Medicare Switching: Patterns Of Enrollment Growth In Medicare Advantage, 2006-22.

Medicare Advantage (MA) has grown rapidly over the course of the past two decades and is projected to continue to grow. We examined sources of new enrollment in MA and analyzed the switching patterns between MA and traditional fee-for-service Medicare, using more recent and more detailed data than in previous analyses. We found that switching from fee-for-service Medicare to MA more than tripled between 2006 and 2022, whereas switching from MA to fee-for-service Medicare decreased, with the change rates accelerating since 2019. The share of switchers among all new MA enrollees rose from 61 percent in 2011 to 80 percent in 2022. Black, dual-eligible, and disabled beneficiaries had higher odds of switching in both directions, whereas younger and healthier beneficiaries had higher odds of switching from fee-for-service Medicare to MA but lower odds of switching from MA to fee-for-service Medicare. Two-thirds of annual switching between MA and fee-for-service Medicare in 2022 occurred in January, likely reflecting the open enrollment period.

Endothelial prostaglandin D2 opposes angiotensin II contractions in mouse isolated perfused intracerebral microarterioles.

HYPOTHESIS: A lack of contraction of cerebral microarterioles to Ang II ("resilience") depends on cyclooxygenase (COX) and lipocalin type prostaglandin D sythase L-PGDS producing PGD2 that activates prostaglandin D type 1 receptors (DP1Rs) and nitric oxide synthase (NOS). MATERIALS & METHODS: Contractions were assessed in isolated, perfused vessels and NO by fluorescence microscopy. RESULTS: The mRNAs of penetrating intraparenchymal cerebral microarterioles versus renal afferent arterioles were >3000-fold greater for L-PGDS and DP1R and 5-fold for NOS III and COX 2. Larger cerebral arteries contracted with Ang II. However, cerebral microarterioles were entirely unresponsive but contracted with endothelin 1 and perfusion pressure. Ang II contractions were evoked in cerebral microarterioles from COX1 -/- mice or after blockade of COX2, L-PGDS or NOS and in deendothelialized vessels but effects of deendothelialization were lost during COX blockade. NO generation with Ang II depended on COX and also was increased by DP1R activation. CONCLUSION: The resilience of cerebral arterioles to Ang II contractions is specific for intraparenchymal microarterioles and depends on endothelial COX1 and two products that are metabolized by L-PGDS to generate PGD2 that signals via DP1Rs and NO.

Concentration of Physician Services Across Insurers and Effects on Quality: Early Evidence From Medicare Advantage.

BACKGROUND: A growing proportion of Medicare beneficiaries is covered by private insurers through Medicare Advantage, yet little is known about how these plans are structured in terms of relationships with physicians and implications for quality of care. OBJECTIVE: The objective of this study was to assess whether greater physician concentration of services across insurers was associated with higher quality in Medicare Advantage (MA), overall and particularly among MA insurers serving a high proportion of vulnerable enrollees. RESEARCH DESIGN: A retrospective cohort design with regression analysis. DATA SOURCES: The primary dataset was 2014 MA encounter records submitted by insurers to the Centers for Medicare and Medicaid Services, covering 600,329 physicians across 119 insurers. These data were merged with Centers for Medicare and Medicaid Services data on MA contract quality rating as well as physician characteristics in the Medicare Data on Provider Practice and Specialty file. MEASURES: Two measures were generated to capture the concentration of physician services across insurers: the percentage of a physician's Medicare services which was through MA (MA penetration); and the percentage of a physician's MA services with a specific insurer (insurer share of MA services). RESULTS: Greater MA penetration and insurer share of MA services were each associated with higher MA plan quality. The relationship between insurer share and quality was stronger in contracts with a relatively high percentage of disabled enrollees. CONCLUSION: Greater physician concentration of services across MA insurers was associated with a higher quality of care overall and especially among vulnerable enrollees.

Town and Gown Differences Among the 100 Largest Medical Groups in the United States.

PURPOSE: The authors undertook a study to determine whether large academic and community-based medical groups differ in terms of their financial stake in Medicare Advantage or Medicare Accountable Care Organizations (ACOs) and whether their participation in these alternative payment models is related to their size, specialty mix, and Medicare physician market share in their local area. METHOD: The authors used the 2013 Medicare Data on Provider Practice and Specialty database and a national database of ACOs to conduct a cross-sectional descriptive study of the 100 largest medical groups in the United States. Medical groups were categorized as academic or community based on matches of their name with a list of U.S. medical schools or the results of a series of Internet search procedures. RESULTS: Sixty-eight of the 100 largest groups were academic, and 32 were community based. On average, community-based groups had more than twice the percentage of primary care physicians as academic groups (mean, 38.4%; 95% CI, 34.7%-42.0%; vs. 18.3%; 95% CI, 17.0%-19.6%). Community groups were significantly (P < .001) more likely than academic groups to have a financial stake in a Medicare ACO or Medicare Advantage plan, but this difference was no longer significant when the percentage of primary care physicians in the group was added to the model. CONCLUSIONS: The specialty mix within academic medical groups may hinder their ability to transform themselves into organizations that can manage the financial responsibilities of caring for a patient population through a Medicare ACO or Medicare Advantage.

Congruent validity and reliability of two metabolic systems to measure resting metabolic rate.

Determine the congruent validity and intra- and inter-day reliability of RMR measures assessed by the ParvoMedics Trueone 2 400 hood dilution method (Parvo) and Cosmed K4b(2) (Cosmed) breath-by-breath metabolic systems. Participants underwent 6 RMR assessments over 2 consecutive mornings, 3 with the Parvo (Day 1: Parvo 1; Day 2: Parvo 2, 3), 3 with the Cosmed (Day 1: Cosmed 1; Day 2: Cosmed 2, 3). Measured VE, FEO(2), FECO(2), VO(2), VCO(2), kcal/day, and HR values were averaged over a minimum of 10 min. Intra- and inter-day reliability within each system was determined with RMANOVA, and congruent validity was assessed via paired sample t-tests.31 participants (13 females, 18 males; 27.3±7 years, 24.8±3.1 kg.m(2)) completed the study. There were no significant differences in any within or between day Parvo values or Cosmed values. When systems were compared, there was a significant difference between VE (Parvo2: 25.03 L/min, Cosmed2: 8.98 L/min) and FEO(2) (Parvo2: 19.68%, Cosmed2: 16.63%), however, there were no significant difference in device-calculated RMR (kcals/day).The Parvo and Cosmed are reliable metabolic system with no intra- or inter-day differences in RMR. Due to differences in measurement technology, FEO(2), V(E) were significantly different between systems, but the resultant RMR values were not significantly different.

Adenosine, type 1 receptors: role in proximal tubule Na+ reabsorption.

Adenosine type 1 receptor (A1 -AR) antagonists induce diuresis and natriuresis in experimental animals and humans. Much of this effect is due to inhibition of A1 -ARs in the proximal tubule, which is responsible for 60-70% of the reabsorption of filtered Na(+) and fluid. Intratubular application of receptor antagonists indicates that A1 -AR mediates a portion of Na(+) uptake in PT and PT cells, via multiple transport systems, including Na(+) /H(+) exchanger-3 (NHE3), Na(+) /PO4(-) co-transporter and Na(+) -dependent glucose transporter, SGLT. Renal microperfusion and recollection studies have shown that fluid reabsorption is reduced by A1 -AR antagonists and is lower in A1 -AR KO mice, compared to WT mice. Absolute proximal reabsorption (APR) measured by free-flow micropuncture is equivocal, with studies that show either lower APR or similar APR in A1 -AR KO mice, compared to WT mice. Inhibition of A1 -ARs lowers elevated blood pressure in models of salt-sensitive hypertension, partially due to their effects in the proximal tubule.

Measuring coding intensity in the Medicare Advantage program.

BACKGROUND: In 2004, Medicare implemented a system of paying Medicare Advantage (MA) plans that gave them greater incentive than fee-for-service (FFS) providers to report diagnoses. DATA: Risk scores for all Medicare beneficiaries 2004-2013 and Medicare Current Beneficiary Survey (MCBS) data, 2006-2011. MEASURES: Change in average risk score for all enrollees and for stayers (beneficiaries who were in either FFS or MA for two consecutive years). Prevalence rates by Hierarchical Condition Category (HCC). RESULTS: Each year the average MA risk score increased faster than the average FFS score. Using the risk adjustment model in place in 2004, the average MA score as a ratio of the average FFS score would have increased from 90% in 2004 to 109% in 2013. Using the model partially implemented in 2014, the ratio would have increased from 88% to 102%. The increase in relative MA scores appears to largely reflect changes in diagnostic coding, not real increases in the morbidity of MA enrollees. In survey-based data for 2006-2011, the MA-FFS ratio of risk scores remained roughly constant at 96%. Intensity of coding varies widely by contract, with some contracts coding very similarly to FFS and others coding much more intensely than the MA average. Underpinning this relative growth in scores is particularly rapid relative growth in a subset of HCCs. DISCUSSION: Medicare has taken significant steps to mitigate the effects of coding intensity in MA, including implementing a 3.4% coding intensity adjustment in 2010 and revising the risk adjustment model in 2013 and 2014. Given the continuous relative increase in the average MA risk score, further policy changes will likely be necessary.

Use of hospitalists by Medicare beneficiaries: a national picture.

OBJECTIVE: To describe the characteristics of hospitalists serving Medicare beneficiaries. DATA SOURCES: Medicare claims from 2009 and 2011 merged with the Provider Enrollment, Chain, and Ownership System file for physician characteristics. STUDY DESIGN: Our construction of the Medicare Data on Physician Practice and Specialty (MD-PPAS) enabled identification of hospitalists based on the attending physician for Medicare admissions (medical and surgical) in 2009 and 2011. PRINCIPAL FINDINGS: In 2011, hospitalists constituted 13.3% of physicians who designated their specialty as primary care and 4.4% of all physicians serving Medicare beneficiaries. Compared to other physicians, hospitalists were more likely to be female, under forty, and in large practices. More than a quarter of Medicare admissions had a hospitalist as the attending physician, though the rate was substantially higher for medical than surgical admissions (31.8% versus 11.3%). Between 2009 and 2011, the percentage of medical admissions with a hospitalist as the attending physician increased by roughly a quarter (from 25.7% to 31.8%). CONCLUSIONS: This analysis provides a more current and complete estimate of the use of hospitalists by the Medicare population than is available from prior studies. The ability to identify hospitalists from claims data will facilitate research on the impact of hospitalist use on quality and cost.

Proportion of physicians in large group practices continued to grow in 2009-11.

Payers and advocates for improved health care quality are raising expectations for greater care coordination and accountability for care delivery, and physician groups may be responding by becoming larger. We used Medicare claims from the period 2009-11, merged with information from the Medicare provider enrollment database, to measure whether physician group sizes have been increasing over time and in association with physician characteristics. All US physicians serving Medicare fee-for-service patients in any practice setting were included. The percentage of physicians in groups of more than fifty increased from 30.9 percent in 2009 to 35.6 percent in 2011. This shift occurred across all specialty categories, both sexes, and all age groups, although it was more prominent among physicians under age forty than those age sixty or older. The movement of physicians into groups is not a new phenomenon, but our data suggest that the groups are larger than surveys have previously indicated. Questions for future studies include whether there are significant cost savings or quality improvements associated with increased practice size.

C-terminal binding protein-2 regulates response of epithelial ovarian cancer cells to histone deacetylase inhibitors.

Ovarian cancer survival rates have stagnated in the last 20 years despite the development of novel chemotherapeutic agents. Modulators of gene expression, such as histone deacetylase (HDAC) inhibitors, are among the new agents being used in clinical trials. Predictors of sensitivity to chemotherapy have remained elusive. In this study, we show that the expression of the transcriptional corepressor C-terminal binding protein-2 (CtBP2) is elevated in human ovarian tumors. Downregulation of CtBP2 expression in ovarian cancer cell lines using short-hairpin RNA strategy suppressed the growth rate and migration of the resultant cancer cells. The knockdown cell lines also showed upregulation of HDAC activity and increased sensitivity to selected HDAC inhibitors. Conversely, forced expression of wild-type CtBP2 in the knockdown cell lines reversed HDAC activity and partially rescued cellular sensitivity to the HDAC inhibitors. We propose that CtBP2 is an ovarian cancer oncogene that regulates gene expression program by modulating HDAC activity. CtBP2 expression may be a surrogate indicator of cellular sensitivity to HDAC inhibitors.

Technique and surgical outcomes of robot-assisted anterior lumbar interbody fusion.

The goal of the study was to determine the effectiveness and safety of a novel technique in which the da Vinci S Surgical Robot (Intuitive Surgical Inc., Sunnyvale, CA, USA) was used in the dissection of the ventral lumbar spine to assist with anterior lumbar interbody fusion (R-ALIF). We performed a retrospective chart review of 11 patients who underwent R-ALIF between 2009 and 2010 at our institution. Due to variations in the surgical technique, the data were separated into three patient groups according to which disc level was operated on: L5-S1 (five patients), L4-L5 (two patients), and combined L4-L5 and L5-S1 (four patients). All patients showed radiographic evidence of fusion, and none of the procedures were converted to open. There were no intraoperative vascular complications, and no postoperative transfusions or ileus. This study shows the feasibility and safety of R-ALIF at L5-S1, L4-L5, and L4-L5 and L5-S1.

Antihypertensive drug use by children: are the drugs labeled and indicated?

As a result of the Food and Drug Administration (FDA) Modernization Act and the Best Pharmaceuticals for Children Act, the number of medications with FDA-approved pediatric labeling has increased. To assess the success of these initiatives, we examined whether antihypertensive drugs used by children with hypertension in 2008 had FDA-approved pediatric labeling and indications. Using a nationwide commercial insurer database, 2915 children with primary (n=2607) and secondary (n=308) hypertension were identified. Drug user rate and days of supply were calculated from pharmacy claims. Drugs were categorized based on pediatric labeling and indication and whether they were recommended for pediatric use. Antihypertensive drugs were used by 889 (34%) children with primary hypertension and 200 children (65%) with secondary hypertension. User rates were 44.3% in hypertensive children younger than 6 years, 30.9% in those 6 years to older than 12 years, and 38.1% in those 12 years to older than 18 years. Seven percent of drugs were neither labeled for pediatric use nor considered recommended for use in children. In children younger than 6 years, 29% of drugs used were not indicated for use in that age group. Despite recent legislative initiatives, many drugs used by hypertensive children still lack pediatric labeling. Additional efforts are needed to close the gap between the availability of drugs that are labeled and indicated for pediatric use and actual drug usage in children.

Fatal PML associated with efalizumab therapy: insights into integrin αLß2 in JC virus control.

OBJECTIVES: Progressive multifocal leukoencephalopathy (PML) has become much more common with monoclonal antibody treatment for multiple sclerosis and other immune-mediated disorders. METHODS: We report 2 patients with severe psoriasis and fatal PML treated for ≥3 years with efalizumab, a neutralizing antibody to αLß2-leukointegrin (LFA-1). In one patient, we conducted serial studies of peripheral blood and CSF including analyses of leukocyte phenotypes, migration ex vivo, and CDR3 spectratypes with controls coming from HIV-infected patients with PML. Extensive pathologic and histologic analysis was done on autopsy CNS tissue of both patients. RESULTS: Both patients developed progressive cognitive and motor deficits, and JC virus was identified in CSF. Despite treatment including plasma exchange (PE) and signs of immune reconstitution, both died of PML 2 and 6 months after disease onset. Neuropathologic examination confirmed PML. Efalizumab treatment was associated with reduced transendothelial migration by peripheral T cells in vitro. As expression levels of LFA-1 on peripheral T cells gradually rose after PE, in vitro migration increased. Peripheral and CSF T-cell spectratyping showed CD8+ T-cell clonal expansion but blunted activation, which was restored after PE. CONCLUSIONS: From these data we propose that inhibition of peripheral and intrathecal T-cell activation and suppression of CNS effector-phase migration both characterize efalizumab-associated PML. LFA-1 may be a crucial factor in homeostatic JC virus control.

Audit of sudden deaths in the accident and emergency department of a tertiary hospital in Trinidad and Tobago.

OBJECTIVE: To determine the proportion of deaths due to confirmed myocardial infarction (CMI) and the aetiology of sudden death at the Port-of-Spain General Hospital (A&E) department for January to June 2008. METHODS: This retrospective study utilized the death register to determine the number of A&E deaths for the study period. Patients dying from MI were investigated using records to obtain ECG and postmortem reports. RESULTS: During the study period, 150 patients were certified dead in the A&E department. Cardiovascular causes accounted for 42.7% (n = 64) of deaths. Confirmed MI accounted for 27.3% (n = 41) of deaths and 3.3% (n = 5) were certified by a private practitioner without post-mortem examination and were classed as unconfirmed MI. Trauma related deaths followed with 27.3% (n = 41). Deaths from firearm injury were the next most common, 19.3% (n = 29). The mean age of patients dying from CMI was 64.1 years with a male to female ratio of 2:1. Males died from CMI on average 6.3 years before females. Mortality peaked for females in the 80 - 89-year age group while for males it was the 60- 69-year age group. Afro-Trinidadians accounted for 58.5% (n = 24) deaths due to CMI. More CMI patients had combined DM and HTN 36.6% (n = 15) than either condition alone. Afro-Trinidadians were more likely to be hypertensive and Indo-Trinidadians, diabetic. Death on arrival was the most common presentation for MI patients, 65.9% (n = 27). CONCLUSIONS: This study shows that the main cause of death in the A&E Department at the Port-of-Spain General Hospital was MI. Trauma related deaths followed. Men died from MI at an earlier age than women. Most MI patients were dead on arrival.

Audit of sudden deaths in the accident and emergency department of a tertiary hospital in Trinidad and Tobago / Auditoría de muertes súbitas en el departamento de accidentes y emergencias de un hospital terciario en Trinidad y Tobago

OBJECTIVES: To determine the proportion of deaths due to confirmed myocardial infarction (CMI) and the aetiology of sudden death at the Port-of-Spain General Hospital (A&E) department for January to June 2008. METHODS: This retrospective study utilized the death register to determine the number of A&E deaths for the study period. Patients dying from MI were investigated using records to obtain ECG and postmortem reports. RESULTS: During the study period, 150 patients were certified dead in the A&E department. Cardiovascular causes accounted for 42.7% (n = 64) of deaths. Confirmed MI accounted for 27.3% (n = 41) of deaths and 3.3% (n = 5) were certified by a private practitioner without post-mortem examination and were classed as unconfirmed MI. Trauma related deaths followed with 27.3% (n = 41). Deaths from firearm injury were the next most common, 19.3% (n = 29). The mean age of patients dying from CMI was 64.1 years with a male to female ratio of 2:1. Males died from CMI on average 6.3 years before females. Mortality peaked for females in the 80 - 89-year age group while for males it was the 60 - 69-year age group. Afro-Trinidadians accounted for 58.5% (n = 24) deaths due to CMI. More CMI patients had combined DM and HTN 36.6% (n = 15) than either condition alone. Afro-Trinidadians were more likely to be hypertensive and Indo-Trinidadians, diabetic. Death on arrival was the most common presentation for MI patients, 65.9% (n = 27). CONCLUSIONS: This study shows that the main cause of death in the A&E Department at the Port-of-Spain General Hospital was MI. Trauma related deaths followed. Men died from MI at an earlier age than women. Most MI patients were dead on arrival.

OBJETIVO: Determinar el número de muertes por infarto del miocardio confirmado (IMC), y la etiología de la muerte súbita en el Departamento de Accidentes y Emergencias (A&E) del Hospital General de Puerto España, en el período de enero a junio de 2008, MÉTODO: Este estudio retrospectivo utilizó el registro de defunciones para determinar las muertes en el Departamento A&E en el período estudiado. Los pacientes fallecidos a causa de infarto del miocardio fueron investigados utilizando sus historias clínicas, con el propósito de obtener sus ECG y reportes post mortem. RESULTADOS: Durante el periodo de estudio, 150 pacientes fueron certificados muertos en el Departamento de A&E. Las causas cardiovasculares representaron el 42.7% (n = 64) de las muertes. El IM confirmado fue la causa del 27.3% (n = 41) de las muertes, y las muertes del 3.3% (n = 5) fueron certificadas sin examen post mortem por un médico general privado, y clasificadas como debidas a IM no confirmado. Las muertes relacionadas con traumas ocuparon el siguiente lugar con 27.3% (n = 41). Las muertes por heridas de arma de fuego constituyeron la siguiente causa más común con un 19.3% (n = 29). La edad promedio de los pacientes que fallecieron debido a IMC fue de 64.1 años, con una proporción varón/hembra de 2:1. Los varones murieron de IMC 6.3 años antes que las hembras, como promedio. La mortalidad alcanzó el máximo para las hembras en el grupo etario de 80-89 años, mientras que para los varones fue en el grupo etario de 60 a 69 años. Los afrotrinitenses representaron el 58.5% (n = 24) de las muertes debido a IMC. Más pacientes de IMC tenían una combinación de diabetes mellitus (DM) e hipertensión arterial (HTA) para una 36.6% (n = 15), que aquellos que presentaban sólo una de estas dos condiciones. Los afrotrinitenses eran más propensos a ser hipertensos, en tanto que los indotrinitenses presentaban una mayor propensión a la diabetes. La muerte al momento del arribo fue la ocurrencia más común entre los pacientes de IM, 65.9% (n = 27). CONCLUSIONES: Este estudio muestra que la causa principal de muerte en el Departamento A&E del Hospital General de Puerto España fue el IM, seguida de las muertes relacionadas con traumas. Los hombres murieron de IM a una edad más temprana que las mujeres. La mayoría de los pacientes con IM fallecieron a su arribo.

Comprehensive simultaneous shipboard and airborne characterization of exhaust from a modern container ship at sea.

We report the first joint shipboard and airborne study focused on the chemical composition and water-uptake behavior of particulate ship emissions. The study focuses on emissions from the main propulsion engine of a Post-Panamax class container ship cruising off the central coast of California and burning heavy fuel oil. Shipboard sampling included micro-orifice uniform deposit impactors (MOUDI) with subsequent off-line analysis, whereas airborne measurements involved a number of real-time analyzers to characterize the plume aerosol, aged from a few seconds to over an hour. The mass ratio of particulate organic carbon to sulfate at the base of the ship stack was 0.23 +/- 0.03, and increased to 0.30 +/- 0.01 in the airborne exhaust plume, with the additional organic mass in the airborne plume being concentrated largely in particles below 100 nm in diameter. The organic to sulfate mass ratio in the exhaust aerosol remained constant during the first hour of plume dilution into the marine boundary layer. The mass spectrum of the organic fraction of the exhaust aerosol strongly resembles that of emissions from other diesel sources and appears to be predominantly hydrocarbon-like organic (HOA) material. Background aerosol which, based on air mass back trajectories, probably consisted of aged ship emissions and marine aerosol, contained a lower organic mass fraction than the fresh plume and had a much more oxidized organic component. A volume-weighted mixing rule is able to accurately predict hygroscopic growth factors in the background aerosol but measured and calculated growth factors do not agree for aerosols in the ship exhaust plume. Calculated CCN concentrations, at supersaturations ranging from 0.1 to 0.33%, agree well with measurements in the ship-exhaust plume. Using size-resolved chemical composition instead of bulk submicrometer composition has little effect on the predicted CCN concentrations because the cutoff diameter for CCN activation is larger than the diameter where the mass fraction of organic aerosol begins to increase significantly. The particle number emission factor estimated from this study is 1.3 x 10(16) (kg fuel)(-1), with less than 1/10 of the particles having diameters above 100 nm; 24% of particles (>10 nm in diameter) activate into cloud droplets at 0.3% supersaturation.

Comparison of inhibitors of superoxide generation in vascular smooth muscle cells.

BACKGROUND AND PURPOSE: We compared the dose-dependent reductions in cellular superoxide anion (O(2)(-)) by catalytic agents: superoxide dismutase (SOD), polyethylene glycol (PEG)-SOD and the nitroxide 4-hydroxy-2,2,6,6,-tetramethylpiperidine-1-oxyl (tempol) with uncharacterized antioxidants: 5,10,15,20-tetrakis (4-sulphonatophenyl) porphyrinate iron (III)(Fe-TTPS), (-)-cis-3,3',4',5,7-pentahydroxyflavane (2R,3R)-2-(3,4-dihydroxyphenyl)-3,4-dihydro-1(2H)-benzopyran-3,5,7-triol (-epicatechin), 2-phenyl-1,2-benzisoselenazol-3(2H)-one (ebselen) and N-acetyl-L-cysteine (NAC) with the spin trap nitroblue tetrazolium (NBT) and with the vitamins or their analogues: ascorbate, alpha-tocopherol and 6-hydroxy-2,5,7,8-tetramethylkroman-2-carboxy acid (trolox). EXPERIMENTAL APPROACH: O(2)(-) was generated in primary cultures of angiotensin II-stimulated preglomerular vascular smooth muscle cells from spontaneously hypertensive rats and detected by lucigenin-enhanced chemiluminescence. KEY RESULTS: SOD, PEG-SOD, NAC and tempol produced a similar maximum inhibition of O(2)(-) of 80-90%. -Epicatechin, NBT, ebselen and Fe-TTPS were significantly (P < 0.0125) less effective (50-70%), whereas trolox, alpha-tocopherol and ascorbate had little action even over 24 h of incubation (<31%). Effectiveness in disrupted and intact cells was similar for the permeable agents, PEG-SOD and tempol, but was enhanced for SOD. Generation of O(2)(-) was increased by NAC and NBT at low concentrations but reduced at high concentrations. CONCLUSIONS AND IMPLICATIONS: Maximum effectiveness against cellular production of O(2)(-) requires cell membrane permeability and catalytic action as exemplified by PEG-SOD or tempol. NAC and NBT have biphasic effects on O(2)(-) production. Vitamins C and E or analogues have low efficacy.

Effect of a c-Met-specific, ATP-competitive small-molecule inhibitor SU11274 on human ovarian carcinoma cell growth, motility, and invasion.

Increased expression of the receptor tyrosine kinase c-Met has been shown to correlate with enhanced cell proliferation, motility, and invasion. The objectives of this study were to characterize total and activated c-Met expression in both normal and malignant human ovarian epithelial cells and to determine the effects of inhibiting the activation of c-Met on ovarian epithelial cell growth, motility, and invasion. Total c-Met was overexpressed in 82 (68%) of 119 ovarian carcinomas, as shown by immunohistochemistry. Quantitative reverse transcription-polymerase chain reaction and Western blot analyses revealed that ovarian carcinoma cell lines had higher levels of c-Met messenger RNA, total protein, and activated protein expression compared to normal ovarian epithelial cell cultures. Using a specific adenosine triphosphate-competitive small-molecule inhibitor, SU11274, activated c-Met was decreased in normal and ovarian carcinoma cell lines. 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assays showed that cell growth inhibition directly correlated to the level of activated c-Met detected in each cell line (r =-0.87, P = 0.012). Using modified Boyden chamber assays, ovarian carcinoma cells treated with SU11274 demonstrated significantly decreased cell motility and invasion compared to untreated cells (P = 0.003 and P < 0.001, respectively). These data indicate that c-Met is overexpressed in the majority of malignant ovarian epithelial cells both in vivo and in vitro and that decreasing activated c-Met in vitro can significantly decrease ovarian carcinoma cell growth, motility, and invasion. Developing therapies that specifically inhibit the activation of c-Met may represent a novel therapeutic modality for patients with ovarian carcinomas expressing high levels of c-Met.

Electronic health records in four community physician practices: impact on quality and cost of care.

OBJECTIVE: To assess the impact of the electronic health record (EHR) on cost (i.e., payments to providers) and process measures of quality of care. STUDY DESIGN: Retrospective before-after-study-control. From the database of a large managed care organization (MCO), we obtained the claims of patients from four community physician practices that implemented the EHR and from about 50 comparison practices without the EHR in the same counties. The diverse patient and practice populations were chosen to be a sample more representative of typical private practices than has previously been studied. MEASUREMENTS: For four chronic conditions, we used commercially-available software to analyze cost per episode over a year and the rate of adherence to clinical guidelines as a measure of quality. RESULTS: The implementation of the EHR had a modest positive impact on the quality measure of guideline adherence for hypertension and hyperlipidemia, but no significant impact for diabetes and coronary artery disease. No measurable impact on the short-term cost per episode was found. Discussions with the study practices revealed that the timing and comprehensiveness of EHR implementation varied across practices, creating an intervention variable that was heterogeneous. CONCLUSIONS: Guideline adherence increased across practices without EHRs and slightly faster in practices with EHRs. Measuring the impact of EHRs on cost per episode was challenging, because of the difficulty of completely capturing the long-term episodic costs of a chronic condition. Few practices associated with the study MCO had implemented EHRs in any form, much less utilizing standardized protocols.

Large calcifications in ovaries otherwise normal on ultrasound.

OBJECTIVE: To evaluate calcifications >or= 5 mm in length in ovaries that are otherwise normal on ultrasound, and to determine whether such large ovarian calcifications are an indicator of ovarian neoplasm. METHODS: This was a retrospective study reviewing pelvic ultrasound results at our unit between October 1994 and April 2002 to identify patients with ovarian calcifications that were >or= 5 mm in maximum length in otherwise normal ovaries, and who also had follow-up imaging studies. Patient medical histories were reviewed, calcification characteristics, including number, size, shape and laterality of calcifications, were recorded and follow-up imaging studies were reviewed to assess change in size of the calcification and to see if a neoplasm had developed. RESULTS: The study group consisted of 28 patients. The mean length of imaging follow-up was 35.2 +/- 30.7 months. The mean size of the calcifications was 7.4 +/- 2.3 (range, 5-13) mm. The calcification remained stable in all 28 patients and no ovarian neoplasms developed in any of the patients. Histological confirmation was available in one patient and this revealed dystrophic calcification in a corpus albicans. CONCLUSION: Calcifications ranging from 5 to 13 mm in length in otherwise normal ovaries remain stable on follow-up imaging and are not an indicator of current or future ovarian neoplasm. Published by John Wiley & Sons, Ltd.