Methods of cost-effectiveness analysis in the evaluation of new antipsychotics: implications for schizophrenia treatment

Because health care payers are increasingly interested in learning whether new treatments offer value for money, there has been an abundance of research into the cost-effectiveness of pharmacologic therapies in the United States. In the past few years, a number of studies comparing the cost-effectiveness of the conventional neuroleptics with that of the atypical antipsychotics have been published. Cost-effectiveness analyses show the relationship between the resources used (costs) and the health benefits achieved (effects) for a health or medical intervention compared with an alternative strategy. Ideally, the analyses can help decision makers improve the health of the population by better allocating society's limited health care resources. However, the extent to which cost-effectiveness data are actually used in decision making is unclear. The analyses are sometimes viewed with skepticism, in part because studies differ in their methodological approaches. Recently, the U.S. Panel on Cost-Effectiveness in Health and Medicine offered recommendations for standard methodological practices, which may help improve the quality of studies and the acceptability of the approach in the future. The issue is particularly important in light of new legislation governing how the Food and Drug Administration will regulate promotional claims made by drug companies regarding health economic information.     

The economic cost of Alzheimer's disease and related dementias to the California Medicaid program ("Medi-Cal") in 1995.

Although state Medicaid programs may bear a large portion of the costs of Alzheimer's disease (AD), current information on spending is not available. Using a health insurance claims database for a 10% random sample of California Medicaid ("Medi-Cal") recipients 60+ years of age, the authors estimated the excess cost of AD to Medi-Cal in 1995 as the difference in expenditures between an AD cohort (those with AD or related dementias) and an age- and sex-matched cohort without AD. Among 62,450 recipients, 2,575 (4.1%) were found to have AD or related dementias, and their average payments were approximately $7,700 higher (P<0.01) than those for the comparison group. These estimates suggest that Medi-Cal spends about $200 million on AD and related dementias annually, a burden that represents nearly 10% of state spending on elderly patients.     

Experiences with the GSB (Geschwend-Scheier-Bähler) III total endoprosthesis in the elbow joint

Studies on the results with elbow prostheses published in the seventies reported on marked problems such as high loosening rates and instabilities of the joints. However, enormous progresses in elbow replacements have been made in the meantime. Therefore, we analyzed the results of the GSB III-elbow-prostheses that were implanted in our department for 9 years. Between January 1, 1987 and April 1995 at our department 34 total elbow replacements were performed in 32 patients. In this study, we reviewed 25 patients with elbow replacements both clinically and radiologically. The clinical outcome was rated according to the score of INGLIS and PELLICI. The mean follow-up time was 3.7 years. Our follow up examination revealed a total complication rate of 22%. Septic prosthesis loosening with explantation of the prostheses occurred in 3 patients resulting in a prosthesis survival-rate of 88%. However, clinical assessment revealed 80% excellent or good results. While the range of motion could only be improved to a small degree, a marked reduction of the preoperative pain could be achieved. Patients were satisfied with the outcome of the operation in 97%. Although the results of total elbow arthroplasties cannot be compared with those of hip or knee arthroplasties, in selected patients with rheumatoid arthritis and osteoathrosis the use of elbow replacements proved to be a successful procedure with satisfactory results. The implantation of elbow prostheses should mainly be considered when debilitating pain, strongly limited range of motion and instability of the joint are the main problems.     

Response of hyperhomocysteinemia to folic acid supplementation in patients with end-stage renal disease

BACKGROUND: Elevated concentrations of homocysteine are associated with an increased risk for cardiovascular disease. Reasons for elevated homocysteine concentrations are folate or vitamin B12 deficiency, renal disease or genetic abnormalities. A high prevalence of hyperhomocysteinemia is found in patients with end-stage renal disease (ESRD). Since these patients are also at increased risk for vitamin deficiency, a supplementation study comparing two doses of folic acid was performed in patients with ESRD treated with maintenance hemodialysis or with peritoneal dialysis. PATIENTS AND METHODS: Patients undergoing hemodialysis (n = 70) or peritoneal dialysis (n = 12) were supplemented with 2.5 mg or 5 mg folic acid (three times per week after each dialysis treatment) for four weeks in a parallel study design. In 20 hemodialysis patients, the effect of folic acid withdrawal was observed after four weeks. RESULTS: Both supplementation schemes reduced homocysteine to a similar extent (35%) but did not normalize homocysteine concentrations in the majority of patients. Dialysis also had a strong homocysteine lowering effect. After supplementation, 74% of the hemodialysis patients had post-dialysis homocysteine concentrations within the reference range (<16 micromol/l). Homocysteine concentrations remained decreased in 20 patients four weeks after withdrawal of folic acid supplementation. CONCLUSIONS: It is concluded that supplementation with 2.5 or 5 mg folic acid has a similar effect on homocysteine concentrations to supplementation regimens using 15 mg folic acid supplements. In contrast to the effect of folic acid supplementation in subjects with normal renal function, folic acid supplementation does not normalize homocysteine concentrations in ESRD patients.     

Surgical management of symptomatic spinal metastases. Postoperative outcome and quality of life

STUDY DESIGN: Eighty-six surgical interventions in 76 consecutive patients with symptomatic spinal metastases were reviewed retrospectively. OBJECTIVES: To evaluate the postoperative outcome and quality of life of patients surgically treated for symptomatic spinal metastases. SUMMARY OF BACKGROUND DATA: The standard surgical treatment for patients with symptomatic spinal metastases is anterior spinal cord decompression with stabilization. However, because therapy is only palliative, satisfactory quality of life and high patient acceptance are essential. METHODS: The medical records of all patients were reviewed retrospectively. Furthermore, all surviving patients or the next of kin of deceased patients were interviewed by telephone, and the family doctors or the care-providing physicians of external institutions were contacted. RESULTS: First-choice surgical treatment was anterior spinal cord decompression with stabilization. Postoperative mean survival was 13.1 months, and mean time at home after spinal surgery was 11.1 months. Neurologic improvement with regard to Frankel classification was observed in 58% of the patients, and 93% were able to walk postoperatively. Pain relief was noted in 89%. Overall, 67% of the patients achieved moderate or good general health as shown by the Karnofsky Index, and 80% were satisfied or very satisfied with the surgical intervention. Moreover, 19% of the surgical interventions were associated with complications, local tumor recurrence developed in 22% of the patients, and paraplegia ultimately developed in 18% of patients. CONCLUSIONS: Surgical management of symptomatic spinal metastases, in particular anterior decompression, is of benefit in most metastatic lesions in terms of satisfactory postoperative outcome and quality of life. However, in patients with melanoma or lung carcinoma, the authors advocate spinal surgery only in very exceptional cases.     

2-(diethylamino)thieno1,3ŏxazin-4-ones as stable inhibitors of human leukocyte elastase

A series of 2-(diethylamino)thieno1,3?xazin-4-ones was synthesized and evaluated in vitro for inhibitory activity toward human leukocyte elastase (HLE). The Gewald thiophene synthesis was utilized to obtain several ethyl 2-aminothiophene-3-carboxylates. These precursors were subjected to a five-step route to obtain thieno2,3-d1,3?xazin-4-ones bearing various substituents at positions 5 and 6. Both thieno2,3-d and thieno3,2-d fused oxazin-4-ones possess extraordinary chemical stability, which was expressed as rate constants of the alkaline hydrolysis. The kinetic parameters of the HLE inhibition were determined. The most potent compound, 2-(diethylamino)-4H-1benzothieno2,3-d1,3?xazin-4-one, exhibited a K(i) value of 5.8 nM. 2-(Diethylamino)thieno1, 3?xazin-4-ones act as acyl-enzyme inhibitors of HLE, similar to the inhibition of serine proteases by 4H-3,1-benzoxazin-4-ones. The isosteric benzene-thiophene replacement accounts for an enhanced stability of the acyl-enzyme intermediates.     

On the contractile function of protein phosphatases in isolated human coronary arteries

It is unknown whether protein phosphatases types 1 and 2A are present in and can regulate the tone of human vascular tissue. The expression and possible function of serine/threonine protein phosphatases (PP) type 1 (PP1) and type 2A (PP2A) were studied in isolated human coronary arteries. Catalytic subunits of PPI and PP2A were identified by means of phosphatase activity measurement in tissue homogenates, by separation of enriched extracts through affinity column chromatography, by immunoblotting with specific antibodies, by hybridization of mRNA with specific DNA probes and PCR of reverse transcribed mRNA. Based on these methods, the catalytic subunits of PP1(alpha,beta,gamma) and PP2A(alpha,beta) were identified. Appropriately, cantharidin, an inhibitor of PP1 and PP2A, increased basal tone of human isolated coronary artery rings with an EC50 of about 16 micromol/l by increasing the phosphorylation state of the regulatory light chains of myosin. In summary, PP1 and PP2A are expressed in human coronary arteries and they can alter vascular tone.     

Expression of endothelial cell-derived nitric oxide synthase (eNOS) is increased during gastric adaptation to chronic aspirin intake in humans

BACKGROUND: Gastric adaptation to aspirin is well-documented. However, the mechanisms underlying the reduction of aspirin-induced mucosal damage despite continued ingestion of the drug remain poorly understood. METHODS: Eight healthy volunteers who received aspirin 1 g b.d. for 14 days were compared with eight placebo-dosed controls. Gastroscopy with mucosal biopsy was performed, and gastric mucosal blood flow was measured before and following 3, 7 and 14 days of aspirin treatment. At the same time points, tissue concentration and the content of prostaglandin E2 in the gastric juice were determined and expression of endothelial cell-derived nitric oxide synthase (eNOS) in mucosal biopsies was measured using Western blot analysis. RESULTS: Aspirin-induced mucosal damage that reached a maximum on day 3, declining significantly by day 14. Concomitantly, mucosal blood flow significantly increased on day 3 and returned to initial values on day 14. Aspirin intake led to a significant decrease in prostaglandin E2 concentration in the gastric mucosa and in gastric juice during the whole period of aspirin consumption. eNOS expression started to increase on day 7 in oxyntic mucosa and on day 3 in antral mucosa, reaching its highest values at the end of the consumption of aspirin. CONCLUSIONS: The human gastric mucosa adapts to prolonged aspirin intake, and this is accompanied by an increase in mucosal blood flow and reduced prostaglandin synthesis. Increase of mucosal eNOS expression might compensate for reduced prostaglandin synthesis and be responsible for gastric adaptation to chronic aspirin intake in humans.     

Situational management

In this paper, the organizational theory of situational planning is used to establish a decentralized management model for complex health units. Because of cultural limitations imposed on a perspective of change and rationalization, considerations are made in relation to a given form of dealing with culture, keeping in mind the feasibility of the management model. A particular type of communicative management emerges as a general need revealed by the analysis of the object at issue: the management of professional organizations.