The systemic complexity of a monogenic disease: the molecular network of spinal muscular atrophy.

Monogenic diseases are well-suited paradigms for the causal analysis of disease-driving molecular patterns. Spinal Muscular Atrophy (SMA) is one such monogenic model caused by mutation or deletion of the Survival of motor neuron 1 (SMN1) gene. Although several functions of the SMN protein have been studied, single functions and pathways alone do not allow to identify critical disease-driving molecules. Here, we analyzed the systemic characteristics of SMA employing proteomics, phosphoproteomics, translatomics and interactomics from two mouse models with different disease-severities and genetics. This systems approach revealed sub-networks and proteins characterizing commonalities and differences of both models. To link the identified molecular networks with the disease-causing SMN protein, we combined SMN-interactome data with both proteomes creating a comprehensive representation of SMA. By this approach, disease hubs and bottlenecks between SMN and downstream pathways could be identified. Linking a disease-causing molecule with widespread molecular dysregulations via multiomics is a concept for analyses of monogenic diseases.

The effect of the Affordable Care Act on patient out-of-pocket cost and use of preventive cancer screenings in Massachusetts.

In an effort to increase use of preventive health care, The Patient Protection and Affordable Care Act (ACA) eliminated cost-sharing for preventive cancer screening services for the privately insured. The impact on patient spending and use of these screenings is still poorly understood. We used an interrupted time series analysis with the Massachusetts All-Payer Claims Database (2009-2012) to assess changes in trends in costs and use of breast, cervical and colorectal cancer screenings after the ACA policy. We find that the ACA was associated with a 0.024 (95% CI: -0.031, -0.017, p < 0.001) and 0.424 (95% CI: -0.481, -0.368, p < 0.001) percentage point decrease in the likelihood of a copayment each week for preventive breast and cervical cancer screenings respectively. The likelihood of copayment for colon cancer screening declined throughout the study period, with the rate of decline slowing following the ACA (trend in percent of screenings with copayment -0.130 before vs -0.071 after ACA, p = 0.014). Overall, we find only weak evidence that the ACA policy increased screenings. We find no significant effect on utilization for cervical cancer or colon cancer screening. For breast cancer screening, we find a small immediate increase in the utilization rate in the month after the policy change, with no change in trend after the ACA policy. Policy makers may need to consider other complementary policy options to increase screening rates.

Perceptual voice characteristics in pediatric unilateral vocal fold paralysis.

OBJECTIVE: To describe the voice characteristics of pediatric unilateral vocal fold paralysis (UVFP). STUDY DESIGN AND SETTING: Retrospective series from a children's hospital, 1996 to present. RESULTS: Forty-two patients with a mean age of 7.1 years were diagnosed with UVFP in our voice clinic (prevalence = 5.4%). Paralysis was left sided in 88%, and was most commonly seen after cardiac surgery (28.5%) and prolonged intubation/prematurity (16.7%). Voice analysis showed a moderate degree of breathiness, mild-to-moderate hoarseness and straining, mild muscle tension, and soft loudness. Twenty-six percent of patients required surgical intervention, including injection into the paralyzed fold (7 patients) and medialization thyroplasty (4 patients). Pre-operatively, breathiness was worse (P < .05) in patients undergoing surgical intervention. CONCLUSIONS: Voice characteristics of pediatric UVFP include increased breathiness, hoarseness, straining, muscle tension, and soft loudness. One-fourth of patients underwent surgical intervention; breathiness was the predominant abnormal voice characteristic in the operative cohort. SIGNIFICANCE: The voice characteristics of pediatric patients with UVFP are described. EBM RATING: C-4.

Taming Healthcare Costs: Promise and Pitfalls for Women's Health.

When it comes to healthcare, women are often the primary decision makers for their families. Therefore, focusing on women and their health needs can have a profound effect on health reform efforts to control costs and improve quality for all segments of the population. The promise and pitfalls of cost containment reform in Massachusetts can serve as an informative case study for policymakers at the local, state, and federal levels as they attempt to reduce costs while maintaining quality of care. Massachusetts cost containment law, Chapter 224, seeks to control the healthcare cost growth through innovative approaches to increase efficiency and transparency including the adoption of new delivery system models, investments in wellness and prevention programs, and implementation of standard quality and evaluation measures. In this paper, we outline four approaches to delivering on the promise of cost containment reform to maximize women's access to comprehensive, quality healthcare while avoiding the pitfalls of cost containment's adverse impact on women's health.

Pediatric vocal nodules: correlation with perceptual voice analysis.

OBJECTIVE: To present the epidemiology and correlation with perceptual analysis of vocal nodules in pediatric patients. METHODS: Retrospective review of patients seen in a tertiary care pediatric hospital's voice center from 1996 to 2003. Six hundred and forty-six patients were evaluated with videostroboscopic examinations and perceptual analysis of voice characteristics by speech pathologists. Appropriate treatment was based on the pathology identified. RESULTS: Two hundred and fifty-four patients (40%) with an average age of 7.7 years (range 0.1-19.3 years) were identified as having vocal nodules. Of these, 72% were male. Six patients (2%) were under the age of 7 months. Nodules were most commonly found in males, aged 3-10 years old. Evidence of gastro-esophageal reflux disease was found in one-quarter of patients; hyperfunction of the larynx was seen in three-fourths. Hyperfunction of the larynx correlates with the size of vocal nodules. Distortion of the vocal fold mucosal wave was not present. Perceptual analysis revealed positive correlation of the severity of hoarseness, breathiness, straining and aphonia with the size of vocal nodules. CONCLUSION: The epidemiology and correlation with perceptual voice analysis in pediatric patients with vocal nodules is presented. Hyperfunction of the larynx correlates with nodule size, while the presence of reflux disease does not. The severity of hoarseness, breathiness, straining and aphonia correlates with the size of vocal nodules.