The effect of divalproex sodium on viral load: a retrospective review of HIV-positive patients with manic syndromes.

OBJECTIVE: In vitro studies report that valproic acid causes an increase in HIV-1 replication. This retrospective study examines a sample of patients with HIV disease and behavioural disturbances, for which the treatment of choice is divalproex sodium (DVP), to determine whether DVP causes an increase in HIV-1 replication. METHOD: A chart and database review identified 15 patients with HIV disease presenting with either 1) mania or hypomania or 2) dementia with mania or with hypomania or behavioural disturbances. HIV-1 viral load was compared before and after mood stabilizer initiation. RESULTS: Eleven patients started therapy with DVP, and 4 patients declined treatment with a mood stabilizer. Nine of the 11 patients taking DVP were also receiving antiretroviral therapy. HIV-1 viral load did not increase in 6 of the 9 patients who had measurements between 1 week and 3.5 months after DVP initiation. No follow-up was available for the other 3 patients. Of the 2 patients receiving DVP but not antiretroviral medication, 1 had an increase of 0.17 log in HIV-1 viral load at 4 months. No follow-up record was available for the second patient. The 4 patients not taking DVP were all on antiretroviral therapy; viral loads in 2 of them remained nondetectable over 3 to 4 months, and 1 had an increase of 0.32 log in HIV-1 viral load at 3 months. No follow-up record was available for the fourth patient. CONCLUSIONS: These preliminary data suggest that, in the presence of effective antiretroviral therapy, HIV-1 viral load appears not to be adversely affected by the administration of DVP. The results for the patients receiving DVP in the absence of antiretroviral medication remain indeterminate. Further prospective study is required.

HIV-1 reverse transcriptase sequence in plasma and cerebrospinal fluid of patients with AIDS dementia complex treated with Abacavir.

OBJECTIVE: To assess HIV-1 RNA levels and the relationship between HIV-1 reverse transcriptase (RT) genotype from plasma and cerebrospinal fluid (CSF) during treatment with abacavir (Ziagen, ABC) or placebo in combination with stable background therapy (SBG) in subjects with AIDS dementia complex (ADC) (study CNA3001). DESIGN: One-hundred and five HIV-1 infected adults with ADC were randomized to receive either ABC (600 mg twice daily) or ABC-matched placebo (twice daily) in addition to SBG for 12 weeks. METHODS: Plasma and CSF were collected for population sequencing at baseline and week 12 (CSF optional). Sequences were analyzed for mutations associated with resistance to nucleoside reverse transcriptase inhibitors (NRTI). RESULTS: Sixty out of sixty-seven subjects with baseline plasma HIV-RT sequence data harbored virus with > or = 1 NRTI-associated mutations; 50 out of 67 had the M184V mutation. At week 12, more subjects in the ABC group had plasma HIV-1 RNA < or = 400 copies/ml than the SBG group (46% versus 13%, P = 0.002). Non-response to ABC was associated with multiple baseline zidovudine (ZDV)/stavudine (d4T)-associated mutations. Baseline RT mutation patterns differed in 14 out of 21 (67%) paired samples from plasma and CSF. Four subjects experienced > 1 log10 copies/ml reductions in CSF HIV-1 RNA, two in the absence of reductions in plasma HIV-1 RNA and two with undetectable plasma HIV-1 RNA at baseline. CONCLUSIONS: Substantial decreases in plasma and CSF HIV-1 RNA following addition of ABC were not precluded by baseline HIV-1 NRTI-associated mutations, including the M184V mutation, but non-responders commonly harbored multiple ZDV/d4T-associated mutations. HIV-1 RNA responses and RT genotype appear to be discordant between CSF and plasma in some subjects.

A comparison of two methods for estimating the technical costs of external beam radiation therapy.

PURPOSE: To accurately assess the cost-effectiveness of treatment with external beam radiation, it is necessary to have accurate estimates of its cost. One of the most common methods for estimating technical costs has been to convert Medicare charges into costs using Medicare Cost-to-Charge Ratios (CCR). More recently, health care organizations have begun to invest in sophisticated cost-accounting systems (CAS) that are capable of providing procedure-specific cost estimates. The purpose of this study was to examine whether these competing approaches result in similar cost estimates for four typical courses of external beam radiation therapy (EBRT). METHODS AND MATERIALS: Technical costs were estimated for the following treatment courses: 1) a palliative "simple" course of 10 fractions using a single field without blocks; 2) a palliative "complex" course of 10 fractions using two opposed fields with custom blocks; 3) a curative course of 30 fractions for breast cancer using tangent fields followed by an electron beam boost; and 4) a curative course of 35 fractions for prostate cancer using CT-planning and a 4-field technique. Costs were estimated using the CCR approach by multiplying the number of units of each procedure billed by its Medicare charge and CCR and then summing these costs. Procedure-specific cost estimates were obtained from a cost-accounting system, and overall costs were then estimated for the CAS approach by multiplying the number of units billed by the appropriate unit cost estimate and then summing these costs. All costs were estimated using data from 1997. The analysis was also repeated using data from another academic institution to estimate their costs using the CCR and CAS methods, as well as the appropriate relative value units (RVUs) and conversion factor from the 1997 Medicare Fee Schedule to estimate Medicare reimbursement for the four treatment courses. RESULTS: The estimated technical costs for the CCR vs. CAS approaches for the four treatment courses were as follows: palliative "simple" $1,285 vs. $1,195; palliative "complex" $2,345 vs. $1,769; curative breast $6,757 vs. $4,850; and curative prostate $9,453 vs. $7,498. Accordingly, the CCR estimates were 8%, 33%, 39%, and 26% higher than the CAS cost estimates, respectively. The primary cause of the difference between the estimates was the daily cost of delivering a "complex" treatment. In fact, if corrected the difference between the estimates fell to 0%, 1%, 4%, and 0%, respectively. Similar results were observed for both methods when the analysis was repeated using data from another academic institution. Medicare reimbursement was also slightly lower than, but remarkably close to, the costs estimated by the CAS approach. CONCLUSIONS: For "complex" treatment courses, which represent the vast majority of external beam treatments, technical costs estimated using the CCR approach appear to be significantly higher than those estimated using procedure-specific cost estimates. Because cost-effectiveness analyses of radiation therapy tend to be sensitive to the cost of treatment, the use of higher costs will result in radiation therapy appearing less cost-effective.

Neurocognitive complaints in HIV-infection and their relationship to depressive symptoms and neuropsychological functioning.

We examined the degree to which depressive symptoms, clinical staging of HIV disease, and neuropsychological (NP) functioning were related to neurocognitive complaints in HIV-infection. One hundred adults with HIV-infection (12 asymptomatic, 41 mildly symptomatic, and 47 with AIDS) were administered NP tests of attention and working memory, language, psychomotor speed, verbal memory, and conceptual problem-solving, the Beck Depression Inventory, and the Patient's Assessment of Own Functioning Inventory (Chelune, Heaton & Lehman, 1986), a subjective neurocognitive complaint questionnaire where patients rated their problems with memory, language and communication, sensory-motor skills, and higher-level cognitive and intellectual functions. Neurocognitive complaints (regardless of specific type) were correlated significantly with depressive symptoms and with NP measures of attention and working memory, psychomotor skills, and learning efficiency. However, multiple regression analyses revealed that depressive symptoms accounted for the majority of variance explained in neurocognitive complaints with psychomotor efficiency generally predicting the remaining variance. Neurocognitive complaints did not differ according to HIV clinical staging.

Neuropsychiatric correlates of memory-metamemory dissociations in HIV-infection.

Ninety-one adults with HIV-infection who varied in the concordance between their subjective memory complaints (or metamemory) on the Patient's Assessment of Own Functioning (Chelune, Heaton, & Lehman, 1986) and their memory performance on the California Verbal Learning Test (CVLT), were compared on the Beck Depression Inventory (BDI), and on neuropsychological (NP) tests of attention, language, psychomotor speed, and conceptual problem-solving. Subjects with low memory complaints and normal CVLT performance (n = 29) had low BDI scores and were normal in all other NP abilities. Subjects with high memory complaints and impaired CVLT performance (n = 20) had elevations on the BDI as well as NP impairments in psychomotor speed and category fluency. Subjects with low memory complaints but impaired CVLT performance (n = 16) had low BDI scores and were selectively impaired in conceptual problem-solving. Subjects with high memory complaints but normal CVLT performance (n = 26) had high BDI scores and normal NP functioning in all other abilities. These results suggest that there are at least two key determinants to metamemory inaccuracy in HIV-infection, namely, frontal executive impairments and mood disturbance.

Anticonvulsant use in the treatment of manic syndromes in patients with HIV-1 infection.

A retrospective chart review identified 11 patients with type 1 human immunodeficiency virus (HIV) who presented to an HIV/AIDS psychiatric service with an acute manic episode. Demographic data, neurodiagnostic studies, and treatment results are discussed. Abnormal brain magnetic resonance imaging significantly predicted poor tolerance of lithium and neuroleptics. Anticonvulsants were an effective alternative.

Fluoxetine and neuroleptic malignant syndrome.

The authors present a case report of neuroleptic malignant syndrome (NMS) in a patient commencing treatment with fluoxetine alone who had previously been treated with several antipsychotic and antidepressant combinations. On reviewing the literature on the pathogenesis of NMS, the authors hypothesize a facilitative role of the neurotransmitter serotonin (5-HT) in conjunction with central dopaminergic blockade in the precipitation of NMS.

Impediments to the course and effectiveness of discharge planning.

This paper examines the proposition that "timing" (of referral) is a crucial element in determining the effectiveness of the discharge planning process. A brief review of the relevant literature is followed by the description of a study undertaken to assess the impact that various impediments had upon discharge planning practice in two matched ward populations of a large, acute care university hospital. Along with timing, three other impediments were identified and their influence assessed; (a) noncompletion of transfer forms required; (b) unavailability of an appropriate (i.e., needed level of care) bed in an approved facility; and(c) unanticipated change in the patient's medical condition. Some implications of the findings are examined and discussed, and directions for future study are identified. Appended are facsimiles of the instruments employed.