High-throughput, real-time monitoring of engineered skeletal muscle function using magnetic sensing.

Engineered muscle tissues represent powerful tools for examining tissue level contractile properties of skeletal muscle. However, limitations in the throughput associated with standard analysis methods limit their utility for longitudinal study, high throughput drug screens, and disease modeling. Here we present a method for integrating 3D engineered skeletal muscles with a magnetic sensing system to facilitate non-invasive, longitudinal analysis of developing contraction kinetics. Using this platform, we show that engineered skeletal muscle tissues derived from both induced pluripotent stem cell and primary sources undergo improvements in contractile output over time in culture. We demonstrate how magnetic sensing of contractility can be employed for simultaneous assessment of multiple tissues subjected to different doses of known skeletal muscle inotropes as well as the stratification of healthy versus diseased functional profiles in normal and dystrophic muscle cells. Based on these data, this combined culture system and magnet-based contractility platform greatly broadens the potential for 3D engineered skeletal muscle tissues to impact the translation of novel therapies from the lab to the clinic.

Development and Initial Validation of the PROMIS®-Plus-HF Profile Measure.

Background Bringing together generic and heart failure (HF)-specific items in a publicly available, patient-reported outcome measure may facilitate routine health status assessment for improving clinical care and shared decision-making, assessing quality of care, evaluating new interventions, and comparing groups with different conditions. Methods and Results We performed a mixed-methods study to develop and validate the PROMIS®-Plus-HF (Patient-Reported Outcomes Measurement Information System®-Plus-Heart Failure) profile measure-a HF-specific instrument based on the generic PROMIS. We conducted 8 focus groups with 61 patients with HF and phone interviews with 10 HF clinicians. The measure was developed via an iterative process of reviewing existing PROMIS items and developing and testing new HF items. In a 600-patient sample, we estimated reliability (internal consistency; test-retest, with n=100 participants). We conducted validity analyses using Pearson r and Spearman ρ correlations with Kansas City Cardiomyopathy Questionnaire subscores. In a longitudinal sample, we performed responsiveness testing (paired t tests) with 75 patients with HF receiving interventions with expected health status improvement. The PROMIS-Plus-HF measure comprises 86 items (64 existing; 22 new) across 18 domains. Internal consistency reliability (Cronbach α) coefficients ranged from 0.52 to 0.96, with α≥0.70 in 12 of 17 domains. Test-retest intraclass correlation coefficients were ≥0.90. Correlations with Kansas City Cardiomyopathy Questionnaire subscores supported expected convergent ( r/ρ>0.60) and divergent validity ( r/ρ<0.30). In the longitudinal sample, 10 of 18 domains had improved ( P<0.05) scores from baseline to follow-up. Conclusions The PROMIS-Plus-HF profile measure-a complete assessment of physical, mental, and social health-exhibited good psychometric characteristics and may facilitate patient-centered care and research. Subsets of domains and items can be used depending on the clinical or research purpose.

Spatiotemporal control of cardiac anisotropy using dynamic nanotopographic cues.

Coordinated extracellular matrix spatiotemporal reorganization helps regulate cellular differentiation, maturation, and function in vivo, and is therefore vital for the correct formation, maintenance, and healing of complex anatomic structures. In order to evaluate the potential for cultured cells to respond to dynamic changes in their in vitro microenvironment, as they do in vivo, the collective behavior of primary cardiac muscle cells cultured on nanofabricated substrates with controllable anisotropic topographies was studied. A thermally induced shape memory polymer (SMP) was employed to assess the effects of a 90° transition in substrate pattern orientation on the contractile direction and structural organization of cardiomyocyte sheets. Cardiomyocyte sheets cultured on SMPs exhibited anisotropic contractions before shape transition. 48 h after heat-induced shape transition, the direction of cardiomyocyte contraction reoriented significantly and exhibited a bimodal distribution, with peaks at ∼45 and -45° (P < 0.001). Immunocytochemical analysis highlighted the significant structural changes that the cells underwent in response to the shift in underlying topography. The presented results demonstrate that initial anisotropic nanotopographic cues do not permanently determine the organizational fate or contractile properties of cardiomyocytes in culture. Given the importance of surface cues in regulating primary and stem cell development, investigation of such tunable nanotopographies may have important implications for advancing cellular maturation and performance in vitro, as well as improving our understanding of cellular development in response to dynamic biophysical cues.

Market variations in intensity of Medicare service use and beneficiary experiences with care.

OBJECTIVE: Examine associations between patient experiences with care and service use across markets. DATA SOURCES/STUDY SETTING: Medicare fee-for-service (FFS) and managed care (Medicare Advantage [MA]) beneficiaries in 306 markets from the 2003 Consumer Assessments of Healthcare Providers and Systems (CAHPS) surveys. Resource use intensity is measured by the 2003 end-of-life expenditure index. STUDY DESIGN: We estimated correlations and linear regressions of eight measures of case-mix-adjusted beneficiary experiences with intensity of service use across markets. DATA COLLECTION/EXTRACTION: We merged CAHPS data with service use data, excluding beneficiaries under 65 years of age or receiving Medicaid. PRINCIPAL FINDINGS: Overall, higher intensity use was associated (p<.05) with worse (seven measures) or no better care experiences (two measures). In higher-intensity markets, Medicare FFS and MA beneficiaries reported more problems getting care quickly and less helpful office staff. However, Medicare FFS beneficiaries in higher-intensity markets reported higher overall ratings of their personal physician and main specialist. Medicare MA beneficiaries in higher-intensity markets also reported worse quality of communication with physicians, ability to get needed care, and overall ratings of care. CONCLUSIONS: Medicare beneficiaries in markets characterized by high service use did not report better experiences with care. This trend was strongest for those in managed care.

Healthcare intensity is associated with lower ratings of healthcare quality by younger adults.

Previous studies suggest a negative relationship between regional intensity of healthcare services and Medicare patients' perceptions of healthcare quality. However, no studies to date have examined the relationship across a broad age range of the population. We describe the responses of 64 088 respondents aged 19 to 69 years to an online interactive patient assessment and feedback system. We learn that in higher-intensive regions, specialty use is higher regardless of patient illness burden and that overall quality of care was lower in higher-intensity regions. The findings that "more is not better" previously associated with Medicare patients seems to apply across a much broader age segment of the population.

Comorbidity risk-adjustment strategies are comparable among persons with hip fracture.

OBJECTIVE: To determine the magnitude and importance of declines in model performance associated with altering the data source and time frame from which comorbid conditions were identified in claims-based risk adjustment among persons with hip fracture. STUDY DESIGN AND SETTING: Medicare claims data were used to identify incident hip fracture cases in 1999. Three risk-adjustment instruments were evaluated: one by Iezzoni, the Charlson Index (Romano adaptation), and the Clinical Classification Software (CCS). Several implementation strategies, defined by altering data source (MedPar and/or Part B claims) and time frame (index hospitalization and/or 1-year preperiod), were assessed for each instrument. Logistic regression was used to predict 1-year mortality, and model performance was compared. RESULTS: Each instrument had modest ability to predict 1-year mortality after hip fracture. The CCS performed best overall (c=0.76), followed by the Iezzoni (c=0.73) and Charlson models (c=0.72). Although each instrument performed most favorably when applied to both inpatient and outpatient claims and when comorbidities were considered during the preperiod, varying data source and time frame had trivial effects on model performance. CONCLUSION: The similar predictive ability of the three risk-adjustment instruments suggests that ease of implementation be a key consideration in choosing an approach for hip fracture populations.

Abstracts in high profile journals often fail to report harm.

BACKGROUND: To describe how frequently harm is reported in the abstract of high impact factor medical journals. DESIGN AND POPULATION: We carried out a blinded structured review of a random sample of 363 Randomised Controlled Trials (RCTs) carried out on human beings, and published in high impact factor medical journals in 2003. Main endpoint: 1) Proportion of articles reporting harm in the abstract; and 2) Proportion of articles that reported harm in the abstract when harm was reported in the main body of the article. ANALYSIS: Corrected Prevalence Ratio (cPR) and its exact confidence interval were calculated. Non-conditional logistic regression was used. RESULTS: 363 articles and 407 possible comparisons were studied. Overall, harm was reported in 135 abstracts [37.2% (CI95%:32.2 to 42.4)]. Harm was reported in the main text of 243 articles [66.9% (CI95%: 61.8 to 71.8)] and was statistically significant in 54 articles [14.9% (CI95%: 11.4 to 19.0)]. Among the 243 articles that mentioned harm in the text, 130 articles [53.5% (CI95% 47.0 to 59.9)] reported harm in the abstract; a figure that rose to 75.9% (CI95%: 62.4 to 86.5) when the harm reported in the text was statistically significant. Harm in the abstract was more likely to be reported when statistically significant harm was reported in the main body of the article [cPR = 1.70 (CI95% 1.47 to 1.92)] and when drug companies (not public institutions) funded the RCTs [cPR = 1.29 (CI95% 1.03 to 1.67)]. CONCLUSION: Abstracts published in high impact factor medical journals underreport harm, even when harm is reported in the main body of the article.