Monitoring Genomic Structural Rearrangements Resulting from Gene Editing.

The cytogenomics-based methodology of directional genomic hybridization (dGH) enables the detection and quantification of a more comprehensive spectrum of genomic structural variants than any other approach currently available, and importantly, does so on a single-cell basis. Thus, dGH is well-suited for testing and/or validating new advancements in CRISPR-Cas9 gene editing systems. In addition to aberrations detected by traditional cytogenetic approaches, the strand specificity of dGH facilitates detection of otherwise cryptic intra-chromosomal rearrangements, specifically small inversions.

Adaptive DNA amplification of synthetic gene circuit opens a way to overcome cancer chemoresistance.

Drug resistance continues to impede the success of cancer treatments, creating a need for experimental model systems that are broad, yet simple, to allow the identification of mechanisms and novel countermeasures applicable to many cancer types. To address these needs, we investigated a set of engineered mammalian cell lines with synthetic gene circuits integrated into their genome that evolved resistance to Puromycin. We identified DNA amplification as the mechanism underlying drug resistance in 4 out of 6 replicate populations.

A reference human induced pluripotent stem cell line for large-scale collaborative studies.

Human induced pluripotent stem cell (iPSC) lines are a powerful tool for studying development and disease, but the considerable phenotypic variation between lines makes it challenging to replicate key findings and integrate data across research groups. To address this issue, we sub-cloned candidate human iPSC lines and deeply characterized their genetic properties using whole genome sequencing, their genomic stability upon CRISPR-Cas9-based gene editing, and their phenotypic properties including differentiation to commonly used cell types. These studies identified KOLF2.

Dual optical force plate for time resolved measurement of forces and pressure distributions beneath shoes and feet.

Frustrated total internal reflection (FTIR) imaging was used to perform remote optical measurements of the forces/pressures exerted beneath shoes and feet during a number of different training activities including countermovement jumps, jogging and drop jumps. A single camera was used to simultaneously image two acrylic, FTIR waveguide imaging elements from below, at frame rates up to 200 frames per second. The images obtained using the camera were converted into pressure/force maps using a previously developed theory which combines the mechanics of contact of soft objects and the scattering of evanescent waves.

Chromosome Translocations, Inversions and Telomere Length for Retrospective Biodosimetry on Exposed U.S. Atomic Veterans.

It has now been over 60 years since U.S. nuclear testing was conducted in the Pacific islands and Nevada, exposing military personnel to varying levels of ionizing radiation.

Meaningful Use and Hospital Performance on Post-Acute Utilization Indicators.

Objectives: To examine trends in hospital post-acute utilization indicators and to determine whether improvement in these indicators is associated with attesting to meaningful use (MU).

Data Sources: Medicare claims-based, repeated measures on 30-day hospital-wide all-cause readmission and emergency department (ED) utilization rates for 160 short-stay hospitals (2009-2012); Medicare EHR Incentive Program Payments files (2011-2012); and other hospital and market data.

Study Design: Interrupted time series with concurrent comparison group.

Hospital Postacute Care Referral Networks: Is Referral Concentration Associated with Medicare-Style Bundled Payments?

Objective: To evaluate whether Medicare-style bundled payments are lower or higher for beneficiaries discharged from hospitals with postacute care (PAC) referrals concentrated among fewer PAC providers.

Data Source: Medicare Part A and Part B claim (2008-2012) for all beneficiaries residing in any of 17 market areas: the Provider of Service file, the Healthcare Cost Report Information System, and the Dartmouth Atlas.

Study Design: An observational study in which hospitals were distinguished according to PAC referral concentration, which is the tendency to utilize fewer rather than more PAC providers.

Linking Spending and Quality Indicators to Measure Value and Efficiency in Health Care.

Policy makers and stakeholders have reached a consensus that both quality and spending or resource use indicators should be jointly measured and prioritized to meet the objectives of our health system. However, the relative merits of alternative approaches that combine quality and spending indicators are not well understood. We conducted a literature review to identify different approaches that combine indicators of quality and spending measures to profile provider efficiency in the context of specific applications in health care.

Effects of Expanded Coverage for Chiropractic Services on Medicare Costs in a CMS Demonstration.

Background: Moderately convincing evidence supports the benefits of chiropractic manipulations for low back pain. Its effectiveness in other applications is less well documented, and its cost-effectiveness is not known. These questions led the Centers for Medicaid and Medicare Services (CMS) to conduct a two-year demonstration of expanded Medicare coverage for chiropractic services in the treatment of beneficiaries with neuromusculoskeletal (NMS) conditions affecting the back, limbs, neck, or head.

Racial/Ethnic disparities in patient experience with communication in hospitals: real differences or measurement errors?

Background: An important aspect of medical care is clear and effective communication, which can be particularly challenging for individuals based on race/ethnicity. Quality of communication is measured systematically in the Hospital Consumer Assessment of Healthcare Providers and Systems (HCAHPS) survey, and analyzed frequently such as in the National Healthcare Disparities Report. Caution is needed to discern differences in communication quality from racial/ethnic differences in perceptions about concepts or expectations about their fulfillment.

Images of imaging: how to process and display imaging utilization for large populations.

Objective: We propose a method of processing and displaying imaging utilization data for large populations.

Conclusion: The comprehensive and finely grained picture of imaging utilization yielded by our methods is a first step toward population-based imaging utilization management. We believe that our methods for the categorization and display of imaging utilization will prove to be widely useful.

Use of Systematic Methods to Improve Disease Identification in Administrative Data: The Case of Severe Sepsis.

Background: Selection of International Classification of Diseases (ICD)-based coded information for complex conditions such as severe sepsis is a subjective process and the results are sensitive to the codes selected. We use an innovative data exploration method to guide ICD-based case selection for severe sepsis.

Methods: Using the Nationwide Inpatient Sample, we applied Latent Class Analysis (LCA) to determine if medical coders follow any uniform and sensible coding for observations with severe sepsis.

Governing board, C-suite, and clinical management perceptions of quality and safety structures, processes, and priorities in U.S. hospitals.

To achieve quality improvement in hospitals requires greater attention to systems thinking than is typical at this time, including a shared understanding across different levels of the hospital of the current state of quality improvement efforts. A self-administered survey assessed the perceptions of board members, C-suite executives, and clinical managers regarding quality activities and structures. This instrument, the Hospital Leadership and Quality Assessment Tool (HLQAT), includes 13 domains in six conceptual areas that we believe are major organizational drivers of quality and safety: (1) commitment of senior leaders, (2) a vision of exemplary quality, (3) a supportive culture, (4) accountable leadership, (5) appropriate organizational structures, and (6) adaptive capability.

Plunging into the pool of death: imagining a dangerous outcome influences distance perception.

We examined whether manipulating the imagined consequences of falling would influence the perception of height, distance, and size. In experiment 1, height and size perception were measured when participants stood at a short height (0.89 m) or a medium height (1.

Association of military deployment of a parent or spouse and changes in dependent use of health care services.

Background: U.S. Armed Forces members and spouses report increased stress associated with combat deployment.

Incidence and cost of pneumonia in medicare beneficiaries.

Background: Pneumonia is a frequent and serious illness in elderly people, with a significant impact on mortality and health-care costs. Lingering effects may influence clinical outcomes and medical service use beyond the acute hospitalization. This study describes the incidence and mortality of pneumonia in elderly Medicare beneficiaries based on treatment setting (outpatient, inpatient) and location of origin (health-care associated, community acquired) and estimates short- and long-term direct medical costs and mortality associated with an inpatient episode of pneumonia.

Substance abuse treatment utilization among adults living with HIV/AIDS and alcohol or drug problems.

This is a prospective cohort study to identify factors associated with receipt of substance abuse treatment (SAT) among adults with alcohol problems and HIV/AIDS. Data from the HIV Longitudinal Interrelationships of Viruses and Ethanol study were analyzed. Generalized estimating equation logistic regression models were fit to identify factors associated with any service utilization.

A randomized trial of telemonitoring heart failure patients.

The purpose of this study was to measure the ability of telemonitoring to reduce hospital days and total costs for Medicare managed care enrollees diagnosed with heart failure. Patients were recruited and randomly assigned for six months to either telemonitoring or standard care. Telemonitoring transmitted vital signs and clinical alerts daily to a central nursing station.

Factors associated with attendance in 12-step groups (Alcoholics Anonymous/Narcotics Anonymous) among adults with alcohol problems living with HIV/AIDS.

Background: Despite the value of 12-step meetings, few studies have examined factors associated with attendance among those living with HIV/AIDS, such as the impact of HIV disease severity and demographics.

Objective: This study examines predisposing characteristics, enabling resources and need on attendance at Alcoholic Anonymous (AA) and Narcotics Anonymous (NA) meetings among those living with HIV/AIDS and alcohol problems.

Methods: Secondary analysis of prospective data from the HIV-Longitudinal Interrelationships of Viruses and Ethanol study, a cohort of 400 adults living with HIV/AIDS and alcohol problems.

Randomized trial of enhanced profiling in substance abuse treatment.

A randomized trial of substance abuse treatment programs tested whether "enhanced profiles," consisting of feedback and coaching about performance indicators, improved the performance of residential, methadone, and detoxification programs. These enhanced profiles were reviewed during quarterly on-site visits between October 2005 and July 2007. The performance indicators were the percentage of clients completing referrals to a lower level of care, and the percentage of clients admitted to a higher level of care within 30 days of discharge.

Emergency department utilization patterns for Medicare beneficiaries with serious mental disorders.

Objective: This study examined emergency department use among Medicare beneficiaries with serious mental disorders.

Methods: Drawn from the 2004 national 5% sample of Medicare beneficiaries, the sample in this study (N=129,805) included fee-for-service enrollees with primary diagnoses of schizophrenia, major depression, other major affective disorders, or other psychoses. Emergency department use was compared by psychiatric diagnostic category and presence of a claim related to substance use disorder.

The relationship between Medicare's process of care quality measures and mortality.

Using Medicare inpatient claims and Hospital Compare process of care quality data from the period 2004-2006, we estimate two model specifications to test for the presence of correlational and causal relationships between hospital process of care performance measures and risk-adjusted (RA) 30-day mortality for heart attack, heart failure, and pneumonia. Our analysis indicates that while Hospital Compare process performance measures are correlated with 30-day mortality for each diagnosis, after we account for unobserved heterogeneity, process of care performance is no longer associated with mortality for any diagnosis. This suggests that the relationship between hospital-level process of care performance and mortality is not causal.

Measuring outcomes and efficiency in medicare value-based purchasing.

The Medicare program may soon adopt value-based purchasing (VBP), in which hospitals could receive incentives that are conditional on meeting specified performance objectives. The authors advocate for a market-oriented framework and direct measures of system-level value that are focused on better outcomes and lower total cost of care. They present a multidimensional framework for measuring outcomes of care and a method to adjust incentive payments based on efficiency.