New technologies and potential cost savings related to morbidity and mortality reduction in Class III/IV heart failure patients in Canada

BACKGROUND: Heart failure affects 1-2% of the Canadian population. The 1-year mortality rates in New York Heart Association Class III/IV heart failure patients range from 11 to 44%. This study evaluates costs associated with current management of Class III/IV heart failure and potential savings if morbidity and mortality are reduced. OBJECTIVES: To construct an economic model to evaluate the components of treating Class III/IV heart failure patients in Canada and the resulting direct medical costs. The model also estimates the potential savings that could result from the introduction of a new technology such as cardiac resynchronization therapy that reduces morbidity and mortality. METHODS: The model evaluates costs of pharmacological therapy, medical care, laboratory and diagnostic tests, and complications, most commonly hospitalization. Estimates are based on a literature review, expert opinion, and standard cost sources using widely accepted health economic methods. RESULTS: The model, under conservative assumptions, estimates that Class III/IV heart failure costs between CAD$1.4 billion and CAD$2.3 billion in Canada overall. Costs are substantial on the provincial level as well and are estimated to be approximately CAD$700 million, CAD$500 million, and CAD$300 million in Ontario, Québec, and British Columbia, respectively. New treatments could bring substantial savings depending on their effectiveness-measured as reduction in morbidity and mortality-and the number of patients who receive that treatment. Potential savings in Canada could reduce the total annual costs for this group of patients by approximately 10% or up to CAD$200 million annually. CONCLUSIONS: The high level of morbidity and mortality in Class III/IV heart failure patients and costs associated with their care are an impetus for the development of new therapies such as cardiac resynchronization therapy, that could deliver long-term benefits including increased exercise tolerance, reduced hospitalizations, and improved quality of life. Successful therapies could provide substantial savings and present a favorable economic profile in the treatment of heart failure. In order to ensure that appropriate technologies are commercialized and marketed, prospective evaluation of new therapies should include critical assessment of direct medical costs in addition to evaluating morbidity, quality of life and survival.     

Human VAT-1: a calcium-regulated activation marker of human epithelial cells

Background and aims Human VAT-1 (hVAT-1) is a homologue of the synaptic vesicle membrane protein of Torpedo californica. Its coding gene is located near the BRCA1 locus and thus hVAT-1 may be linked to an inherited predisposition to breast and ovary cancer. However, the hVAT-1 protein expression pattern in normal epithelial tissues such as skin, mammary gland and ovary, as well as in tumours of the mammary gland and ovary, has not been studied.Methods To address this issue, an immunohistological analysis of biopsies of normal epidermis and lesional epidermis of bullous pemphigoid and pemphigus vulgaris patients was undertaken.Results hVAT-1-expression was observed in basal keratinocytes of lesional epidermis of bullous pemphigoid patients but not in normal epidermis or in lesional epidermis of pemphigus vulgaris patients. Moreover, hVAT-1 expression in HaCaT cells was found to be calcium-dependent. Normal and malignant mammary and ovary epithelium were found to be hVAT-1-negative.Conclusions Our results indicate that hVAT-1 exerts a specific function in keratinocyte physiology, in particular in calcium-regulated processes, with no evident deregulation in malignancies of the breast and ovary.Abbreviations BRCA1 Breast-related cancer antigen 1 - DMEM Dulbecco's modified Eagle's medium - EDTA Ethylenediamine tetraacetate - ELISA Enzyme-linked immunosorbent assay - FCS Fetal calf serum - GAPDH Glyceraldehyde-3-phosphate dehydrogenase - GST Glutathione-S-transferase - HRP Horseradish peroxidase - hVAT-1 Human VAT-1 - NHEK Normal human epidermal keratinocytes - PBS Phosphate-buffered saline - TBS Tris-buffered saline - VAT-1 Vesicle-amine-transport protein-1     

Abuse and violence history of men and women in treatment for methamphetamine dependence

The Methamphetamine Treatment Project offers the opportunity to examine the history of abuse and violence in a sample of 1016 methamphetamine users participating in a multisite study between 1999-2001. Reporting of abuse and violence was extensive, with 80% of women reporting abuse or violence from a partner. Men were more likely to report experiencing violence from friends and others. A high percentage of study participants reported a variety of threatening or coercive experiences with their partners. Past and current interpersonal violence is a characteristic of the lifestyles of the majority entering treatment for methamphetamine dependence.     

Competing risk of household expansion or institutionalization in late life

OBJECTIVES: The purpose of this study was to evaluate predictors of change in household size and institutionalization in late life. METHODS: The Duke Established Populations for Epidemiologic Studies of the Elderly cohort (n = 3730) was assessed annually (1986-1996). Independent variables included home ownership, income, cognitive and functional ability, chronic illness, mood, household size, social support, and stressful life events. Competing risk of household expansion or institutionalization was modeled using (a) hazard of either event and (b) odds of household expansion or institutionalization among elders who experienced an event. RESULTS: Hazard of either event was associated with younger age, Black race, lower income, cognitive problems and stability, functional abilities and deterioration, low chronic illness burden, being unmarried, having more living children, and recent life events. Among those who reported either event, odds of institutionalization (vs. household expansion) were associated with older age, White race, cognitive and functional problems, high chronic illness burden, being married, having fewer living children, smaller household size, social isolation, and exits of nonspouse coresidents. DISCUSSION: Modeling separate effects of whether there was a household expansion or institutionalization, and if so, which type of event occurred, and taking into account acute and evolving states, enabled more precise understanding of the complex mechanisms involved in determining continued community residence or institutionalization.     

Discrete emotions in later life

More positivity than negativity is demonstrated in this analysis of discrete emotions among 353 community-dwelling individuals from 72 to 99 years old. A complexity in positive emotions was displayed, with more happiness, contentment, and gratitude reported than frustration, sadness, and anger. Our results also imply that another individual's presence may elicit negative emotions such as anger and guilt, whereas perceptions of support may elicit various positive emotions. As expected, certain negative emotions were associated with poor health, with a link between sadness and sickness being most prominent. Of note, poor health did not undermine positive emotions. These findings provide an optimistic view of emotions in later life, even among individuals who are poor, not well educated, and/or physically unwell.     

Functional outcomes and quality of life in peripheral arterial disease: current status

This review examines current evidence for baseline functional impairment and changes with therapy in patients with peripheral arterial disease (PAD)--ranging from patients without claudication or critical limb ischemia (CLI) but other exertional leg symptoms (erroneously referred to as asymptomatic in the Fontaine classification system), to patients with claudication and those with CLI. The review points out that the status of functional outcomes research is markedly different in focus and development in the different levels of disease severity--paradoxically less studied in the more severe CLI population than in patients with claudication, for example.     

Atubular glomeruli in a rat model of polycystic kidney disease

BACKGROUND: Autosomal-dominant polycystic kidney disease (ADPKD) is associated with a progressive decline in glomerular filtration rate (GFR) that often leads to end-stage renal disease. The basis for this decline in GFR is poorly understood. METHODS: Glomeruli in heterozygous Han:SPRD rats with ADPKD and their normal litter mates were studied by light microscopy, using serial sectioning techniques. The connections of the renal corpuscles to proximal tubules were classified as normal, atrophied, or absent (atubular glomerulus). Renal corpuscles also were examined by scanning electron microscopy. Single nephron glomerular blood flows were determined using microspheres. RESULTS: In the kidneys of six-month-old rats with ADPKD, 50% of the glomeruli were atubular and another 26% were associated with atrophied neck segments; these glomeruli were most often smaller in size than normal. About 16% of the glomeruli were hypertrophied and had normal connections to proximal tubules. Sclerotic changes in cystic kidney glomeruli were usually mild or moderate, and belied the failure of glomerular function. Glomerular blood flow in the cystic kidneys averaged half of normal and was markedly heterogeneous; the majority of small glomeruli displayed very low blood flows and a few showed relatively high blood flows. Fewer glomerular abnormalities were found in rats treated for five months with potassium citrate in their drinking water. CONCLUSIONS: The diminished GFR in the rat with ADPKD can be accounted for largely by the formation of atubular glomeruli. Compensatory glomerular hypertrophy also is present and may contribute to the progression of the renal disease.