Publications

OBJECTIVE

Two potential barriers to use of oral contraceptives (OCPs) are out-of-pocket expenditures and the inconvenience of monthly pharmacy visits. This study used nationally representative data to examine the out-of-pocket costs of OCPs and whether women obtain more than 1 pack per purchase.

METHODS

We used data from the 1996 Medical Expenditure Panel Survey. Dependent variables were out-of-pocket expenditures per pack and the number of packs obtained per purchase. Chi2 tests were used to examine the bivariate relationships between the dependent variables and covariates. Regression analyses were used to examine the predictors of OCP expenditures and the number of packs obtained per purchase.

RESULTS

Women paid an average of 14 dollars per pack of OCPs, and 73% obtained only 1 pack per purchase. On average, privately insured women paid 60% of the total expenditures for OCPs. Women who had no prescription drug coverage, who were uninsured, or who were privately insured but not in managed care plans had higher out-of-pocket expenditures. Women who were without prescription drug coverage or who were in managed care plans were more likely to obtain only 1 pack per purchase.

CONCLUSION

Out-of-pocket costs and dispensing restrictions may be barriers to consistent use of OCPs. Women's health care providers should consider options to overcome these barriers, such as the use of mail order prescription services.

OBJECTIVE

Buprenorphine and buprenorphine/naloxone combinations are effective pharmacotherapies for opioid dependence, but doses are considerably greater than analgesic doses. Because dose-related buprenorphine opioid agonist effects may plateau at higher doses, we evaluated the pharmacokinetics and pharmacodynamics of expected therapeutic doses.

DESIGN

The first experiment examined a range of sublingual buprenorphine solution doses with an ascending dose design (n = 12). The second experiment examined a range of doses of sublingual buprenorphine/naloxone tablets along with one dose of buprenorphine alone tablets with a balanced crossover design (n = 8).

PARTICIPANTS

Twenty nondependent, opioid-experienced volunteers.

METHODS

Subjects in the solution experiment received sublingual buprenorphine solution in single ascending doses of 4, 8, 16 and 32 mg. Subjects in the tablet experiment received sublingual tablets combining buprenorphine 4, 8 and 16 mg with naloxone at a 4 : 1 ratio or buprenorphine 16 mg alone, given as single doses. Plasma buprenorphine, norbuprenorphine and naloxone concentrations and pharmacodynamic effects were measured for 48-72 hours after administration.

RESULTS

Buprenorphine concentrations increased with dose, but not proportionally. Dose-adjusted areas under the concentration-time curve for buprenorphine 32 mg solution, buprenorphine 1 6 mg tablet and buprenorphine/naloxone 16/4 mg tablet were only 54 +/- 16%, 70 +/- 25% and 72 +/- 17%, respectively, of that of the 4 mg dose of sublingual solution or tablet. No differences were found between dose strengths for most subjective and physiological effects. Pupil constriction at 48 hours after administration of solution did, however, increase with dose. Subjects reported greater intoxication with the 32 mg solution dose, even though acceptability of the 4 mg dose was greatest. Naloxone did not change the bioavailability or effects of the buprenorphine 16 mg tablet.

CONCLUSION

Less than dose-proportional increases in plasma buprenorphine concentrations may contribute to the observed plateau for most pharmacodynamic effects as the dose is increased.

BACKGROUND

Agitation affects up to 70% of older people with dementia. Valproic acid has been used for the past 10 years to control agitation in dementia, but no systematic review of the effectiveness of this drug has been published to date. The current study examines three randomized, placebo-controlled trials of the effect of valproic acid on older people with dementia who were agitated.

OBJECTIVES

To determine whether evidence supports the use of valproic acid in the treatment of agitation of people with dementia.

SEARCH STRATEGY

Trials were identified from a last updated search of the Specialized Register of the Cochrane Dementia and Cognitive Improvement Group on 10 July 2003 using the terms ("agitat*" or "distur*" or "behavi*" or "aggress*") and "valproic" or "valproate" or "divalpro*." This Register contains articles from all major health care databases and many ongoing trials databases and is regularly updated. The reviewers contacted the authors of publications and drug companies manufacturing valproic acid for additional information.

SELECTION CRITERIA

Randomized, placebo-controlled trials with concealed allocation where agitation and dementia of participants were assessed

DATA COLLECTION AND ANALYSIS

1. Two reviewers extracted data from published trials. 2. Odds ratios of average differences were calculated. 3. Only "intention to treat" analyses were included. 4. Analysis compared participants treated with valproic acid with controls.

MAIN RESULTS

Meta-analysis of the pooled results of the included trials could not be performed because of the following problems. In Porsteinsson 2001, although the physicians having direct responsibility for patient care were blinded, a non-blinded physician, who had no direct contact with these physicians, adjusted divalproex sodium dosage on the basis of reports from blinded raters. Therefore, because the physician who controlled therapy knew which patients were receiving divalproex, the trial did not satisfy the criterion of concealed allocation. In Tariot 2001, 54% of the treated patients dropped out compared with 29% of control patients. Of all treated patients, 22% dropped out because of adverse effects, and the study had to be discontinued prematurely. The third trial (Sival 2002) had a cross-over design. No results from the first phase of the study were available, and although the statistical section stated, "the t-test for independent samples is used to analyze the two-period cross-over trial", because the samples were not independent - they are the same patients in the treatment and placebo groups - a question must be raised about the correctness of the analyses. The type of valproate used in the trials varied - one used short-acting sodium valproate, one long-acting divalproex sodium, and the third early-onset acting divalproex sodium. Average doses differed (480mg/d - 1000mg/d), as did duration of therapy (3 wks - 6 wks), and ways of evaluating patients and their response to therapy. A limited meta-analysis, pooling the results concerning adverse effects (Porsteinsson 2001, Tariot 2001) revealed the following: Sedation occurred more frequently in patients treated with valproic acid than in controls Urinary tract infection was more common among patients treated with valproic acid than controls Because of differences in identifying adverse effects it was not possible to pool other observations concerning adverse effects between the two studies that were examined.

REVIEWERS' CONCLUSIONS

The trials reviewed should be regarded as preliminary. Individual reports suggest that low dose sodium valproate is ineffective in treating agitation among demented patients, and that high dose divalproex sodium is associated with an unacceptable rate of adverse effects. More research on the use of valproate preparations for agitation of people with dementia is needed. On the basis of current evidence, valproate preparations cannot be recommended for the treatment of agitation in dementia.

BACKGROUND

Nursing homes provide care for the elderly who require medical, nursing or rehabilitation services. Legislation for the public health model of mental health care for nursing home residents in the USA was enacted in 1987.

OBJECTIVE

To determine whether the USA act regulating psychiatric care for nursing homes may be applied in Israel.

METHODS

Publications analyzing the outcome of the USA regulations demonstrate improved care as reflected by decrease in restraints and better use of psychotropic compounds. The shortcomings as well as benefits of the USA legislation are tested as to their relevance to the specific economic, environmental and medical issues in Israel.

CONCLUSIONS

The adoption of USA legal acts regulating nursing home residents' psychiatric care may not be feasible in Israel. However, quality of care in nursing homes can be significantly improved if such regulations were "tailored" to Israel's unique structure of nursing homes.

The idiopathic interstitial pneumonias are a heterogeneous group of poorly understood diseases with often devastating consequences for those afflicted. Subclassification of the idiopathic interstitial pneumonia based on clinical-radiological-pathological criteria has highlighted important pathogenic, therapeutic and prognostic implications. The most critical distinction is the presence of usual interstitial pneumonia, the histopathological pattern seen in idiopathic pulmonary fibrosis. Idiopathic pulmonary fibrosis has a worse response to therapy and prognosis. New insight into the pathophysiology of usual interstitial pneumonia suggests a distinctly fibroproliferative process, and antifibrotic therapies show promise. While the clinical and radiographic diagnosis of idiopathic interstitial pneumonias can be made confidently in some cases, many patients require surgical lung biopsy to determine their underlying histopathology. A structured, clinical-radiological-pathological approach to the diagnosis of the idiopathic interstitial pneumonias, with particular attention to the identification of idiopathic pulmonary fibrosis, insures proper therapy, enhances prognostication, and allows for further investigation of therapies aimed at distinct pathophysiology.

Using the Genetic Analysis Workshop 13 simulated data set, we compared the technique of importance sampling to several other methods designed to adjust p-values for multiple testing: the Bonferroni correction, the method proposed by Feingold et al., and naïve Monte Carlo simulation. We performed affected sib-pair linkage analysis for each of the 100 replicates for each of five binary traits and adjusted the derived p-values using each of the correction methods. The type I error rates for each correction method and the ability of each of the methods to detect loci known to influence trait values were compared. All of the methods considered were conservative with respect to type I error, especially the Bonferroni method. The ability of these methods to detect trait loci was also low. However, this may be partially due to a limitation inherent in our binary trait definitions.