Evaluation of the total cost of treating elderly hypertensive patients with ACE inhibitors: a comparison of older and newer agents.

We compared total costs and adherence to the regimen of older versus newer angiotensin-converting enzyme (ACE) inhibitors for the treatment of elderly patients with hypertension. A computer search using the data base of a health care insurer identified 6176 subjects age 65 years or older who had ICD-9 coding for hypertension only and had a new prescription for an ACE inhibitor dispensed between April 1, 1992, and January 31, 1993. Subjects receiving concurrent antihypertensive drugs were included. Total cost of therapy included acquisition costs for the ACE inhibitors and concurrent antihypertensive agents, and nondrug costs. Other costs were laboratory tests, hospitalization, and clinic visits associated with monitoring outcomes of antihypertensive therapy. Total median cost per month was greater for older than for newer agents, $59.82 versus $53.09 (p<0.0009). The mean percentage of patients complying with therapy as determined by refill data was greater with newer than with older agents, 66% versus 58% (p<0.0001). Based on our results, newer ACE inhibitors should be first-line antihypertensive therapy in elderly patients. They also should be considered for elderly patients who are unresponsive to older ACE inhibitors.

Cost-effectiveness of levonorgestrel subdermal implants. Comparison with other contraceptive methods available in the United States.

The objective of this analysis was to evaluate and compare the cost-effectiveness of eight contraceptive methods: condoms, diaphragms, oral contraceptives, intrauterine devices, medroxyprogesterone acetate suspension, levonorgestrel subdermal implants, tubal ligation and vasectomy. Based on a comprehensive review of the literature and various additional data sources, this analysis identified, measured and compared direct costs of the methods, physician visits, treatment of adverse effects and cost of failure (i.e., mean cost for all types of deliveries or first-trimester abortion). Medical benefits (if any) resulting from each contraceptive method were calculated and considered in the analysis as cost savings. The cost of method failure proved to be the greatest influence on cost-effectiveness. Sterilization was identified as the most cost-effective method overall. Of the reversible methods, the intrauterine device was found to be the most cost-effective, followed by levonorgestrel implants.

PIP: Cost is an important factor which can influence the choice of a particular contraceptive method. Costs affect not only patients, but the ability of social service systems to provide access to contraception. Levonorgestrel implants were approved by the Food and Drug Administration in December 1990 as the first available contraceptive subdermal implant. They have since been inserted in 780,000 women in the US. The authors developed a cost-effectiveness model to evaluate and compare the cost-effectiveness of these implants against those of condoms, diaphragms, oral contraceptives, IUDs, medroxyprogesterone acetate suspension, tubal ligation, and vasectomy. The model identifies, measures, and compares direct costs of the methods, physician visits, the treatment of adverse effects, and cost of failure, thus calculating an expected cost per year for each method. Medical benefits, if any, resulting from the use of each method were calculated and considered in the analysis as cost savings. A sensitivity analysis was performed using cost parameters and failure rates, both independently and in combination. Data for the analysis were drawn from a comprehensive literature review, physician surveys, manufacturer package inserts, 1992 diagnosis-related group hospital reimbursement rates from Medicaid, and physician interviews. The cost of method failure had the greatest influence upon cost-effectiveness, with sterilization identified as the most cost-effective method overall. Of the reversible methods, the IUD was found to be the most cost-effective, followed by levonorgestrel implants.

Response of murine bone marrow granulocyte-macrophage colony-forming units to hyperthermia in situ.

A detailed understanding of how bone marrow stem cell progenitors are affected by heat is prerequisite to predicting how whole-body or regional hyperthermia protocols may affect bone marrow function. This investigation reports the reproductive integrity of murine tibial bone marrow granulocyte-macrophage colony-forming units (CFU-GM) after in situ hyperthermia. Heat was applied by water bath immersion of the leg of male BALB/c mice anesthetized with 90 mg/kg pentobarbital given subcutaneously. Tibial and rectal temperatures were monitored in representative animals by microthermocouples (tip diameter approximately 100 microns). By approximately 3 min after immersion of the limb, marrow temperature was within 0.3 degree C of water bath temperature (O'Hara et al., Int. J. Hyperthermia 5, 589-601, 1989) and was within 0.1 degree C by 5 min after immersion. The CFU-GM were cultured in "lung-conditioned" McCoy's 5A medium supplemented with 15% fetal calf serum and 0.3% Bacto agar. In situ heating of tibial marrow to exposure temperatures of 42, 42.5, 43, 44, and 45 degrees C gave D0's (+/- 95% CI) of 91 +/- 44, 44 +/- 27, 27 +/- 2.2, 16 +/- 6, and 7 +/- 4 min, respectively. Heating to 41.5 degrees C for up to 180 min did not result in cytotoxicity. Development of thermotolerance after approximately 100 min of heating was apparent by the presence of a "resistant tail" of the 42 degrees C survival curve. A plot of D0 vs water bath temperature was bimodal with an inflection point at approximately 42.5 degrees C. The inactivation enthalpy for temperatures above 42.5 degrees C was 586 kJ/mol (140 kcal/mol) and for temperatures below 42.5 degrees C was estimated to be 1205 kJ/mol (288 kcal/mol). These results show that CFU-GM can be heated predictably in situ, can be inactivated with thermal exposures as low as 42 degrees C, and are capable of developing thermotolerance. These findings underscore the necessity to understand stem cell inactivation by hyperthermia in situ prior to widespread implementation of clinical hyperthermia protocols where bone marrow may be included in the treatment field.

Assessing cost effects of nursing-home-based geriatric nurse practitioners.

Employment of geriatric nurse practitioners (GNPs) is one strategy to improve nursing home care. The effects of GNPs on costs and profitability of nursing homes and on costs of patient medical service use outside the nursing home are examined. Employment of GNPs does not adversely affect nursing home costs or significantly affect profits. There is some evidence of cost savings in medical service use for newly admitted patients but no evidence of savings for continuing residents. GNPs reduce the use of hospital services for both groups, and the reduction is statistically significant for newly admitted patients.

Effects of a geriatric nurse practitioner on process and outcome of nursing home care.

We compared measures of quality of care and health services utilization in 30 nursing homes employing geriatric nurse practitioners with those in 30 matched control homes. Information for this analysis came from reviews of samples of patient records drawn at comparable periods before and after the geriatric NPs were employed. The measures of geriatric nurse practitioner impact were based on comparisons of changes from pre-NP to post-NP periods. Separate analyses were done for newly admitted and long-stay residents; a subgroup of homes judged to be best case examples was analyzed separately as well as the whole sample. Favorable changes were seen in two out of eight activity of daily living (ADL) measures: five of 18 nursing therapies; two of six drug therapies; six of eight tracers. There was some reduction in hospital admissions and total days in geriatric NP homes. Overall measures of medical attention showed a mixed pattern with some evidence of geriatric NP care substituted for physician care. These findings suggest that the geriatric NP has a useful role in nursing home care.

Influence of limb restraint on the thermal response of bone marrow CFU-GM heated in situ.

The method used to restrain anaesthetized (sodium pentobarbital) mice for in situ heating of tibial marrow affects the survival response of CFU-GM. Three methods of limb restraint, in addition to ischaemia induced by tourniquet, were examined for their relative effect on the thermal response of CFU-GM. The three methods of restraint were to secure only the toes with suture material to a submersion post in the water bath, to tape the foot, or to tape the leg. Temperatures in the lumen of the tibia were measured with a 100 micron (tip diameter) microthermocouple during representative experimental conditions. After heating in situ, bone marrow was extruded and CFU-GM cultured in standard soft agar conditions in lung-conditioned medium. The most restrictive restraining method, i.e. taping the leg, produced the greatest thermal response among the three restraining methods examined. The D0 (+/- 95% CI) of the 42 degrees C survival curve for CFU-GM was 22 +/- 4, 46 +/- 8, or 94 +/- 53 min for restraint of leg, foot, or toes, respectively. Survival reached a plateau by 100 min of heating indicative of the development of thermotolerance. The D0 of the 44 degrees C survival curve was 3 +/- 1, 6 +/- 2 and 16 +/- 6 min for restraint of leg, foot, or toes respectively. Ischaemia produced the most pronounced effect on the thermal response of tibial CFU-GM with D0 values of 2 +/- 1 or 3.6 +/- 1.5 min after exposure to 44 degrees C or 42 degrees C, respectively. The method of limb restraint affects the thermal sensitivity of CFU-GM most probably by blood flow obstruction and resultant pH decrease. Thus, precautions must be taken to ensure that limb restriction does not introduce artifacts in the hyperthermia response of normal tissues or tumours during heating in situ.

Long-term digitalis therapy improves left ventricular function in heart failure.

To clarify the controversy regarding the benefits of long-term oral digoxin in the treatment of heart failure, we evaluated hemodynamics at rest and during exercise in nine patients in sinus rhythm with symptomatic heart failure. Patients were studied during long-term digoxin therapy, after withdrawal of the drug, and six hours after readministration. Upon withdrawal of digoxin, pulmonary capillary-wedge pressure increased from 21 +/- 8 to 29 +/- 10 mm Hg, and cardiac index decreased from 2.4 +/- 0.7 to 2.1 +/- 0.6 liters per minute per square meter of body-surface area, suggesting a deterioration in left ventricular function. In addition, heart rate tended to increase and stroke-work index, stroke-volume index, and radioangiographic ejection fraction decreased. Acute readministration restored the hemodynamic values to those observed during long-term digoxin therapy. The improvement in hemodynamics during long-term digoxin administration was also observed during exercise. This improvement demonstrated the value of long-term oral digoxin therapy in congestive heart failure.

Attenuation of prazosin effect on cardiac output in chronic heart failure.

The persistence of the hemodynamic effects of prazosin was studied in 12 patients with chronic congestive heart failure. Multidose evaluation involving five 5-mg doses showed the initial decrease in systemic vascular resistance and increase in cardiac index, stroke work index, and stroke volume index to be transient. Doubling the dose did not restore effect. Modest decreases in pulmonary capillary-wedge and mean arterial pressures persisted throughout the study. In six patients, plasma prazosin concentration measured at times of hemodynamic observations showed the initial hemodynamic effect of prazosin to attenuate upon further administration despite mean plasma concentrations that exceeded those measured after the first dose. In patients with chronic heart failure, resting hemodynamic studies suggest a rapid attenuation of prazosin-mediated hemodynamic effect in the presence of adequate plasma concentration. Recognizing this phenomenon, if long-term prazosin therapy for congestive heart failure is contemplated, we suggest the hemodynamic response in individual patients be monitored.

Diffuse glomerulonephritis in rabbits with Streptococcus viridans endocarditis.

Intravenous administration of live microorganisms to rabitts with cardiac catheters produces an experimental model of infective endocarditis. Despite the development of infected valvular vegetations, positive blood cultures, splenomegaly, and focal embolic renallesions, glomerulonephritis has not been found in these animals. In the present study, acute diffuse proliferative glomerulonephritis, featuring endothelial and mesangial proliferation, capillary occlusion, and leukocytic infiltration was produced in rabbits immunized withthe infecting agent prior to the establishment of left sided alpha-streptococcal endocarditis. Controls receiving immunization alone, immunization and sterileendocarditis, or infective endocarditis alone did not develop diffuse glomerulonephritis. Electron microscopic findings of occasional subendothelial electron-dense deposits and immunofluorescence deposition of IgG and C3 in a peripheral granular capillary pattern were consistent with an immune complex type nephritis. Decreased serum complement levels were demonstrated in those animals developing diffuse glomerulonephritis, and some animals developed circulating rheumatoid factor. In view of the morphologic findings and the necessity of preimmunization for development of glomerular changes, it is concluded that immune mechanisms play a role in the diffuse glomerulonephritis associated with this model of infective endocarditis.