Does spaced education improve clinical knowledge among Family Medicine residents? A cluster randomized controlled trial

Advances in Health Sciences Education - Spaced education is a learning strategy to improve knowledge acquisition and retention. To date, no robust evidence exists to support the utility of spaced...     

Cost-effectiveness of using hepatitis C viremic hearts for transplantation into HCV-negative recipients

Outcomes following hepatitis C virus (HCV)-viremic heart transplantation into HCV-negative recipients with HCV treatment are good. We assessed cost-effectiveness between cohorts of transplant recipients willing and unwilling to receive HCV-viremic hearts. Markov model simulated long-term outcomes among HCV-negative patients on the transplant waitlist. We compared costs (2018 USD) and health outcomes (quality-adjusted life-years, QALYs) between cohorts willing to accept any heart and those willing to accept only HCV-negative hearts. We assumed 4.9% HCV-viremic donor prevalence. Patients receiving HCV-viremic hearts were treated, assuming $39 600/treatment with 95% cure. Incremental cost-effectiveness ratios (ICERs) were compared to a $100 000/QALY gained willingness-to-pay threshold. Sensitivity analyses included stratification by blood type or region and potential negative consequences of receipt of HCV-viremic hearts. Compared to accepting only HCV-negative hearts, accepting any heart gained 0.14 life-years and 0.11 QALYs, while increasing costs by $9418/patient. Accepting any heart was cost effective (ICER $85 602/QALY gained). Results were robust to all transplant regions and blood types, except type AB. Accepting any heart remained cost effective provided posttransplant mortality and costs among those receiving HCV-viremic hearts were not >7% higher compared to HCV-negative hearts. Willingness to accept HCV-viremic hearts for transplantation into HCV-negative recipients is cost effective and improves clinical outcomes.     

Misoprostol Partially Inhibits the Renal Scarring of Chronic Cyclosporine Nephrotoxicity

Chronic cyclosporine (CY) nephrotoxicity is a well-known complication of this immunosuppressive agent, which may, in part, be attributed to abnormalities in renal prostaglandin content. We utilized misoprostol (M), a prostaglandin E(1) analog, in a rat model of chronic CY toxicity at 7 and 28 days to determine effectiveness in prevention of the renal damage. After 7 days, there were no differences in weight change, creatinine clearance, or renal scarring in rats treated with vehicle (V), CY, or CY + M; however, renal procollagen alpha 1(I) mRNA levels were increased in CY versus V rats (p < 0.05). In contrast, after 28 days CY rats had significant reductions in weight gain, glomerular filtration rate, and renal blood flow with increases in renal scarring and procollagen alpha 1 (IV) mRNA levels (all p < 0.05 versus V). Addition of M resulted in partial but significant improvement in GFR, RBF, and procollagen alpha 1(IV) mRNA levels, with lessening of the renal scarring. Skin fibroblasts also were incubated with CY and M to assess impact on procollagen MRNA levels. CY augmented fibroblast procollagen mRNA levels which enhanced by a large dose of M, but inhibited with a moderate dose. These data suggest that M improves renal scarring induced by CY by hemodynamic and/or direct effects.     

Medicare beneficiaries rate their medical care: new data from the MCBS (Medicare Current Beneficiary Survey)

The Medicare Current Beneficiary Survey (MCBS) contains a wealth of information about the people whose care is financed by the program. This article examines their satisfaction with medical care received and explores the relationship of these attitudes with the characteristics of subgroups of the enrolled population. Satisfaction with medical care among Medicare beneficiaries is found to be generally high (80-90 percent). Disabled Medicare beneficiaries are less satisfied than the aged, and health maintenance organization (HMO) enrollees less satisfied than fee-for-service (FFS) patients. Others with lower-than-average satisfaction are people with poorer health status, those covered by Medicaid, and those without supplementary insurance.     

Evaluation of soft-tissue masses using segmented color Doppler velocity images: preliminary observations

OBJECTIVE: We report our initial experience with segmented color Doppler velocity-based estimates of tumor vascularity for various histogically proven soft-tissue masses. SUBJECTS AND METHODS: Color Doppler sonography of 23 histologically proven masses in 22 patients was performed. Digital color Doppler images were acquired directly off the scanner output or from video recordings and stored on a personal computer as 24-bit gray-scale and color composite images. A color Doppler velocity segmentation and analysis algorithm was applied to the digital images, from which we calculated the normalized percentage of color Doppler area. Normalization was determined by expressing color Doppler area as a percentage of the area enclosed by a preselected region of interest. We also calculated mean percentage, SD, and cumulative distribution of color Doppler area, relative to a fixed threshold, for the acquired image data sets. RESULTS: Estimates of mean percentage of color Doppler area showed a dynamic range of at least two or three orders of magnitude between lowest and highest values obtained. A scatterplot of mean percentage of color Doppler area versus SD of percentage of color Doppler area showed a linear monotonic relationship (r2 = .92), illustrating increasing vascular heterogeneity with mean vascularity. Preliminary data also suggest the presence of at least two distinct groups of masses (p < .0001) based on these vascularity estimates. One group corresponds to high-grade lesions in which tumor angiogenesis is expected to be important in predicting biologic behavior. The second group appeared to have little or no relationship to tumor vascularity or was of an intermediate (or lower) histologic grade. CONCLUSION: Quantitative color Doppler estimates of tumor vascularity can be obtained over a wide dynamic range. Such estimates provide a mechanism to assess vascular heterogeneity of soft-tissue tumors. Preliminary data suggest that two biologically distinct groups of masses may be separable on the basis of quantitative velocity-based estimates of tumor vascularity as obtained from color Doppler sonography.     

Multiple single units and population responses during inhibitory gating of hippocampal auditory response in freely-moving rats

Paired clicks were presented to awake, freely-moving rats to examine neuronal activity associated with inhibitory gating of responses to repeated auditory stimuli. The rats had bundles of eight microwires implanted into each of four different brain areas: CA3 region of the hippocampus, medial septal nucleus, brainstem reticular nucleus, and the auditory cortex. Single-unit recordings from each wire were made while the local auditory-evoked potential was also recorded. The response to a conditioning stimulus was compared to the response to a test stimulus delivered 500 ms later: the ratio of the test response to the conditioning response provided a measure of inhibitory gating. Auditory-evoked potentials were recorded at all sites. Overall, brainstem reticular nucleus neurons showed the greatest gating of local auditory-evoked potentials, while the auditory cortex showed the least. However, except for the auditory cortex, both gating and non-gating of the evoked response were recorded at various times in all brain regions. Gating of the hippocampal response was significantly correlated with gating in the medial septal nucleus and brainstem reticular nucleus, but not the auditory cortex. Single-unit neuron firing in response to the clicks was most pronounced in the brainstem reticular nucleus and the medial septal nucleus, while relatively few neurons responded in the CA3 region of the hippocampus and the auditory cortex. Taken together, these data support the hypothesis that inhibitory gating of the auditory-evoked response originates in the non-lemniscal pathway and not in cortical areas of the rat brain.     

A pilot study on the motor effects of rimantadine in Parkinson's disease

The purpose of this pilot study was to determine whether rimantadine, the alpha-methyl derivative of amantadine, might have any antiparkinsonian properties. In an open-label trial, 14 patients (12 de novo and 2 on levodopa treatment) with Hoehn and Yahr stage 2 to 3 Parkinson's disease were placed on rimantadine at doses of 100 to 300 mg/d. No patients had dyskinesias or motor fluctuations. Ten of 14 (71%) reported a mean subjective response of 33% (range 10%-60%) to rimantadine. After treatment, there was a 13% improvement in Hoehn and Yahr staging (p = .01) and a 20% improvement in mean motor Unified Parkinsons Disease Rating Scale scores (p = .02). Rigidity was the most consistently improved feature among the responders. Mean effective dose was 256 mg/d (range 200-300 mg/d). Side effects were mild and transient, with nausea being most common (4/14). We conclude that rimantadine has some motor benefits in Parkinson's disease. A double-blind placebo-controlled study is warranted to validate our findings.     

Pharmacology of A-216546: a highly selective antagonist for endothelin ET(A) receptor

Endothelins, 21-amino acid peptides involved in the pathogenesis of various diseases, bind to endothelin ET(A) and ET(B) receptors to initiate their effects. Here, we characterize the pharmacology of A-216546 ([2S-(2,2-dimethylpentyl)-4S-(7-methoxy-1,3-benzodioxol-5-yl )-1-(N,N-di(n-butyl) aminocarbonylmethyl)-pyrrolidine-3R-carboxylic acid), a potent antagonist with > 25,000-fold selectivity for the endothelin ET(A) receptor. A-216546 inhibited [125I]endothelin-1 binding to cloned human endothelin ET(A) and ET(B) receptors competitively with Ki of 0.46 and 13,000 nM, and blocked endothelin-1-induced arachidonic acid release and phosphatidylinositol hydrolysis with IC50 of 0.59 and 3 nM, respectively. In isolated vessels, A-216546 inhibited endothelin ET(A) receptor-mediated endothelin-1-induced vasoconstriction, and endothelin ET(B) receptor-mediated sarafotoxin 6c-induced vasoconstriction with pA2 of 8.29 and 4.57, respectively. A-216546 was orally available in rat, dog and monkey. In vivo, A-216546 dose-dependently blocked endothelin-1-induced pressor response in conscious rats. Maximal inhibition remained constant for at least 8 h after dosing. In conclusion, A-216546 is a potent, highly endothelin ET(A) receptor-selective and orally available antagonist, and will be useful for treating endothelin-1-mediated diseases.