patients affected with HCM by grade. The increase in HCM prevalence over the 10-year study period is likely due to the increased recording of laboratory values, particularly comparing more recent data to 2003. Our findings suggest that HCM in general is not a common condition.

Renal impairment, hemoglobinuria, and hemoglobinemia among patients with idiopathic thrombocytopenic purpura.

Renal impairment (RI) and events potentially leading to RI were reported in idiopathic thrombocytopenic purpura (ITP) patients with specific medications. This study was conducted to estimate the incidence rate (IR) of RI, hemoglobinuria and hemoglobinemia (HE) and characterize baseline risk factors in ITP and ITP-free patients. Incident ITP and matched non-ITP patients were identified from an electronic medical record database from 1990 to 2002. ITP patients were classified by the treatment first received (initiators) or ever received (users). All cohorts were followed for study outcomes. IRs were calculated and standardized by age and gender. A total of 881 ITP and 4,496 ITP-free patients yielded 3,044 and 16,006 person-years, respectively. The ITP cohort had a slightly higher prevalence of autoimmune diseases and infections than the ITP-free cohort. The IR (/10,000 person-years) for RI, hemoglobinuria and HE was 14.2, 35.7, and 7.1 in the ITP cohort; 10.0, 48.8, and 0 in the ITP-free cohort; and 18.3, 37.1, and 6.1 in untreated ITP patients, respectively. The risk of RI, HE or hemoglobinuria was not found to differ substantially between ITP and non-ITP patients or across ITP treatments.

Power calculations for generalized linear models in observational longitudinal studies: a simulation approach in SAS.

Repeated measurements arising from longitudinal studies occur frequently in applied research. Methods to calculate power in the context of repeated measures are available for experimental settings where the covariate of interest is a discrete treatment indicator. However, no closed form expression exists to calculate power for generalized linear models with non-zero within-cluster correlation that are common in epidemiological and observational studies in which the covariate of interest varies over time and is often measured on a continuous scale, and where the researchers control for several potential confounders. We describe a Monte Carlo simulation approach conducted to calculate power, and illustrate its application in two models frequently encountered in practice, the normal linear mixed model, and the logistic regression model, both with repeated measurements and non-zero within-cluster correlation. This approach can be used to calculate the effect on power of changing various simulation conditions controlled by the researcher, such as sample size, within-cluster correlation structure, smallest meaningful difference to detect, and distributional assumptions.

Association of FEV1 in asthmatic children with personal and microenvironmental exposure to airborne particulate matter.

Exposure to particulate matter (PM) air pollution has been shown to exacerbate children's asthma, but the exposure sources and temporal characteristics are still under study. Children's exposure to PM is likely to involve both combustion-related ambient PM and PM related to a child's activity in various indoor and outdoor microenvironments. Among 19 children with asthma, 9-17 years of age, we examined the relationship of temporal changes in percent predicted forced expiratory volume in 1 sec (FEV1) to personal continuous PM exposure and to 24-hr average gravimetric PM mass measured at home and central sites. Subjects were followed for 2 weeks during either the fall of 1999 or the spring of 2000, in a southern California region affected by transported air pollution. FEV(subscript)1(/subscript) was measured by subjects in the morning, afternoon, and evening. Exposure measurements included continuous PM using a passive nephelometer carried by subjects; indoor, outdoor home, and central-site 24-hr gravimetric PM2.5 (PM of aerodynamic diameter < 2.5 microm) and PM10; and central-site hourly PM10, nitrogen dioxide, and ozone. Data were analyzed with linear mixed models controlling for within-subject autocorrelation, FEV1 maneuver time, and exposure period. We found inverse associations of FEV1 with increasing PM exposure during the 24 hr before the FEV1 maneuver and with increasing multiday PM averages. Deficits in percent predicted FEV1 (95% confidence interval) for given PM interquartile ranges measured during the preceding 24-hr were as follows: 128 microg/m3 1-hr maximum personal PM, -6.0% (-10.5 to -1.4); 30 microg/m3 24-hr average personal PM, -5.9% (-10.8 to -1.0); 6.7 microg/m3 indoor home PM2.5, -1.6% (-2.8 to -0.4); 16 microg/m3 indoor home PM10, -2.1% (-3.7 to -0.4); 7.1 microg/m3 outdoor home PM2.5, -1.1% (-2.4 to 0.1); and 7.5 microg/m3 central-site PM2.5, -0.7% (-1.9 to 0.4). Stronger associations were found for multiday moving averages of PM for both personal and stationary-site PM. Stronger associations with personal PM were found in boys allergic to indoor allergens. FEV1 was weakly associated with NO2 but not with O3. Results suggest mixed respiratory effects of PM in asthmatic children from both ambient background exposures and personal exposures in various microenvironments.

Conception and pregnancy during the Persian Gulf War: the risk to women veterans.

PURPOSE: To enumerate Gulf-War (GW) exposed conceptions and to compare reproductive outcomes of GW-exposed pregnancies with postwar conceptions of women Gulf War veterans (GWV) and women nondeployed veterans (NDV). METHODS: Deployment data and inpatient records from 153 military hospitals identified servicewomen who were pregnant between August 1990 and May 1992 and belonged to military units that were deployed to the Gulf War. Postal surveys were used in 1997 and 1998 to elicit reproductive history; responses were validated against military hospitalization records. Reproductive outcomes of GW-exposed pregnancies were compared with postwar conceptions of women GWVs and NDVs. RESULTS: 3285 women had a pregnancy-related admission; of these, 1558 completed the questionnaire. Self-reported reproductive outcomes and dates, gestational data, and individual deployment dates identified 415 Gulf War-exposed pregnancies, 298 GWV postwar conceptions, and 427 NDV conceptions. Compared with NDV conceptions, adverse reproductive outcomes were similar among GW-exposed pregnancies. However, spontaneous abortions [NDV: 9.1%, GWV postwar: 22.8%, adjusted odds ratio (OR)=2.92, 95% confidence interval (CI): 1.9, 4.6] and ectopic pregnancies (NDV: 1.4%, GWV postwar: 10.7%, adjusted OR=7.70, 95% CI, 3.0, 20) were elevated for GWV postwar conceptions. CONCLUSION: GW-exposed conceptions and nondeployed conceptions had similar outcomes. However, GWV postwar conceptions were at increased risk for ectopic pregnancies and spontaneous abortions.

Self-reported symptoms and medical conditions among 11,868 Gulf War-era veterans: the Seabee Health Study.

US Navy Seabees have been among the most symptomatic Gulf War veterans. Beginning in May 1997, the authors mailed Gulf War-era Seabees a health survey in serial mailings. As of July 1, 1999, 68.6% of 17,559 Seabees contacted had returned the questionnaire. Compared with other Seabees, Gulf War Seabees reported poorer general health, a higher prevalence of all 33 medical problems assessed, more cognition difficulties, and a higher prevalence of four physician-diagnosed multisymptom conditions: chronic fatigue syndrome, posttraumatic stress disorder, multiple chemical sensitivity, and irritable bowel syndrome. Because the four multisymptom conditions were highly associated with one another, the authors aggregated them into a working case definition of Gulf War illness. Among the 3,831 (22% cases) Gulf War Seabee participants, multivariable modeling revealed that female, Reserve, and enlisted personnel and participants belonging to either of two particular Seabee units were most likely to meet the case definition. Twelve of 34 self-reported Gulf War exposures were mildly associated with meeting the definition of Gulf War illness, with exposure to fumes from munitions having the highest odds ratio (odds ratio = 1.9, 95% confidence interval: 1.5, 2.4). While these data do not implicate a specific etiologic exposure, they demonstrate a strong association and a high prevalence of self-reported multisymptom conditions in a large group of symptomatic Gulf War veterans.