The Functional Transcriptomic Landscape Informs Therapeutic Strategies in Multiple Myeloma.

Several therapeutic agents have been approved for treating multiple myeloma (MM), a cancer of bone marrow resident plasma cells. Predictive biomarkers for drug response could help guide clinical strategies to optimize outcomes. Here, we present an integrated functional genomic analysis of tumor samples from MM patients that were assessed for their ex vivo drug sensitivity to 37 drugs, clinical variables, cytogenetics, mutational profiles, and transcriptomes.

Association of Selinexor Dose Reductions With Clinical Outcomes in the BOSTON Study.

Background: Dose modifications in response to adverse events (AEs) can maintain tumor response and improve therapy tolerability. We conducted a post-hoc analysis of the efficacy and safety of reduced selinexor doses in the BOSTON trial (NCT03110562).

Patients And Methods: Efficacy, safety, and quality of life (QoL) in 195 patients with relapsed/refractory multiple myeloma randomized to once-weekly (QW) selinexor (100 mg), QW subcutaneous bortezomib (1.

Selinexor-Based Triplet Regimens in Patients With Multiple Myeloma Previously Treated With Anti-CD38 Monoclonal Antibodies.

Background: The increasing use of anti-CD38 monoclonal antibodies (αCD38 mAbs) for newly diagnosed or early relapsed multiple myeloma (MM), especially in non-transplant eligible patients, may lead to more patients developing αCD38 mAb-refractory disease earlier in the treatment course with fewer treatment options.

Patients And Methods: We analyzed the efficacy and safety of selinexor-based triplets (selinexor+dexamethasone [Sd] plus pomalidomide [SPd, n = 23], bortezomib [SVd, n = 16] or carfilzomib (SKd, n = 23]) in a subset of STOMP (NCT02343042) and BOSTON (NCT03110562) study patients treated previously with αCD38 mAbs.

Results: Sixty-two patients (median 4 prior therapies, range 1 to 11, 90.

Selinexor in Advanced, Metastatic Dedifferentiated Liposarcoma: A Multinational, Randomized, Double-Blind, Placebo-Controlled Trial.

Purpose: Antitumor activity in preclinical models and a phase I study of patients with dedifferentiated liposarcoma (DD-LPS) was observed with selinexor. We evaluated the clinical benefit of selinexor in patients with previously treated DD-LPS whose sarcoma progressed on approved agents.

Methods: SEAL was a phase II-III, multicenter, randomized, double-blind, placebo-controlled study.

A Note on Proposed Estimation Procedures for Claims-Based Frailty Indexes.

Two groups (Segal et al. Med Care. 2017;55(7):716-722; Segal et al.

Formulas and Web Application for Designing a Biospecimen Pooling Study to Compare Group Means.

Background: When research focuses on biomarker assessment in settings where per-assay costs are high relative to per-subject costs, a biospecimen pooling study design can be extremely cost-effective. However, designing a study to maximize cost savings is complicated by the fact that pooled measurements are typically subject to processing error, inducing additional variability caused by combining biospecimens, and may also be affected by assay-related measurement error.

Methods: We provide formulas and an interactive web application (hereafter called app) for designing a pooling study to compare group means.

Gamma models for estimating the odds ratio for a skewed biomarker measured in pools and subject to errors.

Measuring a biomarker in pooled samples from multiple cases or controls can lead to cost-effective estimation of a covariate-adjusted odds ratio, particularly for expensive assays. But pooled measurements may be affected by assay-related measurement error (ME) and/or pooling-related processing error (PE), which can induce bias if ignored. Building on recently developed methods for a normal biomarker subject to additive errors, we present two related estimators for a right-skewed biomarker subject to multiplicative errors: one based on logistic regression and the other based on a Gamma discriminant function model.

Dynamic sitting: Measurement and associations with metabolic health.

Dynamic sitting, such as fidgeting and desk work, might be associated with health, but remains difficult to identify out of accelerometry data. We examined, in a laboratory study, whether dynamic sitting can be identified out of triaxial activity counts. Among 18 participants (56% men, 27.

Logistic regression with a continuous exposure measured in pools and subject to errors.

In a multivariable logistic regression setting where measuring a continuous exposure requires an expensive assay, a design in which the biomarker is measured in pooled samples from multiple subjects can be very cost effective. A logistic regression model for poolwise data is available, but validity requires that the assay yields the precise mean exposure for members of each pool. To account for errors, we assume the assay returns the true mean exposure plus a measurement error (ME) and/or a processing error (PE).

Comparison of Summer and Winter Objectively Measured Physical Activity and Sedentary Behavior in Older Adults: Age, Gene/Environment Susceptibility Reykjavik Study.

In Iceland, there is a large variation in daylight between summer and winter. The aim of the study was to identify how this large variation influences physical activity (PA) and sedentary behavior (SB). Free living PA was measured by a waist-worn accelerometer for one week during waking hours in 138 community-dwelling older adults (61.

Association of change in brain structure to objectively measured physical activity and sedentary behavior in older adults: Age, Gene/Environment Susceptibility-Reykjavik Study.

Many studies have examined the hypothesis that greater participation in physical activity (PA) is associated with less brain atrophy. Here we examine, in a sub-sample (n=352, mean age 79.1 years) of the Age, Gene/Environment Susceptibility-Reykjavik Study cohort, the association of the baseline and 5-year change in magnetic resonance imaging (MRI)-derived volumes of gray matter (GM) and white matter (WM) to active and sedentary behavior (SB) measured at the end of the 5-year period by a hip-worn accelerometer for seven consecutive days.

Part-Time Work and Physical Activity in American High School Students.

Objective: To compare physical activity (PA) in American high school students who work part-time with those who do not work.

Methods: Data were obtained from the National Health and Nutrition Examination Survey 2003 to 2006 (n = 791). Work status was self-reported and PA was measured using accelerometers.

Daily Patterns of Physical Activity by Type 2 Diabetes Definition: Comparing Diabetes, Prediabetes, and Participants with Normal Glucose Levels in NHANES 2003-2006.

Objective: Diabetes is associated with low levels of physical activity (PA), but detailed objective information about how PA patterns vary by diabetes definition is lacking.

Methods: PA was measured with Actigraph accelerometers in older (60+) adults from the 2003-2006 National Health and Nutrition Examination Survey (n= 1,043) and analyzed in 2014. Diabetes definition (normal glucose levels, prediabetes, diabetes) was assessed (fasting glucose, hemoglobin A1C, and self-report).

Changes in daily activity patterns with age in U.S. men and women: National Health and Nutrition Examination Survey 2003-04 and 2005-06.

Objectives: To compare daily and hourly activity patterns according to sex and age.

Design: Cross-sectional, observational.

Setting: Nationally representative community sample: National Health and Nutrition Examination Survey (NHANES) 2003-04 and 2005-06.

A variant of sparse partial least squares for variable selection and data exploration.

When data are sparse and/or predictors multicollinear, current implementation of sparse partial least squares (SPLS) does not give estimates for non-selected predictors nor provide a measure of inference. In response, an approach termed "all-possible" SPLS is proposed, which fits a SPLS model for all tuning parameter values across a set grid. Noted is the percentage of time a given predictor is chosen, as well as the average non-zero parameter estimate.

Association of chronic widespread pain with objectively measured physical activity in adults: findings from the National Health and Nutrition Examination survey.

Unlabelled: Chronic widespread pain (CWP) is a common and potentially debilitating disorder. Patterns of physical activity (PA) in adults with CWP have primarily been investigated using subjective, self-report measures. The current study sought to characterize PA among community-dwelling individuals with CWP, chronic regional pain, or no chronic pain using objective measurements obtained via accelerometry in the 2003 to 2004 National Health and Nutrition Examination Survey.

Is there a sex difference in accelerometer counts during walking in older adults?

Background: Accelerometers have emerged as a useful tool for measuring free-living physical activity in epidemiological studies. Validity of activity estimates depends on the assumption that measurements are equivalent for males and females while performing activities of the same intensity. The primary purpose of this study was to compare accelerometer count values in males and females undergoing a standardized 6-minute walk test.

Objective measurements of daily physical activity patterns and sedentary behaviour in older adults: Age, Gene/Environment Susceptibility-Reykjavik Study.

Background: objectively measured population physical activity (PA) data from older persons is lacking. The aim of this study was to describe free-living PA patterns and sedentary behaviours in Icelandic older men and women using accelerometer.

Methods: from April 2009 to June 2010, 579 AGESII-study participants aged 73-98 years wore an accelerometer (Actigraph GT3X) at the right hip for one complete week in the free-living settings.

Association of sedentary time with mortality independent of moderate to vigorous physical activity.

Background: Sedentary behavior has emerged as a novel health risk factor independent of moderate to vigorous physical activity (MVPA). Previous studies have shown self-reported sedentary time to be associated with mortality; however, no studies have investigated the effect of objectively measured sedentary time on mortality independent of MVPA. The objective our study was to examine the association between objectively measured sedentary time and all-cause mortality.

Employment and physical activity in the U.S.

Background: Physical inactivity is a risk factor for obesity, cardiovascular disease, hypertension, and other chronic diseases that are increasingly prevalent in the U.S. and worldwide.