Annual direct cost of urinary incontinence.

OBJECTIVE: To estimate the annual direct cost of urinary incontinence in 1995 US dollars. METHODS: Epidemiologically based models using diagnostic and treatment algorithms from published clinical practice guidelines and current disease prevalence data were used to estimate direct costs of urinary incontinence. Prevalence and event probability estimates were obtained from literature sources, national data sets, small surveys, and expert opinion. Average national Medicare reimbursement was used to estimate costs, which were determined separately by gender, age group, and type of incontinence. Sensitivity analyses were performed on all variables. RESULTS: The annual direct cost of urinary incontinence in the United States (in 1995 dollars) was estimated as $16.3 billion, including $12.4 billion (76%) for women and $3.8 billion (24%) for men. Costs for community-dwelling women ($8.6 billion, 69% of costs for women) were greater than for institutionalized women ($3.8 billion, 31%). Costs for women over 65 years of age were more than twice the costs for those under 65 years ($7.6 and $3.6 billion, respectively). The largest cost category was routine care (70% of costs for women), followed by nursing home admissions (14%), treatment (9%), complications (6%), and diagnosis and evaluations (1%). Costs were most sensitive to changes in incontinence prevalence, routine care costs, and institutionalization rates and costs. CONCLUSION: Urinary incontinence is a very costly condition, with annual expenditures similar to other chronic diseases in women.

Absence of transitory [Ca2+]i flux during early in vitro metacyclogenesis of Trypanosoma cruzi.

The phorbol ester TPA (phorbol 12-myristate 13-acetate) substitutes for CO2 as an agonist for transforming Trypanosoma cruzi epimastigotes to the metacyclic trypomastigote stage in a starvation medium consisting of phosphate buffered saline + 10 mM proline, 10 mM sodium acetate and 0.035% NaHCO3. Since TPA is thought to stimulate protein kinase C by mimicking the activity of the secondary messenger diacylglycerol, the above result suggested that T. cruzi metacyclogenesis could be activated by a Ca(2+)-dependent protein kinase C signal induction pathway. Accordingly, cytosolic calcium flux ([Ca2+]i) in epimastigotes, activated with 5% CO2 or TPA (10(-7) M), was measured with the Ca2+ molecular probe, fluo-3AM. In addition, [Ca2+]i was measured in cells incubated with putative metacyclogenic agonists (e.g. proline, glutamate, bioamines, ionophores and catecholamines). None of the compounds studies, except for EGTA, affected cytosolic Ca2+ levels. Control assays with 11 microM thapsigargin, which mobilizes noncytoplasmic Ca2+ stores by inhibiting endoplasmic reticulum Ca(2+)-ATPase, validated our fluorometric assay procedure. Although thapsigargin significantly increases cytoplasmic Ca2+ fluorescence, it has no effect on transformation. The protein kinase C inhibitors staurosporine, H-7 and HA 1004 were tested for their effect on T. cruzi metacyclogenesis. Low concentrations of staurosporine and HA 1004 significantly elevated Peru strain transformation while H-7 had no effect on Peru strain metacyclogenesis. Inhibitor H-7 did significantly depress CL transformation. The results indicate that induction of T. cruzi metacyclic trypomastigote formation by CO2 and TPA is not accompanied by changes in cytosolic Ca2+ and do not provide supporting evidence for participation of a protein kinase C-mediated phosphoinositide cascade in metacyclogenesis.

Action of exogenous potassium and calcium ions on in vitro metacyclogenesis in Trypanosoma cruzi.

The cations Ca2+ and K+ and the anions Cl-, HCO3-, and PO4- were studied for their contribution to metacyclic trypomastigote formation of Trypanosoma cruzi in starvation media consisting of phosphate-buffered saline (PBS) + 10 mM proline + 10 mM sodium acetate as well as one of the following salts: 0.035% NaHCO3 (PBSNPA), 0.035% K2CO3 (PBSKPA) or 0.035% K2HPO4 (PBSPPA). Isolates CL and DM28c were activated to transform with 5% CO2 and the percent metacyclogenesis determined after incubation for 96 h in PBS starvation media. Maximal metacyclogenesis was found with CaCl2 and KCl. In the presence of K+, the percent transformation was highest with the phosphate salt, followed by the carbonate and the chloride salts. Cells incubated in PBSNPA and the cationic ionophores A23187 (5 x 10(-6) M), lasalocid (5 x 10(-6) M), and valinomycin (10(-8) M) do not survive; addition of 2 mM CaCl2 or 17 mM KCl to DM28c cells, reversed the lethal action of the ionophores permitting differentiation into metacyclic forms. The addition of CaCl2 to CL cells incubated in ionophores abrogated the lethal effect of the ionophores but transformation was significantly different than in control preparations. Adding KCl to ionophore incubated cells resulted in normal levels of transformation except in the case of valinomycin. DM28c and CL cells incubated in PBSKPA show significantly greater metacyclogenesis in the presence of 5 mM EGTA. These results indicate that exogenous concentrations of several cations and anions significantly influence T. cruzi metacyclogenesis and that the degree of response by the parasite to free ion levels may be strain dependent.