Serum concentrations of protease inhibitors as predictors of HIV-related clinical events in patients on antiretroviral therapy.

Serum concentrations of protease inhibitors (PIs) show large interindividual variations. It is not clear what clinical impact these differences in drug concentrations might have. In this study we explored the association between serum concentration of protease inhibitors and HIV-related disease. 130 patients on PI-containing regimen underwent PI concentration measurement in serum. The results were divided into 3 categories: high level, therapeutic level, and low level. HIV-related events (CDC category B and C) and death were prospectively recorded after the drug monitoring. The results were statistically analysed employing Cox regression. Median follow-up was 709 d, and 22 patients reached an endpoint. For the trough concentrations the hazard ratio (HR) for patients with therapeutic level vs low level was 0.63 (95% CI 0.20-1.95) and high level vs low level was 0.56 (95% CI 0.14-2.26). For the maximum concentrations the HR for therapeutic level vs low level was 1.32 (95% CI 0.48-3.62) and high level vs low level was 0.47 (95% CI 0.06-3.90). In conclusion, in this small pilot study we could not show any association between the serum concentrations of PIs and subsequent clinical HIV-related events. Larger studies are needed to explore this subject further.

Carisoprodol intoxications and serotonergic features.

The symptoms and signs of carisoprodol intoxications do not resemble those caused by its metabolite meprobamate. Meprobamate most probably produces its effects through the GABAergic neurotransmitter system. The signs and symptoms of carisoprodol intoxications, however, are not easily explained by interaction with this neurotransmitter system. In the present study, four cases of carisoprodol intoxications are presented with emphasis on the presence of serotonergic signs and symptoms. All four cases fulfilled three different sets of criteria for the diagnosis of serotonin syndrome. These findings could indicate that an increased serotonin level in the central nervous system could explain some of the symptoms and signs of carisoprodol intoxications. This may have implications for the clinical evaluation and treatment of such intoxications. Since few laboratories routinely screen for carisoprodol it is important to keep this drug in mind when encountering intoxications displaying serotonergic symptoms.

Anion and osmolal gaps in the diagnosis of methanol poisoning: clinical study in 28 patients.

OBJECTIVE: To evaluate anion and osmolal gaps as diagnostic tools in methanol poisoning. DESIGN AND SETTING: Clinical observational study. PATIENTS AND METHODS: In a recent methanol outbreak, the initial triage and treatment decisions in 28 patients were based mainly upon the values of the osmolal and anion gaps on admission. Methanol and formate levels were later compared to these gaps by linear regression analysis. RESULTS: The correlation between the osmolal gaps and serum methanol concentrations on admission was linear (y = 1.03x+12.71, R2 = 0.94). The anion gaps correlated well with the serum formate concentrations (y = 1.12x+13.82, R2 = 0.86). Both gaps were elevated in 24 of the 28 subjects upon admission. Three patients had an osmolal gap within the reference area (because of low serum methanol), but elevated anion gap because of formate accumulation. One patient with probable concomitant ethanol ingestion had a high osmolal gap and a normal anion gap. CONCLUSION: Osmolal and anion gaps are useful in the diagnosis and triage of methanol-exposed subjects. Confounders are low serum methanol and concomitant ethanol ingestion.