Development of an antigen-based approach to noninvasively image CAR T cells in real time and as a predictive tool.

CAR T cell therapy has revolutionized the treatment of a spectrum of blood-related malignancies. However, treatment responses vary among cancer types and patients. Accurate monitoring of CAR T cell dynamics is crucial for understanding and evaluating treatment efficacy.

A CAR enhancer increases the activity and persistence of CAR T cells.

Although chimeric antigen receptor (CAR) T cell therapies have demonstrated promising clinical outcomes, durable remissions remain limited. To extend the efficacy of CAR T cells, we develop a CAR enhancer (CAR-E), comprising a CAR T cell antigen fused to an immunomodulatory molecule. Here we demonstrate this strategy using B cell maturation antigen (BCMA) CAR T cells for the treatment of multiple myeloma, with a CAR-E consisting of the BCMA fused to a low-affinity interleukin 2 (IL-2).

Probing immune infiltration dynamics in cancer by in vivo imaging.

Cancer immunotherapies typically aim to stimulate the accumulation and activity of cytotoxic T-cells or pro-inflammatory antigen-presenting cells, reduce immunosuppressive myeloid cells or regulatory T-cells, or elicit some combination of effects thereof. Notwithstanding the encouraging results, immunotherapies such as PD-1/PD-L1-targeted immune checkpoint blockade act heterogeneously across individual patients. It remains challenging to predict and monitor individual responses, especially across multiple sites of metastasis or sites of potential toxicity.

Value-Driven Population Health: An Emerging Focus for Improving Stakeholder Role Performance.

Health and health care in the United States are being jeopardized by top-end spending whose share of the gross domestic product continues to increase even as aggregate health outcomes remain mediocre. This paper focuses on a new approach for improving stakeholder role performance in the marketplace, value-driven population health (VDPH). Devoted to maximizing the value of every dollar spent on population health, VDPH holds much promise for ameliorating this dilemma and exerting a constructive influence on the reshaping of the Affordable Care Act.

Tracking low back problems in a major self-insured workforce: toward improvement in the patient's journey.

Objective: To assess the cost outcomes of treatment approaches to care for back problems in a major self-insured workforce, using published guidelines to focus on low back pain.

Methods: Longitudinally tracked episodes of three types of International Classification of Diseases, Ninth Revision diagnosis code-identified back problems (n=14,787) during 2001 to 2009. Identified five patterns of care on the basis of the first 6 weeks of claims and compared their total costs per episode with tests that included splits by episode type and duration, use of guidelines, and propensity-derived adjustments.

Managing the burden of chronic obstructive pulmonary disease on workforce health and productivity: upping a leading employer's game.

Objective: To develop new evidence for advancing a leading employer's capacity to manage the burden of chronic obstructive pulmonary disease (COPD).

Methods: Retrospective analyses of an integrated database tracking active employees (n = 19,989) from 2001-2009. Tests on 29 measures of direct/indirect costs and drivers examined unique disease burden and impact over time.

The self-reported health and productivity burden of autoimmune disorders at a major self-insured employer.

Objectives: Examine the self-reported health and productivity burden of three autoimmune disorders: rheumatoid arthritis, psoriasis, and inflammatory bowel disease.

Methods: A 2009 representative survey of a major employer's US workforce, with two approaches for disease identification: (1) self-report and (2) self-report replicated by claims-based International Classification of Diseases, 9th Revision (ICD-9), codes.

Results: Self-reported prevalence: rheumatoid arthritis, 4.

Reducing total health burden from 2001 to 2009: an employer counter-trend success story and its implications for health care reform.

Objectives: To examine total health burden for an employer whose health-related focus is direct and indirect costs. To explore implications for the Final Rule for Accountable Care Organizations recently issued by the Centers for Medicare and Medicaid Services, whose focus includes direct but not indirect costs.

Methods: Used 42 claims and survey-based measures to track this employer's continental US workforce burden in the aggregate and by healthy and selected disease designations from 2001-2002 to 2008-2009.

Optimizing health care delivery by integrating workplaces, homes, and communities: how occupational and environmental medicine can serve as a vital connecting link between accountable care organizations and the patient-centered medical home.

In recent years, the health care reform discussion in the United States has focused increasingly on the dual goals of cost-effective delivery and better patient outcomes. A number of new conceptual models for health care have been advanced to achieve these goals, including two that are well along in terms of practical development and implementation-the patient-centered medical home (PCMH) and accountable care organizations (ACOs). At the core of these two emerging concepts is a new emphasis on encouraging physicians, hospitals, and other health care stakeholders to work more closely together to better coordinate patient care through integrated goals and data sharing and to create team-based approaches that give a greater role to patients in health care decision-making.

Evidence-based benefit design: toward a sustainable health care future for employers.

Health care costs for employers are rising much faster than inflation. The common approach to health benefit design of increasing cost sharing has failed to contain costs. Some employers, however, have been successful at mitigating the cost trend or actually reducing health care costs.

How to align evidence-based benefit design with the employer bottom-line: a case study.

Objective: To illustrate how to use evidence-based benefit design (EBD) by presenting the case study of a major manufacturer.

Method: Key components of the company's measurement and management approach to EBD are introduced. Descriptive results on the direct and indirect cost and utilization trends of the company's US active workforce during 2002 to 2008 are presented.

Using self-reports of symptom severity to measure and manage workplace depression.

Objectives: To test the workplace impact of depression when it is stratified by severity and considered in broader context.

Methods: Structural equation models of health risk appraisal data (n = 39,097) involving 41 measures of contextual characteristics, depression severity, health, and job performance.

Results: Approximately 15.

Age, overtime, and employee health, safety and productivity outcomes: a case study.

Objectives: To expand a study of the impact of overtime on employee health, safety, and productivity outcomes, previously reported in this journal, with tests comparing older versus younger workers on these relationships.

Methods: Secondary analyses of a longitudinal panel (n = 2746) representing workers at US sites for a heavy manufacturer during 2001 to 2002. Structural equation techniques were used to assess two hypotheses in the context of multiple group models positing the prediction of a broad set of employee outcomes using a three-step causal sequence.

Using routinely collected data to augment the management of health and productivity loss.

Objectives: To test models of productivity loss developed from data collected using a health risk appraisal (HRA) designed to examine health in the broader context of work, mental well-being, and the demands of organizational and family life.

Methods: Secondary analyses of a data extract provided by the HRA's developer. These analyses focused on 17,821 respondents whose version of the HRA included the Work Limitation Questionnaire.

Do long workhours impact health, safety, and productivity at a heavy manufacturer?

Objectives: To test the health, safety, and productivity effects of long workhours.

Methods: Secondary analyses of a longitudinal employee panel (n = 2746). Average hours worked during spring 2001 were assessed relative to health, safety, and productivity outcomes spanning summer 2001 through spring 2002.

The burden of pain on employee health and productivity at a major provider of business services.

Objective: The objective of this study was to examine the burden of pain on employee health and productivity at a Fortune 100 company headquartered in the northeastern United States to prioritize target areas for reducing this burden.

Methods: An electronic survey was conducted in late 2004, which produced a reasonably representative national sample of 1039 active employee respondents.

Results: A total of 28.

Using self-report and adverse event measures to track health's impact on productivity in known groups.

The use of survey data to measure and monitor health and productivity differences between groups is an issue of increasing importance. This article examines the capacity of productivity self-reports (derived from surveys) and adverse event measures (derived from administrative sources) to differentiate groups with a priori known characteristics. A replication strategy is used to test the contributions that productivity self-reports make, alone as well as above and beyond measures of adverse events, to the discrimination of 5 pairs of groups classified by clinical, job type, and demographic criteria.

An intervention to promote appropriate management of allergies in a heavy manufacturing workforce: evaluating health and productivity outcomes.

This work presents the evaluation of a first-of-its-kind intervention to improve the management of allergies among workers in a largely blue-collar industrial setting. This intervention implemented eight educational strategies focusing on appropriate medication use in the context of a controlled, nonrandomized, pre-post quasi-experimental study design. Program implementation occurred during summer 2001, with change assessed by means of measures of health and productivity, developed from employee surveys timed to occur at the height of the spring and fall allergy seasons, and measures of contemporaneous adverse events developed from administrative databases.

The burden of allergies--and the capacity of medications to reduce this burden-in a heavy manufacturing environment.

This article addresses the observational findings of the first systematic study undertaken by a manufacturer to address the impact of allergies and use of allergy medications on health, safety, and productivity. It provides background for 3 other papers from the same project, including an evaluation of an intervention to promote appropriate medication use among affected employees, which appear in this issue. The observational data are developed on 10,714 employees from: 1) 2 employee surveys; 2) administrative databases monitoring employee absenteeism, workers compensation, short-term disability, and group health.

Validating self-reported measures of productivity at work: a case for their credibility in a heavy manufacturing setting.

The extent to which employee responses to productivity surveys assess what they are intended to assess has become a pivotal issue for employers and providers. Much work is now being devoted to the validity and reliability of these self-reports. Such issues will likely be resolved only over the long term.