Costs of rheumatoid arthritis: new estimates from the human capital method and comparison to the willingness-to-pay method.

BACKGROUND: Individuals' valuation of changes in health states in monetary terms have been measured by examining changes in the direct and indirect costs of disease and by the willingness-to-pay (WTP) methodology. METHODS: In 2002, a 2-part study was conducted in Quebec. In one part of the study, 121 rheumatoid arthritis (RA) patients from the McGill University Health Centre were mailed the Stanford Cost Assessment Questionnaire, which enabled the elicitation of direct costs and indirect costs, according to the friction cost and the human capital methods. The other part was a phone survey conducted in a representative sample of the general population and in the same sample of patients, aiming to elicit the societal WTP for a complete cure of RA in the context of 2 different scenarios: a public coverage or private insurance. These estimates were then compared. RESULTS: Estimates of the cost of illness of RA ranged from 11,717 to 28,498 Canadian Dollars (CAD) depending on the method. These estimates are higher than those previously published in Canada from the 1990s, which is partly due to the recent and costly biological therapies and to a change in the measurement of productivity losses. These estimates are somewhat lower than the societal WTP elicited from the WTP survey, that is, 26,717 and 36,817 CAD per RA case, depending on the public or private health insurance context in which the cure would be available. CONCLUSION: Given that neither method is ideal, data from both methods would provide an important sensitivity analysis when monetary estimates of health state changes are required.     

Tamoxifen and risk of large bowel cancer in women with breast cancer

Background: The increasingly consistent association between estrogen replacement therapy and colorectal cancer suggests that the anti-estrogen tamoxifen may also be associated with large bowel cancer incidence.Methods: Women with new diagnoses of breast cancer were identified from the Surveillance Epidemiology and End Results (SEER) Program, a set of geographically defined, population based cancer registries representing approximately ten percent of the U.S. population. Of 85,411 women with local or regional breast cancer diagnosed from 1983–90, 14,984 women were reported to have received hormonal therapy and 70,427 were not known to have received hormonal therapy. Subsequent cancer diagnoses were identified in this cohort beginning 6 months after initial breast cancer diagnosis until death, or December 31, 1994. Multivariate Cox proportional hazards models were used to estimate the risk of developing colorectal cancer and other second cancers according to hormonal therapy use.Results: Over the follow-up period 793 colorectal, 2,648 contralateral breast, 506 endometrial, 250 ovarian, 98 gastric, and 1,765 other cancers were identified in the study cohort. While overall there was no association between hormonal therapy use and colorectal cancer (relative risk (RR) 1.09, 95% confidence interval (CI) 0.88–1.35), in the period five or more years after diagnosis, risk was increased significantly by about 50% (95% CI 1.00–2.15). As expected, based upon clinical trials data, cancers of the contralateral breast were significantly decreased, and cancers of the uterine endometrium were significantly increased. No other meaningful associations were observed. When women were excluded for whom hormonal therapy might represent therapy other than tamoxifen (premenopausal women and those who received chemotherapy), this did not meaningfully alter these estimates.Conclusions: The results of this large population based cohort study suggest that tamoxifen therapy may modestly increase risk of large bowel cancer in women, but only after 5 years following initiation of breast cancer therapy.     

Willingness to pay for what? A note on alternative definitions of health care program benefits for contingent valuation studies.

The authors examine a number of ways in which willingness to pay (WTP) can be defined for measurement and use in a cost-benefit analysis (CBA) of a collectively funded health care program. They show how ambiguous specification of the program consequences that respondents should consider in their WTP responses can lead to problems of double counting or zero countingin a subsequent CBA. An example is whether the value of lost time from work because of poor health should be included by a CBA analyst (e.g., valued at the wage rate) as a separate cost item or whether this has already been monetized and included in respondents' WTP data. The authors highlight how differences in assumed or actual institutional structures are often ignored in measures of WTP and the consequences of this for the interpretation of WTP data.     

Response patterns of the Spanish version of the 49-item short form of the Addiction Research Center Inventory after the use of sedatives, stimulants, and opioids.

This report examines the validity of the Spanish version of the 49-item short form of the Addiction Research Center Inventory (ARCI) for measuring subjective effects after the use of sedatives, stimulants, and opioids. Data from four clinical trials in which this questionnaire was used have been analyzed. The Spanish ARCI short form was found to be sensitive in measuring subjective effects after the administration of alcohol, triazolam, and flunitrazepam (sedatives), cocaine (stimulants), and morphine, pentazocine, and naloxone (opioids) and to distinguishing among them. The response patterns were similar to those previously reported for the same drugs with the English version of ARCI. It is concluded that Spanish version of the 49-item short form of ARCI is a valid instrument for assessing the subjective effects of psychoactive drugs in the Spanish-speaking population context.     

The high-affinity HSP90-CHIP complex recognizes and selectively degrades phosphorylated tau client proteins

A primary pathologic component of Alzheimer's disease (AD) is the formation of neurofibrillary tangles composed of hyperphosphorylated tau (p-tau). Expediting the removal of these p-tau species may be a relevant therapeutic strategy. Here we report that inhibition of Hsp90 led to decreases in p-tau levels independent of heat shock factor 1 (HSF1) activation. A critical mediator of this mechanism was carboxy terminus of Hsp70-interacting protein (CHIP), a tau ubiquitin ligase. Cochaperones were also involved in Hsp90-mediated removal of p-tau, while those of the mature Hsp90 refolding complex prevented this effect. This is the first demonstration to our knowledge that blockade of the refolding pathway promotes p-tau turnover through degradation. We also show that peripheral administration of a novel Hsp90 inhibitor promoted selective decreases in p-tau species in a mouse model of tauopathy, further suggesting a central role for the Hsp90 complex in the pathogenesis of tauopathies. When taken in the context of known high-affinity Hsp90 complexes in affected regions of the AD brain, these data implicate a central role for Hsp90 in the development of AD and other tauopathies and may provide a rationale for the development of novel Hsp90-based therapeutic strategies.     

Left main coronary artery aneurysm associated with extensive coronary arterial calcification: case report and review

We present a 68-year-old male with left main coronary artery aneurysm and extensive coronary calcification involving the entire coronary arterial tree detected by coronary angiography and electron beam computerized tomography. With this article we also discussed the relationships between the pathogenesis of coronary atherosclerosis, coronary calcification, and coronary aneurysm formation.     

Long-term outcomes of six patients after partial internal biliary diversion for progressive familial intrahepatic cholestasis

Background

Partial internal biliary diversion (PIBD) is an alternative approach for the treatment of devastating pruritus in patients with progressive familial intrahepatic cholestasis (PFIC). In these patients quality of life can be improved and progression of liver disease can be delayed while waiting for liver transplantation. The aim of our study was to evaluate six patients with PFIC who have undergone PIBD in long-term follow-up.

Detailed cost analysis of care for survivors of severe sepsis

OBJECTIVES: The objectives of our study were to accurately describe the costs and resources required to treat survivors of severe sepsis subsequent to hospital discharge and to determine what factors influenced these costs. DESIGN: Observational cohort study. SETTING: Three regional intensive care units. PATIENTS: Patients with severe sepsis admitted to one of three regional intensive care units in southern Alberta between April 1, 1996, and March 31, 1999. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Patients were identified using an intensive care unit research database; all survivors were followed prospectively for 3 yrs. Information on baseline patient characteristics, including acuity of illness (Acute Physiology and Chronic Health Evaluation II scores) and Charlson comorbidity scores, was collected. Costs considered included all episodes of inpatient and outpatient care and all physician claims. Of 787 patients who were admitted with severe sepsis, 502 survived to hospital discharge and were followed. Subsequent mean cost of care for years 1, 2, and 3 was CAN$20,855, $7,139 and $7,091, respectively. Using various regression models, the Acute Physiology and Chronic Health Evaluation II score and the Charlson comorbidity score were the only factors that consistently predicted higher healthcare costs in the first year after hospital discharge. Diabetes was the comorbid condition that best predicted subsequent cost. CONCLUSIONS: Cost of care for survivors of severe sepsis was highest in the first year after hospital discharge. Acuity of illness and patient comorbidity were the main determinants of cost. In assessing whether new therapeutic innovations for intensive care unit patients with severe sepsis are cost-effective, an accurate estimate of the cost of subsequent health care for survivors treated with and without the new intervention will be important.     

A current review of Ebola virus: pathogenesis,clinical presentation,and diagnostic assessment

Ebola hemorrhagic fever (EHF) is an acute viral syndrome that presents with fever and an ensuing bleeding diathesis that is marked by high mortality in human and nonhuman primates. Fatality rates are between 50% and 100%. Due to its lethal nature, this filovirus is classified as a biological class 4 pathogen. The natural reservoir of the virus is unknown. As a result, little is understood about how Ebola virus is transmitted or how it replicates in its host. Although the primary source of infection is unknown, the epidemiologic mode of transmission is well defined. A variety of tests have proven to be specific and useful for Ebola virus identification. There is no FDA-approved antiviral treatment for EHF. Incubation ranges from 2 to 21 days. Patients who are able to mount an immune response to the virus will begin to recover in 7 to 10 days and start a period of prolonged convalescence. Supportive management of infected patients is the primary method of treatment, with particular attention to maintenance of hydration, circulatory volume, blood pressure, and the provision of supplemental oxygen. Since there is no specific treatment outside of supportive management and palliative care, containment of this potentially lethal virus is paramount. In almost all outbreaks of EHF, the fatality rate among health care workers with documented infections was higher than that of non-health care workers.