Adherence to recommendations for the use of antifungal agents in a tertiary care hospital.

OBJECTIVES: The aim of our study was to assess the adherence to labelling and international guidelines for antifungal prescribing. METHODS: A retrospective study was performed in intensive care units in addition to the oncology and haematology department, which covered 70% of antifungal consumption at Hautepierre Hospital, Strasbourg, France. On reviewing medical charts, the antifungal prescription was examined in relation to the recommendations of indication, dosage, risk of drug-drug interactions and, where appropriate, antifungal susceptibility testing. Treatments were considered appropriate, inappropriate or debatable. RESULTS: Between January and April 2007, 199 treatments were given for 179 different episodes in 133 adult patients. Treatments were prescribed for pre-emptive or targeted therapy (n = 90, with 60 for candidiasis, 26 for aspergillosis and 4 for other mould diseases), empirical therapy (n = 17) and primary (n = 81) or secondary (n = 11) prophylaxis. Fluconazole accounted for 67% of prescriptions, followed by voriconazole (19%), caspofungin (10%), posaconazole (2%), conventional or liposomal amphotericin B (2%), itraconazole (<1%) and terbinafine (<1%). Indication and dosage were found to be appropriate in 65% and 62% of cases, inappropriate in 22% and 21%, and debatable in 13% and 17%, respectively. The overall (by combining all assessment criteria) rate of inappropriate use was 40%. The overall survival rate at 12 weeks was highest in patients receiving appropriate therapy (81% versus 72% and 68% in the debatable and inappropriate therapy groups, respectively), with between-group differences not being significant (P = 0.49). CONCLUSIONS: Our evaluation revealed a high proportion of inappropriate or debatable use of antifungal agents, while highlighting significant issues, such as inadequate dosage or indications.

Emotional electrodermal response in coma and other low-responsive patients.

Emotional processing in coma remains an open question. Skin conductance responses to emotional and neutral auditory stimuli were recorded in 13 low-responsive patients (12 of whom were in coma). A differential response between emotional and neutral stimuli was found, which significantly correlated with the Glasgow Coma Scale and the Cook and Palma score. These correlations indicate that emotional processing can occur in coma patients with relatively high clinical scores of reactivity.

Cortical information processing in coma.

OBJECTIVES: To evaluate cortical information processing (particularly, semantic processing) in acute nontraumatic coma by means of event-related brain potentials (ERPs). METHODS: The tests included measures of obligatory auditory processing (N100), automatic (Mismatch Negativity) and controlled (P300) detection of stimulus deviance, and semantic processing (ERP effects in word pairs and sentences). The tests were presented to 20 healthy participants and 42 coma patients with Glasgow Coma Scale <9. RESULTS: Responders (ie, patients whose ERP data indicate that their brain was able to process the corresponding stimuli) were found in each ERP test, and their distribution was statistically different from that expected by chance. Particularly, 7 responders were found in the word pair paradigm and 3 responders in the sentence paradigm. The P300 responsiveness highly correlated with other ERP responses, with Glasgow Coma Scale and with the future development of coma (ie, P300 on day 4 was related to the clinical state on day 20). CONCLUSIONS: Results suggest a wide range of cortical information processing in coma, including semantic processing. The question is discussed of whether, and to what extent, these processing operations are related to conscious awareness of stimuli.

Factors associated with overall and attributable mortality in invasive aspergillosis.

BACKGROUND: Invasive aspergillosis is associated with high death rates. Factors associated with increased mortality have not yet been identified in a large population of patients with various underlying conditions. METHODS: We retrospectively reviewed 385 cases of suspected or documented aspergillosis that occurred during a 9-year period. We identified 289 episodes that fulfilled the criteria for possible, probable, or proven invasive aspergillosis according to the international definition criteria and that was treated with an anti-Aspergillus active antifungal drug. Clinical and microbiological variables were analyzed for their effects on overall and attributable mortality. Significant variables in univariate analysis were introduced into a multivariate Cox model. RESULTS: Twelve-week overall and disease-specific survival rates were 52.2% (95% confidence interval, 46.5%-57.9%) and 59.8% (95% confidence interval, 54.0%-65.4%), respectively. Receipt of allogeneic hematopoietic stem cell or solid-organ transplant, progression of underlying malignancy, prior respiratory disease, receipt of corticosteroid therapy, renal impairment, low monocyte counts, disseminated aspergillosis, diffuse pulmonary lesions, pleural effusion, and proven or probable (as opposed to possible) aspergillosis are predictors of increased overall mortality. Similar factors are also predictors of increased attributable mortality, with the following exceptions: pleural effusion and low monocyte counts have no impact, whereas neutropenia is associated with a higher attributable mortality. CONCLUSIONS: Identification of predictors of death helps in the identification of patients who could benefit from more-aggressive therapeutic strategies. Initiation of therapy at the stage of possible infection improves outcome, and this finding calls for the development of efficient preemptive strategies to fill the gap between empirical and directed therapy.

Long-term survival in post-transplant lymphoproliferative disorders with a dose-adjusted ACVBP regimen.

Post-transplant lymphoproliferative disorders (PTLD) are severe complications after solid organ transplantation with no consensus on best treatment practice. Chemotherapy is a therapeutic option with a high response and a significant relapse rate leading to a low long-term tolerance rate. Currently, most centres use anthracycline-based drug combinations, such as CHOP (cyclophosphamide, doxorubicin, vincristine and prednisone). We assessed the efficacy and safety of a dose-adjusted ACVBP (doxorubicin reduced to 50 mg/m(2), cyclophosphamide adjusted to renal function, vindesine, bleomycin, prednisone) regimen in patients failing to respond to a reduction in immunosuppressive therapy. Favourable responses were observed in 24 (73%) of the 33 treated patients. Fourteen (42%) patients died, mostly from PTLD progression. Actuarial survival was 60% at 5 years and 55% at 10 years. Survival prognostic factors were: number of involved sites (P = 0.007), clinical stage III/IV (P = 0.004), bulky tumour (P < 0.0001), B symptoms (P = 0.03), decreased serum albumin (P = 0.03) and poor performance status (P = 0.06). Both the international and the PTLD prognostic index were predictive for survival (P = 0.001 and P = 0.002, respectively). Overall 128 cycles were given. Grade 3 or 4 neutropenia was recorded after 26 (20%) chemotherapy cycles in 19 (58%) patients. Forty-one (32%) infections were recorded in 26 (79%) patients. This study demonstrated that an individual dose-adjustment of ACVBP regimen was manageable in PTLD patients and favourably impacted on long-term survival.