Free-for benefit: A stragety to improve the quality of health care and control costs through reimbursement incentives

AbstractObjectives. The purpose of this study was to determine whether reimbursement in direct proportion to expected therapeutic benefit is capable of improving the utilization and cost of health care.Background. The benefit associated with a particular medical or surgical treatment varies widely from patient to patient. Nevertheless, payment to the provider of the treatment is essentially invariant under the current fee-for-service system. Under an alternative fee-for-benefit strategy, empiric data are used to construct a multivariable model to predict the exprcted benefit to an individual patient from a particular health care service on the basis of conventional clinical descriptors. The payers and the providers of the service then openly negotiate an explicit economic relation between expected benefit and monetary payment such that payment is directly proportional to benefit.Methods. Computer simulations were performed to determine the potential impact of this fee-for-benefit strategy with respect to medical versus surgical treatment of coronary artery disease.Results. Compared with conventional fee-for-service, fee-for-benefit resulted in a 12% improvement in patient benefit (quality-adjusted survival), a 22% reduction in provider payments and a 55% increase in cost/benefit (the ratio of benefit to payment).Conclusions. The incentives embodied in a fee-for-benefit strategy can be an effective mechanism for encouraging more appropriate health care utilization while simultaneously controlling health care costs

Statins in Acute Coronary Syndromes Do the Guideline Recommendations Match the Evidence?

On the basis of the evidence obtained from observational studies, randomized controlled trials and their meta-analyses, current guidelines recommend initiating high-dose statin therapy pre-discharge regardless of the baseline low-density lipoprotein (LDL) level in patients with acute coronary syndromes (ACS). Careful review of the evidence indicates that early initiation of high-dose statin therapy reduces recurrent ischemia and may reduce revascularization, but does not confer benefit in terms of hard clinical outcomes such as death or myocardial infarction in any of the randomized controlled trials, and may be associated with increased liver and muscle-related adverse outcomes leading to increased withdrawal and suboptimal long-term adherence. A mortality benefit is apparent in pooled analyses of randomized controlled trials only at long-term (24-month) but not short-term (4-month) follow-up. The critical role of the timing of initiation of therapy (early vs. late) on the benefit-risk profile of statin treatment has not been systematically assessed. It is unclear whether the clinical benefits are attributable to lipid-lowering or lipid-lowering–independent effects. Finally, an optimal LDL threshold for initiating treatment or target LDL level for treatment in ACS remains yet to be defined. On the basis of these observations, and despite a compelling pathophysiologic rationale, the justification for current Class I, Level of Evidence: A recommendation for statin therapy in patients with ACS remains open to question

780-3 Does Estrogen Reduce the Accuracy of Exercise Electrocardiography in Women?

It has been suggested that estrogen has a role in the genesis of false positive exercise electrocardiograms in women. We evaluated 1007 men and 832 women with suspected coronary artery disease concerning the accuracy of exercise electrocardiography. Women were grouped according to estrogen status (ES): ES- = postmenopausal and not on estrogen replacement and ES+ = premenopausal (Premen) or on estrogen replacement. Positive exercise ST criteria were ≥1mm horizontal/downsloping or ≥1.5 mm upsloping depression.ResultsOverall accuracy: sensitivity 44% and specificity 87%; receiver operating characteristic curve (ROC) area 76±3. The following table compares the accuracy of men and subgroups of women.NumberSensitivitySpecificityROC AreaMen100752±791±284±3Women83234±782±2*64±6*ES-31735±1279±5*61±9*ES+51515±1181±2*46±15*Premen25972±4091±5**90±14†*p<0.01 vs Men**p=0.05 vs ES+ or ES-†p<005 vs Women, ES+, or ESThe heart rate-pressure products for Men (26,600±600) and Premen (26,500±500) were the same (p=0.58).ConclusionConcerning exercise electrocardiography, both ES+ and ES- women have lower accuracy than men. However, Premen women (a subgroup of ES+) had exercise performance and accuracy similar to men, especially concerning specificity. These results suggest that not all ES+ women have the same accuracy and argue against a role for naturally occurring estrogen as an etiology for false positive results

Computer-assisted diagnosis in the noninvasive evaluation of patients with suspected coronary artery disease

A microcomputer program called CADENZA, which employs Bayes' theorem to analyze and report the results of various clinical descriptors and noninvasive tests relative to the diagnosis of coronary artery disease, was evaluated in 1,097 consecutive patients without previous myocardial infarction. With this program, each patient was characterized by a probability for coronary artery disease, based on Framingham risk factor analysis, symptom characterization, electrocardiographic stress testing, cardiokymography, cardiac fluoroscopy, thallium perfusion scintigraphy and technetium equilibrium-gated blood pool scintigraphy. A total of 11,808 probability estimates derived from various combinations of the available observations were analyzed: 2,180 in 170 patients undergoing coronary angiography and 9,628 in 969 patients who completed a 1 year follow-up for coronary events.The predicted probability of disease correlated linearly with observed angiographic prevalence in the 170 patients who subsequently had coronary angiography (prevalence = [0.001 ± 0.011] + [0.966 ± 0.019] x probability). The difference between probability and prevalence averaged 3.1%, and the magnitude of this correlation was not affected by the type or amount of data analyzed. The prevalence of multivessel disease in these patients increased as a monotonic function of disease probability. Below a probability of 25%, single vessel disease was slightly more common than multivessel disease. Above a probability of 75%, multivessel disease predominated. In the 969 patients followed up for 1 year from the date of testing, the incidence of cardiac death and nonfatal infarction increased as a cubic function of disease probability (from approximately 0 to 8% per year for each). Above a probability of 90%, however, the standard deviation for predicting these events was wide.These data indicate that Bayes' theorem in general— and CADENZA in particular—is an accurate, clinically applicable means for quantifying the prevalence of angiographic coronary artery disease, the risk of multivessel disease and the incidence of morbid coronary events in the year after testing

A first-in-human, randomized, controlled, subject- and reviewer-blinded multicenter study of Actamax™ Adhesion Barrier

Purpose: Post-surgical adhesions remain a significant concern following abdominopelvic surgery. This study was to assess safety, manageability and explore preliminary efficacy of applying a degradable hydrogel adhesion barrier to areas of surgical trauma following gynecologic laparoscopic abdominopelvic surgery. Methods: This first-in-human, prospective, randomized, multicenter, subject- and reviewer-blinded clinical study was conducted in 78 premenopausal women (18–46 years) wishing to maintain fertility and undergoing gynecologic laparoscopic abdominopelvic surgery with planned clinically indicated second-look laparoscopy (SLL) at 4–12 weeks. The first two patients of each surgeon received hydrogel, up to 30 mL sprayed over all sites of surgical trauma, and were assessed for safety and application only (n = 12). Subsequent subjects (n = 66) were randomized 1:1 to receive either hydrogel (Treatment, n = 35) or not (Control, n = 31); 63 completed the SLL. Results: No adverse event was assessed as serious, or possibly device related. None was severe or fatal. Adverse events were reported for 17 treated subjects (17/47, 36.2%) and 13 Controls (13/31, 41.9%). For 95.7% of treated subjects, surgeons found the device “easy” or “very easy” to use; in 54.5%, some residual material was evident at SLL. For 63 randomized subjects who completed the SLL, adjusted between-group difference in the change from baseline adhesion score demonstrated a 41.4% reduction for Treatment compared with Controls (p = 0.017), with a 49.5% reduction (p = 0.008) among myomectomy subjects (n = 34). Conclusion: Spray application of a degradable hydrogel adhesion barrier during gynecologic laparoscopic abdominopelvic surgery was performed easily and safely, without evidence of clinically significant adverse outcomes. Data suggest the hydrogel was effective in reducing postoperative adhesion development, particularly following myomectomy

Transcription profiling reveals potential mechanisms of dysbiosis in the oral microbiome of rhesus macaques with chronic untreated SIV infection.

A majority of individuals infected with human immunodeficiency virus (HIV) have inadequate access to antiretroviral therapy and ultimately develop debilitating oral infections that often correlate with disease progression. Due to the impracticalities of conducting host-microbe systems-based studies in HIV infected patients, we have evaluated the potential of simian immunodeficiency virus (SIV) infected rhesus macaques to serve as a non-human primate model for oral manifestations of HIV disease. We present the first description of the rhesus macaque oral microbiota and show that a mixture of human commensal bacteria and "macaque versions" of human commensals colonize the tongue dorsum and dental plaque. Our findings indicate that SIV infection results in chronic activation of antiviral and inflammatory responses in the tongue mucosa that may collectively lead to repression of epithelial development and impact the microbiome. In addition, we show that dysbiosis of the lingual microbiome in SIV infection is characterized by outgrowth of Gemella morbillorum that may result from impaired macrophage function. Finally, we provide evidence that the increased capacity of opportunistic pathogens (e.g. E. coli) to colonize the microbiome is associated with reduced production of antimicrobial peptides

Effective risk stratification using exercise myocardial perfusion SPECT in women: Gender-related differences in prognostic nuclear testing

AbstractObjectives. This study was designed to evaluate the incremental prognostic value over clinical and exercise variables of rest thallium-201/exercise technetium-99m sestamibi single-photon emission computed tomography (SPECT) in women compared with men and to determine whether this test can be used to effectively risk stratify patients of both genders.Background. To minimize the previously described gender-related bias in the evaluation of coronary artery disease in women, there is a need to identify a noninvasive testing strategy that is able to accurately and effectively risk stratify women.Methods. We identified 4,136 consecutive patients (2,742 men, 1,394 women) who underwent dual-isotope SPECT. The incremental value of nuclear testing was determined using both a stepwise Cox proportional hazards model and Kaplan-Meier survival analysis. Receiver operating characteristic curve analysis was performed to determine test discrimination for high risk patients in men and women.Results. The patient population was followed up for 20 ± 5 months for events (cardiac death or nonfatal myocardial infarction). During this time, 63 myocardial infarctions and 32 cardiac deaths occurred in the men, and 31 myocardial infarctions and 14 cardiac deaths occurred in the women. Nuclear testing significantly stratified both men and women irrespective of their rest electrocardiogram. Cox proportional hazards analysis revealed that nuclear testing added incremental prognostic value in both men and women after inclusion of the most predictive clinical and exercise variables (overall chi-square 89 in men vs. 120 in women, p < 0.005). Kaplan-Meier survival analysis demonstrated that nuclear testing further stratified men and women with both intermediate to high and low prescan likelihoods of coronary artery disease (p < 0.005 for all). Receiver operating characteristic curve analysis demonstrated superior discrimination for the nuclear scan results in identifying high risk women than men (area under the curve: 0.84 ± 0.03 vs. 0.71 ± 0.03 in men, p < 0.0005). The odds ratio comparing event rates in patients with abnormal versus those with normal scan results was greater in women than in men, suggesting superior stratification using nuclear testing in women.Conclusions. Dual-isotope myocardial perfusion imaging yields incremental prognostic value in both men and women. This modality identifies low risk women and men equally well but relatively high risk women more accurately than relatively high risk men and, thus, is able to stratify women more effectively than men

A Powassan virus domain III nanoparticle immunogen elicits neutralizing and protective antibodies in mice

Powassan virus (POWV) is an emerging tick borne flavivirus (TBFV) that causes severe neuroinvasive disease. Currently, there are no approved treatments or vaccines to combat POWV infection. Here, we generated and characterized a nanoparticle immunogen displaying domain III (EDIII) of the POWV E glycoprotein. Immunization with POWV EDIII presented on nanoparticles resulted in significantly higher serum neutralizing titers against POWV than immunization with monomeric POWV EDIII. Furthermore, passive transfer of EDIII-reactive sera protected against POWV challenge in vivo. We isolated and characterized a panel of EDIII-specific monoclonal antibodies (mAbs) and identified several that potently inhibit POWV infection and engage distinct epitopes within the lateral ridge and C-C\u27 loop of the EDIII. By creating a subunit-based nanoparticle immunogen with vaccine potential that elicits antibodies with protective activity against POWV infection, our findings enhance our understanding of the molecular determinants of antibody-mediated neutralization of TBFVs

Mid-Infrared Properties of the Swift Burst Alert Telescope Active Galactic Nuclei Sample of the Local Universe. I. Emission-Line Diagnostics

We compare mid-infrared emission-line properties, from high-resolution Spitzer spectra of a hard X-ray (14 -- 195 keV) selected sample of nearby (z < 0.05) AGN detected by the Burst Alert Telescope (BAT) aboard Swift. The luminosity distribution for the mid-infrared emission-lines, [O IV] 25.89 micron, [Ne II] 12.81 micron, [Ne III] 15.56 micron and [Ne V] 14.32/24.32 micron, and hard X-ray continuum show no differences between Seyfert 1 and Seyfert 2 populations, however six newly discovered BAT AGNs are under-luminous in [O IV], most likely the result of dust extinction in the host galaxy. The overall tightness of the mid-infrared correlations and BAT fluxes and luminosities suggests that the emission lines primarily arise in gas ionized by the AGN. We also compare the mid-infrared emission-lines in the BAT AGNs with those from published studies of ULIRGs, PG QSOs, star-forming galaxies and LINERs. We find that the BAT AGN sample fall into a distinctive region when comparing the [Ne III]/[Ne II] and the [O IV]/[Ne III] ratios. These line ratios are lower in sources that have been previously classified in the mid-infrared/optical as AGN than those found for the BAT AGN, suggesting that, in our X-ray selected sample, the AGN represents the main contribution to the observed line emission. These ratios represent a new emission line diagnostic for distinguishing between AGN and star forming galaxies.Comment: 54 pages, 9 Figures. Accepted for publication in The Astrophysical Journal