Prospective Evaluation of Genetic Variation in Platelet Endothelial Aggregation Receptor 1 Reveals Aspirin-Dependent Effects on Platelet Aggregation Pathways.

Genetic variation in the platelet endothelial aggregation receptor 1 (PEAR1) gene, most notably rs12041331, is implicated in altered on-aspirin platelet aggregation and increased cardiovascular event risk. We prospectively tested the effects of aspirin administration at commonly prescribed doses (81, 162, and 324 mg/day) on agonist-induced platelet aggregation by rs12041331 genotype in 67 healthy individuals. Prior to aspirin administration, rs12041331 minor allele carriers had significantly reduced adenosine diphosphate (ADP)-induced platelet aggregation compared with noncarriers (P = 0.03) but was not associated with other platelet pathways. In contrast, rs12041331 was significantly associated with on-aspirin platelet aggregation when collagen and epinephrine were used to stimulate platelet aggregation (P < 0.05 for all associations), but not ADP. The influence of PEAR1 rs12041331 on platelet aggregation is pathway-specific and is altered by aspirin at therapeutic doses, but not in a dose-dependent manner. Additional studies are needed to determine the impact of PEAR1 on cardiovascular events in aspirin-treated patients.

The effects of state-level expenditures for home- and community-based services on the risk of becoming a long-stay nursing home resident after hip fracture.

SUMMARY: This study measures the effect of spending policies for long-term care services on the risk of becoming a long-stay nursing home resident after a hip fracture. Relative spending on community-based services may reduce the risk of long-term nursing home residence. Policies favoring alternative sources of care may provide opportunities for older adults to remain community-bound. INTRODUCTION: This study aims to understand how long-term care policies affect outcomes by investigating the effect of state-level spending for home- and community-based services (HCBSs) on the likelihood of an individual's nursing home placement following hip fracture. METHODS: This study uses data from the 5% sample of Medicare beneficiaries from 2005 to 2010 to identify incident hip fractures among dual-eligibility, community-dwelling adults aged at least 65 years. A multilevel generalized estimating equation (GEE) model estimated the association between an individual's risk of nursing home residence within 1 year and the percent of states' Medicaid long-term support service (LTSS) budget allocated to HCBS. Other covariates included expenditures for Title III services and individual demographic and health status characteristics. RESULTS: States vary considerably in HCBS spending, ranging from 17.7 to 83.8% of the Medicaid LTSS budget in 2009. Hip fractures were observed from claims among 7778 beneficiaries; 34% were admitted to a nursing home and 25% died within 1 year. HCBS spending was associated with a decreased risk of nursing home residence by 0.17 percentage points (p 0.056). CONCLUSIONS: Consistent with other studies, our findings suggest that state policies favoring an emphasis on HCBS may reduce nursing home residence among low-income older adults with hip fracture who are at high risk for institutionalization.

Mortality following bone metastasis and skeletal-related events among men with prostate cancer: a population-based analysis of US Medicare beneficiaries, 1999-2006.

Information on the impact of bone metastasis and skeletal-related events (SREs) on mortality among prostate cancer patients is limited. Using the linked Surveillance, Epidemiology and End Results (SEER)-Medicare database, we identified men aged 65 years or older diagnosed with prostate cancer between July 1 1999 and December 31 2005 and followed to determine deaths through December 31 2006. We classified subjects as having bone metastasis and SREs as indicated by Medicare claims. Using Cox regression, we estimated mortality hazards ratios (HR) among men with bone metastasis with or without SRE, compared with men without bone metastasis. Among 126,978 men with prostate cancer (median follow-up, 3.3 years), 9746 (7.7%) had bone metastasis at prostate cancer diagnosis (1.7%) or during follow-up (5.9%). SREs occurred in 4296 (44%) men with bone metastasis. HRs for risk of death were 6.6 (95% CI=6.4-6.9) and 10.2 (95% CI=9.8-10.7), respectively, for men with bone metastasis but no SRE and for men with bone metastasis plus SRE, compared with men without bone metastasis. Bone metastasis was associated with mortality among prostate cancer patients. This association appeared to be stronger for bone metastasis plus SRE than for bone metastasis without SRE.

Clinical and demographic factors associated with fractures among older Americans.

UNLABELLED: Medicare claims data were used to investigate associations between history of previous fractures, chronic conditions, and demographic characteristics and occurrence of fractures at six anatomic sites. The study confirmed previously established associations for hip and spine fractures and identified several new associations of interest for nonhip, nonspine fractures. INTRODUCTION: This study investigates the associations of a history of fracture, comorbid chronic conditions, and demographic characteristics with incident fractures among Medicare beneficiaries. The majority of fracture incidence studies have focused on the hip and on white females. This study examines a greater variety of fracture sites and more population subgroups than prior studies. METHODS: We used Medicare claims data to examine the incidence of fracture at six anatomic sites in a random 5% sample of Medicare beneficiaries during the time period 2000 through 2005. RESULTS: For each type of incident fracture, women had a higher rate than men, and there was a positive association with age and an inverse association with income. Whites had a higher rate than nonwhites. Rates were lowest among African-Americans for all sites except ankle and tibia/fibula, which were lowest among Asian-Americans. Rates of hip and spine fracture were highest in the South, and fractures of other sites were highest in the Northeast. Fall-related conditions and depressive illnesses were associated with each type of incident fracture, conditions treated with glucocorticoids with hip and spine fractures and diabetes with ankle and humerus fractures. Histories of hip and spine fractures were associated positively with each site of incident fracture except ankle; histories of nonhip, nonspine fractures were associated with most types of incident fracture. CONCLUSIONS: This study confirmed previously established associations for hip and spine fractures and identified several new associations of interest for nonhip, nonspine fractures.

"Pathologic" fractures: should these be included in epidemiologic studies of osteoporotic fractures?

UNLABELLED: Pathologic fractures are often excluded in epidemiologic studies of osteoporosis. Using Medicare administrative data, we identified persons with vertebral and hip fractures. Among these, 48% (vertebral) and 3% (hip) of the fractures were coded as pathologic. Only 25% and 66% of persons with these pathologic fractures had evidence for malignancy. INTRODUCTION: Analyses of osteoporosis-related fractures that use administrative data often exclude pathologic fractures (ICD-9 733.1x) due to concern that these are caused by cancer. We examined "pathologic" fractures of the vertebrae and hip to evaluate their contribution to fracture incidence and assessed the evidence for a malignancy. METHODS: We studied US Medicare beneficiaries age > or =65 with new fractures identified using ICD-9 diagnosis codes 733.13 (pathologic vert), 805.0, 805.2, 805.4, 805.8 (nonpathologic vert); and 733.14 (pathologic hip), 820.0, 820.2, 820.8 (nonpathologic hip). We further examined the proportion of cases with a diagnosis of a malignancy proximate to the fracture. RESULTS: We identified 44,120 individuals with a vertebral fracture and 60,354 with a hip fracture. Approximately 48% of vertebral fractures and 3% of hip fractures were coded as pathologic. For only approximately 25% of persons with a "pathologic" vertebral fracture ICD-9 code, but 66% of persons with a "pathologic" hip fracture, there was evidence of a possible cancer diagnosis. CONCLUSION: Among US Medicare beneficiaries, one fourth of pathologic vertebral fracture and two thirds of pathologic hip fracture cases had evidence for a malignancy. Particularly for vertebral fractures, excluding persons with pathologic fractures in epidemiologic analyses that utilize administrative claims data substantially underestimates the burden of fractures due to osteoporosis.

Estimated prevalence and patterns of presumed osteoporosis among older Americans based on Medicare data.

INTRODUCTION: Estimates of osteoporosis (OP) prevalence based on bone mineral density testing and fracture occurrence may be imprecise for small demographic groups. Medicare data are a useful supplemental source of information on OP. METHODS: We studied people ages > or = 65 years covered by Medicare 2005. Cases of presumed OP were beneficiaries with physician services or inpatient claims for OP or for an associated fracture (hip, distal forearm, spine) in 1999-2005. RESULTS: Among 911,327 beneficiaries with 6 or 7 years of Medicare coverage, the overall prevalence of OP and associated fractures was 29.7%. Prevalence was four times higher for women than men, increased with age, and was two times higher for whites, Hispanic Americans, and Asian Americans than African Americans. Among people with OP-associated fracture claims, the proportion with an OP diagnosis was 49.7% overall (women, 57.1%; men, 21.9%) and was lower for men than women and for African Americans than other ethnic groups. CONCLUSIONS: The low proportion of beneficiaries who had an OP-associated fracture and also had an OP diagnosis, particularly among men and African American women, suggests suboptimal recognition and management of OP. Study limitations included lack of validation of our definition of OP and potential misclassification of race/ethnicity.

The geographic availability and associated utilization of dual-energy X-ray absorptiometry (DXA) testing among older persons in the United States.

UNLABELLED: Using national Medicare data from 1999-2006, we evaluated the relationship between travel distance and receipt of dual-energy X-ray absorptiometry (DXA). After adjusting for potentially confounding factors, travel distance was strongly associated with DXA testing. Rural residents were most strongly dependent on the availability of DXAs performed in physician offices. INTRODUCTION: Medicare reimbursement for DXAs performed in non-facility settings (e.g., physician offices) decreased in 2007. With declining reimbursement, some DXA providers may cease providing this service, which would increase travel distance for some people. The impact of travel distance on access to DXA is unclear. METHODS: Using national Medicare data, we identified claims for DXA to evaluate trends in the number and locations of DXAs performed. Travel distance was the distance from beneficiaries' residence and the nearest DXA provider. Binomial regression evaluated the relationship between travel distance and receipt of DXA. RESULTS: In 2006, 2.9 million DXAs were performed, a 103% increase since 1999. In 2005-2006, 8.0% of persons were tested at non-facility sites versus 4.2% at facility sites. The remainder (88%) had no DXA. Persons traveling 5-9, 10-24, 25-39, and 40-54, and > or = 55 miles were less likely to receive DXA (adjusted risk ratios = 0.92, 0.79, 0.43, 0.32, and 0.26, respectively, < 5 miles referent). Rural residents were more dependent than urban residents on the availability of DXA from non-facility providers. CONCLUSION: Approximately two-thirds of DXAs in 2005-2006 were performed in non-facility settings (e.g., physician offices). Rural residents would have preferentially reduced access to DXA if there were fewer non-facility sites.

CEO perceptions of competition--and strategic response in hospital markets.

Physician-organization integration (POI) has emerged as a key issue for hospitals and health systems seeking to improve the quality and cost-effectiveness of care. Although competition and managed care are often cited as primary market drivers of the adoption of POI strategies, prior research has shown only weak associations between these market attributes and POI. This article argues that the role of key organizational decision makers has not been adequately accounted for in explaining strategic change. The study examines the role of hospital CEO perceptions of competition in predicting the adoption of five different approaches to POI. CEO perceptions of general market competition are explained by a combination of market and organizational attributes. Furthermore, when controlling for objective characteristics of the environment and organization, CEO perceptions of competition have consistent, statistically significant associations with four of five measures of POI examined.

Competition in hospital and health insurance markets: a review and research agenda.

OBJECTIVES: To review the empirical literature on the effects of selective contracting and hospital competition on hospital prices, travel distance, services, and quality; to review the effects of managed care penetration and competition on health insurance premiums; and to identify areas for further research. PRINCIPAL FINDINGS: Selective contracting has allowed managed care plans to obtain lower prices from hospitals. This finding is generalizable beyond California and is stronger when there is more competition in the hospital market. Travel distances to hospitals of admission have not increased as a result of managed care. Evidence on the diffusion of technology in hospitals and the extent to which hospitals have specialized as a result of managed care is mixed. Little research on the effects on quality has been undertaken, but preliminary evidence suggests that hospital quality has not declined and may have improved. Actual mergers in the hospital market have not affected hospital prices. Much less research has been focused on managed care markets. Greater market penetration and greater competition among managed care plans are associated with lower managed care premiums. Greater HMO penetration appears to be much more effective than PPO penetration in leading to lower premiums. While workers are willing to change plans when faced with higher out-of-pocket premiums, there is little evidence of the willingness of employers to switch plan offerings. Preliminary evidence suggests that greater managed care penetration has led to lower overall employer premiums, but the results differ substantially between employers with and without a self-insured plan. CONCLUSIONS: Much more research is needed to examine all aspects of managed care markets. In hospital markets, particular attention should be focused on the effects on quality and technology diffusion.

Endogenous fringe benefits, compensating wage differentials and older workers.

Employers are the principal source of health insurance for Americans under age 65. Economic theory argues that workers pay for health insurance in the form of lower wages or reductions in other forms of compensation. This paper uses 1994 and 1998 Health and Retirement Survey data to examine the wage-health insurance trade-off for older U.S. workers. Job and insurance choice are treated as endogenous in a two stage least squares framework. There is strong evidence supporting the treatment of nonwage benefits as endogenous. The preferred specification indicates an annual health insurance wage adjustment of $6,300. The magnitude of the trade-off is fragile, however.

A cost-effectiveness analysis of biliary anastomosis with or without T-tube after orthotopic liver transplantation.

Biliary reconstruction continues to be a major source of morbidity following orthotopic liver transplantation. We wished to determine if choledochocholedochostomy without a T-tube was associated with fewer biliary complications and was less costly than choledochocholedochostomy with a T-tube. A retrospective cohort study of patients who underwent liver transplantation was performed. Patients were stratified into two groups: group I had bile duct reconstruction with T-tube and group II did not have a T-tube. The results were interpreted on an intention-to-treat analysis. We identified 147 adult patients who underwent initial liver transplantation. There were 76 patients in group I and 71 patients in group II. There were no statistical differences between the two groups regarding underlying cause of liver disease, patient age, gender or United Network for Organ Sharing status. As the decision to use a T-tube was made at the time of surgery, the two groups may not be strictly comparable. The mean hospital stay was longer in group I (31.1 +/- 27.9d) than in group II (18.8 +/- 15.5d) (p = 0.001). Biliary complications were statistically more frequent in patients from group I patients (25/76, 32.9%) than in patients from group II (11/71, 15.5%) (p = 0.01). There was a trend for the costs associated with diagnostic and therapeutic procedures for the management of biliary complications to be greater for group I than for group II, although this was not statistically significant (p = 0.235). Our study suggests choledochocholedochostomy without T-tube reconstruction is the preferred strategy for biliary reconstruction in orthotopic liver transplantation. It is not only associated with fewer biliary complications, but also less costly than using choledochocholedochostomy over a T-tube. Randomized prospective studies are needed to confirm our results.

The effect of state regulations on motor vehicle fatalities for younger and older drivers: a review and analysis.

Policymakers have had a long-standing interest in improving the motor vehicle safety of both younger and older drivers. Although younger and older drivers share the distinction of having more crashes and fatalities per mile driven than other age groups, the problems posed by these two groups stem from different origins and manifest in different ways. A number of state-level policies and regulations may affect the number of motor vehicle crashes and fatalities in these two high-risk groups. A critical review of the existing literature in regard to the risk factors and the effects of various policy measures on motor vehicle crashes in these two high-risk populations provides direction for policymakers and high-priority areas of interest for the research community.

Small group reform and insurance provision by small firms, 1989-1995.

Since 1989, states have enacted legislation to dismantle barriers facing small businesses that wish to purchase health insurance. Using data on the insurance offerings of 2,472 small firms (one to 49 employees) observed from 1989 to 1995, we assess whether state reforms encouraged more small firms to sponsor health benefits. We find that small group reforms did not spur uninsured firms to offer insurance. Firms without health insurance say that the high price of coverage is still the major barrier they face to offering a plan. Our findings suggest that the small group reforms within the 1996 Health Insurance Portability and Accountability Act are not likely to have an effect on the small group market. Most states already had implemented measures similar to those found in the act, and not much changed.

The effects of managed care on physician and clinical integration in hospitals.

OBJECTIVE: To empirically estimate the effects that managed care has had on physician and clinical integration in urban hospitals. DATA SOURCES: The 1993 Hospital-Physician Relationship Survey conducted for the Prospective Payment Assessment Commission, augmented with data from a variety of secondary sources. The entire 1,495 responding hospitals were used to construct measures of integration; 591 responding hospitals in urban areas were used for the managed care analysis. STUDY DESIGN: Factor analysis was used to reduce 23 integration variables into 5 physician and 3 clinical integration factors. Two-stage least-squares regression techniques were used to estimate the effects of endogenous managed care. Models were estimated for all urban hospitals and for hospital subsets based upon ownership, multi-hospital system status, and teaching. PRINCIPAL FINDINGS: Other things equal, physician involvement in hospital management and governance increased with managed care involvement; to a lesser degree, the use of physician organization arrangements and other joint ventures also increased. Practice management and support services were lower in hospitals with high managed care activity. Larger hospitals, investor owned, system, and non-teaching hospitals had larger managed care revenues. Managed care revenues were lower in more concentrated hospital markets. CONCLUSIONS: The relationship between managed care and physician and clinical integration is relatively modest. Much of the realignment under managed care has been limited to certain types of efforts. Those efforts can best be described as foundation-building rather than comprehensive or fundamental.

A simple model to estimate survival after retransplantation of the liver.

To formulate a model predicting survival after liver retransplantation, we analyzed in detail the last 150 cases of hepatic retransplantation at UCLA. Cox proportional hazards regression analysis identified five variables that demonstrated independent simultaneous prognostic value in estimating patient survival after retransplantation: (1) age group (pediatric or adult), (2) recipient requiring preoperative mechanical ventilation, (3) donor organ cold ischemia > or =12 hr, (4) preoperative serum creatinine, and (5) preoperative serum total bilirubin. The Cox regression equation that predicts survival based on these covariates was simplified by assigning individual patients a risk classification based on a 5-point scoring system. We demonstrate that this system can be employed to identify a subgroup of patients in which the expected outcome is too poor to justify retransplantation. These findings may assist in the rational selection of patients suitable for retransplantation.

A phase II study of 5-fluorouracil, leucovorin, and interferon-alpha in the treatment of patients with metastatic or recurrent gastric carcinoma: an Eastern Cooperative Oncology Group study (E5292).

BACKGROUND: Chemotherapy has a limited impact on adenocarcinoma of the stomach. Although biochemical modulation of 5-fluorouracil (5-FU) by leucovorin (LV) and interferon-alpha (IFN-alpha) has improved the outcomes of patients with metastatic colorectal carcinoma compared with 5-FU alone, this approach has not been extensively evaluated in the treatment of advanced gastric carcinoma. METHODS: Twenty-seven patients with bidimensionally measurable, metastatic gastric carcinoma and an Eastern Cooperative Oncology Group performance status of 0 or 1 received the combination of IFN-alpha (5 million U/m2 administered subcutaneously daily on Days 1-7), LV (500 mg/m2 administered intravenously over 30 minutes immediately after IFN-alpha on Days 2-6), and 5-FU (370 mg/m2 given as an intravenous bolus 60 minutes after LV on Days 2-6), with treatment repeated every 4 weeks. Oral cryotherapy was administered routinely before each dose of 5-FU to reduce the incidence of severe stomatitis. RESULTS: The median age of the patients was 58 years (range, 20-76), and 22 patients had residual, unresectable primary lesions. The median number of cycles received was 3 (range, 1-11). Of 24 patients who received at least 2 cycles of treatment, 15 (62.5%) did not require dose reduction for toxicity during the initial 2 cycles. The predominant toxicities were gastrointestinal: diarrhea and stomatitis of Grade 3-4 occurred in 28.6% and 35.7% of patients, respectively. Other severe (Grade 3-4) toxicities were granulocytopenia (which occurred in 21.4% of patients) and fatigue (in 10.7%). Fever and flu-like symptoms were common but usually mild. Of 24 patients who were evaluable for response, 3 had partial responses (PR) of 16, 23, and 33 weeks' duration, respectively, for a response rate of 12.5% (95% confidence interval = 2.7-32.4%). Two additional patients had reductions in tumor size sufficient for PR, but scans to document the minimum required response duration of 4 weeks were not obtained before progressive disease occurred. The median progression-free and overall survivals were 2.5 and 7.8 months, respectively. CONCLUSIONS: Although this regimen can be administered safely with appropriate supportive care to patients with good performance status, it has limited therapeutic activity in patients with advanced gastric carcinoma.

Employer-sponsored health insurance and mandated benefit laws.

Regulations for the content of private health plans, called mandated benefit laws, are widespread and growing in the United States, at both state and federal levels. Three aspects of these laws are examined: their current scope; some economic reasons for their existence; and the theory and empirical evidence for their effects in health insurance markets. A growing body of literature suggests that society is paying a high price for enhanced coverage via mandated benefits. These laws increase insurance premiums, cause declines in wages and other fringe benefits, and lead some employers and their workers to forgo health benefits altogether. The cost of mandated benefit laws falls disproportionately on workers in small firms.

The spread of state any willing provider laws.

OBJECTIVE: To describe the growth of any willing provider (AWP) and freedom of choice (FOC) laws applicable to managed care firms and to explore empirically the determinants of their enactment. STUDY SETTING: A 1996 compendium of state laws and state-level data from the 1991-1994 period. STUDY DESIGN: Pooled cross-section time-series logistic regression of the decision to enact various types of AWP and FOC laws. Analysis uses a public choice framework to examine enactment. Key variables include proxy measures of proponent and opponent strength and the political environment. PRINCIPAL FINDINGS: The model works well for laws affecting hospitals, but performs poorly for physician and pharmacy laws. More providers are associated with the enactment of AWP and FOC laws. More large employers are associated with a reduced likelihood of enactment of some forms of the laws but not others. Conservative states are more likely to enact laws limiting selective contracting with hospitals and physicians. States with greater interparty competition are also more likely to adopt some types of legislation. CONCLUSIONS: The empirical results generally are consistent with the view that AWP and FOC laws are often enacted as a defensive strategy on the part of providers, but additional research is needed to provide a more definitive assessment of the determinants of these laws. Suggestions for future research are provided.