Consumer Directed Healthcare: Except for the Healthy and Wealthy It’s Unwise

Many politicians and business leaders are advocating high deductible health insurance plans linked with health savings accounts—so-called consumer-directed healthcare. These policies penalize the sick, discourage needed care (especially primary and preventive care), and direct tax subsidies towards the wealthiest Americans. They offer little hope of slowing the growth of health care costs and add further bureaucratic costs and complexity to our health care financing system

Neural Tube Defects and Folate Pathway Genes: Family-Based Association Tests of Gene–Gene and Gene–Environment Interactions

BACKGROUND: Folate metabolism pathway genes have been examined for association with neural tube defects (NTDs) because folic acid supplementation reduces the risk of this debilitating birth defect. Most studies addressed these genes individually, often with different populations providing conflicting results. OBJECTIVES: Our study evaluates several folate pathway genes for association with human NTDs, incorporating an environmental cofactor: maternal folate supplementation. METHODS: In 304 Caucasian American NTD families with myelomeningocele or anencephaly, we examined 28 polymorphisms in 11 genes: folate receptor 1, folate receptor 2, solute carrier family 19 member 1, transcobalamin II, methylenetetrahydrofolate dehydrogenase 1, serine hydroxymethyl-transferase 1, 5,10-methylenetetrahydrofolate reductase (MTHFR), 5-methyltetrahydrofolate-homo-cysteine methyltransferase, 5-methyltetrahydrofolate-homocysteine methyltransferase reductase, betaine-homocysteine methyltransferase (BHMT), and cystathionine-beta-synthase. RESULTS: Only single nucleotide polymorphisms (SNPs) in BHMT were significantly associated in the overall data set; this significance was strongest when mothers took folate-containing nutritional supplements before conception. The BHMT SNP rs3733890 was more significant when the data were stratified by preferential transmission of the MTHFR rs1801133 thermolabile T allele from parent to offspring. Other SNPs in folate pathway genes were marginally significant in some analyses when stratified by maternal supplementation, MTHFR, or BHMT allele transmission. CONCLUSIONS: BHMT rs3733890 is significantly associated in our data set, whereas MTHFR rs1801133 is not a major risk factor. Further investigation of folate and methionine cycle genes will require extensive SNP genotyping and/or resequencing to identify novel variants, inclusion of environmental factors, and investigation of gene–gene interactions in large data sets

Primary myxoid liposarcoma of the supraglottic larynx

Sarcomas are a rare occurrence accounting for roughly 1% of all cancer cases reported. Of these, 9–18% will be identified as liposarcoma. Overall, only 4–9% of all liposarcomas occur in the head and neck region. As such, it is a rare event to see a primary liposarcoma of the aerodigestive tract. These tumors are typically misdiagnosed secondary to their indolent, asymptomatic course and similarities in appearance to other benign lesions. An understanding of these lesions will help clinicians appropriately manage their patients. We present a case of a 60-year male with a primary supraglottic myxoid liposarcoma, and provide relevant information about liposarcomas

Both “illness and temptation of the enemy”: melancholy, the medieval patient and the writings of King Duarte of Portugal (r. 1433–38)

Recent historians have rehabilitated King Duarte of Portugal, previously maligned and neglected, as an astute ruler and philosopher. There is still a tendency, however, to view Duarte as a depressive or a hypochondriac, due to his own description of his melancholy in his advice book, the Loyal Counselor. This paper reassesses Duarte's writings, drawing on key approaches in the history of medicine, such as narrative medicine and the history of the patient. It is important to take Duarte's views on his condition seriously, placing them in the medical and theological contexts of his time and avoiding modern retrospective diagnosis. Duarte's writings can be used to explore the impact of plague, doubt and death on the life of a well-educated and conscientious late-medieval ruler

Safety and diagnostic efficacy of gadoteridol for magnetic resonance imaging of the brain and spine in children 2 years of age and younger.

BACKGROUND: Neonates and young children require efficacious magnetic resonance imaging (MRI) examinations but are potentially more susceptible to the short- and long-term adverse effects of gadolinium-based contrast agents due to the immaturity of their body functions. OBJECTIVE: To evaluate the acute safety and diagnostic efficacy of gadoteridol (ProHance) for contrast-enhanced MRI of the central nervous system (CNS) in children ≤2 years of age. MATERIALS AND METHODS: One hundred twenty-five children ≤2 years old (including 57 children <6 months old) who underwent contrast-enhanced MRI of the CNS with gadoteridol at 0.1 mmol/kg body weight were retrospectively enrolled at five imaging centers. Safety data were assessed for acute/subacute adverse events in the 48 h following gadoteridol administration and, when available, vital signs, electrocardiogram (ECG) and clinical laboratory values obtained from blood samples taken from 48 h before until 48 h following the MRI exam. The efficacy of gadoteridol-enhanced MRI compared to unenhanced MRI for disease diagnosis was evaluated prospectively by three blinded, unaffiliated readers. RESULTS: Thirteen changes of laboratory values (11 mild, 1 moderate, 1 unspecified) were reported as adverse events in 7 (5.6%) patients. A relationship to gadoteridol was deemed possible though doubtful for two of these adverse events in two patients (1.6%). There were no clinical adverse events, no serious adverse events and no clinically meaningful changes in vital signs or ECG recordings. Accurate differentiation of tumor from non-neoplastic disease, and exact matching of specific MRI-determined diagnoses with on-site final diagnoses, was achieved in significantly more patients by each reader following the evaluation of combined pre- and post-contrast images compared to pre-contrast images alone (84.6-88.0% vs. 70.9-76.9%; P≤0.006 and 67.5-79.5% vs. 47.0-66.7%; P≤0.011, respectively). CONCLUSION: Gadoteridol at 0.1 mmol/kg body weight is safe, well tolerated and effective for contrast-enhanced MRI of the CNS in children ≤2 years of age

Identification of Chiari Type I Malformation subtypes using whole genome expression profiles and cranial base morphometrics.

BACKGROUND: Chiari Type I Malformation (CMI) is characterized by herniation of the cerebellar tonsils through the foramen magnum at the base of the skull, resulting in significant neurologic morbidity. As CMI patients display a high degree of clinical variability and multiple mechanisms have been proposed for tonsillar herniation, it is hypothesized that this heterogeneous disorder is due to multiple genetic and environmental factors. The purpose of the present study was to gain a better understanding of what factors contribute to this heterogeneity by using an unsupervised statistical approach to define disease subtypes within a case-only pediatric population. METHODS: A collection of forty-four pediatric CMI patients were ascertained to identify disease subtypes using whole genome expression profiles generated from patient blood and dura mater tissue samples, and radiological data consisting of posterior fossa (PF) morphometrics. Sparse k-means clustering and an extension to accommodate multiple data sources were used to cluster patients into more homogeneous groups using biological and radiological data both individually and collectively. RESULTS: All clustering analyses resulted in the significant identification of patient classes, with the pure biological classes derived from patient blood and dura mater samples demonstrating the strongest evidence. Those patient classes were further characterized by identifying enriched biological pathways, as well as correlated cranial base morphological and clinical traits. CONCLUSIONS: Our results implicate several strong biological candidates warranting further investigation from the dura expression analysis and also identified a blood gene expression profile corresponding to a global down-regulation in protein synthesis