The Shadows of Life: Medicaid\u27s Failure of Health Care\u27s Moral Test

North Carolina Medicaid covers one-fifth of the state’s population and makes up approximately one-third of the budget. Yet the state has experienced increasing costs and worsening health outcomes over the past decade, while socioeconomic disparities persist among communities. In this article, the authors explore the factors that influence these trends and provide a series of policy lessons to inform the state’s current reform efforts following the recent approval of North Carolina’s Section 1115 waiver by the Centers for Medicare and Medicaid Services. The authors used health, social, and financial data from the state Department of Health and Human Services, the Robert Wood Johnson Foundation, and the University of North Carolina to identify the highest cost counties in North Carolina. They found higher per beneficiary spending to be inversely related to population health, with many counties with the most expensive beneficiaries also reporting poor health outcomes. These trends appear to be attributed to a breakdown in access to basic health services, with high cost counties often lacking adequate numbers of health care providers and possessing limited health care services, leading patients to primarily engage the health care system in a reactive manner and predominantly in institutional care settings. To illustrate this pattern, the authors developed case studies of Tyrrell County and Graham County, which respectively are home to the state’s worst health outcomes and most expensive Medicaid beneficiaries. The authors combined stories of these counties with the larger historical trends to offer policy recommendations to help reorient North Carolina Medicaid around patient needs. The results shed light on traditionally understudied hotspots of cost and poor outcomes in North Carolina, while proposing tangible steps to support reform

ΔNp63α suppresses cells invasion by downregulating PKCγ/Rac1 signaling through miR-320a

ΔNp63α, a member of the p53 family of transcription factors, is overexpressed in a number of cancers and plays a role in proliferation, differentiation, migration, and invasion. ΔNp63α has been shown to regulate several microRNAs that are involved in development and cancer. We identified miRNA miR-320a as a positively regulated target of ΔNp63α. Previous studies have shown that miR-320a is downregulated in colorectal cancer and targets the small GTPase Rac1, leading to a reduction in noncanonical WNT signaling and EMT, thereby inhibiting tumor metastasis and invasion. We showed that miR-320a is a direct target of ΔNp63α. Knockdown of ΔNp63α in HaCaT and A431 cells downregulates miR-320a levels and leads to a corresponding elevation in PKCγ transcript and protein levels. Rac1 phosphorylation at Ser71 was increased in the absence of ΔNp63α, whereas overexpression of ΔNp63α reversed S71 phosphorylation of Rac1. Moreover, increased PKCγ levels, Rac1 phosphorylation and cell invasion observed upon knockdown of ΔNp63α was reversed by either overexpressing miR-320a mimic or Rac1 silencing. Finally, silencing PKCγ or treatment with the PKC inhibitor Gö6976 reversed increased Rac1 phosphorylation and cell invasion observed upon silencing ΔNp63α. Taken together, our data suggest that ΔNp63α positively regulates miR-320a, thereby inhibiting PKCγ expression, Rac1 phosphorylation, and cancer invasion.Fil: Aljagthmi, Amjad A.. Wright State University; Estados UnidosFil: Hill, Natasha T.. Wright State University; Estados UnidosFil: Cooke, Mariana. University of Pennsylvania; Estados UnidosFil: Kazanietz, Marcelo Gabriel. University of Pennsylvania; Estados UnidosFil: Abba, Martín Carlos. Universidad Nacional de La Plata. Facultad de Ciencias Médicas. Centro de Investigaciones Inmunológicas Básicas y Aplicadas; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata; ArgentinaFil: Long, Weiwen. Wright State University; Estados UnidosFil: Kadakia, Madhavi P.. Wright State University; Estados Unido

Treatment of peroneal nerve injuries with simultaneous tendon transfer and nerve exploration

Abstract Background Common peroneal nerve palsy leading to foot drop is difficult to manage and has historically been treated with extended bracing with expectant waiting for return of nerve function. Peroneal nerve exploration has traditionally been avoided except in cases of known traumatic or iatrogenic injury, with tendon transfers being performed in a delayed fashion after exhausting conservative treatment. We present a new strategy for management of foot drop with nerve exploration and concomitant tendon transfer. Method We retrospectively reviewed a series of 12 patients with peroneal nerve palsies that were treated with tendon transfer from 2005 to 2011. Of these patients, seven were treated with simultaneous peroneal nerve exploration and repair at the time of tendon transfer. Results Patients with both nerve repair and tendon transfer had superior functional results with active dorsiflexion in all patients, compared to dorsiflexion in 40% of patients treated with tendon transfers alone. Additionally, 57% of patients treated with nerve repair and tendon transfer were able to achieve enough function to return to running, compared to 20% in patients with tendon transfer alone. No patient had full return of native motor function resulting in excessive dorsiflexion strength. Conclusion The results of our limited case series for this rare condition indicate that simultaneous nerve repair and tendon transfer showed no detrimental results and may provide improved function over tendon transfer alone.http://deepblue.lib.umich.edu/bitstream/2027.42/109530/1/13018_2014_Article_67.pd

Comprehensive serial molecular profiling of an “N of 1” exceptional non-responder with metastatic prostate cancer progressing to small cell carcinoma on treatment

Abstract Importance Small cell carcinoma/neuroendocrine prostate cancer (NePC) is a lethal, poorly understood prostate cancer (PCa) subtype. Controversy exists about the origin of NePC in this setting. Objective To molecularly profile archived biopsy specimens from a case of early-onset PCa that rapidly progressed to NePC to identify drivers of the aggressive course and mechanisms of NePC origin and progression. Design, setting, and participants A 47-year-old patient presented with metastatic prostatic adenocarcinoma (Gleason score 9). After a 6-month response to androgen deprivation therapy, the patient developed jaundice and liver biopsy revealed exclusively NePC. Targeted next generation sequencing (NGS) from formalin-fixed paraffin-embedded (FFPE)-isolated DNA was performed from the diagnostic prostate biopsy and the liver biopsy at progression. Intervention Androgen deprivation therapy for adenocarcinoma followed by multiagent chemotherapy for NePC. Main outcomes and measures Identification of the mutational landscape in primary adenocarcinoma and NePC liver metastasis. Whether the NePC arose independently or was derived from the primary adenocarcinoma was considered based on mutational profiles. Results A deleterious somatic SMAD4 L535fs variant was present in both prostate and liver specimens; however, a TP53 R282W mutation was exclusively enriched in the liver specimen. Copy number analysis identified concordant, low-level alterations in both specimens, with focal MYCL amplification and homozygous PTEN, RB1, and MAP2K4 losses identified exclusively in the NePC specimen. Integration with published genomic profiles identified MYCL as a recurrently amplified in NePC. Conclusions and relevance NGS of routine biopsy samples from an exceptional non-responder identified SMAD4 as a driver of the aggressive course and supports derivation of NePC from primary adenocarcinoma (transdifferentiation).http://deepblue.lib.umich.edu/bitstream/2027.42/113670/1/13045_2015_Article_204.pd

Prospective assessment of patient-reported outcomes and estradiol and drug concentrations in patients experiencing toxicity from adjuvant aromatase inhibitors

PURPOSE: Aromatase inhibitors (AI), which decrease circulating estradiol concentrations in post-menopausal women, are associated with toxicities that limit adherence. Approximately one-third of patients will tolerate a different AI after not tolerating the first. We report the effect of crossover from exemestane to letrozole or vice versa on patient-reported outcomes (PROs) and whether the success of crossover is due to lack of estrogen suppression. METHODS: Post-menopausal women enrolled on a prospective trial initiating AI therapy for early-stage breast cancer were randomized to exemestane or letrozole. Those that discontinued for intolerance were offered protocol-directed crossover to the other AI after a washout period. Changes in PROs, including pain [Visual Analog Scale (VAS)] and functional status [Health Assessment Questionnaire (HAQ)], were compared after 3 months on the first versus the second AI. Estradiol and drug concentrations were measured. RESULTS: Eighty-three patients participated in the crossover protocol, of whom 91.3% reported improvement in symptoms prior to starting the second AI. Functional status worsened less after 3 months with the second AI (HAQ mean change AI #1: 0.2 [SD 0.41] vs. AI #2: -0.05 [SD 0.36]; p = 0.001); change in pain scores was similar between the first and second AI (VAS mean change AI #1: 0.8 [SD 2.7] vs. AI #2: -0.2 [SD 2.8]; p = 0.19). No statistical differences in estradiol or drug concentrations were found between those that continued or discontinued AI after crossover. CONCLUSIONS: Although all AIs act via the same mechanism, a subset of patients intolerant to one AI report improved PROs with a different one. The mechanism of this tolerance remains unknown, but does not appear to be due to non-adherence to, or insufficient estrogen suppression by, the second AI

The Transit Ingress and the Tilted Orbit of the Extraordinarily Eccentric Exoplanet HD 80606b

We present the results of a transcontinental campaign to observe the 2009 June 5 transit of the exoplanet HD 80606b. We report the first detection of the transit ingress, revealing the transit duration to be 11.64 +/- 0.25 hr and allowing more robust determinations of the system parameters. Keck spectra obtained at midtransit exhibit an anomalous blueshift, giving definitive evidence that the stellar spin axis and planetary orbital axis are misaligned. The Keck data show that the projected spin-orbit angle is between 32-87 deg with 68.3% confidence and between 14-142 deg with 99.73% confidence. Thus the orbit of this planet is not only highly eccentric (e=0.93), but is also tilted away from the equatorial plane of its parent star. A large tilt had been predicted, based on the idea that the planet's eccentric orbit was caused by the Kozai mechanism. Independently of the theory, it is noteworthy that all 3 exoplanetary systems with known spin-orbit misalignments have massive planets on eccentric orbits, suggesting that those systems migrate differently than lower-mass planets on circular orbits.Comment: ApJ, in press [13 pg

Central aortic valve coaptation area during diastole as seen by 64-multidetector computed tomography (MDCT)

As multiple new procedures now require better visualization of the aortic valve, we sought to better define the central aortic valve coaptation area seen during diastole on multi-detector row cardiac computed tomography (MDCT). 64-MDCT images of 384 symptomatic consecutive patients referred for coronary artery disease evaluation were included in the study. Planimetric measurements of this area were performed on cross-sectional views of the aortic valve at 75% phase of the cardiac cycle. Planimetric measurement of central regurgitation orifice area (ROA) seen in patients with aortic regurgitation and Hounsfield units of the central aortic valve coaptation area were performed. Mean area of the central aortic valve coaptation area was 5.34 ± 5.19 mm2 and Hounsfield units in this area were 123.69 ± 31.31 HU. The aortic valve coaptation area (mm2) measurement in patients without AR was: 4.90 ± 0.17 and in patients with AR: 10.53 ± 0.26 (P = <0.05). On Bland–Altman analysis a very good correlation between central aortic valve coaptation area and central ROA was found (r = 0.80, P = <0.001). Central aortic valve coaptation area is a central area present at the coaptation of nodules of arantius of aortic cusps during diastole; it is incompetent and increased in size in patients with aortic regurgitation

Maternal corticotropin-releasing hormone is associated with LEP DNA methylation at birth and in childhood: an epigenome-wide study in Project Viva

BackgroundCorticotropin-releasing hormone (CRH) plays a central role in regulating the secretion of cortisol which controls a wide range of biological processes. Fetuses overexposed to cortisol have increased risks of disease in later life. DNA methylation may be the underlying association between prenatal cortisol exposure and health effects. We investigated associations between maternal CRH levels and epigenome-wide DNA methylation of cord blood in offsprings and evaluated whether these associations persisted into mid-childhood.MethodsWe investigated mother-child pairs enrolled in the prospective Project Viva pre-birth cohort. We measured DNA methylation in 257 umbilical cord blood samples using the HumanMethylation450 Bead Chip. We tested associations of maternal CRH concentration with cord blood cells DNA methylation, adjusting the model for maternal age at enrollment, education, maternal race/ethnicity, maternal smoking status, pre-pregnancy body mass index, parity, gestational age at delivery, child sex, and cell-type composition in cord blood. We further examined the persistence of associations between maternal CRH levels and DNA methylation in children's blood cells collected at mid-childhood (n = 239, age: 6.7-10.3 years) additionally adjusting for the children's age at blood drawn.ResultsMaternal CRH levels are associated with DNA methylation variability in cord blood cells at 96 individual CpG sites (False Discovery Rate &lt;0.05). Among the 96 CpG sites, we identified 3 CpGs located near the LEP gene. Regional analyses confirmed the association between maternal CRH and DNA methylation near LEP. Moreover, higher maternal CRH levels were associated with higher blood-cell DNA methylation of the promoter region of LEP in mid-childhood (P &lt; 0.05, β = 0.64, SE = 0.30).ConclusionIn our cohort, maternal CRH was associated with DNA methylation levels in newborns at multiple loci, notably in the LEP gene promoter. The association between maternal CRH and LEP DNA methylation levels persisted into mid-childhood