Pharmacokinetic interactions and side effects resulting from concomitant administration of lithium and divalproex sodium

BACKGROUND: Valproic acid is added to the lithium regimens of many patients with bipolar disorder, especially those with mania refractory to lithium treatment. METHOD: We evaluated the pharmacokinetic effects and safety of coadministration of lithium and valproate in 16 healthy volunteers in this randomized, placebo-controlled, two-period (12 days each) crossover trial. Valproate or placebo was given twice daily. On Days 6-10, lithium was added. Blood samples drawn on Days 5 and 10 were analyzed for valproate by high-pressure liquid chromatography (HPLC) and for lithium by atomic absorption spectrophotometry. RESULTS: Lithium pharmacokinetics were unchanged by valproate, but valproate C(max), C(min), and AUC rose slightly during lithium coadministration. Adverse events did not change significantly. CONCLUSION: Concomitant administration of lithium and valproate appears to be safe in patients with bipolar disorder.     

Cost-effectiveness of laparoscopic cholecystectomy versus open cholecystectomy

To assess the cost-effectiveness of laparoscopic cholecystectomy versus open cholecystectomy from the payer's perspective, we estimated the probabilities of potential outcomes of each procedure, associated quality-of-life effects, and related direct medical charges and incorporated these estimates into a computerized simulation model. The model projects that laparoscopic cholecystectomy will be more effective than open surgery in terms of total mortality and quality-adjusted survival, for both sexes and all ages. Projected 5-year cumulative charges are lower for laparoscopic cholecystectomy than for open cholecystectomy ($5,354 versus $5,525 for 45-year-old women; $6,036 versus $6,830 for 45-year-old men), and the differences increase substantially with increasing age. We concluded that laparoscopic cholecystectomy is likely to be less costly and more effective than open cholecystectomy for most patients, as long as it does not routinely require preoperative cholangiography and is not associated with increased professional fees or increased risks of retained stones or bile duct injury.     

Risperidone versus haloperidol: II. Cost-effectiveness

Australia and Canada are currently the only Western nations with government guidelines for analyzing the cost-effectiveness of drugs. We used guidelines issued by the Australian Pharmaceutical Benefits Advisory Committee to construct a model for comparing the cost-effectiveness of risperidone and haloperidol over a 2-year period in patients with chronic schizophrenia. Use of clozapine was also included in the analysis as an alternative treatment given to patients who proved unresponsive to therapy with haloperidol or risperidone. Results are expressed in Australian dollars. Cost-effectiveness was determined by using decision-analytic modeling to compare clinical outcomes and costs. The analytic model contained a decision tree for each of the compared agents that tracked the distribution of patients between treatment outcome pathways (i.e., scenarios). Distributions were based on probabilities derived from our meta-analysis results reported elsewhere and from other sources. Each scenario had an associated monetary cost that included all significant direct costs (i.e., hospital costs; outpatient costs; and the cost of drugs, the services of health care professionals, and government-subsidized hostel accommodation). The cost for a given outcome was the sum of costs for all scenarios leading to that outcome. Cost-effectiveness was expressed as the total cost per favorable outcome. The definition of a favorable outcome was one in which the patient was in a response phase at the end of the 2-year period. The probability of a patient experiencing a favorable outcome at the end of 2 years was 78.9% for risperidone versus 58.9% for haloperidol. The total cost of treatment for 2 years was $15,549.00 for risperidone versus $18,332.00 for haloperidol. The expected cost per favorable outcome was $19,709.00 for risperidone and $31,104.00 for haloperidol. Risperidone was more cost-effective than haloperidol and therefore was "dominant" in pharmacoeconomic terms because it produced a higher proportion of favorable outcomes at lower cost. Sensitivity analysis showed that the difference in clinical response rate was a key determinant of cost-effectiveness.     

Cost-effectiveness comparison of sequential ofloxacin versus standard switch therapy

OBJECTIVE: To compare the cost-effectiveness of sequential intravenous-to-oral ofloxacin versus intravenous-to-oral standard switch therapy for the treatment of patients with sepsis who are hospitalized with bacterial infections. DESIGN: Cost-effectiveness analysis from a provider perspective, including resources important to an integrated healthcare network, of a randomized, open-label, controlled, clinical trial. SETTING: Millard Fillmore Health System, Buffalo, NY. PATIENTS: Hospitalized adults requiring parenteral antibiotics for a complicated urinary tract infection, lower respiratory tract infection, or skin and soft tissue infection. INTERVENTIONS: Sequential intravenous-to-oral ofloxacin or standard intravenous-to-oral switch antibiotics. OUTCOME MEASURES: Clinical outcomes and direct costs associated with hospitalization, primary physician services, specialist physician services, and outpatient care. RESULTS: Eighty-two of 89 patients randomized into the two treatment groups were evaluable. Standard switch therapy failed with 12 patients versus 10 patients receiving ofloxacin. Complete economic data were available for 74 patients. Sequential ofloxacin therapy resulted in a 1-day-shorter antibiotic-related hospitalization without evidence of recurrent infection during the posttherapy follow-up evaluations. An average cost savings of $399 per patient was achieved in the sequential ofloxacin group. Although this difference did not attain statistical significance (probably due to the large variance), it is an economically significant finding. The cost-effectiveness ratios were $5735 per successful outcome for the standard switch therapy group versus $5126 per successful outcome in the sequential ofloxacin group. CONCLUSIONS: Sequential ofloxacin was as effective and consistently less expensive than standard switch antibiotics in the initial evaluation and in the sensitivity analysis of room cost and drug acquisition cost. Standard switch therapy would have to be greater than 25% more effective than sequential ofloxacin therapy to change the economic decision.     

A pharmacoeconomic model of divalproex vs. lithium in the acute and prophylactic treatment of bipolar I disorder

BACKGROUND: Divalproex and lithium are the two most rigorously studied pharmacologic treatments for acute mania in bipolar I disorder in randomized, controlled trials. The differences between the drugs in their time course of onset, predictors of response, and side effects have potentially important pharmacoeconomic implications. METHOD: Utilizing data from published studies, the University of Cincinnati Mania Project, and a consensus panel of psychiatrists, we developed a decision-analytic model to estimate the costs of treating patients with bipolar I disorder, acutely and prophylactically, for 1 year with divalproex or lithium. RESULTS: In the overall group of patients with bipolar I disorder, initial treatment with divalproex led to costs that were 9% lower than costs for initial treatment with lithium. Cost savings associated with divalproex were greatest for patients with mixed mania and rapid cycling, whereas cost savings for patients with classic mania were greater for lithium. CONCLUSION: According to the decision-analytic model developed in this study, divalproex, possibly because of a more rapid rate of antimanic activity associated with oral loading, is a less costly treatment than lithium in the acute and prophylactic treatment of patients with bipolar I disorder over 1 year.     

Cost-effectiveness of open versus laparoscopic repair for primary inguinal hernia

A cost-effectiveness (CE) analysis was performed of Bassini versus laparoscopic repair for primary inguinal hernia. Incremental costs per 1-year recurrence-free patient were calculated for the societal and hospital perspective. From the hospital perspective, the incremental CE ratio of laparoscopic repair is 5.348 guilders. From the societal perspective, laparoscopic repair is both less costly and more effective than Bassini repair. Results were sensitive to assumptions about recurrence rates, laparoscopic operating time, and return to work. Laparoscopic repair should replace Bassini repair in order to benefit society. From the hospital perspective, the decision to accept laparoscopic repair depends on the willingness to pay.     

A pilot study of lithium carbonate plus divalproex sodium for the continuation and maintenance treatment of patients with bipolar I disorder

PURPOSE OF STUDY: To assess whether selected periapical radiographs, taken according to High Yield Criteria, can reveal as much intra-osseous pathology as universal panoramic screening. POPULATION STUDIED: The records of 1101 RAF recruits enlisted in 1988-89, average age 19 years (range 16-26). METHODS: The clinical records and bitewing radiographs of the recruits were examined and the requirement for periapical radiographs determined according to high yield criteria. A template, cut out to simulate the area covered by a periapical bitewing radiograph, was placed over the suspect region on the panoramic film and any findings found within the template recorded. The entire dental panoramic tomograph was then examined on a masked screen under 2X magnification and any further findings recorded. FINDINGS: There was a considerable number of findings reported, including three large isolated radiolucent areas, 75 periradicular radiolucent areas, four probable cysts and 1187 unerupted mandibular third molars. However, when the clinical significance of these 'lesions' was assessed only those related to dental causes appeared to have significant clinical implications and the results indicated that these could have been detected by selective radiology. CONCLUSION: This study showed that the only pathology which occurs frequently enough to justify radiographic screening of the jaws in young adults is related to teeth. It seems probable that this type of pathology can be at least as well detected by selective periapical screening, using high yield criteria, as is possible by universal panoramic screening.     

Cost-effectiveness of enoxaparin versus low-dose heparin for prophylaxis against venous thrombosis after major trauma

We attempted to determine health and economic outcomes from the perspective of an integrated health system of administering enoxaparin 30 mg twice/day versus heparin 5000 U twice/day for prophylaxis against venous thrombosis after major trauma. A decision-analytic model was developed from best literature evidence, institutional data, and expert opinion. We assumed that 40% of proximal deep vein thromboses (DVTs) and 5% of distal DVTs are diagnosed and confirmed with initial or repeat duplex scanning; 50% of undiagnosed proximal DVTs result in pulmonary embolism; 2% and 1% of undiagnosed proximal DVTs will lead to readmission for DVT and pulmonary embolism, respectively, and pulmonary embolism-related mortality rates range from 8-30%. Length of hospital stay data and 1996 institutional drug use and acquisition cost data were used to estimate the cost of enoxaparin and heparin therapy. Diagnosis and treatment costs for DVT and pulmonary embolism were derived from institutional charge data using cost:charge ratios. A second analysis of patients with lower extremity fractures was completed. One-way and multiway sensitivity analyses were performed. For 1000 mixed trauma patients receiving enoxaparin versus heparin, our model showed that 62.2 (95% CI -113 to -12) DVTs or pulmonary emboli would be avoided, resulting in 67.6 (8 to 130) life-years saved at a net cost increase of $104,764 (-$329,300 to $159,600). Enoxaparin versus heparin resulted in a cost of $1684 (-$3600 to $9800) for each DVT or pulmonary embolus avoided and a discounted cost/life-year saved of $2303 (-$8100 to $19,000). For 1000 patients with lower extremity fractures, enoxaparin versus heparin resulted in a cost of $751 (-$4200 to $3300) for each DVT or pulmonary embolus avoided and a discounted cost/life-year saved of $1017 (-$10,200 to $6300). Although enoxaparin increases overall health care costs, it is associated with a cost/additional life-year saved of only $2300, which is generally lower than the commonly used hurdle rate of $30,000/life-year saved. The cost-effectiveness ratio is more favorable in patients with lower extremity fractures than in the general mixed trauma population.     

Cost-effectiveness analysis

When different health care interventions are not expected to produce the same outcomes both the costs and the consequences of the options need to be assessed. This can be done by cost-effectiveness analysis, whereby the costs are compared with outcomes measured in natural units--for example, per life saved, per life year gained, and per pain or symptom free day. Many cost-effective analyses rely on existing published studies for effectiveness data as it is often too costly or time consuming to collect data on cost and effectiveness during a clinical trial. Where there is uncertainty about the costs and effectiveness of procedures sensitivity analysis can be used, which examines the sensitivity of the results to alternative assumptions about key variables. In this article Ray Robinson describes these methods of analysis and discusses possibilities for how the benefits of alternative interventions should be valued.     

Substitution of immediate-release valproic acid for divalproex sodium for adult psychiatric inpatients

In a prospective open-label study, the substitution of immediate-release valproic acid for divalproex sodium was evaluated in the treatment of 47 adult psychiatric inpatients who had been stabilized on divalproex for at least one month. After two weeks, no significant change in Clinical Global Impressions scale (CGI) scores or in seizure frequency occurred, and serum valproate concentrations decreased by 14.4 percent (p=.001). One patient was restarted on divalproex because of gastrointestinal complaints. Among the 19 patients remaining hospitalized at six months, mean CGI scores did not significantly change. Costs were reduced 83 percent; annual savings per patient was approximately $905. These preliminary results suggest that many chronic psychiatric inpatients stabilized on divalproex may be safely switched to valproic acid.     

Cost-effectiveness of ultrasound-guided liver biopsy

The risk of a major complication from "blind" percutaneous liver biopsy is reported to be in the range of 0.24% to 3.8%. In a recent randomized trial, patients whose liver biopsies were performed with ultrasonography had a significant reduction in complications requiring hospitalization compared with patients without ultrasound-guided biopsies (0.5% vs. 2.2%, P < .05). Despite this, routine use of ultrasonography for liver biopsies has not been implemented because of controversies with respect to cost-effectiveness. The aim of our study was to analyze the relative cost-effectiveness of performing ultrasound-guided liver biopsies using decision analysis. A decision tree was constructed to compare a strategy of liver biopsy using ultrasonography with a strategy without ultrasonography. The major outcomes included were minor complications such as pain requiring analgesics and major complications, which require hospitalization. Costs included were direct medical costs from the payer's perspective. In our baseline model, the cost from complications per patient with and without ultrasonography was $62 and $129, respectively. The marginal effectiveness expressed as the number of major complications avoided was 1.2/100 liver biopsies. The incremental cost to avoid one major complication was $2,731. The model was most sensitive to the frequency of major complications and the additional cost of ultrasonography. Our decision analysis model suggests that ultrasound-guided liver biopsy is cost-effective. Future studies assessing the efficacy of image-guided liver biopsies should be conducted.     

Cost-effectiveness of statin medications.

Responds to the F. B. Garfield (see record 2001-00625-014) comments on the R. M. Kaplan (see record 2000-08148-002) discussion on the enhancement of population health status through disease prevention. Garfield described recent research on cholesterol lowering that might impact Kaplan's findings. Kaplan and Golomb agree that the exclusion of statins from the original article was an oversight, but doubt that greater attention to statins would have changed his original conclusions. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Cost-effectiveness calculations from trials

EFFECTIVENESS OF ANTIHYPERTENSIVE THERAPY: Data on the effectiveness of antihypertensive therapy derived from the results of large clinical trials are of great importance, but also have a number of significant flaws and probably underestimate the real effectiveness of treatment. In the next few years much more information is likely to become available on the effects of the newer classes of drugs and thus evaluations of cost-effectiveness will have fewer limitations than at present. ECONOMIC VALUE OF SAVING A LIFE: Today, in every country worldwide, priority should be given to determining the economic cost of avoiding the morbidity and mortality caused by hypertension. Each society must decide the price per life-year gained that it is willing to pay. This is the most difficult task of all, since the economic value of saving a life is not easily evaluable.