Lung function impairment and risk of incident heart failure: the NHLBI Pooled Cohorts Study.

AIMS: The aim is to evaluate associations of lung function impairment with risk of incident heart failure (HF). METHODS AND RESULTS: Data were pooled across eight US population-based cohorts that enrolled participants from 1987 to 2004. Participants with self-reported baseline cardiovascular disease were excluded. Spirometry was used to define obstructive [forced expiratory volume in 1 s/forced vital capacity (FEV1/FVC) <0.70] or restrictive (FEV1/FVC ≥0.70, FVC <80%) lung physiology. The incident HF was defined as hospitalization or death caused by HF. In a sub-set, HF events were sub-classified as HF with reduced ejection fraction (HFrEF; EF <50%) or preserved EF (HFpEF; EF ≥50%). The Fine-Gray proportional sub-distribution hazards models were adjusted for sociodemographic factors, smoking, and cardiovascular risk factors. In models of incident HF sub-types, HFrEF, HFpEF, and non-HF mortality were treated as competing risks. Among 31 677 adults, there were 3344 incident HF events over a median follow-up of 21.0 years. Of 2066 classifiable HF events, 1030 were classified as HFrEF and 1036 as HFpEF. Obstructive [adjusted hazard ratio (HR) 1.17, 95% confidence interval (CI) 1.07-1.27] and restrictive physiology (adjusted HR 1.43, 95% CI 1.27-1.62) were associated with incident HF. Obstructive and restrictive ventilatory defects were associated with HFpEF but not HFrEF. The magnitude of the association between restrictive physiology and HFpEF was similar to associations with hypertension, diabetes, and smoking. CONCLUSION: Lung function impairment was associated with increased risk of incident HF, and particularly incident HFpEF, independent of and to a similar extent as major known cardiovascular risk factors.

Associations between emphysema-like lung on CT and incident airflow limitation: a general population-based cohort study.

Emphysema on CT is associated with accelerated lung function decline in heavy smokers and patients with COPD; however, in the general population, it is not known whether greater emphysema-like lung on CT is associated with incident COPD. We used data from 2045 adult participants without initial prebronchodilator airflow limitation, classified by FEV1/FVC<0.70, in the Multi-Ethnic Study of Atherosclerosis. Emphysema-like lung on baseline cardiac CT, defined as per cent low attenuation areas<-950HU>upper limit of normal, was associated with increased odds of incident airflow limitation at 5-year follow-up on both prebronchodilator (adjusted OR 2.62, 95% CI 1.47 to 4.67) and postbronchodilator (adjusted OR 4.38, 95% CI 1.63 to 11.74) spirometry, independent of smoking history. These results support investigation into whether emphysema-like lung could be informative for COPD risk stratification.

Contextualizing the first-round failure of the AHCA: down but not out.

On 8 November 2016 the American electorate voted Donald Trump into the Presidency and a majority of Republicans into both houses of Congress. Since many Republicans ran for elected office on the promise to 'repeal and replace' Obamacare, this election result came with an expectation that campaign rhetoric would result in legislative action on healthcare. The American Health Care Act (AHCA) represented the Republican effort to repeal and replace the Affordable Care Act (ACA). Key elements of the AHCA included modifications of Medicaid expansion, repeal of the individual mandate, replacement of ACA subsidies with tax credits, and a broadening of the opportunity to use healthcare savings accounts. Details of the bill and the political issues which ultimately impeded its passage are discussed here.

The Burwell roadmap.

In January 2015 the current Secretary of the Department of Health and Human Services (HHS) outlined a bold initiative to shape the delivery of healthcare through a set of strategies aimed at improving the quality of care and reducing the growth of healthcare costs. The strategies include increasing payment incentives tied to higher value care, increasing care coordination and integration, and increasing access to information to guide patients and clinicians. Significantly, the proposal includes specific goals for alternative payment models and value-based payments for the first time in the history of the Medicare program.

The Bundled Payments for Care Improvement Initiative.

The Affordable Care Act enters its fifth year firmly entrenched in our national consciousness. One method that has entered the vernacular for achieving cost savings is accountable care. There are other approaches that are less well known. The Bundled Payments for Care Improvement Initiative has the potential to significantly impact neurointerventionalists. We review that initiative here.

MACRA: background, opportunities and challenges for the neurointerventional specialist.

The legislative branch of government took many by surprise when it announced the Medicare Access and CHIP Reauthorization Act of 2015. Once the Act was passed, President Obama quickly signed this bipartisan, bicameral effort into law. A foundational element of this legislation was the permanent repeal of the sustainable growth rate formula. Physicians and their patients were appropriately enthusiastic about this development. The Medicare Access and CHIP Reauthorization Act of 2015 included additional elements of considerable interest to neurointerventional specialists.

Current procedural terminology; a primer.

In 1966, The American Medical Association (AMA) working with multiple major medical specialty societies developed an iterative coding system for describing medical procedures and services using uniform language, the Current Procedural Terminology (CPT) system. The current code set, CPT IV, forms the basis of reporting most of the services performed by healthcare providers, physicians and non-physicians as well as facilities allowing effective, reliable communication among physician and other providers, third parties and patients. This coding system and its maintenance has evolved significantly since its inception, and now goes well beyond its readily perceived role in reimbursement. Additional roles include administrative management, tracking new and investigational procedures, and evolving aspects of 'pay for performance'. The system also allows for local, regional and national utilization comparisons for medical education and research. Neurointerventional specialists use CPT category I codes regularly--for example, 36,215 for first-order cerebrovascular angiography, 36,216 for second-order vessels, and 37,184 for acute stroke treatment by mechanical means. Additionally, physicians add relevant modifiers to the CPT codes, such as '-26' to indicate 'professional charge only,' or '-59' to indicate a distinct procedural service performed on the same day.

Diagnostic carotid and cerebral angiography: a historical summary of the evolving changes in coding and reimbursement in a complex procedure family.

Carotid and cerebral angiography have been a mainstay of neurointerventional and neuroradiologic practice for years. Centers for Medicare and Medicaid Services (CMS) and Relative Value Scale Update Committee (RUC) initiatives have compelled the professional societies to bundle component codes under threat of unilateral CMS revision and revaluation. Code bundling usually results in a decrease in the professional Relative Value Unit (RVU) valuation, and thus the MD reimbursement. The year 2013 saw a dramatic revision to the Current Procedural Terminology (CPT) code set that defines carotid and cerebral procedures. This paper reviews the process that led to that code set being revised and estimates the impact on professional reimbursement. We show the current and previous carotid angiography CPT codes and use clinical examples to assess professional RVU valuation before and after code revision.

Affordable care 2014: a tale of two boards.

The Patient Protection and Affordable Care Act (ACA) became law on 23 March 2010. As part of the law, two independent boards were established. The Patient-Centered Outcomes Research Institute embodies national aspirations for employing comparative effectiveness research in healthcare decision-making, and the Independent Payment Advisory Board is focused on the need for a group of impartial experts to establish anticipatable growth rates for Medicare. Approximately 4 years after the bill was passed into law, these independent boards are at very different points in their life cycles. This article provides a status update.

The RUC: a primer for neurointerventionalists.

The Relative Value Scale Update Committee (RUC) plays a critical role in determining physician payment. When the Centers for Medicare and Medicaid Services (CMS) transitioned to paying physicians based on the Resource-Based Relative Value Scale, the American Medical Association developed this unique multispecialty committee. Physicians at the RUC determine the resources required to provide physician services and recommend appropriate payment for those services. The RUC then submits its recommendations to CMS. Physicians have thus been important in determining relative value and hence payment for the services they provide.

LLY-2707, a novel nonsteroidal glucocorticoid antagonist that reduces atypical antipsychotic-associated weight gain in rats.

Weight gain and diabetes have been reported during treatment with atypical antipsychotic drugs (AAPDs). Patients treated with the glucocorticoid receptor antagonist (GRA) and the progesterone receptor antagonist (PRA) mifepristone [estra-4,9-dien-3-one, 11-[4-(dimethylamino)phenyl]-17-hydroxy-17-(1-propynyl)-(11ß,17ß)-(9CI)] experienced significant reduction in the weight gain observed when patients were treated with olanzapine or risperidone. To understand the pharmacology responsible for this finding, we discovered LLY-2707 [N-(5-(tert-butyl)-3-(2-fluoro-5-methylpyridin-4-yl)-2-methyl-1H-indol-7-yl)methanesulfonamide], a novel and selective GRA, and evaluated its utility in preclinical models of AAPD-associated weight gain and diabetes. In vitro, LLY-2707 was a highly selective and potent GRA. GR occupancy in vivo was assessed using ex vivo binding where LLY-2707 inhibited [(3)H]dexamethasone binding to the liver. Modest but statistically significant decreases in brain ex vivo binding were observed with high doses of CORT-108297 [(R)-4α-(ethoxymethyl)-1-(4-fluorophenyl)-6-((4-(trifluoromethyl)phenyl)sulfonyl)-4,4a,5,6,7,8-hexahydro-1H-pyrazolo[3,4-g]isoquinoline] and LLY-2707, but mifepristone inhibited at all doses. Central activity of the GRAs was confirmed by their ability to suppress amphetamine-induced increases in locomotor activity. The increases in the body weight of female rats treated with olanzapine (2 mg/kg PO) over 14 days were reduced in a dose-dependent manner by coadministration of LLY-2707. Similar decreases, although less robust, in body weight were seen with mifepristone and CORT-108297. In addition, sGRAs prevented the glucose excursion after intragastric olanzapine infusions consistent with a direct effect on the hyperglycemia observed during treatment with AAPDs. At doses effectively preventing weight gain, LLY-2707 did not substantially interfere with the dopamine D2 receptor occupancy by olanzapine. Therefore, GRA coadministration may provide a novel treatment modality to prevent the weight gain and diabetes observed during treatment with AAPDs.

Professional efficiencies for diagnostic imaging services rendered by different physicians: analysis of recent medicare multiple procedure payment reduction policy.

PURPOSE: The aim of this study was to quantify potential physician work efficiencies and appropriate multiple procedure payment reductions for different same-session diagnostic imaging studies interpreted by different physicians in the same group practice. METHODS: Medicare Resource-Based Relative Value Scale data were analyzed to determine the relative contributions of various preservice, intraservice, and postservice physician diagnostic imaging work activities. An expert panel quantified potential duplications in professional work activities when separate examinations were performed during the same session by different physicians within the same group practice. Maximum potential work duplications for various imaging modalities were calculated and compared with those used as the basis of CMS payment policy. RESULTS: No potential intraservice work duplication was identified when different examination interpretations were rendered by different physicians in the same group practice. When multiple interpretations within the same modality were rendered by different physicians, maximum potential duplicated preservice and postservice activities ranged from 5% (radiography, fluoroscopy, and nuclear medicine) to 13.6% (CT). Maximum mean potential duplicated work relative value units ranged from 0.0049 (radiography and fluoroscopy) to 0.0413 (CT). This equates to overall potential total work reductions ranging from 1.39% (nuclear medicine) to 2.73% (CT). Across all modalities, this corresponds to maximum Medicare professional component physician fee reductions of 1.23 ± 0.38% (range, 0.95%-1.87%) for services within the same modality, much less than an order of magnitude smaller than those implemented by CMS. For services from different modalities, potential duplications were too small to quantify. CONCLUSIONS: Although potential efficiencies exist in physician preservice and postservice work when same-session, same-modality imaging services are rendered by different physicians in the same group practice, these are relatively minuscule and have been grossly overestimated by current CMS payment policy. Greater transparency and methodologic rigor in government payment policy development are warranted.

Physician payment outlook for 2012.

Physician spending is complex and intrinsically related to national health care spending, government regulations, health care reform, private insurers, physician practice and patient utilization patterns. Consequently, since the inception of Medicare programs in 1965, several methods have been used to determine the amounts paid to physicians for each covered service. The sustainable growth rate (SGR) was enacted in 1997 to determine physician payment updates under Medicare part B with an intent to reduce Medicare physician payment updates to offset the growth and utilization of physician services that exceeds the gross domestic product growth. This is achieved by setting an overall target amount of spending for physicians' services and adjusting payment rates annually to reflect differences between actual spending and the spending target. Since 2002, the SGR has annually recommended reductions in Medicare reimbursements. Payments were cut by 4.8% in 2002. Since then, Congress has intervened on 13 separate occasions to prevent additional cuts from being imposed. This manuscript describes certain important aspects of the 2012 physician fee schedule.

Prediction of the tissue-specificity of selective estrogen receptor modulators by using a single biochemical method.

Here, we demonstrate that a single biochemical assay is able to predict the tissue-selective pharmacology of an array of selective estrogen receptor modulators (SERMs). We describe an approach to classify estrogen receptor (ER) modulators based on dynamics of the receptor-ligand complex as probed with hydrogen/deuterium exchange (HDX) mass spectrometry. Differential HDX mapping coupled with cluster and discriminate analysis effectively predicted tissue-selective function in most, but not all, cases tested. We demonstrate that analysis of dynamics of the receptor-ligand complex facilitates binning of ER modulators into distinct groups based on structural dynamics. Importantly, we were able to differentiate small structural changes within ER ligands of the same chemotype. In addition, HDX revealed differentially stabilized regions within the ligand-binding pocket that may contribute to the different pharmacology phenotypes of the compounds independent of helix 12 positioning. In summary, HDX provides a sensitive and rapid approach to classify modulators of the estrogen receptor that correlates with their pharmacological profile.

Resultados preliminares da artroplastia do quadril metal-metal de superfície: análise dos primeiros 40 casos com seguimento médio de 3 anos / Preliminary outcomes of hip metal-on-metal resurfacing arthroplasty: an analysis of the first 40 cases with mean follow-up time of 3 years

Quarenta quadris (39 pacientes) foram submetidos à artroplastia total metal-metal de superficie "resurfacing" entre 2002 e 2005. Todos foram estudados e analisados clinicamente e radiograficamente. Foram utilizados critérios clínicos, no pré e pós-operatório, pela avaliação de D'Aubigné e Postel. Radiograficamente, as áreas de radiolucência ao redor do acetábulo foram classificadas de acordo com DeLee e Charnley e, no fêmur nas zonas descritas por Amstutz et al. A idade média foi de 54,40 anos. O seguimento mínimo foi de 14 meses e o máximo de 51(média de 37,36 meses). 94,44 por cento dos resultados clínicos foram satisfatórios no pós-operatório. Ocorreram 2 casos de soltura asséptica. Não houve fratura do fêmur durante o seguimento. Os autores consideraram esta opção técnica e de implante satisfatória e, com bons resultados no seguimento médio de 3 anos.

Forty hips (39 patients) were submitted to metal-on-metal hip replacement (resurfacing) between 2002 and 2005. Evaluation was provided by clinical examination and X-ray tests. The authors performed clinical evaluations before and after surgery. The specific criterion applied was the D'Aubigné and Postel's classification. X-ray images showed radiolucent lines around the acetabular component on the zones described by DeLee and Charnley and around the femoral component on the zones described by Amstutz et al. The mean age was 54.40 years. The minimum follow-up period was 14 months (range:12 to 51 months). The outcomes of 94.44 percent of the patients in the study were postoperatively rated as satisfactory. There were 2 cases of aseptic loose and no neck-femoral fractures during the follow-up period. The authors concluded that this technique and implant alternative is satisfactory, with good early outcomes in a mean follow-up time of three years.

A randomised comparison of melphalan with prednisone or dexamethasone as induction therapy and dexamethasone or observation as maintenance therapy in multiple myeloma: NCIC CTG MY.7.

The effectiveness of melphalan plus dexamethasone (M-Dex) with melphalan plus prednisone (MP) as induction therapy and dexamethasone with observation as maintenance therapy was compared in 585 older patients with multiple myeloma. Randomization to the M-Dex arm was stopped as a result of an analysis performed which met a predetermined event-related criterion. Of 466 patients randomised to MP or M-Dex, no differences were detected in the respective median progression-free survivals (PFS) [1.8 vs. 1.9 years; Hazard Ratio (HR) = 0.88, 95% CI 0.72-1.07; P = 0.2] or overall survivals (OS) (2.5 vs. 2.7 years; HR = 0.91, 95% CI 0.74-1.11; P = 0.3). Of the initial 585 patients, 292 remained evaluable for maintenance therapy. Patients randomised to maintenance dexamethasone had a superior median PFS (2.8 years vs. 2.1 years; HR = 0.61, 95% CI 0.47-0.79; P = 0.0002). No difference in median OS was detected (4.1 years vs. 3.8 years; HR = 0.88, 95% CI 0.65-1.18; P = 0.4). The maintenance therapy results were robust when analysed by using two additional methodologies. Dexamethasone did not improve clinical outcome when combined with melphalan during induction; maintenance dexamethasone improved PFS, but this did not translate into a detectable survival advantage.

Benzopyrans are selective estrogen receptor beta agonists with novel activity in models of benign prostatic hyperplasia.

Benzopyran selective estrogen receptor beta agonist-1 (SERBA-1) shows potent, selective binding and agonist function in estrogen receptor beta (ERbeta) in vitro assays. X-ray crystal structures of SERBA-1 in ERalpha and beta help explain observed beta-selectivity of this ligand. SERBA-1 in vivo demonstrates involution of the ventral prostate in CD-1 mice (ERbeta effect), while having no effect on gonadal hormone levels (ERalpha effect) at 10x the efficacious dose, consistent with in vitro properties of this molecule.

Bilateral disk edema with unilateral macular serous fluid secondary to neurocysticercosis.

PURPOSE: The purpose of this article is to document a case of neurocysticercosis that manifested clinically with bilateral disk edema and serous fluid accumulation in the macula of the left eye. We also describe the recovery of visual-field loss (O.D.) and diminution of bilateral disk edema following anti-helminthic treatment. CASE REPORT: A 41-year-old woman reporting headaches came to us with bilateral disk edema and co-existing serous macular fluid in the left eye. RESULTS: Magnetic resonance imaging (MRI) revealed the presence of large multi-septated cysts that exhibited peripheral enhancement, with minimal surrounding edema at the posterior left temporal lobe. Scattered punctate lesions, suggesting areas of calcification, were also observed within both temporal lobes. The optic chiasm appeared compressed. This presentation was considered characteristic of neurocysticercosis and the patient was prescribed a regimen of 200mg albendazole b.i.d. The patient responded well to the treatment, with progressive resolution of the bilateral disk edema and macular fluid. CONCLUSION: Although rare, cases of cysticercosis and neurocysticercosis may still be encountered in industrialized nations, where the parasite has been almost eradicated. Ocular signs of disk edema and macular serous fluid secondary to neurocysticercosis may correspond to optic nerve, parenchymal, or extraparenchymal disease.

The hypolipidemic natural product guggulsterone is a promiscuous steroid receptor ligand.

Guggulsterone (GS) is the active substance in guggulipid, an extract of the guggul tree, Commiphora mukul, used to treat a variety of disorders in humans, including dyslipidemia, obesity, and inflammation. The activity of GS has been suggested to be mediated by antagonism of the receptor for bile acids, the farnesoid X receptor (FXR). Here, we demonstrate that both stereoisomers of the plant sterol, (E)- and (Z)-GS, bind to the steroid receptors at a much higher affinity than to FXR. Both stereoisomers bind to the mineralocorticoid receptor (MR) with a Ki value of approximately 35 nM, which is greater than 100 times more potent than their affinity for FXR. Both (E)- and (Z)-GS also displayed high affinity for other steroid receptors, including the androgen (AR), glucocorticoid (GR), and progesterone receptors (PR) with Ki values ranging from 224 to 315 nM. In cell-based functional cotransfection assays, GSs behaved as antagonists of AR, GR, and MR, but as agonists of PR. Agonist activity was also demonstrated with estrogen receptor (ER) alpha; however, the potency was very low (EC50 > 5000 nM). In addition, GS displayed activity in functional assays in cell lines expressing endogenous AR, GR, ER, and PR. These data suggest that the variety of pharmacological effects exhibited by GS may be mediated by targeting several steroid receptors.