Change in Alcohol Use Based on Self-Report and a Quantitative Biomarker,Phosphatidylethanol, in People With HIV

AIDS and Behavior - The timeline followback (TLFB) takes more resources to collect than the Alcohol Use Disorder Identification Test (AUDIT-C). We assessed agreement of TLFB and AUDIT-C with the...     

Noninvasive Methods for Determining Pulmonary Vascular Function in Children with Pulmonary Arterial Hypertension: Application of a Mechanical Oscillator Model

Objective. Noninvasive diagnostics for pulmonary arterial hypertension (PAH) have traditionally sought to predict main pulmonary artery pressure from qualitative or direct quantitative measures of the flow velocity pattern obtained from spectral Doppler ultrasound examination of the main pulmonary artery. A more detailed quantification of flow velocity patterns in the systemic circuit has been obtained by parameterizing the flow trace with a simple dynamic system model. Here, we investigate such a model's utility as a noninvasive predictor of total right heart afterload and right heart function. Design. Flow velocity and pressure was measured within the main pulmonary artery during right heart catheterization of patients with normal hemodynamics (19 subjects, 20 conditions) and those with PAH undergoing reactivity evaluation (34 patients, 69 conditions). Our model parameters were obtained by least‐squares fitting the model velocity to the measured flow velocity. Results. Five parameter means displayed significant (P < .05) differences between normotensive and hypertensive groups. The model stiffness parameter correlated to actual pulmonary vascular resistance (r = 0.4924), pulmonary vascular stiffness (r = 0.6811), pulmonary flow (r = 0.6963), and stroke work (r = 0.7017), while the model initial displacement parameter had good correlation to stiffness (r = 0.6943) and flow (r = 0.6958). Conclusions. As predictors of total right heart afterload (resistance and stiffness) and right ventricle work, the model parameters of stiffness and initial displacement offer more comprehensive measures of the disease state than previous noninvasive methods and may be useful in routine diagnostic monitoring of patients with PAH.     

Recent trends in National Institutes of Health funding for surgery: 2003 to 2013

Background

The purpose of this study is to compare the compositions of federally funded surgical research between 2003 and 2013, and to assess differences in funding trends between surgery and other medical specialties.

Data Sources

The National Institutes of Health (NIH) Research Portfolio Online Reporting Tool database was queried for grants within core surgical disciplines during 2003 and 2013. Funding was categorized by award type, methodology, and discipline. Application success rates for surgery and 5 nonsurgical departments were trended over time.

Conclusions

Inflation-adjusted NIH funding for surgical research decreased 19% from $270M in 2003 to $219M in 2013, with a shift from R-awards to U-awards. Proportional funding to outcomes research almost tripled, while translational research diminished. Nonsurgical departments have increased NIH application volume over the last 10 years; however, surgery’s application volume has been stagnant. To preserve surgery’s role in innovative research, new efforts are needed to incentivize an increase in application volume.     

A functional description of the canine choledochoduodenal flutter valve

Forward- and reverse-opening pressures of the choledochoduodenal junction were measured in anesthetized, vagotomized dogs. Mean reverse-opening pressures were found to be significantly greater in most cases including those following the intraductal administration of vasoactive agents which are known to significantly influence mean forward-opening pressures. The polypeptides CCK-PZ and CCK-C8 were ineffective in reducing mean forward-opening pressures regardless of the route of administration. Previously published observations have indicated that mean forward-opening pressures are also unaffected by nervous activity. It is concluded that the canine choledochoduodenal junction possesses the physical and functional properties of a passive flutter valve during duodenal relaxation.     

Anti-Alpha-Toxin Monoclonal Antibody and Antibiotic Combination Therapy Improves Disease Outcome and Accelerates Healing in a Staphylococcus aureus Dermonecrosis Model

Alpha-toxin (AT) is a major virulence determinant in Staphylococcus aureus skin and soft tissue infection models. We previously demonstrated that prophylactic administration of 2A3, an AT-neutralizing monoclonal antibody (MAb), prevents S. aureus disease in a mouse dermonecrosis model by neutralizing AT-mediated tissue necrosis and immune evasion. In the present study, MEDI4893*, an affinity-optimized version of 2A3, was characterized for therapeutic activity in the dermonecrosis model as a single agent and in combination with two frontline antibiotics, vancomycin and linezolid. MEDI4893* postinfection therapy was found to exhibit a therapeutic treatment window similar to that for linezolid but longer than that for vancomycin. Additionally, when combined with either vancomycin or linezolid, MEDI4893* resulted in reduced tissue damage, increased neutrophil and macrophage infiltration and abscess formation, and accelerated healing relative to those with the antibiotic monotherapies. These data suggest that AT neutralization with a potent MAb holds promise for both prophylaxis and adjunctive therapy with antibiotics and may be a valuable addition to currently available options for the treatment of S. aureus skin and soft tissue infections.     

Design and Implementation of a Web-Based Reporting and Benchmarking Center for Inpatient Glucometrics

Background:Insulin is a top source of adverse drug events in the hospital, and glycemic control is a focus of improvement efforts across the country. Yet, the majority of hospitals have no data to gauge their performance on glycemic control, hypoglycemia rates, or hypoglycemic management. Current tools to outsource glucometrics reports are limited in availability or function.Methods:Society of Hospital Medicine (SHM) faculty designed and implemented a web-based data and reporting center that calculates glucometrics on blood glucose data files securely uploaded by users. Unit labels, care type (critical care, non–critical care), and unit type (eg, medical, surgical, mixed, pediatrics) are defined on upload allowing for robust, flexible reporting. Reports for any date range, care type, unit type, or any combination of units are available on demand for review or downloading into a variety of file formats. Four reports with supporting graphics depict glycemic control, hypoglycemia, and hypoglycemia management by patient day or patient stay. Benchmarking and performance ranking reports are generated periodically for all hospitals in the database.Results:In all, 76 hospitals have uploaded at least 12 months of data for non–critical care areas and 67 sites have uploaded critical care data. Critical care benchmarking reveals wide variability in performance. Some hospitals achieve top quartile performance in both glycemic control and hypoglycemia parameters.Conclusions:This new web-based glucometrics data and reporting tool allows hospitals to track their performance with a flexible reporting system, and provides them with external benchmarking. Tools like this help to establish standardized glucometrics and performance standards.     

Dicyanovinylnaphthalenes for neuroimaging of amyloids and relationships of electronic structures and geometries to binding affinities

The positron-emission tomography (PET) probe 2-(1-[6-[(2-fluoroethyl)(methyl)amino]-2-naphthyl]ethylidene) (FDDNP) is used for the noninvasive brain imaging of amyloid-β (Aβ) and other amyloid aggregates present in Alzheimer’s disease and other neurodegenerative diseases. A series of FDDNP analogs has been synthesized and characterized using spectroscopic and computational methods. The binding affinities of these molecules have been measured experimentally and explained through the use of a computational model. The analogs were created by systematically modifying the donor and the acceptor sides of FDDNP to learn the structural requirements for optimal binding to Aβ aggregates. FDDNP and its analogs are neutral, environmentally sensitive, fluorescent molecules with high dipole moments, as evidenced by their spectroscopic properties and dipole moment calculations. The preferred solution-state conformation of these compounds is directly related to the binding affinities. The extreme cases were a nonplanar analog t-butyl-FDDNP, which shows low binding affinity for Aβ aggregates (520 nM K_i) in vitro and a nearly planar tricyclic analog cDDNP, which displayed the highest binding affinity (10 pM K_i). Using a previously published X-ray crystallographic model of 1,1-dicyano-2-[6-(dimethylamino)naphthalen-2-yl]propene (DDNP) bound to an amyloidogenic Aβ peptide model, we show that the binding affinity is inversely related to the distortion energy necessary to avoid steric clashes along the internal surface of the binding channel.     

Should dentists be concerned about the weight of their patients?

This opinion paper considers obesity and its relationship to dental practice. Twenty-three per cent of people in England are estimated to be obese, a figure that is predicted to continue rising. It follows that obese patients are frequently encountered in general dental practice. The authors review the links between obesity and dental health, the possible barriers and challenges to providing dental care for obese people, and how these may be overcome. They also report the findings of a London survey investigating the current provision of specialist dental services for obese patients who cannot be treated in a standard dental chair. Services across London were highly variable and in some areas no provision was identified. The implications of the rising prevalence of obesity for service planners and practitioners are also discussed.